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Introduction Neutropenia is a life-threatening and dose-limiting toxicity of palliative lung cancer chemotherapy. Whilst some neutropenias are inevitable, evidence suggests that patients with a previous neutropenic event are 50% more likely to have a further neutropenic event. The aim of this research is to evaluate the variables associated with the risk of secondary neutropenic events and the role of chemotherapy dose reductions. Methods A retrospective analysis was carried out on 361 biochemical neutropenic events in palliative lung cancer patients across 5 sites in South Yorkshire and Bassetlaw. Predictors for a secondary neutropenic event were investigated in univariate and multivariate logistic regression analysis. The predictive model was validated through discrimination statistics, described by Receiver Operating Characteristic Area Under Curve (ROC-AUC). Results The incident rate for secondary neutropenic events was 32.7%. Patients with a successful intervention received a higher mean Relative Dose Intensity (RDI) of 75.65% compared to 65.05%, across the 2 chemotherapy cycles. The univariate analysis found that the biochemical type of neutropenia (depth and length of suppression) (p=0.003), dose reduction of drug 1 (p=0.042), average dose reduction (p=0.019), and cumulative dose reduction (p=0.018) were significant at reducing the risk of secondary neutropenia. Granulocyte-Colony Stimulating Factor did not offer a protective effect. The final logistic regression model evaluated 357 events and included all variables due to significant interrelationship. The model had a ROC-AUC of 0.76 (0.71-0.81) (p= 0.0021), explaining 27% of the variance. Conclusion Appropriate dose reductions play a vital role in preventing secondary neutropenic events and delivering optimal RDIs. The results of this study can aid in identifying high-risk patients.

Yes / Experimental values of permeability coefficients, as log Kp, of chemical compounds across human skin were collected by carefully screening the literature, and adjusted to 37 °C for the effect of temperature. The values of log Kp for partially ionized acids and bases were separated into those for their neutral and ionic species, forming a total data set of 247 compounds and species (including 35 ionic species). The obtained log Kp values have been regressed against Abraham solute descriptors to yield a correlation equation with R2 = 0.866 and SD = 0.432 log units. The equation can provide valid predictions for log Kp of neutral molecules, ions and ionic species, with predictive R2 = 0.858 and predictive SD = 0.445 log units calculated by the leave-one-out statistics. The predicted log Kp values for Na+ and Et4N+ are in good agreement with the observed values. We calculated the values of log Kp of ketoprofen as a function of the pH of the donor solution, and found that log Kp markedly varies only when ketoprofen is largely ionized. This explains why models that neglect ionization of permeants still yield reasonable statistical results. The effect of skin thickness on log Kp was investigated by inclusion of two indicator variables, one for intermediate thickness skin and one for full thickness skin, into the above equation. The newly obtained equations were found to be statistically very close to the above equation. Therefore, the thickness of human skin used makes little difference to the experimental values of log Kp.

Yes / For overbank flows in meandering channels, the flow direction along a meander varies and is affected by floodplain vegetation. This study proposes a model for predicting the depth-averaged two-dimensional flow direction (depth-averaged flow angle) along a meander in smooth and vegetated meandering compound channels. Laboratory experiments were performed in smooth and vegetated channels. Measurements show that the height of the secondary current cell in the main channel is increased by dense floodplain vegetation comparing with that in a non-vegetated channel. A method of determining the height of the cell is proposed. At the middle section between the apex and exit sections, where the secondary current cell is absent, the depth-averaged flow angle is independent of the height of the cell. Beyond the middle section, a new secondary current cell is formed, and the flow angle is highly dependent on the height of the cell. The proposed model is thoroughly verified using the flume experimental and field observed data. Good agreement is obtained between predictions and measurements, indicating that the proposed model is capable of accurately predicting the depth-averaged flow angle along a meander in smooth and vegetated meandering compound channels. / National Key Research and Development Program of China (No. 2016YFC0402302), and the National Natural Science Foundation of China (Nos. 51709022, 51609160 and 51539007)

