text:
Radiation Oncology/Head & Neck/Nasopharynx/Early Stage

Nasopharyngeal Cancer - Early Stage

Overview

 * Early-stage (I-II) outcomes are good with radiation alone
 * 5-year RFS is 75-95% and OS is 70-80%
 * Most historical series use 2D radiation, but several reports with a short follow up show good outcomes with IMRT
 * IMRT in particular has significantly better sparing of the objective (stimulated/unstimulated flow) parotid function in a randomized setting
 * Dose tends to be 66-72 Gy in 2 Gy/fraction; elective sites receive 50-60 Gy using dose painting

ChemoRT for Stage II

 * Chinese Stage II Trial PMID 22056739 -- "Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial." (Chen QY JNCI 2011)
 * Methods: 230/236 pts with stage II (used Chinese staging) NPC randomized to RT vs chemoRT with weekly cisplatin 30mg/m2 x 7c
 * RT: Conventional 2D RT: 68-70Gy/34-35fx to primary, 60-62Gy to node positive neck, 50Gy to node negative neck
 * Primary endpoint OS
 * Results: Median f/u: 60 months
 * ChemoRT improved:
 * 5 yr OS: 95% vs 86%, HR=0.30, P =0.007
 * 5 yr PFS: 88% vs 79%, HR 0.45, P=0.017
 * 5 yr DMFS: 95% vs. 84%, HR = 0.27, P =0.007
 * No difference in LRC: 93% vs 91%, P=0.29
 * Toxicity: More acute toxicity with chemoRT:64% vs 41% P = 0.001, no difference in late toxicity
 * Conclusion: ChemoRT improves survival in stage II NPC

Radiotherapy alone

 * Taiwan; 2005 (1983-1998) PMID 15936544 -- "Treatment outcomes and late complications of 849 patients with nasopharyngeal carcinoma treated with radiotherapy alone." (Yeh SA, Int J Radiat Oncol Biol Phys. 2005)
 * Retrospective. 849 consecutive NPC patients (Stage I 6%, Stage IIA 3%, Stage IIB 35%, Stage III 32%, Stage IVA 19%, Stage IVB 5% by AJCC-5), WHO type I 1%, II 62%, type III 37%. RT median 70 Gy, if BT boost median 74 Gy
 * Outcome: 5-year OS 59%, DFS 52%; OS by Stage: I 82%, II 72%, III 55%, IVA 42%, IVB 39%
 * Toxicity: xerostomia 90%, hearing impairment 54%, tinnitus 52%, Lhermitte's sign 21%, trismus 12%, temporal necrosis 6%

 * RTOG (Marcial et al) - PMID 6993442 (no abstract) — complete response to local tumor, 96% for T1, 88% for T2, 81% for T3, and 74% for T4. For N+ neck, ranged from 93% to 71%. 5-year survival overall was 40%.

Altered fractionation

 * RTOG 71-03 (1971-1979)
 * Randomized. 121 patients. All Stages. Arm 1) split course RT (30/10, 3 week rest, 30/10) vs. Arm 2) 66/33 or 66/30
 * 1980 PMID 6993442 -- "Split-course radiation therapy of carcinoma of the nasopharynx: results of a national collaborative clinical trial of the Radiation Therapy Oncology Group." (Marcial VA, Int J Radiat Oncol Biol Phys. 1980 Apr;6(4):409-14.)
 * 5-year outcome: LC 86% vs. 80% (NS), LRC 86% vs. 78% (NS), DFS 40% vs. 30% (NS)
 * Late toxicity: comparable, except edema worse with continuous RT (42% vs. 24%)
 * Conclusion: No difference between fractionation schedules, less social impact with split course

 * Wang et al. - PMID 2720596 — Not randomized. Accelerated hyperfractionation (twice a day). Compared to similar stage patients treated with once a day XRT, and 5-year local control for T1-2 was 89% (hyperfract) vs 55%, and 77% vs 45% for T3-4.

Use of IMRT

 * UCSF experience
 * 2000 PMID 11020568 — "Three-dimensional intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: the University of California-San Francisco experience." Sultanem K et al. Int J Radiat Oncol Biol Phys. 2000 Oct 1;48(3):711-22.
 * 65-70 Gy to GTV (including + LN), 60 Gy to CTV, 50-60 Gy to the negative neck. Treated at 1.8 Gy per day to CTV and neck and 2.12-2.25 Gy/day to GTV. CTV consisted of entire nasopharynx, posterior 1/3 of nasal cavity and maxillary sinuses, retropharyngeal LN region, clivus, skull base, pterygoid fossae, parapharyngeal space, inferior sphenoid sinus.
 * 4-year local PFS was 97%, local-regional PFS 98%, and DM-free rate 66%. 4-year OS 88%
 * 2002 PMID 12007936 — "Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience." Lee N et al. Int J Radiat Oncol Biol Phys. 2002 May 1;53(1):12-22.
 * 2004 Dose constraints PMID 15183492
 * First group of pts treated with IMRT for the primary tumor and conventional fields for the lymph nodes. This group retrospectively reviewed to determine dose endpoints to critical normal structures. Second group of pts treated with IMRT to both primary and nodes. Based on dose endpoints defined, new plans were developed for the second group of pts and compared to the original plans.
 * Prescription dose 70 Gy at 2.12 Gy/fx (33 fx) to GTV, 59.4 Gy at 1.8 to PTV.

Side Effect Trials
IMRT salivary function
 * Prince of Wales Hospital; 2007 (Hong Kong)(2001-2003) PMID 17971582 -- "Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients." (Kam MK, J Clin Oncol. 2007 Nov 1;25(31):4873-9.)
 * Randomized. 60 patients with T1-2bN0-1 nasopharynx. Arm 1) IMRT 66 Gy (CTV=GTV + 1cm; at-risk anatomic sites; LN Levels IB-II, LN upper Level V, LN retropharyngeal; PTV=CTV+3mm), lower neck LN+ 66 Gy anterior field, LN- 54-60 Gy + intracavitary BT boostvs. Arm 2) 66 Gy 2D + intracavitary BT boost
 * Outcome: observer-rated severe xerostomia IMRT 39% vs. 2D-RT 82% (SS), stimulated parotid flow (SS), unstimulated parotid flow (SS), but no difference in patient-reported feeling of xerostomia
 * Conclusion: IMRT superior in preserving objective parotid function, but no difference in patient-reported benefit
 * Editorial (PMID 17971579): Observer-rated scoring underestimates patient reports and has low agreement among various observers. Suspect sparing of parotid alone not sufficient. Parotid gland produces saliva without mucins (lubricants, bind water, and provide selective permeability barrier). Mucin-secreting glands (e.g. minor salivary glands, submandibular glands) produce <10% saliva but >50% mucins. May need to spare these glands as well for subjective feeling of benefit

 * Queen Mary Hospital; 2006 (Hong Kong)(2000-2004) PMID 17145528 -- "Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial." (Pow EH, Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):981-91.)
 * Randomized. 51 patients, Stage II (T2N0-1, AJCC 1997). Arm 1) conventional RT 68 Gy, neck 66 Gy vs. Arm 2) IMRT, GTV dose 68-72 Gy, PTV 66-68 Gy. Stimulated whole (SWS) and parotid (SPS) saliva flow evaluated, QoL SF-36, EORTC Core, EORTC QLQ-H&N35 questionnaires. Minimum F/U 1 years
 * 1-year outcome: 25% whole flow (SWS) IMRT 50% vs. 2D 5% (SS), 25% parotid flow (SPS) 83% vs. 9% (SS). At 2 months, both group had xerostomia, but IMRT group improved significantly better over time. Also improvements in QoL
 * Conclusion: IMRT significantly better than conventional RT for salivary function and QoL

Middle ear ventilation tube
 * Hong Kong; 2002 PMID 12512893 -- "Randomized evaluation of the audiologic outcome of ventilation tube insertion for middle ear effusion in patients with nasopharyngeal carcinoma." (Ho WK, J Otolaryngol. 2002 Oct;31(5):287-93.)
 * Randomized. ? patients. NPC and middle ear effusion. Arm 1) pre-RT ventilation tube insertion vs. Arm 2) observation. Audiologic assessment throughout. F/U 4 years
 * Outcome: No difference in hearing changes up to 4 years
 * Conclusion: Ventilation tube insertion before RT did not offer hearing benefit

Pointers
 * Pre-treatment
 * Nutrition consult, with consideration for G-tube
 * Dental evaluation
 * Set-up
 * Supine, head extended
 * Thermoplast mask to shoulders


text: User:Recent Runes/French Verb Families

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title: User:Recent Runes/French Verb Families


text:
Radiation Oncology/Head & Neck/Nasopharynx/Advanced Stage

Nasopharyngeal Cancer - Advanced Stage

Chemotherapy with radiation

 * Because Stage III-IV NPC has a fairly poor prognosis with RT alone, multiple efforts were made to add chemotherapy to the regimen
 * Induction chemotherapy was evaluated in 5 randomized trials; two showed small benefit for disease-free survival, but none showed an overall survival benefit. As a result, induction chemotherapy is currently not indicated
 * Adjuvant chemotherapy was evaluated in 3 randomized trials; there was no benefit
 * Phase II RTOG 81-17 demonstrated the feasibility of concurrent cisplatin with RT in advanced H&N cancers; it included 22% NPC. Subsequent Intergroup trial 0099 showed a survival benefit for concurrent cisplatin with RT, followed by adjuvant chemotherapy. This was the first trial to do so; however, the RT only arm had an unexpectedly low survival, compared with results from RT alone in Asian (endemic) studies
 * Concurrent chemo-RT benefits were confirmed by a randomized trial from Taiwan in an endemic population, which used concurrent cisplatin + 5-FU. However, a re-analysis of the data suggests that concurrent chemo-RT is only beneficial for "low-risk" advanced stage patients. "High-risk" advanced stage patients did not gain any benefit from that chemo regimen, and may require more intense, neoadjuvant, or further adjuvant chemotherapy
 * A Singaporean trial used the INT 0099 regimen, and again demonstrated a survival benefit
 * Concurrent chemo-RT is now considered a standard of care in Stage III-IV NPC; given previously different staging, some IIB patients were included in the trials and may benefit from concurrent chemotherapy as well. The INT 0099 regimen is the best characterized; unfortunately, compliance with the regimen is only 60-70%
 * Because concurrent chemo-RT results in reasonable local control, but adjuvant chemo has not resulted in good systemic control, efforts are underway to try induction -> concurrent chemo-RT. Several Phase II trials have reported encouraging results in patients with significant N disease

 * Meta-analysis; 2006 PMID 16377415 -- "Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients." (Baujat B, Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1):47-56.)
 * 8 trials, 1753 patients (concurrent: INT 0099, PWH-QEH Hong Kong, QMH Hong Kong, induction: PWH Hong Kong, AOCOA, VUMCA, Hokkaido, adjuvant: Taiwan). Individual updated patient data. Median F/U 6 years
 * Outcome: Addition of chemo absolute survival benefit of 6% at 5 years (56% to 62%), absolute EFS benefit of 10% (42% to 52%)
 * Significant interaction between timing of chemo and OS; highest benefit from concurrent chemo
 * Conclusion: Chemotherapy has small but significant benefit for OS and EFS, seen when administered concomitantly

