Farm management and husbandry practices associated with spontaneous humeral fractures in New Zealand dairy heifers.

AIMS: To use a farm-based survey to identify characteristics of the New Zealand dairy system associated with the risk of spontaneous humeral fracture in dairy heifers. METHODS: A questionnaire was designed and made available in print and online to collect information from dairy farmers and/or veterinarians, across New Zealand, about the management and nutrition of cows from birth to first lactation. Data were collected from July 2019 to March 2020 from farms that either had recorded (case farms) or not recorded (control farms) cases of humeral fractures in dairy heifers. RESULTS: A total of 68 completed questionnaires were returned, with 35 responses from case farms and 33 responses from control farms. Twenty-six responses (38%) were from the South Island (13 case farms and 13 control farms) and 38 responses (56%) were from the North Island (20 case farms and 18 control farms). For four questionnaires (6%) farm location was not given. Adjusting for the effect of age when calves accessed pasture, case farms had increased odds of having Holstein-Friesian Jersey crossbreed cows as the predominant breed (OR = 9.7; 95% CI = 3.1-36.0; p < 0.001). Adjusting for the effect of breed, allowing calves access to pasture a week later decreased the odds of being a case farm (OR = 0.68; 95% CI = 0.47-0.90; p = 0.006). CONCLUSIONS: Cows being Holstein-Friesian Jersey crossbreed was identified as a possible risk factor associated with spontaneous humeral fracture in dairy heifers in New Zealand. Given the small sample size, the likely multifactorial aetiology for humeral fractures, and the non-randomised survey, this risk factor, and the possible association between age at turn out and herd production with humeral fractures, all require further investigation.

Comparing Hearing Loss in Children with Adults Living with Sickle Cell Disease and Sickle Cell Traits.

BACKGROUND: Hearing loss is a neurological sequelae associated with sickle cell disease (SCD) and probably sickle cell trait (SCT) in children and adults but remains understudied. AIM: This study aimed to compare the hearing impairment among children and adults living with SCD or SCT. METHODS: A comparative cross-sectional study conducted in four departments with SCD outpatient clinic in a tertiary hospital in Nigeria. Participants with Sickle cell disease (HbSS) and Sickle cell trait (HbAS) (cohort) and HbAA (control) had comprehensive ear and hearing assessments for sensorineural hearing loss. Audiometric results were categorized according to WHO classifications and data analysed with Statistical Analysis System (SAS 9.4). RESULTS: A total of 212 participants (106 cohort and control, respectively), aged 6 months to 55 years, were enrolled. Of these, 35% of children with SCD and 25% with SCT had hearing impairment, while 30% of adults with SCD, 36.1% with SCT, and 11% with HbAA had hearing impairment. There was asymmetry in the hearing impairment, with the left ear more affected in children and the right ear in adults. The odds ratio (OD) of hearing impairment was higher in HbSS (2.48 (95% confidence interval (CI):1.51-4.14); P = 0.0004) and HbAS (2.28 (95% CI: 1.1-4.58); P = 0.02) participants compared with HbAA but was not statistically significant when adjusted for frequency of hospitalization, crises, blood transfusion and routine drugs in HbAS (P = 0.49) unlike HbSS (P = 0.03). CONCLUSION: The prevalence of hearing loss among children and adults with SCD is higher than in those with HbA genotype. The frequency of hospitalization, crises, blood transfusion and taking routine drugs may influence hearing impairment in SCT but may not in SCD.

Sociocultural influences on dietary behavior and meal timing among Native Hawaiian and Pacific Islander women at risk of endometrial cancer: a qualitative investigation.

