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The epidemiological and societal burden of dementia is expected to increase in the coming decades due to the world population aging. In this context, the evaluation of the potential impact of intervention scenarios aiming at reducing the prevalence of dementia risk factors is an active area of research. However, such studies must account for the associated changes in mortality and the dependence between the risk factors. Using micro-simulations, this study aims to estimate the changes in dementia burden in France in 2040 according to intervention scenarios targeting the prevention of hypertension, diabetes and physical inactivity. Accounting for their communality and their effects on mortality, the results show that the disappearance of hypertension, diabetes and physical inactivity in France in 2020 could decrease dementia prevalence by 33% among men and 26% among women in 2040 and increase the life expectancy without dementia at age 65 by 3.4 years (men) and 2.6 years (women). Among the three factors, the prevention of hypertension would be the most efficient. These projections rely on current estimates of the risk of dementia and death associated with risk factors. Thanks to the R package developed they could be refined for different countries or different interventions and updated with new estimates.

Il trauma maggiore nei paesi occidentali è un problema rilevante in quanto costituisce la principale causa di morte e disabilità nella popolazione più giovane. Per garantire il miglior livello di assistenza in termini di efficacia e di efficienza del Sistema Integrato di Assistenza al Trauma l'appropriatezza e l'accuratezza dei criteri di triage sono fondamentali.

INTRODUZIONE: L’ accesso vascolare difficile si manifesta nel 30% degli assistiti che necessitano un accesso vascolare. E’ una condizione clinica che determina l’esecuzione di molteplici tentativi di incannulamento della vena. La gestione è affidata ad un team infermieristico dedicato con competenze avanzate nell’impianto di cateteri venosi periferici (CVP), PICC e Midline tramite tecnica ad ultrasuoni. OBIETTIVO:Effettuare un’analisi della letteratura indagando outcome e benefici della gestione di questi assistiti da parte di un team infermieristico con competenze avanzate negli accessi vascolari. METODI: Sono state consultate le banche dati PubMed, CINAHL, EMBASE, Cochrane Library, ILISI e Web of Science ed i siti ufficiali dell’ INS e del GAVeCeLT. RISULTATI: Sette studi sono stati inclusi. Il team è composto in media da 15 infermieri e 4 medici specialisti. Emerge un tasso di successo della procedura al primo tentativo dell’88-100% ed una riduzione del 90% e 70 % dei tassi di CLABSI e infezioni catetere-correlate. In media il 44.1% dei device sono stati rimossi per termine del trattamento. L’ attesa del device idoneo si è ridotta dell’ 80%. Il tasso medio di soddisfazione è risultato dell’ 88.23% (score medio registrato 8.56/10) ed una media di 2.85/10 per il dolore percepito. Le aziende hanno riportato una riduzione media di 261.358,27 euro/anno sulle spese aziendali. CONCLUSIONI: Un team dedicato per gli accessi vascolari difficili rappresenta una risorsa fondamentale per l’ erogazione di cure di qualità grazie ad una gestione tempestiva, una riduzione dei tassi di complicazioni, un’ ottimizzazione del timing assistenziale e delle spese aziendali.