 * Meta-analysis; 2002 - PMID 12040275 — "Combined chemoradiation versus radiation therapy alone in locally advanced nasopharyngeal carcinoma: results of a meta-analysis of 1,528 patients from six randomized trials." (Huncharek M et al. Am J Clin Oncol. 2002 Jun;25(3):219-23.)
 * 6 trials, 1528 patients (concurrent: INT 0099; induction: Hong Kong, Guangzhou, AOCOA, VUMCA; adjuvant: Italian). Chemoradiation vs radiation alone in locally advanced patients, either adjuvantly, neoadjuvantly, or concurrently.
 * Outcome: DFS/PFS improved 2 years 37%, 3 years 40%, 4 years 34%. OS improved 2 years 20% (NS), 3 years 19% (NS), 4 years 21% (SS)
 * Conclusion: Addition of chemotherapy improves DFS/PFS and OS

Concurrent chemo-RT vs RT alone

 * Hong Kong NPC-9902 (T-disease) (1999-2004)
 * Randomized, 2x2 design. Closed early due to slow accrual. 189 patients, WHO grade II-III, Stage T3-4N0-1 (AJCC-5)(key problem locoregional failure; see companion trial NPC-9901). Arm 1) conventional RT alone vs. Arm 2) accelerated RT vs. Arm 3) conventional RT + concurrent chemo vs. Arm 4) accelerated RT + concurrent chemo. Conventional RT >=66 in 2 Gy/fx, 5 days/week. Accelerated same regimen but 6 days/week. Technique 2D or 3D-CRT or IMRT boost. Concurrent chemo cisplatin 100 mg/m2 q3 weeks, adjuvant chemo cisplatin 80 mg/m2 + 5-FU 1000 mg/m2
 * 3-years; 2006 PMID 16904519 -- "Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma." (Lee AW, Int J Radiat Oncol Biol Phys. 2006 Sep 1;66(1):142-51.). Median F/U 2.9 years
 * Outcome: 3-year FFS RT 70%, AFRT 63%, chemo-RT 74%, chemo-AFRT 94% (SS). On multivariate analysis, concurrent chemo significant, accelerated RT not significant. OS 83%, 73%, 87%, 88% (NS)
 * Toxicity Grade 3-5: Acute: RT 55%, AFRT 70%, chemo-RT 83%, chemo-AFRT 86% (concurrent chemo SS worse). Late: 17%, 21%, 27%, 32% (chemo-AFRT borderline p=0.05 worse). Most late toxicity otologic.
 * Conclusion: Preliminary, concurrent chemo with accelerated fractionation could significantly improve local tumor control

 * Hong Kong NPC-9901 (N-disease) (1999-2004)
 * Randomized. 348 patients, WHO grade II-III, T1-4N2-N3 (AJCC-5)(key problem distant failure; see companion trial NPC-9902). Arm 1) RT alone vs. Arm 2) RT + concurrent cisplatin 100 mg/m2 q3 weeks. RT >= 66 Gy (2D, 3D-CRT or IMRT)
 * 3-years; 2005 PMID 16192584 -- "Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group." (Lee AW, J Clin Oncol. 2005 Oct 1;23(28):6966-75.) Median F/U 2.3 years
 * Outcome: DFS chemo-RT 72% vs. RT alone 62% (SS), LRC 92% vs. 82% (SS), DM 76% vs. 73% (NS), OS 78% vs. 78% (NS)
 * Toxicity: acute chemo-RT 84% vs. RT alone 53% (SS); late 28% vs. 13% (SS), most late toxicity otologic
 * Conclusion: Preliminary, significant benefit for tumor control at the cost of higher toxicity. No early OS benefit

 * Singapore SQNP01 (1997-2003)
 * Randomized. 221 patients, WHO II-III, T3-4 or N2-3 (AJCC-5). Arm 1) RT alone vs. Arm 2) RT + concurrent cisplatin 100 mg/m2 q3 weeks + adjuvant cisplatin 80 mg/m2 + 5-FU 1000 mg/m2 x3 cycles. RT technique 70 Gy primary, 60 Gy neck + 10 Gy electron boost to lymph nodes. 71% patients received all 3 cycles of concurrent chemo
 * 3-years; 2005 PMID 16170180 -- "Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety." (Wee J, J Clin Oncol. 2005 Sep 20;23(27):6730-8.) Median F/U 3.2 years
 * Outcome: 3-year DFS chemo-RT 72% vs. RT 53% (SS); OS 80% vs. 65% (SS); 2-year DM chemo-RT 13% vs. RT alone 30% (SS)
 * Toxicity: Grade 3-5 in 48%, mucositis chemo-RT 48% vs. RT 32% (SS), anorexia 22% vs. 4% (SS), emesis 5% vs. 0% (SS). Also significant hematologic toxicity
 * Conclusion: Confirmation of INT 0099 results; also applicable in endemic NPC

 * Queen Mary Hospital, Hong Kong (1995-2001)
 * Randomized, 2x2 design (concurrent chemo vs. none, adjuvant chemo vs. none). Ho's Stage T3 or N2-3 or LN >=4 cm (AJCC 6th II-IV). Arm 1) RT alone vs. Arm 2) concurrent chemo-RT vs. Arm 3) RT + adjuvant chemo vs. Arm 4) concurrent chemo-RT + adjuvant RT. Concurrent chemo was FU prodrug uracil/tegafur, adjuvant chemo was cisplatin/5-FU and vincristine/bleomycin/MTX x3+3 cycles. RT 1995-1997 62.5/25 split course with 1 week break; 1997-2001 68/34 primary and 66/33 neck. If parapharyngeal extension or residual disease, 10 Gy boost
 * 3-years; 2004 PMID 15226332 -- "Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: a factorial study." (Kwong DL, J Clin Oncol. 2004 Jul 1;22(13):2643-53.)
 * Outcome: 3-year concurrent CRT vs. RT alone FFS 69% vs. 58% (NS), OS 86% vs. 77% (p=0.06), LRC 80% vs. 72% (NS), DM 15% vs. 29% (SS). 3-year adjuvant chemo vs. none FFS 62% vs. 65% (NS), OS 80% vs. 83% (NS), no difference on LRC or DM.
 * Conclusion: Trend to improvement with concurrent chemo-RT over RT alone (p=0.06), no benefit to adjuvant chemo

 * Prince of Wales Hospital / Queen Elizabeth Hospital, Hong Kong (1994-1999)
 * Randomized. 350 patients, Ho's Stage N2-3 or N1 with LN >=4 cm (AJCC-6 Stage II-IVB). Arm 1) RT with concurrent cisplatin 40 mg/m2 q week vs. Arm 2) RT alone. RT 66 Gy, parapharyngeal boost 10-20 Gy allowed. Primary end point PFS
 * 2-years; 2002 PMID 11956263 -- "Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial." (Chan AT, J Clin Oncol. 2002 Apr 15;20(8):2038-44.) Median F/U 2.7 years
 * Outcome: 2-year PFS chemo-RT 76% vs. RT alone 69% (NS). Subgroup analysis benefit for Ho's T3
 * Conclusion: Concurrent chemo-RT well tolerated, but no benefit
 * 5-years; 2005 PMID 15812080 -- "Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma." (Chan AT, J Natl Cancer Inst. 2005 Apr 6;97(7):536-9.) Median F/U 5.5 years
 * Outcome: 5-year OS chemo-RT 70% vs. RT 59% (p=0.07). Subgroup analysis no benefit for T1-2, but benefit for T3-4 (HR 0.51)
 * Conclusion: Trend for survival benefit; promising treatment strategy

 * Taiwan (1993-1999)
 * Randomized. 284 patients, NPC Stage III-IV M0, histology WHO I (3%), WHO II (73%), WHO III (24%). Arm 1) RT 70-74 Gy alone vs. Arm 2) concurrent cisplatin 20 mg/m2 + 5-FU 400 mg/m2 during week 1 and 5. RT: CTV = GTV+2cm, included entire base of skull, sphenoid sinus, 2cm beyond mastoid process, posterior half of maxillary sinus/nasal cavity. Dose 70-74 Gy primary tumor and LN+, 50-60 Gy N0 neck. Chemo completed by 94% patients
 * 5-years; 2003 PMID 12586799 -- "Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival." (Lin JC, J Clin Oncol. 2003 Feb 15;21(4):631-7.). Median F/U 5.4 years
 * 5-year outcome: PFS RT alone 53% vs. chemo-RT 72% (SS); OS 54% vs. 72% (SS)
 * Toxicity Grade 3-4: mucositis 35% vs. 45%, skin 26% vs. 35%
 * Conclusion: Concurrent chemo-RT superior to RT alone for advanced NPC
 * Re-analysis; 2004 PMID 15337551 -- "Another way to estimate outcome of advanced nasopharyngeal carcinoma--is concurrent chemoradiotherapy adequate?" (Lin JC, Int J Radiat Oncol Biol Phys. 2004 Sep 1;60(1):156-64.)
 * Original (AJCC 1992) stage: Stage III 20%, Stage IV 80%. Restaged (AJCC 1997): Stage II/III 71%, Stage IV 29%. New risk definition: high-risk (LN >6cm or SCV LN or AJCC 1992 T4N2 or multiple LN mets with 1 LN >4cm) 42% vs. low-risk 58%
 * Low-risk group (chemo-RT vs. RT): LC 95% vs. 77% (SS), neck control 100% vs. 96% (NS), DM 90% vs. 78% (SS), PFS 87% vs. 61% (SS), OS 83% vs. 60% (SS). Chemo-RT significantly better
 * High-risk group (chemo-RT vs. RT): LC 75% vs. 68% (NS), neck control 92% vs. 87% (NS), DM 60% vs. 60% (NS), PFS 44% vs. 43% (NS), OS 56% vs. 46% (NS). No difference with concurrent chemo
 * Conclusion: Concurrent chemo-RT superior for low-risk patients, but inadequate for high-risk patients

 * NYU; 2000 (1995-1997) - PMID 10863053 — "Improved outcome secondary to concurrent chemoradiotherapy for advanced carcinoma of the nasopharynx: preliminary corroboration of the intergroup experience." (Cooper JS et al. Int J Radiat Oncol Biol Phys. 2000 Jul 1;47(4):861-6.)
 * Retrospective single institution. Repeated regimen of Intergroup 0099. Stage III-IV.
 * Outcome: 3-year OS was 93% and DFS was 65%; both substantially better than historical controls
 * Conclusion: INT 0099 regimen should be standard of care

 * Intergroup 0099 / RTOG 88-17 (1989-1995)
 * Randomized. Trial stopped early due to significant survival benefit. 147 patients. NPC Stage III-IV (Stage IV 91%; but also included few N1 patients, which are IIB today), histology WHO I (25%), WHO II (35%), WHO III (41%). Arm 1) RT 70 Gy alone vs RT 70 Gy with concurrent cisplatin 100 mg/m2 q3 weeks and adjuvant cisplatin + 5-Fu . CT-based treatment planning. Fields: included 2 cm margin on gross disease and included entire base of skull and sphenoid sinus, 2 cm posterior to mastoid process; anteriorly included posterior 1/3 of maxillary sinus and nasal cavity. Dose: 70 Gy to primary. For neck to clavicle, 50 Gy for N0 disease, 66 Gy for nodes <= 2 cm, and 70 Gy for nodes > 2 cm. Cisplatin given every 3 weeks at 100 mg/m2 x 3 cycles. Then adjuvant chemo began 4 weeks after finishing RT: cisplatin 80 mg/m2 and 5-FU 1000 mg/m2/d by 96-hr infusion q4w x 3 cycles. Partial or radical neck dissections for persistent neck disease. Chemo completed by 55%
 * 1998 PMID 9552031 - "Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099." Al-Sarraf et al. J Clin Oncol. 1998 Apr;16(4):1310-7. Median F/U 2.7 years
 * 3-year outcome: PFS chemo-RT 69% vs. RT alone 24% (SS); OS 78% vs 47% (SS). Median OS not reached for chemo-RT vs. 2.5 years for RT alone.
 * Toxicity Grade 3-4: stomatitis 29% vs. 19%, nausea 14% vs. 5%, leukopenia 23% vs. 1%
 * Conclusion: Concurrent chemo-RT superior to RT alone for advanced NPC
 * Comment: First randomized trial to show a survival benefit for the use of concurrent chemo, unexpectedly low RT alone outcome (several retrospective series showed >70% OS with RT alone in endemic patients), RT technique considered less aggressive than that practiced in Asia (particularly lack of parapharyngeal and intracavitary boost), not applicable to non-US patients

