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Flagellar dyneins are the molecular motors responsible for producing the propagating bending motions of cilia and flagella. They are located within a densely packed and highly organised super-macromolecular cytoskeletal structure known as the axoneme. Using the mesoscale simulation technique Fluctuating Finite Element Analysis (FFEA), which represents proteins as viscoelastic continuum objects subject to explicit thermal noise, we have quantified the constraints on the range of molecular conformations that can be explored by dynein-c within the crowded architecture of the axoneme. We subsequently assess the influence of crowding on the 3D exploration of microtubule-binding sites, and specifically on the axial step length. Our calculations combine experimental information on the shape, flexibility and environment of dynein-c from three distinct sources; negative stain electron microscopy, cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET). Our FFEA simulations show that the super-macromolecular organisation of multiple protein complexes into higher-order structures can have a significant influence on the effective flexibility of the individual molecular components, and may, therefore, play an important role in the physical mechanisms underlying their biological function.
The first episode of psychosis is a critical period in the emergence of cardiometabolic risk.
We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis.
This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months.
Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol).
Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.
Crisis resolution teams (CRTs) offer brief, intensive home treatment for people experiencing mental health crisis. CRT implementation is highly variable; positive trial outcomes have not been reproduced in scaled-up CRT care.
To evaluate a 1-year programme to improve CRTs’ model fidelity in a non-masked, cluster-randomised trial (part of the Crisis team Optimisation and RElapse prevention (CORE) research programme, trial registration number: ISRCTN47185233).
Fifteen CRTs in England received an intervention, informed by the US Implementing Evidence-Based Practice project, involving support from a CRT facilitator, online implementation resources and regular team fidelity reviews. Ten control CRTs received no additional support. The primary outcome was patient satisfaction, measured by the Client Satisfaction Questionnaire (CSQ-8), completed by 15 patients per team at CRT discharge (n = 375). Secondary outcomes: CRT model fidelity, continuity of care, staff well-being, in-patient admissions and bed use and CRT readmissions were also evaluated.
All CRTs were retained in the trial. Median follow-up CSQ-8 score was 28 in each group: the adjusted average in the intervention group was higher than in the control group by 0.97 (95% CI −1.02 to 2.97) but this was not significant (P = 0.34). There were fewer in-patient admissions, lower in-patient bed use and better staff psychological health in intervention teams. Model fidelity rose in most intervention teams and was significantly higher than in control teams at follow-up. There were no significant effects for other outcomes.
The CRT service improvement programme did not achieve its primary aim of improving patient satisfaction. It showed some promise in improving CRT model fidelity and reducing acute in-patient admissions.
A lasting legacy of the International Polar Year (IPY) 2007–2008 was the promotion of the Permafrost Young Researchers Network (PYRN), initially an IPY outreach and education activity by the International Permafrost Association (IPA). With the momentum of IPY, PYRN developed into a thriving network that still connects young permafrost scientists, engineers, and researchers from other disciplines. This research note summarises (1) PYRN’s development since 2005 and the IPY’s role, (2) the first 2015 PYRN census and survey results, and (3) PYRN’s future plans to improve international and interdisciplinary exchange between young researchers. The review concludes that PYRN is an established network within the polar research community that has continually developed since 2005. PYRN’s successful activities were largely fostered by IPY. With >200 of the 1200 registered members active and engaged, PYRN is capitalising on the availability of social media tools and rising to meet environmental challenges while maintaining its role as a successful network honouring the legacy of IPY.
Nighttime eating is often associated with a negative impact on weight management and cardiometabolic health. However, data from recent acute metabolic studies have implicated a benefit of ingesting a bedtime snack for weight management. The present study compared the impact of ingesting a milk snack containing either 10 (BS10) or 30 g (BS30) protein with a non-energetic placebo (BS0) 30 min before bedtime on next morning metabolism, appetite and energy intake in mildly overweight males (age: 24·3 (sem 0·8) years; BMI: 27·4 (sem 1·1) kg/m2). Next morning measurements of RMR, appetite and energy intake were measured using indirect calorimetry, visual analogue scales and an ad libitum breakfast, respectively. Bedtime milk ingestion did not alter next morning RMR (BS0: 7822 (sem 276) kJ/d, BS10: 7482 (sem 262) kJ/d, BS30: 7851 (sem 261) kJ/d, P=0·19) or substrate utilisation as measured by RER (P=0·64). Bedtime milk ingestion reduced hunger (P=0·01) and increased fullness (P=0·04) during the evening immediately after snack ingestion, but elicited no effect the next morning. Next morning breakfast (BS0: 2187 (sem 365) kJ, BS10: 2070 (sem 336) kJ, BS30: 2582 (sem 384) kJ, P=0·21) and 24 h post-trial (P=0·95) energy intake was similar between conditions. To conclude, in mildly overweight adults, compared with a non-energetic placebo, a bedtime milk snack containing 10 or 30 g of protein does not confer changes in next morning whole-body metabolism and appetite that may favour weight management.
