Frédérique Larrarte
email: frederique.larrarte@lcpc.fr

Claude Joannis

Hossein Bonakdari

Qualification and design of flow meter measurement sites within sewer networks ■ AbstrAct Measurement devices are more readily being implemented in sewer networks for a variety of purposes. Selecting the specific sites for conducting these measurements may prove difficult since the efficiency of available devices is heavily dependent on hydraulic conditions. Our research project makes use of numerical and experimental investigations in order to improve the representativeness of measurements performed in sewer networks, by taking into account the specificities of each particular site. The aim here is to develop a methodology for designing the instrumentation of a sewer section, including site qualification, sensor placement and post-processing of measurement results. This paper presents the framework of such a methodology, along with an application for assessing the influence of a 90° bend on velocity fields and the implications identified on flow measurements. Celle-ci est ensuite illustrée par son application à l'influence d'un coude à 90° sur la répartition des vitesses, et ses implications sur une mesure de débit.

IntroductIon

Sewer networks account for a considerable number of engineering facilities. According to data from the IFEN (French Institute for the Environment) [1], 24.8 million housing units were connected to wastewater collection networks in France as of 2004, with a total linear network coverage exceeding 280,000 km. Moreover, financial estimations of the nation's system rehabilitation needs [2] amount to nearly €7 billion over the short term with annual outlays reaching €1 billion so as to keep up with system modernization needs.

These figures suggest the magnitude of the stakes involved when determining how to efficiently manage sewer networks, which constitute a major component in the area of urban water resources management both now and in the future [3]. System operations often differ substantially from hypotheses adopted during the design phase, especially regarding the flow rates actually conveyed through the system. The installation of networked measurement stations is thus a preferred component of any sewer system management policy [4]. Measurement results are interpreted on a deferred time scale and offer a precise view of sewer network performance over a one-year period, which makes it possible to create appropriate indicators focusing on discharge quantities, quality of effluent received at the plant and structural condition of the facilities [2]. Moreover, some of these sensors may be connected as input to real-time management systems, helping optimize the utilization of facility capacity, depending on specific circumstances and particularly during rainfall events. This technical evolution is being backed by regulatory action (joint Ministerial decrees enacted on December 22, 1994 andJune 22, 2007) and the adoption of new standards , which request in detailed terms facility managers to: supervise networks, evaluate network performance, respond quickly in the case of non-systemic malfunctions, and inform the project owner of improvements likely to enhance performance while increasing sewer collection reliability. Though the practice of installing sensors is becoming more widespread, it is still constrained by a lack of sites satisfying the prerequisites, such as a rectilinear network section (without any deposit accumulation), that ensure compliance with safety conditions for both personnel and equipment. Another constraint encountered involves the spatial representativeness of sensor measurements, and more specifically the velocity measurements carried out using Doppler effect sensors within the ultrasonic domain [4, 5].

A research program was launched to develop an effective methodology for qualifying measurement sites and measurement equipment design; program goals consisted of: prequalifying a candidate site by highlighting cases that indicate a favorable profile, unfavorable profile, or potentially favorable while awaiting further investigations;

qualifying the site according to the outcome of such investigations; establishing the procedure for a sensor installation campaign; defining the protocol to interpret sensor output, whereby measured values can be translated into the targeted physical magnitudes; evaluating the level of data uncertainty introduced. -

The present article will describe such a methodology and follow up by demonstrating, on a selected example, the feasibility of these methodological underpinnings, namely the use of generic modeling. This approach involves models that yield results not necessarily dedicated to a single measurement site, but lead instead to a determination of velocity fields both inside circular collector pipes of any diameter and through diversions of any angle.

sIte quAlIfIcAtIon methodology

The measured parameters helpful to managing a sewer system are multifold, yet flow rates tend to be the key element, given that flow rates are critical not only to facility operations but to evaluating pollutant flows as well.

Moreover, the choice of measurement section within a system must acknowledge a number of constraints, including accessibility from the ground surface, safety issues, and service connection to energy and telecommunications networks. These demands placed on the configuration impose matching the measurement target with the instrumentation, in addition to severely limiting investment and operating costs.

Current practices encompass the steps of setting objectives and selecting the site (steps 0 and 1 in Figure 1), and these are to be combined with an empirical assessment of potential problems arising. Such practices tend to be satisfactory, yet difficulties persist, especially involving large-sized collector lines and/or non-standardized cross-sections. Regarding the various recurrent difficulties observed, the following needs to be stated:

Those sites meeting all specification criteria are indeed rare, since the number of unique cases and conditions is fairly high. Compromises must be accepted, yet without necessarily being able to evaluate their consequences (see below); Verification of measurement results often proves difficult and infrequent at the lower end of the flow rate measurement range (i.e. dry weather rates), which in turn limits the ability to calibrate the average velocity calculation and to control uncertainties;

Assessing the risks of silt or sediment deposition can, in certain cases, lead to (bad) surprises. -Some sites do not display chronic sedimentation, yet might temporarily cause problems not easily anticipated or detected by means of simple observation.

Our work program seeks to streamline the guidelines specific to flow meter installation and, where need be, simplify protocol so as to enable measurements at sites exhibiting suboptimal conditions while maintaining control over result uncertainty. This effort has entailed modeling flows, with an emphasis on velocity distribution within a given sewer line volume. Knowledge of this distribution is critical to identifying the representativeness of flow rate measurements derived from velocity sensors. The velocity field adjacent to the line bottom also serves to evaluate sedimentation risks. Since the hydrodynamic model is quite sophisticated to implement in an operational setting, we have sought to develop an intermediate methodology between current empirical practices and a systematic modeling of measurement sites. Figure 1 provides a detailed description of this methodology, with the second and third steps lying at the core and presumably requiring the preliminary completion of generic models. These models would need to depict standard configurations in parametric form, thus facilitating the eventual transposition to real-world situations. When reaching step 4 therefore, the site can be either rejected with a return to step 0 or else qualified with continuation to step 5, during which the measurement point is designed. Another option would be to consider the case uncertain, which leads to introducing a specific modeling approach.

methodology feAsIbIlIty

The methodology feasibility study [7] focuses on the generic model ( seeStep 3) by considering the case study of velocity field evolution in a collector line downstream of a pipe elbow, in order to determine the radius of influence of such a singularity or, on the other hand, the zone with a profile favorable to installing a flow meter for the purpose of measuring velocity.

Singularity index and extent of influence ■

To quantify the influence of a particular singularity on the velocity field, we propose adopting a singularity index at the level of cross-section S x , which is to be based on the average quadratic deviation between a given discretized velocity field and a developed field, as normalized by average velocity:

(1)

where U(x,y,z) is the local velocity in the abscissa section x, calculated from the exit of the elbow bend (Fig. 2); U(∞,y,z) the velocity in a cross-section where the flow is fully developed; and the average velocity in the cross-section.

For information, if the same calculation protocol were applied to compare a uniform field with a developed field, a value of 2.8% would be obtained for a circular cross-section 1.5 m in diameter filled at 55% of capacity. This value might seem small, yet in fact it reflects strong transverse and vertical velocity gradients. Further downstream of this singularity (the notion of downstream infinity will be applicable in the following discussion), velocity equals U(∞,y,z), and the index should equal zero; due to numerical diffusion however, a zero index value is very difficult to obtain. Moreover, for this bent circular collector pipe, simulations indicate that an index value of 0.2% corresponds to the fact that just 10% of the wetted surface area is exposed to a local velocity U(x,y,z) that differs by more than 10% with respect to velocity U(∞,y,z). In addition, this 0.2% value corresponds to the deviation existing between the developed profiles calculated by a single-phase model (where the free surface condition is replaced by a rigid hanging side) and by a two-phase model (where the free surface is modeled).

The singularity index must not therefore be interpreted in absolute value terms, but instead in terms of variations and position within the 0.2%-3% interval. For the following discussion, the 0.2% value will conventionally define the radius of influence downstream of a bend, also known as the re-establishment length and denoted L R .

Parameterization considerations ■

The numerical study is intended to identify parameters with the most sensitive effect on the singularity index and to describe this effect in the most generic form possible, by expressing the singularity index as a function of the parameters yet to be defined, with preference for an adimensional form.

Among the set of parameters capable of varying in actual configurations and exerting an influence on the re-establishment length, let's cite the following: size of collector pipe cross-sectional shape material roughness pipe bend angle bend radius filling height flow velocity slope of the apron. -Even when combining the practical range of variations applicable to each parameter with just a few procedures, the resulting array is still multifaceted and incompatible with the computation time required for each simulation. To explore this avenue further, we established a number of parameters, including: cross-sectional shape: circular roughness: 2 mm angle: 90°. -

The circular shape is standard and encompasses a large number of potential scenarios. The roughness effect was tested during a preliminary step and to remain limited. As for the 90° angle, it would appear to be the least favorable. For the bend radius, we introduced a three-value range: 6 m, 9 m, and 12 m.

For the collector size, we tested the two values of 0.8 m and 1.5 m to span a wide range of situations. This range may be subsequently extended depending on the results obtained. The effect of filling height was examined in detail over the range 0.66 m to 1.2 m, for a filling rate of between 44% and 80%; associating this parameter with an average upstream velocity corresponds to a uniform flow for a 0.04% slope.

Moreover, the effect of average velocity was studied over a range of 0.7 m/s to 1.2 m/s, which corresponds to input conditions according to a uniform flow profile, as determined by water height and a slope varying from 0.04% to 0.1% for a 50% filling rate of a 1.5 m-diameter collector pipe. This range is somewhat narrow and may subsequently be extended.

For the collectors studied herein (see Table 1), flow is turbulent and the Reynolds number is greater than 10 +5 , where D h is the hydraulic radius, g = 9.81 m•s -2 the gravitational acceleration, and υ = 10 -6 m 2 •s -1 the kinematic viscosity of water.