 * RTOG 81-17 (1981-1984)
 * Phase II. 124 patients, locally advanced inoperable H&N cancer (oropharynx 39%, nasopharynx 22%, oral cavity 18%, hypopharynx 7%, larynx 7%, sinuses 7%). Stage III 18%, Stage IV 82%. Concurrent RT 66-73.8 Gy with cisplatin 100 mg/m2 q3 weeks. 60% completed planned treatment
 * Overall; 1987 PMID 3802013 -- "Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. An RTOG Study." (Al-Sarraf M, Cancer. 1987 Jan 15;59(2):259-65.)
 * Severe toxicity: stomatitis 31%, leukopenia 11%, anemia 8%, N/V 6%
 * Outcome: 1-year DFS 51%, OS 66%. Nasopharynx CR 82%
 * Conclusion: Concurrent cisplatin effective and safe in advanced H&N
 * NPC Subset; 1990 PMID 2199621 -- "Chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma: a radiation therapy oncology group study." (Al-Sarraf M, J Clin Oncol. 1990 Aug;8(8):1342-51.)
 * Subset analysis, 27 NPC patients, 96% Stage IV, 67% poorly differentiated. All patients received >64.5 Gy. Median F/U 1.5 years
 * Severe toxicity: stomatitis 41%, xerostomia 15%
 * Outcome: 4-year DFS 45%, OS 55%
 * Conclusion: Chemo-RT in NPC effective, should be evaluated in phase III

Concurrent RT with biologics

 * Beijing Hospital, China (2001-2003) -- RT +/- recombinant adenovirus-p53
 * Randomized. 82 patients with NPC. Arm 1) RT 70/35 alone vs. Arm 2) RT + recombinant adenovirus-p53 (rAd-p53) injected intratumorally QW x8
 * 2008 PMID 19103729 -- "Effect of Recombinant Adenovirus-p53 Combined With Radiotherapy on Long-Term Prognosis of Advanced Nasopharyngeal Carcinoma." (Pan JJ, J Clin Oncol. 2008 Dec 22. [Epub ahead of print]) Median F/U 5.1 years
 * Outcome: p53 mRNA detected in 94% postinjection biopsies, with upregulation of p21 and Bax. 5-year LRF RT 28% vs RT + rAd-p53 3% (SS); 5-year DFS 57% vs. 67% (NS); 5-year OS 59% vs. 67% (NS)
 * Toxicity: Transient fever after rAd-p53 administration
 * Conclusion: rAd-p53 was safe and biologically active, and improves tumor control and survival rate

Sequential Chemo and RT vs. RT alone

 * Pooled long-term AOCOA/Guangzhou data
 * Pooled data from 2 similar PIII trials comparing induction chemo->RT vs. RT alone. 784 patients. Induction cisplatin, bleomycin, 5-FU or cisplatin, epirubicin. RT 70 Gy. Median F/U 5.6 years
 * 5-years; 2005 PMID 15657403 -- "Long-term survival after cisplatin-based induction chemotherapy and radiotherapy for nasopharyngeal carcinoma: a pooled data analysis of two phase III trials." (Chua DT, J Clin Oncol. 2005 Feb 20;23(6):1118-24.)
 * Outcome: 5-year DFS induction chemo 63% vs. RT 58% (SS), OS 62% vs. 58% (NS). LRF decreased by 18%, DM decreased by 13%, but no significant difference in failure patterns
 * Conclusion: Induction chemo-RT modest decrease in DFS, but no impact on OS. Concurrent chemo-RT should remain standard of care
 * Early Stage NPC; 2006 PMID 16750333 -- "Improvement of survival after addition of induction chemotherapy to radiotherapy in patients with early-stage nasopharyngeal carcinoma: Subgroup analysis of two Phase III trials." (Chua DT, Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1300-6. Epub 2006 Jun 5.)
 * Subset analysis. AJCC 1997 Staging. Group 1 (T1-2N0-1, was entirely IIB) vs. Group 2 (T1-2N2-3) vs. Group 3 (T3-4N0-1) vs. Group 4 (T3-4N2-3).
 * Outcome: no difference in LRC, DM, or OS for Groups 2-4. Group 1 5-year OS induction chemo 79% vs. RT alone 67% (p=0.048), DM 86% vs. 74% (SS)
 * Conclusion: Group 1 (T1-2N0-1; all IIB) relatively poor survival due to mets, improved with induction chemo. No benefit for induction in Groups 2-4

 * Guangzhou (1993-1994) - cisplatin, 5-FU, bleomycin
 * Randomized. 456 patients. Chinese stage III-IV M0. Arm 1) RT alone vs. Arm 2) Neoadjuvant cisplatin 100 mg/m2, bleomycin 10 mg/m2, and 5-FU 800 mg/m2 x2-3 cycles, followed by RT within 2 weeks. RT 68-72 Gy primary tumor, involved neck 60-62 Gy, uninvolved neck 60 Gy. If residual tumor after RT, could boost 10-14 Gy EBRT or 20-24 Gy HDR in 4-5 fractions
 * 5-years; 2001 PMID 11230478 -- "Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma." (Ma J, J Clin Oncol. 2001 Mar 1;19(5):1350-7.)
 * Outcome: 5-year OS induction chemo 63% vs. RT alone 56% (NS); RFS 59% vs. 49% (SS); LRC 82% vs. 74% (p=0.05); no difference on DM
 * Conclusion: No survival benefit for induction chemotherapy

 * Hokkaido RTOG (1991-1998) -- cisplatin, 5-FU
 * Randomized. 80 patients. Stage I-IV M0. Arm 1) RT alone vs. Arm 2) Neoadjuvant cisplatin 80 mg/m2, 5-FU 800 mg/m2 q3 weeks x2 cycles. RT 66-68 Gy to primary tumor and LN+, 50 Gy to negative LNs
 * 5-years; 2002 PMID 12001120 -- "A prospective, randomized trial comparing neoadjuvant chemotherapy with radiotherapy alone in patients with advanced nasopharyngeal carcinoma." (Hareyama M, Cancer. 2002 Apr 15;94(8):2217-23.). Median F/U 4.1 years
 * Outcome: 5-year OS induction chemo 60% vs. RT alone 48% (NS); DFS 55% vs. 43% (NS). No difference in LRC; most patients experienced LR failure before DM failure
 * Conclusion: Neoadjuvant chemo didn't improve DFS or OS

 * Asian-Oceanic Clinical Oncology Association (AOCOA) (1989-1993) -- cisplatin, epirubicin
 * Randomized. 286 patients. Ho's staging T3 or N2-N3 disease or LN+ >= 3cm. Arm 1) neoadjuvant cisplatin 60 mg/m2 + epirubicin 110 mg/m2 x2-3 cycles followed by RT vs. Arm 2) RT alone. RT dose 66-74 Gy (median 71 Gy) to primary tumor, 60-76 Gy (median 66 Gy) to neck.
 * 3-years; 1998 PMID 9840526 -- "Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Asian-Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group." (Chua DT, Cancer. 1998 Dec 1;83(11):2270-83.). Median F/U 2.5 years
 * Outcome: 3-year RFS induction chemo 48% vs. RT 42% (NS); OS 78% vs. 71% (NS)
 * Conclusion: No benefit for induction chemo

 * International Nasopharynx Cancer Study Group: VUMCA I (1989-1993) -- cisplatin, epirubicin, bleomycin
 * Randomized. 339 patients. Undifferentiated carcinoma (WHO 2 or 3), any T stage, N2-3, M0. Arm 1) RT 70 Gy alone vs. Arm 2) induction BEC (bleomycin, epirubicin, cisplatinum) q3 weeks x 3 cycles followed by RT.
 * 1996 PMID 8655368 — "Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV(> or = N2, M0) undifferentiated nasopharyngeal carcinoma: a positive effect on progression-free survival." (No Authors, Int J Radiat Oncol Biol Phys. 1996 Jun 1;35(3):463-9.) Median F/U 4.1 years
 * Toxicity: treatment-related deaths RT alone 1% vs chemo->RT 8%
 * Outcome: 2-year DFS RT alone 40% vs. chemo->RT 60% (per graph), no difference in LRC. No difference in OS.
 * Conclusion: BEC chemotherapy improves DFS, no impact on OS

 * Prince of Wales Hospital PWH-88, Hong Kong (1988-1991) -- cisplatin, 5-FU
 * Randomized. 82 patients. Ho's classification N3 or LN+ >4 cm. Arm 1) Neoadjuvant cisplatin 100 mg/m2 + 5-FU 1000 mg/m2, 4 weeks later RT 66 Gy with lower neck to 58 Gy, then 4 cycles of adjuvant chemo vs. Arm 2) RT alone. Could boost residual disease after RT to 18-24 Gy in 3 fractions with Ir-192 HDR
 * 2-years; 1995 PMID 7558945 — "A prospective randomized study of chemotherapy adjunctive to definitive radiotherapy in advanced nasopharyngeal carcinoma." (Chan AT, Int J Radiat Oncol Biol Phys. 1995 Oct 15;33(3):569-77.) Median F/U 2.4 years
 * Outcome: 2-year DFS chemo-RT 68% vs. RT alone 72% (NS); OS 80% vs. 80% (NS); no difference in LRC, DM, or time-to-relapse
 * Conclusion: No benefit for sequential chemo-RT

Induction chemo plus chemo-RT vs primary chemo-RT

 * China; 2016 (2011-13) -- "Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial." (Lancet Oncology - Sun)
 * Phase 3, multicenter
 * Stage III-IVB NPX cancer randomized to CRT with cisplatin +/- induction chemotherapy with TPF
 * 3 year FFS (primary endpt) induction 80% vs. none 72% (SS)
 * 3 year OS induction 92% vs 86% (SS)
 * Prince of Wales, Hong Kong; 2009 (2002-2004) PMID 19064973 -- "Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma." (Hui EP, J Clin Oncol. 2009 Jan 10;27(2):242-9. Epub 2008 Dec 8.)
 * Randomized Phase II. 65 patients, Stage III-IVB NPC. Arm 1) Neoadjuvant docetaxel 75 mg/m2 + cisplatin 75 mg/m2 Q3W x2 cycles, followed by concurrent cisplatin 40 mg/m2 with RT vs Arm 2) Chemo-RT alone
 * Outcome: 3-year PFS neoadjuvant 88% vs control 59% (HR 0.49, NS), 3-year OS 94% vs 68% (HR 0.24, SS)
 * Conclusion: Neoadjuvant chemo followed by chemo-RT well tolerated with positive impact on survival

