bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Administration of Astrovirus Capsid Protein Is Sufficient To Induce Acute Diarrhea
In Vivo
Authors: Meliopoulos Victoria A. , Marvin Shauna A. , Freiden Pamela , Moser Lindsey A. , Nighot Prashant , Ali Rizwana , Blikslager Anthony , Reddivari Muralidhar , Heath Richard J. , Koci Matthew D. , Schultz-Cherry Stacey
Published: November 2016

The disease mechanisms associated with the onset of astrovirus diarrhea are unknown. Unlike other enteric virus infections, astrovirus infection is not associated with an inflammatory response or cellular damage.
In vitro
studies in differentiated Caco-2 cells demonstrated that human astrovirus serotype 1 (HAstV-1) capsid protein alone disrupts the actin cytoskeleton and tight junction complex, leading to increased epithelial barrier permeability. In this study, we show that oral administration of purified recombinant turkey astrovirus 2 (TAstV-2) capsid protein results in acute diarrhea in a dose- and time-dependent manner in turkey poults. Similarly to that induced by infectious virus, TAstV-2 capsid-induced diarrhea was independent of inflammation or histological changes but was associated with increased intestinal barrier permeability, as well as redistribution of sodium hydrogen exchanger 3 (NHE3) from the membrane to the cytoplasm of the intestinal epithelium. Unlike other viral enterotoxins that have been identified, astrovirus capsid induces diarrhea after oral administration, reproducing the natural route of infection and demonstrating that ingestion of intact noninfectious capsid protein may be sufficient to provoke acute diarrhea. Based on these data, we hypothesize that the astrovirus capsid acts like an enterotoxin and induces intestinal epithelial barrier dysfunction.

IMPORTANCE
Acute gastroenteritis, with its sequela diarrhea, is one of the most important causes of childhood morbidity and mortality worldwide. A variety of infectious agents cause gastroenteritis, and in many cases, an enterotoxin produced by the agent is involved in disease manifestations. Although we commonly think of bacteria as a source of toxins, at least one enteric virus, rotavirus, produces a protein with enterotoxigenic activity during viral replication. In these studies, we demonstrate that oral administration of the turkey astrovirus 2 (TAstV-2) structural (capsid) protein induces acute diarrhea, increases barrier permeability, and causes relocalization of NHE3 in the small intestine, suggesting that rotavirus may not be alone in possessing enterotoxigenic activity.
Miliary tuberculosis in an immunocompetent male with a fatal outcome
Authors: Dunphy Louise , Keating Elizabeth , Parke T
Published: November 2016

A man aged 33 years, born in Nepal, but resident in the UK for 7 years presented to the emergency department with a 4-day history of general malaise, fever (temperature 38.6°C) and a non-productive cough. His medical history was unremarkable and no high-risk behaviour was identified. Clinical examination confirmed decreased air entry bilaterally with bibasal crackles. He was tachycardic, with a heart rate of 120 bpm. Further investigation with a 12-lead ECG confirmed supraventricular tachycardia (SVT) which was terminated with vagal manoeuvres. His chest radiograph demonstrated left basal consolidation. His white cell count was 11×109/L and his C reactive protein was 43.2 mg/L. His blood cultures revealed no growth. He was diagnosed with community-acquired pneumonia and started treatment with amoxicillin and clarithromycin. 3 days post admission, he was intubated for 24 hours in the Department of Intensive Care Medicine. Further episodes of SVT were observed and an ECHO showed a severely dilated and impaired left ventricle. Further chest radiographs illustrated diffuse consolidation with evidence of pulmonary oedema. HIV serology was negative. He developed transaminitis and thrombocytopenia. An ultrasound scan of his liver showed no obvious liver pathology. He remained tachypnoeic and due to worsening pulmonary oedema and extensive consolidation, he was readmitted to the intensive care unit. A CT abdomen with contrast showed an unusual pattern of lymphadenopathy with disproportionately enlarged coeliac axis nodes (5×7×5 cm) and minor para-aortic adenopathy, suspicious for lymphoma. On inserting his central venous catheter in his right internal jugular vein, pus was inadvertently aspirated from his right neck. Acid alcohol fast bacilli (AAFFB) were isolated from the pus and was subsequently identified asMycobacterium tuberculosis. He started treatment with antitubercular medication rifater: a combination of rifampicin 720 mg od, isoniazid 300 mg po od and pyrazinamide 1750 mg. In addition, he received ethambutol 1000 mg po od and pyridoxine 5 mg. He developed worsening metabolic acidosis, pH 7.19, loss of respiratory compensation and pancytopenia. Right heart strain was evident on his Focused Intensive Care Echo. He developed an increased oxygen requirement and respiratory distress on the ventilator. An erect chest radiograph showed bilateral pneumothoraces and bronchopleural fistulae. A chest drain was inserted. Following discussion with the Cardiothoracic Surgeons, pleurodesis was not deemed possible. He developed inotropic-dependent shock with worsening lung compliance. As a result of his deteriorating ventilation, acidosis and hyperkalaemia, he started treatment with continuous veno-venous haemofiltration. With a diagnosis of miliary tuberculosis and SVT causing cardiogenic pulmonary oedema, this man sadly died with his family at his bedside 10 weeks following initial hospital presentation.
THE DEVELOPMENT AND VALIDATION OF A RUGBY LEAGUE MATCH SIMULATION – INTERCHANGE PROTOCOL WITH COLLISION ELEMENTS
Authors: Williamson P , Weston M
Published: November 2016

