Electronuclear Transition into a Spatially Modulated Magnetic State in YbRh_{2}Si_{2}.

The nature of the antiferromagnetic order in the heavy fermion metal YbRh_{2}Si_{2}, its quantum criticality, and superconductivity, which appears at low mK temperatures, remain open questions. We report measurements of the heat capacity over the wide temperature range 180 µK-80 mK, using current sensing noise thermometry. In zero magnetic field we observe a remarkably sharp heat capacity anomaly at 1.5 mK, which we identify as an electronuclear transition into a state with spatially modulated electronic magnetic order of maximum amplitude 0.1 µ_{B}. We also report results of measurements in magnetic fields in the range 0 to 70 mT, applied perpendicular to the c axis, which show eventual suppression of this order. These results demonstrate a coexistence of a large moment antiferromagnet with putative superconductivity.

Trajectories of Alcohol Use and Related Harms for Managed Alcohol Program Participants over 12 Months Compared with Local Controls: A Quasi-Experimental Study.

AIM: Investigate changes in alcohol use and related harm using the first multisite, controlled, longitudinal study of Managed Alcohol Programs (MAPs). MAPs provide regular doses of alcohol, accommodation, social supports and healthcare to unstably housed people with alcohol dependence. METHODS: A multisite, quasi-experimental, longitudinal study was conducted in day centres, shelters and residential programs for unstably housed people. There were 59 MAP participants from six Canadian cities and 116 local controls. Self-reported alcohol consumption and harms were assessed at 0-2, 6 and 12 months. Liver function test results were accessed for MAP participants. RESULTS: Both groups had similar reductions in mean drinks per day (MAP: -8.11; controls: -8.54 controls, P < 0.001) and days drinking per month (MAP: -2.51 days, P < 0.05; control: -4.81 days, P = 0.0001) over 6--12 months. Both reduced non-beverage alcohol consumption. MAP participants reported significantly fewer harms at both 0-2 and 6 months than controls. MAP participants had similar total consumption to controls, but spread out over more days (25.41 versus 19.64 days per month, P = 0.001). After leaving a MAP, participants' liver status deteriorated, with increases in both aspartate transaminase and bilirubin levels. MAP sites with effective policies on outside drinking drank less and had fewer harms. CONCLUSION: MAP participants drank less hazardously than controls, especially with effective management of non-MAP drinking. Reductions in alcohol use and harms occurred for both groups, although MAP participants reported fewer harms at 0-6 months. Departing an MAP was associated with deterioration in liver status. Although providing stable housing, MAPs did not worsen health or increase alcohol use.

Impact of postoperative complications on disease recurrence and long-term survival following oesophagogastric cancer resection.

BACKGROUND: Postoperative complications after resection of oesophagogastric carcinoma can result in considerable early morbidity and mortality. However, the long-term effects on survival are less clear. METHODS: All patients undergoing intentionally curative resection for oesophageal or gastric cancer between 2006 and 2016 were selected from an institutional database. Patients were categorized by complication severity according to the Clavien-Dindo classification (grades 0-V). Complications were defined according to an international consensus statement. The effect of leak and severe non-leak-related complications on overall survival, recurrence and disease-free survival was assessed using Kaplan-Meier analyses to evaluate differences between groups. All factors significantly associated with survival in univariable analysis were entered into a Cox multivariable regression model with stepwise elimination. RESULTS: Some 1100 patients were included, with a median age of 69 (range 28-92) years; 48·1 per cent had stage III disease and cancer recurred in 428 patients (38·9 per cent). Complications of grade III or higher occurred in 244 patients (22·2 per cent). The most common complications were pulmonary (29·9 per cent), with a 13·0 per cent incidence of pneumonia. Rates of atrial dysrhythmia and anastomotic leak were 10·0 and 9·6 per cent respectively. Patients with a grade III-IV leak did not have significantly reduced overall survival compared with those who had grade 0-I complications. However, patients with grade III-IV non-leak-related complications had reduced median overall survival (19·7 versus 42·7 months; P < 0·001) and disease-free survival (18·4 versus 36·4 months; P < 0·001). Cox regression analysis identified age, tumour stage, resection margin and grade III-IV non-leak-related complications as independent predictors of poor overall and disease-free survival. CONCLUSION: Beyond the acute postoperative period, anastomotic leak does not adversely affect survival, however, other severe postoperative complications do reduce long-term overall and disease-free survival.