Adjuvant chemo after RT

 * Queen Mary Hospital (Hong Kong)(1995-2001)
 * Randomized, 2x2 design (concurrent chemo vs. none, adjuvant chemo vs. none). Ho's Stage T3 or N2-3 or LN >=4 cm (AJCC 6th II-IV). Arm 1) RT alone vs. Arm 2) concurrent chemo-RT vs. Arm 3) RT + adjuvant chemo vs. Arm 4) concurrent chemo-RT + adjuvant RT. Concurrent chemo was FU prodrug uracil/tegafur, adjuvant chemo was cisplatin/5-FU and vincristine/bleomycin/MTX x3+3 cycles. RT 1995-1997 62.5/25 split course with 1 week break; 1997-2001 68/34 primary and 66/33 neck. If parapharyngeal extension or residual disease, 10 Gy boost
 * 3-years; 2004 PMID 15226332 -- "Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: a factorial study." (Kwong DL, J Clin Oncol. 2004 Jul 1;22(13):2643-53.)
 * Outcome: 3-year concurrent CRT vs. RT alone FFS 69% vs. 58% (NS), OS 86% vs. 77% (p=0.06), LRC 80% vs. 72% (NS), DM 15% vs. 29% (SS). 3-year adjuvant chemo vs. none FFS 62% vs. 65% (NS), OS 80% vs. 83% (NS), no difference on LRC or DM.
 * Conclusion: Trend to improvement with concurrent chemo-RT over RT alone (p=0.06), no benefit to adjuvant chemo

 * Taiwan COG (1994-1999) -- observation vs. cisplatin/5-FU/leucovorin
 * Randomized. 154 patients. Stage IV M0 (AJCC 1992). Arm 1) RT 70-72 Gy vs. Arm 2) weekly cisplatin 20 mg/m2, 5-FU 2200 mg/m2, leucovorin 120 mg/m2 x9 weeks
 * 5-years; 2002 PMID 11955734 -- "A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients." (Chi KH, Int J Radiat Oncol Biol Phys. 2002 Apr 1;52(5):1238-44.) Median F/U 4.1 years
 * Outcome: 5-year OS RT alone 60% vs. adjuvant chemo 50% (NS), RFS 54% vs. 54% (NS)
 * Toxicity: No Grade 3+ mucositis; Grade 3+ leukopenia 2%
 * Conclusion: Adjuvant chemo after RT offers no benefit for OS or RFS

 * Italian NRC (1979-83) -- observation vs. vincristine/cyclophosphamide/adriamycin
 * Randomized. 229 NPC patients, T1N1-T4N3. Complete remission after RT, then Arm 1) observation vs. Arm 2) VCA (vincristine, cyclophosphamide, adriamycin) x 6 monthly cycles. RT 60-70 Gy to primary tumor, base of skull, and involved nodes, negative LN 50 Gy (frequently split course over 8-10 weeks)
 * 4-years; 1988 PMID 3047335 — "Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: results of a 4-year multicenter randomized study." (Rossi A et al. J Clin Oncol. 1988 Sep;6(9):1401-10.)
 * Outcome: 4-year RFS observation 56% vs. chemo 58% (NS), no difference in OS; Similar pattern of failure with distant mets in about 50% who failed.
 * Toxicity: mild to moderate in most patients
 * Conclusion: No benefit for adjuvant VCA chemo
 * Comment: more patients at low risk for distant failure; less active chemo combination

Dose Escalation

 * Queen Mary Hospital; 2006 (Hong Kong)(2000-2004) PMID 16213105 -- "Preliminary results of radiation dose escalation for locally advanced nasopharyngeal carcinoma." (Kwong DL, Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):374-81. Epub 2005 Oct 5.)
 * Retrospective. 50 patients, T3-T4 NPC (Stage III 28%, Stage IVA/B 72%). RT dose: GTV 76 Gy (whole NP, tumor extending outside NP, skull-base erosions, intracranial disease), PTV 70 Gy, enlarged LNs 72 Gy, all given in 35 fractions. 34 patients concurrent cisplatin (initial 11 were RT only to establish safety, subsequent patients offered INT 0099 protocol). Median F/U 2.1 years
 * Outcome: 2-year LRC 96%, DM-free 94%, DFS 93%, OS 92%. 4 recurrences: 2 LR and 2 DM. All patients with recurrence did not have chemo.
 * Toxicity: 1 treatment-related death from adjuvant chemo; 2 late carotid pseudoaneurysms with torrential epistaxis
 * Conclusion: Dose-escalation to 76 Gy combined with chemo is feasible in T3-T4 NPC

Brachytherapy boost
 * Long Beach Memorial Hospital; 2000 (1978-97) PMID 10889385 -- "Brachytherapy for primary and recurrent nasopharyngeal carcinoma: 20 years' experience at Long Beach Memorial." (Syed AM, Int J Radiat Oncol Biol Phys. 2000 Jul 15;47(5):1311-21.)
 * Retrospective. 56 patients (primary n=15, recurrent/persistent n=34, NPC with prior H&N RT n=7). A wide variety of treatments described.
 * Conclusion: Interstitial brachytherapy can be effective

Technique

 * RTOG 0225 (2003-2005) Protocol PMID 19564532 -- "Intensity-Modulated Radiation Therapy With or Without Chemotherapy for Nasopharyngeal Carcinoma: Radiation Therapy Oncology Group Phase II Trial 0225." (Lee N, J Clin Oncol. 2009 Jun 29. [Epub ahead of print])
 * Phase II. Multi-institutional IMRT use. 68 patients, Stage I-IVb NPC (94% WHO type 2-3). IMRT 70/33; if T2b+ or N+ concurrent cisplatin, adjuvant cisplatin/5-FU.
 * Outcome: Prescribed IMRT given to 84%; prescribed chemo 65%. 2-year LC 93%, LRC 89%, DMFR 85%. 2-year PFS 93%, OS 80%
 * Toxicity: Acute Grade 4 mucositis 4%; Late Grade 3 dysphagia 5%, xerostomia 3%. Long-term PEG-dependent 4%
 * Conclusion: IMRT feasible in multi-institutional setting

Reirradiation

 * Guangzhou; 2007 (China)(1999-2005) PMID 17601682 -- "Outcome of fractionated stereotactic radiotherapy for 90 patients with locally persistent and recurrent nasopharyngeal carcinoma." (Wu SX, Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):761-9.)
 * Retrospective. 90 patients with persistent (n=34) or recurrent (n=56) treated with SRT. Median dose 18/3 or 48/6. Median F/U 1.7 years
 * Outcome: 3-year PFS 55%, DSS 57%
 * Toxicity: late complications 19%, 2 fatal hemorrhage
 * Conclusion: SRT effective, lower risk than reported SRS

 * Harvard; 1987 PMID 3597157 — "Re-irradiation of recurrent nasopharyngeal carcinoma--treatment techniques and results." Wang CC et al.  Int J Radiat Oncol Biol Phys. 1987 Jul;13(7):953-6.

Local Radiation in the setting of Metastatic Disease

 * No randomized data currently available, but paradigms adding local radiation to chemotherapy are included in the NCCN guidelines due to the low rates of complete response with chemotherapy alone (~0-20%), the morbidity and mortality associated with local tumor progression in this region, and series showing long term survival in the setting of M1 NPCa.

 * National Cancer Database (NCDB); 2017 (2004-2013) PMID 28433411 -- Rusthoven CG et al, "Metastatic nasopharyngeal carcinoma: Patterns of care and survival for patients receiving chemotherapy with and without local radiotherapy" Radiother Oncol. 2017 Apr 19
 * 718 patients with M1 disease at diagnosis, 39% received chemotherapy alone, 61% receiced chemotherapy and radiation to the primary tumor
 * OS improved with local radiation: median OS 21.4 vs 15.5 months; 5-year OS 28% vs 10%, p<0.001
 * OS benefits remain on multivariate and propensity score-matched analyses, and models accounting for single vs multi-organ metastases and anatomic sites of metastatic involvement
 * RT dose was an independent prognostic factor as both a continuous and categorical variable, with OS benefits observed among patients receiving ≥50 Gy
 * Long-term survival of >10 years was only observed in the RT cohort
 * Conclusion: "This analysis supports strategies incorporating local RT with chemotherapy for mNPC. Prospective trials evaluating RT integration for mNPC are warranted."

 * Memorial Sloan Kettering; 2012 (1999-2008) PMID 22488786 -- Setton J et al, "Definitive treatment of metastatic nasopharyngeal carcinoma: Report of 5 cases with review of literature" Head Neck. 2012 May;34(5):753-7
 * Case series of 5 patients with metastatic nasopharyngeal carcinoma at diagnosis
 * All patients received platinum-based chemotherapy + 70 Gy of radiation
 * At last follow up, 2 had no evidence of diease (at 29 and 91 months). The remaining 3 patients had progression of disease within 12 months of treatment.
 * Conclusion: "Long-term disease-free survival is possible in a select group of patients with M1 disease at presentation treated with platinum-based chemotherapy and definitive radiotherapy."

Proton Therapy

 * Orsay; 2002 PMID 12504770 -- "[Comparison with dose-volume histograms of two conformal irradiation techniques used for the treatment of T4N0M0 nasopharyngeal cancer, one with association of photons and protons and another with photons alone] - [Article in French]" (Noel G, Cancer Radiother. 2002 Dec;6(6):337-48.)
 * Treatment planning. 5 patients with T4N0 NPC, treated with concurrent chemo-RT using combined photon/proton beams. Photons to 44 or 54 Gy using 3D-CRT, proton boost 16 or 26 Gy in 1.8-2.0 Gy/fx
 * Outcome: Conformality ratio for photon/proton plan 3.1 vs. photons only 5.7 for CTV1, no difference for CTV2. Normal tissues favored photon/proton plan
 * Conclusion: Combined photons/protons improve conformality over photons alone

 * Loma Linda; 1999 (1991-1997) PMID 10551231 -- "Nasopharyngeal carcinoma: repeat treatment with conformal proton therapy--dose-volume histogram analysis." (Lin R, Radiology. 1999 Nov;213(2):489-94.)
 * Retrospective. 16 patients with NPC. Initial treatment 50-88 Gy (1 postop RT 50 Gy, 16 primary 65-88 Gy). Retreatment mean dose 62.8 Gy (59.4-70.2 GGE). Mean F/U 2 years
 * Outcome: 2-year LRFS 50%, OS 50%. By DVH coverage "optimal" 83% vs "suboptimal" 17% (SS)
 * Toxicity: No CNS side effects
 * Conclusion: Adequate tumor coverage important for LRC and survival

 * Lawrence Berkely Laboratory; 1992 PMID 1618678 -- "Recurrent locally advanced nasopharyngeal carcinoma treated with heavy charged particle irradiation." (Feehan PE, Int J Radiat Oncol Biol Phys. 1992;23(4):881-4.)
 * Retrospective. 11 patients. Recurrent NPC, with base of skull invasion, CN deficit 64%. Heavy charged particles. Initial treatment median 70.2 Gy (61-81 Gy). Median time to recurrence 1.5 years. Median retreatment dose 50 GyE (32-62)
 * Outcome: LC 45%. 5-year OS 31%
 * Conclusion: Results appear superior to others using conventional photon therapy

 * Harvard; 1989 PMID 2542199 -- "Proton therapy for carcinoma of the nasopharynx: a study in comparative treatment planning." (Brown AP, Int J Radiat Oncol Biol Phys. 1989 Jun;16(6):1607-14.)
 * Treatment planning. Proton vs photon comparison
 * Outcome: Proton superior dose-distribution, increase 5 Gy in median tumor dose, substantial reduction in normal tissue dose
 * Conclusion: Superior dose distribution of protons should translate into improved control and reduced morbidity


text:
Design of Main Memory Database System/Storage Engine Overview

Table of Contents — Previous: Storage Engine — Next: Database Management

Chapter 4: Storage Engine Overview

Storage engine usually takes care of data organization, access methods and transactions in Database Management Systems (DBMS). This is the lowest subsystem in DBMS that interacts with operating system services. Generally, products interact through OS Layer subsystem (wrapper to OS system calls) to ease the porting effort.

