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In this paper, several identities concerning expectation, variance, covariance, cumulative distribution functions, the coefficient of variation, and the Lorenz curve are obtained and they are used in establishing theoretical results. Furthermore, a graphical representation of the variance is proposed which, together with the aforementioned identities, enables the square of the coeficient of variation to be considered as an equality measure in the sameway as is the Gini index. A study of the similarities between the theoretical expression of the Gini index and the square of the coefficient of variation is also carried out in this paper. || En este trabajo se obtienen diversas identidades relativas a la espezanza, varianza, covarianza, función de distribución acumulada, coeficiente de variación y curva de Lorenz que se usarán para obtener resultados teóricos interesantes. Se construye, además, una representación gráfica de la varianza, la cual, utilizando las propiedades obtenidas, nos indica que el cuadrado del coeficiente de variación se puede considerar como una medida de igualdad, de igual forma que se considera al índice de Gini. En este artículo también se lleva a cabo un estudio de las similitudes entre la expresión teórica delíndice de Gini y el cuadrado del coeficiente de variación.

En este trabajo, a partir de la continuación de las bifurcaciones de codimensión 1 en un modelo dinámico discreto aplicado al mercado actual y potencial de las organizaciones, se establecen las condiciones necesarias para la existencia de bifurcaciones de codimensión 2. Como caso práctico, se estudia el caso del mercado cervecero español, considerando como referencia la marca “San Miguel”, analizando su evolución e interpretación económica. = In this work we establish the necessary conditions for the existence of bifurcations of codimension 2 in a discrete dynamic model applied to the current and potential market of the organizations, starting from the continuation of the codimension 1 bifurcations. The case of the market Spanish brewer is studied and we analyse its evolution and interpret the economical results obtained.

El objetivo del trabajo se centra en un análisis transversal y longitudinal de la pobreza en Alemania en el período de 1985 a 1996, utilizando la base de datos Panel Comparability Project. El análisis transversal nos permite conocer cómo el proceso de reunificación alemana influye en el nivel de pobreza y en la intensidad de la misma. Por su parte, el análisis longitudinal nos permite seguir a los individuos en el tiempo, posibilitando la observación de los períodos en el estado de pobreza, la transición al estado de no pobreza, así como la longitud de su permanencia por debajo del umbral de pobreza. Dado que los datos contienen información de características individuales y del hogar, un análisis basado en las estimaciones de la función riesgo y de supervivencia hace posible la identificación de aquellas características socioeconómicas más destacables de la población que son propias de la pobreza permanente y transitoria. = The objective of this research focuses on both a cross-sectional and longitudinal analyses of poverty in Germany from 1986 to 1996, using the Panel Comparability Project data set. On the one hand, the cross-sectional analysis allows us to know how the Reunification Process influences on the level and the intensity of poverty. On the other hand, the longitudinal analysis allows us to follow up the individuals in time, and therefore to observe the permanence in poverty, and the transition out of poverty. Since the data set contains information about household and individual characteristics, an analysis based on the estimations of the risk and survival function makes possible the identification of those socioeconomic characteristics of the population which are more proper of the permanent and transitory poverty.

Abstract A 25-year-old, with type I Diabetes Mellitus with a previous diagnosis of Protamine Allergy but not to human Insulin, started to notice anaphylactic reactions inmmediatly after bolus with Insulin. Skin prick and intradermal test were positive to all insulins. Skin tests to other potential allergens resulted negative. Examination after bolus of Human Insulin revealed urticaria. Daily insulin requirement were around 2-2,4 U/Kg/day. Slow desensitisation with Aspart insulin, the insulin with lowest size of skin test, was performed using subcutaneous insulin pump. Six months after the end of desensitisation his daily insulin requirement decreased to 0.8 U/Kg/day and oral corticosteroids are being reduced with no symptoms.

The aim of the present work is to define a theoretical framework which facilitates the analysis of the structure of a network at an individual level. To this end, we propose the integration of co-word analysis together with the analysis of social networks. As a result of this study, a series of diagrams called “structural diagrams” has been obtained. Thanks to these diagrams a pattern can be assigned to each node of the network, and a network can be classified into a set of typologies. The information provided by this theoretical framework will allow a deeper understanding of the dynamics of systems, modeled in the form of networks. In this context, structural diagrams technique improves strategies of the visual exploration of the networks as well as to orientate the definition of those procedures which enable the transformation of one typology of network into another. As a specific example of a real application of this theoretical framework, the social network of the Journal of Software Engineering and Databases (JISBD) scientific community has been analyzed, based on its co-authorship networks.