Numerical modeling ■

This study has run the CFX industrial computing code in order to calculate velocity fields in a straight vertical cross-section of sewer pipe. Three-dimensional flow modeling is based on both the mass and motion quantity conservation equations for an average Reynolds number and incompressible flow:

(2)

(3)
where x i represents the Cartesian coordinates, U i the velocity components in the x i direction, ρ the mass density, P the pressure, ν the kinematic viscosity, and the Reynolds tensor components, which describe the effects of turbulent fluctuations on average flow and raise a closure problem with respect to the system of equations. Turbulence models are intended to close the system, by adopting a set of hypotheses that allow determining the Reynolds constraints and hence solving the system.

The computation code relies on a finite volume method with tetrahedral control volumes and a structured Cartesian mesh. The computation domain comprises a circular collector pipe and extends 50 m in length upstream of the elbow and 120 m downstream (Fig. 2).

The upstream boundary conditions are water height h and uniform velocity throughout the cross-section. The upstream length is sufficient to obtain, based on this information, a developed velocity field. A hydrostatic pressure condition is applied downstream (constant water height over the entire length). Flow near the solid walls is modeled by means of a constitutive law, which remains a function of the type of wall [8].

Given the anisotropic nature of flows running inside narrow free-surface channels, we decided to use the turbulence model proposed in [9].

To keep computation times compatible with systematic testing, the free surface is depicted by a rigid hanging side. While this simplification does not extend to representing the "dip phenomenon", i.e. the fact that maximum velocity lies beneath the free surface in the developed flow zone through a narrow channel, it was still selected for four main reasons: The zero shear rate condition at the free surface is well reproduced by this type of numerical simulation and, as a consequence, has been used by various authors [10-12] to numerically simulate free-surface flow;

Downstream of the elbow

Flow direction

While remaining within the non-developed flow zone, the secondary currents of the first type of -Prandtl are critical and the "dip phenomenon" is absent, as could be experimentally verified [13];

Numerical results are in good agreement with experimental findings -

[13];

In the zone where flow is developed, the average quadratic deviation between single-phase and two-phase simulation results is small (less than or equal to 0.2% depending on water height).

results

These simulation results allow describing the influence of an elbow by distinguishing 3 zones downstream of the elbow: a highly heterogeneous zone: the vortex is produced by a centrifugal force that creates secondary n currents of the first Prandtl type. A single and substantial vortex exists, with the maximum velocity of secondary currents on the order of 10% to 25% of maximum velocity U max within the cross-section, where v and w are the velocity components in the transverse and vertical directions, respectively;

a transition zone: the heterogeneity is minimal, but flow is not fully developed; just a single o vortex remains, yet velocity U s is on the order of 2% to 3% of maximum velocity; a zone where flow is developed: medium vortices are produced by the effect of Reynolds con-p straints. Two contra-rotating currents can be observed centered in the middle of the cross-section with a decreasing vertical velocity mid-section (velocity U s equals roughly 2% of maximum velocity).

Influence of filling height ■

In this study, both the diameter and radius of curvature have been fixed. Figure 3 shows the velocity fields at ten times the free-surface width downstream of a 90° bend, featuring a 9 m radius of curvature in a 1.5-m diameter circular collector with an input velocity corresponding to the average value in a uniform flow regime created by a 0.04% slope.

It can be seen that the velocity fields are not symmetrical with respect to the median vertical plane of the collector, in addition to the fact that maximum velocities U max are offset in the direction towards the outerwall regardless of water level.

The singularity indices, lying between 1 and 1.6, correspond to velocities extending locally from 70% at the inner wall to 100% of maximum velocity at the level of the outer wall. We have been able to verify that the ratio of average velocity to maximum velocity in the cross-section remains between 0.85 and 0.87 for the range of water levels investigated, which is in agreement with the range listed in Standard NF EN ISO 748 regarding velocity field exploration methods.

Figure 4 indicates that for a given radius of curvature, diameter and slope, the singularity index immediately downstream of an elbow is greater with lower water height. Influences exerted by diameter and radius of curvature ■ Figure 5 illustrates that for a given filling rate (0.44), the radius of curvature only exerts a small impact on the singularity index, except at very short distances downstream of the elbow. Further downstream, the index tends towards the common value of 0.2. It is also observed that for a given radius of curvature R, the diameter D of the sewer pipe significantly influences the singularity index up to a distance equal to 20 times the free surface width downstream of the elbow.

Influence of average velocity or slope ■

Figure 6 shows that for the targeted range, i.e. 0.70 m/s to 1.20 m/s, the imposed upstream velocity exerts no influence on the adimensional velocity field U/U max . This result is noteworthy for the transposition of generic models, yet would still need to be confirmed over a wider range of velocities. Attempt at generalization ■ Figure 7, which was derived for a slope equal to 0.04% and its associated velocity, indicates that for a given collector pipe diameter and radius of curvature, the re-establishment length decreases slightly with filling rate. For a given filling rate, this length is directly influenced by collector diameter since it drops by 33% when the diameter is halved. It is essential to point out that Dean's number, which is typically defined for flows in closed pipes as the quotient of tube radius divided by elbow radius of curvature, does not lead to a generic formulation of the results displayed below. In time, it would be necessary to express these results with respect to the adimensional numbers yet to be identified.

conclusIon

Incorporating the hydraulic setting is a critical aspect in the design of a measurement point within a sewer collection system, and moreover the measurement cross-section must be chosen in conjunction with an appropriate method and technology. Regarding the example developed herein, the targeted method has been based on measuring average velocity through an entire cross-section. This method can potentially be adapted to a wide array of site configurations, yet the various technologies available all remain sensitive to the spatial distribution of velocities through a section. The prediction of this distribution at a given site for an entire range of hydraulic loadings has required introducing hydrodynamic models, once the particular site proves to be somewhat complex. These studies might also be somewhat cumbersome to conduct. We sought to evaluate the possible contributions of a "generic" modeling of standard configurations in order to approximate the hydraulic behavior of special sites corresponding to these configurations.

On a given example, we examined the benefit and feasibility of adopting such an approach, which entails setting the re-establishment distance of a developed velocity profile downstream of a unique type of singularity, specifically an elbow on a circular sewer collector pipe. A single-phase representation of free surface flow depicts well the major modification in secondary currents caused by the singularity. After creating a singularity index of the velocity field and proposing a conventional definition of re-establishment length, we were able to identify the set of most influential parameters,

  Qualification et conception de sites de mesures débitmétriques en réseaux d'assainissement résumé ■ Afin de répondre à des objectifs aussi bien techniques que réglementaires ou financiers, les besoins en instrumentation des réseaux d'assainissement sont en constante progression. Mais le choix des sites adaptés à l'implantation du matériel de mesures peut s'avérer délicat car les performances de ces matériels sont très tributaires des conditions d'écoulement. Les recherches en cours au GEMCEA combinent des études numériques et expérimentales afin de mieux décrire et prévoir les conditions hydrauliques dans les collecteurs. L'objectif à terme est de disposer d'une méthodologie d'aide à l'instrumentation, incluant la qualification des sites, l'implantation des capteurs et le post-traitement des mesures. Cet article présente d'abord les différentes étapes de la méthodologie.

0

  Figure 1 A detailed view of the methodology proposedto qualify a flow meter measurement site and proceed with instrumentation design

Figure 2

 2 Figure 2Modeled domain

Figure 4

 4 Figure4indicates that for a given radius of curvature, diameter and slope, the singularity index immediately downstream of an elbow is greater with lower water height. Figure 4 also shows that this index decreases and tends towards a common value beyond a width 20 times that at the free surface downstream of the elbow. Note that the index only drops below the threshold value, regardless of water height, at 35 times the free surface width, i.e. 3.5 times further downstream than what was listed in the sensor manufacturer's specifications [14].

Figure 3

 3 Figure 3Velocity field U i /U max at 10*B downstream of an elbow on a 1.5-m diameter collector for various water levels.

Figure 4

 4 Figure 4Influence of water height on the singularity index for a collector with a 1.5-m diameter, 9-m radius of curvature and 0.04% slope.

  figure 5Influence of both elbow radius and diameter on the singularity index for h/D = 44%

figure 7

 7 figure 7Influence of filling rate on the re-establishment length

Table 1

 1 Case study examples.

	Geometry	Diameter (m)	Filling rate (%)	Average velocity	Radius of
				(m/s)	curvature (m)
	Circular	1.5	44	0.65	6
	Circular	1.5	44	0.65	9
	Circular	1.5	44	0.65	12
	Circular	1.5	44	0.85	9
	Circular	1.5	44	1.00	9
	Circular	1.5	44	1.15	9
	Circular	1.5	51	0.73	9
	Circular	1.5	59	0.77	9
	Circular	1.5	75	0.80	9
	Circular	1.5	80	0.83	9

namely filling rate and collector pipe diameter. The influence of radius of curvature seems to be less pronounced, while average velocity has a negligible impact over these test value ranges.

Progress is still needed to refine the expression of results in an adimensional form and assess the influence of other parameters, such as the bend angle of the elbow or cross-sectional shape.

The next step could consist of extending the approach by a parameterization of the re-establishment length of a developed field, in addition to the velocity field in cross-sections located within the disturbed zone. This information could then be combined with a knowledge of spatial sampling carried out by sensors, in order to: optimize sensor implementation inside a given cross-sectional configuration, and specify the corrections to be applied to measurements for the purpose of evaluating both the average velocity and result uncertainty.


Erik Hollnagel

How Resilient Is Your Organisation? An Introduction to the Resilience Analysis Grid (RAG)

How Resilient Is Your Organisation?