Data shall be stored in one of the following components of the computer system
 * 1) Memory
 * 2) Secondary Storage - Disk
 * 3) Tertiary storage - Tape

These components have data capacities, cost per byte, speed ranging over many orders of magnitude. Devices with smallest capacity offer the fastest access speed and have the highest cost per byte.

Current Trend:Tertiary storage are now replaced by disks because of its huge capacity and low cost per byte. Future Trend: Disks are replaced by main memory because of its increase in capacity and decrease in cost per byte.

One disk block transfer takes approximately 5 milliseconds whereas main memory access takes 100 nanoseconds. By keeping the whole database in memory, these disk I/Os are converted to memory access, thereby improves the throughput by many-folds. Memory being a volatile devices losses the data stored in it, when the power goes off. But disk being a non-volatile device keeps the content intact even for long periods when there is a power failure. This makes main memory storage manager difficult to implement. It uses logging and checkpointing mechanisms to cope up with power failure and make the data stored in main memory persistant.

Table of Contents — Previous: Storage Engine — Next: Database Management


text:
Design of Main Memory Database System/Database Management

Table of Contents — Previous: Storage Engine Overview — Next: Allocator

Chapter 5 Database Management

Database is a collection of objects that hold and manipulate data. Every database management system will have a limit on the total number of databases supported. Most of the databases support up to 10K databases per instance. Because of the virtual address space limitation, MMDB may not be able to support 100 databases per instance. Lets assume that database size is set to 100MB, then instance shall support 4 GB/ 100 MB= 40 databases maximum.

Database is a collection of many relational objects such as tables, views, and constraints. A user owns a database; the owners shall give special access to other users.

Functions of Database Management

 * Create and delete databases
 * Grant/Revoke privileges to users to access
 * Grow/Shrink database based on its size
 * Persistency of data
 * Recovery of database in case of system crash
 * Archive/Restore

Validation Techniques for stray pointer writes
This is one of the major concerns in MMDBs during the application development cycle. MMDB expose the actual pointer to data, which may lead the application to do stray pointer write. This will corrupt the data. MMDB should provide a mechanism to detect this and recover the database in the event of corruption.

Database VS Schema
In the ANSI SQL-92 standard, a schema is defined as a collection of database objects that are owned by single user and form a single namespace. A namespace is a set of objects that cannot have duplicate names. For example, two tables can have same name if and only if they both belong to two different schemas.

Schema VS User
There is an implicit relationship between schemas and users. This relationship is so close that, many of the database users are unaware about this. If you create a user, DBMS creates a user and a schema and grants all privileges to the user on the created schema. Some DBMS expect the user to do the above in three different steps.

Default Database, Schema and User
Every DBMS will have at least one default database, schema and user with preset password. This is done to ensure that DBMS is ready to soon after the installation.

Database Security
In a multi-user database management system, DBMS should provide techniques to enable certain users to access selected portions of a database without gaining access to the rest of the database. This is very important, when a large integrated database is to be used by many different users within the same organization. For example sensitive information such as salary should be kept confidential from most of the other database system users. DBMS accomplishes this by having authorization subsystem that is responsible for ensuring security of portions of database against unauthorized access. Another security issue with databases that work across network shall be handled though data encryption. Encryption can also be used to provide additional protection for sensitive portions of database as well. The data is encoded using some coding algorithm. An unauthorized user who accesses encoded data will have difficulty in decoding the data. Authorized users will be given the decryption algorithms using which they shall access the data.

Database Administrator
Database Administrator is the central authority for managing a database system. The DBA’s responsibility include creating, deleting users, changing user passwords, granting privileges to user on database objects and revoking the privileges in accordance with the policy of the organization. DBA is responsible for the overall security of the database system.

Access protection, user accounts and database
1. Whenever a person or group of person s need to access a database system, the individual or group must first apply for a user account. The DBA will then create a new account number and password for the user if there is a legitimate need to access the database. 2. The user must log in to the DBMS by entering account number and password whenever database access is needed. 3. The DBMS checks that the account number and password are valid; if they are, the user is permitted to use the DBMS and to access the database. Application programs can also be considered as users and can be required to supply passwords. 4. It is straightforward to keep track of database users and their accounts and passwords by creating an encrypted table or file with the two fields account number and password. This table can easily be maintained by the DBMS. Whenever a new account is created, a new record is inserted into the table. When an account is canceled, the corresponding record must be deleted from the table. 5. The database system must also keep track of all operations on the database that are applied by a certain user throughout each login session, which consists of the sequence of the database interactions that a user performs from the time of logging in to the time of logging off. When a user logs in, the DBMS can record the user's account number and associate it with the terminal are attributed to the user's account until the user logs off. It is particularly important to keep track of update operations that are applied to the database so that, if the database is tampered with, the DBA can find out which user did the tampering. 6. To keep a record of all updates applied to the database and of the particular user who applied each update, we can modify system log, which includes an entry for each operation applied to the database that may be required for recovery from a transaction failure or system crash. We can expand the log entries so that they also include the account number of the user and the on line terminal ID that applied each operation recorded in the log. If any tampering with the database is suspected, a database audit is performed, which consists of reviewing the log to examine all accesses and operations applied to the database during a certain time period. When an illegal or unauthorized operation is found, the DBA can determine the account number used to perform this operation. Database audits are particularly important for sensitive databases that are updated by many transactions and users, such as a banking database that is updated by many bank tellers. A database log that is used mainly for security purposes is sometimes called an audit trail.

Database Audits
If any tampering with the database is suspected, a database audit is performed, which consists of reviewing the log to examine all accesses and operations applied to the database during a certain time period. When an illegal or unauthorized operation is found, the DBA can determine the account number used to perform this operation. Database audits are particularly important for sensitive databases that are updated by many transactions and users, such as a banking database that is updated by many bank tellers. A database log that is used mainly for security purposes is sometimes called an audit trail.

Types of Databases
Control Database - one

Catalog Database - one

User database - many

Memory Pages
Usually 8 KB. should be same as OS page size.

Table of Contents — Previous: Storage Engine Overview — Next: Allocator


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Design of Main Memory Database System/Transaction

Table of Contents —

Chapter 7: Transaction Management

A transaction is basic unit of work that comprises many database operations. Transactions shall either be committed or rolled back. This means it shall decide whether to submit all the changes to DBMS or to neglet all the changes and take the database state to the state when that transaction started.

Transaction Stages
For recovery purposes, DBMS should maintain the state of the transaction. A transaction state changes are given below
 * Transaction Start
 * Database operations (INSERT, UPDATE, DELETE, SELECT)
 * Commit or Abort

Database operations include read and modifications of data records. The effect of running SELECT statement is read and effect of running INSERT, UPDATE and DELETE is data record modifications.

The commit operation informs the successful end of transaction to the transaction manager. After commit operation, database should be in consistent state and all the updates made by that transaction should be made permanent.

The rollback or abort operation informs the transaction manager that there is an error in one of the operations involved in the transaction and database is in inconsistent state. All the updates made by the transaction must be undone on the database to get it back to the previous consistent state; that is state at which the transaction started.

Transaction pseudo code for money transfer
BEGIN TRANSACTION;

Read account1 balance

If read failed GOTO UNDO;

Reduce Rs 100 from account1 balance

If reduce failed GOTO UNDO;

Read account2 balance

If read failed GOTO UNDO;

Add Rs 100 to account2 balance

If add failed GOTO UNDO;

COMMIT;

GOTO FINISH;

UNDO:

ROLLBACK;

FINISH:

RETURN;

Transaction Properties
Transaction processing guarantees four important properties (referred as ACID properties)

 Atomicity  — Each transaction is treated as all or nothing- it either commits or aborts. If a transaction commits, all its effects remain. If it aborts, all its effects are undone.

 Consistency  — Transactions preserve data consistency; it always takes the database from one consistent state to another consistent state. Intermediate state shall be inconsistent, but commit or rollback operation should again take the database to another new consistent state or to the old consistent state.

 Isolation  — Transactions should be isolated from one another. Even though all transactions run in parallel, updates made by one transaction should not be visible to other and vice versa until the transaction commits.

 Durability  — Transaction commit should ensure that its updates are present in the database, even if there is a subsequent system crash.

Correctness Principle
If a transaction executes in the absence of any other transaction or system error, and it starts with the database in a consistent state, then the database is also in a consistent state when the transaction ends. This means that if we control simultaneous transactions and system errors, transactions always ensure correctness.The former is controlled by concurrency manager and the later is controlled by logging and recovery manager.


text:
User:Mark Botirius

Hello,

I'm new to this and I'm not really sure how it's done yet. Regardless, I've been playing the guitar off and on for over 25 years now and I've been reading over the Music Theory books and articles and I feel I can make a positive contribution in respect to writing a book that will be better understood by the novice or even the non-musician. The current articles seem to me to be extremely technical and complex and I have noticed several comments on the discussion pages that complain that the material requires a background in music theory in order to be understood. I would like to write a book that is basic, easy to read and understand, and provides a solid foundation that will enable the reader to understand and appreciate the more complex and technical information found in the other Wikibooks and articles.

title: User:Mark Botirius


text:
Talk:Organic Chemistry/Foundational concepts of organic chemistry/Electron dot structures

Helium is almost never diatomic (only at millikelvin temperatures), so I think that example should be removed, and perhaps replaced with something like diatomic oxygen. 24.92.255.104 (talk) 21:42, 20 January 2008 (UTC)


text:
Blender 3D: Noob to Pro/Intro to Bezier Curves

Note: Some pictures are outdated.

Bézier Curves

 * First start a new Blender project, and delete the default cube.
 * Press: → Curve → Bezier to create a new curve. Switch to top view  for a clearer look. You may want to zoom in a bit as well.  into Edit mode.

The black line with the extra angled lines like centipede legs coming off it is the Bézier curve. The white or orange dots are the control points, with the ones in the middles of the pink handle lines defining the endpoints of the curve segment.

Press to deselect the selection, so that all the control points turn black, and the lines connecting them turn red. You can on any point to select it; however, selecting a curve endpoint selects the entire handle line passing through it.

You can move a selected point in the usual way, with : note how moving an endpoint causes the curve to bend so it always connects to the endpoint. Moving just a point at the end of a control handle affects the inner part of the curve, making it bend more or less sharply away from the endpoint: try moving one of these points around, and note how the handle gets longer or shorter, and automatically rotates as necessary to remain a single straight line.

Alternatively, you can select an endpoint (which selects the entire control handle, remember) and use to rotate the handle, and  to make it longer or shorter.

Resolution
In the Curve Context in the Properties window, further down you will see the Active Spline panel. (This is only visible in Edit mode.) Note the editable field next to the label “Resolution:”, probably showing “U: 12”. That number governs the number of straight-line segments that the curve is converted into for rendering purposes; the more of these, the smoother the result, but it will add a bit to the render time.

This resolution setting is also used when converting the curve to a mesh.

Extending Your Curve
So far your Bézier curve only has one segment. You can add segments in several different ways:

 * Back in EDIT mode, on an endpoint at either end of the whole curve, and use  to extend a new curve segment connected to the same endpoint. (We won’t say “extrude”, to avoid confusion with a different extrusion function discussed further down.)
 * on an endpoint at either end of the whole curve, and where the endpoint of the new segment will go; the new segment will immediately be added between the previous endpoint and the new one.
 * Select the endpoints of a single curve segment, press and choose “Subdivide” from the menu. This splits the curve segment into two new connected segments.

Note that if you when the selection is not precisely one endpoint of the whole curve, it will add a new handle that is not connected to any part of the existing curve. You can extend from this handle to create a whole set of new curve segments that are still part of the same curve object, even though there are no lines running between this piece of curve and the previous one. You can join two separate pieces of the curve with a new segment by selecting an endpoint of each and pressing.