Rugby league is a collision sport that is intermittent in nature. Players require highly developed maximal aerobic power, muscular strength and power and speed and agility, to perform through an eighty minute game. In contrast to starting players, interchange players often perform 2 short (∼20 minutes) and more intense play. The aim of the investigation was to further develop a rugby league match simulation protocol for interchange players and determine the external validity and test – retest reliability among semi-professional rugby league players. Our modified Rugby League Movement Simulation Protocol for Interchange players included more realistic contact elements during the ‘Ball in Play’ portion of testing. Eight semi-professional Championship Rugby League players (age=26±3 years, height=180±3.4 cm, body mass=102.3±11.5 kg) performed the RLMSP-i twice, separated by one week. The protocol involved walking, jogging, running, sprinting and contact elements, based upon GPS data recorded during Super League matches. Movement was recorded using 5 Hz GPS device and heart rate (HR) was recorded by HR monitor and later calculated as a percentage of each participant's age-predicted maximum. Based on previous research, the threshold for smallest worthwhile change (SWC) was 0.2 SDs. The coefficient of variation (CV±95% CL) of the RLMSP-i for Heart Rate Peak (SWC=2.54) was 0.5 (±0.7), RPE (SWC=0.22) 4.5 (±6.6), peak speed (SWC=0.31) 8.6 (±11.0), distance (SWC=1.58) 15.6 (±16.0), and ≥HIT running m/min (SWC=0.47) 23 (±20). In only one case (Heart Rate Peak) case was the CV smaller than the smallest worthwhile change, whilst in only Heart Rate Peak was very large change (10 x SWC) larger than the CV observed. These data suggest that our modified protocol produces comparable responses in heart rate and ≥HIT m/min as observed during Super League match performances, but lower values of total m/min and peak speed. Due to the presence of an enhanced contact element, contributing to the overall physiological load of the participant, it provides a reliable measure of physical performance for Heart Rate Peak, Heart Rate and ratings of perceived exertion, but not for distance, ≥HIT m/min or peak speed.
ALLOMETRIC SCALING OF VO2max: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Lolli L , Batterham AM , Weston KL , Atkinson G
Published: November 2016

We aimed to provide the first quantitative synthesis of derived static allometric coefficients (b) used for scaling maximal oxygen uptake (VO2max) to whole-body mass and fat-free mass in human samples. Eight electronic databases were searched for relevant peer-reviewed articles. Inclusion criteria comprised human cardiorespiratory fitness data; cross-sectional study designs; an empirical derivation of the exponent; reported precision statistics; and reported information regarding participant sex, age and sports background, VO2maxprotocol, body composition protocol and line-fitting methods. Thirty-seven studies, involving 7,851 participants, met the eligibility criteria and were dichotomized into two main domains relevant to whole-body mass (n=28) and fat-free mass (n=16), respectively. The pooled allometric exponent (95% CL) was found to be 0.71 (0.65 to 0.77) for body mass and 0.91 (0.83 to 0.98) for fat-free mass. The among-studies heterogeneity was substantial for both whole-body mass and fat-free mass (τ =±0.15). Participant sex explained 33% of the between-study variability in the whole body mass exponent, but only 5% of the variability in the fat-free mass exponent. While the body mass exponent was substantially lower in women (b=0.52; 95% CL: 0.41 to 0.64) than for men (b=0.77; 95% CL: 0.71 to 0.83), the fat-free mass exponent was similar for both sexes. None of the identified moderator variables was statistically significant. The body mass exponent estimate encompassed both ⅔- and ¾-power laws. Conversely, the fat-free mass exponent was substantially larger and more generalisable due to the heterogeneity of body composition in human samples. We conclude that the scaling of VO2maxin humans is consistent with the allometric cascade model, with an estimated pooled exponent that precludes ⅔- and ¾-power scaling.
THE QUANTIFICATION OF CHANGES IN CARDIORESPIRATORY FITNESS INDEPENDENT FROM CHANGES IN BODY MASS: ILLUSTRATION OF AN ALLOMETRIC APPROACH
Authors: Lolli L , Batterham AM , Weston K L , Atkinson G
Published: November 2016

Both obesity and a low level of cardiorespiratory fitness (VO2max) are strong predictors of morbidity and mortality. Therefore, in any lifestyle intervention study, it is important to ascertain if any changes in VO2maxare clinically important, while considering any parallel changes in body mass and/or composition. Most researchers adopt a simple ratiometric approach to normalising VO2max(ml·kg−1·min−1), even though this is associated with several important assumptions, which are rarely confirmed by researchers. Using data from the Activity Counselling Trial (ACT), we developed and applied a novel allometric approach for comparing normalised changes in VO2maxbetween different treatment arms. Overall, 874 participants were randomly allocated into advice only (n=292), assistance (n=293) and counselling group (n=289), respectively. A repeated-measures allometric model was adopted to adjust the changes in VO2maxfor the concurrent changes in body mass and fat-free mass from baseline to 24-month follow-up. Magnitude thresholds for standardized differences in VO2maxof 0.20, 0.60, 1.20, 2.0 and 4.0 were considered as a small, moderate, large, very large and extremely large effect, respectively. The within-subjects allometric exponent (90% CL) for body mass was 0.46 (0.40 to 0.53) and 0.37 (0.31 to 0.43) in men and women, respectively. The respective fat-free mass exponents were 0.79 (0.71 to 0.87) and 0.64 (0.56 to 0.73). Ratio-scaled VO2maxincreased 4.5% (2.1% to 7.0%) more in the assistance vs advice group. This increase was slightly smaller when allometrically scaled to body mass [3.9% (1.7% to 6.1%)] and fat-free mass [3.7% (1.5% to 6.0%)], although standardised mean differences were similar between approaches (≈ 0.2). Similar findings were obtained for the counselling vs advice groups. Changes in VO2maxwere small in all study arms for men. Contrary to the original study report and subsequent citations, scaled intervention effects on cardiorespiratory fitness in the ACT are unlikely to be clinically important. Given the non-linear relationship between changes in body size and VO2max, a within-subjects allometric modelling approach is recommended for accurately quantifying any intervention-induced effects in future studies.
ADDUCTOR LONGUS ACTIVATION DURING TWO COMMON HIP ADDUCTION EXERCISES
Authors: Long C , Light N
Published: November 2016