An Introduction to the Resilience Analysis Grid (RAG) Erik Hollnagel DRAFT, April 2010

The Difference Between Safety and Resilience

Although there are several different definitions of safety, they all tend to emphasize the importance of avoiding unwanted outcomes (losses, harm, incidents, accidents). The common understanding is furthermore that a higher level of safety corresponds to fewer adverse outcomes -and vice versa. Two illustrations follow:

The International Civil Aviation Organisation (ICAO) defines safety as 'the state in which the risk of harm to persons or of property damage is reduced to, and maintained at or below, an acceptable level through a continuing process of hazard identification and risk management.' The Patient Safety Indicator guide published by the US AHQR (Agency for Healthcare Research and Quality) defines safety as 'freedom from accidental injury,' or 'avoiding injuries or harm to patients from care that is intended to help them.' There is, however, more to safety than avoiding that things go wrong or reducing the number of adverse events. Resilience Engineering argues that it is necessary to focus on what can go right (successes) as well as on what can go wrong (failures). A resilient organisation can recognise when day-to-day operations are at the margins of expected performance and safety, and is able to adjust practice to return the organisation to a less precarious level of functioning. As a practical discipline, Resilience Engineering looks for ways to enhance the ability of an organisation to continue to function in as many different situations as possible. Safety is consequently defined as the ability to succeed under varying conditions, rather than as the ability to avoid unwanted outcomes. The more formal definition is that:

Resilience is the intrinsic ability of a system or an organisation to adjust its functioning prior to, during, or following changes and disturbances, so that it can sustain required operations under both expected and unexpected conditions.

If an organisation is resilient, then it is also safe. This follows from the simple fact that it is impossible for something to go right and wrong -to succeed and to fail -at the same time. If the number of things that go right increase, then the number of things that go wrong will consequently decrease. The opposite is, however, not true, i.e., an organisation that is safe is not necessarily resilient.

The Four Essential Abilities of Resilience

So what does an organisation need to be resilient? Resilience Engineering emphasizes that resilience, and therefore also safety, is something an organisation does, rather than something an organisation has. Resilience Engineering thus emphasizes function over structure and ability over capacity. In order to be resilient, an organisation must be able to certain things, which can be expressed practically by four basic abilities.

The Ability to Respond

A resilient organisation must be able to respond to regular and irregular variability, disturbances, and opportunities. A resilient organisation must know what to do and when to do it. This is the ability to address the actual.

• No system, organisation, or organism can exist unless it is able to respond to what happens -whether that is a threat or an opportunity. Responses must furthermore be both timely and effective so that they can bring about the desired outcomes or changes before it is too late. In order to respond, the organisation must be able to detect something has happened and to recognise it and rate it as being so important that a response is necessary; it must know how and when to respond, and finally have the resources necessary to implement the response.

The Ability to Monitor

A resilient organisation must be able to monitor that which happens, and recognise if something changes so much that it may affect the organisation's ability to carry out current or intended operations. A resilient organisation must know what to focus on -at least for the duration of the current activity or operation. This is the ability to address the critical.

• In order to survive in the long run, an organisation must be able flexibly to monitor both its own performance and developments in the environment, and address potential nearterm threats and opportunities before they become real. Monitoring must be based on valid leading indicators, i.e., reliable precursors for events that are about to happen. (Monitoring cannot be based on lagging indicators, since these by definition are known only after the fact.) Their effectiveness depends on how easy it is to interpret them, which in turn requires a good understanding of how the organisation functions. In the absence of 'leading' indicators are often defined by association or spurious correlations.

The Ability to Anticipate

A resilient organisation must be able to anticipate developments that lie further into the future, beyond the range of current operations. It must be able to consider the possible future events, conditions, or state changes that may affect the organisation's ability to function -either positively or negatively -such as technological innovation, changes in customer needs, new legislation, etc. This is the ability to address the potential.

• Dealing with the potential goes beyond conventional risk assessment. It is not just a question of what could go wrong in organisation (hazards, wrong decisions, technological failures, etc.) or in the immediate environment (raw materials, energy, suppliers, communication, etc.). Dealing with the potential must also consider the organisation's environment in a wider sense such as changes to demands and resources or changes to constraints and opportunities. In order to envisage or imagine these, it is necessary to have an articulated understanding (or model) of the organisation and of the environment in which it must function and survive. To deal with the potential it is necessary to acknowledge that the future is uncertain and be willing to bet on new ways of thinking.

The Ability to Learn

A resilient organisation must finally be able to learn from experience. It is necessary to understand what has happened, and be able to learn the right lessons from the right experience. This is the ability to address the factual.

• Future performance can only be improved if there is a change in behaviour as a result of experience. In order to learn, it is necessary that there are frequent opportunities to learn, that events have some degree of similarity, and that it is possible to confirm that something has been learned. (That is why it is difficult to learn from rare events.) The effect of learning is that behaviours change so that some outcomes become more likely and others less likely. If there is no change in behaviour, then probably nothing has been learned. And if the changes go in the wrong direction, then the wrong lessons have been learned.

In learning from experience it is important to separate what is easy to learn from what is meaningful to learn. Compiling extensive accident statistics or populating data bases is not the same as learning. In fact, since the number of things that go right, including near misses, is many orders of magnitudes larger than the number of things that go wrong, it makes sense to try to learn from the former as well as the latter.

How Resilient Is Your Organisation?

Since resilience is defined by the organisation's ability to adjust its functioning to expected and unexpected conditions, a resilience 'measure' will be different from traditional measures of safety. And because resilience refers to something that the organisation does rather than to something that it has, it is not possible to represent resilience by a single or simple measurement. The solution is to assess each of the four abilities that together define resilience. This can by done by means of a Resilience Analysis Grid, i.e., four sets of questions where the answers can be used to construct a resilience profile.

The detailed assessment of the four abilities requires some competence in resilience engineering and safety management, but mostly a good knowledge of how the organisation operates. The starting point for the assessment is four sets of generic questions, which, of course, must be tailored to address the specifics of the target organisation. Since a detailed assessment does require some effort, it may be useful to begin by considering the four 'wholesale,' and to rate them using the categories of <excellent | satisfactory | acceptable | unacceptable | deficient | missing>, for example.

When giving the answers, it is essential to keep in mind that the purpose is to rate the typical way in which the organisation works rather than to 'score' recent accidents and incidents. The rating should describe how well the organisation normally is able to do something, rather than how badly things can turn out.

Resilience Engineering cannot prescribe a certain balance or proportion among the four qualities. For a fire brigade, for instance, it is more important to be able to respond to the actual than to consider the potential, while for a sales organisation the ability to anticipate may be just as important as the ability to respond. But it is clearly necessary for any organisation to address each of these qualities to some extent in order to be resilient. All organisations traditionally put some effort into the ability to respond to the actual. Many also put some effort into the ability to learn from the factual, although often in a very stereotypical manner. Fewer organisations make a sustained effort to monitor the critical, particularly if there has been a long period of stability. And very few organisations put any serious effort into the ability to anticipate the potential.

Apr 10 © Erik Hollnagel, 2010 1

Apr 10 © Erik Hollnagel, 2010

© Erik Hollnagel, 2010

Apr 10 © Erik Hollnagel, 2010 6

Overall Assessment of the Organisation's Degree of Resilience

By way of illustration, the four main abilities can be evaluated using the following brief questionnaire.

The ability to respond: How ready is the organisation to respond and how able (quickly and efficiently) is it to respond when something unexpected happens?

The rating of this ability can be helped by asking some more detailed questions, for instance:

• How complete is the set of events for which the organisation is ready to respond?

• How fast can a response be given and how long can it be sustained?

• How is the readiness to respond ensured and maintained?

The ability to monitor: How well is the organisation able to detect smaller or larger changes to work conditions (internal and/or external) that may affect the organisation's ability to carry out current or intended operations?

The rating of this ability can be helped by asking some more detailed questions, for instance:

• How does the organisation monitor the situation and how are the indicators defined?

• How is the validity of the indicators established?

• How are the 'readings' used and communicated? The rating of this ability can be helped by asking some more detailed questions, for instance:

• How does the organisation (or people in charge) think about the future? What is the 'model of the future' that the organisation uses?

• How long is the organisation's time horizon (for instance, number of years)?

• How is the cost-benefit of investments in the future established?

The ability to learn: How well does the organisation make use of formal and informal opportunities to learn from what happened in the past?

The rating of this ability can be helped by asking some more detailed questions, for instance:

• How selective is the basis for learning? Does the organisation consider both failures and successes?

• How often does the organisation try to learn? Continuously or when something has happened?

• How is learning expressed? (rules, procedures, attitudes, skills, etc.)?

Balancing the Four Abilities

The four basic abilities are represented symbolically in Figure 1.


François De Larrard

The High-Performance Cementitious Material (HPCM), a Cousin of UHPFRC for Long-Life Pavement

Keywords: Abrasion resistance, Calcined bauxite, Cracking, Fatigue, Fibres, Freeze-and-thaw, Long-life pavement, Restrained shrinkage, Ultra-high performance concrete

Under the framework of OECD/CEMT JTRC, an international team of road research laboratories worked together in order to evaluate technical solutions for long-life pavement. As a matter of fact, there are in many countries highly trafficked road sections where any traffic disruption brings high external costs. For such a case, the aim was to study wearing courses that could last several decades with no maintenance. The paper presents an innovative technical solution, called HPCM (High-Performance Cementitious Material), consisting of a thin layer of ultra-high performance fibrereinforced mortar with calcined bauxite aggregate embedded in the surface at the fresh state. Many laboratory and two full-scale tests were carried out, dealing with surface resistance (abrasion, wear, shocks, freeze-and-thaw, acid attacks), cracking under restrained shrinkage and fatigue resistance due to heavy traffic loading. New projects were launched recently to continue this coordinated research: a French national project called CLEAN, and an international project called LLPS3. Both of them aim at building circulated road sections to fully validate this promising technology.

.

