Predicting Distribution of Aedes Aegypti and Culex Pipiens Complex, Potential Vectors of Rift Valley Fever Virus in Relation to Disease Epidemics in East Africa.

The East African region has experienced several Rift Valley fever (RVF) outbreaks since the 1930s. The objective of this study was to identify distributions of potential disease vectors in relation to disease epidemics. Understanding disease vector potential distributions is a major concern for disease transmission dynamics. DIVERSE ECOLOGICAL NICHE MODELLING TECHNIQUES HAVE BEEN DEVELOPED FOR THIS PURPOSE: we present a maximum entropy (Maxent) approach for estimating distributions of potential RVF vectors in un-sampled areas in East Africa. We modelled the distribution of two species of mosquitoes (Aedes aegypti and Culex pipiens complex) responsible for potential maintenance and amplification of the virus, respectively. Predicted distributions of environmentally suitable areas in East Africa were based on the presence-only occurrence data derived from our entomological study in Ngorongoro District in northern Tanzania. Our model predicted potential suitable areas with high success rates of 90.9% for A. aegypti and 91.6% for C. pipiens complex. Model performance was statistically significantly better than random for both species. Most suitable sites for the two vectors were predicted in central and northwestern Tanzania with previous disease epidemics. Other important risk areas include western Lake Victoria, northern parts of Lake Malawi, and the Rift Valley region of Kenya. Findings from this study show distributions of vectors had biological and epidemiological significance in relation to disease outbreak hotspots, and hence provide guidance for the selection of sampling areas for RVF vectors during inter-epidemic periods

Arthroscopic evaluation of the ACL double bundle structure

In order to describe the arthroscopic presence of the double bundle structure and to evaluate the value of different portals in knee arthroscopy, we assessed the AM and PL bundle anatomy. We prospectively examined the knees of 60 patients undergoing arthroscopic surgery for pathology unrelated to the ACL. Arthroscopy was performed in a two portal technique using an anterolateral (ALP) and an anteromedial (AMP) portal. With the arthroscope in the ALP, we could distinguish an AM and PL bundle in 28%. Switching the arthroscope to the AMP, differentiation of the bundles was possible in 67%. In all remaining cases visualization of the PL bundle was possible after retraction of the AM bundle. Use of AMP increased visualization of the PL bundle. It seems reasonable to perform arthroscopy for ACL reconstruction with the arthroscope in the AMP and to establish an additional medial working portal to increase the visualization of the femoral ACL insertion sites for optimal femoral tunnel placement

Arabidopsis thaliana MIRO1 and MIRO2 GTPases Are Unequally Redundant in Pollen Tube Growth and Fusion of Polar Nuclei during Female Gametogenesis

MIRO GTPases have evolved to regulate mitochondrial trafficking and morphology in eukaryotic organisms. A previous study showed that T-DNA insertion in the Arabidopsis MIRO1 gene is lethal during embryogenesis and affects pollen tube growth and mitochondrial morphology in pollen, whereas T-DNA insertion in MIRO2 does not affect plant development visibly. Phylogenetic analysis of MIRO from plants revealed that MIRO 1 and 2 orthologs in dicots cluster in two separate groups due to a gene/genome duplication event, suggesting that functional redundancy may exists between the two MIRO genes. To investigate this possibility, we generated miro1(+/−)/miro2-2(−/−) plants. Compared to miro1(+/−) plants, the miro1(+/−)/miro2-2(−/−) plants showed increased segregation distortion. miro1(+/−)/miro2-2(−/−) siliques contained less aborted seeds, but more than 3 times the number of undeveloped ovules. In addition, reciprocal crosses showed that co-transmission through the male gametes was nearly absent, whereas co-transmission through the female gametes was severely reduced in miro1(+/−)/miro2-2(−/−) plants. Further investigations revealed that loss of MIRO2 (miro2(−/−)) function in the miro1(+/−) background enhanced pollen tube growth defects. In developing miro1(+/−)/miro2(−/−) embryo sacs, fusion of polar nuclei was further delayed or impaired compared to miro1 plants. This phenotype has not been reported previously for miro1 plants and coincides with studies showing that defects in some mitochondria-targeted genes results in the same phenotype. Our observations show that loss of function in MIRO2 in a miro1(+/−) background enhances the miro1(+/−) phenotype significantly, even though miro2(−/−) plants alone does not display any phenotypes. Based on these findings, we conclude that MIRO1 and MIRO2 are unequally redundant and that a proportion of the miro1(+/−)/miro2(−/−) plants haploid gametes displays the complete null phenotype of MIRO GTPase function at key developmental stages