PURPOSE: Determine sociocultural influences on dietary behavior, body image, weight loss, and perceptions of the cultural appropriateness of a meal-timing intervention design and menu among Native Hawaiian and Pacific Islander (NHPI) women at risk of endometrial cancer. METHODS: Six 90-min videoconference focus groups among NHPI women (n = 35) recruited by a community champion in Utah. Eligible women were aged ≥ 18 years at risk of endometrial cancer (i.e., BMI ≥ 25 kg/m2, history of non-insulin-dependent diabetes or complex atypical endometrial hyperplasia) had a working cell phone capable of downloading a phone app, could use their cell phone during the day, and were not night-shift workers. Twelve semi-structured questions were posed during the focus groups. Using inductive qualitative methods based on Hatch's 9-step approach, de-identified transcript data were analyzed. RESULTS: Overarching themes included economic factors, cultural influences, meal choice and timing, and perceptions of health. Subthemes included affordability, waste avoidance, inundated schedules, and cultural influences. Perceptions of body size and weight loss were influenced by family, community, and social media, whose messages could be conflicting. Important intervention components included satisfying, convenient pre-made meals, while barriers included the need to cook for family members. CONCLUSIONS: Dietary interventions targeting metabolic health among NHPI women should consider the multitude of sociocultural and economic factors that influence food choices and meal timing in this population, including affordability, hectic schedules, and immigrant adjustment. Promoting the link between physical and mental well-being as opposed to weight loss is a key approach to reaching this population.

Biochemical profile of heifers with spontaneous humeral fractures suggest that protein-energy malnutrition could be an important factor in the pathology of this disease.

CASE HISTORY: Serum and liver samples from 35, 2-year-old dairy heifers that had fractured one or both humeri post-calving between July and December 2019 were submitted to a diagnostic laboratory for analysis. Serum samples were analysed for albumin, ß-hydroxybutyrate (BHB), creatinine, Ca, Mg, phosphate, non-esterified fatty acids (NEFA), and serum Cu concentration. Liver samples were analysed for liver Cu concentration. Data were compared to published reference intervals. Data values for heifers that prior to fracture had grazed fodder beet were also compared to values for those that had grazed pasture. CLINICAL FINDINGS: Sixty-nine percent of heifers with humeral fracture had serum creatinine concentrations below the lower value of the reference range (55-130 µmol/L). In 3/32 (9%) heifers, serum NEFA concentrations were increased above the reference value indicating body fat mobilisation (≥1.2 mmol/L for peri-partum cows) and in 20/35 (57%) heifers BHB serum concentrations were above the reference value indicating subclinical ketosis (≥1.1 mmol/L for peri-partum cows). In 24/35 (69%) heifers, liver Cu concentration was low (≤ 44 µmol/kg) or marginal (45-94 µmol/kg). The concentration of Cu in serum was low (≤ 4.5 µmol/L) in 2/33 (6%) heifers and marginal (4.6-7.9 µmol/L) in 5/33 (15%) heifers. There was moderate positive correlation between the logged concentrations of Cu in paired liver and serum samples, r(31) = 0.43; (95% CI = 0.1-0.79; p = 0.014). One heifer had a serum phosphate concentration below the lower limit of the reference range (< 1.10 mmol/L). For all heifers, the concentrations of albumin, Ca, and Mg in serum were within the reference intervals (23-38 g/L, 2.00-2.60 mmol/L, and 0.49-1.15 mmol/L respectively). Over winter, 15/35 (43%) heifers grazed predominantly pasture, 14/35 (40%) grazed fodder beet and 6/35 (17%) had a mixed diet. CLINICAL RELEVANCE: In some of these heifers with humeral fractures, there was evidence for protein and/or energy malnutrition in the form of elevated NEFA and BHB concentrations and low creatinine concentrations in serum. Liver Cu concentrations were also reduced in most affected heifers. However, the absence of a control group means it is not possible to determine if these are risk factors for fracture or features common to all periparturient heifers. Clinical trials and molecular studies are needed to determine the true contribution of Cu and protein-energy metabolism to the pathogenesis of spontaneous humeral fractures in dairy heifers. ABBREVIATIONS: BHB: ß-hydroxybutyrate; NEFA: Non-esterified fatty acids.

Scoping Review of Predisposing Factors Associated with Sensorineural Hearing Loss in Sickle Cell Disease.

