Reliability of recommended non-invasive chairside screening tests for diabetes-related peripheral neuropathy : a systematic review with meta-analyses

The objective is to determine, by systematic review, the reliability of testing methods for diagnosis of diabetes-related peripheral neuropathy (DPN) as recommended by the most recent guidelines from the International Diabetes Foundation, International Working Group on the Diabetic Foot and American Diabetes Association. Electronic searches of Cochrane Library, EBSCO Megafile Ultimate and EMBASE were performed to May 2021. Articles were included if they reported on the reliability of recommended chairside tests in diabetes cohorts. Quality appraisal was performed using a Quality Appraisal of Reliability Studies checklist and where possible, meta-analyses, with reliability reported as estimated Cohen's kappa (95% CI). Seventeen studies were eligible for inclusion. Pooled analysis found acceptable inter-rater reliability of vibration perception threshold (VPT) (κ=0.61 (0.50 to 0.73)) and ankle reflex testing (κ=0.60 (0.55 to 0.64)), but weak inter-rater reliability for pinprick (κ=0.45 (0.22 to 0.69)) and 128 Hz tuning fork (κ=0.42 (0.15 to 0.70)), though intra-rater reliability of the 128 Hz tuning fork was moderate (κ=0.54 (0.37 to 0.73)). Inter-rater reliability of the four-site monofilament was acceptable (κ=0.61 (0.45 to 0.77)). These results support the clinical use of VPT, ankle reflexes and four-site monofilament for screening and ongoing monitoring of DPN as recommended by the latest guidelines. The reliability of temperature perception, pinprick, proprioception, three-site monofilament and Ipswich touch test when performed in people with diabetes remains unclear

Episodic Radiations in the Fly Tree of Life

Flies are one of four superradiations of insects (along with beetles, wasps, and moths) that account for the majority of animal life on Earth. Diptera includes species known for their ubiquity (Musca domestica house fly), their role as pests (Anopheles gambiae malaria mosquito), and their value as model organisms across the biological sciences (Drosophila melanogaster). A resolved phylogeny for flies provides a framework for genomic, developmental, and evolutionary studies by facilitating comparisons across model organisms, yet recent research has suggested that fly relationships have been obscured by multiple episodes of rapid diversification. We provide a phylogenomic estimate of fly relationships based on molecules and morphology from 149 of 157 families, including 30 kb from 14 nuclear loci and complete mitochondrial genomes combined with 371 morphological characters. Multiple analyses show support for traditional groups (Brachycera, Cyclorrhapha, and Schizophora) and corroborate contentious findings, such as the anomalous Deuterophlebiidae as the sister group to all remaining Diptera. Our findings reveal that the closest relatives of the Drosophilidae are highly modified parasites (including the wingless Braulidae) of bees and other insects. Furthermore, we use micro-RNAs to resolve a node with implications for the evolution of embryonic development in Diptera. We demonstrate that flies experienced three episodes of rapid radiation—lower Diptera (220 Ma), lower Brachycera (180 Ma), and Schizophora (65 Ma)—and a number of life history transitions to hematophagy, phytophagy, and parasitism in the history of fly evolution over 260 million y

Assessment of function and clinical utility of alcohol and other drug web sites: An observational, qualitative study

Background The increasing popularity and use of the internet makes it an attractive option for providing health information and treatment, including alcohol/other drug use. There is limited research examining how people identify and access information about alcohol or other drug (AOD) use online, or how they assess the usefulness of the information presented. This study examined the strategies that individuals used to identify and navigate a range of AOD websites, along with the attitudes concerning presentation and content. Methods Members of the general community in Brisbane and Roma (Queensland, Australia) were invited to participate in a 30-minute search of the internet for sites related to AOD use, followed by a focus group discussion. Fifty one subjects participated in the study across nine focus groups. Results Participants spent a maximum of 6.5 minutes on any one website, and less if the user was under 25 years of age. Time spent was as little as 2 minutes if the website was not the first accessed. Participants recommended that AOD-related websites should have an engaging home or index page, which quickly and accurately portrayed the site’s objectives, and provided clear site navigation options. Website content should clearly match the title and description of the site that is used by internet search engines. Participants supported the development of a portal for AOD websites, suggesting that it would greatly facilitate access and navigation. Treatment programs delivered online were initially viewed with caution. This appeared to be due to limited understanding of what constituted online treatment, including its potential efficacy. Conclusions A range of recommendations arise from this study regarding the design and development of websites, particularly those related to AOD use. These include prudent use of text and information on any one webpage, the use of graphics and colours, and clear, uncluttered navigation options. Implications for future website development are discussed

A mixed-methods study using a nonclinical sample to measure feasibility of ostrich community : a web-based cognitive behavioral therapy program for individuals with debt and associated stress