Yes / Hospital-acquired Acute Kidney Injury (H-AKI) is a common cause of avoidable morbidity and mortality. To determine if the patients’ vital signs data as defined by a National Early Warning Score (NEWS), can predict H-AKI following emergency admission to hospital. Methods: Analyses of emergency admissions to York hospital over 24-months with NEWS data. We report the area under the curve (AUC) for logistic regression models that used the index NEWS (model A0), plus age and sex (A1), plus subcomponents of NEWS (A2) and two-way interactions (A3). Likewise for maximum NEWS (models B0,B1,B2,B3). Results: 4.05% (1361/33608) of emergency admissions had H-AKI. Models using the index NEWS had the lower AUCs (0.59 to 0.68) than models using the maximum NEWS AUCs (0.75 to 0.77). The maximum NEWS model (B3) was more sensitivity than the index NEWS model (A0) (67.60% vs 19.84%) but identified twice as many cases as being at risk of H-AKI (9581 vs 4099) at a NEWS of 5. Conclusions: The index NEWS is a poor predictor of H-AKI. The maximum NEWS is a better predictor but seems unfeasible because it is only knowable in retrospect and is associated with a substantial increase in workload albeit with improved sensitivity. / The Health Foundation

The main purpose of this study was to produce and test the reliability of predictive models of cetacean distributions off the west coast of Scotland. Passive acoustic and visual surveys were carried out from platforms of opportunity between 2003 and 2005. Acoustic identifications were made primarily of harbour porpoises (Phocoena phocoena), delphinids, and sperm whales (Physeter macrocephalus). Generalised Additive Models (GAMs) were used to relate species’ distributions to a range of environmental variables over a range of temporal and spatial scales. Predictive models of delphinid distributions showed both inter-annual and inter-month variations. Combining all data for all months and years resulted in a model that combined the environmental influences from each monthly and yearly model. Overall, delphinids were found to associate with the deep (> 400m) warm water (10.5°C-12.5°C), and in areas of deep thermocline. Relationships between sperm whales and environmental variables were consistent over changes in grain size (9 km or 18 km), but not between areas. Although sperm whales were distributed in deep water characterised by weak thermoclines and strong haloclines in the most northerly area (Faroe-Shetland Channel), they were found in deep productive areas with cold surface temperature in the more southerly waters (Rockall Trough). Within the southern Inner Hebrides, high use areas for harbour porpoises were consistently predicted over time (in years) and with differing survey techniques (acoustic versus visual), but not over space (southern Inner Hebrides versus whole of the Inner Hebrides). Harbour porpoises were mainly distributed in areas with low tidal currents and with higher detection rates during spring tides. The use of prey as a predictor variable within models of delphinid distribution shows some promise: there were correlations between delphinid and herring (Clupea harengus) in shelf-waters in 2005 but not in 2004. These models can be used in mitigating acoustic threats to cetaceans in predicted high use areas off the west coast of Scotland.