PURPOSE: Sickle cell disease (SCD) is a genetically inherited red blood cell disorder that affects people all over the world but is more common among blacks of African ancestry than other races. The condition is linked to sensorineural hearing loss (SNHL). This scoping review aims to evaluate studies that reported SNHL in SCD patients and to identify demographic and contextual risk factors for SNHL in SCD patients. METHODS: We conducted scoping searches for relevant studies in PubMed, Embase, Web of Science, and Google Scholar. All articles were evaluated independently by two authors. The checklist Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) was used. SNHL was detected at hearing levels above 20 decibels. RESULTS: In terms of methodology, the studies reviewed were diverse, with 15 being prospective and four being retrospective. Fourteen of the 19 articles chosen from 18,937 search engine results were case-control studies. Sex, age, foetal haemoglobin (HbF), SCD type, painful vaso-occlusive crisis (PVO), blood parameters, flow-mediated vasodilation (FMV), and hydroxyurea use were all extracted. Few studies investigated SNHL risk factors with noticeable knowledge gaps. Age, PVO, and certain blood parameters appear to predispose to SNHL, whereas decreased FMV, the presence of HbF, and the use of hydroxyurea appear to have an inverse relationship with the development of SNHL in SCD. CONCLUSION: There is a clear gap in the existing literature regarding the knowledge of demographic and contextual risk factors that is required for the prevention and management of SNHL in SCD.

OBJECTIF: La drépanocytose est une maladie héréditaire des globules rouges qui touche des personnes partout dans le monde, mais qui est plus fréquente chez les Noirs d'ascendance africaine que dans les autres races. Cette maladie est liée à la perte auditive neurosensorielle (SNHL). L'objectif de cette revue est d'évaluer les études qui rapportent une perte auditive neurosensorielle chez les patients atteints de DICS et d'identifier les facteurs de risque démographiques et contextuels de cette perte auditive chez les patients atteints de DICS. MÉTHODES: Nous avons effectué des recherches pour trouver des études pertinentes dans PubMed, Embase, Web of Science, et Google Scholar. Tous les articles ont été évalués indépendamment par deux auteurs. La liste de contrôle Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) a été utilisée. Le SNHL a été détecté à des niveaux d'audition supérieurs à 20 décibels. RÉSULTATS: En termes de méthodologie, les études examinées étaient diverses, 15 étant prospectives et quatre rétrospectives. Quatorze des 19 articles choisis parmi les 18 937 résultats du moteur de recherche étaient des études cas-témoins. Le sexe, l'âge, l'hémoglobine fœtale (HbF), le type de DICS, la crise vaso-occlusive douloureuse (PVO), les paramètres sanguins, la vasodilatation médiée par le flux (FMV) et l'utilisation de l'hydroxyurée ont tous été extraits. Peu d'études se sont penchées sur les facteurs de risque du SNHL, avec des lacunes notables dans les connaissances. L'âge, la PVO et certains paramètres sanguins semblent prédisposer au SNHL, tandis qu'une diminution de la FMV, la présence d'HbF et l'utilisation d'hydroxyurée semblent avoir une relation inverse avec le développement du SNHL chez les patients atteints de DICS. CONCLUSION: Il existe une lacune évidente dans la littérature existante en ce qui concerne la connaissance des facteurs de risque démographiques et contextuels qui sont nécessaires pour aider à la prévention et à la gestion du SNHL dans la DICS. Mots Clés: Perte auditive sensoriell; drépanocytose.

Regional anaesthesia practice for arteriovenous fistula formation surgery.