Genetically modified Komagataella phaffii strain MXY0541 was developed to produce soy leghemoglobin by introducing the LGB2 coding sequence encoding leghemoglobin from soybean ( Glycine max ). The molecular characterisation data and bioinformatic analyses do not raise any safety concerns. The safety of soy leghemoglobin as a food additive has already been assessed by the EFSA FAF Panel (EFSA-Q-2022-00031). The GMO Panel does not identify safety concerns regarding the toxicity and allergenicity of soy leghemoglobin protein as expressed in K. phaffii , and finds no evidence that the genetic modification would change its overall allergenicity. The GMO Panel concludes that the LegH Prep derived from genetically modified K. phaffii strain MXY0541 is safe for human consumption with regard to the effects of the genetic modification. No environmental impact from the use of this product is expected regarding the recombinant DNA sequences possibly remaining in the product. The GMO Panel concludes that LegH Prep from genetically modified K. phaffii strain MXY0541 is safe with respect to potential effects on human health and the environment at the proposed use and use level as far as the impact of the genetic modification is concerned. The overall conclusion is that the genetic modification does not lead to safety issues., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Background: Suicide has become a first-order public health concern after the negative impact of COVID-19 on the general population's mental health. Several studies have analyzed the trends in suicide attempts (SA) before and after the onset of the pandemic, but few studies focus on the impact of the pandemic on medically serious suicide attempts (MSSA)., Methods: Participants were 385 hospitalized individuals ≥ 16 years old who made MSSA identified retrospectively through a review of e-medical records between 2018 and 2022 ("pre-COVID-19" and "COVID" periods). The two groups were compared on sociodemographic and clinical variables using Chi-square or Exact Fisher's tests for categorical variables and a Mann-Whitney test for continuous variables. To study the variation in MSSA over time, MSSA were aggregated monthly. Joinpoint regression analyses were used to assess time trends., Results: A sample of 161 MSSA patients, 80 women and 81 men, were selected from 385 admissions after a suicide attempt (SA) in the four years (n = 160 pre-COVID period vs. n = 225 COVID period) (OR = 1.41; CI 95% = 1.0003-1.7223, p < 0.001). Sixty-eight patients with MSSA were admitted during the first period, and 93 during the COVID period (OR = 1.4 ; CI 95% = 1-1.9 ; p < 0.05). MSSA patients were more likely to be admitted to an intensive care unit during the COVID period than during the pre-COVID period (OR = 3.5; CI 95% = 1.7-6.9; p < 0.001)., Conclusions: This study highlights the need for research on suicide risk during and after crisis periods, such as the COVID-19 pandemic. It provides valuable knowledge on the incidence of SA needing hospitalization, MSSA, and highly severe MSSA for four years before and after the pandemic onset., (© 2024. The Author(s).)

Loop-Mediated Isothermal Loop-Mediated Isothermal Amplification (LAMP) is a widely used technique for nucleic acid amplification due to its high specificity, sensitivity, and rapid results. Advances in microfluidic lab-on-chip (LOC) technology have enabled the integration of LAMP into miniaturized devices, known as μ-LAMP, which require precise thermal control for optimal DNA amplification. This paper introduces a novel thermal bed design using PCB copper traces and FR-4 dielectric materials, providing a reliable, modular, and repairable heating platform. The system achieves accurate and stable temperature control, which is critical for μ-LAMP applications, with temperature deviations within ±1.0 °C. The thermal bed's performance is validated through finite element method (FEM) simulations, showing uniform temperature distribution and a rapid thermal response of 2.5 s to reach the target temperature. These results highlight the system's potential for applications such as disease diagnostics, biological safety, and forensic analysis, where precision and reliability are paramount.

