Integration over song classification replicates: Song variant analysis in the hihi

Human expert analyses are commonly used in bioacoustic studies and can potentially limit the reproducibility of these results. In this paper, a machine learning method is presented to statistically classify avian vocalizations. Automated approaches were applied to isolate bird songs from long field recordings, assess song similarities, and classify songs into distinct variants. Because no positive controls were available to assess the true classification of variants, multiple replicates of automatic classification of song variants were analyzed to investigate clustering uncertainty. The automatic classifications were more similar to the expert classifications than expected by chance. Application of these methods demonstrated the presence of discrete song variants in an island population of the New Zealand hihi (Notiomystis cincta). The geographic patterns of song variation were then revealed by integrating over classification replicates. Because this automated approach considers variation in song variant classification, it reduces potential human bias and facilitates the reproducibility of the results

Reversible DNA micro-patterning using the fluorous effect

We describe a new method for the immobilisation of DNA into defined patterns with sub-micron resolution, using the fluorous effect. The method is fully reversible via a simple solvent wash, allowing the patterning, regeneration and re-patterning of surfaces with no degradation in binding efficiency following multiple removal/attachment cycles of different DNA sequences

Obesity-related perivascular adipose tissue damage is reversed by sustained weight loss in the rat

Objective – Perivascular adipose tissue (PVAT) exerts an anticontractile effect in response to various vasoconstrictor agonists and this is lost in obesity. A recent study reported that bariatric surgery reverses the damaging effects of obesity on PVAT function. However, PVAT function has not been characterised following weight loss induced by caloric restriction, which is often the first line treatment for obesity. Approach and Results – Contractility studies were performed using wire myography on small mesenteric arteries with and without PVAT from control, diet-induced obese, calorie restricted and sustained weight loss rats. Changes in the PVAT environment were assessed using immunohistochemistry. PVAT from healthy animals elicited an anticontractile effect in response to norepinephrine. This was abolished in diet-induced obesity through a mechanism involving increased local TNFα and reduced nitric oxide bioavailability within PVAT. Sustained weight loss led to improvement in PVAT function associated with restoration of adipocyte size, reduced TNFα and increased nitric oxide synthase function. This was associated with reversal of obesity-induced hypertension and normalisation of plasma adipokine levels, including leptin and insulin. Conclusions – We have shown that diet-induced weight loss reverses obesity-induced PVAT damage through a mechanism involving reduced inflammation and increased nitric oxide synthase activity within PVAT. These data reveal inflammation and nitric oxide synthase, particularly eNOS, as potential targets for the treatment of PVAT dysfunction associated with obesity and the metabolic syndrome

Standardising the collection of patient-reported experience measures to facilitate benchmarking and drive service improvement

Patient experience teams in NHS Wales’ Health Boards and Trusts are working across the country to collect patient experience feedback from members of the public who access health care services. Although this work is advanced in many areas, there is currently no way of benchmarking across organisations, reducing opportunities for shared learning. We aimed to work with patients and colleagues across Wales to agree a set of universal Patient Reported Experience Measures (PREMs) questions. Working with patient experience teams, patient groups and Welsh Government, the NHS Wales Patient Reported Outcome Measures (PROMs), Patient Reported Experience Measures (PREMs) and Effectiveness Programme team has agreed a national set of PREMs questions for use across Wales. This process led on from previous work and included patient focus groups, patient experience leads and clinical input. Patients using secondary care services in Wales will be invited to complete the agreed PREMs survey along with patient outcome measures, via an electronic platform. This will provide a consistent method of data collection which will allow us to benchmark across hospitals and organisations in NHS Wales, identifying areas of good practice, as well as areas where patients report poorer experiences. This will allow local patient experience teams to target more in-depth experience gathering initiatives and carry out appropriate improvement programmes, making better use of resources. Identifying and sharing good practice will allow NHS Wales to advance patient experience, while triangulation with patient and clinical outcomes will drive the Prudent Healthcare agenda

A malaria parasite subtilisin propeptide-like protein is a potent inhibitor of the egress protease SUB1.

Subtilisin-like serine peptidases (subtilases) play important roles in the life cycle of many organisms, including the protozoan parasites that are the causative agent of malaria, Plasmodium spp. As with other peptidases, subtilase proteolytic activity has to be tightly regulated in order to prevent potentially deleterious uncontrolled protein degradation. Maturation of most subtilases requires the presence of an N-terminal propeptide that facilitates folding of the catalytic domain. Following its proteolytic cleavage, the propeptide acts as a transient, tightly bound inhibitor until its eventual complete removal to generate active protease. Here we report the identification of a stand-alone malaria parasite propeptide-like protein, called SUB1-ProM, encoded by a conserved gene that lies in a highly syntenic locus adjacent to three of the four subtilisin-like genes in the Plasmodium genome. Template-based modelling and ab initio structure prediction showed that the SUB1-ProM core structure is most similar to the X-ray crystal structure of the propeptide of SUB1, an essential parasite subtilase that is discharged into the parasitophorous vacuole (PV) to trigger parasite release (egress) from infected host cells. Recombinant Plasmodium falciparum SUB1-ProM was found to be a fast-binding, potent inhibitor of P. falciparum SUB1, but not of the only other essential blood-stage parasite subtilase, SUB2, or of other proteases examined. Mass-spectrometry and immunofluorescence showed that SUB1-ProM is expressed in the PV of blood stage P. falciparum, where it may act as an endogenous inhibitor to regulate SUB1 activity in the parasite

