Trade-offs between succulent and non-succulent epiphytes underlie variation in drought tolerance and avoidance.

Epiphyte communities comprise important components of many forest ecosystems in terms of biomass and diversity, but little is known regarding trade-offs that underlie diversity and structure in these communities or the impact that microclimate has on epiphyte trait allocation. We measured 22 functional traits in vascular epiphyte communities across six sites that span a microclimatic gradient in a tropical montane cloud forest region in Costa Rica. We quantified traits that relate to carbon and nitrogen allocation, gas exchange, water storage, and drought tolerance. Functional diversity was high in all but the lowest elevation site where drought likely limits the success of certain species with particular trait combinations. For most traits, variation was explained by relationships with other traits, rather than differences in microclimate across sites. Although there were significant differences in microclimate, epiphyte abundance, and diversity, we found substantial overlap in multivariate trait space across five of the sites. We found significant correlations between functional traits, many of which related to water storage (leaf water content, leaf thickness, hydrenchymal thickness), drought tolerance (turgor loss point), and carbon allocation (specific leaf area, leaf dry matter content). This suite of trait correlations suggests that the epiphyte community has evolved functional strategies along with a drought avoidance versus drought tolerance continuum where leaf succulence emerged as a pivotal overall trait.

Incidence, outcomes and outcome prediction of unplanned extubation in critically ill children: An 11year experience.

PURPOSE: Unplanned extubation represents loss of control in the ICU, is associated with harm and is used as a measure of quality of care. We evaluated the rates and consequences of unplanned extubation. MATERIALS AND METHODS: Eligible patients were intubated, <18years, and in ICU. Patient, care-related and environmental characteristics were compared in patients who did and did not receive positive pressure ventilation in the 24h after events. Rates are expressed per 100 intubation-days. RESULTS: The 11,310 eligible patient-admissions identified were intubated for 75,519days; 410 (3.39%) patients had 458 unplanned extubation events (0.61 events/100 intubation-days). Annual rates of unplanned extubation reduced from 0.98 in 2004 to 0.37 in 2014. Consequences occurred in 245 (53.5%) events and included cardiac arrest in 9 (2%), bradycardia 52 (11%), and stridor 63 (14%). Positive pressure was provided after 263 (57%) events, and was independently associated with pre-event sedative and muscle relaxant drugs, non-use of restraints, respiratory reason for intubation and recent care by more nurses. CONCLUSION: Unplanned extubation was associated with both significant and no morbidity. Modification of factors including more consistent nurse staffing, restraint use, and increased vigilance in patients with previous events may potentially reduce rates and adverse consequences of unplanned extubation.

Application of biological simulation models in estimating feed efficiency of finishing steers.

Data on individual daily feed intake, BW at 28-d intervals, and carcass composition were obtained on 1,212 crossbred steers. Within-animal regressions of cumulative feed intake and BW on linear and quadratic days on feed were used to quantify initial and ending BW, average daily observed feed intake (OFI), and ADG over a 120-d finishing period. Feed intake was predicted (PFI) with 3 biological simulation models (BSM): a) Decision Evaluator for the Cattle Industry, b) Cornell Value Discovery System, and c) NRC update 2000, using observed growth and carcass data as input. Residual feed intake (RFI) was estimated using OFI (RFI(EL)) in a linear statistical model (LSM), and feed conversion ratio (FCR) was estimated as OFI/ADG (FCR(E)). Output from the BSM was used to estimate RFI by using PFI in place of OFI with the same LSM, and FCR was estimated as PFI/ADG. These estimates were evaluated against RFI(EL) and FCR(E). In a second analysis, estimates of RFI were obtained for the 3 BSM as the difference between OFI and PFI, and these estimates were evaluated against RFI(EL). The residual variation was extremely small when PFI was used in the LSM to estimate RFI, and this was mainly due to the fact that the same input variables (initial BW, days on feed, and ADG) were used in the BSM and LSM. Hence, the use of PFI obtained with BSM as a replacement for OFI in a LSM to characterize individual animals for RFI was not feasible. This conclusion was also supported by weak correlations (<0.4) between RFI(EL) and RFI obtained with PFI in the LSM, and very weak correlations (<0.13) between RFI(EL) and FCR obtained with PFI. In the second analysis, correlations (>0.89) for RFI(EL) with the other RFI estimates suggest little difference between RFI(EL) and any of these RFI estimates. In addition, results suggest that the RFI estimates calculated with PFI would be better able to identify animals with low OFI and small ADG as inefficient compared with RFI(EL). These results may be due to the fact that computer models predict performance on an individual-animal basis in contrast to a LSM, which estimates a fixed relationship for all animals; hence, the BSM may provide RFI estimates that are closer to the true biological efficiency of animals. In addition, BSM may facilitate comparisons across different data sets and provide more accurate estimates of efficiency in small data sets where errors would be greater with a LSM.