Purpose: Trials demonstrating benefits of tamoxifen for women with ductal carcinoma in situ (DCIS) were published > 20 years ago; yet subsequent uptake of endocrine therapy was low. We estimated endocrine therapy initiation in women with DCIS between 2001 and 2018 in a community setting, reflecting more recent years of diagnosis than previous studies., Methods: This retrospective cohort included adult females ≥ 20 years diagnosed with first primary DCIS between 2001 and 2018, followed through 2019, and enrolled in one of three U.S. integrated healthcare systems. We collected data on endocrine therapy dispensings (tamoxifen, aromatase inhibitors [AIs]) from electronic pharmacy records within 12 months after DCIS diagnosis. Using generalized linear models with a log link and Poisson distribution, we estimated endocrine therapy initiation rates over time and by patient, tumor (including estrogen receptor [ER] status), and treatment characteristics., Results: Among 2020 women with DCIS, 587 (29%) initiated endocrine therapy within 12 months after diagnosis (36% among 1208 women with ER-positive DCIS). Among women who used endocrine therapy, 506 (86%) initiated tamoxifen and 81 (14%) initiated AIs. Age-adjusted endocrine therapy initiation declined from 34 to 21% between 2001 and 2017; between 2015 and 2018, AI use increased from 8 to 35%. Women less likely to initiate endocrine therapy were ER-negative or had borderline/unknown or no ER test results, ≥ 65 years at diagnosis, Black, and received no radiotherapy., Conclusion: One-third of women diagnosed with DCIS initiated endocrine therapy, and use decreased over time. Understanding why women eligible for endocrine therapy do not initiate is important to maximizing disease-free survival following DCIS diagnosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Calcium binding proteins are essential for neural development and cellular activity. Calretinin, encoded by calb2a and calb2b, plays a role during early zebrafish development and has been proposed as a marker for distinct neuronal populations within the locomotor network. We generated a calb2b:hs:eGFP transgenic reporter line to characterize calretinin expressing cells in the developing spinal cord and describe morphological and behavioral defects in calretinin knock-down larvae. eGFP was detected in primary and secondary motor neurons, as well as in dI6 and V0v interneurons. Knock-down of calretinin lead to disturbed development of motor neurons and dI6 interneurons, revealing a crucial role during early development of the locomotor network. Primary motor neurons showed delayed axon outgrowth and the distinct inhibitory CoLo neurons, originating from the dI6 lineage, were absent. These observations explain the locomotor defects we observed in calretinin knock-down animals where the velocity, acceleration and coordination were affected during escapes. Altogether, our analysis suggests an essential role for calretinin during the development of the circuits regulating escape responses and fast movements within the locomotor network., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The accumulation of relatively higher dose of zinc oxide nanoparticles in brain was reported to produce neurotoxicity. Indeed, nanoparticles have a high ability to penetrate biological membranes and be uptaken by cells, which may cause cell disorders and physiological dysfunctions. The aim of the current study was to evaluate, whether oral administration of saffron extract, in rats, can protect from neurotoxicity and behavioural disturbances induced by chronic administration of ZnO-NPs. Daily oral administration of ZnO-NPs was performed for 21 consecutive days to induce oxidative stress-like situation. Then after the saffron extract was concomitantly administrated in several rat groups to overcome the nanotoxicological effect induced by ZnO-NPs. In the frontal cortex, the hippocampus and the cerebellum, ZnO-NPs induced a H 2 O 2 -oxydative stress-like effect reflected in reduced enzymatic activities of catalase, superoxide dismutase and glutathione S-transferase, and decreased acetylcholinesterase activity. In addition, increased levels of proinflammatory interleukins IL-6 and IL-1-⍺ occurred in the hippocampus, reveal the existence of brain inflammation. The concomitant administration of saffron extract to animals exposed to ZnO-NPs prevented the enhanced anxiety-related to the behaviour in the elevated plus-maze test, the open field test and preserved spatial learning abilities in the Morris water maze. Moreover, animals exposed to ZnO-NPs and saffron showed abnormal activity of several antioxidant enzymes as well as acetylcholinesterase activity, an effect that may underly the preserved anxiety-like behaviour and spatial learning abilities observed in these animals. Saffron extract has a potential beneficial therapeutic effect: antioxidant, anti-inflammatory and neuroprotective agent., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Purpose: To report the case of a patient with X-linked juvenile retinoschisis (XLRS), caused by an in-frame deletion of the RS1 gene, who presented visual loss due to bilateral central serous chorioretinopathy (CSC).Methods: Observational case report., Results: A 34-year-old man, with type-A personality, presented with a one-month history of decreased visual acuity and metamorphopsia in his right eye. Funduscopic examination showed a dome-like foveal elevation in both eyes (OU), as well as subtle pigmentary changes of the retinal pigment epithelium with a tapetal reflex in the fovea. Spectral-domain optical coherence tomography revealed intraretinal cystic foveal changes and serous retinal detachment in OU. Fundus fluorescein angiography of OU showed a focal area of intense hyperfluorescence with leakage in late phases. Electroretinogram revealed a markedly attenuated b-wave and a diminished a-wave in photopic and scotopic phases. Genetic testing revealed a hemizygous c.282&#95;284delCTT deletion in the RS1 gene, predicting a p.Ser95del change at the protein level. The patient was diagnosed with XLRS and central serous chorioretinopathy as a coexisting condition. Patient was observed during a 3-month period but showed no improvement. Therefore, subthreshold micropulse laser was applied, achieving complete resolution of signs and symptoms of CSC., Conclusion: CSC can be a cause of acute or subacute visual loss in patients with XLRS when other complications such as vitreous hemorrhage and retinal detachment have been excluded.

Motivation: Epidemiological studies face two important challenges: the need to ingest ever more complex data types, and mounting concerns about participant privacy and data governance. These two challenges are compounded by the expectation that data infrastructure will eventually need to facilitate cross-registration of participants by multiple epidemiological studies. Implementation: The portable web-service epiDonate was developed using the serverless model known as FaaS (Function-as-a-Service). The reference implementation uses nodejs. The implementation relies on a simple tokenization scheme, mediated by a public API, that a) distinguishes admin from participant roles, with b) extensible permission configuration operating a read/write structure. General Features: The critical design feature of epiDonate is the absence of business logic on the server-side (the web service). The simplicity removes the need to customize virtual machines and enables ecosystems of multiple web Applications backed by one or more data donation deployments. Availability: https://episphere.github.io/donate., (©2023 AMIA - All rights reserved.)

Competing Interests: Competing interests: TG is a member of Independent SAGE and an unpaid adviser to a philanthropic fund (Balvi) which donates to long covid research. NG is a patron of PoTS-UK, the national PoTS charity; the role is unpaid. NR is a trustee of the UK charity Long Covid Support.

