Clarifying misconceptions of extinction risk assessment with the IUCN Red List

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.The identification of species at risk of extinction is a central goal of conservation. As the use of data compiled for IUCN Red List assessments expands, a number of misconceptions regarding the purpose, application and use of the IUCN Red List categories and criteria have arisen. We outline five such classes of misconception; the most consequential drive proposals for adapted versions of the criteria, rendering assessments among species incomparable. A key challenge for the future will be to recognize the point where understanding has developed so markedly that it is time for the next generation of the Red List criteria. We do not believe we are there yet but, recognizing the need for scrutiny and continued development of Red Listing, conclude by suggesting areas where additional research could be valuable in improving the understanding of extinction risk among species

Containing the burden of infectious diseases is everyone’s responsibility.:A call for an integrated strategy for developing and promoting hygiene behaviour change in home and everyday life

Across the world, health agencies recognize the profound impact of infectious disease on health and prosperity. Equally, they recognize that prevention is central to fighting infection, and that hygiene in home and everyday life (HEDL) is a key part of this. A current driver is the part that hygienei plays in tackling antibiotic resistance, but it also reflects growing numbers of people at greater risk of infection being cared for in the community. Sustaining the quality of state-funded healthcare requires that the public take greater responsibility for their own health, including protecting themselves and their families against infection. Hygiene must be must be everyone’s responsibility. However, if we are to be successful in promoting hygiene as part of public health, there are barriers which need to be overcome. A key issue is the need to balance evidence of the health benefits of hygiene against possible risks, such as environmental impacts and toxicity issues. Another issue is the role of microbes in human health and whether we have become “too clean”. Lack of a unified voice advocating for hygiene means these issues have tended to take precedence. Another barrier to change is public confusion about the need for hygiene and the difference between hygiene and cleanliness. To address this, we must work together to provide the public with a clear, consistent restatement of the importance of hygiene, and to change public perceptions about hygiene and good hygiene practice. This paper is unique because it examines these issues in an integrated manner and focuses on making achievable, constructive recommendations for developing an effective and sustainable approach. The paper lays out a risk management strategy for hygiene in home and everyday life which gives hygiene appropriate priority within the context of environmental and other health concerns. This “targeted hygiene” approach needs to be placed at the heart of a multimodal prevention strategy, alongside vaccination and other interventions. Based on the findings of this paper, we issue a call to action to national and international policy makers, health agencies and health professionals to recognize the need for an integrated, family-centredii approach to hygiene, and provide effective leadership to achieve this. This paper shows that many of the components of a behaviour change strategy are already in place, but need to be integrated rather than developed independently. We also issue a call to scientists, health professionals, environmental and regulatory agencies, immunologists, microbiomists, the private sector (hygiene appliance and product manufacturers) and the media to work together, through innovative research and communication policies. A collaborative effort is vital if we are to overcome barriers to change and action integrated behaviour change programmes that really work. The report represents the consensus views of an international, interdisciplinary group of experts in the field of infection prevention and hygiene. We recognise that this paper leaves many questions unanswered and would welcome further dialogue with stakeholders on how to develop policy. The aim of this paper is to provide a sound basis for such dialogue. At the 2016 launch of the European Human Biomonitoring Initiative, the EU commissioner for food safety said the followingiii which encapsulates the aim of this report. “We must collectively recognise that risk and uncertainty are part and parcel of every decision we take. We need to engage people in a serious and rational debate. But in this world of information overload – from old media and new – information, misinformation, opinions, prejudices, truths, half-truths and un-truths all compete for public attention. We need better communication of science so that people can be better informed about risk assessment and management decisions

A systematic review of strategies to recruit and retain primary care doctors

Background There is a workforce crisis in primary care. Previous research has looked at the reasons underlying recruitment and retention problems, but little research has looked at what works to improve recruitment and retention. The aim of this systematic review is to evaluate interventions and strategies used to recruit and retain primary care doctors internationally. Methods A systematic review was undertaken. MEDLINE, EMBASE, CENTRAL and grey literature were searched from inception to January 2015.Articles assessing interventions aimed at recruiting or retaining doctors in high income countries, applicable to primary care doctors were included. No restrictions on language or year of publication. The first author screened all titles and abstracts and a second author screened 20%. Data extraction was carried out by one author and checked by a second. Meta-analysis was not possible due to heterogeneity. Results 51 studies assessing 42 interventions were retrieved. Interventions were categorised into thirteen groups: financial incentives (n=11), recruiting rural students (n=6), international recruitment (n=4), rural or primary care focused undergraduate placements (n=3), rural or underserved postgraduate training (n=3), well-being or peer support initiatives (n=3), marketing (n=2), mixed interventions (n=5), support for professional development or research (n=5), retainer schemes (n=4), re-entry schemes (n=1), specialised recruiters or case managers (n=2) and delayed partnerships (n=2). Studies were of low methodological quality with no RCTs and only 15 studies with a comparison group. Weak evidence supported the use of postgraduate placements in underserved areas, undergraduate rural placements and recruiting students to medical school from rural areas. There was mixed evidence about financial incentives. A marketing campaign was associated with lower recruitment. Conclusions This is the first systematic review of interventions to improve recruitment and retention of primary care doctors. Although the evidence base for recruiting and care doctors is weak and more high quality research is needed, this review found evidence to support undergraduate and postgraduate placements in underserved areas, and selective recruitment of medical students. Other initiatives covered may have potential to improve recruitment and retention of primary care practitioners, but their effectiveness has not been established

Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth

AbstractCell commitment to tumourigenesis and the onset of uncontrolled growth are critical determinants in cancer development but the early events directing tumour initiating cell (TIC) fate remain unclear. We reveal a single-cell transcriptome profile of brain TICs transitioning into tumour growth using the brain tumour (brat) neural stem cell-based Drosophila model. Prominent changes in metabolic and proteostasis-associated processes including ribogenesis are identified. Increased ribogenesis is a known cell adaptation in established tumours. Here we propose that brain TICs boost ribogenesis prior to tumour growth. In brat-deficient TICs, we show that this dramatic change is mediated by upregulated HEAT-Repeat Containing 1 (HEATR1) to promote ribosomal RNA generation, TIC enlargement and onset of overgrowth. High HEATR1 expression correlates with poor glioma patient survival and patient-derived glioblastoma stem cells rely on HEATR1 for enhanced ribogenesis and tumourigenic potential. Finally, we show that HEATR1 binds the master growth regulator MYC, promotes its nucleolar localisation and appears required for MYC-driven ribogenesis, suggesting a mechanism co-opted in ribogenesis reprogramming during early brain TIC development.</jats:p

Interfacing low-energy SAW nebulization with liquid chromatography-mass spectrometry for the analysis of biological samples

Soft ionization methods for the introduction of labile biomolecules into a mass spectrometer are of fundamental importance to biomolecular analysis. Previously, electrospray ionization (ESI) and matrix assisted laser desorption-ionization (MALDI) have been the main ionization methods used. Surface acoustic wave nebulization (SAWN) is a new technique that has been demonstrated to deposit less energy into ions upon ion formation and transfer for detection than other methods for sample introduction into a mass spectrometer (MS). Here we report the optimization and use of SAWN as a nebulization technique for the introduction of samples from a low flow of liquid, and the interfacing of SAWN with liquid chromatographic separation (LC) for the analysis of a protein digest. This demonstrates that SAWN can be a viable, low-energy alternative to ESI for the LC-MS analysis of proteomic samples

Low expression of aldehyde deyhdrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Aldehyde deyhdrogenase 1 (ALDH1) has been characterised as a cancer stem cell marker in different types of tumours. Additionally, it plays a pivotal role in gene regulation and endows tumour cells with augmented chemoresistance. Recently, ALDH1A1 has been described as a prognostic marker in a pancreatic cancer tissue microarray. The aim of this study was to reevaluate the expression of ALDH1A1 as a prognostic marker on whole-mount tissue sections.</p> <p>Methods</p> <p>Real-time-quantitative-PCR (qRT-PCR) and Western blotting were used to evaluate the expression profile of ALDH1A1 in seven pancreatic cancer cell lines and one non-malignant pancreatic cell line. Immunostaining against ALDH1A1 and Ki-67 was performed on paraffin-embedded samples from 97 patients with pancreatic cancer. The immunohistochemical results were correlated to histopathological and clinical data.</p> <p>Results</p> <p>qRT-PCR and Western blotting revealed a different expression pattern of ALDH1A1 in different malignant and non-malignant pancreatic cell lines. Immunohistochemical analysis demonstrated that ALDH1A1 was confined to the cellular cytoplasm and occurred in 72 cases (74%), whereas it was negative in 25 cases (26%). High expression of ALDH1A1 was significantly correlated to an increased proliferation rate (Spearman correlation, p = 0.01). Univariate and multivariate analyses showed that decreased expression of ALDH1A1 is an independent adverse prognostic factor for overall survival.</p> <p>Conclusions</p> <p>Immunonhistochemical analysis on whole-mount tissue slides revealed that ALDH1A1 is more abundantly expressed in pancreatic cancer than initially reported by a tissue microarray analysis. Moreover, high expression of ALDH1A1 correlated significantly with the proliferation of tumour cells. Intriguingly, this study is the first which identifies low expression of ALDH1A1 as an independent adverse prognostic marker for overall survival in pancreatic cancer.</p

A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis

<p>Abstract</p> <p>Background</p> <p>Long-term immunosuppression is often required in myasthenia gravis (MG). There are no published trials using methotrexate (MTX) in MG. The steroid-sparing efficacy of azathioprine (AZA) has been demonstrated after 18-months of starting therapy. However, AZA is considered expensive in Africa. We evaluated the steroid-sparing efficacy of MTX (17.5 mg weekly) compared with AZA (2.5 mg/kg daily) in subjects recently diagnosed with generalized MG by assessing their average monthly prednisone requirements.</p> <p>Methods</p> <p>The primary outcome was the average daily prednisone requirement by month between the two groups. Prednisone was given at the lowest dose to manage MG symptoms and adjusted as required according to protocol. Single-blinded assessments were performed 3-monthly for 2-years to determine the quantitative MG score and the MG activities of daily living score in order to determine those with minimal manifestations of MG.</p> <p>Results</p> <p>Thirty-one subjects (AZA n = 15; MTX n = 16) satisfied the inclusion criteria but only 24 were randomized. Baseline characteristics were similar. There was no difference between the AZA- and MTX-groups in respect of prednisone dosing (apart from months 10 and 12), in quantitative MG Score improvement, proportions in sustained remission, frequencies of MG relapses, or adverse reactions and/or withdrawals. The MTX-group received lower prednisone doses between month 10 (p = 0.047) and month 12 (p = 0.039). At month 12 the prednisone dose per kilogram bodyweight in the MTX-group (0.15 mg/kg) was half that of the AZA-group (0.31 mg/kg)(p = 0.019).</p> <p>Conclusions</p> <p>This study provides evidence that in patients with generalized MG methotrexate is an effective steroid-sparing agent 10 months after treatment initiation. Our data suggests that in generalized MG methotrexate has similar efficacy and tolerability to azathioprine and may be the drug of choice in financially constrained health systems.</p> <p>Trial registration</p> <p>SANCTR:DOH-27-0411-2436</p