O steoid osteoma is a relatively common benign primary bone tumor that is typically encountered in young patients, with a male-to-female ratio of 2:1 [START_REF] Kransdorf | Osteoid osteoma[END_REF][START_REF] Unni | s bone tumours: general aspects and data on 11,087 cases[END_REF]. Patients present with pain, which is characteristically more pronounced at night and relieved by nonsteroidal antiinflammatory drugs, especially acetylsalicylic acid [START_REF] Huang | Radiofrequency ablation of osteoid osteoma: difficult-to-reach places[END_REF]. At imaging, this bone-forming tumor consists of a small, round, or oval well-demarcated nidus, with or without central mineralization, associated with a surrounding zone of reactive bone formation [START_REF] Kransdorf | Osteoid osteoma[END_REF]. The lesion is typically associated with adjacent bone marrow and soft-tissue edema. In contrast with osteoblastoma, osteoid osteoma has limited growth potential and usually measures less than 15-20 mm in diameter [START_REF] Yalcinkaya | Clinical and morphological characteristics of osteoid osteoma and osteoblastoma: a retrospective singlecenter analysis of 204 patients[END_REF]. Most osteoid osteomas are found in the appendicular skeleton, with more than half of tumors occurring in the femur and tibia, while spinal osteoid osteoma accounts for 7%-20% of all lesions [START_REF] Rosenthal | Critical review and state of the art in interventional oncology: benign and metastatic disease involving bone[END_REF][START_REF] Tsoumakidou | Percutaneous image-guided laser photocoagulation of spinal osteoid osteoma: A single-institution series[END_REF].

Although percutaneous ablation of such tumors may be performed using any thermal ablation technology, radiofrequency (RF) ablation is the most commonly used technique [START_REF] Rosenthal | Ablation of osteoid osteomas with a percutaneously placed electrode: a new procedure[END_REF][START_REF] Gangi | Osteoid osteoma: percutaneous laser ablation and follow-up in 114 patients[END_REF][START_REF] Rimondi | Radiofrequency ablation for nonspinal osteoid osteomas in 557 patients[END_REF]. Because RF ablation is successful in more than 90% of patients after a single treatment and has a very low complication rate, it has replaced surgery as the firstline treatment option since the late 1990s [START_REF] Rosenthal | Percutaneous radiofrequency coagulation of osteoid osteoma compared with operative treatment[END_REF][START_REF] Rosenthal | Osteoid osteoma: percutaneous treatment with radiofrequency energy[END_REF][START_REF] Lanza | Osteoid osteoma treated by percutaneous thermal ablation: when do we fail? A systematic review and guidelines for future reporting[END_REF].

On the other hand, cryoablation is currently playing an increasing role in percutaneous treatment of bone tumors, affording several distinct advantages over heatbased ablation techniques [START_REF] Callstrom | Percutaneous ablation for bone and soft tissue metastases: why cryoablation?[END_REF]. First, the evolution of the cryosphere generated with cryoablation can be monitored intraprocedurally using intermittent nonenhanced CT scans. The second advantage of the cryoablation systems is that, as opposed to the inductive nature of RF heat generation, the conductive nature of ice formation allows the ice ball to be transmitted across sclerotic bone, which is particularly useful when treating bone-forming tumors such as osteoid osteoma and osteoblastoma [START_REF] Cazzato | Percutaneous Image-Guided Cryoablation of Osteoblastoma[END_REF][START_REF] Poullain | Percutaneous cryoablation of osteoblastoma in the proximal femur[END_REF]. Furthermore, in the setting of osteoid osteoma, cryoablation may even allow the treatment of the lesion from an extraosseous position, avoiding direct placement of the probe tip within the nidus to destroy the tumor [START_REF] Coupal | CTguided percutaneous cryoablation for osteoid osteoma: initial experience in adults[END_REF][START_REF] Santiago | Percutaneous cryoablation for the treatment of osteoid osteoma in the adult population[END_REF]. A third major advantage of this technology is that cryoablation is well tolerated by patients under conscious sedation and is associated with less postprocedural pain than RF ablation [START_REF] Thacker | Palliation of painful metastatic disease involving bone with imaging-guided treatment: comparison of patients' immediate response to radiofrequency ablation and cryoablation[END_REF].

Background: Cryoablation is playing an increasing role in the percutaneous treatment of bone tumors. However, despite its potential advantages over heat-based ablation techniques, the clinical safety and efficacy of cryoablation have not been established for osteoid osteoma treatment.

Purpose:

To evaluate percutaneous CT-guided cryoablation for the treatment of osteoid osteoma in young patients and adults.

Materials and Methods:

This retrospective study reviewed data from 50 consecutive patients who underwent percutaneous CT-guided cryoablation for the treatment of osteoid osteoma between January 2013 and June 2019 in a single institution. In 30 of 50 patients (60%), the procedure was carried out with the patient under local anesthesia and conscious sedation, with the cryoprobe covering the lesion from an extraosseous position, avoiding direct penetration of the nidus. Clinical and radiologic features, procedurerelated data, visual analog scale (VAS) pain scores, complications, and overall success rate were evaluated. Statistical analyses were performed by using the nonparametric Friedman test and Wilcoxon signed rank test for repeated measures.

Results: Fifty patients (median age, 24 years; interquartile range [IQR], 19-38 years; 31 men) underwent CT-guided cryoablation for the treatment of osteoid osteoma, with a 96% (48 of 50 patients) overall clinical success rate. Of the two patients without clinical success, one patient had incomplete pain relief and the other experienced a recurrence of osteoid osteoma at 11 months, which was successfully treated with a second cryoablation procedure. The median VAS pain score was 8 (IQR, 7-8) before the procedure and 0 (IQR, 0-1; P , .001) after the procedure at both primary (6 weeks) and secondary (18-90 months) follow-up. Three of the 50 patients had minor complications (6%); no major complications were reported.

Conclusion:

Osteoid osteoma was safely, effectively, and durably treated with CT-guided percutaneous cryoablation. In the majority of patients, treatment could be performed without general anesthesia, with the cryosphere covering the nidus from an extraosseous position.

Osteoid Osteoma: Percutaneous CT-guided Cryoablation Is a Safe, Effective, and Durable Treatment Option in Adults

Thomas Le Corroller, MD, PhD • Thomas Vives, MD • Jean-Camille Mattei, MD • Vanessa Pauly, PhD • Daphné Guenoun, MD, PhD • Alexandre Rochwerger, MD, PhD • Pierre Champsaur, MD, PhD

to June 2019 were identified by research performed in our institutional radiologic information system (Xplore, EDL). A total of 53 patients were identified. Three patients were excluded because no follow-up data were available after their discharge from the hospital. Consequently, 50 patients were included in the study (Fig 1).

Of note, the initial results for 21 of the 50 patients in this series were reported in a previously published article that evaluated the technical feasibility and preliminary efficacy of percutaneous cryoablation for the treatment of osteoid osteoma [START_REF] Santiago | Percutaneous cryoablation for the treatment of osteoid osteoma in the adult population[END_REF]. In the present study, we evaluate patient outcomes after performing cryoablation treatment of osteoid osteoma in a larger sample of patients.