Purpose: Hospital-acquired venous thromboembolisms (HA-VTEs) are increasingly common in pediatric inpatients and associated with significant morbidity and cost. The Braden QD Scale was created to predict the risk of hospital-acquired pressure injury (HAPI) and is used broadly in children's hospitals. This study evaluated the ability of the Braden QD Total score to predict risk of HA-VTE at a quaternary children's hospital., Methods: To analyze the predictive potential of the Braden QD Total score and subscores for HA-VTEs, the researchers performed univariate logistic regressions. The increase in a patient's odds of developing an HA-VTE for every 1-point increase in each Braden QD score was evaluated. Each model was evaluated using a 5-fold cross-validated area-under-the-curve of the corresponding receiver operating characteristic curve (AUROC)., Results: This study analyzed 27,689 pediatric inpatients. HA-VTE occurred in 135 patients. The odds of HA-VTE incidence increased by 29% (odds ratio 1.29, 95% confidence interval [CI] 1.25-1.34, p < 0.001) for every 1-point increase in a patient's Braden QD Total score. The AUROC was 0.81 (95% CI 0.77-0.85)., Conclusion: The Braden QD Scale is a predictor for HA-VTE, outperforming its original intended use for predicting HAPI and performing similarly to other HA-VTE predictive models. As the Braden QD Total score is currently recorded in the electronic health records of many children's hospitals, it could be practically and easily implemented as a tool to predict which patients are at risk for HA-VTE., (Copyright © 2022. Published by Elsevier Inc.)

Background: It has been well-established that acute radiation exposures increase the risk of leukemia. However, it is still unknown whether these leukemia risk estimates could be extrapolated to occupational populations who receive repeated low-dose radiation exposure. The purpose of this study was to estimate quantified associations between low-dose radiation exposures and leukemia., Methods: The Chinese medical X-ray worker study (CMXW) included 27,011 medical X-ray workers employed at major hospitals in 24 provinces in China from 1950 to 1980, and a control population of 25,782 physicians matched by hospital, who were unexposed to X-ray equipment. Poisson regression models were used to estimate the excess relative risk (ERR) and excess absolute risk (EAR) for the incidence of leukemia associated with cumulative doses. A meta-analysis of the published literature on low-dose occupational radiation exposure and leukemia risk was also conducted., Results: The incidence rates of leukemia in X-ray workers and the control group were 6.70 and 3.39 per 100,000 person-years, respectively. Among X-ray workers, the average cumulative red bone marrow dose was 0.046 Gy. We found a positive relationship between 2-year lagged cumulative red bone marrow dose and risk of leukemia excluding chronic lymphocytic leukemia (CLL) (ERR = 0.66 per 100 mGy, 90% CI: 0.09, 1.53; EAR = 0.29 per 10 4 PY-100 mGy, 90% CI: 0.07, 0.56). The excess risk was largely driven by myeloid leukemia (ERR = 1.06 per 100 mGy, 90% CI: 0.22, 2.51). Based on the meta-analysis, the pooled ERR at 100 mGy was 0.19 (95% CI: 0.08, 0.31)., Conclusion: This study provides strong evidence of a positive and linear doseresponse relationship between cumulative red bone marrow dose and the incidence of non-CLL leukemia., Competing Interests: The authors declare that they have no conflict of interests., (© 2022 Chinese National Cancer Center. Published by Elsevier B.V.)

Background: Since the start of the COVID-19 pandemic, efforts have been made to develop early warning risk scores to help clinicians decide which patient is likely to deteriorate and require hospitalization. The RECAP (Remote COVID-19 Assessment in Primary Care) study investigates the predictive risk of hospitalization, deterioration, and death of patients with confirmed COVID-19, based on a set of parameters chosen through a Delphi process performed by clinicians. We aim to use rich data collected remotely through the use of electronic data templates integrated in the electronic health systems of several general practices across the United Kingdom to construct accurate predictive models. The models will be based on preexisting conditions and monitoring data of a patient's clinical parameters (eg, blood oxygen saturation) to make reliable predictions as to the patient's risk of hospital admission, deterioration, and death., Objective: This statistical analysis plan outlines the statistical methods to build the prediction model to be used in the prioritization of patients in the primary care setting. The statistical analysis plan for the RECAP study includes the development and validation of the RECAP-V1 prediction model as a primary outcome. This prediction model will be adapted as a three-category risk score split into red (high risk), amber (medium risk), and green (low risk) for any patient with suspected COVID-19. The model will predict the risk of deterioration and hospitalization., Methods: After the data have been collected, we will assess the degree of missingness and use a combination of traditional data imputation using multiple imputation by chained equations, as well as more novel machine-learning approaches to impute the missing data for the final analysis. For predictive model development, we will use multiple logistic regression analyses to construct the model. We aim to recruit a minimum of 1317 patients for model development and validation. We will then externally validate the model on an independent dataset of 1400 patients. The model will also be applied for multiple different datasets to assess both its performance in different patient groups and its applicability for different methods of data collection., Results: As of May 10, 2021, we have recruited 3732 patients. A further 2088 patients have been recruited through the National Health Service Clinical Assessment Service, and approximately 5000 patients have been recruited through the DoctalyHealth platform., Conclusions: The methodology for the development of the RECAP-V1 prediction model as well as the risk score will provide clinicians with a statistically robust tool to help prioritize COVID-19 patients., Trial Registration: ClinicalTrials.gov NCT04435041; https://clinicaltrials.gov/ct2/show/NCT04435041., International Registered Report Identifier (irrid): DERR1-10.2196/30083., (©Francesca Fiorentino, Denys Prociuk, Ana Belen Espinosa Gonzalez, Ana Luisa Neves, Laiba Husain, Sonny Christian Ramtale, Emma Mi, Ella Mi, Jack Macartney, Sneha N Anand, Julian Sherlock, Kavitha Saravanakumar, Erik Mayer, Simon de Lusignan, Trisha Greenhalgh, Brendan C Delaney. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 05.10.2021.)