Introduction

Under the framework of OECD (Organisation for Economic Cooperation and Development), ECMT (European Conference of Ministers of Transport) and their Joint Transport Research Centre (JTRC), a number of road laboratories have worked together to develop the concept of a long-life wearing course for highly trafficked pavements. As a matter of fact, pavements usually consist in base and subbase layers, which last 20-40 years or more, covered by a wearing course having a much shorter life expectancy (typically 7-15 years). However, maintenance works for these surface layers are less and less accepted, and induce high external costs. The first phase of the JTRC-IM3 project (LLP 1) indicated through an economic analysis, that, for some specific applications, it was worth studying technical solutions that could extend the service life for up to 20, 30 or 40 years, with no maintenance nor traffic disruption during this period [START_REF]Economic evaluation of long-life pavements[END_REF]. In Phase 2 of the project (LLP 2), two technical families were evaluated; a bituminous and a cementitious surfacing. The innovative High-Performance Cementitious Material (HPCM) solution consists of applying an 8-mm layer of ultra-high performance, fibre reinforced fine mortar, in which hard, polish-resistant aggregate particles are embedded [START_REF] De | Preliminary tests on a hydraulic surface dressing for wearing courses with a long life[END_REF][START_REF] De | A high-performance cementitious surface dressing for long-life wearing courses[END_REF][START_REF] Oecd/Ecmt | Long-Life Surfaces for Busy Roads -Economic evaluation of longlife pavements. Phase II[END_REF][START_REF] De | A cementitious long-life wearing course to reduce frequency of maintenance works on high-traffic roads[END_REF]. The paper gives the results of the HPCM material development. In conclusion, the perspectives opened by this new technology are briefly presented, together with the programme of two recently launched new projects, including the phase 3.

Design of the HPCM complex

One of the most important requirements of a wearing course is the need for good skid resistance, which is dependent upon the aggregate in the surfacing. For a long-life top layer, it is thus necessary to choose an aggregate with a superior polishing resistance. According to general experience, calcined bauxite, an artificial aggregate obtained by subjecting a natural mineral to a thermal treatment, is recognised as one of the best solutions. However, it is an expensive material, with limited suppliers: its unit cost may range from 30 to 40 times that of ordinary aggregates. Therefore, a surface dressing which only comprises a single layer of particles is relevant. Among available aggregate fractions, the 3-7 mm size has been chosen, because a maximum size of aggregate of around 6 mm tends to be the optimum size when a combination of adequate skid resistance and limited noise emission is required.

The next requirement is the design of the binder, the key function of which is to stick the calcined bauxite chippings to the pavement. When the option of using a hydraulic binder is taken, one must develop a fine material with the maximum tensile strength obtainable on site. From the experience gained with the ultra-high performance concretes [START_REF] De | Optimization of Ultra-High Performance Concrete by Using a Packing Model[END_REF][START_REF] Richard | Les bétons de poudres réactives (BPR) à ultra-haute résistance (200 à 800 MPa)[END_REF], a design mix of sand, Portland cement, silica fume, superplasticizer and water, with a low water/binder ratio is suitable. As in the ultra-thin white topping technology [START_REF] Rasmussen R | Thin and Ultra-Thin Whitetopping -A Synthesis of Highway Practice[END_REF], a good bond is expected between the cementitious mortar and the bituminous substrate. However, due to the shrinkage of the mortar which will be restrained by the pavement structure, cracking is likely to occur. To limit the crack opening, some sort of reinforcement is needed, but, given the thinness of the mortar layer, only fibres added to the mix are appropriate. The thickness of this fibre-reinforced mortar should be minimal for economic reasons. However, it should prevent the chippings from coming into direct contact with the asphalt layer. Moreover, the chippings/mortar composite should form a strong protecting layer for the lower pavement layers. Thus a thickness of 8 mm is selected for the mortar. As for the mixture proportions, three ratios were fixed arbitrarily: the water/cement ratio (0.2), the silica-fume/cement ratio (0.2) and the dry superplasticizer/cement ratio (0.003), based on previous experience. As for the fibrous reinforcement, both the type and dosage rate of the fibres had to be determined later, after the results of some specific tests.

A first mortar recipe was developed and tested among the different participants. Later, it was adjusted in order to get a more stable rheological behavior at the fresh state and a better bond, thanks to a softer consistency. Table 1 displays the optimised recipe used in most of the tests performed during the project. This mortar had to incorporate fibres in order to resist to the shrinkage-induced tensile stresses.

Plain mortar tests

Table 2 displays the main mechanical properties of the mortar, with 4% PVA fibres. The shrinkage of plain mortar was measured on 7x7x28 cm specimens, from 1 day up to 250 days. The final autogenous shrinkage was about 650 microstrains, and total shrinkage at 50 % R.H. attained a value of 800 microstrains. Also, the coefficient of thermal expansion was found to be equal to 17.6x10 -6 . Therefore, it was verified that this material has the ability to crack in restrained conditions, whatever the outer humidity; fibres are definitely required if cracking is to be avoided. The fiber reinforced mortar was also subjected to up to 25-million of flexural fatigue cycles. With at least 2 % of fibres, it was found that the material could resist, only showing a decrease and a stabilisation of the apparent E-modulus, whatever the nature of the fibres.

Cracking tests

The cracking tests were decisive in selecting the type and dosage of fibres. Two campaigns of insitu cracking tests were carried out, where 6-m long, 14-cm wide strips were laid in parallel on an old asphalt pavement (see Fig. 2). After some months, it was tentatively concluded that either 3 % of steel fibres or 4 % of PVA fibres could equally well prevent cracking. The latter solution was preferred, owing to better workability and lower cost induced by these synthetic fibres. A large, 20x2 m test pad was cast, in order to check that no cracking would appear at full scale. Unfortunately, after a hot early summer, it was found that PVA fibres tended to soften; this reinforcement was then no longer able to overcome the crack development in the strips, unlike steel fibres. Consequently, the final solution recommended by the authors is to use at least 3% of steel fibres to eliminate any visible cracking. This finding is also confirmed by a series of laboratory cracking tests performed on the mortar phase.

Surface resistance tests

Various tests were applied on laboratory specimens, in order to investigate the likelihood of surface distress under traffic. Rutting testers, with a cornering angle, resulted in a chipping loss of about 7.5 % in a HPCM specimen, a value that can be compared to 4.5 % obtained with a typical epoxy-asphalt surface dressing. ASTM abrasion tests showed the importance of the embedment process for limiting the amount of chipping loss. A more specific test using a tribometer (see Fig. 3) was then carried out on a series of wearing course materials. At 20°C, the performance of HPCM was intermediate between conventional bituminous materials and epoxy-asphalt materials (concrete or surface dressing). This result is quite satisfactory, given the fact that the temperature should not affect the HPCM behaviour in the 20-50°C range, unlike bituminous materials, whose resistance rapidly drops when the temperature increases.

Figure 3. The 'Tribometer' test, recently developed at LCPC (France)

Climatic aggressions were simulated through conventional freeze-and-thaw scaling tests, normally devoted to conventional cement concrete. The results obtained led to classify HPCM behavior in the "very good" category. Then, a more aggressive test called "total test", encompassing acid attack, freeze-thaw and shocks was carried out. In the absence of a control material, no HPCM classification can be deduced from this last tests. However, it was found that with up to 20 % of chipping loss, the texture characteristics and skid resistance of HPCM are hardly affected, showing the level of safety that can be attained with such a wearing course material.

Miscellaneous

The original texture of a cracking strip was acquired and processed through software aiming at simulating the noise generation likely to occur under traffic. It was found that HPCM should behave as an exposed-aggregate cement concrete of similar texture. Finally, a key performance test was carried out with the TRL Pavement Testing Facility (TRL, see Fig. 4) including an equivalent of 1.0 M standard axles at 20°C, followed by 0.5 M standard axles at 35°C. This structural test could help in evaluating a pavement structure with various wearing courses, even if the number of loading cycles remained small with regard to the expected traffic for a long-life pavement.

Three test pads were tested, covered with HPCM, SMA (stone-mastic asphalt) and EA (epoxyasphalt) concrete, respectively. The loading programme at ambient temperature only provoked a slight level of rutting, which greatly amplified when temperature was raised. The HPCM succeeded in limiting the rutting level to 1.5 mm, although much higher values were attained with the epoxy asphalt (6 mm) and the SMA (8 mm). The HPCM surface remained sound, with a high skid resistance (SRT value of 92). Some delamination happened at the edges of the HPCM pad in the bituminous base course. This distress was due to the rutting of the base course and the lack of tensile strength at 35°C. It was therefore concluded that HPCM had to be applied on a quite stiff asphalt concrete, with a low rutting and a low sensitivity to temperature. These requirements are a direct consequence of the search for a long-life pavement, whatever the wearing course could be.

The way forward: two new projects to continue the development of HPCM

After the completion of the OECD/CEMT JTRC "Long-Life Pavement" project phase 2, most participating countries decided to continue their efforts for practical implementation of long-life pavement technologies. Therefore, the OECD/ITF JTRC "Long-Life Pavement Surfacings" project phase 3 (LLPS 3) was officially launched in early "2009, coordinated by LCPC. Ten countries will build experimental, circulated test sections using one or both of the materials developed in the previous phase. A common approach regarding the specification, design, control and monitoring of the pavements will be taken as much as possible, and all collected data and experiences will be summarised in a final report. This document shall be a major reference to implement Long-Life Pavement Technology in many countries.

At the French level, a national project was launched at the same time, called CLEAN ("Chaussées à Longévité Environnementale Adhérente et Nettoyante"). The aims are similar to those of LLPS3, but restricted to the hydraulic solution (HPCM). For this material, although much research was performed within LLP 2, it was considered that more research was needed on the production and laying technique, a critical phase for any pavement material. Hence, the requirements are very strict: material quality control, correct bond with base layer, skid-resistance, limited noise generation and superior mechanical durability under high-traffic. CLEAN is gathering eight partners (including road owners, material providers, construction facility builders and research laboratories) with the objective of two successful experimental sites. The first one is scheduled during the fall of 2009, near Le Mans (Sarthe). It is a roundabout, a type of pavement quite appropriate to test a heavy-duty wearing course. For this first site, a semi-mechanised technique will be used to lay the HPCM (see Fig. 5).

The year after, a second construction site will take place in the Loire-Atlantique department, not far from Nantes. A straight street will be covered with HPCM, using a fully mechanised technique. A secondary, depollution function will be added to the material, through the use of titanium dioxide (TiO 2 ). Both test sections will be monitored until the end of the project.

