The Euler spiral of rat whiskers

This paper reports on an analytical study of the intrinsic shapes of 523 whiskers from 15 rats. We show that the variety of whiskers on a rat’s cheek, each of which has different lengths and shapes, can be described by a simple mathematical equation such that each whisker is represented as an interval on the Euler spiral. When all the representative curves of mystacial vibrissae for a single rat are assembled together, they span an interval extending from one coiled domain of the Euler spiral to the other. We additionally find that each whisker makes nearly the same angle of 47∘ with the normal to the spherical virtual surface formed by the tips of whiskers, which constitutes the rat’s tactile sensory shroud or “search space.” The implications of the linear curvature model for gaining insight into relationships between growth, form, and function are discussed

Leflunomide/hydroxychloroquine combination therapy targets type I IFN-associated proteins in patients with Sjögren's syndrome that show potential to predict and monitor clinical response

OBJECTIVES: To assess to what extent leflunomide (LEF) and hydroxychloroquine (HCQ) therapy in patients with primary Sjögren's syndrome (RepurpSS-I) targets type I IFN-associated responses and to study the potential of several interferon associated RNA-based and protein-based biomarkers to predict and monitor treatment. METHODS: In 21 patients treated with LEF/HCQ and 8 patients treated with placebo, blood was drawn at baseline, 8, 16 and 24 weeks. IFN-signatures based on RNA expression of five IFN-associated genes were quantified in circulating mononuclear cells and in whole blood. MxA protein levels were measured in whole blood, and protein levels of CXCL10 and Galectin-9 were quantified in serum. Differences between responders and non-responders were assessed and receiver operating characteristic analysis was used to determine the capacity of baseline expression and early changes (after 8 weeks of treatment) in biomarkers to predict treatment response at the clinical endpoint. RESULTS: IFN-signatures in peripheral blood mononuclear cell and whole blood decreased after 24 weeks of LEF/HCQ treatment, however, changes in IFN signatures only poorly correlated with changes in disease activity. In contrast to baseline IFN signatures, baseline protein concentrations of galectin-9 and decreases in circulating MxA and Galectin-9 were robustly associated with clinical response. Early changes in serum Galectin-9 best predicted clinical response at 24 weeks (area under the curve 0.90). CONCLUSIONS: LEF/HCQ combination therapy targets type-I IFN-associated proteins that are associated with strongly decreased B cell hyperactivity and disease activity. IFN-associated Galectin-9 is a promising biomarker for treatment prediction and monitoring in pSS patients treated with LEF/HCQ.</p

The Generation R Study Biobank: a resource for epidemiological studies in children and their parents

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health from fetal life until young adulthood. In total, 9,778 mothers were enrolled in the study. Prenatal and postnatal data collection is conducted by physical examinations, questionnaires, interviews, ultrasound examinations and biological samples. Major efforts have been conducted for collecting biological specimens including DNA, blood for phenotypes and urine samples. In this paper, the collection, processing and storage of these biological specimens are described. Together with detailed phenotype measurements, these biological specimens form a unique resource for epidemiological studies focused on environmental exposures, genetic determinants and their interactions in relation to growth, health and development from fetal life onwards

Leflunomide/hydroxychloroquine combination therapy targets type I IFN-associated proteins in patients with Sjögren's syndrome that show potential to predict and monitor clinical response

Objectives To assess to what extent leflunomide (LEF) and hydroxychloroquine (HCQ) therapy in patients with primary Sjögren's syndrome (RepurpSS-I) targets type I IFN-associated responses and to study the potential of several interferon associated RNA-based and protein-based biomarkers to predict and monitor treatment. Methods In 21 patients treated with LEF/HCQ and 8 patients treated with placebo, blood was drawn at baseline, 8, 16 and 24 weeks. IFN-signatures based on RNA expression of five IFN-associated genes were quantified in circulating mononuclear cells and in whole blood. MxA protein levels were measured in whole blood, and protein levels of CXCL10 and Galectin-9 were quantified in serum. Differences between responders and non-responders were assessed and receiver operating characteristic analysis was used to determine the capacity of baseline expression and early changes (after 8 weeks of treatment) in biomarkers to predict treatment response at the clinical endpoint. Results IFN-signatures in peripheral blood mononuclear cell and whole blood decreased after 24 weeks of LEF/HCQ treatment, however, changes in IFN signatures only poorly correlated with changes in disease activity. In contrast to baseline IFN signatures, baseline protein concentrations of galectin-9 and decreases in circulating MxA and Galectin-9 were robustly associated with clinical response. Early changes in serum Galectin-9 best predicted clinical response at 24 weeks (area under the curve 0.90). Conclusions LEF/HCQ combination therapy targets type-I IFN-associated proteins that are associated with strongly decreased B cell hyperactivity and disease activity. IFN-associated Galectin-9 is a promising biomarker for treatment prediction and monitoring in pSS patients treated with LEF/HCQ