You can also add new pieces with in Edit mode.

Removing Points and Segments
You can delete any control points by selecting them and using the familiar or. The menu that pops up asks you if you want to remove the “Selected” points, the “Segment”, or “All”.
 * “Selected” removes all points that are part of the same handle(s) as the selected point(s). Removing an endpoint of a curve piece removes the connected segment. Removing an interior endpoint causes the replacement of the curve segments on either side of it with a new one running directly between their remaining endpoints. Thus, the curve piece of which that segment was a part remains a single curve piece afterwards.
 * “Segment” removes a segment between two connected endpoints. If neither endpoint was an endpoint of the curve piece, then the remainder of that piece of the curve becomes two disconnected pieces.
 * “All” removes all of the control points, leaving an empty curve object!

Handle Types
So far, all the handles on your curve have been aligned. This means that adjacent curve segments are guaranteed to join smoothly. If you select a control point and press, you will get a menu allowing you to set other types for the handle:
 * Free means the two parts of the handle on either side of the endpoint are free to rotate independently, so the two curve segments can now meet at a corner.
 * Vector means the selected part of the handle points at the other endpoint of the same curve segment, and will keep pointing that way even if you move either endpoint. If you set the part of the handle from the other endpoint pointing back this way to “Vector” as well, then the curve segment becomes a straight line. However, as soon as you explicitly move the handle itself, it reverts to being “free”.
 * Automatic is like “aligned”, except Blender will automatically adjust the orientation of the handles as you move the endpoints, to try to keep the curve smooth. Moving either end of the handle will change it back to “aligned” type.

2D Versus 3D
At the top of the Shape panel in the Curve Context in the Properties window, you will see buttons labelled “2D” and “3D”. “2D” means the points of the curve are constrained to lie in a single plane, while “3D” means they are free to be located anywhere in 3D space relative to each other. Initially “3D” should be selected.

Try moving one point along the Z axis. Now click the “2D” button, and you should see all the points you moved snap back into the same plane as the rest. Also the “centipede legs” along the curve should have disappeared (their presence indicates a 3D curve). You can alter the orientation of this plane by bing into Object mode and then rotating the whole curve about any desired axis.

Closing, Filling and Extruding
Each curve piece can be individually closed, meaning that an extra curve segment is automatically added between the two endpoints of the piece. This is governed by the “Cyclic: U” checkbox in the Active Spline panel in the Curve Context. Each closed piece of a 2D curve is automatically filled to form a flat surface.

The curve can also be extruded into the third dimension, effectively turning it into a ribbon-like shape. Look for the “Extrude:” editable field in the Geometry panel, and put a nonzero value into that to specify the extrude width.

If you extrude a 2D closed curve, the flat surface becomes a solid object, and the result is a prism—a solid shape with a uniform, but arbitrarily complicated, cross-section.

Scaling and Tilting
Turn your curve into a ribbon by specifying a nonzero Extrude value. Change your view so it is not exactly from the top or bottom, but at some angle. Notice how the ribbon is of constant width and always perpendicular to the plane of your curve.

Select an endpoint, and press. As you move the mouse, you are changing the radius of the endpoint from its default 1.0 value, and this causes a corresponding scale factor to be applied to the width of the ribbon at that point. You can see (and also edit) this radius value in the Properties Shelf, in the Transform panel at the top.

With an endpoint selected, now try (Note: This only has an effect with 3D curves, not 2D ones). Now as you move the mouse, you are applying a tilt angle, which correspondingly alters the angle of the ribbon at that point. This value is also accessible in the Transform panel in the Properties Shelf.

The scale radius and tilt become particularly useful when you apply a bevel shape to the curve—then you will start to get much more complicated shapes than simple ribbons.

NURBS Curves
Start a new Blender document, and get rid of the default cube.

This time, do → Curve → Nurbs Curve, and  into Edit mode. The result looks a bit similar to a Bézier, except there are no control handles, only the segment endpoints. Instead of dragging handles, you can adjust a weighting assigned to each control point. Bring up the Properties Shelf with if it is not already visible. If you have a single point selected, in the Transform panel at the top, you should see four editable fields under the heading “Control Point:”, labelled “X:”, “Y:”, “Z:”, and “W:”. The first three are of course the position of the point; the “W” value is like a gravitational field strength that attracts the curve to the point. Try adjusting this, and see how it influences the shape of the curve near that point.

You can move endpoints in the usual way, but there are no handles to rotate. All the other options for add and deleting endpoints apply as for Bézier curves: or xtend, →Subdivide, eting Select/Segment/All. The curve can be 2D/3D, extruded and cyclic, and each endpoint has a cale radius and a ilt angle. In the “Active Spline” panel in Object Properties, there is an additional “Endpoint: U” checkbox which forces the curve to pass through the endpoints (this is ignored if Cyclic is enabled).

→Curve→Nurbs Circle inserts a NURBS curve with eight control points arranged in a square, “Cyclic: U” enabled, and the weights of the corner points adjusted so the curve is an exact circle.

→Curve→Path inserts a NURBS curve with five control points in a straight line, and the “Endpoint: U” option already checked.

Which Curves To Use?
As mentioned earlier, NURBS curves are heavily used in CAD applications, while Béziers are popular in 2D drawing applications. If you are importing data from these applications, then you won’t have any choice about which one you end up with.

But if you are creating your own curves, then you have a choice. If you have done drawing with Bézier curves a lot, then you should feel at home with them. If you just want simple curves to deform a shape or guide an animation, NURBS curves could very well do the trick—you could even leave the W values at the default, and just add, delete and position points to get a suitable curve.

Extruding from 2D to 3D
You may have noticed you can only modify the curve in two dimensions, and now it's time to explore the third dimension! Extruding is where you define a two dimensional 'profile' shape, and it is 'swept' through space to create a volume.

Noob note Bézier circles are not true circles, they are approximations. For artistic purposes, this may not really matter, but for precision modelling only NURBS circles should be used. This is due to the math used to describe the Bézier and NURBS curves.

Make a Simple Face of Bézier Curves
.
 * Make a curve and fill it: Being sure you are in 2D mode, Use the steps above to create something simple, and fill it in using

Noob note: you may find it easier to use Bézier circles, instead of filling discrete curves.

Note that the eyes and mouth of the face above are parts of the same curve object. Blender can only identify holes in a filled curve if the holes are part of the same object as the outer curve. If you had created four separate curves then filling the outer curve would have covered the eyes and mouth. To create a detached section of a curve, be in edit mode and deselect all the points. Then create new points (you will need two or three) with +. Alternatively you can create the pieces as separate curve objects and join them later with in object mode. You might prefer the alternative way if you don't want a lot of control handles and "centipede legs" to distract you.

Extrude the Simple Face

Set the extrude depth: Click on the Object Data button and find the Geometry panel. (Older versions: find the 'Curve and Surface' box in the Editing tab of the Buttons window.) There is a slider called Extrude. Set the Extrude depth to something other than 0, and probably less than 1.

Behold, your 2d curve has transformed into a neat 3d structure. The great thing is, you can still edit the curve as if it were just 2d, and the changes will update in real time.

Bevel the Simple Face
Now you have an extruded shape, you should start playing around with some of the other curve settings on offer, so here is a description of how the Bevel depth and Bevel resolution sliders work.

Try setting the Bevel depth to a small value, say 0.02. This will cut off all of the sharp edges, and give a bevelled effect all around the shape.

As you may guess, Bevel resolution decides how many times the algorithm divides up an edge. Higher values than 0 result in smooth curves rather than sharp edges, but dramatically increase the number of vertices in the shape.

Try setting the resolution to 3 or 4, you should see an effect like this:


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Self-Reliance Handbook/Rock Construction

Rock Construction

This construction method can be used to create a long-term home. The practice differs from creating a brick homes in that the rock is not going to be a standard size and shape. Care needs to be taken to create the best fit possible especially in the outside facing portion on the wall. Standard clay mortar can be used and when possible shaping of the stones should be attempted. This method is anything but fast but is unrivaled in permanence if done correctly. Even the floor can be of flat stones especially if you have a stream nearby. If water has run over the stone for any length of time the stone will be very smooth.

Depending on the size of the stone you have available to you methods can vary. If you have large stone one wall is sufficient. If the stone is smaller you may need to build and outside and inside wall and as you build them fill them with rounder stones and mortar. The more the temperature varies from room temperature the thicker the walls need to be. Using large rock can increase the thermal mass of the wall. However in cold climates the greatest concern would be the ceiling and roof. This is not an improvised shelter. While the home can be built for next to nothing, best construction methods will require a good set of tools for working the rock. You can get away with only one or two hand tools if you would like and this can even be done with no tools but it increases your need for planning and careful selection for stone placement.

A good combination of clay soil and some type of dried grass can make a great mortar. This may sound like a poor quality home for people living in "modern housing" but don't be fooled. If built as to keep water away from the home especially these homes can last hundreds of years.

Structurally, this type of home can be extremely resilient to bad weather and debris hitting the home. The outside walls on these homes are very thick. If you have the time this home can be built for almost no out of pocket expense and can be fitted at some expense with any modern convenience.


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Volcanoes/Volcanism

Volcanism There are three (3) major types of lavas formed by volcanoes: Mafic, Intermediate, and Felsic. Mafic (Basaltic) %SiO2: < 50% %FeMg: 4% Temp: up to 1500C Viscosity: Low Eruptive Behavior: gentle
Distribution: divergent plate boundaries, hot spots, convergent plate boundaries

Intermediate (Andesitic)
%SiO2: ~60%

%FeMg: ~3%

Temp: ~1000C

Viscosity: Intermediate

Eruptive Behavior: explosive

Distribution: convergent plate boundaries

Felsic (Rhyolitic)
%SiO2: >70%

%FeMg: 2%

Temp: 700C

Viscosity: High

Eruptive Behavior: explosive

Distribution: hot spots in continental crusts (Yellowstone National Park)

 An interesting exception to this classification is the carbonatite volcanoes. These volcanoes have a significant amount of calcium/magnesium carbonates in their magma. While low in Silica and with a low viscosity, which would place these lavas in the mafic class, they are also low in iron and vary in their magnesium. The origin of the CO (typically CO3) in these magmas is a geologic puzzle at present. Is it present in the original magma coming up from the mantle or has it been incorporated by the melting of rocks that the magma has passed through? Solving this puzzle is made harder since there is only one volcano known to have carbonitite lava eruptions in recent times, Ol Doinyo Lengai in the East African Rift Valley. This volcano has a gentle eruptive behavior today but in the past has been explosive. The fossil footprints of Laetoli, Kenya (showing bipedal hominids existing 3.7 million years ago) are preserved in a carbonitite ashfall.

 An interesting, though very technical, article showing how geologists are using chemistry to try to determine the origins of carbonitite magmas is at

title: Volcanoes/Volcanism


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User talk:Dparsons08

Welcome!
Come introduce yourself at the new users page. If you have any questions, you can ask there or contact me personally.--Laleena (talk) 22:35, 20 January 2008 (UTC)

title: User talk:Dparsons08


text:
Muggles' Guide to Harry Potter/Characters/Gabrielle Delacour

Overview
Gabrielle Delacour is Fleur Delacour's sister.

Goblet of Fire
We first see Gabrielle when she is one of the hostages for the Four Champions in the Second Task of the Triwizard Tournament. Each of the Champions is given one hour to rescue that which is most dear to them from the bottom of the lake. Gabrielle is what is most precious to Fleur. Fleur fails in her attempt to reach Gabrielle, and is so relieved when Harry surfaces with her that she runs over and kisses him, and also Ron who had some incidental role in her return.