Conclusion

A new material for a long-life wearing course was developed through a large, collaborative scientific project involving thirteen countries, of which seven were active participants. The main idea for the design of HPCM is the use of best quality materials in minimal quantity. The data acquired in the phase 2 program are globally encouraging, and one may expect a much longer lifespan, as compared to current asphalt wearing courses (which last generally between 7 and 15 years). With such a material one may expect 30 to 40 years of mobility without neither maintenance nor traffic disruption. The phase 3 is now engaged, where practical implementations on trafficked test sections will be carried out, supported by the French national project CLEAN. Further development will be necessary during this next phase to develop a suitable construction facility, and to investigate the sensitivity to water dosage and two-dimensional cracking behaviour.

Fig. 1

 1 displays the design of HPCM.

Figure 1 .

 1 Figure 1.Principle of the HPCM solution[START_REF] De | Preliminary tests on a hydraulic surface dressing for wearing courses with a long life[END_REF].

Figure 2 .

 2 Figure 2.Testing site for the cracking strips (tests performed at LCPC Nantes).

Figure 4 .

 4 Figure 4. The TRL Pavement Testing Facility (Crowthorne, UK)

Figure 5 .

 5 Figure 5. Project of the first HPCM test section in France (in Brette-les-Pins, 72).

Table 1 .

 1 Mixture-proportions of the plain mortar C.

	Components	kg/m 3
	Siliceous coarse sand 0.2/1	429
	Siliceous fine sand 0.08/0.315	429
	CEM I Portland cement	985
	Silica fume	197
	Superplasticizer (dry powder)	4.40
	Retarder	4.95
	Water	207
	w/c	0.21
	Slump (cm)	21

Table 2 .

 2 Properties of the hardened mortar C with 4% of PVA fibres (fresh state properties: slump 23 cm, air content 4.5 %), after a 28-day curing at 100 % R.H.

	Dimensions of	Type of test	Mean value
	specimens (cm)		(MPa)
	Prisms 4x4x16	Flexural	28.5
	Prisms 4x4x16	Compressive	164
	Cubes 10x10x10	Compressive	148
	Cylinders Ø11x22	E-modulus	43 000
	Cylinders Ø11x22	Compressive	129

Acknowledgements : the SIKA France company is gratefully acknowledged for the advice in the choice of constituents and the delivery of HPCM premix samples to all participants.


Santhini Jeyarajah
email: sanjeyarajah@doctors.net.uk

Savvas Papagrigoriadis

The Pathogenesis of Diverticular Disease -Current Perspectives on Motility and Neurotransmitters

Keywords: Diverticular disease < Disease-based, Motility < Topics, Clinical pharmacology < Topics, X Diverticular Disease, Motility, Clinical Pharmacology, Neurotransmitters

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Introduction

Although the pathogenesis of Diverticular Disease (DD remains) unclear, it is suggested that it may be a multifactorial disease comprising environmental factors, structural and motility disorders [START_REF] Simpson | Colonic diverticular disease[END_REF][START_REF] Mcajaw | Differences in colonic tone and phasic response to a meal in the transverse and sigmoid human colon[END_REF]. Increasingly neurotransmitters are speculated to underpin the different motility factors leading to the development and symptomatology of this condition. It is suggested that diverticulosis may be attributable to colonic smooth muscle dysfunction that results from vagal attrition associated with aging [START_REF] Yun | A new mechanism for diverticular diseases: agingrelated vagal withdrawal[END_REF]. This may be related to an abnormality in cholinergic activity in smooth muscle is important in the uncomplicated form of the disease with cholinergic denervation hypersensitivity affecting smooth muscle and upregulation of smooth muscle M3 receptors possibly accounting for physiological, and pharmacological abnormalities associated with diverticular disease [START_REF] Golder | Smooth muscle cholinergic denervation hypersensitivity in diverticular disease[END_REF]. It is these hypotheses and findings that have contributed to increasing amounts of work being carried out to delineate the role of neurotransmitters in pathogenesis of DD. It is the aim of this review to review the numerous motility and neurotransmitter factors implicated.

Methods

Medline, GoogleScholar and Pubmed were searched for evidence on this subject using the terms search terms: neurotransmitters, motility, Diverticular Disease and pathogenesis up to the year 2009. Articles in English relevant to the subject were cited and linked references were also reviewed.

Dietary

Traditionally, low fibre diets in western societies have been attributed to the prevalence of this disease in the West (5); ( 6); [START_REF] Painter | Diverticular disease of the colon, a 20th century problem[END_REF]. Low fibre intake is associated with prolonged colonic transit time, increased water resorption, smaller stool volume, constipation and straining which increases colonic intraluminal pressure, and results in the formation of pulsion diverticula [START_REF] Burkitt | Diverticular disease of the colon epidemiological evidence relating it to fibre-depleted diets[END_REF][START_REF] Burkitt | Effect of dietary fibre on stools and transit-times and its role in the causation of disease[END_REF]. Consistent with this hypothesis, vegetarians have been shown to have significantly higher fiber intake than non vegetarians and a lower prevalence of diverticulosis [START_REF] Gear | Dietary fibre and asymptomatic diverticular disease of the colon[END_REF].

a. Diet and Geography

Geography and differences in dietary fibre has long been implicated in the different rates of DD. Prevalence appears to be quite homogenous throughout Europe, without a geographical gradient [START_REF] Delvaux | Diverticular disease of the colon in Europe: epidemiology, impact on citizen health and prevention[END_REF]. DD had been found to be 80 times more common in Scotland compared with the native population of Fiji, Singapore and Nigeria and forty times more common in Europeans living in these places likely to be due to their low residue diet [START_REF] Kyle | Incidence of diverticulitis[END_REF].

Interestingly however, when people from these areas migrate to high-incidence areas, such as the United States, Europe, and Australia, their rates of diverticular disease increase significantly to match the local population [START_REF] Stollman | Diverticular disease NJ[END_REF]. As eluded to previously, in Western countries, diverticula are seen predominantly in the sigmoid and distal descending colon but in the Asian, Africa and Middle Eastern populations diverticular disease occurs almost exclusively in the right colon [START_REF] Schoetz | Diverticular disease of the colon: a century-old problem[END_REF]. These racial/ethnic differences in anatomic distribution are probably genetic. When Asians migrate, their diverticulosis occurrence increases, but the anatomic location in the bowel appears to remain unchanged [START_REF] Mimura | Pathophysiology of diverticular disease[END_REF]. In a retrospective colonoscopy study in urban London, DD had a lower frequency in migrant Indians compared with other ethnic groups. These patients were significantly younger than the other age groups however the numbers in this study were small. Here was no difference between first and second generation migrants and it is difficult to draw firm conclusions from this study [START_REF] Kang | Diverticular disease of the colon: ethnic differences in frequency[END_REF].

In an endoscopy study of Turkish migrants in the Netherlands, diverticulosis was diagnosed significantly more often in migrant men and immigrants with diverticulosis were significantly younger than the authentic Dutch. [START_REF] Loffeld | Diverticulosis of the colon is rare amongst immigrants living in the Zaanstreek region in the Netherlands[END_REF]. In a population based study in Sweden the risk of hospital admission because of diverticular disease, after adjustment for age, sex and socioeconomic indicators, was lower in non-Western immigrants compared with natives and the risk increased with time after the settlement. The overall 10 year cumulative incidence was 0.44% in men and 0.7% in women and the incidence increased linearly with age. Socioeconomic status, residency or housing situation were not risk factors which led the authors to conclude that diverticular disease appears to be an acquired disorder and acculturation to a Western lifestyle has an impact on the risk (17) and a similar cause may be an explanation for the other studies cited.

Structural pathogenetic factors

It has been suggested that a primary abnormality of muscularis propria in DD leading to its shortening and thickening, causing it to behave like myostatic contracture might exist and was the most consistent feature of diverticular disease [START_REF] Morson | The Muscle Abnormality in Diverticular Disease of the Colon[END_REF]. Muscle cells retain a normal, non-hypertrophic appearance, and rather, the thickened taenias were due to increased elastin deposition, leading to contraction and secondary thickening of the circular layer [START_REF] Whiteway | Elastosis in diverticular disease of the sigmoid colon[END_REF]. The consequent plication of the circular layer narrows the lumen, thus increasing the intraluminal pressure according to Laplace's law. The resulting hypersegmentation is thought to be important in the pathogenesis of the diverticula [START_REF] Painter | Diverticular disease of the colon--a disease of the century[END_REF].

The muscle abnormality leading to a non-compliant wall seems to be due to mychosis and the intrinsic derangement of collagen fibres [START_REF] Thomson | Submucosal collagen changes in the normal colon and in diverticular disease[END_REF]. Mychosis refers to the progressive elastosis of the taenia coli attributed to the increased proline in the western diet [START_REF] Whiteway | Elastosis in diverticular disease of the sigmoid colon[END_REF]. Abnormalities in increased collagen deposition and cross linking are also implicated in decreased colonic tensile strength [START_REF] Wess | Collagen alteration in an animal model of colonic diverticulosis[END_REF][START_REF] Wess | Cross linking of collagen is increased in colonic diverticulosis[END_REF].

Increased cross-linking of colonic collagen with age and in patients with diverticulosis may lead to rigidity and loss of tensile strength [START_REF] Wess | Collagen alteration in an animal model of colonic diverticulosis[END_REF][START_REF] Wess | Cross linking of collagen is increased in colonic diverticulosis[END_REF], an increased synthesis of type III collagen may decrease the tensile strength of the circular muscle [START_REF] Bode | Type I and III collagens in human colon cancer and diverticulosis[END_REF] and collagen fibrils have also been seen to be smaller and more tightly packed in the left colon with increasing age and DD which may also contribute to the weakness [START_REF] Thomson | Submucosal collagen changes in the normal colon and in diverticular disease[END_REF].