The progression and distribution of the SARS-CoV-2 pandemic are continuously changing over time and can be traced by blood donors' serological survey. Here, we investigated the seroprevalence of anti-SARS-CoV-2 antibodies in blood donors in Nuevo Leon, Mexico during 2020 as a strategy for the rapid evaluation of the spread of SARS-CoV-2 and asymptomatic case detection. We collected residual plasma samples from blood donors who attended two regional donation centers from January to December of 2020 to identify changes in anti-SARS-CoV-2 IgG prevalence. Plasma samples were analyzed on the Abbott Architect instrument using the commercial Abbott SARS-CoV-2 IgG chemiluminescent assay. We found a total of 99 reactive samples from 2068 analyzed plasma samples, resulting in a raw prevalence of 4.87%. Donors aged 18-49 years were more likely to be seropositive compared to those aged >50 years ( p < 0.001). Weekly seroprevalence increased from 1.8% during the early pandemic stage to 27.59% by the end of the year. Prevalence was 1.46-fold higher in females compared to males. Case geographical mapping showed that Monterrey city recorded the majority of SARS-CoV-2 cases. These results show that there is a growing trend of seroprevalence over time associated with asymptomatic infection that is unnoticed under the current epidemiological surveillance protocols.

The zebrafish lateral line is a sensory system used to detect changes in water flow. It is comprized of clusters of superficial hair cells called neuromasts. Modulation occurs via excitatory and inhibitory efferent neurons located in the brain. Using mosaic transgenic labeling we provide an anatomical overview of the lateral line projections made by individual inhibitory efferent neurons in 5-day old zebrafish larvae. For each hemisphere we estimate there to be six inhibitory efferent neurons located in two different nuclei. Three distinct cell types were classified based on their projections; to the anterior lateral line around the head, to the posterior lateral line along the body, or to both. Our analyses corroborate previous studies employing back-fills, but our transgenic labeling allowed a more thorough characterization of their morphology. We found that individual inhibitory efferent cells connect to multiple neuromasts and that a single neuromast is connected by multiple inhibitory efferent cells. The efferent axons project to the sensory ganglia and follow the sensory axon tract along the lateral line. Time-lapse imaging revealed that inhibitory efferent axons do not migrate with the primordium as the primary sensory afferent does, but follow with an 8-14 h lag. These data bring new insights into the formation of a sensory circuit and support the hypothesis that different classes of inhibitory efferent cells have different functions. Our findings provide a foundation for future studies focussed toward unraveling how and when sensory perception is modulated by different efferent cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Manuel, Iglesias Gonzalez, Habicher, Koning and Boije.)

Background: During the pandemic, remote consultations have become the norm for assessing patients with signs and symptoms of COVID-19 to decrease the risk of transmission. This has intensified the clinical uncertainty already experienced by primary care clinicians when assessing patients with suspected COVID-19 and has prompted the use of risk prediction scores, such as the National Early Warning Score (NEWS2), to assess severity and guide treatment. However, the risk prediction tools available have not been validated in a community setting and are not designed to capture the idiosyncrasies of COVID-19 infection., Objective: The objective of this study is to produce a multivariate risk prediction tool, RECAP-V1 (Remote COVID-19 Assessment in Primary Care), to support primary care clinicians in the identification of those patients with COVID-19 that are at higher risk of deterioration and facilitate the early escalation of their treatment with the aim of improving patient outcomes., Methods: The study follows a prospective cohort observational design, whereby patients presenting in primary care with signs and symptoms suggestive of COVID-19 will be followed and their data linked to hospital outcomes (hospital admission and death). Data collection will be carried out by primary care clinicians in four arms: North West London Clinical Commissioning Groups (NWL CCGs), Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), Covid Clinical Assessment Service (CCAS), and South East London CCGs (Doctaly platform). The study involves the use of an electronic template that incorporates a list of items (known as RECAP-V0) thought to be associated with disease outcome according to previous qualitative work. Data collected will be linked to patient outcomes in highly secure environments. We will then use multivariate logistic regression analyses for model development and validation., Results: Recruitment of participants started in October 2020. Initially, only the NWL CCGs and RCGP RSC arms were active. As of March 24, 2021, we have recruited a combined sample of 3827 participants in these two arms. CCAS and Doctaly joined the study in February 2021, with CCAS starting the recruitment process on March 15, 2021. The first part of the analysis (RECAP-V1 model development) is planned to start in April 2021 using the first half of the NWL CCGs and RCGP RSC combined data set. Posteriorly, the model will be validated with the rest of the NWL CCGs and RCGP RSC data as well as the CCAS and Doctaly data sets. The study was approved by the Research Ethics Committee on May 27, 2020 (Integrated Research Application System number: 283024, Research Ethics Committee reference number: 20/NW/0266) and badged as National Institute of Health Research Urgent Public Health Study on October 14, 2020., Conclusions: We believe the validated RECAP-V1 early warning score will be a valuable tool for the assessment of severity in patients with suspected COVID-19 in the community, either in face-to-face or remote consultations, and will facilitate the timely escalation of treatment with the potential to improve patient outcomes., Trial Registration: ISRCTN registry ISRCTN13953727; https://www.isrctn.com/ISRCTN13953727., International Registered Report Identifier (irrid): DERR1-10.2196/29072., (©Ana Belen Espinosa-Gonzalez, Ana Luisa Neves, Francesca Fiorentino, Denys Prociuk, Laiba Husain, Sonny Christian Ramtale, Emma Mi, Ella Mi, Jack Macartney, Sneha N Anand, Julian Sherlock, Kavitha Saravanakumar, Erik Mayer, Simon de Lusignan, Trisha Greenhalgh, Brendan C Delaney. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 25.05.2021.)