Gabrielle is present in the audience for the Third Task, though she plays very little part. She does wave to Harry, who waves back at her.

Half-Blood Prince
Gabrielle is mentioned in passing by Fleur as part of her planning for her wedding to Bill Weasley along with the fact that she never stops talking about Harry.

Deathly Hallows
Gabrielle is one of the bridesmaids at the wedding of Fleur Delacour and Bill Weasley. She arrives two days before the ceremony, with Monsieur and Madame (Apolline) Delacour, and follows Fleur around, prattling away at her in French and trying to help out. She flirts with Harry by batting her eyelashes, much to Ginny's annoyance. She served as a bridesmaid alongside Ginny.

Relationships with Other Characters
Gabrielle clearly has a strong connection to her sister.


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Muggles' Guide to Harry Potter/Characters/Walburga Black

Overview
The late Walburga Black is seen only as a portrait on the wall at Number 12, Grimmauld Place, her ancestral home. She is introduced to us by her son, Sirius Black. Her husband was apparently Orion Black, never seen in the books, but mentioned in passing.

Order of the Phoenix
We first see Walburga when Nymphadora Tonks knocks an umbrella stand over in the hall at Grimmauld Place. The curtains covering Walburga's portrait fly open, and she starts cursing the inhabitants of the house, as being Mudbloods and Blood traitors, among other things. Her screaming wakes up the other portraits in the hall, who join in. Nobody can get her to shut up until Sirius appears from the kitchen and wrenches the curtains over her portrait shut. Sirius then comments that he sees Harry has met his mother. He later says that he had been trying to remove her portrait from the wall, but she had apparently put it on with a Permanent Sticking Charm.

When we are later introduced to Kreacher, Sirius tells us that he has been taking instructions for ten years from the portrait of his mad mother. He also, showing a tapestry of the Ancient and Honorable House of Black, mentions that Walburga had evidently burned a hole in the tapestry anywhere there was mention of someone who was not true to her standards of Blood purity. Sirius points out the holes in the tapestry where his name and Andromeda Black's had been, saying that Andromeda had been burned out of the tapestry for daring to marry a Muggle-born, Ted Tonks. Apparently Walburga had also used a Permanent Sticking Charm on the tapestry, because they could not remove that either.

We hear her screaming again when Harry is leaving for school.

While she is certainly still present at Christmas, we don't see much of her then.

Deathly Hallows
When Harry first returns to Grimmauld Place with Ron and Hermione, the portrait of Walburga starts screaming at them as soon as they enter the hall. Harry, as the owner of the house, is able to shut her up quickly with, apparently, a single spell.

While she no doubt remains present in the hall as long as the Trio are there resident, she is part of the house at that point and the Trio don't particularly pay her any heed.

Strengths
Evidently, Walburga was a strong witch, and very strong-willed. Unfortunately, our only experience is with her "half-mad portrait", which leaves us very little to judge by.

Weaknesses
Being a painting, and apparently unwilling or unable to leave her own frame, Walburga can do little apart from scream. Her only way of accomplishing anything is by ordering Kreacher around; in the absence of any commands from the rightful owners of the house (initially Sirius, and later Harry), Kreacher will take Walburga's orders.

Relationships with Other Characters
Walburga was angry with her son Sirius because of his rejection of the Black family Pureblood values, and his leaving the family home to stay with James Potter's parents at age 16. It was because of this apparent sympathy for Muggles that she disowned Sirius, blasting his name off the tapestry of the Black family tree. It was a similar action on the part of her brother Alphard that got him similarly disowned and removed.

Sirius tells us that she had liked Regulus because he had remained true to the family Pureblood beliefs. It is uncertain whether she approved of his becoming a Death Eater, but it is certain that she did not disapprove.

Questions

 * 1) Did Walburga treat Kreacher well, or not? If not, why he talking to, and taking instructions from, her portrait?
 * 2) When did she die?


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Muggles' Guide to Harry Potter/Characters/Gibbon

Overview
Gibbon (no first name given) is a Death Eater who takes part in the battle at the Hogwarts Astronomy tower.

Half-Blood Prince
Gibbon is one of the Death Eaters who takes part in the Battle under the Astronomy Tower at Hogwarts. When we first see him, he is dead; a large, blond Death Eater, who we later learn is Thorfinn Rowle, had tried to kill Remus Lupin, and Lupin had ducked. The curse had hit Gibbon, who had apparently run up to the top of the Astronomy Tower to conjure the Dark Mark, and was then returning to the battle.


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Cookbook talk:Eggplant Parmesan (Melanzane alla Parmigiana) II

Any other improvements to the article?


text:
User talk:64.231.180.31

Join Us!
--Laleena (talk) 23:50, 20 January 2008 (UTC)

title: User talk:64.231.180.31


text:
User:Paolor

See my user page on Wikipedia

title: User:Paolor


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Muggles' Guide to Harry Potter/Characters/Jugson

Overview
Jugson (no first name given) is a Death Eater who takes part in the battle at the Department of Mysteries.

Order of the Phoenix
Jugson is one of the twelve Death Eaters who initially confront Harry and his five companions in the Department of Mysteries. He is first named when Lucius Malfoy is sending parties out to search for Harry and his companions, who have escaped; Jugson is teamed up with Antonin Dolohov. Jugson and Dolohov meet Harry, Hermione, and Neville Longbottom; Harry Petrifies Jugson, shortly after Hermione Silences Dolohov.

Later in the battle, ten Death Eaters face Harry and Neville. We believe two Death Eaters are permanently disabled, one being Nott, and one never named, so we have to assume Jugson is amongst their number, though as Harry doesn't recognize him, he is never named.

Strengths
Obviously one of Voldemort's most trusted Death Eaters, as Voldemort trusted him to try and capture Harry along with a few others of his top Death Eaters.


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XForms/Venn Diagram

Motivation
You want to interactively change Venn Diagram parameters.

Method
Use XForms range controls to change values in a form. Use the bind to concatenate input parameters. Use the incremental attribute to allow the user to see the changes as the range controls change. Sending a submit will alter the Venn Diagram REST parameters.

Link to Executable Example
Load Example Form

Program Code

   </xf:model> Google Venn Diagram Demo <xf:range ref="instance('tmp')/sa" start="2" end="30" step="1" incremental="true"> <xf:label>Size A: </xf:label> </xf:range> <xf:range ref="instance('tmp')/sb" start="2" end="30" incremental="true"> <xf:label>Size B: </xf:label> </xf:range> <xf:range ref="instance('tmp')/sc" start="2" end="30" incremental="true"> <xf:label>Size C: </xf:label> </xf:range> <xf:range ref="instance('tmp')/ab" start="0" end="20" incremental="true"> <xf:label>AB Distance: </xf:label> </xf:range> <xf:range ref="instance('tmp')/ac" start="0" end="20" incremental="true"> <xf:label>AC Distance: </xf:label> </xf:range> <xf:range ref="instance('tmp')/bc" start="0" end="20" incremental="true"> <xf:label>BC Distance: </xf:label> </xf:range> <xf:range ref="instance('tmp')/abc" start="0" end="20" incremental="true"> <xf:label>ABC Overlap: </xf:label> </xf:range> <xf:output ref="chd"> <xf:label>Data:</xf:label> </xf:output> <xf:input ref="instance('tmp')//la"> <xf:label>Label A: </xf:label> </xf:input> <xf:input ref="instance('tmp')/lb"> <xf:label>Label B: </xf:label> </xf:input> <xf:input ref="instance('tmp')/lc"> <xf:label>Label C: </xf:label> </xf:input> <xf:output ref="instance('chart-params')/chd"> <xf:label>Distance Data:</xf:label> </xf:output> <xf:output ref="instance('chart-params')/chdl"> <xf:label>Labels:</xf:label> </xf:output> <xf:submit submission="get-chart"> <xf:label>Create Venn Diagram</xf:label> </xf:submit>

title: XForms/Venn Diagram


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Muggles' Guide to Harry Potter/Characters/Frank Bryce

Overview
Frank Bryce is the elderly Muggle caretaker and gardener of the old Riddle manor in Little Hangleton.

Goblet of Fire
Frank Bryce, a villager from Little Hangleton, had been invalided out of the war (timing suggests this would have been World War II) and had come home, where he had started work for the Riddle family as caretaker and gardener. When the Riddle family, Tom and his parents, had been found dead, he was the natural suspect and had been brought in for questioning; however, when they were unable to find a cause of death, Frank had been released. He had continued to keep the old manor house as best he was able, while it apparently changed ownership several times, and eventually fell vacant, though the village was never entirely sure of him. It was as part of his caretaking duties that, now quite elderly, he happened upon a couple of people who had apparently taken up residence in the house; investigating, he overheard them planning to kill someone, one Harry Potter, and discussing Bertha Jorkins who they had already, apparently, killed. While he is listening to this, a very large snake passes by; Frank is amazed when the snake evidently reports on his presence to the occupants of the room. The two people in the room, Wormtail and Lord Voldemort, then kill Frank.

Albus Dumbledore later remarks that he believes Frank's death is part of a pattern of deaths and disappearances that marks Voldemort's return to power, though the Ministry do not agree.

In the climactic duel between the now-returned Voldemort and Harry, their two brother wands are forced to duel each other. This results in the appearance of the Priori Incantatem effect, in which Voldemort's wand is forced to disgorge the last few spells it has performed. Frank Bryce is one of the five recent victims of Voldemort's wand whose shades appear as a result. Although somewhat shocked and amazed to find out Voldemort was indeed a wizard and that Harry is also one, he nonetheless reveals to Harry that Voldemort killed him, and shows the boy his support as his spell and Voldemort's clash, and as long after as the effect allows.

Weaknesses
Frank Bryce's weaknesses become apparent as we explore his relationship with the village characters. He appears to be very antisocial as a result of the war. This estrangement prevents his correcting the village people's belief that he murdered the Riddles. Though he was proven innocent, people still continue to distrust him. An additional weakness is that he has a stiff leg as a result of the war wound that returned him home. This makes it harder for him to move around, and renders him incapable of chasing the village boys when they tear up the garden or try to damage the big house.


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Muggles' Guide to Harry Potter/Characters/Hepzibah Smith

Overview
Hepzibah Smith is a very old, very rich witch, still vain and convinced of her own beauty, who shows some valuable artefacts to a young Tom Riddle. He is hinted to be a regular visitor to her house, where he buys for Borgin and Burkes.

Half-Blood Prince
In the memories of the house-elf Hokey, we see Hepzibah primping herself in preparation of a visit by Tom Riddle. Tom, acting as a buyer for Borgin and Burkes, is there to make an offer on some Goblin-made armour, but Hepzibah, charmed by him, shows him her two fondest possessions, a cup originally owned by Helga Hufflepuff, from whom she claims distant descent, and a locket owned by Salazar Slytherin. Tom recognizes the locket as being the one that his mother had sold to try and support herself. Shortly afterwards, Hepzibah Smith dies, apparently mistakenly poisoned by Hokey.

Strengths
Hepzibah is incredibly rich and in possession of some very valuable, unique artefacts of wizarding history.

Weaknesses
She is a vain character and is easily won over by Riddle's charm. In her fondness for him she does not seem to notice that he may be dangerous. We note that her house is cluttered, perhaps hinting that she is a disorganised character, at least in her old age.

Relationships with Other Characters
Hepzibah has a lot of fondness for her house-elf Hokey, although Hokey (like most of her kind) does appear to be nothing but subservient - Harry notes that Hokey calls her appearance "lovely", despite the fact that she looks nothing of the sort. Hokey appears to be her company in her old age, so is something of a companion as well as a servant.