The Cochrane 2018 Review on Brief Interventions in Primary Care for Hazardous and Harmful Alcohol Consumption: A Distillation for Clinicians and Policy Makers.

AIMS: An updated Cochrane systematic review assessed effectiveness of screening and brief intervention to reduce hazardous or harmful alcohol consumption in general practice or emergency care settings. This paper summarises the implications of the review for clinicians. METHODS: Cochrane methods were followed. Reporting accords with PRISMA guidance. We searched multiple resources to September 2017, seeking randomised controlled trials of brief interventions to reduce hazardous or harmful alcohol consumption in people attending general practice, emergency care or other primary care settings for reasons other than alcohol treatment. Brief intervention was defined as a conversation comprising five or fewer sessions of brief advice or brief lifestyle counselling and a total duration of less than 60 min. Our primary outcome was alcohol consumption, measured as or convertible to grams per week. We conducted meta-analyses to assess change in consumption, and subgroup analyses to explore the impact of participant and intervention characteristics. RESULTS: We included 69 studies, of which 42 were added for this update. Most studies (88%) compared brief intervention to control. The primary meta-analysis included 34 studies and provided moderate-quality evidence that brief intervention reduced consumption compared to control after one year (mean difference -20 g/wk, 95% confidence interval -28 to -12). Subgroup analysis showed a similar effect for men and women. CONCLUSIONS: Brief interventions can reduce harmful and hazardous alcohol consumption in men and women. Short, advice-based interventions may be as effective as extended, counselling-based interventions for patients with harmful levels of alcohol use who are presenting for the first time in a primary care setting.

Neighbourhood typologies and associations with body mass index and obesity: A cross-sectional study.

Little research has investigated associations between a combined measure of the food and physical activity (PA) environment, BMI (body-mass-index) and obesity. Cross-sectional data (n=22,889, age 18-86years) from the Yorkshire Health Study were used [2010-2013]. BMI was calculated using self-reported height and weight; obesity=BMI≥30. Neighbourhood was defined as a 2km radial buffer. Food outlets and PA facilities were sourced from Ordnance Survey Points of Interest (PoI) and categorised into 'fast-food', 'large supermarkets', 'convenience and other food retail outlets' and 'physical activity facilities'. Parks were sourced from Open Street Map. Latent class analysis was conducted on these five environmental variables and availability was defined by quartiles of exposure. Linear and logistic regressions were then conducted for BMI and obesity respectively for different neighbourhood types. Models adjusted for age, gender, ethnicity, area-level deprivation, and rural/urban classification. A five-class solution demonstrated best fit and was interpretable. Neighbourhood typologies were defined as; 'low availability', 'moderate availability', 'moderate PA, limited food', 'saturated' and 'moderate PA, ample food'. Compared to low availability, one typology demonstrated lower BMI (saturated, b=-0.50, [95% CI=-0.76, -0.23]), while three showed higher BMI (moderate availability, b=0.49 [0.27, 0.72]; moderate PA, limited food, b=0.30 [0.01, 0.59]; moderate PA, ample food, b=0.32 [0.08, 0.57]). Furthermore, compared to the low availability, saturated neighbourhoods showed lower odds of obesity (OR=0.86 [0.75, 0.99]) while moderate availability showed greater odds of obesity (OR=1.18 [1.05, 1.32]). This study supports population-level approaches to tackling obesity however neighbourhoods contained features that were health-promoting and -constraining.

Charge Density Waves in Graphite: Towards the Magnetic Ultraquantum Limit.