Opening out and closing down: The treatment of uncertainty in transport planning’s forecasting paradigm

© 2019, The Author(s). Since the 1960s, development of the transport system has been framed by the notion of forecasting future demand. Yet the past decade or more appears to signal some significant changes to the role of travel in society which are having a material impact on how much people travel (and may travel in the future). Coupled with the potential for major technological changes and a range of climate adaptation scenarios, the future of mobility presents today’s decision making on transport strategy and investment with a broader set of uncertainties than has previously been considered. This paper examines current mainstream practice for incorporating uncertainty into decision-making, through an illustrative case study of the highly codified approaches of the Department for Transport in England. It deconstructs the issue by first focussing on different ways in which there is an opening out or acceptance of new uncertainties and how this creates a (wider) set of potential futures. It then turns to consider how this set of futures is used, or not, in decision-making, i.e. the process of closing down uncertainty to arrive at or at least inform a decision. We demonstrate that, because the range of uncertainties has broadened in scope and scale, the traditional technocratic approach of closing down decisions through sensitivity testing is at odds with the greater breadth now being called for at the opening out stage. We conclude that transport decision-making would benefit from a rebalancing of technical depth with analytical breadth. The paper outlines a plausible new approach to opening out and closing down that is starting to be applied in practice. This approach must be accompanied by an opening up of the processes by which technical advice for decisions are reached and how uncertainties are understood and negotiated

A new interdisciplinary treatment strategy versus usual medical care for the treatment of subacromial impingement syndrome: a randomized controlled trial

BACKGROUND: Subacromial impingement syndrome (SIS) is the most frequently recorded shoulder disorder. When conservative treatment of SIS fails, a subacromial decompression is warranted. However, the best moment of referral for surgery is not well defined. Both early and late referrals have disadvantages – unnecessary operations and smaller improvements in shoulder function, respectively. This paper describes the design of a new interdisciplinary treatment strategy for SIS (TRANSIT), which comprises rules to treat SIS in primary care and a well-defined moment of referral for surgery. METHODS/DESIGN: The effectiveness of an arthroscopic subacromial decompression versus usual medical care will be evaluated in a randomized controlled trial (RCT). Patients are eligible for inclusion when experiencing a recurrence of SIS within one year after a first episode of SIS which was successfully treated with a subacromial corticosteroid injection. After inclusion they will receive injection treatment again by their general practitioner. When, after this treatment, there is a second recurrence within a year post-injection, the participants will be randomized to either an arthroscopic subacromial decompression (intervention group) or continuation of usual medical care (control group). The latter will be performed by a general practitioner according to the Dutch National Guidelines for Shoulder Problems. At inclusion, at randomization and three, six and 12 months post-randomization an outcome assessment will take place. The primary outcome measure is the patient-reported Shoulder Disability Questionnaire. The secondary outcome measures include both disease-specific and generic measures, and an economic evaluation. Treatment effects will be compared for all measurement points by using a GLM repeated measures analyses. DISCUSSION: The rationale and design of an RCT comparing arthroscopic subacromial decompression with usual medical care for subacromial impingement syndrome are presented. The results of this study will improve insight into the best moment of referral for surgery for SIS

Mapping polyclonal antibody responses to bacterial infection using next generation phage display