Along with changes in colonic motility, Arfwidsson et al, noted thickening of both the circular muscle layer and taenia of sigmoid diverticular specimens when compared with normal controls [START_REF] Arfwidsson | Pathogenesis of Multiple Diverticula of the Sogmoid Colon in Diverticular Disease[END_REF]. The prevalence of colonic DD is strongly correlated with advancing age. It is relatively uncommon before the age of 40 (5%), and increases progressively to as much as 60% in the 80s and older seen in post mortem and radiological studies [START_REF] Parks | Motility studies in diverticular disease of the colon[END_REF][START_REF] Parks | Natural history of diverticular disease of the colon[END_REF][START_REF] Hughes | Postmortem survey of diverticular disease of the colon. II. The muscular abnormality of the sigmoid colon[END_REF][START_REF] Gear | Symptomless diverticular disease and intake of dietary fibre[END_REF]. This may be due to weakening of the bowel due to aging and reduction in tensile strength of the colon [START_REF] Iwasaki | Study on the strength of human intestinal walls[END_REF][START_REF] Watters | Mechanical properties of the colon: comparison of the features of the African and European colon in vitro[END_REF].

Age

Collagen fibrils demonstrate increased crosslinking with age leading to reduced tensile strength [START_REF] Wess | Cross linking of collagen is increased in colonic diverticulosis[END_REF]. Is has also been demonstrated that the collagen tissue layer between the longtitudinal and circular layers of smooth muscle of the bowel is reduced by increasing age (Pace, 1966). Elastin contents increases throughout life in all layers of the colon which contributes to the elastosis seen in DD [START_REF] Parks | Motility studies in diverticular disease of the colon[END_REF][START_REF] Smith | Colonic muscle in diverticular disease[END_REF][START_REF] Smith | Proceedings: The stength of the colon wall in diverticular disease[END_REF].

There appears to be no clear hereditary pattern to colonic diverticular disease although more and more this disease seems to be migrating to younger patients. The incidence varies from less than 10% in people younger than 40 years to an estimated 50-80% in patients older than 80 years [START_REF] Stollman | Diverticular disease NJ[END_REF][START_REF] Wolff | Surgical management of diverticulitis[END_REF][START_REF] Marinella | Acute diverticulitis in patients 40 years of age and younger[END_REF].

From an outcome perspective it is this younger age group which is of great clinical interest as it is thought to be a more virulent form of the condition. In a study in New Mexico, 6% of patients with symptomatic disease were aged 40 years of age or younger [START_REF] Acosta | Colonic diverticular disease in patients 40 years old or younger[END_REF], in other studies the prevalence is even lower representing only 2-5% [START_REF] Roberts | Current management of diverticulitis[END_REF][START_REF] Parks | Natural history of diverticular disease of the colon. A review of 521 cases[END_REF]. This younger group has disproportionately more men [START_REF] Acosta | Colonic diverticular disease in patients 40 years old or younger[END_REF] and 25-80% require surgery with a higher chance of recurrence in those managed conservatively. [START_REF] Acosta | Colonic diverticular disease in patients 40 years old or younger[END_REF][START_REF] Roberts | Current management of diverticulitis[END_REF][START_REF] Konvolinka | Acute diverticulitis under age forty[END_REF][START_REF] Freischlag | Complications of diverticular disease of the colon in young people[END_REF][START_REF] Vignati | Long-term management of diverticulitis in young patients[END_REF][START_REF] Spivak | Acute colonic diverticulitis in the young[END_REF]. Similarly in a British hospital admission study younger patients were more likely than older patients to undergo an operation following admission for diverticular disease. [START_REF] Kang | Diverticular disease of the colon--on the rise: a study of hospital admissions in England between 1989/1990 and 1999/2000[END_REF]. Younger patients are more commonly offered elective surgery which may explain this increase (45) [START_REF] Boudart | Management of sigmoid diverticulitis: a retrospective study of 268 patients[END_REF].

There is however an increasing awareness of DD in younger patients where previously it was regarded as a disease of the elderly, and where before other diagnoses may be sought to explain symptoms in younger patients, there may be more recognition of DD in this age group [START_REF] Janes | The place of elective surgery following acute diverticulitis in young patients: when is surgery indicated? An analysis of the literature[END_REF]. The change in this pattern of disease could be due not only to increased awareness but may also reflect cultural and dietary effects previously discussed. Low fibre diet may be more prevalent in this age group resulting in the increased incidence seen.

These traditional aetiological factors are summarised in Table 1.

Motility factors in pathogenesis

The commonest motor pattern seen in the colon is tonic segmenting and rhythmic contraction, serving to slow down faecal flow thereby maintaining continence and permitting water absorption and electrolyte exchange. There are also propulsive peristaltic contractions that usually move in the caudal direction that occur on average 6 times a day [START_REF] Bassotti | Twenty-four hour recordings of colonic motility in patients with diverticular disease: evidence for abnormal motility and propulsive activity[END_REF][START_REF] Bassotti | Alterations in colonic motility and relationship to pain in colonic diverticulosis[END_REF].

The colon has electrical activity in the form of slow waves and fast activity spikes, or action potentials and this activity is implicated in the pathogenesis of DD (50-55). Left-sided diverticula which are pulsion pseudo-diverticula, occur most often in the sigmoid colon, which has the smallest diameter, lowest compliance and therefore the highest intraluminal pressures [START_REF] Waldron | Pressure response of human colon to intraluminal distension[END_REF][START_REF] Ford | Differences in colonic tone and phasic response to a meal in the transverse and sigmoid human colon[END_REF].

Not only do patients with diverticular disease have higher colonic intraluminal pressures than control subjects (58) [START_REF] Arfwidsson | Pathogenesis of Multiple Diverticula of the Sogmoid Colon in Diverticular Disease[END_REF][START_REF] Shafik | Diverticular disease: electrophysiologic study and a new concept of pathogenesis[END_REF][START_REF] Parks | Motor responses in unresected and resected diverticular disease of the colon[END_REF][START_REF] Trotman | Sigmoid motility in diverticular disease and the irritable bowel syndrome[END_REF] but it has also been shown that basal and post prandial intraluminal pressures are higher in patients with symptomatic DD compared to those with asymptomatic DD [START_REF] Cortesini | Usefulness of colonic motility study in identifying patients at risk for complicated diverticular disease[END_REF]. The motility patterns in DD show similarity to those of Irritable Bowel Syndrome (IBS) to the extent that some researchers have suggested that the two conditions may be two forms of the same.

Painter et al, 1965 used manometry and simultaneous cinematography to claim that hypersegmentation led to formation of diverticula and this phenomenon was confirmed by more recent studies [START_REF] Mimura | Pathophysiology of diverticular disease[END_REF][START_REF] Brodribb | Diverticular disease: three studies. Part I--Relation to other disorders and fibre intake[END_REF][START_REF] Painter | Segmentation and the Localization of Intraluminal Pressures in the Human Colon, with Special Reference to the Pathogenesis of Colonic Diverticula[END_REF][START_REF] Painter | The cause of diverticular disease of the colon, its symptoms and its complications. Review and hypothesis[END_REF] Colonic transit studies in DD show conflicting results. Diverticular disease patients showed delayed colonic transit which was expedited by bran [START_REF] Kirwan | Colonic propulsion in diverticular disease, idiopathic constipation, and the irritable colon syndrome[END_REF]. Conversely, another study showed faster transit time between caecum and sigmoid colon in patients with DD compared to controls but the mean total time of gastrointestinal emptying was no different in either group [START_REF] Leandro | Gastrointestinal motility in normal subjects and patients with diverticulosis of the colon[END_REF]. Similarly, Eastwood et al in 1978 found that 60 patients with DD failed to show prolonged intestinal transit time, a reduced stool weight or increased intracolonic pressure compared to the normal patients [START_REF] Eastwood | Colonic function in patients with diverticular disease[END_REF].

Myoelectrical activity

Myoelectrical recordings from implanted catheters in the normal colon reveal a combination of slow waves, corresponding to colonic pacemaker activity, and spikes, reflecting muscle contractions. It is believed that the slow waves originate from the interstitial cells of Cajal [START_REF] Sanders | A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract[END_REF]. An early investigation of the myenteric plexus in diverticulosis, found no morphological abnormalities (Vuong et al, 1985). It has been found since that patients with colonic diverticulosis have significantly reduced numbers of colonic ICC and enteric glial cells compared with controls [START_REF] Bassotti | Alterations in colonic motility and relationship to pain in colonic diverticulosis[END_REF]. The consistently significant reduction of all subpopulations of ICC and of enteric glial cells, might explain the colonic motor abnormalities documented in patients with diverticulosis and there may exist an interaction between neurotransmitters and these cellular elements.

In vivo studies have produced contradictory evidence as slow wave activity has been shown to be both unaltered [START_REF] Suchowiecky | Effect of secoverine on colonic myoelectric activity in diverticular disease of the colon[END_REF][START_REF] Katschinski | Myoelectric and manometric patterns of human rectosigmoid colon in irritable bowel syndrome and diverticulosis[END_REF] or possibly increased in DD (71-73) Segmental activity is increased in response to cholinergic stimuli [START_REF] Huizinga | Electrophysiology of human colon motility in health and disease[END_REF][START_REF] Huizinga | Abnormal response to cholinergic stimulation in the circular muscle layer of the human colon in diverticular disease[END_REF] in patients with DD. Fast wave activity is increased in patients with DD and these changes have a tendency to persist following resection of the affected segment, suggesting an inherent alteration in electrical activity.

However the exact relevance of any myoelectrical changes in relation to mechanical events remains uncertain [START_REF] Parks | Motor responses in unresected and resected diverticular disease of the colon[END_REF].