Intensive training over 5 days improves colonoscopy skills long-term.

BACKGROUND AND AIMS: Poor standards in colonoscopy services and the introduction of a colorectal cancer screening program in the United Kingdom have highlighted the need to establish high-quality training and competency assessments in colonoscopy. The aims of this study were to evaluate the effectiveness of a 1-week hands-on colonoscopy course utilizing novel assessment tools. METHODS: Twenty-one doctors with varying colonoscopy experience who attended an accelerated colonoscopy training week (ACTW) were prospectively studied. They were trained and assessed in key aspects of colonoscopy. Knowledge was assessed with a multiple choice question (MCQ) paper. Practical hand skills were taught and evaluated using a computer simulator and live case teaching. Actual colonoscopy performance was assessed using Direct Observation of Procedural Skills scores (DOPS) and an objective tri-split video score of insertion technique. Two independent trainers taught and assessed the trainees at the start and end of the ACTW and at a median of 9 months' follow-up. RESULTS: Following training there were significant improvements in the MCQ score (P < 0.001), the simulator test case times (P = 0.02, P = 0.003), and the global DOPS score (P < or = 0.02). All improvements following the accelerated training were sustained at a median follow-up of 9 months. CONCLUSIONS: This study is the first in the literature to describe the positive, sustained impact of an intensive hands-on colonoscopy training course. Measurements of performance in key areas of skill acquisition improved following training.

Using simulation models to predict feed intake: phenotypic and genetic relationships between observed and predicted values in cattle.

The objectives of this study were to evaluate the accuracy of the Decision Evaluator for the Cattle Industry (DECI) and the Cornell Value Discovery System (CVDS) in predicting individual DMI and to assess the feasibility of using predicted DMI data in genetic evaluations of cattle. Observed individual animal data on the average daily DMI (OFI), ADG, and carcass measurements were obtained from postweaning records of 504 steers from 52 sires (502 with complete data). The experimental data and daily temperature and wind speed data were used as inputs to predict average daily feed DMI (kg) required (feed required; FR) for maintenance, cold stress, and ADG; maintenance and cold stress; ADG; maintenance and ADG; and maintenance alone, with CVDS (CFRmcg, CFRmc, CFRg, CFRmg, and CFRm, respectively) and DECI (DFRmcg, DFRmc, DFRg, DFRmg, and DFRm, respectively). Genetic parameters were estimated by REML using an animal model with age on test as a covariate and with genotype, age of dam, and year as fixed effects. Regression equations for observed on predicted DMI were OFI = 1.27 (SE = 0.27) + 0.83 (SE = 0.04) x CFRmcg [R2 = 0.44, residual SD (s(y.x)) = 0.669 kg/d] and OFI = 1.32 (SE = 0.22) + 0.8 (SE = 0.03) x DFRmcg (R2 = 0.53, s(y.x) = 0.612 kg/d). Heritability of OFI was 0.27 +/- 0.12, and heritabilities ranged from 0.33 +/- 0.12 to 0.41 +/- 0.13 for predicted measures of DMI. Phenotypic and genetic correlations between OFI and CFRmcg, CFRmc, CFRg, CFRmg, CFRm, DFRmcg, DFRmc, DFRg, DFRmg, and DFRm were 0.67, 0.73, 0.41, 0.63, 0.78, 0.73, 0.82, 0.45, 0.77, and 0.86 (P < 0.001 for all phenotypic correlations); and 0.95 +/- 0.07, 0.82 +/- 0.13, 0.89 +/- 0.09, 0.95 +/- 0.07, 0.91 +/- 0.09, 0.96 +/- 0.07, 0.89 +/- 0.09, 0.88 +/- 0.09, 0.96 +/- 0.06, and 0.96 +/- 0.07, respectively. Phenotypic and genetic correlations between CFRmcg and DFRmcg, CFRmc and DFRmc, CFRg and DFRg, CFRmg and DFRmg, and CFRm and DFRm were 0.98, 0.94, 0.99, 0.98, and 0.95 (P < 0.001 for all phenotypic correlations), and 0.99 +/- 0.004, 0.98 +/- 0.017, 0.99 +/- 0.004, 0.99 +/- 0.005, and 0.97 +/- 0.021, respectively. The strong genetic relationships between OFI and CFRmcg, CFRmg, DFRmcg, and DFRmg indicate that these predicted measures of DMI may be used in genetic evaluations and that DM requirements for cold stress may not be needed, thus reducing model complexity. However, high genetic correlations for final weight with OFI, CFRmcg, and DFRmcg suggest that the technology needs to be further evaluated in populations with genetic variance in feed efficiency.