Graphite is a model system for the study of three-dimensional electrons and holes in the magnetic quantum limit, in which the charges are confined to the lowest Landau levels. We report magneto-transport measurements in pulsed magnetic fields up to 60 T, which resolve the collapse of two charge density wave states in two, electron and hole, Landau levels at 52.3 and 54.2 T, respectively. We report evidence for a commensurate charge density wave at 47.1 T in the electron Landau level, and discuss the likely nature of the density wave instabilities over the full field range. The theoretical modeling of our results predicts that the ultraquantum limit is entered above 73.5 T. This state is an insulator, and we discuss its correspondence to the "metallic" state reported earlier. We propose that this (interaction-induced) insulating phase supports surface states that carry no charge or spin within the planes, but does, however, support charge transport out of plane.

Primary current-sensing noise thermometry in the millikelvin regime.

The use of low-temperature platforms with base temperatures below 1 K is rapidly expanding, for fundamental science, sensitive instrumentation and new technologies of potentially significant commercial impact. Precise measurement of the thermodynamic temperature of these low-temperature platforms is crucial for their operation. In this paper, we describe a practical and user-friendly primary current-sensing noise thermometer (CSNT) for reliable and traceable thermometry and the dissemination of the new kelvin in this temperature regime. Design considerations of the thermometer are discussed, including the optimization of a thermometer for the temperature range to be measured, noise sources and thermalization. We show the procedure taken to make the thermometer primary and contributions to the uncertainty budget. With standard laboratory instrumentation, a relative uncertainty of 1.53% is obtainable. Initial comparison measurements between a primary CSNT and a superconducting reference device traceable to the PLTS-2000 (Provisional Low Temperature Scale of 2000) are presented between 66 and 208 mK, showing good agreement within the k=1 calculated uncertainty.

Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways.

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.

To dance or not to dance? A comparison of balance, physical fitness and quality of life in older Irish set dancers and age-matched controls.

OBJECTIVE: The objective of this study is to determine if older adults regularly participating in Irish set dancing have superior balance, physical fitness and quality of life compared to age-matched controls. STUDY DESIGN: This study used a community-based, observational cross-sectional design. METHODS: Regular set dancers (n = 39) and age-matched controls (n = 33) were recruited. Participants were assessed using the physical activity scale for the elderly (physical activity levels), mini-BESTest (balance) and senior fitness test (battery of functional fitness tests). Quality of life was also assessed using the EuroQol EQ visual analogue scale. RESULTS: When controlling for between-group differences in levels of physical activity (ANCOVA analysis), the dancers had significantly better balance, functional capacity and quality of life (all P < 0.05) compared to controls. No differences between the groups were observed in other measures of functional fitness. CONCLUSION: The findings of this study suggest regular participation in set dancing is associated with health benefits for older adults. These results may inform future studies prospectively examining the role of set dancing for falls prevention, emotional well-being and cognitive function in community-dwelling older adults.

A Direct Oral Anticoagulant as a Cost Effective Alternative to Warfarin for Treatment of Provoked Venous Thrombosis.

In Ireland, Warfarin is the primary anticoagulant prescribed in the secondary prevention of provoked DVT. We completed a comprehensive cost analysis of a trial group of 24 patients treated with Rivaroxaban (between November 2013 and December 2014), versus a control group treated with Warfarin (between January 2008 and November 2013). The groups were matched for gender (3/7 M/F ratio), DVT type (5 proximal, 19 distal DVTs), provoking factor (20 traumatic, 4 atraumatc), and age. We calculated the cost for each group based on drug administration and clinic costs (labour, sample analysis, and additional costs). Warfarin patients attended clinic 14.58 times; Rivaroxaban patients attended 2.92 times. Overall, the cost per patient on Rivaroxaban is €273.30 versus €260.68 with warfarin. This excludes patient costs which would further increase cost of Warfarin therapy.

Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults.

VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing HIV-1 monoclonal antibody (mAb) isolated from the B cells of an HIV-infected patient. It is directed against the HIV-1 CD4 binding site and is capable of potently neutralizing the majority of diverse HIV-1 strains. This Phase I dose-escalation study in healthy adults was conducted at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA). Primary objectives were the safety, tolerability and pharmacokinetics (PK) of VRC01 intravenous (i.v.) infusion at 5, 20 or 40 mg/kg, given either once (20 mg/kg) or twice 28 days apart (all doses), and of subcutaneous (s.c.) delivery at 5 mg/kg compared to s.c. placebo given twice, 28 days apart. Cumulatively, 28 subjects received 43 VRC01 and nine received placebo administrations. There were no serious adverse events or dose-limiting toxicities. Mean 28-day serum trough concentrations after the first infusion were 35 and 57 µg/ml for groups infused with 20 mg/kg (n = 8) and 40 mg/kg (n = 5) doses, respectively. Mean 28-day trough concentrations after the second infusion were 56 and 89 µg/ml for the same two doses. Over the 5-40 mg/kg i.v. dose range (n = 18), the clearance was 0.016 l/h and terminal half-life was 15 days. After infusion VRC01 retained expected neutralizing activity in serum, and anti-VRC01 antibody responses were not detected. The human monoclonal antibody (mAb) VRC01 was well tolerated when delivered i.v. or s.c. The mAb demonstrated expected half-life and pharmacokinetics for a human immunoglobulin G. The safety and PK results support and inform VRC01 dosing schedules for planning HIV-1 prevention efficacy studies.

Predictors of the physical impact of Multiple Sclerosis following community-based, exercise trial.

BACKGROUND: Studies evaluating exercise interventions in people with multiple sclerosis (PwMS) demonstrate small to medium positive effects and large variability on a number of outcome measures. No study to date has tried to explain this variability. OBJECTIVE: This paper presents a novel exploration of data examining the predictors of outcome for PwMS with minimal gait impairment following a randomised, controlled trial evaluating community-based exercise interventions (N = 242). METHODS: The primary variable was the physical component of the Multiple Sclerosis Impact Scale-29, version 2 (MSIS-29, v2) after a 10-week, controlled intervention period. Predictors were identified a priori and were measured at baseline. Multiple linear regression was conducted. RESULTS: Four models are presented lower MSIS-29, v2 scores after the intervention period were best predicted by a lower baseline MSIS-29,v2, a lower baseline Modified Fatigue Impact Score (physical subscale), randomisation to an exercise intervention, a longer baseline walking distance measured by the Six Minute Walk Test and female gender. This model explained 57.4% of the variance (F (5, 211) = 59.24, p < 0.01). CONCLUSION: These results suggest that fatigue and walking distance at baseline contribute significantly to predicting MSIS-29, v29 (physical component) after intervention, and thus should be the focus of intervention and assessment. Exercise is an important contributor to minimising the physical impact of MS, and gender-specific interventions may be warranted.

Psychosomatic Medicine for Non-Psychiatric Residents: Video Education and Incorporation of Technology.

OBJECTIVES: Psychiatric education for non-psychiatric residents varies between training programs, and may affect resident comfort with psychiatric topics. This study's goals were to identify non-psychiatric residents' comfort with psychiatric topics and to test the effectiveness of a video intervention. METHODS: Residents in various departments were given a survey. They were asked to rank their comfort level with multiple psychiatric topics, answer questions about medical decision making capacity (MDMC), watch a 15-min video about MDMC, and answer a post-test section. RESULTS: In total, 91 Internal Medicine, General Surgery, and Obstetrics and Gynecology residents responded to the study. Of the 91 residents, 55 completed the pre- and post-test assessments. There was no significant difference in correct responses. Residents' comfort levels were assessed, and a significant improvement in comfort level with MDMC was found. CONCLUSIONS: This study highlights potential opportunities for psychiatric education, and suggests brief video interventions can increase resident physicians' comfort with a psychiatric topic.

Quantitation OF ARGS aggrecan fragments in synovial fluid, serum and urine from osteoarthritis patients.