Evaluating the successful implementation of evidence into practice using the PARiHS framework : theoretical and practical challenges

Background The PARiHS framework (Promoting Action on Research Implementation in Health Services) has proved to be a useful practical and conceptual heuristic for many researchers and practitioners in framing their research or knowledge translation endeavours. However, as a conceptual framework it still remains untested and therefore its contribution to the overall development and testing of theory in the field of implementation science is largely unquantified. Discussion This being the case, the paper provides an integrated summary of our conceptual and theoretical thinking so far and introduces a typology (derived from social policy analysis) used to distinguish between the terms conceptual framework, theory and model – important definitional and conceptual issues in trying to refine theoretical and methodological approaches to knowledge translation. Secondly, the paper describes the next phase of our work, in particular concentrating on the conceptual thinking and mapping that has led to the generation of the hypothesis that the PARiHS framework is best utilised as a two-stage process: as a preliminary (diagnostic and evaluative) measure of the elements and sub-elements of evidence (E) and context (C), and then using the aggregated data from these measures to determine the most appropriate facilitation method. The exact nature of the intervention is thus determined by the specific actors in the specific context at a specific time and place. In the process of refining this next phase of our work, we have had to consider the wider issues around the use of theories to inform and shape our research activity; the ongoing challenges of developing robust and sensitive measures; facilitation as an intervention for getting research into practice; and finally to note how the current debates around evidence into practice are adopting wider notions that fit innovations more generally. Summary The paper concludes by suggesting that the future direction of the work on the PARiHS framework is to develop a two-stage diagnostic and evaluative approach, where the intervention is shaped and moulded by the information gathered about the specific situation and from participating stakeholders. In order to expedite the generation of new evidence and testing of emerging theories, we suggest the formation of an international research implementation science collaborative that can systematically collect and analyse experiences of using and testing the PARiHS framework and similar conceptual and theoretical approaches. We also recommend further refinement of the definitions around conceptual framework, theory, and model, suggesting a wider discussion that embraces multiple epistemological and ontological perspectives

Safety and Efficacy of Intermittent High-Dose Liposomal Amphotericin B Antifungal Prophylaxis in Haemato-Oncology: An Eight-Year Single-Centre Experience and Review of the Literature.

Triazoles remain first-line agents for antifungal prophylaxis in high-risk haemato-oncology patients, but their use is increasingly contraindicated due to drug-drug interactions and additive toxicities with novel treatments. In this retrospective, single-centre, observational study, we present our eight-year experience of antifungal prophylaxis using intermittent high-dose liposomal Amphotericin B (L-AmB). All adults identified through our Antifungal Stewardship Programme as receiving L-AmB prophylaxis at 7.5 mg/kg once-weekly between February 2012 and January 2020 were included. Adverse reactions, including infusion reactions, electrolyte loss, and nephrotoxicity, were recorded. 'Breakthrough' invasive fungal infection (IFI) occurring within four weeks of L-AmB was classified using European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Moreover, 114 courses of intermittent high-dose L-AmB prophylaxis administered to 92 unique patients were analysed. Hypokalaemia was the most common grade 3-4 adverse event, with 26 (23%) courses. Grade 3 nephrotoxicity occurred in 8 (7%) and reversed in all six patients surviving to 90 days. There were two (1.8%) episodes of breakthrough IFI, one 'probable' and one 'possible'. In this study, the largest evaluation of intermittent high-dose L-AmB prophylaxis conducted to date, toxicity was manageable and reversible and breakthrough IFI was rare. L-AmB prophylaxis represents a viable alternative for patients with a contraindication to triazoles

Can adverse maternal and perinatal outcomes be predicted when blood pressure becomes elevated? Secondary analyses from the CHIPS (Control of Hypertension In Pregnancy Study) randomized controlled trial.