Development and delivery of an exercise programme for falls prevention: the Prevention of Falls Injury Trial (PreFIT)

This paper describes the development and implementation of an exercise intervention to prevent falls within The Prevention of Fall Injury Trial (PreFIT), which is a large multi-centred randomised controlled trial based in the UK National Health Service (NHS).Using the template for intervention description and replication (TIDieR) checklist, to describe the rationale and processes for treatment selection and delivery of the PreFIT exercise intervention.Based on the results of a validated falls and balance survey, participants were eligible for the exercise intervention if they were at moderate or high risk of falling.Intervention development was informed using the current evidence base, published guidelines, and pre-existing surveys of clinical practice, a pilot study and consensus work with therapists and practitioners. The exercise programme targets lower limb strength and balance, which are known, modifiable risk factors for falling. Treatment was individually tailored and progressive, with seven recommended contacts over a six-month period. Clinical Trials Registry (ISCTRN 71002650)

A Multi-Model Pipeline for Translational Intracerebral Haemorrhage Research

From Springer Nature via Jisc Publications RouterHistory: received 2020-05-15, rev-recd 2020-06-18, accepted 2020-06-23, registration 2020-06-24, pub-electronic 2020-07-07, online 2020-07-07, pub-print 2020-12Publication status: PublishedFunder: Stroke Association; doi: http://dx.doi.org/10.13039/501100000364; Grant(s): TSA LECT 2017/02, SA L-RC 19\100000Funder: Medical Research Council; doi: http://dx.doi.org/10.13039/501100000265; Grant(s): MR/N013751/1Abstract: Apart from acute and chronic blood pressure lowering, we have no specific medications to prevent intracerebral haemorrhage (ICH) or improve outcomes once bleeding has occurred. One reason for this may be related to particular limitations associated with the current pre-clinical models of ICH, leading to a failure to translate into the clinic. It would seem that a breakdown in the ‘drug development pipeline’ currently exists for translational ICH research which needs to be urgently addressed. Here, we review the most commonly used pre-clinical models of ICH and discuss their advantages and disadvantages in the context of translational studies. We propose that to increase our chances of successfully identifying new therapeutics for ICH, a bi-directional, 2- or 3-pronged approach using more than one model species/system could be useful for confirming key pre-clinical observations. Furthermore, we highlight that post-mortem/ex-vivo ICH patient material is a precious and underused resource which could play an essential role in the verification of experimental results prior to consideration for further clinical investigation. Embracing multidisciplinary collaboration between pre-clinical and clinical ICH research groups will be essential to ensure the success of this type of approach in the future

Is there a difference in physical activity levels in patients before and up to one year after unilateral total hip replacement? A systematic review and meta-analysis

Objective: To determine if there is a difference in physical activity levels before and up to one year after unilateral primary total hip replacement. Data sources: A search was performed on 13th July 2016. Studies were eligible for inclusion if they presented pre-operative and up to one year post-operative measures of physical activity for patients who had undergone unilateral primary total hip replacement. Review methods: Any paper that used a measure of physical activity pre and up to one year post unilateral primary total hip replacement. Data was synthesised using a meta-analysis with 95% confidence intervals (CI), if appropriate. The Critical Appraisal Skills Programme cohort study checklist was used to assess the quality of evidence. Results: From 6024 citations, nine studies were analysed in a meta-analysis and eight studies were analysed qualitatively. The quality of the evidence was ‘low’ to ‘moderate’. There was no statistically significant difference in physical activity pre- to post-total hip replacement when assessed using: movement-related activity (mean difference (MD): -0.08; 95% CI: 1.60, 1.44; I2=0%; n=77), percentage of 24-hours spent walking (MD: -0.21; 95% CI: -1.36, 0.93; I2=12%; n=65), six-minute walk test (MD: -60.85; 95% CI: -122.41, 0.72; I2=84%; n=113) or the cardiopulmonary exercise test (MD: -0.24; 95% CI: -1.36, 0.87; I2=0%;n=76). Conclusion: There is no statistically significant difference in physical activity levels before and up to one year after unilateral primary total hip replacement. However the low to moderate methodological quality of the included papers should be taken into consideration when drawing conclusions