Twenty four hour manometry studies showed an overall increase in basal motility of diverticula segments, an abnormal colonic motor response to eating, and a qualitatively and quantitatively abnormal forceful propulsive activity [START_REF] Bassotti | Twenty-four hour recordings of colonic motility in patients with diverticular disease: evidence for abnormal motility and propulsive activity[END_REF]. Other studies have looked at the role of colonic pacemakers. The colon is thought to have at least four pacemakers, located at the caecal pole, the caeco-colonic junction, the mid transverse colon, and the colo-sigmoid junction [START_REF] Shafik | Electrophysiologic identification of the location of the colonic pacemakers. A human study[END_REF] . These pacemakers generate slow waves (SW) which initiate and govern colonic contractions [START_REF] Quigley | Myoelectric activity and intraluminal pressure of the canine ileocolonic sphincter[END_REF][START_REF] Bueno | Evaluation of colonic myoelectrical activity in health and functional disorders[END_REF][START_REF] Shafik | Sigmoido-rectal junction reflex: role in the defecation mechanism[END_REF]. It has been found that "tachyrhythmic" electrical activity is seen in the early-DD patients who had loose stools or constipation and "bradyrhythmic" or "silent" activity with an irregular rhythm and low frequency, amplitude, and conduction velocity in the late-DD patients. These patients complained of constipation with pellet-like stools. These "dysrhythmias" may result from a disordered colonic pacemaker. The resulting colonic spasm seems to result in an intraluminal colonic pressure rise.

Heterogeneity in studies

There is conflicting evidence on the role of raised intramural pressure and increased myoelectrical activity in DD. The inconsistencies that arise are probably a result of a number of factors including methodological differences, heterogeneity of patients and disease states compounded by studies with relatively small numbers and differences in anatomical sites of investigation.

On these grounds it is difficult to draw a firm conclusion from these investigations although it seems reasonable to accept that higher pressures and increased electrical activity are likely to be seen in patients with DD but it is unclear whether this a cause or result of the disease.

A Summary of the motility factors implicated in the pathogenesis of DD is presented in Table 2.

Neurotransmitters and Diverticular Disease

The alterations of colonic motility in DD described above have not been adequately investigated or understood at a molecular level. Our hypothesis is that disorders of neurotransmitters may be responsible for the main motility changes underlying the pathogenesis of DD. In the following section we will try to review some of the known facts about neurotransmitters and the colon and postulate a possible mechanism implicated in DD.

Serotonin

Serotonin (5-HT) is 3-(β-aminoethyl)-5-hydroxyindole. It has been found to be the neurotransmitter of a subset of myenteric interneurons, which evoke a slow excitatory postsynaptic response. Seven subtypes of serotonin receptors have been identified, 5-HT3 and 5-HT4 receptors are most relevant in gastrointestinal physiology [START_REF] Camilleri | Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome[END_REF].

The gut contains over 95% of the body's 5-HT [START_REF] Gershon | Serotonergic neurons in the peripheral nervous system: identification in gut by immunohistochemical localization of tryptophan hydroxylase[END_REF]. Enteric neurones synthesize 5-HT and store it. Serotonergic neurons constitute about 2% of all myenteric neurons. The major enteric depot of 5-HT is found in mucosal enterochromaffin cells, which are sensory transducers that utilize 5-HT to activate both intrinsic (via 5-HT 1P and 5-HT 4 receptors) and extrinsic (via 5-HT 3 receptors) primary afferent nerves.

The early experiments implicating 5-HT as an enteric neurotransmitter also revealed that enteric 5-HT-containing nerves exhibit the same Na + -dependent reuptake mechanism for 5-HT as that utilized by the serotonergic neurones of the central nervous system (CNS) known as SERT on the plasma membrane [START_REF] Robinson | Synthesis and uptake of 5-hydroxytryptamine by the myenteric plexus of the guinea-pig ileum. A histochemical study[END_REF][START_REF] Drossman | AGA technical review on irritable bowel syndrome[END_REF][START_REF] Richardson | Identification of serotonin Mreceptor subtypes and their specific blockade by a new class of drugs[END_REF][START_REF] Bearcroft | Postprandial plasma 5-hydroxytryptamine in diarrhoea predominant irritable bowel syndrome: a pilot study[END_REF]. It is inhibited by fluoxetine and by tricyclic Serotonin and serotonin binding protein (SBP) ( 92) is released from the bowel when enteric nerves are stimulated electrically or by vagi [START_REF] Gershon | Release of endogenous 5-hydroxytryptamine from resting and stimulated enteric neurons[END_REF] 5-HT evokes contractions of gut smooth muscle cells, either by stimulating 5-HT 3 receptors on nerve cells or 5-HT 2 receptors on muscle [START_REF] Richardson | Identification of serotonin Mreceptor subtypes and their specific blockade by a new class of drugs[END_REF]. Serotonin is also a potent intestinal secretagogue as administration of subcutaneous serotonin caused ileal secretion and reduced jejunal absorption of water and electrolyte [START_REF] Donowitz | Effect of serotonin treatment on intestinal transport in the rabbit[END_REF], and serotonin also increased serosal to mucosal fluxes of chloride in animal models [START_REF] Siriwardena | A 5-HT2 receptor mediates serotonin-induced electrolyte transport in rat left colon[END_REF].

Neuronal 5-HT 3 receptors are responsible for rapid depolarization responses in myenteric neurons, leading to increased release of acetylcholine from cholinergic neurons, facilitating the induction of fast excitatory postsynaptic potentials (EPSPs) [START_REF] Gershon | Review article: roles played by 5-hydroxytryptamine in the physiology of the bowel[END_REF]. 5-HT 4 receptors are involved in the peristaltic reflex (97-100) A. 5-HT 3 receptors are not just restricted to excitatory cholinergic motor nerves; 5-HT 3 receptor activation also releases "inhibitory" neurotransmitters in various regions of the gut, leading to smooth muscle relaxation during appropriate conditions (101). At present, the serotonin receptors with the greatest potential for therapeutic manipulation are the 5-HT 3 and 5-HT 4 receptor subtypes.

a. Action of serotonin and its modulators on the Gastrointestinal tract

In vivo studies have shown that serotonin agonists such as prucalopride (5-HT4 agonist) (102) accelerate colonic motility, whereas serotonin antagonists, especially on 5-HT3 receptors (96, 103, 104) inhibit colonic transit or motility leading to the inference that serotonin has an excitatory effect on the gut. Serotonin selective reuptake inhibitor (SSRI), fluoxetine, which inhibits mucosal 5-HT uptake increases activation of 5-HT [START_REF] Chen | Guinea pig 5-HT transporter: cloning, expression, distribution, and function in intestinal sensory reception[END_REF]. The secretory action of serotonin is blocked by cisapride [START_REF] Siriwardena | A 5-HT2 receptor mediates serotonin-induced electrolyte transport in rat left colon[END_REF]105).

Granisetron, a 5-HT 3 antagonist, had no effect on the colonic peristaltic reflex, even though it blunted the human gastrocolonic response without altering antral compliance (106).

b. Serotonin and its role in GI pathology

Serotonin in IBS has been extensively studied and most information is available in this area.

Biopsies of patients with IBS had significantly lower mucosal concentrations of serotonin than normal controls along with lower concentrations of tryptophan hydroxylase which is a rate limiting enzyme in serotonin synthesis (107). In another study, lower serotonin levels were observed in mucosal biopsy samples and post prandial blood samples from patients with IBS with constipation (IBS-C) than in patients with IBS with diarrhoea (IBS-D) or in healthy volunteers (108) [START_REF] Bearcroft | Postprandial plasma 5-hydroxytryptamine in diarrhoea predominant irritable bowel syndrome: a pilot study[END_REF] with a lower level of SERT mRNA and SERT protein expression in the intestinal epithelial cells of IBS patients compared with that of healthy volunteers (107). Systemic review of IBS treatment concluded that there is strong evidence for the improvement of global IBS symptoms with two serotonergic agents: the 5-HT4 selective agonist tegaserod (IBS with constipation) and the 5-HT3 antagonist alosetron (IBS with diarrhoea). Further data are required for the 5-HT3 antagonist, cilansetron, and the mixed 5-HT3antagonist/5-HT4 agonist renzapride before their utility in IBS can be appraised (109) however as IBS is not the focus of this review, this will not be discussed further.

Serotonin has been found to be increased in the colonic mucosa of resected specimens in patients with DD (110). This relates to the increased colonic motility seen in DD. Therefore serotonin antagonists may have a role in slowing progression of this disease and also reducing symptoms, particularly in those patients whose predominant symptom is diarrhoea.

More directed therapy could also be instituted by carrying out biopsies in patients with DD and identifying if there is an increase in serotonin and correlation with symptoms. However a more recent study contradicts this finding where no difference has been found between serotonin content in normal and Diverticular colonic mucosa (111) Serotonin which has been found to be an excitatory colonic neurotransmitter has been found in early studies to be increased in colonic enterochromaffin cells (Banerjee, 2005). Serotonin agonists may therefore may have a role in alleviating the symptoms and possible worsening of DD. GABA which is thought to be an inhibitory agent, although not yet clearly identified to have a role in DD, may have a converse role to serotonin.

Acetylcholine

Acetylcholine is an important neurotransmitter in normal bowel smooth muscle (112) that mediates contraction via postsynaptic muscarinic M3 receptors (113). In-vitro myoelectric experiments have shown that there is an increase in low frequency and uncoordinated muscle contraction in patients with diverticular disease who have been given exogenous acetylcholine compared with controls [START_REF] Huizinga | Abnormal response to cholinergic stimulation in the circular muscle layer of the human colon in diverticular disease[END_REF]. It has also been found that activity of choline acetyltransferase was lower in smooth muscle of patients with diverticular disease, M3 receptors have been found to be higher, and sensitivity to exogenous acetylcholine was increased compared to controls. Amplified expression of bowel-muscle M3 receptors could be a compensatory response to a reduction in cholinergic innervation and a mechanism by which smooth-muscle cells increase their sensitivity to acetylcholine, in an attempt to maintain intrinsic background tone (4). This suggests that cholinergic denervation hypersensitivity can affect smooth muscle in DD, and this along with upregulation of smooth muscle M3 receptors might account for specific clinical, physiological, and pharmacological abnormalities associated with diverticular disease including exaggerated post prandial responses and higher than normal colonic motility (114).