Preprocedural Evaluation

All patients were referred for treatment by a multidisciplinary tumor board including orthopedic surgeons and musculoskeletal radiologists. Cryoablation treatment was proposed for young patients and adults (age 15 years) with typical clinical presentation, a pain score of 5 or above on a visual analog scale (VAS), and characteristic imaging findings.

Imaging evaluation involved the review of nonenhanced CT scans, MRI scans, and, in some patients, technetium-99m methylene diphosphonate isotope bone scans that were available before the cryoablation procedure. CT scan findings suggestive of osteoid osteoma included the presence of a round or ovoid tumor with a maximum diameter of 20 mm exhibiting a radiolucent nidus, well-defined margins, and surrounding osteosclerosis [START_REF] Kransdorf | Osteoid osteoma[END_REF]. Upon examining the MRI scans, there was evidence of bone marrow edema around the tumor; after intravenous contrast material injection, the nidus showed typical enhancement. When bone scintigraphy was performed, the tumor constantly manifested a focal higher uptake of the radionuclide tracer because of a large vascular supply and high osteoblastic activity.

Cryoablation Technique

All patients were treated by a single operator specialized in musculoskeletal intervention and experienced in performing cryoablation procedures (T.L.C., with 10 years of experience). Between 2 and 8 weeks before the procedure, patients were informed of the cryoablation technique and the benefits and potential complications during a preprocedural consultation with the interventional radiologist. All procedures were performed on an inpatient basis because this is the standard of care for cryoablation in our institution. When possible (30 of 50 patients, 60%), procedures were carried out with the patient under local anesthesia with 1% lidocaine and 0.2% ropivacaine at the skin entry site and periosteum, combined with conscious sedation using nitrous oxide administered by inhalation (50% N 2 O, 50% oxygen; duration, 10-30 minutes). In addition, tramadol (100-200 mg) and paracetamol (1-2 g) were intravenously administered before the procedure for pain management.

However, despite its potential advantages over heat-based ablation techniques, cryoablation has been less thoroughly studied for the treatment of osteoid osteoma than RF ablation and larger studies on clinical results remain lacking [START_REF] Coupal | CTguided percutaneous cryoablation for osteoid osteoma: initial experience in adults[END_REF][START_REF] Santiago | Percutaneous cryoablation for the treatment of osteoid osteoma in the adult population[END_REF][START_REF] Liu | Cryoablation of osteoid osteoma: two case reports[END_REF][START_REF] Wu | CT-guided percutaneous cryoablation of osteoid osteoma in children: an initial study[END_REF][START_REF] Whitmore | Cryoablation of Osteoid Osteoma in the Pediatric and Adolescent Population[END_REF]. Therefore, the aim of our study was to evaluate percutaneous CT-guided cryoablation for the treatment of osteoid osteoma in young patients and adults.

Materials and Methods

Study Design

Institutional review board approval was obtained for this retrospective study, with a waiver for the requirement of written informed consent because the study was a review of clinical and imaging data. All consecutive patients who underwent primary treatment of osteoid osteoma with CT-guided percutaneous cryoablation at a single academic hospital offering tertiary services to adult patients (age 15 years) (Institute for Locomotion, Aix-Marseille Université, Marseille, France) from January 2013 The remaining 20 patients received general anesthesia to allow direct penetration of the nidus (15 of 50 patients, 30%) or because of patient anxiety (five of 50 patients, 10%).

Multidetector CT (LightSpeed VCT 64, GE Healthcare) without contrast material injection was used to localize the lesion and plan the approach. Then, cryoablation was conducted under strict aseptic conditions using a cryoablation system (VISUAL-ICE System, Galil Medical) and a single 17-gauge cryoablation needle with ablation zone diameters measuring either 20 3 27 mm at 220°C (IceSeed 1.5, Galil Medical) or 26 3 32 mm at 220°C (IceSphere 1.5, Galil Medical).

Every time the ablation zone could cover the lesion from an extraosseous position (35 of 50 patients, 70%), the cryoprobe was placed at the cortex, parallel to the lesion, avoiding bone drilling and direct penetration of the nidus (Figs 2,3) [START_REF] Coupal | CTguided percutaneous cryoablation for osteoid osteoma: initial experience in adults[END_REF][START_REF] Santiago | Percutaneous cryoablation for the treatment of osteoid osteoma in the adult population[END_REF]. In the remaining patients (15 of 50 patients, 30%), an 11-gauge bone biopsy needle (Laurane Bone Biopsy Kit, Laurane Medical) was inserted into the bone up to the nidus margin and bone biopsy was performed using a 12.5-gauge trephine needle. Then, the cryoprobe was placed coaxially through the access needle within the nidus (Fig 4). The access needle was finally withdrawn slightly so that the distal 2 cm of the cryoprobe was exposed. To prevent skin injury, a surgical glove filled with warm saline solution was placed on the skin at the puncture area. A freezethaw-freeze cycle was performed with a time frame consisting of two 10-minute freezing phases around an intermediate 8-minute thawing phase, itself divided into a 7-minute passive thawing phase and a 1-minute active thawing phase using either helium gas or helium-free active thawing. However, according to the size of the target lesion and the need for the protection of nearby nontarget structures, freezing cycles were terminated prematurely or reduced in power (60%-100%) when the cryosphere extended within 10 mm of adjacent critical structures such as nerves or cartilage. When necessary, carbodissection allowed the displacement and insulation of vulnerable organs by injecting CO 2 (Fig 3) [START_REF] Garnon | Adjunctive Thermoprotection During Percutaneous Thermal Ablation Procedures: Review of Current Techniques[END_REF]. Intermittent noncontrast CT images were obtained intraprocedurally to visualize the ice ball extension during freezing phases and to monitor for changes in the surrounding tissue. The ablation zone could be observed on CT scans as a hypoattenuating area in the soft tissue but was often less conspicuous within the bone or adjacent to the dense metallic probe in the soft tissue [START_REF] Wu | CT-guided percutaneous cryoablation of osteoid osteoma in children: an initial study[END_REF]. In addition, to evaluate a particular vulnerable motor pathway, the interventional radiologist conducted a focused neurologic physical examination on patients under conscious sedation during the ablation procedure.

Technical success was defined as the ability to visualize the ice ball adequately covering the osteoid osteoma nidus. Signs of complications were monitored if the ablation zone extended into the neurovascular bundle, skin, or articular cartilage [START_REF] Wu | CT-guided percutaneous cryoablation of osteoid osteoma in children: an initial study[END_REF].

After ablation, the cryoprobe was removed and a final CT examination was performed to check for immediate complications. Patients were observed for 30 minutes in the interventional radiology department and then returned to the ward if there was no discomfort. In case of immediate posttreatment residual symptoms, ketoprofen (100 mg) was intravenously administered in addition to the premedication regimen described earlier for a complete prostaglandin blockade. Patients were discharged home the day following the procedure and were asked to limit high-impact athletic activities and cyclic-loading activities during the 4 weeks after treatment. Patient Follow-up All patients were primarily reassessed at 6 weeks after cryoablation to evaluate clinical success and potential postprocedural complications. The postprocedure VAS score was collected at this time. In addition, a follow-up MRI examination was performed on the same day to evaluate the ablation zone and identify potential complications (including stress fractures, osteonecrosis, synovitis, and adjacent tissue damage) [START_REF] Coupal | CTguided percutaneous cryoablation for osteoid osteoma: initial experience in adults[END_REF]. Then, to collect the latest available clinical data, all patients were contacted for secondary follow-up and outcome evaluation between 18 and 90 months after the procedure regarding the recurrence of pain or delayed complications. The VAS score was again collected at that time.