Review article: Population screening for colorectal cancer.

Colorectal cancer is a common cancer and common cause of death. The mortality rate from colorectal cancer can be reduced by identification and removal of cancer precursors, adenomas, or by detection of cancer at an earlier stage. Pilot screening programmes have demonstrated decreased colorectal cancer mortality; as a result many countries are developing colorectal cancer screening programmes. The most common modalities being evaluated are faecal occult blood testing, flexible sigmoidoscopy and colonoscopy. Implementation of screening tests has been hampered by cost, invasiveness, availability of resources and patient acceptance. New technologies such at computed tomographic colonography and stool screening for molecular markers of neoplasia are in development as potential minimally invasive tools. This review considers who should be screened, which test to use and how often to screen.

Technical note: a dynamic model to predict the composition of fat-free matter gains in cattle.

Composition of empty BW (EBW) was described in terms of ether-extractable lipid (FAT) and fat-free matter (FFM), and the terms dEBW, dFAT, and dFFM were used to represent daily gains in these components. The dFFM comprised protein, water, and ash, and a model was developed to predict the composition of dFFM. The conceptual approach used in model development was based on experimental data that showed as cattle grew from birth to maturity: 1) the water content of FFM decreased and the protein and ash content increased; 2) the protein content of FFM increased at a decreasing rate; and 3) the protein-to-ash ratio in the fat-free DM was approximately constant. These results suggest that the protein content of dFFM would be high at birth and decrease at a decreasing rate as the animal grows. The protein content of dFFM was predicted as a function of the fraction of dEBW that was dFFM, FAT content of EBW, and dFFM. A fixed protein-to-ash ratio of 4.1:1 was used to calculate the quantity of ash, and water was obtained as a residual. Growth and body composition of Hereford x Angus steers from birth to 500 kg BW were simulated with a previously published model using the experimental growth data as input, and the model under discussion was used to predict the composition of dFFM. Predicted response curves of the EBW components over the growth period were similar in shape to observed data. Predicted curvilinearity in response of protein weight against FFM weight for Hereford x Angus steers was similar to observed data. The standard error about the regression of predicted on observed protein weight was 1.87 kg, and the average bias of the model was to underpredict protein weight by 0.64%. Compared with using a constant value for the protein fraction of dFFM, the model provided more accurate predictions of dEBW in an independent evaluation data set.

Coccidiosis immunization: effects of mushroom and herb polysaccharides on immune responses of chickens infected with Eimeria tenella.