Background: There are increasing concerns about the health and well-being of individuals facing financial troubles. For instance, in the United Kingdom, the relationship between debt and mental health difficulties is becoming more evident due to the economic downturn and welfare reform. Access to debt counseling services is limited and individuals may be reluctant to access services due to stigma. In addition, most of these services may not be appropriately resourced to address the psychological impact of debt. This study describes outcomes from an Internet-based cognitive behavioral therapy (ICBT) program, Ostrich Community (OC), which was developed to provide support to those struggling with debt and associated psychological distress. Objective: The aim of this feasibility study was to assess the suitability and acceptability of the OC program in a nonclinical sample and examine mental health and well-being outcomes from using the program. Methods: A total of 15 participants (who were not suffering from severe financial difficulty) were assisted in working through the 8-week ICBT program. Participants rated usability and satisfaction with the program, and after completion 7 participants took part in a semistructured interview to provide further feedback. Before the first session and after the final session all participants completed questionnaires to measure well-being and levels of depression, stress, and anxiety and pre- and postscores were compared. Results: Satisfaction was high and themes emerging from the interviews indicate that the program has the potential to promote effective financial behaviors and improve financial and global psychosocial well-being. When postcompletion scores were compared with those taken before the program, significant improvements were identified on psychometric measures of well-being, stress, and anxiety. Conclusions: The OC program is the first ICBT program that targets poor mental health associated with financial difficulty. This feasibility study indicates that OC may be an effective intervention for increasing financial resilience, supporting individuals to become financially independent, and promoting positive financial and global well-being. Further work with individuals suffering from debt and associated emotional difficulties will help to examine clinical effectiveness more closely

Should applicants to Nottingham University Medical School study a non-science A-level? A cohort study

<p>Abstract</p> <p>Background</p> <p>It has been suggested that studying non-science subjects at A-level should be compulsory for medical students. Our admissions criteria specify only Biology, Chemistry and one or more additional subjects. This study aimed to determine whether studying a non-science subject for A-level is an independent predictor of achievement on the undergraduate medical course.</p> <p>Methods</p> <p>The subjects of this retrospective cohort study were 164 students from one entry-year group (October 2000), who progressed normally on the 5-year undergraduate medical course at Nottingham. Pre-admission academic and socio-demographic data and undergraduate course marks were obtained. T-test and hierarchical multiple linear regression analyses were undertaken to identify independent predictors of five course outcomes at different stages throughout the course.</p> <p>Results</p> <p>There was no evidence that the choice of science or non-science as the third or fourth A-level subject had any influence on course performance. Demographic variables (age group, sex, and fee status) had some predictive value but ethnicity did not. Pre-clinical course performance was the strongest predictor in the clinical phases (pre-clinical Themes A&B (knowledge) predicted Clinical Knowledge, p < 0.001, and pre-clinical Themes C&D (skills) predicted Clinical Skills, p = < 0.01).</p> <p>Conclusion</p> <p>This study of one year group at Nottingham Medical School provided no evidence that the admissions policy on A-level requirements should specify the choice of third or fourth subject.</p

Biomineralisation by earthworms: an investigation into the stability and distribution of amorphous calcium carbonate

Background Many biominerals form from amorphous calcium carbonate (ACC), but this phase is highly unstable when synthesised in its pure form inorganically. Several species of earthworm secrete calcium carbonate granules which contain highly stable ACC. We analysed the milky fluid from which granules form and solid granules for amino acid (by liquid chromatography) and functional group (by Fourier transform infrared (FTIR) spectroscopy) compositions. Granule elemental composition was determined using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and electron microprobe analysis (EMPA). Mass of ACC present in solid granules was quantified using FTIR and compared to granule elemental and amino acid compositions. Bulk analysis of granules was of powdered bulk material. Spatially resolved analysis was of thin sections of granules using synchrotron-based μ-FTIR and EMPA electron microprobe analysis. Results The milky fluid from which granules form is amino acid-rich (≤ 136 ± 3 nmol mg−1 (n = 3; ± std dev) per individual amino acid); the CaCO3 phase present is ACC. Even four years after production, granules contain ACC. No correlation exists between mass of ACC present and granule elemental composition. Granule amino acid concentrations correlate well with ACC content (r ≥ 0.7, p ≤ 0.05) consistent with a role for amino acids (or the proteins they make up) in ACC stabilisation. Intra-granule variation in ACC (RSD = 16%) and amino acid concentration (RSD = 22–35%) was high for granules produced by the same earthworm. Maps of ACC distribution produced using synchrotron-based μ-FTIR mapping of granule thin sections and the relative intensity of the ν2: ν4 peak ratio, cluster analysis and component regression using ACC and calcite standards showed similar spatial distributions of likely ACC-rich and calcite-rich areas. We could not identify organic peaks in the μ-FTIR spectra and thus could not determine whether ACC-rich domains also had relatively high amino acid concentrations. No correlation exists between ACC distribution and elemental concentrations determined by EMPA. Conclusions ACC present in earthworm CaCO3 granules is highly stable. Our results suggest a role for amino acids (or proteins) in this stability. We see no evidence for stabilisation of ACC by incorporation of inorganic components