Various exercises are prescribed in the management of adductor-related groin pain. Isometric adductor ball squeeze exercises are commonly incorporated into both prevention and rehabilitation training, as is the Copenhagen Adduction exercise, which offers a more dynamic and challenging alternative. The adductor longus (AL) muscle is commonly indicated in adductor pathology and may be considered a ‘target’ tissue, yet there is minimal literature examining adductor muscle activation during such exercises. Understanding variation in levels of AL activation during differing exercises, may inform exercise selection. Nine healthy university football players completed a number of repetitions of adductor ball squeezes (45° hip flexion) and Copenhagen adductions, with surface electromyography (sEMG) measuring their AL activity. Results showed that isometric ball squeezes produced larger average AL activity than the Copenhagen adduction exercise (p<0.046). The ball squeeze exercise also demonstrated higher percentage of peak sEMG activity (33%) compared to the Copenhagen adduction exercise (26%). No statistically significant differences between peak sEMG values were observed. The results suggest that AL activation is higher during an isometric ball squeeze when compared with the Copenhagen adduction exercise, despite being a more dynamic and stressful exercise. This may be related to altered synergistic muscle recruitment and varying working muscle lengths, which have been shown to alter EMG activity levels. Adductor ball squeezes are safe, load adjustable and simple to instruct requiring no assistance. Subsequently, they remain ideally suited in various contexts, for example pre-activation exercises prior to activity (prevention) and during early phase loading post adductor related injury (treatment), where the Copenhagen adduction exercise is not indicated.
BIOMECHANICAL DIFFERENCES BETWEEN CASES WITH CECS AND ASYMPTOMATIC CONTROLS DURING RUNNING
Authors: Roberts A , Roscoe D , Hulse D , Bennett A , Dixon S
Published: November 2016

Chronic exertional compartment syndrome (CECS) presents as exertional pain in the lower limb as a result of elevation of intramuscular compartment pressure. Treatment of CECS through a change in running style has recently been suggested to improve symptoms however no primary research has investigated whether patients with CECS run differently to controls. This study aimed to compare the kinematic differences in cases with CECS and controls. 20 men with symptoms of CECS of the anterior compartment and 20 asymptomatic male controls participated. Barefoot and shod running 3D kinematics; and anthropometry were compared. Cases were heavier than controls with no differences in height. This result contrasts with our recent study that reported that cases in that cohort were on average 10 cm shorter than controls; with no differences in weight. As such we have previously suggested that small stature may be a risk factor for CECS in the military. Further work is now needed to provide more robust data on this theory. Our findings are the first to demonstrate that CECS patients run with a different gait pattern to controls. Cases displayed less anterior trunk lean and less anterior pelvic tilt throughout the whole gait cycle and a more upright shank inclination angle during late swing. Cases demonstrated greater step length and stance time, although this was not consistent across conditions. Alterations to running style that have been used in an attempt to reduce the anterior compartment activity of CECS patients typically encouraged greater forward lean; along with other more distal changes. Clinical observations have also suggested increased ankle dorsiflexion and reduced heel lift during swing phase. The differences reported in this study only partially match the anecdotal observations previously described in the literature. However, no consistent differences were found at the ankle joint. Our results therefore demonstrate the importance of acquiring higher level evidence before implementing gait re-education programs. Assuming the reported interventions reduce anterior compartment muscle activity, they may simply modify activity, rather than changing pathological gait. The longer stride length is a continuing theme in this population and as such we believe this may be a key component in the development of the condition.
NO EFFECT OF PRE-EXERCISE SUCRALOSE INGESTION ON GASTRIC EMPTYING RATE OF A CARBOHYDRATE-ELECTROLYTE SOLUTION
Authors: Evans GH , Moran A , Phenton C , Pocock T , Sheader E , Yau AMW
Published: November 2016