Background: General practitioners (GPs) play a key role in managing the COVID-19 outbreak. However, they may encounter difficulties adapting their practices to the pandemic. We provide here an analysis of guidelines for the reorganisation of GP surgeries during the beginning of the pandemic from 15 countries., Methods: A network of GPs collaborated together in a three-step process: (i) identification of key recommendations of GP surgery reorganisation, according to WHO, CDC and health professional resources from health care facilities; (ii) collection of key recommendations included in the guidelines published in 15 countries; (iii) analysis, comparison and synthesis of the results., Results: Recommendations for the reorganisation of GP surgeries of four types were identified: (i) reorganisation of GP consultations (cancelation of non-urgent consultations, follow-up via e-consultations), (ii) reorganisation of GP surgeries (area partitioning, visual alerts and signs, strict hygiene measures), (iii) reorganisation of medical examinations by GPs (equipment, hygiene, partial clinical examinations, patient education), (iv) reorganisation of GP staff (equipment, management, meetings, collaboration with the local community)., Conclusions: We provide here an analysis of guidelines for the reorganisation of GP surgeries during the beginning of the COVID-19 outbreak from 15 countries. These guidelines focus principally on clinical care, with less attention paid to staff management, and the area of epidemiological surveillance and research is largely neglected. The differences of guidelines between countries and the difficulty to apply them in routine care, highlight the need of advanced research in primary care. Thereby, primary care would be able to provide recommendations adapted to the real-world settings and with stronger evidence, which is especially necessary during pandemics.

Genetic screens have been used to identify genes involved in the regulation of different biological processes. We identified growth mutants in a Flp/FRT screen using the Drosophila melanogaster eye to identify conditional regulators of cell growth and cell division. One mutant identified from this screen, B.2.16 , was mapped and characterized by researchers in undergraduate genetics labs as part of the Fly-CURE. We find that B.2.16 is a non-lethal genetic modifier of the Dark 82 mosaic eye phenotype., (Copyright: © 2021 by the authors.)

Vertebrate locomotion is orchestrated by spinal interneurons making up a central pattern generator. Proper coordination of activity, both within and between segments, is required to generate the desired locomotor output. This coordination is altered during acceleration to ensure the correct recruitment of muscles for the chosen speed. The transcription factor Dmrt3 has been proposed to shape the patterned output at different gaits in horses and mice. Here, we characterized dmrt3a mutant zebrafish, which showed a strong, transient, locomotor phenotype in developing larvae. During beat-and-glide swimming, mutant larvae showed fewer and shorter movements with decreased velocity and acceleration. Developmental compensation likely occurs as the analyzed behaviors did not differ from wild-type at older larval stages. However, analysis of maximum swim speed in juveniles suggests that some defects persist within the mature locomotor network of dmrt3a mutants. Our results reveal the pivotal role Dmrt3 neurons play in shaping the patterned output during acceleration in vertebrates., (Copyright © 2020 Cano et al.)

In Japan, cervical cancer incidence has increased since the late 1990s especially among young women, despite a decreasing trend in most developed countries. Here, we examined age, period and birth cohort trends in cervical cancer incidence rates from 1985 to 2012. Incidence rates were ascertained using three population-based cancer registries and analyzed using Joinpoint regression and age-period-cohort models. We compared the findings in Japan to trends among Japanese-Americans in the Surveillance, Epidemiology, and End Results Registries and among women in South Korea using the Korea Central Registry. Age-standardized incidence rates in Japan decreased by 1.7% per year (95% confidence interval - 3.3%, 0.0%) until 1997 and thereafter increased by 2.6% per year (1.1%, 4.2%). Incidence rates increased among women under age 50, were stable among women aged 50-54, and decreased or remained stable among women aged 55 and over. The age-standardized incidence rate ratio by birth cohort showed a U-shaped pattern with the lowest rates in women born in the late 1930s and 1940s. In comparison, women born before 1920 and after 1970 had about double the incidence. Increasing risk in recent birth cohorts was not evident in Japanese-American or South Korean women. The trends in Japan may be attributable to increasing prevalence of human papillomavirus (HPV) infection among young women. Screening and vaccination have been shown to be highly effective and would help reverse these trends., (© 2018 UICC.)

The optic cup houses multipotent retinal progenitor cells that proliferate and differentiate to form the mature retina, containing five main types of neurons and a single glial cell type, the Müller cell. Progenitors of the zebrafish optic cup generate clones that vary regarding the number and types of neurons, a process we previously showed could be described by stochastic models. Here, we present data indicating that each retinal progenitor cell, in the 24 hrs post-fertilization optic cup, is predestined to form a single Müller cell. This striking fate assignment of Müller cells reveals a dual nature of retinal lineages where stochastic mechanisms produce variable numbers of neurons while there is a strong deterministic component governing the formation of glia cells. A possible mechanism for this stereotypic fate assignment could be the maintenance of a clonal backbone during retina development, which would be similar to invertebrate and rodent cortical neurogenesis., (© 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and JohnWiley & Sons Ltd.)