She has a very obvious crush on the handsome young Tom Riddle.

Analysis
Hokey and Hepzibah here are used primarily as a means to highlight that Tom Riddle can be exceptionally charming when he chooses to be. Despite being present only as a buyer for a Dark magic store, and despite presenting what would apparently be a laughable offer for items Hepzibah is selling, he has managed to lower Hepzibah's defences to the point that she shows him her dearest treasures.

It may be that, having been exposed to two artefacts of the Founders at once, Tom decides here that the remaining four Horcruxes that he plans will be made of artefacts of the four Founders. We suspect that by this time, he knew where the Diadem of Rowena Ravenclaw was hidden, but may not yet have retrieved it or made it into a Horcrux.


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Muggles' Guide to Harry Potter/Characters/Hokey

Overview
Hokey is the House-elf of Hepzibah Smith. She is extremely old.

Half-Blood Prince
In Hokey's memories, we see Hepzibah primping herself in preparation of a visit by Tom Riddle. Tom, acting as a buyer for Borgin and Burkes, is there to make an offer on some Goblin-made armour, but Hepzibah, charmed by him, shows him her two fondest possessions, a cup originally owned by Helga Hufflepuff, from whom she claims distant descent, and a locket owned by Salazar Slytherin. Tom recognizes the locket as being the one that his mother had sold to try and support herself. Shortly afterwards, Hepzibah Smith dies, apparently mistakenly poisoned by Hokey. Hokey admits responsibility for Hepzibah's death, and goes to Azkaban, but Albus Dumbledore is able to visit her there and retrieve this memory of Tom Riddle.

Weaknesses
Hokey is apparently quite aged, and so may be susceptible to Tom Riddle's flattery and magic.

Relationships with Other Characters
Like all house-elves, Hokey is devoted to her mistress, Hepzibah. Because Hepzibah trusts, and is perhaps slightly infatuated with, Tom Riddle, we believe Hokey also trusts Tom to at least a limited extent.

Analysis
Hokey and Hepzibah here are used primarily as a means to highlight that Tom Riddle can be exceptionally charming when he chooses to be. Despite being present only as a buyer for a Dark magic store, and despite presenting what would apparently be a laughable offer for items Hepzibah is selling, he has managed to lower Hepzibah's defences to the point that she shows him her dearest treasures. It is significant in this case that Hokey does not warn Hepzibah about Tom. We are aware that Tom discounts non-human magical races even more than he does human wizards born of Muggle parents, so we would expect that he would equally abuse or ignore Hokey. That Hokey does not seem to be wary of Tom suggests that he has elected to charm Hokey as well, despite his dislike of her race.


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Template:Could Sherlock Holmes Have Been a Good Geologist?/Page

 Could Sherlock Holmes Have Been a Good Geologist?  Summary — Introduction — The Measurement — Systematizing the Information — The Primary Document — Conclusions and Recommendations — References — Licensing — Discuss


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Could Sherlock Holmes Have Been a Good Geologist?/Summary

The efficiency of a field geologist depends of his/her capacity of observation. The correct observation of a phenomenon contributes to its better understanding and allows a more rational and effective orientation of the investigation. That is why is so important to master the steps that guarantee a correct observation of any phenomenon. These steps are: (1) the perception of the object, (2) the primary observation (first impressions) and (3) the elaboration of a plan for the description of the phenomenon. Here we included the statistical pre elaboration of the data, and a model for the codification of the information during lithogeochemical sampling.


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Could Sherlock Holmes Have Been a Good Geologist?/Introduction

" ‑ I can't explain how I miss it‑

said the Inspector with expression of nuisance.

‑ It was invisible because it was buried in the mud.

If I discovered it, was because I was looking for it."

Sherlock Holmes, in "The Silver Star"

Observation is the basis of all the empiric procedures and is the most elemental form of the scientific knowledge. There isn't any specialty or branch of the sciences where measurements, descriptions or observations in the broad sense of the word, are not carried out. The correct observation of a phenomenon contributes to its better comprehension, also allowing a more rational and effective orientation of the investigation.

A scientific observation not only should supply information about the investigated object, but it must also provoke the formulation of new problems or should reveal new facets of the same problem.

In this paper, we show that observation is an interpretive process and we argue its cyclical character, suggesting the steps to follow during the observation of a phenomenon. We believe it is imperative that the researcher possesses at least an hypothesis or initial idea about of the process under study before beginning its analysis. This way the objective of the observation is reduced to verify the certainty of the hypothesis, on the basis of only a few observations.

Now, the question that needs to be answered is "How can I achieve a correct observation?"


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Could Sherlock Holmes Have Been a Good Geologist?/The Measurement

"-But, ... the height of the murderer...

how could you find it out, if we have never seen the man?

-Dear Watson, you saw me doing measurements in the room.

The distance between two footsteps showed me clearly the size of our man..."

Sherlock Holmes, in "Study in Scarlet".

Measurement is a quantified observation of a phenomenon and it is one of the more commonly forms employed in investigative work. However, almost never the results of a measurement are informative by itself. Therefore, it is necessary to "refine" them to reach to conclusions based on these data. To "refine" the data we suggest two procedures:

a‑ the search for experimental errors, and

b‑ the synthesis of the information.

The search for experimental errors is based on the determination and subsequent correction of the systematic error and the evaluation of the casual error. To determine the systematic error, we use equation (1).

 * $$S_{sist} = 10[\frac{1}{n} ' (\log x_i^a \log y_i)]$$

Where,

Ssist - is the systematic error of the data

xi - is the basic result (the result of the analysis)

yi - is the control result

n - is the amount of data, which in this type of test should be equal or bigger than 100 pair of events.

If the systematic error oscillates between 0.95 and 1.05 (both values included), we can assume that there isn't any systematic error, so we can calculate directly the casual error. Otherwise, we first eliminate this error by subtracting the systematic error to each basic value in the studied sample.

The casual error is calculated using equation (2).

 * $$S_c = 10[\frac{1}{n\sqrt{2}}'(log x_{max_i}^a log x_{min_i})]$$

For quantitative analysis, Soloviov and Matvieiev (1985) indicate that if the casual error is superior to 1.6, we can't relay on the quality of the data. For qualitative or semi-quantitative analysis, other authors (N.A.S.S.S.R., 1983) propose a limit value of 3. In any case, if the casual error is superior to the established limit, it should be recommended the repetition of the analysis with another methodology or with a more accurate equipment.

The synthesis of the information also consists of two stages:

a- The construction of histograms and polygons of frequencies, and

b‑ The statistic pre‑elaboration of the measurements.

The histograms and polygons of frequencies not only permit a graphic and compact representation of the measurements, but they also can give us other characteristics of the sample, such as the existence of outliers values, the value of the modes, the median, the average, etc. (Ostle, 1973; Valls, 1985).

A detailed explanation of the statistic pre‑elaboration of the data remains out of the objective of this paper. Here we will only mention some steps that are common to most of the geological data.

a- Detection and processing of the statistical outliers and of the extreme values of the studied sample,

b‑ Transformation of the data (optional),

c‑ Determination of the Distribution Law (Kashdan et al., 1979),

d‑ Determination of the median and the relative and absolute modes,

e‑ Determination of the mean, the standard deviation, the variability coefficient, and their confidence intervals, and

f‑ The determination of the thresholds.

Though these are not the only possible variables to be calculated, they are sufficient to refine the results, allowing us to present them in a more understandable way. The use of tables and comparative graphics is very recommendable.


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Could Sherlock Holmes Have Been a Good Geologist?/Systematizing the Information

"-Dear Watson -said Holmes approaching to his incredibly detailed and orderly archive

- I am sure that we will find a reference to that type of letter in this file..."

Sherlock Holmes, in "The Hound of the Baskerville"

When most of the variables of the phenomenon under study are well known, and especially when our descriptions have a discreet character, it is very recommendable the use of codified systems for the systematization of the information.

The codification guarantees a uniform observation of the essential parameters of the phenomenon, even when in the process intervene more than one researcher. It also presents the advantage of reducing the subjective factor of the obtained information (Valls, 1990).

The codified information (Kashdan, 1982) is easy to understand, to process, to regroup and study, all of which influences positively in the final quality of the observation and in the rapidity of its interpretation. The codified systems are not difficult to prepare. First we establish the basic parameters that we want to observe or measure at each point, and all possible variables of its results. Don't forget to include always a field under the name "and other" to save any forgetfulness or unexpected result.

Next we order the selected parameters in a logical way and we represent them in card of 3 for 5", for example. The centre of each card and its back will remain free for "irregular" descriptions (those that are extremely variable or when we don't know all their possible behaviors). We will use the edges of the card to codify the information. As an illustration, Figure 1shows a card created by the author for the codification of the lithogeochemical sampling (Valls, 1990).

'''Figure 1. A codified card for lithogeochemical sampling.'''

Each card is an independent and complete unit of information, where we can reflect all the useful information, from the date and hour of the observation until the results of the measurements and analysis accomplished. The combination of these cards will form the database of our investigation than can be easily exported to any computerized data system.


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Could Sherlock Holmes Have Been a Good Geologist?/The Primary Document

"-Mr. Mac, the more practical thing that you could do

in all your life is to lock yourself for three months

to read during twelve ours a day the annals of the crime".

Sherlock Holmes, in "The Valley of the Terror".

The main objective of all this process is to obtain a quality primary documentation, which keeps its informational value even after the publication of the results. When the primary documentation is made correctly, the data can become very useful in the case of a reevaluation of the studied area.

A good primary documentation will fulfil the conditions listed bellow:

a- UNIFORMITY; represented by the same investigator, the same analytical equipment, the same technology or work technique, etc. The use of

codified cards or any other codification method will be of great help to achieve uniformity, mainly in those occasions when more than one person works in the same place.

b‑ PRECISION; all the statistical treatment, experimental designs, etc., most be accomplished with the same degree of precision.

c‑ REPRODUCIBILITY; the observations collected in the primary documentation should answer to some description system that will allow its later verification. All the key samples should have a duplicated.

d‑ READABILITY AND EASY ACCESS; the primary documentation should be located in adequate places, duly ordered, to ease their consultation and conservation. The text, unless it is in microfilms, codified or typewritten, should be written with legible letter. It is expected that the primary documentation will be simple and objective, so that its study will be quick and effective.


text:
Could Sherlock Holmes Have Been a Good Geologist?/Conclusions and Recommendations

Given the importance of a correct observation for the verification of an hypothesis and for the development of the scientific ideas, it is necessary to pay attention to the collection and conservation of the primary documentation.

Before beginning an observation, it is very useful to have an idea or objective defined. This will allow us to verify the accuracy or incongruity of our initial hypothesis, with only some key observations. Also is important to remember that the observation must be selective and interpretive, to become scientific.

Don't "tie" yourself to a hypothesis. It is the hypothesis which must adapt to the facts and not the other way around.

Since observations by themselves are almost never a source of sure and univocal information, it is always advisable to process statistically the obtained results. The calculations proposed in this paper are usually sufficient for the preliminary elaboration of any assemblage of geological measurements.

The practical application of these recommendations, plus a constant search of improvement based in the comparison and the critic analysis of previous observations (you’re own or someone else's) will soon allow you to improve the quality of your observations.

As for the codification of the information, it is recommended chiefly when the studied system is well known and when the observations are accomplished only at independent points, and we assume that among both points does not exist meaningful differences. If so, we recommend establishing a codification system to save time and to increase the interpretive quality of the observations. We are sure that Sherlock Holmes has done it in that way... if he has been a geologist!!!