The association of music with madness is very longstanding. But is it more than myth, and if so what is the nature of this relationship? We tested the hypotheses that musicians possess greater schizotypy and symptoms of bipolar disorder. A total of 102 musicians were found to have greater positive and negative schizotypal traits when compared to matched norms on the shortened Oxford–Liverpool Inventory of Feelings and Experiences. Based on the Mood Disorder Questionnaire, 10.8% of musicians also met criteria for lifetime bipolar disorder. Rock musicians appeared to have greater symptoms than those performing in other musical genres.
This paper reports on a theoretical analysis of the rich variety of spatio-temporal patterns observed recently in inclined layer convection at medium Prandtl number when varying the inclination angle
and the Rayleigh number
. The present numerical investigation of the inclined layer convection system is based on the standard Oberbeck–Boussinesq equations. The patterns are shown to originate from a complicated competition of buoyancy driven and shear-flow driven pattern forming mechanisms. The former are expressed as longitudinal convection rolls with their axes oriented parallel to the incline, the latter as perpendicular transverse rolls. Along with conventional methods to study roll patterns and their stability, we employ direct numerical simulations in large spatial domains, comparable with the experimental ones. As a result, we determine the phase diagram of the characteristic complex 3-D convection patterns above onset of convection in the
plane, and find that it compares very well with the experiments. In particular we demonstrate that interactions of specific Fourier modes, characterized by a resonant interaction of their wavevectors in the layer plane, are key to understanding the pattern morphologies.
The discovery of Neolithic houses at Durrington Walls that are contemporary with the main construction phase of Stonehenge raised questions as to their interrelationship. Was Durrington Walls the residence of the builders of Stonehenge? Were the activities there more significant than simply domestic subsistence? Using lipid residue analysis, this paper identifies the preferential use of certain pottery types for the preparation of particular food groups and differential consumption of dairy and meat products between monumental and domestic areas of the site. Supported by the analysis of faunal remains, the results suggest seasonal feasting and perhaps organised culinary unification of a diverse community.
Despite the economic benefits of organic farming, the conversion rates to this production method are low. The reasons for this reluctance are largely unknown; however, understanding this behavior is important for policy recommendations. Therefore, we experimentally investigate and compare the investment behavior of organic and conventional hog farmers. We examine whether the investment behavior depends on the organic or conventional farmers’ status quo of their production method. Our results show that farmers are more reluctant to invest in production methods they are not currently using compared with those already in use on their farm. Conventional, more risk-averse farmers, and those farmers holding a university degree, invest later in a hog barn. The results provide evidence that investment decisions depend on the status quo production method of a farmer and, thus, reveal that current subsidy structures may be ineffective in encouraging farmers to invest in production methods they are not currently using on their farms.
In this study, three patients presenting with early or late postoperative Fontan complications were identified to suffer from restriction of the native atrial septum. This caused significant obstruction to pulmonary venous return and elevated systemic venous pressure. Dobutamine stress testing was used in one patient to identify this lesion. Transcatheter stenting was performed in the other two patients. Patients improved after relief of the obstruction.
We surveyed hospital epidemiologists and infection preventionists on their usage of and satisfaction with infection prevention–specific software supplementing their institution’s electronic medical record. Respondents with supplemental software were more satisfied with their software’s infection prevention and antimicrobial stewardship capabilities than those without. Infection preventionists were more satisfied than hospital epidemiologists.
The mechanical and thermal behavior of nanoglasses (NGs) were studied with a focus on the effect of the microstructure. The thermal expansion was measured to track changes in excess free volume during heating. It was found that the excess free volume, which is initially more dominant in the interphase region between the denser amorphous particles, is partially lost as well as redistributed during annealing. This relaxation during heating causes the nanoglass to behave like a melt-spun ribbon after heating while remaining amorphous. Nanomechanical tests were used to probe the local incipient plasticity and the influence of the interphase region. This interphase appears to affect the mechanical response of the NGs by inhibiting the propagation of shear bands and thus offers a novel approach for the introduction of plasticity in bulk metallic glasses. The results suggest that the NGs consist of two distinct amorphous phases with different glass transition temperatures.