Ingestion of carbohydrate during exercise is common in order to provide an exogenous substrate for oxidation and to improve performance. The rate at which a solution is emptied from the stomach is an important step in this process. Acute changes in blood glucose concentration significantly influence gastric emptying rate (GER). Animal studies have suggested that exposing the intestine to glucose and artificial sweeteners leads to an increase in mRNA transcription and the number of SGLT-1 transporters within the intestine. This may influence the rate of glucose absorption and GER. The aim of this study was to investigate the effects of pre-exercise sucralose ingestion on GER during exercise. Nine healthy males volunteered to participate in this study, which involved completion of two experimental trials undertaken in a fasted state. Over a two hour period, participants ingested 400 mL of water (C) or 400 mL of water containing 159 mg sucralose (S) in equal aliquots every 15 minutes. Following this, 600 mL of a commercially available carbohydrate-electrolyte solution containing 100 mg13C sodium acetate was ingested prior to undertaking 90 minutes of cycle exercise at 70% of heart rate reserve. Breath samples were collected pre- ingestion and at 15 minute intervals throughout exercise for measurement of GER. No differences (P>0.05) were observed between trials in heart rate or rating of perceived exertion during exercise. Half emptying time of the solution was 47±16 (C) and 44±15 (S) minutes (P=0.555) while time of maximum rate of gastric emptying was 39±10 (C) and 34±10 (S) minutes (P=0.160). No difference (P>0.05) between the trials was observed in delta over baseline breath values. The results of this study indicate that pre-exercise sucralose ingestion does not influence GER during exercise. This may be due to the time period of sucralose ingestion not being sufficient for adaptation to occur.
TRUNK MUSCLE ACTIVATION IN FREE BARBELL AND SUPPORT MACHINE SQUAT AT THE SAME RELATIVE LOADS
Authors: Clark DR , Lambert MI , Hunter AM
Published: November 2016

Measurement of trunk muscle activation (TMA) using surface electromyography (sEMG) in BS is novel and has focussed on squats on unstable surfaces. The hack squat (HS) has more support than BS and is performed at greater absolute loads but lower trunk muscle activation. This has implications for the application of both exercises in exercise training programmes. The purpose of this study was to compare 1RM and TMA in BS and HS at 4 relative loads, 65, 75, 85 and 95% of system mass max (SM). Ten males completed three test sessions: 1) BS and HS 1RM; 2) TMA test familiarization, and; 3) TMA for 3 reps at 4 loads for BS and HS. Kinematics measured by linear transducer and sEMG for rectus abdominus (RA), external oblique (EO), upper lumbar erector spinae (ULES) and lumbar sacral erector spinae (LSES). Vastus lateralis (VL) sEMG reference lower limb muscle activation. sEMG amplitude determined by root mean square (RMS) processing. Mean RMS for each phase of BS and HS at 75, 85 and 95% SM were normalized to mean concentric (con) BS RMS at 65% SM (Balshaw & Hunter,JEK2012,22,308–319). Mean HS 1RM was 18.2% greater than BS, hence 4 test loads in HS were significantly (p<0.01) higher than BS. Eccentric (ecc) bar displacement was significantly (p<0.001) less in HS than BS for 4 loads. Duration of ecc phase was shorter (p<0.001) in BS than HS. Duration increased (p<0.01) in both phases and exercises with load. BS TMA was greater than HS for all muscles, phases and loads. This was significant (p<0.05) in 14/24 instances (3 loads x 4 muscles x 2 phases). TMA increased significantly (p<0.05) with load in all muscles for both exercises and phases apart from HS LSES in ecc phase. VL RMS was greater in BS than HS for all loads but only significant (p<0.05) in con phase. Despite higher absolute test loads and force in HS, TMA was higher in BS. BS is an effective method of developing trunk strength and TMA is sensitive to load in both BS and HS.
Evaluation of clinicians' knowledge and practices regarding medical radiological exposure: findings from a mixed-methods investigation (survey and qualitative study)
Authors: Lumbreras B , Vilar J , González-Álvarez I , Guilabert M , Parker L A , Pastor-Valero M , Domingo M L , Fernández-Lorente M F , Hernández-Aguado I
Published: November 2016

Objectives

To assess the impact of initiatives aiming to increase clinician awareness of radiation exposure; to explore the challenges they face when communicating with patients; to study what they think is the most appropriate way of communicating the long-term potential risks of medical radiological exposure to patients.

Design

A quantitative and qualitative evaluation through a survey and focal groups.

Setting

San Juan Hospital and Dr Peset Hospital (Southeast Spain) and clinicians from Spanish scientific societies.

Participants

The surveys were answered (a) in person (216: all the radiologists (30), urologists (14) and surgeons (44) working at both participant hospitals; a sample of general practitioners from the catchment area of one hospital (45), and a consecutive sample of radiologists attending a scientific meeting (60)) or (b) electronically through Spanish scientific societies (299: radiologists (45), pneumologists (123), haematologists (75) and surgeons (40)). Clinicians were not randomly selected and thus the results are limited by the diligence of the individuals filling out the survey.

Primary and secondary outcome measures

Clinicians' knowledge and practices regarding medical radiological exposure, and what they considered most appropriate for communicating information to patients.

Results

Nearly 80% of the clinicians surveyed had never heard of the European recommendations. Fewer than 20% of the clinicians surveyed identified correctly the radiation equivalence dose of intravenous urography or barium enema. It was reported by 31.7% that they inform patients about the long-term potential risks of ionising radiation. All participants agreed that the most appropriate way to present information is a table with a list of imaging tests and their corresponding radiation equivalence dose in terms of chest X-rays and background radiation exposure.