Background and Objectives: To describe the patterns of failure in patients with in-transit (IT) melanoma undergoing surgical excision., Methods: A retrospective review of patients who underwent their first IT lesion(s) resection between May 2005 and September 2014. Cumulative incidence of local failure (new lesion within 2 cm of IT resection) was estimated. Associations between clinicopathologic characteristics, local failure, and any recurrence were analyzed., Results: One hundred and thirty patients presented to our institution with IT disease over the study period and met the inclusion criteria. The 2-year cumulative incidence of local failure was 19.5%. Twenty-four patients developed disease within 2 cm of the resected IT disease; however, only eight were isolated local events. Cumulative incidence of local failure and of any disease differed with respect to less than 1 year disease-free interval (DFI) from primary melanoma to first IT event, and having greater than 1 IT lesion at presentation. Incidence of local failure was not found to differ with respect to gross margin greater than 5 mm, after adjusting for DFI and greater than 1 IT lesions., Conclusions: Patients with greater than 1 IT lesion and a DFI less than 1 year are at a higher risk of failure after surgical excision of a first IT event. Very few failures were isolated local disease within 2 cm of the IT resection scar, regardless of IT excision margin., (© 2018 Wiley Periodicals, Inc.)

Background: Patients with regionally advanced melanoma are at high risk of distant failure and unlikely to be cured by surgery alone. Neoadjuvant therapy may provide benefit in these patients., Objectives: To evaluate our experience with neoadjuvant systemic therapy in high-risk stage III patients., Methods: Retrospective review of patients with advanced stage III disease who received neoadjuvant therapy between August 2009 and August 2016 at Mayo Clinic Rochester., Results: Twenty-three cases met our inclusion criteria, 16 with resectable disease and 7 with unresectable disease. No patients with resectable disease and one patient with borderline resectable disease progressed regionally, prohibiting surgical resection. Five of seven patients with unresectable disease were down-staged to a resectable state. Six of twenty-three (26%) had a CR and five are alive at last follow-up. Fifteen of twenty three patients (65%) progressed with a median progression free survival of 11 months; however, the 5 year overall survival estimate was 84%., Conclusions: Neoadjuvant systemic therapy is a reasonable approach for patients with advanced but resectable/borderline resectable disease and the risk of losing regional control is low. Our data also suggest some patients with unresectable disease will be converted to resectable and a complete clinical response to treatment can be obtained in approximately one quater of patients., (© 2017 Wiley Periodicals, Inc.)

For patients with ductal carcinoma In Situ (DCIS), sentinel lymph node (SLN) surgery is generally reserved for patients at high risk of being upstaged to invasive disease. The use of frozen section (FS) pathologic analysis of the primary tumor may allow for selective surgical nodal staging within one procedure. We sought to define the reliability of FS for detection of upstaging. Eight hundred and twenty-seven patients were identified with DCIS on core needle biopsy that underwent 834 operations at our institution between January 2004 and October 2014. We calculated the rate of upstage from DCIS to invasive cancer on both intraoperative FS and final pathology to determine the performance of FS. Upstage rate on final pathology was 118/834 (14.1%) 95 per cent confidence interval 11.8 to 16.7 per cent. FS identified 88/118 (74.6%) of the upstages. Specificity was 99.3 per cent (711/716). Overall accuracy was 95.8 per cent (799/834) and the positive predictive value was 96.0 per cent (711/741 patients). Mean size of invasive cancers identified on FS was 5.6 mm, versus 3.5 mm for those identified only on permanent section, P = 0.11. Intraoperative FS analysis of DCIS is useful for identification of upstage to invasive disease. This may facilitate a selective approach to SLN surgery that both decreases unnecessary SLN surgery and the need for a second operation.

Background: Approximately 8-56% of patients with a core needle biopsy (CNB) diagnosis of ductal carcinoma in situ (DCIS) will be upstaged to invasive disease at the time of excision. Patients with invasive disease are recommended to undergo axillary nodal staging, most often requiring a second operation. We developed and validated a nomogram to preoperatively predict percentage of risk for upstaging to invasive cancer., Methods: We reviewed 834 cases of DCIS on CNB between January 2004 and October 2014. Multivariable analysis was used to evaluate CNB and imaging factors to develop a nomogram to predict the risk of upstaging from DCIS to invasive cancer. This nomogram was validated with an external dataset of 579 similar patients between November 1998 and September 2016. An area under the receiver operating characteristic curve was constructed to evaluate nomogram discrimination., Results: The rate of upstaging to invasive disease was 118/834 (14.1%). On multivariable analysis, grade on CNB and imaging factors, including mass lesion, multicentric disease, and largest linear dimension, were associated with upstage to invasive disease, and was used to develop a nomogram (c-statistic 0.71). In the external validation dataset, 62/579 (10.7%) patients were upstaged to invasive disease. Our nomogram was validated in this dataset with a c-statistic of 0.71., Conclusion: For patients with a CNB diagnosis of DCIS, our validated nomogram using DCIS grade on biopsy, and imaging factors of mass lesion, multicentric disease, and largest linear dimension, may be used for preoperative assessment of risk of upstaging to invasive disease, allowing patient counseling regarding axillary staging at the time of definitive surgery.