Study protocol: a randomised controlled trial investigating the effect of a healthy lifestyle intervention for people with severe mental disorders

<p>Abstract</p> <p>Background</p> <p>The largest single cause of death among people with severe mental disorders is cardiovascular disease (CVD). The majority of people with schizophrenia and bipolar disorder smoke and many are also overweight, considerably increasing their risk of CVD. Treatment for smoking and other health risk behaviours is often not prioritized among people with severe mental disorders. This protocol describes a study in which we will assess the effectiveness of a healthy lifestyle intervention on smoking and CVD risk and associated health behaviours among people with severe mental disorders.</p> <p>Methods/Design</p> <p>250 smokers with a severe mental disorder will be recruited. After completion of a baseline assessment and an initial face-to-face intervention session, participants will be randomly assigned to either a multi-component intervention for smoking cessation and CVD risk reduction or a telephone-based minimal intervention focusing on smoking cessation. Randomisation will be stratified by site (Newcastle, Sydney, Melbourne, Australia), Body Mass Index (BMI) category (normal, overweight, obese) and type of antipsychotic medication (typical, atypical). Participants will receive 8 weekly, 3 fortnightly and 6 monthly sessions delivered face to face (typically 1 hour) or by telephone (typically 10 minutes). Assessments will be conducted by research staff blind to treatment allocation at baseline, 15 weeks, and 12-, 18-, 24-, 30- and 36-months.</p> <p>Discussion</p> <p>This study will provide comprehensive data on the effect of a healthy lifestyle intervention on smoking and CVD risk among people with severe mental disorders. If shown to be effective, this intervention can be disseminated to treating clinicians using the treatment manuals.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry (ANZCTR) identifier: <a href="http://www.anzctr.org.au/ACTRN12609001039279.aspx">ACTRN12609001039279</a></p

Evolution of H3N2 Influenza Virus in a Guinea Pig Model

Studies of influenza virus evolution under controlled experimental conditions can provide a better understanding of the consequences of evolutionary processes with and without immunological pressure. Characterization of evolved strains assists in the development of predictive algorithms for both the selection of subtypes represented in the seasonal influenza vaccine and the design of novel immune refocused vaccines. To obtain data on the evolution of influenza in a controlled setting, naïve and immunized Guinea pigs were infected with influenza A/Wyoming/2003 (H3N2). Virus progeny from nasal wash samples were assessed for variation in the dominant and other epitopes by sequencing the hemagglutinin (HA) gene to quantify evolutionary changes. Viral RNA from the nasal washes from infection of naïve and immune animals contained 6% and 24.5% HA variant sequences, respectively. Analysis of mutations relative to antigenic epitopes indicated that adaptive immunity played a key role in virus evolution. HA mutations in immunized animals were associated with loss of glycosylation and changes in charge and hydrophobicity in and near residues within known epitopes. Four regions of HA-1 (75–85, 125–135, 165–170, 225–230) contained residues of highest variability. These sites are adjacent to or within known epitopes and appear to play an important role in antigenic variation. Recognition of the role of these sites during evolution will lead to a better understanding of the nature of evolution which help in the prediction of future strains for selection of seasonal vaccines and the design of novel vaccines intended to stimulated broadened cross-reactive protection to conserved sites outside of dominant epitopes

Excitonic recombination dynamics in shallow quantum wells

We report a comprehensive study of carrier-recombination dynamics in shallow AlxGa1-xAs/GaAs quantum wells. At low crystal temperature (2 K), the excitonic radiative recombination time is shown to be strongly enhanced in shallow quantum wells with x>0.01, consistently with a model that takes into account the thermal equilibrium between the three-dimensional exciton gas of the barrier and the two-dimensional exciton gas, which are closer in energy as x decreases. Furthermore, we demonstrate the existence of a thermally activated escape mechanism due to the low effective barrier height in these structures. The nonradiative recombination is shown to dominate the carrier dynamics for temperatures as low as 10 K for x≈0.01. Our experimental observations are analyzed using three different variational exciton calculations. In particular, we study the crossover from the two-dimensional to the three-dimensional behavior of the exciton, which occurs for x as low as 0.01 and affects mainly the oscillator strength, whereas the transition energies in shallow quantum wells can be calculated, to a large extent, using the same approximations as for conventional quantum wells. The peculiar behavior of the oscillator strength at the crossover to the weak confinement regime is obtained by expansion in a large basis