Conclusions

Medical radiological exposure is frequently underestimated and rarely explained to patients. With a clear understanding of medical radiological exposure and proper communication tools, clinicians will be able to accurately inform patients.
Prospective Register Of patients undergoing repeated OFfice and Ambulatory Blood Pressure Monitoring (PROOF-ABPM): protocol for an observational cohort study
Authors: Sheppard James P , Martin Una , Gill Paramjit , Stevens Richard , McManus Richard J
Published: November 2016

Introduction

The diagnosis and management of hypertension depends on accurate measurement of blood pressure (BP) in order to target antihypertensive treatment appropriately. Most BP measurements take place in a clinic setting, but it has long been recognised that readings taken out-of-office (via home or ambulatory monitoring) estimate true underlying BP more accurately. Recent studies have shown that the change in clinic BP over multiple readings is a significant predictor of the difference between clinic and out-of-office BP. Used in combination with patient characteristics, this change has been shown to accurately predict a patient's out-of-office BP level. The present study proposes to collect real-life BP data to prospectively validate this new prediction tool in routine clinical practice.

Methods and analysis

A prospective, multicentre observational cohort design will be used, recruiting patients from primary and secondary care. All patients attending participating centres for ambulatory BP monitoring will be eligible to participate. Anonymised clinical data will be collected from all eligible patients, who will be invited to give informed consent to permit identifiable data to be collected for data linkage to external outcome registries. Descriptive statistics will be used to calculate the sensitivity, specificity, positive and negative predictive values of the out-of-office BP prediction tool. Area under the receiver operator characteristic curve statistics will be used to examine model performance.

Ethics and dissemination

Ethical approval for this study has been obtained from the National Research. Ethics Service Committee South Central—Oxford A (reference; 15/SC/0184), and site-specific R&D approval has been acquired from the relevant NHS trusts. All findings will be presented at relevant conferences and published in peer-reviewed journals, on the study website and disseminated in lay and social media where appropriate.
Do acute myocardial infarction and stroke mortality vary by distance to hospitals in Switzerland? Results from the Swiss National Cohort Study
Authors: Berlin Claudia , Panczak Radoslaw , Hasler Rebecca , Zwahlen Marcel
Published: November 2016

Objective

Switzerland has mountains and valleys complicating the access to a hospital and critical care in case of emergencies. Treatment success for acute myocardial infarction (AMI) or stroke depends on timely treatment. We examined the relationship between distance to different hospital types and mortality from AMI or stroke in the Swiss National Cohort (SNC) Study.

Design and setting

The SNC is a longitudinal mortality study of the census 2000 population of Switzerland. For 4.5 million Swiss residents not living in a nursing home and older than 30 years in the year 2000, we calculated driving time and straight-line distance from their home to the nearest acute, acute with emergency room, central and university hospital (in total 173 hospitals). On the basis of quintiles, we used multivariable Cox proportional hazard models to estimate HRs of AMI and stroke mortality for driving time distance groups compared to the closest distance group.

Results

Over 8 years, 19 301 AMI and 21 931 stroke deaths occurred. Mean driving time to the nearest acute hospital was 6.5 min (29.7 min to a university hospital). For AMI mortality, driving time to a university hospital showed the strongest association among the four types of hospitals with a hazard ratio (HR) of 1.19 (95% CI 1.10 to 1.30) and 1.10 (95% CI 1.01 to 1.20) for men and women aged 65+ years when comparing the highest quintile with the lowest quintile of driving time. For stroke mortality, the association with university hospital driving time was less pronounced than for AMI mortality and did not show a clear incremental pattern with increasing driving time. There was no association with driving time to the nearest hospital.

Conclusions

The increasing AMI mortality with increasing driving time to the nearest university hospital but not to any nearest hospital reflects a complex interplay of many factors along the care pathway.
Disease activity indices in coeliac disease: systematic review and recommendations for clinical trials
Authors: Hindryckx Pieter , Levesque Barrett G , Holvoet Tom , Durand Serina , Tang Ceen-Ming , Parker Claire , Khanna Reena , Shackelton Lisa M , D'Haens Geert , Sandborn William J , Feagan Brian G , Lebwohl Benjamin , Leffler Daniel A , Jairath Vipul
Published: November 2016

Objective

Although several pharmacological agents have emerged as potential adjunctive therapies to a gluten-free diet for coeliac disease, there is currently no widely accepted measure of disease activity used in clinical trials. We conducted a systematic review of coeliac disease activity indices to evaluate their operating properties and potential as outcome measures in registration trials.

Design

MEDLINE, EMBASE and the Cochrane central library were searched from 1966 to 2015 for eligible studies in adult and/or paediatric patients with coeliac disease that included coeliac disease activity markers in their outcome measures. The operating characteristics of histological indices, patient-reported outcomes (PROs) and endoscopic indices were evaluated for content and construct validity, reliability, responsiveness and feasibility using guidelines proposed by the US Food and Drug Administration (FDA).

Results

Of 19 123 citations, 286 studies were eligible, including 24 randomised-controlled trials. Three of five PROs identified met most key evaluative criteria but only the Celiac Disease Symptom Diary (CDSD) and the Celiac Disease Patient-Reported Outcome (CeD PRO) have been approved by the FDA. All histological and endoscopic scores identified lacked content validity. Quantitative morphometric histological analysis had better reliability and responsiveness compared with qualitative scales. Endoscopic indices were infrequently used, and only one index demonstrated responsiveness to effective therapy.