We conducted a survey and semi-structured qualitative interviews to investigate current anaesthetic practice for arteriovenous fistula formation surgery in the UK. Responses were received from 39 out of 59 vascular centres where arteriovenous access surgery is performed, a response rate of 66%. Thirty-five centres reported routine use of brachial plexus blocks, but variation in anaesthetic skill-mix and practice were observed. Interviews were conducted with 19 clinicians from 10 NHS Trusts including anaesthetists, vascular access and renal nurses, surgeons and nephrologists. Thematic analysis identified five key findings: (1) current anaesthetic practice showed that centres could be classified as 'regional anaesthesia dominant' or 'local anaesthesia/mixed'; (2) decision making around mode of anaesthesia highlighted the key role of surgeons as frontline decision makers across both centre types; (3) perceived barriers and facilitators of regional block use included clinicians' beliefs and preferences, resource considerations and patients' treatment preferences; (4) anaesthetists' preference for supraclavicular blocks emerged, alongside acknowledgement of varied practice; (5) there was widespread support for a future randomised controlled trial, although clinician equipoise issues and logistical/resource-related concerns were viewed as potential challenges. The use of regional anaesthesia for arteriovenous fistula formation in the UK is varied and influenced by a multitude of factors. Despite the availability of anaesthetists capable of performing regional blocks, there are other limiting factors that influence the routine use of this technique. The study also highlighted the perceived need for a large multicentre, randomised controlled trial to provide an evidence base to inform current practice.

Local anaesthesia for endovascular repair of ruptured abdominal aortic aneurysm.

BACKGROUND: Case series and a post hoc subgroup analysis of a large randomized trial have suggested a potential benefit in treating ruptured abdominal aortic aneurysms (rAAAs) using endovascular aneurysm repair (EVAR) with local anaesthesia (LA) rather than general anaesthesia (GA). The uptake and outcomes of LA in clinical practice remain unknown. METHODS: The UK National Vascular Registry was interrogated for patients presenting with rAAA managed with EVAR under different modes of anaesthesia between 1 January 2014 and 31 December 2016. The primary outcome was in-hospital mortality. Secondary outcomes included: the number of centres performing EVAR under LA; the proportion of patients receiving this technique; duration of hospital stay; and postoperative complications. RESULTS: Some 3101 patients with rAAA were treated in 72 hospitals during the study: 2306 underwent on open procedure and 795 had EVAR (LA, 319; GA, 435; regional anaesthesia, 41). Overall, 56 of 72 hospitals (78 per cent) offered LA for EVAR of rAAA. Baseline characteristics and morphology were similar across the three EVAR subgroups. Patients who had surgery under LA had a lower in-hospital mortality rate than patients who received GA (59 of 319 (18·5 per cent) versus 122 of 435 (28·0 per cent)), and this was unchanged after adjustment for factors known to influence survival (adjusted hazard ratio 0·62, 95 per cent c.i. 0·45 to 0·85; P = 0·003). Median hospital stay and postoperative morbidity from other complications were similar. CONCLUSION: The use of LA for EVAR of rAAA has been adopted widely in the UK. Mortality rates appear lower than in patients undergoing EVAR with GA.

Towards global consensus on core outcomes for hidradenitis suppurativa research: an update from the HISTORIC consensus meetings I and II.

BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items. OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains. METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey. RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments. CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.

Muons at ISIS.

For the last 30 years, muon experiments at ISIS pulsed neutron and muon facility at the Rutherford Appleton Laboratory, Oxfordshire have been making a significant contribution to a number of scientific fields. The muon facilities at ISIS consist of eight experimental areas. The European Commission Muon facility consists of three experimental areas with a fixed momentum (28 MeV c-1). The RIKEN-RAL facility has a variable momentum (17-90 MeV c-1) and a choice of negative or positive muons delivering muons to four experimental areas. There is also an area recently used for a muon ionization cooling experiment. In this paper, the ISIS pulsed muon facilities are reviewed, including the beam characteristics that could be useful for muography experiments.This article is part of the Theo Murphy meeting issue 'Cosmic-ray muography'.

Clinical Neuroscience in Practice: An Experiential Learning Course for Undergraduates Offered by Neurosurgeons and Neuroscientists.