Clinical success was defined as complete relief of pain at the primary and secondary follow-up without the use of any pain medication and with full return to normal activities. Minor complications were defined as complications that resulted in no sequelae, whereas major complications were defined as complications that resulted in prolonged or permanent adverse sequelae [START_REF] Wu | CT-guided percutaneous cryoablation of osteoid osteoma in children: an initial study[END_REF].

Statistical Analysis

Statistical tests were performed by a statistical analyst (V.P., with 10 years of experience) using SPSS software (SPSS). Categorical variables were described using numbers and percentages, and quantitative variables were described using medians and interquartile range (IQR). To test whether there were changes in VAS scores before and after the procedure (6 weeks and 18-90 months after), we performed the nonparametric Friedman test for repeated measures.

Then, two-way comparisons were performed using the nonparametric Wilcoxon signed rank test for repeated measures data. All significance tests were two sided, and P , .05 was considered indicative of a statistically significant difference.

Results

Patient Characteristics Among the 50 patients who were enrolled in the study, there were 31 male and 19 female patients, with a median age of 24 years (IQR, 19-38 years; age range, 15-75 years) (Table 1). Lesions were located in the femur (n = 20), spine (n = 9), tibia (n = 5), humerus (n = 5), talus (n = 4), cuboid (n = 2), coxal bone (n = 1), patella (n = 1), fibula (n = 1), calcaneus (n = 1), and intermediate cuneiform (n = 1). The median ni-dus diameter was 6 mm (IQR, 4-9 mm; range, 3-16 mm). Eight osteoid osteomas (16%) were intra-articular, located in the hip (n = 3), knee (n = 2), midfoot (n = 2), and ankle joints (n = 1).

Cryoablation Treatment

Table 2 summarizes the procedural factors related to cryoablation treatment. The median entire procedure duration was 80 minutes (IQR, 60-100 minutes; range, 40-120 minutes), with an effective cryoablation median time of 28 minutes. The cryoablation procedure was technically successful in 98% of patients (49 of 50), with the ice ball adequately covering the lesion and no sign of immediate complication. In one patient, retrospective imaging review revealed a suboptimal placement of the cryoprobe with an inadvertent eccentric position of the probe tip next to the nidus center and incomplete coverage of the lesion by the ice ball on CT images during ablation [START_REF] Santiago | Percutaneous cryoablation for the treatment of osteoid osteoma in the adult population[END_REF]. Patient Outcomes At 6 weeks, the ablation zone was clearly visible on postprocedure MRI scans in only 27 of the 50 patients (54%), with a "target-like" appearance encompassing the nidus (Figs 2, 5) [START_REF] Santiago | Percutaneous cryoablation for the treatment of osteoid osteoma in the adult population[END_REF]. Median VAS scores were 8 (IQR, 7-8; range, 5-10) before the procedure and 0 (IQR, 0-1; range, 0-5) (P , .001) after the procedure at the 6-week follow-up. At the secondary follow-up (18-90 months), the median VAS score was 0 (IQR, 0-1; range, 0-7) (P , .001) (Table 3). The comparison between the postprocedure pain scores at the primary and secondary follow-up did not show any statistically significant difference (P = .23).

The overall clinical success rate was 96% (48 of 50 patients), with one patient experiencing incomplete pain relief and another experiencing a recurrence of osteoid osteoma at 11 months, which was successfully treated with a second cryoablation procedure. We noted that this single case of recurrence was related to the suboptimal placement of the cryoprobe, described above as a technical failure [START_REF] Santiago | Percutaneous cryoablation for the treatment of osteoid osteoma in the adult population[END_REF]. Interestingly, the patient with incomplete pain relief after cryoablation treatment of a femoral neck osteoid osteoma demonstrated complete resolution of his proximal femur bone marrow edema at follow-up MRI examinations; however, he presented with cam-type femoro-acetabular impingement related to residual hypertrophy of the femoral head-neck junction at the site of tumor ablation (Fig 6). Three of the 50 patients (6%) experienced minor complications: two patients had transient pain and soft-tissue swelling during the week that followed the treatment of midfoot osteoid osteomas, and one patient had mild skin burn at the ankle. No major complications were reported.

Finally, when a bone biopsy was performed before ablation, the diagnosis of osteoid osteoma was histologically proven in only 40% of patients (six of 15), while inconclusive findings were observed in 60% of patients (nine of 15).

Discussion

Cryoablation can provide additional benefits over radiofrequency ablation in patients scheduled for CT-guided treatment of osteoid osteoma. Most importantly, cryoablation treatment can be performed with an eccentric position of the cryoprobe tip with regard to the tumor center as long as the nidus is fully included in the 220°C isotherm. In the majority of osteoid osteomas, ablation can even be performed from an extraosseous position with the cryoprobe placed at the cortex, parallel to the lesion, which avoids bone drilling and direct penetration of the nidus [START_REF] Coupal | CTguided percutaneous cryoablation for osteoid osteoma: initial experience in adults[END_REF][START_REF] Santiago | Percutaneous cryoablation for the treatment of osteoid osteoma in the adult population[END_REF]. However, despite its advantages over heat-based ablation techniques, the clinical safety and efficacy of cryoablation have not been established for osteoid osteoma treatment. Our objective was to retrospectively evaluate patient outcomes after cryoablation treatment of osteoid osteoma. In our study of 50 consecutive patients, osteoid osteoma was effectively treated with percutaneous CT-guided cryoablation, with a significant pain score decrease (P , .001) after the procedure both at the primary and secondary follow-up. In 70% of patients (35 of 50), cryoablation was performed with the cryoprobe placed at the cortex parallel to the lesion, covering the nidus from an extraosseous position, which avoided bone drilling; in 60% of patients (30 of 50), cryoablation was even performed without general anesthesia, providing a faster workflow.