Conclusions

Current best evidence suggests that the CDSD and the CeD PRO are appropriate for use in the definition of primary end points in coeliac disease registration trials. Morphometric histology should be included as a key secondary or co-primary end point. Further work is needed to optimise end point configuration to inform efficient drug development.
Evidence of nonlocal muscle fatigue in male youth
Authors: Ben Othman Aymen , Chaouachi Anis , Hammami Raouf , Chaouachi Mehdi M. , Kasmi Sofien , Behm David G.
Published: November 2016

Evidence for nonlocal muscle fatigue (NLMF) has been inconsistent in adults, with no studies investigating youth. The objective was to examine NLMF in youth. Forty-two young males (age, 10–13 years) were tested for maximal voluntary isometric contraction (MVIC) force of the ipsilateral and contralateral knee extensors at 90° and 120° knee flexion, elbow flexors at 90°, handgrip, knee extensor isokinetic torque (300°·s−1 analyzed at 90° and 120° knee flexion), as well as a unilateral countermovement jump (CMJ) and Y Balance test (YBT). Isokinetic fatigue group (n = 15) had unilateral fatigue induced with 10 sets of 20 repetitions of maximal isokinetic knee extensor contractions at 300°·s−1. Isometric fatigue group (n = 15) used 10 repetitions of 6-s knee extensor MVIC whereas the control group (n = 12) were not fatigued. There was no significant difference in the response to the isometric- or isokinetic-fatigue intervention protocols. Main time effects indicated that NLMF was evident with the contralateral knee extensor MVIC at 90° (p = 0.008; 8.9%), knee extensor isokinetic torque at 90° (p < 0.001; 11.4%), and 120° (p = 0.05; 5.4%), CMJ (p = 0.02; 11.5%), handgrip (p = 0.06; 4.5%), elbow flexors (p < 0.001; 7.7%), and YBT (p = 0.001; 5.6%). Ipsilateral NLMF deficits occurred with handgrip (p < 0.001; 7.3%), elbow flexors MVICs (p < 0.001; 10.7%), CMJ (p = 0.02; 12.2%), and YBT (p = 0.002; 3.8%). NLMF with similar relative fatigue-induced deficits of fatigued and nonfatigued limbs suggest that youth fatigue is highly dependent upon the extent of activation or inhibition of the nervous system. Coaches of young athletes might consider developing technical motor skills before fatiguing exercise components, which might hinder the proficiency of their performance.
Accuracy of determining pre-consolidation pressure from laboratory tests
Authors: Umar Muhammad , Sadrekarimi Abouzar
Published: November 2016

Shear strength and compressibility of fine-grained soils is strongly influenced by their stress history and the maximum (pre-consolidation) pressure ([Formula: see text]). Accurate determination of [Formula: see text] is thus critical for settlement and stability analysis involving fine-grained soils. Many graphical techniques are available for estimating [Formula: see text] from the interpretation of soil compression in laboratory consolidation (oedometer) tests. However, the accuracy of these methods has not been extensively proven or compared with each other. A series of 30 laboratory oedometer tests is carried out in this study based on controlled rate of strain and incrementally loaded testing techniques. Several Canadian clay specimens are subject to cycles of one-dimensional compression loading and unloading to produce a known stress history and [Formula: see text]. The imposed [Formula: see text] values are compared with the predictions of 11 methods for determining [Formula: see text]. The accuracies of these methods are subsequently evaluated by comparing their predictions with [Formula: see text] imposed during the consolidation experiments. While these methods mostly overestimate [Formula: see text], it is determined that a bilogarithmic graphical approach based on the slopes of the virgin compression and recompression segments of a soil compression curve provides the most accurate predictions of [Formula: see text]. The potential ranges of errors associated with the application of each method are also presented.
Dioxygen binding to Fe-MOF-74: microscopic insights from periodic QM/MM calculations
Authors: Moeljadi Adhitya Mangala Putra , Schmid Rochus , Hirao Hajime
Published: November 2016

Accurate MOF-FF parameter sets were determined for the ferrous and ferric forms of an iron-based metal–organic framework (MOF) called Fe-MOF-74. For this purpose, density functional theory (DFT) calculations were applied to truncated cluster models of Fe-MOF-74, and the DFT-calculated geometries and energy derivatives were used for the force-field parameterization. The resultant parameter sets performed remarkably well in reproducing the experimentally determined structure of the MOF. We also performed periodic quantum mechanics (QM) / molecular mechanics (MM) calculations employing a subtractive scheme called ONIOM, with the optimized MOF-FF parameters used for the MM calculations, in an attempt to evaluate the binding energies between O2and several Fe-MOF-74 variants. The calculated binding energy for Fe-MOF-74 agreed very well with the experimental value, and QM/MM geometry optimization calculations confirmed that the O2-bound complex has a side-on geometry. Our calculations also predicted that, when the two neighboring iron ions around the O2-binding site are replaced with other metal ions (Mg2+, Ni2+, Zn2+, Co2+, or Mn2+), there are noticeable variations in the binding energy, indicating that these substituted metal ions affect the O2binding indirectly.
Synthesis of novel α-aminoecdysteroids via regio- and stereoselective oximation/hydrogenation of 20-hydroxyecdysone derivatives
Authors: Savchenko Rimma G. , Kostyleva Svetlana A. , Meshcheryakova Ekaterina S. , Khalilov Leonard M. , Parfenova Lyudmila V. , Odinokov Victor N.
Published: November 2016