An experiment was conducted to investigate the effects of polysaccharide extracts (E) of two mushrooms, Lentinus edodes (LenE) and Tremella fuciformis (TreE), and an herb, Astragalus membranaceus (AstE), on the immune responses of chickens infected with Eimeria tenella. A total of 180 broiler chickens were assigned to nine groups: three groups were fed with each of the extracts (LenE, TreE, and AstE), three groups were fed with the extracts and immunized with live oocyst vaccine (LenE+V, TreE+V, and AstE+V), a group was immunized with the vaccine only, and there were two controls (E. tenella-infected and noninfected groups). The oocyst vaccine was given at 4 days of age, and the extracts (1 g/kg of the diet) were supplemented from 8 to 14 days of age. At 18 days of age, all birds except those in the noninfected group were infected with 9 x 10(4) sporulated oocysts. The results showed that at 7 days postinfection (p.i.), birds fed the extracts without vaccination had lower body weight (BW) gain than those given the vaccine only. However, the extracts in conjunction with the vaccine significantly enhanced BW gain of the infected chickens compared with the vaccine group. Of the three extracts, LenE and TreE showed a better growth-promoting effect. The extracts largely increased oocyst excretion of droppings during the primary response postvaccination. The cecal peak oocyst output and lesion scores measured at 7 days p.i. were higher in the groups fed the extracts than in the group immunized with the vaccine only, whereas those of the groups fed with the extracts and immunized with the vaccine were not significantly different from the vaccine group. Of the three extracts, both LenE- and AstE-fed groups showed lower cecal oocyst output. Thus, as compared with the extracts, the live, attenuated vaccine showed better results with significantly increased immune response in coccidial infected birds. The polysaccharide extracts may prove useful against avian coccidiosis, and, particularly when they are used in conjunction with vaccine, they have shown preliminary promise against the experimental coccidial infection.

Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk.

BACKGROUND AND AIMS: The risk of colorectal cancer is increased in ulcerative colitis (UC). Patients with UC have diverse colonoscopic appearances. Determining colonoscopic markers for cancer risk could allow patient risk stratification. PATIENTS AND METHODS: Following on from an earlier study which demonstrated a correlation between inflammation severity and neoplasia risk, a case control study was performed to look for colonoscopic markers of colorectal neoplasia risk in UC. Each patient with neoplasia detected between 1988 and 2002 was matched with two non-dysplastic colitic controls. Data were collected on post-inflammatory polyps, scarring, strictures, backwash ileitis, a shortened, tubular, or featureless colon, severe inflammation, and normal looking surveillance colonoscopies. RESULTS: Cases (n = 68) and controls (n = 136) were well matched. On univariate analysis, cases were significantly more likely to have post-inflammatory polyps (odds ratio (OR) 2.14 (95% confidence interval 1.24-3.70)), strictures (OR 4.22; 1.08-15.54), shortened colons (OR 10.0; 1.17-85.6), tubular colons (OR 2.03; 1.00-4.08), or segments of severe inflammation (OR 3.38; 1.41-10.13), and less likely to have had a macroscopically normal looking colonoscopy (OR 0.40; 0.21-0.74). After multivariate analysis, a macroscopically normal looking colonoscopy (OR 0.38; 0.19-0.73), post-inflammatory polyps (2.29; 1.28-4.11), and strictures (4.62; 1.03-20.8) remained significant. The five year risk of colorectal cancer following a normal looking colonoscopy was no different from that of matched general population controls. CONCLUSIONS: Macroscopic colonoscopic features help predict neoplasia risk in UC. Features of previous/ongoing inflammation signify an increased risk. A macroscopically normal looking colonoscopy returns the cancer risk to that of the general population: it should be possible to reduce surveillance frequency to five years in this cohort.

A prospective study of colonoscopy practice in the UK today: are we adequately prepared for national colorectal cancer screening tomorrow?

AIM: To study the availability and quality of adult and paediatric colonoscopy in three National Health Service (NHS) regions. METHOD: A prospective four month study of colonoscopies in North East Thames, West Midlands, and East Anglia. PATIENTS: Subjects undergoing colonoscopy in 68 endoscopy units. RESULTS: A total of 9223 colonoscopies were studied. The mean number of colonoscopies performed over the four month period was 142 in district general hospitals and 213 in teaching hospitals. Intravenous sedation was administered in 94.6% of procedures, but 2.2% and 11.4% of "at risk" patients did not have continuous venous access or did not receive supplemental oxygen, respectively. Caecal intubation was recorded in 76.9% of procedures but the adjusted caecal intubation rate was only 56.9%. Reasons for failing to reach the caecum included patient discomfort (34.7%), looping (29.7%), and poor bowel preparation (19.6%). A normal colonoscopy was reported in 42.1%. The most common diagnosis was polyps (22.5%) followed by diverticular disease (14.9%). Inflammatory bowel disease was recorded in 13.9% and carcinoma in 3.8%. Only half of the patients remembered being told of possible adverse events prior to the procedure. Rectal bleeding requiring admission following colonoscopy was reported in six patients. The overall perforation rate was 1:769 and colonoscopy was considered a possible factor in six deaths occurring within 30 days of the procedure. Only 17.0% of colonoscopists had received supervised training for their first 100 colonoscopies and only 39.3% had attended a training course. CONCLUSION: There is serious under provision of colonoscopy service in most NHS hospitals. Endoscopy sedation guidelines are not always adhered to and there is a wide variation in practice between units. Colonoscopy is often incomplete and does not achieve the target 90% caecal intubation rate. Serious complications of colonoscopy were comparable with previous studies. Training in colonoscopy is often inadequate and improved practice should result from better training.