OBJECTIVE: To characterise ARGS neoepitope concentrations in various matrices from patients with knee osteoarthritis (OA) and assess performance of an immunoassay to facilitate clinical development of therapeutics affecting the A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5) pathway. DESIGN: Matched sera, urine, and synovial fluid (SF) (surgical subjects only) were collected from healthy subjects, subjects with knee OA (non-surgical OA), and OA subjects undergoing total knee replacement (OA-TKR; n = 20 per group). Diurnal and inter-day variation was evaluated in the non-surgical OA group over 3 separate visits. Serum and urine samples were collected on two visits for the OA-TKR group with SF taken only at the time of surgery. ARGS neoepitope was quantitated using an optimized immunoassay. RESULTS: Serum ARGS neoepitope concentrations were elevated in OA-TKR subjects compared to non-surgical OA subjects (P = 0.005) and healthy subjects (P = 0.0002). Creatinine corrected urinary ARGS neoepitope concentrations were more variable, but were also elevated in the OA-TKR subjects compared to healthy subjects (P = 0.008). No significant diurnal effect or inter-day variance was observed in serum or urine. Serum ARGS neoepitope concentrations correlated with age (P = 0.0252) but not with total number of joints with OA involvement. SF ARGS neoepitope concentrations correlated with Western Ontario and MacMaster OA Index (WOMAC) stiffness score (P = 0.04) whereas a weaker, non-significant trend towards positive correlation with combined WOMAC score and the number of concurrent joints was observed. CONCLUSIONS: This study utilized a sensitive and robust assay to evaluate ARGS neoepitope concentrations in various matrices in OA patients and healthy volunteers. ARGS neoepitope appears promising as a prognostic/stratification marker to facilitate patient selection and as an early pharmacodynamic marker for OA therapeutic trials.

Design and synthesis of novel small molecule CCR2 antagonists: evaluation of 4-aminopiperidine derivatives.

A novel N-(2-oxo-2-(piperidin-4-ylamino)ethyl)-3-(trifluoromethyl)benzamide series of human CCR2 chemokine receptor antagonists was identified. With a pharmacophore model based on known CCR2 antagonists a new core scaffold was designed, analogues of it synthesized and structure­affinity relationship studies derived yielding a new high affinity CCR2 antagonist N-(2-((1-(4-(3-methoxyphenyl)cyclohexyl)piperidin-4-yl)amino)-2-oxoethyl)-3-(trifluoromethyl)benzamide.

Colorectal cancer is reliably excluded in the frail and elderly population by minimal preparation CT.

BACKGROUND: This study aimed to retrospectively assess the accuracy of minimal preparation computed tomography (MPCT) in the detection of colorectal cancer (CRC) within the frail and elderly population and to evaluate the relevance of extra-colonic findings (ECF). METHODS: Radiology reports, clinical notes and follow-up reports from 207 patients who underwent MPCT to investigate for CRC between 2005 and 2009 were analysed. Patients were scanned following the administration of oral contrast for 48 h, without bowel preparation or colonic insufflation. MPCT results were measured against patient outcomes, with a minimum of 2 years of follow-up. RESULTS: Twelve cases of clinically relevant CRC were confirmed (5.8 %). MPCT correctly identified 11 of these lesions (sensitivity 91.6 %). Thirty-one patients had a possible CRC identified by MPCT, which was not confirmed by further examination (specificity 84.1 %). This results in a positive predictive value of 26.2 % and a negative predictive value of 99.4 %. Five of the patients with colon cancer underwent curative surgery. Sixty-eight clinically relevant ECF were confirmed, including 14 previously undiagnosed extra-colonic malignancies. ECF were considered to account for the presenting complaint in 15.0 % (31/207) of all patients. CONCLUSIONS: Minimal preparation computed tomography is an effective and reliable investigation for the exclusion of clinically relevant CRC in this population. It provides clinicians with a valuable and pragmatic alternative to colonoscopy and CT colonography when invasive examination or cathartic bowel preparation will be poorly tolerated and small polyps are of limited significance. MPCT has an advantage over purely luminal imaging in the detection of extra-colonic pathology and appears to have an equally important role in the detection of CRC.

An audit of smoking prevalence and awareness of HSE smoking cessation services among HSE staff.

This audit estimated smoking prevalence and awareness of quit services among Health Service Executive (HSE) staff. A questionnaire posted to a random sample of 1,064 staff received a 71% response rate. Staff smoking prevalence was 15.0% overall, and 4.4% among Medical/Dental staff. Front-line-healthcare staff were less likely to smoke than other staff categories (adjusted OR 0.38, p < 0.001). Only 63.6% of staff were aware of HSE quit services. Targeted interventions are required to help staff to quit smoking and to boost awareness of quit services.