Abnormal LDIflare but Normal Quantitative Sensory Testing and Dermal Nerve Fiber Density in Patients with Painful Diabetic Neuropathy

OBJECTIVE—Abnormal small nerve fiber function may be an early feature of diabetic neuropathy and may also underlie painful symptoms. Methods for assessing small-fiber damage include quantitative sensory testing (QST) and determining intraepidermal nerve fiber density. We recently described a reproducible physiological technique, the LDIflare, which assesses small-fiber function and thus may reflect early dysfunction before structural damage. The value of this technique in painful neuropathy was assessed by comparing it with QST and dermal nerve fiber density (NFD)

When increasing population density can promote the evolution of metabolic cooperation.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via the DOI in this record.Microbial cooperation drives ecological and epidemiological processes and is affected by the ecology and demography of populations. Population density influences the selection for cooperation, with spatial structure and the type of social dilemma, namely public-goods production or self-restraint, shaping the outcome. While existing theories predict that in spatially structured environments increasing population density can select either for or against cooperation, experimental studies with both public-goods production and self-restraint systems have only ever shown that increasing population density favours cheats. We suggest that the disparity between theory and empirical studies results from experimental procedures not capturing environmental conditions predicted by existing theories to influence the outcome. Our study resolves this issue and provides the first experimental evidence that high population density can favour cooperation in spatially structured environments for both self-restraint and public-goods production systems. Moreover, using a multi-trait mathematical model supported by laboratory experiments we extend this result to systems where the self-restraint and public-goods social dilemmas interact. We thus provide a systematic understanding of how the strength of interaction between the two social dilemmas and the degree of spatial structure within an environment affect selection for cooperation. These findings help to close the current gap between theory and experiments.RJL and IG: European Research Council No. 647292 MathModExp. BJP: Engineering and Physical Sciences Research Council Doctoral training grant studentship

The utility of clinical decision tools for diagnosing osteoporosis in postmenopausal women with rheumatoid arthritis

BACKGROUND: Patients with rheumatoid arthritis have a higher risk of low bone mineral density than normal age matched populations. There is limited evidence to support cost effectiveness of population screening in rheumatoid arthritis and case finding strategies have been proposed as a means to increase cost effectiveness of diagnostic screening for osteoporosis. This study aimed to assess the performance attributes of generic and rheumatoid arthritis specific clinical decision tools for diagnosing osteoporosis in a postmenopausal population with rheumatoid arthritis who attend ambulatory specialist rheumatology clinics. METHODS: A cross-sectional study of 127 ambulatory post-menopausal women with rheumatoid arthritis was performed. Patients currently receiving or who had previously received bone active therapy were excluded. Eligible women underwent clinical assessment and dual-energy-xray absorptiometry (DXA) bone mineral density assessment. Clinical decision tools, including those specific for rheumatoid arthritis, were compared to seven generic post-menopausal tools to predict osteoporosis (defined as T score < -2.5). Sensitivity, specificity, positive predictive and negative predictive values and area under the curve were assessed. The diagnostic attributes of the clinical decision tools were compared by examination of the area under the receiver-operator-curve. RESULTS: One hundred and twenty seven women participated. The median age was 62 (IQR 56-71) years. Median disease duration was 108 (60-168) months. Seventy two (57%) women had no record of a previous DXA examination. Eighty (63%) women had T scores at femoral neck or lumbar spine less than -1. The area under the ROC curve for clinical decision tool prediction of T score <-2.5 varied between 0.63 and 0.76. The rheumatoid arthritis specific decision tools did not perform better than generic tools, however, the National Osteoporosis Foundation score could potentially reduce the number of unnecessary DXA tests by approximately 45% in this population. CONCLUSION: There was limited utility of clinical decision tools for predicting osteoporosis in this patient population. Fracture prediction tools that include risk factors independent of BMD are needed

Randomized clinical trial of surgery versus conservative therapy for carpal tunnel syndrome [ISRCTN84286481]