Percutaneous RF ablation for the treatment of osteoid osteoma was first introduced in 1992 by Rosenthal et al [START_REF] Rosenthal | Ablation of osteoid osteomas with a percutaneously placed electrode: a new procedure[END_REF]. Since then, RF ablation has been the most thoroughly studied and commonly performed ablation method for the treatment of osteoid osteoma, with published success rates ranging from 88% to 95% [START_REF] Rimondi | Radiofrequency ablation for nonspinal osteoid osteomas in 557 patients[END_REF][START_REF] Rosenthal | Osteoid osteoma: percutaneous treatment with radiofrequency energy[END_REF][START_REF] Hage | Percutaneous radiofrequency ablation for the treatment of osteoid osteoma in children and adults: a comparative analysis in 92 patients[END_REF]. On the other hand, cryoablation has only recently been applied in the treatment of osteoid osteoma [START_REF] Coupal | CTguided percutaneous cryoablation for osteoid osteoma: initial experience in adults[END_REF][START_REF] Santiago | Percutaneous cryoablation for the treatment of osteoid osteoma in the adult population[END_REF][START_REF] Thacker | Palliation of painful metastatic disease involving bone with imaging-guided treatment: comparison of patients' immediate response to radiofrequency ablation and cryoablation[END_REF][START_REF] Liu | Cryoablation of osteoid osteoma: two case reports[END_REF][START_REF] Wu | CT-guided percutaneous cryoablation of osteoid osteoma in children: an initial study[END_REF][START_REF] Whitmore | Cryoablation of Osteoid Osteoma in the Pediatric and Adolescent Population[END_REF][START_REF] Callstrom | Percutaneous image-guided cryoablation of painful metastases involving bone: multicenter trial[END_REF][START_REF] Auloge | Complications of Percutaneous Bone T umor Cryoablation: A 10-year Experience[END_REF][START_REF] Jennings | Is Percutaneous Bone Cryoablation Safe?[END_REF]. Our data suggest at least equal efficacy between RF ablation and cryoablation for the treatment of osteoid osteoma, which is of particular importance given the additional benefits of cryoablation. W e report a 98% technical success rate with a single case of technical failure, which may be more related to the learning curve phenomenon than to an intrinsic limitation of this ablation technology [START_REF] Santiago | Percutaneous cryoablation for the treatment of osteoid osteoma in the adult population[END_REF]. Our overall clinical success rate was 96%, with one patient experiencing a recurrence of osteoid osteoma related to the suboptimal placement of the cryoprobe described earlier and another experiencing incomplete pain relief secondary to cam-type femoro-acetabular impingement after technically successful treatment of a femoral neck osteoid osteoma. The complication rate was 6%, with no major complications observed. Our results are comparable to the findings of previous case series and preliminary studies describing cryoablation treatment of osteoid osteoma, with reported success rates between 89% and 100%, recurrence rates between 0% and 8%, and complication rates between 0% and 14% [START_REF] Coupal | CTguided percutaneous cryoablation for osteoid osteoma: initial experience in adults[END_REF][START_REF] Lindquester | Percutaneous thermal ablation for treatment of osteoid osteoma: a systematic review and analysis[END_REF].

Special attention was given in our study to the ablation of osteoid osteomas in the more challenging locations that are represented by intra-articular and spinal lesions. First, the treatment of intra-articular osteoid osteoma is associated with a risk of joint damage and cartilage injury [START_REF] Lindquester | Percutaneous thermal ablation for treatment of osteoid osteoma: a systematic review and analysis[END_REF]. In our study, although the number of intra-articular osteoid osteomas was relatively small (eight of 50), we did not observe any joint-specific complications over at least an 18-month clinical follow-up interval. However, we acknowledge that longer term follow-up will be needed to exactly determine the risk of chondrolysis and subsequent osteoarthritis in intra-articular osteoid osteomas. As described earlier, we observed one case of femoro-acetabular impingement after cryoablation treatment of a femoral neck osteoid osteoma related to a residual bump at the femoral head-neck junction. Similar bone changes, such as osteophytes mimicking early osteoarthritis or a widening of the femoral neck, are known to be associated with hip osteoid osteoma [START_REF] Malghem | Osteoid osteoma of the hip: imaging features[END_REF].

Spinal lesions (n = 9) were treated in the same way and given particular attention because of the proximity to critical structures such as the spinal nerves and cord [START_REF] Tsoumakidou | Percutaneous image-guided laser photocoagulation of spinal osteoid osteoma: A single-institution series[END_REF][START_REF] Lindquester | Percutaneous thermal ablation for treatment of osteoid osteoma: a systematic review and analysis[END_REF]. Nevertheless, no transient or permanent neurologic complications were noted in our patients. Protective measures were taken in lesions with less than 10 mm distance between the nidus and the neural structure at risk, with epidural and/or foraminal carbon dioxide insufflation administered during the procedure [START_REF] Tsoumakidou | Percutaneous image-guided laser photocoagulation of spinal osteoid osteoma: A single-institution series[END_REF][START_REF] Garnon | Adjunctive Thermoprotection During Percutaneous Thermal Ablation Procedures: Review of Current Techniques[END_REF][START_REF] Kurup | Avoiding complications in bone and soft tissue ablation[END_REF]. In addition, in patients treated with local anesthesia, real-time functional assessment of nerve function during the procedure provided greater safety in the vicinity of critical neural structures [START_REF] Santiago | Percutaneous cryoablation for the treatment of osteoid osteoma in the adult population[END_REF][START_REF] Kurup | Avoiding complications in bone and soft tissue ablation[END_REF].

Potential disadvantages of cryoablation for the percutaneous treatment of osteoid osteoma should also be discussed. First, cryoablation is theoretically more time consuming than RF ablation because of the typical time frame consisting of two 10-minute freezing phases around an intermediate 8-minute thawing phase. However, in our study, the median duration of the entire procedure was only 80 minutes and varied from 40 minutes for the simplest lesions treated under conscious sedation to 120 minutes for the most complex lesions that needed bone drilling under general anesthesia. Wu et al [START_REF] Wu | CT-guided percutaneous cryoablation of osteoid osteoma in children: an initial study[END_REF] reported in their pediatric case series a mean duration of 90 minutes for the entire cryoablation procedure, which is comparable to the 90-120-minute average duration reported by Rosenthal et al [START_REF] Rosenthal | Osteoid osteoma: percutaneous treatment with radiofrequency energy[END_REF] when using RF ablation. In fact, cryoablation should instead be considered time saving when the patient is treated under conscious sedation, with less time spent in both the CT unit and the postinterventional care unit, providing a faster workflow as compared with RF ablation. Second, because cryoablation does not necessitate a direct approach to the nidus, histologic confirmation of osteoid osteoma was not systematically performed. However, performing periprocedural biopsies before RF ablation of osteoid osteoma may lead to disappointing results because of highly variable histopathologic confirmation rates, regardless of the needle caliber or quality of the sample [START_REF] Laredo | Percutaneous biopsy of osteoid osteomas prior to percutaneous treatment using two different biopsy needles[END_REF]. Finally, the equipment required for cryoablation is more expensive than that for RF ablation, with an average cryoprobe cost approximately three times higher than that of an RF needle. However, cryoablation is associated with less postprocedure pain, less analgesic use, and shorter hospital stays when compared with RF ablation [START_REF] Thacker | Palliation of painful metastatic disease involving bone with imaging-guided treatment: comparison of patients' immediate response to radiofrequency ablation and cryoablation[END_REF]. Cryoablation treatment for osteoid osteoma can even be performed on an outpatient basis in experienced centers as a way to reduce costs [START_REF] Coupal | CTguided percutaneous cryoablation for osteoid osteoma: initial experience in adults[END_REF].