Many pre-health students pursue extracurricular shadowing opportunities to gain clinical experience. The Virginia Tech School of Neuroscience introduced a formal course that provides a clinical experience superior to that received by many medical students. This course is composed of weekly 75-minute seminars that cover diseases affecting the nervous system, their diagnosis and treatment, complemented by weekly half-day intensive clinical experiences with unprecedented access to a team of neurosurgeons (in hospital operating rooms, Intensive Care Units, emergency room, angiographic suites, and wards). In the operating rooms, students routinely "scrub-in" for complex surgeries. On hospital rounds, students experience direct patient care and receive in-depth exposure to modern nervous system imaging. Students participate in two 24-hour "on-call" experiences with team providers. After call, students participate in cognitive and psychological studies to assess physiological and psychological effects of call-related sleep deprivation. Students prepare weekly essays on challenging socioeconomic and ethical questions, exploring subjects such as the cost of medicine and inequalities in access to health care. Towards the end of the course, students meet with the admission dean of the Virginia Tech Carilion medical school; they prepare a personal statement for medical school/graduate school applications, and attend a half-day block of mock medical school/graduate school interviews delivered by experienced clinicians. In lieu of a final exam, each student presents to the entire neurosurgery department, an in-depth clinical analysis of a case in which they participated. We provide details on implementation, challenges and outcomes based on experiences from three semesters with a total enrollment of approximately 60 students.

Enabling recruitment success in bariatric surgical trials: pilot phase of the By-Band-Sleeve study.

BACKGROUND: Randomized controlled trials (RCTs) involving surgical procedures are challenging for recruitment and infrequent in the specialty of bariatrics. The pilot phase of the By-Band-Sleeve study (gastric bypass versus gastric band versus sleeve gastrectomy) provided the opportunity for an investigation of recruitment using a qualitative research integrated in trials (QuinteT) recruitment intervention (QRI). PATIENTS/METHODS: The QRI investigated recruitment in two centers in the pilot phase comparing bypass and banding, through the analysis of 12 in-depth staff interviews, 84 audio recordings of patient consultations, 19 non-participant observations of consultations and patient screening data. QRI findings were developed into a plan of action and fed back to centers to improve information provision and recruitment organization. RESULTS: Recruitment proved to be extremely difficult with only two patients recruited during the first 2 months. The pivotal issue in Center A was that an effective and established clinical service could not easily adapt to the needs of the RCT. There was little scope to present RCT details or ensure efficient eligibility assessment, and recruiters struggled to convey equipoise. Following presentation of QRI findings, recruitment in Center A increased from 9% in the first 2 months (2/22) to 40% (26/65) in the 4 months thereafter. Center B, commencing recruitment 3 months after Center A, learnt from the emerging issues in Center A and set up a special clinic for trial recruitment. The trial successfully completed pilot recruitment and progressed to the main phase across 11 centers. CONCLUSIONS: The QRI identified key issues that enabled the integration of the trial into the clinical setting. This contributed to successful recruitment in the By-Band-Sleeve trial-currently the largest in bariatric practice-and offers opportunities to optimize recruitment in other trials in bariatrics.

Adaptation of the By-Band randomized clinical trial to By-Band-Sleeve to include a new intervention and maintain relevance of the study to practice.

BACKGROUND: Recruitment into surgical RCTs can be threatened if new interventions available outside the trial compete with those being evaluated. Adapting the trial to include the new intervention may overcome this issue, yet this is not often done in surgery. This paper describes the challenges, rationale and methods for adapting an RCT to include a new intervention. METHODS: The By-Band study was designed in the UK in 2009-2010 to compare the effectiveness of laparoscopic adjustable gastric band and Roux-en-Y gastric bypass for severe obesity. It contained a pilot phase to establish whether recruitment was possible, and the grant proposal specified that an adaptation to include sleeve gastrectomy would be considered if practice changed and recruitment was successful. Information on changing obesity surgery practice, updated evidence and expert opinion about trial design were used to inform the adaptation. RESULTS: The pilot phase recruited over 13 months in 2013-2014 and randomized 80 patients (79 anticipated). During this time, major changes in obesity practice in the UK were observed, with gastric band reducing from 32·6 to 15·8 per cent and sleeve gastrectomy increasing from 9·0 to 28·1 per cent. The evidence base had not changed markedly. The British Obesity and Metabolic Surgery Society and study oversight committees supported an adaptation to include sleeve gastrectomy, and a proposal to do so was approved by the funder. CONCLUSION: Adaptation of a two-group surgical RCT can allow evaluation of a third procedure and maintain relevance of the RCT to practice. It also optimizes the use of existing trial infrastructure to answer an additional important research question. Registration number: ISRCTN00786323 (http://www.isrctn.com/).