Mapping polyclonal antibody responses to infectious diseases to identify individual epitopes has the potential to underpin the development of novel serological assays and vaccines. Here, phage-peptide library panning coupled with screening using next generation sequencing was used to map antibody responses to bacterial infections. In the first instance, pigs experimentally infected with Salmonella enterica serovar Typhimurium was investigated. IgG samples from twelve infected pigs were probed in parallel and phage binding compared to that with equivalent IgG from pre-infected animals. Seventy- seven peptide mimotopes were enriched specifically against sera from multiple infected animals. Twenty-seven of these peptides were tested in ELISA and twenty-two were highly discriminatory for sera taken from pigs post-infection (P < 0.05) indicating that these peptides are mimicking epitopes from the bacteria. In order to further test this methodology, it was applied to differentiate antibody responses in poultry to infections with distinct serovars of Salmonella enterica. Twenty-seven peptides were identified as being enriched specifically against IgY from multiple animals infected with S. Enteritidis compared to those infected with S. Hadar. Nine of fifteen peptides tested in ELISA were highly discriminatory for IgY following S. Enteritidis infection (p < 0.05) compared to infections with S. Hadar or S. Typhimurium

Guideline for diagnosis and treatment of subacromial pain syndrome

Treatment of "subacromial impingement syndrome" of the shoulder has changed drastically in the past decade. The anatomical explanation as "impingement" of the rotator cuff is not sufficient to cover the pathology. "Subacromial pain syndrome", SAPS, describes the condition better. A working group formed from a number of Dutch specialist societies, joined by the Dutch Orthopedic Association, has produced a guideline based on the available scientific evidence. This resulted in a new outlook for the treatment of subacromial pain syndrome. The important conclusions and advice from this work are as follows: (1) The diagnosis SAPS can only be made using a combination of clinical tests. (2) SAPS should preferably be treated non-operatively. (3) Acute pain should be treated with analgetics if necessary. (4) Subacromial injection with corticosteroids is indicated for persistent or recurrent symptoms. (5) Diagnostic imaging is useful after 6 weeks of symptoms. Ultrasound examination is the recommended imaging, to exclude a rotator cuff rupture. (6) Occupational interventions are useful when complaints persist for longer than 6 weeks. (7) Exercise therapy should be specific and should be of low intensity and high frequency, combining eccentric training, attention to relaxation and posture, and treatment of myofascial trigger points (including stretching of the muscles) may be considered. (8) Strict immobilization and mobilization techniques are not recommended. (9) Tendinosis calcarea can be treated by shockwave (ESWT) or needling under ultrasound guidance (barbotage). (10) Rehabilitation in a specialized unit can be considered in chronic, treatment resistant SAPS, with pain perpetuating behavior. (11) There is no convincing evidence that surgical treatment for SAPS is more effective than conservature management. (12) There is no indication for the surgical treatment of asymptomatic rotator cuff tears

Lifestyle variables and the risk of myocardial infarction in the General Practice Research Database

<p>Abstract</p> <p>Background</p> <p>The primary objective of this study is to estimate the association between body mass index (BMI) and the risk of first acute myocardial infarction (AMI). As a secondary objective, we considered the association between other lifestyle variables, smoking and heavy alcohol use, and AMI risk.</p> <p>Methods</p> <p>This study was conducted in the general practice research database (GPRD) which is a database based on general practitioner records and is a representative sample of the United Kingdom population. We matched cases of first AMI as identified by diagnostic codes with up to 10 controls between January 1^st, 2001 and December 31^st, 2005 using incidence density sampling. We used multiple imputation to account for missing data.</p> <p>Results</p> <p>We identified 19,353 cases of first AMI which were matched on index date, GPRD practice and age to 192,821 controls. There was a modest amount of missing data in the database, and the patients with missing data had different risks than those with recorded values. We adjusted our analysis for each lifestyle variable jointly and also for age, sex, and number of hospitalizations in the past year. Although a record of underweight (BMI <18.0 kg/m²) did not alter the risk for AMI (adjusted odds ratio (OR): 1.00; 95% confidence interval (CI): 0.87–1.11) when compared with normal BMI (18.0–24.9 kg/m²), obesity (BMI ≥30 kg/m²) predicted an increased risk (adjusted OR: 1.41; 95% CI: 1.35–1.47). A history of smoking also predicted an increased risk of AMI (adjusted OR: 1.81; 95% CI: 1.75–1.87) as did heavy alcohol use (adjusted OR: 1.15; 95% CI: 1.06–1.26).</p> <p>Conclusion</p> <p>This study illustrates that obesity, smoking and heavy alcohol use, as recorded during routine care by a general practitioner, are important predictors of an increased risk of a first AMI. In contrast, low BMI does not increase the risk of a first AMI.</p