INTRODUCTION: For women with chronic or gestational hypertension in CHIPS (Control of Hypertension In Pregnancy Study, NCT01192412), we aimed to examine whether clinical predictors collected at randomization could predict adverse outcomes. MATERIAL AND METHODS: This was a planned, secondary analysis of data from the 987 women in the CHIPS Trial. Logistic regression was used to examine the impact of 19 candidate predictors on the probability of adverse perinatal (pregnancy loss or high level neonatal care for >48 h, or birthweight <10th percentile) or maternal outcomes (severe hypertension, preeclampsia, or delivery at <34 or <37 weeks). A model containing all candidate predictors was used to start the stepwise regression process based on goodness of fit as measured by the Akaike information criterion. For face validity, these variables were forced into the model: treatment group ("less tight" or "tight" control), antihypertensive type at randomization, and blood pressure within 1 week before randomization. Continuous variables were represented continuously or dichotomized based on the smaller p-value in univariate analyses. An area-under-the-receiver-operating-curve (AUC ROC) of ≥0.70 was taken to reflect a potentially useful model. RESULTS: Point estimates for AUC ROC were <0.70 for all but severe hypertension (0.70, 95% CI 0.67-0.74) and delivery at <34 weeks (0.71, 95% CI 0.66-0.75). Therefore, no model warranted further assessment of performance. CONCLUSIONS: CHIPS data suggest that when women with chronic hypertension develop an elevated blood pressure in pregnancy, or formerly normotensive women develop new gestational hypertension, maternal and current pregnancy clinical characteristics cannot predict adverse outcomes in the index pregnancy

TALPID3/KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and Human

TALPID3/KIAA0586 is an evolutionary conserved protein, which plays an essential role in protein trafficking. Its role during gastrointestinal (GI) and enteric nervous system (ENS) development has not been studied previously. Here, we analyzed chicken, mouse and human embryonic GI tissues with TALPID3 mutations. The GI tract of TALPID3 chicken embryos was shortened and malformed. Histologically, the gut smooth muscle was mispatterned and enteric neural crest cells were scattered throughout the gut wall. Analysis of the Hedgehog pathway and gut extracellular matrix provided causative reasons for these defects. Interestingly, chicken intra-species grafting experiments and a conditional knockout mouse model showed that ENS formation did not require TALPID3, but was dependent on correct environmental cues. Surprisingly, the lack of TALPID3 in enteric neural crest cells (ENCC) affected smooth muscle and epithelial development in a non-cell-autonomous manner. Analysis of human gut fetal tissues with a KIAA0586 mutation showed strikingly similar findings compared to the animal models demonstrating conservation of TALPID3 and its necessary role in human GI tract development and patterning

Go-stimuli proportion influences response strategy in a sustained attention to response task

The sustained attention to response task (SART) usefulness as a measure of sustained attention has been questioned. The SART may instead be a better measure of other psychological processes and could prove useful in understanding some real-world behaviours. Thirty participants completed four Go/No-Go response tasks much like the SART, with Go-stimuli proportions of .50, .65, .80 and .95. As Go-stimuli proportion increased, reaction times decreased while both commission errors and self-reported task-related thoughts increased. Performance measures were associated with task-related thoughts but not taskunrelated thoughts. Instead of faster reaction times and increased commission errors being due to absentmindedness or perceptual decoupling from the task, the results suggested participants made use of two competing response strategies, in line with a response strategy or response inhibition perspective of SART performance. Interestingly, performance measures changed in a nonlinear manner, despite the linear Go proportion increase. A threshold may exist where the prepotent motor response becomes more pronounced, leading to the disproportionate increase in response speed and commission errors. This research has implications for researchers looking to employ the SAR

The importance of anaemia in diagnosing colorectal cancer: a case–control study using electronic primary care records

Although anaemia is recognised as a feature of colorectal cancer, the precise risk is unknown. We performed a case–control study using electronic primary care records from the Health Improvement Network database, UK. A total of 6442 patients had a diagnosis of colorectal cancer, and were matched to 45 066 controls on age, sex, and practice. We calculated likelihood ratios and positive predictive values for colorectal cancer in both sexes across 1 g dl−1 haemoglobin and 10-year age bands, and examined the features of iron deficiency.In men, 178 (5.2%) of 3421 cases and 47 (0.2%) of 23 928 controls had a haemoglobin <9.0 g dl−1, giving a likelihood ratio (95% confidence interval) of 27 (19, 36). In women, the corresponding figures were 227 (7.5%) of 3021 cases and 58 (0.3%) of 21 138 controls, a likelihood ratio of 41 (30, 61). Positive predictive values increased with age and for each 1 g dl−1 reduction in haemoglobin. The risk of cancer for current referral guidance was quantified. For men over 60 years with a haemoglobin <11 g dl−1 and features of iron deficiency, the positive predictive value was 13.3% (9.7, 18) and for women with a haemoglobin <10 g dl−1 and iron deficiency, the positive predictive value was 7.7% (5.7, 11). Current guidance for urgent investigation of anaemia misses some patients with a moderate risk of cancer, particularly men