Microdissection testicular sperm extraction (mTESE) has been proposed as a salvage treatment option for men with a previously failed classic TESE (cTESE), but data are scarce. We aimed to assess the outcome of and potential predictors of successful salvage mTESE in a cohort of men previously submitted to unfruitful cTESE. Data from 61 men who underwent mTESE after a failed cTESE between 01/2014 and 10/2020, at 6 tertiary-referral centres in Italy were analysed. All men were investigated with semen analyses, testicular ultrasound, hormonal and genetic blood testing. Pathological diagnosis from TESE was collected in every man. Descriptive statistics and logistic regression models were used to investigate potential predictors of positive sperm retrieval (SR+) after salvage mTESE. Baseline serum Follicle-Stimulating hormone (FSH) and total testosterone levels were 17.2 (8.6–30.1) mUI/mL and 4.7 (3.5-6.4) ng/mL, respectively. Sertoli-cell-only syndrome (SCOS), maturation arrest (MA) and hypospermatogenesis were found in 24 (39.3%), 21 (34.4%) and 16 (26.2%) men after cTESE, respectively. At mTESE, SR+ was found in 30 (49.2%) men. Patients with a diagnosis of hypospermatogenesis had a higher rate of SR+ (12/16 (75%)) compared to MA (12/21 (57.1%)) and SCOS (6/24 (25%)) patients at mTESE (p < 0.01). No clinical and laboratory differences were observed between SR+ and SR- patients at mTESE. There were no significant complications after mTESE. At multivariable logistic regression analysis, only hypospermatogenesis (OR 9.5; p < 0.01) was independently associated with SR+ at mTESE, after accounting for age and FSH. In conclusion, salvage mTESE in NOA men with previous negative cTESE was safe and promoted SR+ in almost 50%. A baseline pathology of hypospermatogenesis at cTESE emerged as the only independent predictor of positive outcomes at salvage mTESE.

Purpose: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. Materials and Methods: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological As- sociation [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. Results: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/ uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the re- sponses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identi- fied where no guidelines are available. Conclusions: This study is the largest global survey performed to date on the clinical management of varicocele for male in- fertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical prac- tice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

Epilepsy is a neurological disorder characterized by recurrent seizures. Automated prediction of epileptic seizures is essential in monitoring the health of an epileptic individual to avoid cognitive problems, accidental injuries, and even fatality. In this study, scalp electroencephalogram (EEG) recordings of epileptic individuals were used to predict seizures using a configurable Extreme Gradient Boosting (XGBoost) machine learning algorithm. Initially, the EEG data was preprocessed using a standard pipeline. We investigated 36 minutes before the onset of the seizure to classify between the pre-ictal and inter-ictal states. Further, temporal and frequency domain features were extracted from the different intervals of the pre-ictal and inter-ictal periods. Then, the XGBoost classification model was utilized to optimize the best interval for the pre-ictal state to predict the seizure by applying Leave one patient out cross-validation. Our results suggest that the proposed model could predict seizures 10.17 minutes before the onset. The highest classification accuracy achieved was 83.33 %. Thus, the suggested framework can be optimized further to select the best features and prediction interval for more accurate seizure forecasting.

Quantum mechanics exists in living biological systems on all biologically significant scales, from subatomic proton-proton spin interactions in biomolecules at room temperature, to low temperature super cool biological chemistry, signalling, oxidative phosphorylation, even in laptop computers and smartphones. In this treatise we take a first step into understanding the application of quantum mechanics to biology, with a focus on its relevance to cell elementary function and dysfunction in humans (e.g., by free radicals). In doing so we will explore the mechanics of critical physiochemical events associated with a support base in biology: strategy (‘ABC’ of evolution), metabolism, and transmission of hereditary information through the DNA double helix.

Purpose: Most currently available chemotherapeutic agents target rampant cell division in cancer cells, thereby affecting rapidly dividing normal cells resulting in toxic side-effects. This nonspecificity necessitates identification of novel cellular pathways that are reprogrammed selectively in cancer cells and can be exploited to develop pharmacologically superior and less toxic therapeutics. Despite growing awareness on dysregulation of lipid metabolism in cancer cells, targeting lipid biosynthesis is still largely uncharted territory. Herein, we report development of a novel nontoxic orally deliverable anticancer formulation of monoethanolamine (Etn) for prostate cancer by targeting the Kennedy pathway of phosphatidylethanolamine (PE) lipid biosynthesis.Experimental Design: We first evaluated gastrointestinal tract stability, drug–drug interaction liability, pharmacokinetic, and toxicokinetic properties of Etn to evaluate its suitability as a nontoxic orally deliverable agent. We next performed in vitro and in vivo experiments to investigate efficacy and mechanism of action.Results: Our data demonstrate that Etn exhibits excellent bioavailability, gastrointestinal tract stability, and no drug–drug interaction liability. Remarkably, orally fed Etn inhibited tumor growth in four weeks by approximately 67% in mice bearing human prostate cancer PC-3 xenografts without any apparent toxicity. Mechanistically, Etn exploits selective overexpression of choline kinase in cancer cells, resulting in accumulation of phosphoethanolamine (PhosE), accompanied by downregulation of HIF-1α that induces metabolic stress culminating into cell death.Conclusions: Our study provides first evidence for the superior anticancer activity of Etn, a simple lipid precursor formulation, whose nontoxicity conforms to FDA-approved standards, compelling its clinical development for prostate cancer management. Clin Cancer Res; 23(14); 3781–93. ©2017 AACR.