Limitations of our study are mainly the retrospective analysis of data and the lack of systematic histologic tumor verification. First, we acknowledge that the present work is a retrospective, single-arm, noncontrolled, and single-institution study. Because the perception of pain is influenced by a placebo effect, the lack of placebo condition is a major weakness of our study. Thus, cryoablation treatment of osteoid osteoma, while demonstrating promising results, still requires more published data for comparative efficacy. Second, because a major advantage of cryoablation is to allow juxtacortical treatment of osteoid osteoma, we did not perform a biopsy in most patients. Rather, the diagnosis was made preoperatively by a multidisciplinary tumor board and relied only on characteristic clinical and radiologic presentation. Finally, because our institution offers tertiary services to patients aged 15 years and older, we acknowledge that our data may not be generalized to younger patients and believe further research is required to evaluate cryoablation as a new technique for treating children with osteoid osteoma.

In conclusion, our study suggests at least that osteoid osteoma can be safely, effectively, and durably treated with percutaneous cryoablation in the adult population. In most patients, treatment was performed without general anesthesia and cortical drilling, with the cryosphere covering the nidus from an extraosseous position. Overall, our data indicate that cryoablation should be considered in patients scheduled for percutaneous treatment of osteoid osteoma given its additional benefits, such as decreased pain and faster workflow, over radiofrequency ablation.

Figure 1 :

 1 Figure 1: Flowchart illustrates number of patients treated with cryoablation (CA), excluded patients, study population, and follow-up. OO = osteoid osteoma.

Figure 2 :

 2 Figure 2: Images in an 18-year-old man with a right tibia osteoid osteoma. (A) Axial noncontrast T1weighted spin-echo MRI scan demonstrates the 5-mm nidus (arrow) and adjacent cortical sclerosis of the anterolateral shaft of the right tibia. (B) Axial noncontrast CT image shows the intracortical nidus with subtle central mineralization. (C) Axial noncontrast CT image obtained intraprocedurally to visualize the ice ball extension (arrowheads) during the freezing phase. The parallel placement of the cryoprobe is crucial for juxtacortical treatment because the cryosphere does not develop in axis distally from the tip of the probe. (D) Axial fat-suppressed T1-weighted spin-echo MRI scan obtained at 6-week follow-up after intravenous injection of gadolinium-based contrast material shows the ablation zone (arrowheads) with a target-like appearance encompassing the nidus (arrow).

Figure 3 :

 3 Figure 3: Images in a 48-year-old woman with a spinal osteoid osteoma of L4. (A) Axial noncontrast CT image obtained with the patient in the prone position demonstrates the 9-mm nidus (arrow) and adjacent cortical sclerosis of the left pars interarticularis. (B) Axial noncontrast CT image shows the cryoprobe (straight arrow) placed at the cortex parallel to the nidus. Carbodissection allowed the insulation of the dural sac and, most important, the spinal nerve by injecting CO 2 (curved arrow) using a spinal needle placed within the intervertebral foramen. (C) Axial noncontrast CT image obtained intraprocedurally to visualize the ice ball extension (arrowheads) during the freezing phase. Of note, the spinal needle used for carbodissection is only partially seen.

Figure 4 :

 4 Figure 4: Images in a 24-year-old woman with a spinal osteoid osteoma of T8. (A) Axial noncontrast CT image obtained with patient in the prone position demonstrates the 10-mm nidus (arrow) and hyperostosis of the adjacent left rib (arrowheads). (B) Axial noncontrast CT image shows the cryoprobe (arrow) placed within the nidus coaxially through the access needle. (C) Axial fat-suppressed T1-weighted spin-echo MRI scan obtained at 6-week follow-up after intravenous injection of gadolinium-based contrast material shows the ablation zone (arrow) with a target-like appearance of central necrosis and bright edematous periphery.

Figure 5 :

 5 Figure 5: Images in a 26-year-old woman with an osteoid osteoma of the left acetabulum. (A) Axial noncontrast CT image obtained with the patient in the supine position demonstrates a 4-mm intra-articular nidus (arrow) of the anterior acetabulum. (B) Axial noncontrast CT image obtained intraprocedurally shows that to prevent damage to the articular cartilage, treatment was performed in this patient with an eccentric position of the cryoprobe tip (arrow) with regard to the lesion center, still allowing the nidus to be fully included in the 220°C isotherm. (C) Axial fat-suppressed T1-weighted spin-echo MRI scan obtained at 6-week follow-up after intravenous injection of gadolinium-based contrast material shows the ablation zone (arrowheads) encompassing the nidus (arrow). No complications were observed.

Figure 6 :

 6 Figure 6: Images in a 32-year-old man with an intra-articular osteoid osteoma of the left hip. (A) Axial noncontrast CT image obtained with patient in the supine position demonstrates a 3-mm intra-articular nidus (arrow) of the proximal femur. (B) Axial noncontrast CT image shows the cryoprobe (arrow) placed at the cortex parallel to the nidus. (C) Axial fat-suppressed T1-weighted spin-echo MRI scan obtained after intravenous injection of gadolinium-based contrast material shows a small intra-articular nidus (arrow) of the proximal femur with adjacent bone marrow edema and joint effusion. (D) Axial fat-suppressed T1-weighted spin-echo MRI scan obtained at 6-week follow-up after intravenous injection of gadoliniumbased contrast material shows the ablation zone (arrow) with a target-like appearance encompassing the nidus. (E) Axial fat-suppressed T1weighted spin-echo MRI scan obtained at 4-year follow-up after intravenous injection of gadolinium-based contrast material demonstrates complete resolution of the previous nidus and adjacent bone marrow abnormalities (arrow). However, this patient had femoro-acetabular impingement related to residual hypertrophy of the femoral head-neck junction.

Table 1 : Baseline Patient Characteristics

 1

	Characteristic	Value
	No. of patients	50
	Patient age (y)*	24 (19-38)
	Sex
	M	31 (62)
	F	19 (38)
	Tumor size (mm)*	6 (4-9)
	Tumor anatomic location
	Femur	20 (40)
	Vertebra	9 (18)
	Tarsus	8 (16)
	Tibia	5 (10)
	Humerus	5 (10)
	Other	3 (6)
	Tumors in challenging locations
	Articular lesion	8 (16)
	Spinal lesion	9 (18)

Note.-Unless otherwise noted, data are numbers of patients, with percentages in parentheses. * Median value, with interquartile range in parentheses.

Table 2 : Procedural Factors Related to Cryoablation Treatment

 2

	Factor	Value
	Complete treatment duration (min)*	80 (60-100)
	Effective treatment duration (min)	28
	Anesthesia type
	Local	30 (60)
	General	20 (40)
	Cryoprobe position
	Extraosseous	35 (70)
	Intraosseous	15 (30)
	Bone biopsy required	15 (30)
	Technical success	49 (98)

Note.-Unless otherwise noted, data are numbers of patients, with percentages in parentheses. * Median value, with interquartile range in parentheses.