BACKGROUND: Conservative treatment remains the standard of care for treating mild to moderate carpal tunnel syndrome despite a small number of well-controlled studies and limited objective evidence to support current treatment options. There is an increasing interest in the usefulness of wrist magnetic resonance imaging could play in predicting who will benefit for various treatments. METHOD AND DESIGN: Two hundred patients with mild to moderate symptoms will be recruited over 3 1/2 years from neurological surgery, primary care, electrodiagnostic clinics. We will exclude patients with clinical or electrodiagnostic evidence of denervation or thenar muscle atrophy. We will randomly assign patients to either a well-defined conservative care protocol or surgery. The conservative care treatment will include visits with a hand therapist, exercises, a self-care booklet, work modification/ activity restriction, B6 therapy, ultrasound and possible steroid injections. The surgical care would be left up to the surgeon (endoscopic vs. open) with usual and customary follow-up. All patients will receive a wrist MRI at baseline. Patients will be contacted at 3, 6, 9 and 12 months after randomization to complete the Carpal Tunnel Syndrome Assessment Questionnaire (CTSAQ). In addition, we will compare disability (activity and work days lost) and general well being as measured by the SF-36 version II. We will control for demographics and use psychological measures (SCL-90 somatization and depression scales) as well as EDS and MRI predictors of outcomes. DISCUSSION: We have designed a randomized controlled trial which will assess the effectiveness of surgery for patients with mild to moderate carpal tunnel syndrome. An important secondary goal is to study the ability of MRI to predict patient outcomes

Quality Measures for the Diagnosis and Non-Operative Management of Carpal Tunnel Syndrome in Occupational Settings

Introduction: Providing higher quality medical care to workers with occupationally associated carpal tunnel syndrome (CTS) may reduce disability, facilitate return to work, and lower the associated costs. Although many workers’ compensation systems have adopted treatment guidelines to reduce the overuse of unnecessary care, limited attention has been paid to ensuring that the care workers do receive is high quality. Further, guidelines are not designed to enable objective assessments of quality of care. This study sought to develop quality measures for the diagnostic evaluation and non-operative management of CTS, including managing occupational activities and functional limitations. Methods: Using a variation of the well-established RAND/UCLA Appropriateness Method, we developed draft quality measures using guidelines and literature reviews. Next, in a two-round modified-Delphi process, a multidisciplinary panel of 11 U.S. experts in CTS rated the measures on validity and feasibility. Results: Of 40 draft measures, experts rated 31 (78%) valid and feasible. Nine measures pertained to diagnostic evaluation, such as assessing symptoms, signs, and risk factors. Eleven pertain to non-operative treatments, such as the use of splints, steroid injections, and medications. Eleven others address assessing the association between symptoms and work, managing occupational activities, and accommodating functional limitations. Conclusions: These measures will complement existing treatment guidelines by enabling providers, payers, policymakers, and researchers to assess quality of care for CTS in an objective, structured manner. Given the characteristics of previous measures developed with these methods, greater adherence to these measures will probably lead to improved patient outcomes at a population level

Killing by type VI secretion drives genetic phase separation and correlates with increased cooperation

By nature of their small size, dense growth and frequent need for extracellular metabolism, microbes face persistent public goods dilemmas. Genetic assortment is the only general solution stabilizing cooperation, but all known mechanisms structuring microbial populations depend on the availability of free space, an often unrealistic constraint. Here we describe a class of self-organization that operates within densely packed bacterial populations. Through mathematical modelling and experiments with Vibrio cholerae, we show how killing adjacent competitors via the Type VI secretion system (T6SS) precipitates phase separation via the ‘Model A' universality class of order-disorder transition mediated by killing. We mathematically demonstrate that T6SS-mediated killing should favour the evolution of public goods cooperation, and empirically support this prediction using a phylogenetic comparative analysis. This work illustrates the twin role played by the T6SS, dealing death to local competitors while simultaneously creating conditions potentially favouring the evolution of cooperation with kin

Challenges in microbial ecology: building predictive understanding of community function and dynamics.

The importance of microbial communities (MCs) cannot be overstated. MCs underpin the biogeochemical cycles of the earth's soil, oceans and the atmosphere, and perform ecosystem functions that impact plants, animals and humans. Yet our ability to predict and manage the function of these highly complex, dynamically changing communities is limited. Building predictive models that link MC composition to function is a key emerging challenge in microbial ecology. Here, we argue that addressing this challenge requires close coordination of experimental data collection and method development with mathematical model building. We discuss specific examples where model-experiment integration has already resulted in important insights into MC function and structure. We also highlight key research questions that still demand better integration of experiments and models. We argue that such integration is needed to achieve significant progress in our understanding of MC dynamics and function, and we make specific practical suggestions as to how this could be achieved