A dynamic model of metabolizable energy utilization in growing and mature cattle. I. Metabolizable energy utilization for maintenance and support metabolism.

Models to predict heat production attributable to maintenance and support metabolism in growing and mature cattle were developed on the basis of three concepts. The first concept is that animals fed fixed amounts of the same diet achieve weight equilibrium over an extended feeding period, and that the ME consumed at weight equilibrium is the maintenance requirement. The second concept is that a part of the heat production resulting from ME consumed above the maintenance requirement is associated with an elevation of vital functions (support metabolism), and this heat production can be modeled as a function of the level of feeding. The third concept is that previous levels of nutrition affect current estimates of heat production, and that this impact can be modeled as a delayed response in heat production associated with support metabolism. Experimental data on feed consumption showed that maintenance requirements varied in simple proportion to BW, not only for different breeds of mature cattle at BW equilibrium, but also for calves and growing steers held at BW stasis. Experimental data in which different breeds of cattle achieved weight equilibrium when fed fixed amounts of a specific diet were used to estimate breed parameters associated with maintenance for 21 breeds of cattle and 15 biological types of crossbred cattle. Level of feeding was estimated as a multiple of the maintenance intake and used to model heat production associated with support metabolism. Other experimental data on growing cattle were used to estimate breed parameters for predicting heat production associated with support metabolism for 21 breeds of cattle and 15 biological types of crossbred cattle. A distributed lag function was used to model the delayed response in heat production associated with support metabolism with changes in plane of nutrition. The models were tested by simulating experimental data for three breeds of weaned steers finished on high-energy diets. Results for the total heat production associated with maintenance and support metabolism expressed on a unit BW basis showed a similar response with stage of maturity when compared with other experimental data.

A dynamic model of metabolizable energy utilization in growing and mature cattle. II. Metabolizable energy utilization for gain.

Component models were developed to predict the net efficiency of ME utilization for gain in cattle and to predict daily gain using recovered energy as the input. These models were integrated into a single model to predict daily gain from ME available for gain. One component model predicts the net efficiency of ME utilization for gain using constant partial net efficiencies of 0.2 and 0.75 for ME retention as protein and fat, respectively. This model predicts net efficiency of ME utilization for gain as a function of the ratio of the energy recovered in protein to the total energy recovered. The other component model predicts daily gain as a function of recovered energy and is represented by a system of ordinary differential equations that are numerically integrated on a daily basis. This model was developed by reformulating the equations in a published body composition model that uses daily gain to predict composition of gain since recovered energy is a function of gain and composition of gain. The equations in the two component models interact in that net efficiency is used to predict recovered energy from ME for gain, and in turn, recovered energy is used to predict gain in empty BW, which determines net efficiency through composition of gain. The numeric integration procedure provides an iterative solution for net efficiency. Simulated response of net efficiency for Hereford x Angus steers at 400 kg of empty BW decreased from 0.57 to 0.52 on diets with ME densities of 3.1 and 2.6 Mcal/kg of DM, and restricting the lower-quality diet to 75% of ad libitum intake resulted in a simulated net efficiency of 0.47. These responses in net efficiency were shown to be a result of composition of gain, with leaner gains resulting in lower net efficiencies.

A dynamic model of metabolizable energy utilization in growing and mature cattle. III. Model evaluation.