Randomized trial of near-infrared spectroscopy for personalized optimization of cerebral tissue oxygenation during cardiac surgery.

BACKGROUND: We assessed whether a near-infrared spectroscopy (NIRS)-based algorithm for the personalized optimization of cerebral oxygenation during cardiopulmonary bypass combined with a restrictive red cell transfusion threshold would reduce perioperative injury to the brain, heart, and kidneys. METHODS: In a randomized controlled trial, participants in three UK centres were randomized with concealed allocation to a NIRS (INVOS 5100; Medtronic Inc., Minneapolis, MN, USA)-based 'patient-specific' algorithm that included a restrictive red cell transfusion threshold (haematocrit 18%) or to a 'generic' non-NIRS-based algorithm (standard care). The NIRS algorithm aimed to maintain cerebral oxygenation at an absolute value of > 50% or at > 70% of baseline values. The primary outcome for the trial was cognitive function measured up to 3 months postsurgery. RESULTS: The analysis population comprised eligible randomized patients who underwent valve or combined valve surgery and coronary artery bypass grafts using cardiopulmonary bypass between December 2009 and January 2014 ( n =98 patient-specific algorithm; n =106 generic algorithm). There was no difference between the groups for the three core cognitive domains (attention, verbal memory, and motor coordination) or for the non-core domains psychomotor speed and visuo-spatial skills. The NIRS group had higher scores for verbal fluency; mean difference 3.73 (95% confidence interval 1.50, 5.96). Red cell transfusions, biomarkers of brain, kidney, and myocardial injury, adverse events, and health-care costs were similar between the groups. CONCLUSIONS: These results do not support the use of NIRS-based algorithms for the personalized optimization of cerebral oxygenation in adult cardiac surgery. CLINICAL TRIAL REGISTRATION: http://www.controlled-trials.com , ISRCTN 23557269.

Home-based Reach-to-Grasp training for people after stroke is feasible: a pilot randomised controlled trial.

OBJECTIVE: To determine feasibility of a randomised controlled trial (RCT) of home-based Reach-to-Grasp training after stroke. DESIGN: single-blind parallel group RCT. PARTICIPANTS: Residual arm deficit less than 12 months post-stroke. INTERVENTIONS: Reach-to-Grasp training in 14 one-hour therapist's visits over 6 weeks, plus one hour self-practice per day (total 56 hours). CONTROL: Usual care. MAIN MEASURES: Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), pre-randomisation, 7, 12, 24 weeks post-randomisation. RESULTS: Forty-seven participants (Reach-to-Grasp=24, usual care=23) were randomised over 17 months. Reach-to-Grasp participants received a median (IQR) 14 (13,14) visits, and performed 157 (96,211) repetitions per visit; plus 30 minutes (22,45) self-practice per day. Usual care participants received 10.5 (5,14) therapist visits, comprising 38.6 (30,45) minutes of arm therapy with 16 (6,24) repetitions of functional tasks per visit. Median ARAT scores in the reach-to-grasp group were 8.5 (3.0,24.0) at baseline and 14.5 (3.5,26.0) at 24 weeks compared to median of 4 at both time points (IQR: baseline (3.0,14.0), 24 weeks (3.0,30.0)) in the usual-care group. Median WMFT tasks completed at baseline and 24 weeks were 6 (3.0,11.5) and 8.5 (4.5,13.5) respectively in the reach-to-grasp group and 4 (3.0,10.0), 6 (3.0,14.0) in the usual care group. Incidence of arm pain was similar between groups. The study was stopped before 11 patients reached the 24 weeks assessment. CONCLUSIONS: An RCT of home-based Reach-to-Grasp training after stroke is feasible and safe. With ARAT being our preferred measure it is estimated that 240 participants will be needed for a future two armed trial.

New insights into Brunner syndrome and potential for targeted therapy.