However, Tomita et al, did not show a significant rise in sensitivity of longitudinal muscle strips to exogenous acetylcholine, despite noting upregulation of M3 receptors in circular and longitudinal muscle (114). As mentioned, diverticular taeniae have been shown by results of immunohistochemical experiments and electron-microscopic analysis, to contain more elastin than controls. Circular muscle elastin content is normal [START_REF] Whiteway | Elastosis in diverticular disease of the sigmoid colon[END_REF]. Therefore, despite an upregulation of M3 receptors in longitudinal taeniae, muscle might not express hypersensitivity to exogenous acetylcholine because its contraction is mechanically restricted by the presence of abnormal concentrations of elastin. NO has also be found to stimulate basal acetylcholine release from myenteric neurones through activation of guanylyl cyclase and inhibits the depolarization evoked release of acetylcholine by a presynaptic mechanism unrelated to cyclic GMP by pro-contractile cholinergic nerves implying that NO is not only an inhibitory transmitter to intestinal smooth muscles through NANC but also a modulator of cholinergic neurotransmission in the myenteric plexus (116). Nitrergic neurones project to both circular and longitudinal muscles (112, 117) and are important mediators of resting colonic smooth muscle tone (118) It has been found that the diverticular colon was more strongly innervated by cholinergic nerves than the normal colon and NANC inhibitory nerves were found to act on the normal colon and to a lesser extent in the diverticular colon. There is also reduction of nitric oxide mediation on the relaxation reaction of NANC nerves in the normal colon compared to in the diverticular colon. This suggested that diminution of action of non-adrenergic noncholinergic inhibitory nerves and substances such as nitric oxide may result in the high intraluminal pressure caused by colonic segmentation observed in the left-sided colon with diverticula (119). This was also found to be true for right and left sided diverticular (114, An abnormally low concentration of VIP in all the colon wall except mucosa, circular muscle and taenia has been shown in idiopathic constipation and would possibly correlate to excess segmenting and reduced propulsion (126, 127). Conversely, in diverticular disease, the VIP content of the mucosa and whole wall minus the mucosal layer was increased when compared with control tissue but was unaltered in the circular muscle and taenia coli. Substance P and neuropeptide Y levels in all layers of colonic wall were unaltered in these two diseases. The disturbances in the normal neural content of VIP in the bowel wall in idiopathic constipation and diverticular disease may initiate or contribute to the functional changes seen in these disorders (127).

Substance P is the main neurotransmitter after Acetylcholine for excitatory motor neurones.

Other than the above study however, little is known about its role in Diverticular Disease (128). Similar to Ach however, it may be shown to be have attenuated activity in this condition. A summary of these neurotransmitters and their actions in the pathogenesis of DD is presented in Table 3.

The interplay between pathogenesis and neurotransmitters

As mentioned in the pathogenesis section, motility of colon in DD is abnormal. The effects seen as reported in the literature vary however it can generally be surmised that intraluminal pressures are likely to be increased both basally and post prandially, [START_REF] Mimura | Pathophysiology of diverticular disease[END_REF][START_REF] Arfwidsson | Pathogenesis of Multiple Diverticula of the Sogmoid Colon in Diverticular Disease[END_REF][START_REF] Shafik | Diverticular disease: electrophysiologic study and a new concept of pathogenesis[END_REF][START_REF] Painter | The Intraluminal Pressure Patterns in Diverticulosis of the Colon. I. Resting Patterns of Pressure. Ii. the Effect of Morphine[END_REF][START_REF] Trotman | Sigmoid motility in diverticular disease and the irritable bowel syndrome[END_REF][START_REF] Painter | The cause of diverticular disease of the colon, its symptoms and its complications. Review and hypothesis[END_REF]. This was also seen in right sided DD (129).

Serotonin which has been found to be an excitatory colonic neurotransmitter has been found in early studies to be increased in colonic enterochromaffin cells (110). Serotonin agonists may therefore may have a role in alleviating the symptoms and possible worsening of DD.

Acetylcholine which is thought to be an excitatory neurotransmitter and cholinergic activity has also seen to be increased in DD may again have a role. These findings may suggest that an increase in excitatory neurotransmitters may result in the hypersegmentation thought to the cause of pulsion diverticula. Similarly, a decrease of Nitric Oxide which is inhibitory is found.

Conversely, Vasoactive intestinal polypeptide which is inhibitory is found to be increased and may related to formation of pulsion diverticula due to slow transit and constipation however there is no clear evidence of this at present. The interactions between these neurotransmitters and their subsequent effect on colonic motility and pathogenesis in DD is presented in Figure 1.

Conclusions

These neurotransmitter studies number in single reports, having not been reproduced, usually carrying only small sample sizes and a great deal more work is required to clearly delineate the role of neurotransmitters in the pathogenesis of DD particularly in in vivo human studies.

As far as therapeutic interventions are concerned for control and disease progression control, there may be roles for 5-HT4 selective agonists tegaserod and the 5-HT3 antagonists depending on symptoms, similar to their potential use in IBS. M3 receptor antagonists and Nitric oxide agonists which encourage relaxation may also have a role. For VIP however, the current data are contradictory. • Increased basal motility

Tables & Figures

• Decreased frequency of mass movements and increased segmental activity in aging leading to hypersegmentation.

• Disordered "colonic pacemaker" activity leading to increased activity in early DD and slower activity in late DD.

F o r P e e r R e v i e w

  tricyclic antidepressants display the same order of potency in inhibiting enteric and central reuptake of 5-HT.When colonic intraluminal pressure increases, enterochromaffin (EC) cells release 5-HT, which stimulates vagal and intrinsic (enteric) afferent nerve fibers. As a result, 5-HT plays a role in initiating responses as diverse as nausea, vomiting, intestinal secretion, and the peristaltic reflex[START_REF] Bulbring | The release of 5-hydroxytryptamine in relation to pressure exerted on the intestinal mucosa[END_REF][START_REF] Bulbring | Observations concerning the action of 5-hydroxytryptamine on the peristaltic reflex[END_REF][START_REF] Bulbring | The effect of intraluminal application of 5-hydroxytryptamine and 5-hydroxytryptophan on peristalsis; the local production of 5-HT and its release in relation to intraluminal pressure and propulsive activity[END_REF][START_REF] Sidhu | Role for 5-HT and ACh in submucosal reflexes mediating colonic secretion[END_REF][START_REF] Kirchgessner | Identification and stimulation by serotonin of intrinsic sensory neurons of the submucosal plexus of the guinea pig gut: activity-induced expression of Fos immunoreactivity[END_REF][START_REF] Kirchgessner | Identification of cells that express 5-hydroxytryptamine1A receptors in the nervous systems of the bowel and pancreas[END_REF][START_REF] Blackshaw | Effects of 5-hydroxytryptamine on discharge of vagal mucosal afferent fibres from the upper gastrointestinal tract of the ferret[END_REF][START_REF] Hillsley | Direct and indirect actions of 5-hydroxytryptamine on the discharge of mesenteric afferent fibres innervating the rat jejunum[END_REF][START_REF] Chen | Guinea pig 5-HT transporter: cloning, expression, distribution, and function in intestinal sensory reception[END_REF].

  oxide Non-adrenergic non-cholinergic (NANC) inhibitory nerves are important nerves in the enteric nervous system of the human gut. Recently, it has been established that nitric oxide (NO) is released by stimulation of NANC nerves and the NANC inhibitory transmission in the longitudinal muscle of the taenia coli of human colon leads to colonic relaxation (113, 115).

  119)Most recently uncomplicated diverticular longitudinal muscle has been shown to have lower nitric oxide immunoreactivity compared with controls and increased elastosis. This lowered again led to the postulation that decreased relaxation in the colon and uncoordinated peristaltic activity leading to "closed hypersegmentation" and the high pressure generated may lead to the formation of diverticula (120)4. NeuropeptidesVasoactive Intestinal Polypeptide (VIP) containing nerve cells in the myenteric plexus have been shown to project to the circular muscle, the submucous plexus and other cell bodies within the myenteric plexus (121). It is known that VIP has an inhibitory role in peristalsis (122-125).

Figure 1 :

 1 Figure 1: Interactions between colonic neurotransmitters and implications on the

  The percentage of admissions with an operation decreased with age from 54.2% in the 25-34-year age group to 13.4% in the ≥ 85-

	year age group
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Table 1 :

 1 Summary of traditional aetiological factors implicated in DD

	Factor	Anomaly
	Diet	Decreased Fibre
	Structural	Abnormality of muscularis propria in the form of mychosis
	Ageing	Weakening of bowel wall due to decreased cross linking and deposition of
		collagen fibres and increased elastosis

Table 2 :

 2 Summary of Motility Changes implicated in the pathogenesis of DD

	Motility Factors	Changes Seen
	Pressures	• Increased intraluminal pressures demonstrated in DD colon
		• Hypersegmentation
	Colonic transit	• Conflicting results
	Myoelectrical activity	• Increased and unaltered slow wave activity had been found
		the relevance of which is uncertain

Table 3 :

 3 Summary of characteristics and actions of neurotransmitters on the colon and the implications in Diverticular Disease

	Neurotransmitter	Characteristics & Actions	Role in GI pathology	Avenues for further research
	SEROTONIN	Found in colonic mucosal	IBS	Increased DD studies to further
		enterochromaffin cells acting via 5-	• Decreased mucosal and post	clarify the role of serotonin
		HT3 and 4 receptors with SERT, a	prandial release in IBS-	including the action of 5-HT
		mucosal Na+ dependent reuptake	Constipation	modulation on the clinical
		mechanism	DD	syndrome
			• Increased serotonin in
		Increased colonic intraluminal	enterochromaffin cells of DD
		pressure leads to 5-HT release from	resected colons
		enterochromaffin cells resulting in:
		• increased contraction of
		smooth muscle cells
		• intestinal ileal secretion and
		lack of jejunal absorption
		• evokes fast excitatory post -
		synaptic potentials
		Serotonin agonists accelerates
		colonic motility and antagonists
		inhibit colonic motility
	ACETYLCHOLINE	Well defined role in increasing	DD	Therapeutic modulation of Ach
		bowel smooth muscle via post-
		synaptic muscarinic M3 receptors	• Decreased density in old age