Background and Objectives: Current randomized controlled trials are investigating the outcomes of non-surgical treatment for patients with ductal carcinoma in situ (DCIS). We sought to evaluate pre-operative factors associated with no residual disease at definitive resection following a core needle biopsy (CNB) diagnosis of DCIS., Methods: Eight hundred and thirty-four operations for DCIS were performed at our institution between January 2004 and October 2014. We evaluated patient and biopsy tumor characteristics to determine pre-operative factors associated with no residual disease at surgical resection using uni- and multivariable analyses., Results: Sixty-nine patients (8%) had no residual disease on final pathology. On multivariable analysis, low- or intermediate-grade lesions, <1 cm in size on mammography, and lesions where ≥90% of calcifications were removed correlated with finding no residual disease on final pathology, c-statistic 0.84. Of the 14 patients with all three low-risk factors, 36% had no residual disease on final pathology., Conclusions: Although our multivariable analysis performed well, its clinical utility would be limited as we were unable to identify a subset of patients with DCIS in whom the probability of finding no residual disease is low enough to consider routine use of non-surgical management., (© 2017 Wiley Periodicals, Inc.)

Importance: Whether the use of sterile vs nonsterile gloves in outpatient cutaneous procedures affects the rate of postoperative wound infection is unknown., Objective: To explore rates of surgical site infection (SSI) with the use of sterile vs nonsterile gloves in outpatient cutaneous surgical procedures., Data Sources: This systematic review and meta-analysis identified studies from Ovid MEDLINE (1946 to present), Ovid Cochrane Central Register of Controlled Trials (1991 to present), Ovid EMBASE (1988 to present), EBSCO Cumulative Index to Nursing and Allied Health Literature (1980 to present), Scopus (1996 to present), and Web of Science (1975 to present)., Study Selection: Studies with information on sterile vs nonsterile gloves in outpatient surgical procedures were retrieved. Only randomized clinical trials and comparative studies were included for final analysis., Data Extraction: Data of trial design, surgery characteristics, and outcomes from published manuscripts and unpublished data were independently extracted., Main Outcomes and Measures: Randomized clinical trials were considered high quality if randomization, allocation concealment, blinding, and follow-up completeness were appropriate. Relative risk and 95% CIs were derived for postoperative wound infections., Results: Fourteen articles met eligibility and inclusion criteria for systematic review; they included 12 275 unique patients who had undergone 12 275 unique outpatient procedures with sterile or nonsterile gloves and had follow-up regarding SSI. With the exclusion of 1 single-arm observational study of 1204 patients, 11 071 patients from 13 studies remained in the meta-analysis. Of these, 228 patients were documented as having postoperative SSI (2.1%), including 107 of 5031 patients in the nonsterile glove group (2.1%) and 121 of 6040 patients in the sterile glove group (2.0%). Overall relative risk for SSI with nonsterile glove use was 1.06 (95% CI, 0.81-1.39)., Conclusions and Relevance: No difference was found in the rate of postoperative SSI between outpatient surgical procedures performed with sterile vs nonsterile gloves.

Atherosclerosis is a chronic inflammatory vascular wall disease, and endothelial cell dysfunction plays an important role in its development and progression. Under the influence of laminar shear stress, however, the endothelium releases homeostatic factors such as nitric oxide and expresses of vasoprotective microRNAs that are resistant to atherosclerosis. Adhesion molecules such as E-selectin, exhibited on the endothelial surface, recruit monocytes that enter the vessel wall to form foam cells. Accumulation of these foam cells form fatty streaks that may progress to atherosclerotic plaques in the blood vessel wall. Interestingly, E-selectin may also serve as an affinity moiety for targeted drug delivery against atherosclerosis. We have recently developed an E-selectin-targeted platform that enriches therapeutic microRNAs in the inflamed endothelium to inhibit formation of vulnerable atherosclerotic plaques.

Introduction: Hyperthermic isolated limb perfusion (HILP) has an established role in the management of melanoma, but its role for Merkel cell carcinoma (MCC) is less well defined., Methods: Retrospective review of our institutional experience with HILP for MCC was conducted (2009-2015). Literature search was performed through 04/2015 and 10 studies met inclusion criteria., Results: Four patients underwent HILP for MCC at our institution. There were no major complications and complete response was achieved in all patients. Early metastatic recurrence developed in two patients. The remaining two had no evidence of disease at last follow-up (36 months) or death (39 months). Systematic review identified an additional 12 pts that underwent HILP for MCC, for a total of 16 cases. Median age was 73 [IQR 69-78] years and 56% were men. Of the patients with reported follow-up, 12 (86%) had complete response, 1 had stable disease, and 1 partial response. Four patients developed local-regional recurrence and six distant metastases, all within 6 months. Overall median follow-up time was 15 [7-36] months., Conclusion: Among a highly selective group of patients, regional perfusion for MCC is safe and has a high complete response rate. HILP is an acceptable therapeutic modality for obtaining durable loco-regional control but early distant metastatic disease remains a significant cause of mortality. J. Surg. Oncol. 2016;114:187-192. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)