We report two families with Brunner syndrome living in one state of Australia. The first family had a predicted protein-truncating variant of monoamine oxidase A (MAOA) (p.S251KfsX2). Affected males had mild intellectual disability (ID), obsessive behaviour, limited friendships and were introverted and placid during clinical interview. The family disclosed episodic explosive aggression after a diagnosis was made. The second family had a missense variant in MAOA (p.R45W). Affected males had borderline-mild ID, attention deficit disorder and limited friendships. One had a history of explosive aggression in childhood and episodic symptoms of flushing, headaches and diarrhoea. Their carrier mother had normal intelligence but similar episodic symptoms. Characteristic biochemical abnormalities included high serum serotonin and urinary metanephrines and low urinary 5-hydroxyindoleacetic acid (5-HIAA) and vanillylmandelic acid (VMA). Symptomatic individuals in the second family had particularly high serotonin levels, and treatment with a serotonin reuptake inhibitor and dietary modification resulted in reversal of biochemical abnormalities, reduction of 'serotonergic' symptoms and behavioural improvement. Brunner syndrome should be considered as a cause of mild ID with paroxysmal behavioural symptoms. It can be screened for with serum/urine metanephrine and serotonin measurement. Cautious treatment with a serotonin reuptake inhibitor, dietary modifications and avoidance of medications contraindicated in patients on monoamine oxidase inhibitors can improve symptoms.

Nanosecond pulse shaping at 780 nm with fiber-based electro-optical modulators and a double-pass tapered amplifier.

We describe a system for generating frequency-chirped and amplitude-shaped pulses on time scales from sub-nanosecond to ten nanoseconds. The system starts with cw diode-laser light at 780 nm and utilizes fiber-based electro-optical phase and intensity modulators, driven by an arbitrary waveform generator, to generate the shaped pulses. These pulses are subsequently amplified to several hundred mW with a tapered amplifier in a delayed double-pass configuration. Frequency chirps up to 5 GHz in 2 ns and pulse widths as short as 0.15 ns have been realized.

Standardizing and monitoring the delivery of surgical interventions in randomized clinical trials.

BACKGROUND: The complexity of surgical interventions has major implications for the design of RCTs. Trials need to consider how and whether to standardize interventions so that, if successful, they can be implemented in practice. Although guidance exists for standardizing non-pharmaceutical interventions in RCTs, their application to surgery is unclear. This study reports new methods for standardizing the delivery of surgical interventions in RCTs. METHODS: Descriptions of 160 surgical interventions in existing trial reports and protocols were identified. Initially, ten reports were scrutinized in detail using a modified framework approach for the analysis of qualitative data, which informed the development of a preliminary typology. The typology was amended with iterative sequential application to all interventions. Further testing was undertaken within ongoing multicentre RCTs. RESULTS: The typology has three parts. Initially, the overall technical purpose of the intervention is described (exploration, resection and/or reconstruction) in order to establish its constituent components and steps. This detailed description of the intervention is then used to establish whether and how each component and step should be standardized, and the standards documented within the trial protocol. Finally, the typology provides a framework for monitoring the agreed intervention standards during the RCT. Pilot testing within ongoing RCTs enabled standardization of the interventions to be agreed, and case report forms developed to capture deviations from these standards. CONCLUSION: The typology provides a framework for use during trial design to standardize the delivery of surgical interventions and document these details within protocols. Application of this typology to future RCTs may clarify details of the interventions under evaluation and help successful interventions to be implemented.

Pressure-actuated microfluidic devices for electrophoretic separation of pre-term birth biomarkers.