Component models of heat production identified in a proposed system of partitioning ME intake and a dynamic systems model that predicts gain in empty BW in cattle resulting from a known intake of ME were evaluated. Evaluations were done in four main areas: 1) net efficiency of ME utilization for gain, 2) relationship between recovered energy and ME intake, 3) predicting gain in empty BW from recovered energy, and 4) predicting gain in empty BW from ME intake. An analysis of published data showed that the net partial efficiencies of ME utilization for protein and fat gain were approximately 0.2 and 0.75, respectively, and that the net efficiency of ME utilization for gain could be estimated using these net partial efficiencies and the fraction of recovered energy that is contained in protein. Analyses of published sheep and cattle experimental data showed a significant linear relationship between recovered energy and ME intake, with no evidence for a nonlinear relationship. Growth and body composition of Hereford x Angus steers simulated from weaning to slaughter showed that over the finishing period, 20.8% of ME intake was recovered in gain. These results were similar to observed data and comparable to feedlot data of 26.5% for a shorter finishing period with a higher-quality diet. The component model to predict gain in empty BW from recovered energy was evaluated with growth and body composition data of five steer genotypes on two levels of nutrition. Linear regression of observed on predicted values for empty BW resulted in an intercept and slope that were not different (P < 0.05) from 0 and 1, respectively. Evaluations of the dynamic systems model to predict gain in empty BW using ME intake as the input showed close agreement between predicted and observed final empty BW for steers that were finished on high-energy diets, and the model accurately predicted growth patterns for Angus, Charolais, and Simmental reproducing females from 10 mo to 7 yr of age.

Endoscopic resection of large sessile colonic polyps by specialist and non-specialist endoscopists.

BACKGROUND: Patients with large sessile colonic polyps for which endoscopic resection might be feasible are often referred directly for operation. The aim of this study was to determine the outcome of patients with such polyps diagnosed by specialist and non-specialist colonoscopists. METHODS: Patients with large (greater than 2 cm) sessile polyps detected at colonoscopy from January 1995 to July 2000 were identified. Resection technique and clinical and endoscopic outcomes were recorded. Two of the colonoscopists (B.P.S., C.B.W.) are recognized as specialists. RESULTS: Some 130 polyps were identified, 100 detected by either of two specialist endoscopists (including 14 cancers) and 30 by 14 non-specialist endoscopists (including ten cancers). Endoscopic resection of benign polyps was attempted by experts in 80 (93 per cent) of 86 cases and by non-experts in 15 of 20 cases (P = 0.03), with successful management by endoscopy alone in 61 (76 per cent) of 80 and in six of 15 cases respectively (P = 0.01). Complications occurred following three polypectomies performed by an expert (bleeding, two; pain, one) and one by a non-expert (bleeding). The estimated end-cost of management by specialists was less than half of that by non-specialists. CONCLUSION: Endoscopic resection of large sessile colonic polyps is feasible in the majority of patients and should be considered as first-line therapy. Prompt referral to a specialist endoscopist may improve outcomes by avoiding operation or enabling complete excision at a single endoscopy session.

Patient pain during colonoscopy: an analysis using real-time magnetic endoscope imaging.

BACKGROUND AND STUDY AIMS: Colonoscopy is generally perceived as being a painful procedure. Contributory factors are: stretching of the colonic wall and mesenteric attachments from looping of the instrument shaft, overinsufflation, the degree of torque or force applied to the colonoscope shaft, and patient pain threshold. The aim of this study was to determine the frequency of pain episodes experienced during diagnostic colonoscopy and the corresponding colonoscope configuration, utilizing real-time magnetic endoscope imaging (MEI). PATIENTS AND METHODS: Consecutive outpatients undergoing colonoscopy were studied. Patients with previous colonic resections were excluded. Procedures were commenced with antispasmodics only, and patient sedation was self-administered whenever significant discomfort was experienced, using a patient-controlled analgesia (PCA) syringe pump. All "demands" were correlated with the MEI record, which was subsequently analysed. RESULTS: A total of 650 demands were recorded in 102 patients. Seventy-seven percent of all demands occurred with the colonoscope tip in the sigmoid colon, 7 % in the descending colon, 6 % at the splenic flexure, 5 % in the transverse colon, and 4 % in the proximal colon. Ninety percent of all pain episodes coincided with either looping (79 %) or straightening of the colonoscope shaft (11 %); presumed overinsufflation being an infrequent cause of pain (9 %). Of the loops encountered during colonoscopy, the N-sigmoid spiral loop was associated with the majority of pain episodes (56 %). Looping was both more frequent ( P = 0.0002) and less well tolerated in women than in men ( P = 0.0140). CONCLUSIONS: This study is the first to document pain at colonoscopy accurately. Looping, particularly in the variable anatomy of the sigmoid colon, is the major cause of pain, especially in women. Use of MEI may improve pain control by facilitating the straightening of loops within the sigmoid colon, and by enabling the endoscopist to target patient analgesia.