Oximation of 20-hydroxyecdysone oxo derivatives proceeds regio- and stereoselectively and provides (E)-configured oximes in quantitative yields. The Ni–Ra-catalyzed hydrogenation of the oximes affords novel α-aminoecdysteroids with the unchanged 14α-hydroxy-7-en-6-on native chromophore of ecdysteroids. The structures of synthesized compounds were confirmed by the means of homo- and heteronuclear one-dimensional and two-dimensional 1H and 13C NMR spectroscopy and X-ray crystallography.
Branched-chain and dendritic lipids for nanoparticles
Authors: Meanwell Michael W. , O’Sullivan Connor , Howard Perry , Fyles Thomas M.
Published: November 2016

Lipid nanoparticles (LNPs) for drug-delivery applications are largely derived from natural lipids. Synthetic lipids, particularly those incorporating branched hydrocarbons and hyper-branched hydrocarbon architectures, may afford enhanced lipophilicity with enhanced fluidity and thereby lead to LNP stabilization. Hydrocarbon anchors based on serinol diesters were prepared from linear Cn (n = 14, 16, 18) and branched (n = 16) acids with Boc-protected serinol. These diesters were further dimerized on an iminodiacetamide backbone to provide eight branched-chain and dendritic lipid anchors. Derivatization of these core structures provided eight PEG-lipids and seven thiopurine linked lipid–drug conjugates. LNPs were prepared by microfluidic mixing from mixed lipids in ethanol diluted into aqueous media. The lipid–drug conjugates incorporated 5 mol% of a phosphocholine and 5 mol% of a commercial PEG-lipid to form LNPs with a thiopurine drug loading of 15 wt%. The PEG–lipids prepared were formulated at 1.5 mol% as a surface stabilizer to LNPs containing dsDNA lipoplexes. The stability of the LNPs was assessed under different storage conditions through monitoring of particle size. For both LNPs from lipid–thiopurine conjugates and the PEG-lipid systems, there is strong preliminary evidence that hydrocarbon branching results in LNP stabilization. Four of the lipid–drug conjugate formulations were stable to cell culture conditions (10% serum, 37 °C) and the toxicity of these LNPs was assessed in two cell lines relative to the free thiopurines in the medium. The observed toxicity is consistent with cellular uptake of the LNPs and reductive release of the cargo thiopurine within the cell.
A comparative study of the vibrational spectra of HCN in exact vibron model and in mean field approximation
Authors: Acharjee Mahua , Sen Rupam , Mohanta Bidhan
Published: November 2016

The aim of this work is to study the highly excited vibrational states of hydrogen cyanide HCN in the exact vibron model and with mean field approximation in the vibron model. Considering the U(4) ⊗ U(4) spectrum-generating algebra for linear triatomic molecules, the standard Hamiltonian is constructed using the linear and quadratic combination of Casimir operators. For higher order corrections, the quadratic contributions of Casimir operators are used to construct the Hamiltonian. Using this Hamiltonian the higher excited vibrational levels of HCN are calculated in the local mode approximation. The energy levels are observed as a function of vibron number N. The best fit is obtained for N = 184 (N1 = 139, N2 = 45) with root mean square (r.m.s.) deviation 5.598 cm−1. The intermodal coupling within the same polyad is studied and addressed properly by introducing Majorana operator. The r.m.s. deviation is then reduced to 4.755 cm−1. The modification is negligible, which indicates the local nature of HCN. In this work, 35 experimental levels are taken for fit, out of which only two sets of levels are accidentally degenerate. The Fermi resonances of the accidentally degenerate levels are studied using the Fermi operator and r.m.s. deviation becomes 4.835. The coefficient of Majorana and Fermi coupling for different levels are obtained by diagonalzing the Majorana and Fermi matrices for each polyad. The Majorana and Fermi matrices for each polyad are diagonalized with the MATRIX CALCULATOR program. The algebraic parameters are evaluated by a least square fit against the experimental data using MATLAB R2015a. Using this model, a set of energy levels is predicted up to 30 000 cm−1, with very good accuracy. HCN is chosen for this study, because, its vibrational states can be fairly described without any modification due to Fermi resonance. The fundamental vibrational levels of HCN are again calculated, using mean field approximation and compared to those obtained using the vibron model. A good agreement is observed.
The physics of galactic spin
Authors: Hofmeister Anne M. , Criss Robert E.
Published: November 2016

Spiral galaxies are discrete spheroidal objects with highly organized, circular internal motions about a special axis. Available models do not describe these key features or explain why the central regions rotate like a solid body. Practically all previous models describe galaxies as a collection of orbiting test particles, utilize numerous fitting parameters, and require either copious amounts of surrounding dark matter that have not been detected, or modifications to Newton’s law, to fit the observed dependence of equatorial velocity on radius. Our paper probes the reasonable alternative that galaxies are discrete, spinning objects. Our analytical forward models, constructed by applying the virial theorem and Newton’s law to Maclaurin’s spinning spheroids with varying internal density, explain why galactic rotation is organized into this three-dimensional shape. Without invoking dark matter, our spin model explains why the outermost rotational velocities are nearly constant, yet depend on galaxy size, and, with no free parameters, provides masses of 14 important galaxies consistent with their luminosities. We show that proposed modifications to Newton’s law compensate for the dynamical differences between a flattened, spinning, Newtonian spheroid, and a collection of orbits.
Sulforaphane protects against sodium valproate–induced acute liver injury
Authors: Nazmy Entsar A. , El-Khouly Omar A. , Atef Hoda , Said Eman
Published: November 2016