Table 3 : Clinical Outcome after Percutaneous Cryoablation

 3

	Parameter	Value	Observation
	Baseline vs primary	8 (7-8) vs	Significant difference
	follow-up	0 (0-1)	(P , .001)
	VAS score*
	Baseline vs secondary	8 (7-8) vs	Significant difference
	follow-up	0 (0-1)	(P , .001)
	VAS score*
	Clinical success	96 (48)	Recurrence (n = 1),
	rate (%)		persistent pain related
			to hip FAI (n = 1)
	Recurrence rate (%)	2 (1)	Successful treatment
			obtained with a
			second cryoablation
			procedure
	Complication	6 (3)	Soft-tissue swelling
	rate (%)		(n = 2), mild skin
			burn (n = 1)

Note.-Unless otherwise noted, data in parentheses are numbers of patients. FAI = femoro-acetabular impingement, VAS = visual analog scale. * Median value, with interquartile range in parentheses.

n In a retrospective study of 50 consecutive patients, osteoid osteoma was treated with percutaneous CT-guided cryoablation, with a 96% overall clinical success rate.n In 70% of patients (35 of 50), treatment was performed with the cryoprobe placed at the cortex parallel to the lesion, covering the nidus from an extraosseous position, which avoided bone drilling.n In 60% of patients (30 of 50), cryoablation was performed with the patient under local anesthesia combined with conscious sedation, providing a faster workflow.

Abbreviations IQR = interquartile range, RF = radiofrequency, VAS = visual analog scale Summary CT-guided cryoablation should be considered in patients scheduled for percutaneous treatment of osteoid osteoma because it has decreased pain and faster workflow compared with radiofrequency ablation.

Author contributions: Guarantors of integrity of entire study, T.L.C., T.V., J.C.M., D.G., P.C.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; agrees to ensure any questions related to the work are appropriately resolved, all authors; literature research, T.L.C., T.V., J.C.M., D.G.; clinical studies, T.L.C., T.V., J.C.M., D.G.; experimental studies, T.L.C., T.V., J.C.M.; statistical analysis, T.L.C., T.V., V.P.; and manuscript editing, T.L.C., T.V., J.C.M., A.R.

Disclosures of Conflicts of


Treton Cécile
email: cecile.treton@paris.fr

Christian Bourret
email: christian.bourret@u-pem.fr

Dicen

Loneliness and Relational Biography Affective communication

Keywords: loneliness, strategy of relations, emotional social network, age, friendly

This paper addresses the problem of loneliness in the increasing elderly community. This can be considered as a health and social problem. The objective of this research is to identify the relational patterns of the elderly in order to help them recreate a network of relationships suited to their unique needs. The research method examines the dynamics of relationships, which include interactions such alliances and breaks, commonalities and affinities, meeting places, including the use of social networks on the web. Our work is integrated in the field of affective communication as defined by F. Martin-Juchat. The proposed work will rely on observation methods and interviews with elderly and on the notion of situation, described by A. Mucchielli. We want to create a model of intervention which uses narrative methods to understand how a person builds his social network.

I. BACKGROUND AND PURPOSE

The medico-social sector is subject to numerous changes and problems. In this context, there are two aspects that we wish to explore and connect, even though they seem unrelated at first. On one hand, the health sector, led by the goals of streamlining services to the population, explores the development of individualized and modeled benefits, provided remotely through digital technologies in the context of the e-health. On the other hand, the social sector whose demand is increasing in terms of compliance with standards of hygiene, safety and care, is moved by the increasing isolation situations that mainly affect marginalized people, because of their health status, their age, or their social status. It appears that the infrastructure that offers many opportunities for communication and security cannot resolve the appearance of a feeling of loneliness for a growing part of the population. The paradoxical aspect of this situation raises issues pertaining to the humanities. It seems conducive to questions that fall within the field of social innovation in terms of communication sciences. The suffering caused by loneliness disturbs. It emerges in a society characterized by the diversity of its technological possibilities of communication: mobile phones, digital social networking, mails, Web 2.0, etc.

It challenges the institutions. Indeed, E. Durkheim [START_REF] Durkheim | The division and labour in society[END_REF] demonstrated the consequences of the transition from a traditional to a modern society. In traditional society, the family ensures the protection of individual. In modern society, the concept of family disappears and the State supports the vulnerable individual's protection according to common standards. According to S. Paugam [START_REF] Paugam | The social bond[END_REF], the institutions contribute in reality to the emergence of this loneliness. They use intervention models that tend to dehumanize the relational practices perceived only as "services".

Our question is how resolve this deficiency of systems and technologies which seems unable to find a solution to those needs expressed through this feeling of loneliness?

Our research is based on three questions.

With the first question we have attempted to theoretically clarify how individuals build their relational environment? For this, we favored specific approaches belonging to sociology, including structural sociology.

Our second question concerns the meaning that the person gives to its communication activities. Indeed, we consider the person as the driving element of the relation that is established. To answer this question, we borrowed our intellectual support from philosophy and from psychology but also from neurobiology which is very active in the field of emotion and cognition.

Our third question deals with the transformation and is particularly relevant with regard to our subject. The question is to identify if there are possibilities of reorganization of the relational environment of a person and, if there are, how these changes of relation can be developed? This third question is nourished by our tools of investigations applied to the qualitative inquiries which we led, but also by the constructivist and phenomenological approaches, belonging to the sciences of communication and to the sciences of education.

II. METHODOLOGICAL FRAMEWORK

In this sense, our work is integrated in the field of affective communication as defined by F. Martin-Juchat [START_REF] Martin-Juchat | Think the emotional body as a media, anthropology of affective communication[END_REF], who perceives the emotional body as "moved by the emotion" F. Martin-Juchat [START_REF] Martin-Juchat | Think the emotional body as a media, anthropology of affective communication[END_REF], highlights the lack of studies on this emotional dimension, in the field of science of information and communication which is shared between two conceptual approaches. The first concerns the question of the interpersonal relationship and considers the body in terms of signs verbal and nonverbal (gestures). This approach refers to the work of F. Saussure and of the Invisible College of Palo Alto. The second highlights the manipulative attempts of mass media. In both cases, the receiver is not considered in its ability to act as if he had not feelings. According F. Martin-Juchat, [START_REF] Martin-Juchat | Think the emotional body as a media, anthropology of affective communication[END_REF], the receiver's action must be considered as a media. She proposes to put the "emotional body" in the heart of the communication device like a media. This approach requires paradigm shifts on two levels. First, as part of our subject, it needs to change the perception of social actors involved in the implementation of services, particularly those integrate technologies. Moreover, it is dependent on a change in posture of the person himself who becomes actor in the established communication system. By an action research, our goal is to bring the people who suffer of a feeling of loneliness to change their behavior. This transformation process must change the perceptions of actors in their relational environment and modify the perception of the way of seeing the technological communication supports. Our approach takes as reference the paradigm of "engaging communication" to the meaning of F. Bernard [START_REF] Bernard | Link, meaning and action : Towards an engaging communication[END_REF]. The concept of commitment is used to demonstrate the link between the action and the meaning given to action. The commitment depends on the situation. The "engaging communication" is based on the action as a mean of change.

The identification is integrated in the processing of change through the action. The role of a mediator is to create situations conducive to changing actions.