A leishmaniose visceral americana (LVA) é uma doença em expansão no Brasil, para a qual se dispõem de poucas, e aparentemente ineficientes, estratégias de controle. Um dos grandes problemas para a contenção da leishmaniose visceral americana é a falta de um método acurado de identificação dos cães infectados, considerados os principais reservatórios da doença no meio urbano. Neste sentido, a caracterização de marcadores clínico-laboratoriais da infecção neste reservatório e a avaliação mais adequada do desempenho de testes para diagnóstico da infecção podem contribuir para aumentar a efetividade das estratégias de controle da LVA. Com isso, o presente estudo tem dois objetivos principais: (1) desenvolver e validar um modelo de predição para o parasitismo por Leishmania chagasi em cães, baseado em resultados de testes sorológicos e sinais clínicos e (2) avaliar a sensibilidade e especificidade de critérios clínicos, sorológicos e parasitológicos para detecção de infecção canina por L. chagasi mediante análise de classe latente. O primeiro objetivo foi desenvolvido a partir de estudo em que foram obtidos dados de exames clínico, sorológico e parasitológico de todos os cães, suspeitos ou não de LVA, atendidos no Hospital Veterinário Universitário da Universidade Federal do Piauí (HVU-UFPI), em Teresina, nos anos de 2003 e 2004, totalizando 1412 animais. Modelos de regressão logística foram construídos com os animais atendidos em 2003 com a finalidade de desenvolver um modelo preditivo para o parasitismo com base nos sinais clínicos e resultados de sorologia por Imunofluorescência Indireta (IFI). Este modelo foi validado nos cães atendidos no hospital em 2004. Para a avaliação da área abaixo da curva ROC (auROC), sensibilidade, especificidade, valores preditivos positivo (VPP), valores preditivos negativo (VPN) e acurácia global, foram criados três modelos: um somente baseado nas variáveis clínicas, outro considerando somente o resultado sorológico e um último considerando conjuntamente a clínica e a sorologia. Dentre os três, o último modelo apresentou o melhor desempenho (auROC=90,1%, sensibilidade=82,4%, especificidade=81,6%, VPP=73,4%, VPN=88,2% e acurácia global=81,9%). Conclui-se que o uso de modelos preditivos baseados em critérios clínicos e sorológicos para o diagnóstico da leishmaniose visceral canina pode ser de utilidade no processo de avaliação da infecção canina, promovendo maior agilidade na contenção destes animais com a finalidade de reduzir os níveis de transmissão. O segundo objetivo foi desenvolvido por meio de um estudo transversal com 715 cães de idade entre 1 mês e 13 anos, com raça variada avaliados por clínicos veterinários no HVU-UFPI, no período de janeiro a dezembro de 2003. As sensibilidades e especificidades de critérios clínicos, sorológicos e parasitológicos para detecção de infecção canina por Leishmania chagasi foram estimadas por meio de análise de classe latente, considerando quatro modelos de testes e diferentes pontos de corte. As melhores sensibilidades estimadas para os critérios clínico, sorológico e parasitológico foram de 60%, 95% e 66%, respectivamente. Já as melhores especificidades estimadas para os critérios clínico, sorológico e parasitológico foram de 77%, 90% e 100%, respectivamente. Conclui-se que o uso do exame parasitológico como padrão-ouro para validação de testes diagnósticos não é apropriado e que os indicadores de acurácia dos testes avaliados são insuficientes e não justificam que eles sejam usados isoladamente para diagnóstico da infecção com a finalidade de controle da doença. / American visceral leishmaniasis (AVL) is an expanding disease in Brazil, for which few, and apparently inefficient, control strategies are available. A major problem for the containment of visceral leishmaniasis is the lack of an accurate test for the identification of infected dogs, which are considered the main reservoirs of the disease in urban areas. In this sense, the characterization of clinical and laboratory markers of the infection in this reservoir, as well as, a more appropriate assessment of the performance of tests for the diagnosis of infection, might increase the effectiveness of control strategies for AVL. Thus, this study has two main objectives: (1) to develop and validate a prediction model for parasitism by Leishmania chagasi in dogs, based on the results of serological tests and clinical signs and (2) to evaluate the sensitivity and specificity of a clinical criterion, and of parasitological and serological tests for canine infection by L. chagasi using latent class analysis. The first goal was developed from a study in which clinical, serological and parasitological data were obtained for all dogs, suspicious or not to AVL, admitted at the Veterinary Hospital at the Federal University of Piauí, Teresina, in the years of 2003 and 2004, totaling 1412 animals. Logistic regression models were constructed with the animals admitted in 2003 with the aim of developing a predictive model for parasitism based on clinical signs and results of serology by indirect immunofluorescence (IIF). This model was validated in dogs admitted at the hospital in 2004. To evaluate the area under the ROC curve (AuROC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy, three models were developed: one based only on clinical variables, other only with the serological results and a final model based on both the clinical and serological data. Among the three, the last model showed the best performance (AuROC=90.1%, sensitivity 82.4%, specificity=81.6%, PPV=73.4% NPV=88.2% and overall accuracy=81.9%). It is concluded that the use of predictive models based on clinical and serological data for diagnosis of canine visceral leishmaniasis might be useful in the evaluation of canine infection, allowing the anticipation of ontainment of these animals in order to reduce transmission levels. The second goal was developed through a cross-sectional study of 715 dogs aged between 1 month and 13 years, with varied races evaluated by veterinarians at VUH-UFPI in the period January to December 2003. The sensitivities and specificities of clinical, parasitological and serological tests for detection of canine infection by Leishmania chagasi were estimated using latent class analysis, considering four types of models and different cutoffs. The best sensitivity estimates for the clinical, serological and parasitological tests were 60%, 95% and 66% respectively. The best estimates for the specificity of clinical, serological and parasitological tests were 77%, 90% and 100% respectively. It is concluded that the use of parasitological assays as the gold standard for validation of diagnostic tests is not appropriate and that the indicators of accuracy of the tests evaluated are insufficient to justify that they are used alone for diagnosis of infection in order to control the disease.