We have developed microfluidic devices with pressure-driven injection for electrophoretic analysis of amino acids, peptides, and proteins. The novelty of our approach lies in the use of an externally actuated on-chip peristaltic pump and closely spaced pneumatic valves that allow well-defined, small-volume sample plugs to be injected and separated by microchip electrophoresis. We fabricated three-layer poly(dimethylsiloxane) (PDMS) microfluidic devices. The fluidic layer had injection and separation channels, and the control layer had an externally actuated on-chip peristaltic pump and four pneumatic valves around the T-intersection to carry out sample injection. An unpatterned PDMS membrane layer was sandwiched between the fluidic and control layers as the actuated component in pumps and valves. Devices with the same peristaltic pump design but different valve spacings (100, 200, 300, and 400 µm) from the injection intersection were fabricated using soft lithographic techniques. Devices were characterized through fluorescent imaging of captured plugs of a fluorescein-labeled amino acid mixture and through microchip electrophoresis separations. A suitable combination of peak height, separation efficiency, and analysis time was obtained with a peristaltic pump actuation rate of 50 ms, an injection time of 30 s, and a 200-µm valve spacing. We demonstrated the injection of samples in different solutions and were able to achieve a 2.4-fold improvement in peak height and a 2.8-fold increase in separation efficiency though sample stacking. A comparison of pressure-driven injection and electrokinetic injection with the same injection time and separation voltage showed a 3.9-fold increase in peak height in pressure-based injection with comparable separation efficiency. Finally, the microchip systems were used to separate biomarkers implicated in pre-term birth. Although these devices have initially been demonstrated as a stand-alone microfluidic separation tool, they have strong potential to be integrated within more complex systems.

DNA transfer through nonintimate social contact.

The UK and Ireland Association of Forensic Science Providers' (AFSP) Body Fluid Forum (BFF) set out to assist in the interpretation of sexual offence cases where semen is absent on vaginal swabs but female DNA is present on penile swabs or male underwear, and the issue to be addressed is whether or not sexual intercourse occurred. This study aims to investigate the frequency and amount of female DNA transferred to the penis and underwear of males following staged nonintimate social contact with females and to compare the findings with the amount of female DNA transferred to the penis and subsequently to the underwear of a male who had engaged in unprotected sexual intercourse with a female. In this study, no matching female DNA was detected on the inside front of the 44 items of male underwear used in this research following staged contact of a nonintimate nature and subsequent secondary transfer to the penis. After sexual intercourse, full profiles matching the female participant were found on the inside front of the males underwear with maximum peak heights in the range between 1898 and 3157 rfu. It was possible to demonstrate that DNA can occasionally transfer to the waistband and outside front of underwear worn by a male following staged nonintimate social contact. Data obtained in this study suggest that a matching female DNA profile below a peak height of 1000 rfu on the waistband of a male's underwear might be explained by nonintimate social contact with secondary transfer of female DNA from the male's hands.

Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1.

OBJECTIVE: Development of brown-like/beige adipocytes in white adipose tissue (WAT) helps to reduce obesity. Thus we investigated the effects of resveratrol, a dietary polyphenol capable of preventing obesity and related complications in humans and animal models, on brown-like adipocyte formation in inguinal WAT (iWAT). METHODS: CD1 female mice (5-month old) were fed a high-fat diet with/without 0.1% resveratrol. In addition, primary stromal vascular cells separated from iWAT were subjected to resveratrol treatment. Markers of brown-like (beige) adipogenesis were measured and the involvement of AMP-activated protein kinase (AMPK) α1 was assessed using conditional knockout. RESULTS: Resveratrol significantly increased mRNA and/or protein expression of brown adipocyte markers, including uncoupling protein 1 (UCP1), PR domain-containing 16, cell death-inducing DFFA-like effector A, elongation of very long-chain fatty acids protein 3, peroxisome proliferator-activated receptor-γ coactivator 1α, cytochrome c and pyruvate dehydrogenase, in differentiated iWAT stromal vascular cells (SVCs), suggesting that resveratrol induced brown-like adipocyte formation in vitro. Concomitantly, resveratrol markedly enhanced AMPKα1 phosphorylation and differentiated SVC oxygen consumption. Such changes were absent in cells lacking AMPKα1, showing that AMPKα1 is a critical mediator of resveratrol action. Resveratrol also induced beige adipogenesis in vivo along with the appearance of multiocular adipocytes, increased UCP1 expression and enhanced fatty acid oxidation. CONCLUSIONS: Resveratrol induces brown-like adipocyte formation in iWAT via AMPKα1 activation and suggest that its beneficial antiobesity effects may be partly due to the browning of WAT and, as a consequence, increased oxygen consumption.