III. RELATIONSHIP IN THE CONTEXT OF AGING

Our work integrates knowledge available in social psychology. The main causes of the sense of loneliness are related to a need for security and a lack of recognition. S. Paugam [START_REF] Paugam | The social bond[END_REF] believes that the feeling of vulnerability expresses a research of security. A. Honneth [START_REF] Honneth | The struggle for recognition[END_REF], N. Elias [START_REF] Elias | Society of individuals[END_REF], D.W. Winnicott [START_REF] Winnicott | Capacity to be alone[END_REF] highlight the need of recognition of individuals. They are shared between the desire to affirm its uniqueness and to be socially approved. The ageing is a stage of life that seems to reactivate these needs. Building on the contributions of sociologists and gerontologists, we find that the old age -estimated at the retirement age -is a period marked by many transitions and changes. V. Caradec [START_REF] Caradec | Sociology of the elderly and aging[END_REF] and P. Pitaud [START_REF] Pitaud | Loneliness and isolation of the elderly[END_REF] observe that the elderly person is faced with a multiplicity of events and ruptures. These changes are due to recurrent affective losses, changes in material and economic living conditions, a decline in physical abilities, often affecting motor skills and the initial conditions of life. The old age is a particularly intense period of identity recomposition. The life changes impact the modes of socialization of the person. C. Bidart [START_REF] Bidart | Studying networks, contributions and prospects for social sciences[END_REF] emphasizes socialization change with age with a tendency to build proximity links and to keep more distance in the relation. She notes the need to more moments of intimacy. For gerontologist M. Billé [START_REF] Billé | Manifesto for age and life, reenchant old age[END_REF], these times of intimacy and relational distancing correspond to the need for "interior narrative work." The elderly need to remember the past to ensure a temporal continuity at their life and preserve a consistent and positive image of their life.

IV. RELATIONAL INVESTIGATIONS AND BIOGRAPHIES

From this theoretical knowledges,we studied the relational dynamics of the elderly in order to highlight their mode of action, the uniqueness of their subjective experience and confirm temporal and spatial changes. We chose to proceed by biographical interviews for two reasons. The biographical interview allows the collection of data revealing the subjectivity of relational experience. It can be used as a means to train the person to take action. As stated by C. Delory-Momberger [START_REF] Delory-Momberger | The biographical condition. Essai on self-narrative in the advanced modernity[END_REF], the biography enables a work on the self images which precede action. We agree with this approach that considers the individual as an agent of his own socialization by the action. This method of data collection takes into account the "emotional body". C. Delory-Momberger notes that it is the place of biographical investment.

We conducted fifteen qualitative interviews with women and men, aged 65 to 99 years, on the theme of friendship.

To analyze the biographies we used categorization method proposed by A. Mucchielli [START_REF] Mucchielli | Situation and Communication[END_REF] through situational semiotics. A. Mucchielli raises the question of social identification. He writes: "Identify the other is a judgement for define him in a specific context. Identify others is a means to give a meaning to my "being" situated also in a context." This method allowed us to establish a frame of reference from a categorization that we have defined. These categories form "interpretive frameworks' of intentions and needs of the actor, its reference standards, its positioning in relation to other actors, the quality of relationships in a historic, temporal and sensory setting. The meaning is defined in a constructivist perspective and shows a schematic representation of the operation of the phenomena studied.

The following table shows an extract of the interpretative grid. Our goal is to highlight three aspects common to all the interviews. We find that relational environment evolves according to life events. Relationships are always built on the same pattern. This pattern is established from emotional factors related to values and beliefs. It shows the specific needs of each person and his way of composing relations through the choice of communication spaces and rhythms of interactions. The study of intentions of people and their recurrent pattern of actions show that there is a proper relationship strategy for each.

V. CHARACTERISTICS OF THE STRATEGY OF

RELATIONSHIP

This work from the interpretations of the actors in their friendly relations helped to highlight the dependence between the events of life and the appearance of new relationships. The person makes a classification and tells for example: "my friends from before." There is therefore a relational biography. Each phase change appears to activate a clean relationship strategy to each person and built on perennial patterns. This strategy is established on the basis of affective elements through values such as the value placed on friendship, beliefs and expectations. They direct the sympathies or antipathies. They provide data on the image that the person has of itself in an idealized form. The relational choices appear homogeneous, standardized, selective based on distinguishing elements of social status, age, etc. These emotional factors determine the level of commitment in the relationship ex. "When they suffer, I suffer." They compose an imaginary of the relationship: "I wanted to have news from him because it was my first love". The person creates, in this case, an ideal relational environment that is considered like a game. This is particularly noticeable when the person uses digital communication media. "I am in relation to a community of artists". The relationship strategy takes the form of ritualized interactions whose rhythm varies among individuals: annual exchange of holidays wishes, weekly meal, evening conversations on Skype, etc. They take singular forms appropriate to the needs of the person such as sharing of activities or friendly moments, or its values: "to give is my life ..." etc. The interactions are located in social contexts and spaces that have a symbolic value as: schools, companies, unions, associations of hikers, etc. They reinforce the value of belonging. These spaces increase connectivity levels cited by G. Simmel [START_REF] Simmel | Studies on forms of socialization[END_REF] and structural sociology (circles, networks). The aging is mentioned systematically in the relational biography. It concerns the disappearance of friendships: "of my generation has disappeared ...", "we were ten friends... we are no more than two". It expresses itself by the regret of the bonds of the past by comparison with those present: "Yes I have had really good friends, it was great ... today, it is different." It indicates a feeling of loneliness evoked on the mode of a battle to fight, "for not to be alone, you have to go out! " The information collected shows activation of affects in the implementation of the social network and the importance of biographical and identity work that is developed. The experience through the implementation of the relationship strategy own to everyone appears as the essential element of identity's recomposition.

The role of emotions in action and the impact on the selfimage of phases of changes were the subject of many studies in the field of neurosciences and the social sciences more broadly. The psychiatrist L. Ciompi [START_REF] Ciompi | Emotions, affects, and affective logic, their places in our understanding of the world[END_REF] states that pure thought does not exist. Cognition is defined "as part of the emotional logic". It defines the affect as "a psychophysical condition, with quality, duration and varying degrees of consciousness" and insists on "the energy aspect of affects." For the neurobiologist A. Damasio [START_REF] Damasio | The feeling of what happens, body, emotions, conscience[END_REF], the affects enable an adaptive learning. The process triggered by the emotion at the level of the body and brain, with the manner whose appears the feeling and his awareness, create new emotional dispositions. He concludes that "emotions are part of bioregulators devices with which we are equipped to survive." Emotion is generated through our experiences. According to P. Ricoeur [START_REF] Ricoeur | Oneself as another[END_REF], it allows man to recompose his understanding of his environment through a phenomenology of desire. P. Ricoeur distinguishes a permanent form of personality, "selfhood", around which are developed changing identities. Researches of A. Damasio confirm this hypothesis and distinguish in the constitution of personality a "central self" of an "autobiographical self." P. Ricoeur emphasizes man's anxiety in front of these continual identity changes. He needs to reassure himself by searching for clues of permanence. According to P. Ricoeur, friendship is "a promise in time of a self-preservation."