Drug-induced hepatotoxicity is one of the most commonly encountered obstacles in the field of medical practice. Sodium valproate (VPA) is among many drugs with reported hepatotoxic effects. Sulforaphane (SFN) is a thiol compound found in wide abundance in cruciferous plants that has numerous reported therapeutic efficacies. The current investigation sheds light on the potential hepatoprotective effect of SFN against VPA-induced liver injury in rats. Twice daily VPA (700 mg/kg, i.p.) for 7 days induced significant biochemical alterations and hepatic histopathological damage. SFN (0.5 mg/kg, orally) for 7 days significantly boosted liver function biomarkers; it reduced serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase, and restored serum albumin concentration in a significant manner. Meanwhile, SFN significantly mitigated VPA-induced histopathological alterations. To highlight the mechanisms implicated in the observed hepatoprotective action, hepatic malondialdehyde and tumour necrosis factor α content significantly declined with concomitant increase in hepatic heme oxygenase-1 content and glutathione concentration with SFN treatment. In conclusion, SFN can significantly ameliorate VPA-induced hepatotoxicity and liver injury primarily by direct association between antioxidant and anti-inflammatory properties.
Generalized Connes–Chern characters inKK-theory with an application to weak invariants of topological insulators
Authors: Prodan Emil , Schulz-Baldes Hermann
Published: November 2016

We use constructive bounded Kasparov [Formula: see text]-theory to investigate the numerical invariants stemming from the internal Kasparov products [Formula: see text], [Formula: see text], where the last morphism is provided by a tracial state. For the class of properly defined finitely-summable Kasparov [Formula: see text]-cycles, the invariants are given by the pairing of [Formula: see text]-theory of [Formula: see text] with an element of the periodic cyclic cohomology of [Formula: see text], which we call the generalized Connes–Chern character. When [Formula: see text] is a twisted crossed product of [Formula: see text] by [Formula: see text], [Formula: see text], we derive a local formula for the character corresponding to the fundamental class of a properly defined Dirac cycle. Furthermore, when [Formula: see text], with [Formula: see text] the algebra of continuous functions over a disorder configuration space, we show that the numerical invariants are connected to the weak topological invariants of the complex classes of topological insulators, defined in the physics literature. The end products are generalized index theorems for these weak invariants, which enable us to predict the range of the invariants and to identify regimes of strong disorder in which the invariants remain stable. The latter will be reported in a subsequent publication.
Power spectrum of flow fluctuations in relativistic heavy-ion collisions
Authors: Saumia P. S. , Srivastava Ajit M.
Published: November 2016

We carry out hydrodynamical simulation of the evolution of fluid in relativistic heavy-ion collisions with random initial fluctuations. The time evolution of power spectrum of momentum anisotropies shows very strong correspondence with the physics of cosmic microwave anisotropies as was earlier predicted by us. In particular, our results demonstrate suppression of superhorizon fluctuations and the correspondence between the location of the first peak in the power spectrum of momentum anisotropies and the length scale of fluctuations and expected freeze-out time-scale (more precisely, the sound horizon size at freeze-out).
On spacetime structure and electrodynamics
Authors: Ni Wei-Tou
Published: November 2016

Electrodynamics is the most tested fundamental physical theory. Relativity arose from the completion of Maxwell–Lorentz electrodynamics. Introducing the metric [Formula: see text] as gravitational potential in 1913, versed in general (coordinate-)covariant formalism in 1914 and shortly after the completion of general relativity, Einstein put the Maxwell equations in general covariant form with only the constitutive relation between the excitation and the field dependent on and connected by the metric in 1916. Further clarification and developments by Weyl in 1918, Murnaghan in 1921, Kottler in 1922 and Cartan in 1923 together with the corresponding developments in electrodynamics of continuous media by Bateman in 1910, Tamm in 1924, Laue in 1952 and Post in 1962 established the premetric formalism of electrodynamics. Since almost all phenomena electrodynamics deal with have energy scales much lower than the Higgs mass energy and intermediate boson energy, electrodynamics of continuous media should be applicable and the constitutive relation of spacetime/vacuum should be local and linear. What is the key characteristic of the spacetime/vacuum? It is the Weak Equivalence Principle I (WEP I) for photons/wave packets of light which states that the spacetime trajectory of light in a gravitational field depends only on its initial position and direction of propagation, and does not depend on its frequency (energy) and polarization, i.e. nonbirefringence of light propagation in spacetime/vacuum. With this principle it is proved by the author in 1981 in the weak field limit, and by Lammerzahl and Hehl in 2004 together with Favaro and Bergamin in 2011 without assuming the weak-field condition that the constitutive tensor must be of the core metric form with only two additional degrees of freedom — the pseudoscalar (Abelian axion or EM axion) degree of freedom and the scalar (dilaton) degree of freedom (i.e. metric with axion and dilaton). In this paper, we review this connection and the ultrahigh precision empirical tests of nonbirefringence together with present status of tests of cosmic Abelian axion and dilaton. If the stronger version of WEP is assumed, i.e. WEP II for photons (wave packets of light) which states in addition to WEP I also that the polarization state of the light would not change (e.g. no polarization rotation for linear polarized light) and no amplification/attenuation of light, then no Abelian (EM) axion and no dilaton, and we have a pure metric theory.