Requirement for Ca2+/calmodulin-dependent kinase type IV/Gr in setting the thymocyte selection threshold.

The outcome of thymocyte selection is influenced by the nature of Ca2+ signals transduced by the TCR. Robust Ca2+ responses characterize high-affinity, negatively selecting peptide/TCR interactions, while modest responses typify lower-affinity, positively selecting interactions. To elucidate mechanisms by which thymocytes decode distinct Ca2+ signals, we examined selection events in mice lacking Ca2+/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr), which is enriched in thymocytes. CaMKIV/Gr-deficient thymocytes exhibited impaired positive selection and defective Ca2+-dependent gene transcription. Significantly, CaMKIV/Gr deficiency raised the selection threshold of peptide/TCR interactions such that a peptide that normally induced weak negative selection instead promoted positive selection. These results demonstrate an important role for CaMKIV/Gr in sensitizing thymocytes to selection by low-affinity peptides.

Design of a multicentre randomised trial to evaluate flexible sigmoidoscopy in colorectal cancer screening.

A randomised, controlled trial in progress in 14 United Kingdom and six Italian centres is evaluating screening for colorectal cancer using a single flexible sigmoidoscopy (FS) at around the age of 60 with removal during FS of all small adenomas, and colonoscopy for "high risk" polyps. The regimen aims to ensure that 95% of people (with either no polyps or only low risk polyps) complete the entire screening process in a single visit. This paper describes the rationale and design of the trial. Participants were patients aged between 55 and 64 on the lists of designated general practitioners (GPs) who were not excluded by their GP. A two stage recruitment procedure was employed to raise compliance rates in the intervention group. Potentially eligible persons were sent an "interest in screening" questionnaire; those who responded positively were randomised to the intervention or control groups. The trial is sufficiently large to estimate within narrow confidence intervals the magnitude of benefit and the duration of effect and optimum age for a single screen. It also examines the feasibility and acceptability of the screening regimen, and will identify training and quality assurance issues. Recruitment and screening are now complete and all baseline data have been collected. The first analysis of the effect on colorectal cancer incidence and mortality rates and suitability for a national screening programme can be expected in 2004.

Contour interaction for an easily resolvable stimulus.

It is well known that adjacent contours can reduce the visual acuity of single letters. Although this has traditionally been considered only in terms of a neural-based interaction, it has recently been suggested that the information content in the stimulus may account for the interaction. Here we ask the question, "Do similar interference effects occur for the discrimination of low-contrast letters whose size is larger than that corresponding to the resolution limit?" If so, previous acuity-based interaction results may be of more general importance. We show that while there are interference effects of nearby contours, they are of a form different from that observed at the resolution limit. In particular, the contrast polarity of the nearby contour is unimportant, which in turn suggests that a physical explanation is inappropriate. Also, the discrimination of an easily resolvable, unflanked Landolt C target requires information over a much wider spatial-frequency range than its counterpart at the resolution limit.

Risk factors predictive of positive findings at colonoscopy(1).

PURPOSE:The surgery department at our institution has become the primary provider of colonoscopy. We sought to determine which risk factors, if any, were most predictive of positive findings on colonoscopy.Between March and December 1999, 202 consecutive patients referred for colonoscopy were identified. Each patient was interviewed and a standard questionnaire completed before colonoscopy to establish possible risk factors for the presence of colorectal cancer or polyps. The colonoscopy findings, including pathology reports, were correlated with the questionnaire and subjected to chi-square analysis to determine statistical significance.The risk factors most likely to be associated with a finding of colorectal cancer or polyp were family history of colorectal cancer (65%), bleeding (65%), fecal occult blood positive (64%), abdominal pain (60%), and alteration of bowel habits (53%).No risk factor by history or presenting symptoms reached statistical significance as an independent predictor of a positive colonoscopy finding. However, most frequently associated with positive colonoscopy findings were a family history of colorectal cancer, bleeding, positive fecal occult blood test, presence of abdominal pain, and alteration of bowel habits. A history to include these risk factors can serve to prioritize the need for a colonoscopic examination.