VI. CONCLUSION

The theories and works highlighted reveal two crucial needs for the human being related to safety and selfawareness. These needs are expressed through communication with the external environment composed of other people. This constitutes the means for a person to validate their existence through recognition and to strengthen their feeling of protection. The relation which takes shape in the form of mutual identical projections is transformed into attachment when the reliable feeling (implicit protection) evolves and strengthens. This reliable feeling comes along with the certainty of a common cultural belonging which expresses itself through shared activities and symbolic exchanges. This process consolidates the commitment in the relationship.

In this selective configuration, the relation contributes to strengthen a positive self-awareness based on the mutual identification. The aspects of identity are expressed through emotions and feelings. The self-awareness answers a desire of self-idealization through values which direct the emotions. The feelings are the mainspring of the composition of the relational environment because they play beforehand a role in the choice of selected people.

The relation evolves during the relational process between the people and is transformed. It constitutes a story made up of events of which the meeting with the person is a part, and is characterized by the importance of the moments and shared activities. From this point of view, the story of the relation can be the object of a biography characterized by the ascendancy of its emotional contents.

In conclusion, the relationship strategy composed of the elements highlighted in our study in progress shows the importance of the building of the relationship as a sensitive experience. It reveals a space essential to the individual and which seems to correspond to what F. Guattari [START_REF] Guattari | Chaosmose[END_REF] calls "weaving" about the friendship relation. D.W. Winnicott [START_REF] Winnicott | Playing and reality[END_REF] considers that "the experience of the body" goes through a third space, next to the inner space and the emotional environment of the individual, which he called "cultic area". It offers a creative space game. The condition for the individual to invest in this space depends on his confidence level. The feeling of loneliness that we prefer to call "relational vulnerability" in the sense of insecurity and lack of assertiveness, could come from a relational model unsuitable strategy. Our work opens other perspectives. It seems that the question of the relation of elderly to digital communication tools can be studied through the experience felt. These are the tracks that remain to be explored.

Table :

 : study of biographies

			Categorizations
		Biographical frame	characterization of the relationship	Methods activation
	D.	Boarding school Work Marriage Death	Compensatory mode and selective strongly linked to the stages of change and	favors the communal group activity
			emotional traumas
	A.	Childhood Studies Work Travels Marriage Death	Adaptive mode and links marked by complicity siituational Links with family friends value Friendship is a family	friend and ritualized moments : New Year's Day / birthday / holiday
	N.	War/Childhood (holocaust) Marriage Accident (vision loss)	friends by period Selective mode marked by mistrust, emotional distancing, sharing the difficulty, Classification of	search for help, support, taking account of disability

Copyright (c) IARIA, 2015. ISBN: 978-1-61208-447-3

Copyright (c) IARIA, 2015. ISBN: 978-1-61208-447-3 HUSO 2015 : The First International Conference on Human and Social Analytics


Christian Mougin

Jean-Claude Fournier

Michel Alvinerie

Philippe Berny

Dominique Kerboeuf

Jean-Pierre Lumaret

Pierre Galtier

INTRODUCTION

Fate of ivermectin in soil and impact on micro-organisms -Avermectins are a class of macrocyclic lactone drugs with insecticidal and anthelmintic properties, which have been developped for the protection of animals, humans and crops -The intraruminal-sustained release bolus of ivermectin is considered an important advance in the control of endoparasitic nematodes in ruminants because of the long-term protection of animals -High levels of faecal excretion of the drug could induce toxic effects on key dung-colonizing families of insects, and on soil or aquatic ecosystems inhabiting (micro)-organisms → We present here our results concerning the fate of ivermectin in soils, as a basis for exposure assessment, and its impact on bacteria and fungi. Faecal concentrations of ivermectin are obtained after the administration of a sustained-release bolus to calves (initial amount:1.72 g per animal)

EXCRETION OF IVERMECTIN

→ ≈ 1mg/kg untransformed drug is released in faeces during a 4-month period

BIOAVAILABILITY OF IVERMECTIN

Amount of ivermectin measured in the soil solution was 24 ± 14 ng → 0.

LONG-TERM EFFECTS OF IVERMECTIN ON FUNGI

Fungal cultures have been inoculated with spores, without ivermectin (•) or in the presence of the drug (•) at 10 -5 M. The culture were then allowed to grow and sporulate for 10 days. Spores were harvested and the experiments were still repeated 3-times. The spore multiplication factor reflected the ratio between the amounts of spores produced by a culture versus the amounts of spores used for inoculation.

→ Ivermectin diversely affected fungal sporulation, according to the strains → It was without effect on fungal growth (data not shown)

1 -Ivermectin can reach the soil in high amounts after the treatment of cattle with the intraruminal sustained release bolus 2 -In the soil, the drug undergoes minor transformation reactions, only due to photo-isomerization 3 -The bioavailability of ivermectin for soil micro-organisms is very reduced 4 -Ivermectin induces no negative effect on bacteria 5 -It only impacts fungal reproduction, with positive or negative effects according to the strains

FATE•

  2 % of initial amount in soil → 6 µg/L → 10 -8 M soil in darkness Non-sterile soil exposed to sunlight A silt loam from Versailles has been treated with 1 mg/kg ivermectin, and incubated under various conditions for 12 weeks at 25°C. → The drug was only transformed through photocatalysis to isomers 8-9-and 10,11-Z, with a half-life amounting to 21 IVERMECTIN ON BACTERIA No effect of ivermectin (10, 50 and 250 mg/kg) on the number of colony-forming organisms after 15 days on solid media No effect of ivermectin (10, 50 and 250 mg/kg) on the microbial biomass after 15 days in the soil (carbon extracted after fumigation) No effect of ivermectin (10 and 50 mg/kg) on the nitrification of NH4 + in the soil No effect of ivermectin (10 mg/kg) on the mineralization of labeled carbofuran (insecticide) No effect of ivermectin (10, 50 and 250 mg/kg) on the turn-over of microbial carbon (using labeled glucose) in the soil No effect of ivermectin (10 mg/l) on the metabolic activities of soil isolates using Biolog plates → No effect of the drug was detected either on the size of the microbial biomass or functions, even at high concentrations Acknowledgements : this study was supported by INRA (AIP Ecotox) and PNETOX ( contract N° 03177)CONCLUSIONS INDUCTION OF ENZYMATIC ACTIVITIES BY IVERMECTINFungal cultures have been grown in liquid media in the presence of 10 -5 M ivermectin. Enzymatic activities were then measured using colorimetric assays Laccases of T. versicolor after 3 days of Fungal strains, namely Trametes versicolor (•), Fusarium solani (o), Mucor racemosus (▼), and Fusarium solani (∆) have been cultured in liquid media in the presence of ivermectin at various concentrations • Fungal cultures, inoculated with spore suspensions, were allowed to growth in the presence of ivermecin (10 -4 M). The spores produced by the new hyphae have been harvested and counted. (T. versicolor, unable to produce spores, was replaced by P. chrysosporium, another white-rot strain)→ No negative impact of the drug has been evidenced on the fungal biomass production after 4, 8 and 12 days of growth → Ivermectin was also unable to inhibit the germination of fungal spores, even at high concentrations (10 -3 M, data not shown) → The drug diversely affected fungal sporulation, according to the strains Spores produced (% of the controls)