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This file contains supplementary figures.

When interviewing vulnerable witnesses, such as children, investigative interviewers in England and Wales are advised to follow the Achieving Best Evidence (ABE) in Criminal Proceedings guidelines (MoJ, 2022). These guidelines recommend that practitioners engage in a truth-lies discussion with child witnesses at the end of the rapport phase of an interview. Such discussions aim to make children aware of the importance of telling the truth, thus encouraging them to provide an honest and truthful statement. However, there is no standardised procedure involving the employment of truth-lies discussions in practice and to date, little is known about whether, and how, these discussions are employed in the field. This study will explore police officers’ perceptions and experiences of promoting honesty in child witnesses through interviewing strategies such as truth-lies discussions. Police officers, trained in ABE guidelines and who regularly interview child witnesses, will be invited to complete an online survey. Multiple choice and open-ended questions will explore (i) practitioners’ experiences of promoting honesty during interviews with children, (ii) potential obstacles encountered, and (iii) recommendations for alternative honesty-promoting strategies.

Summary While employing a phenomenological perspective, the present study aimed to explore the varied experiences of transgender individuals in Kashmir, concerning their health-seeking behavior, and the constraints they face while accessing healthcare resources on a day-to-day basis in their life world. Participants were recruited through the purposive and snowball sampling strategies and the sufficiency of sample size was determined by data saturation. Data were collected using face-to-face in-depth interviews and analyzed through Colaizzi’s procedure of extracting recurrent themes and their interwoven relationships in qualitative research. Three main themes of awareness and the preferences for healthcare, gender identity and persistent stigmatization in care settings, and intra-community support and the resultant caregiving were prominent. Results of the study revealed that the transgender individuals in Kashmir experience inappropriate health-seeking behaviour primarily due to their unawareness regarding health, diseases and public healthcare programs/schemes, financial constraints, social exclusion, improper support and social stigma. They often prefer treating their health issues, mostly through local pharmacies or patent medicine vendors (PMVs), instead of visiting the medical professionals in the organized sector. Moreover, in many instances, they were also found to delay their decisions to seek care or simply decided to remain far from any medical intervention. As a result, the transgender individuals in Kashmir usually experience underutilization of formal healthcare services, which undermines their right to proper health and well-being.

Supplemental material, sj-pdf-1-smm-10.1177_09622802231163331 for A multistate approach for the study of interventions on an intermediate time-to-event in health disparities research by Linda Valeri, Cecile Proust-Lima, Weijia Fan, Jarvis T. Chen and Helene Jacqmin-Gadda in Statistical Methods in Medical Research

Por muito tempo, o governo brasileiro não realizou investimentos condizentes com as necessidades na área de infraestrutura de transportes, em todas suas modalidades, especialmente nos aeroportos. Nesse contexto, a presente pesquisa buscou apresentar soluções técnicas de traçados geométricos para a melhoria dos acessos urbanos e rodoviários no Aeroporto Afonso Pena. Foi aplicada a revisão da literatura com base no Portal da CAPES e Oasisbr, revisão documental nos órgãos públicos competentes e pesquisa de campo nos anos de 2021 e 2022 no entroncamento urbano e rodoviário do Aeroporto. Quanto à revisão bibliográfica e documental, a literatura se demonstrou muito escassa em informações, assim como o plano diretor. Durante o período observado foram constatadas melhorias de infraestrutura urbana no local, contudo restritas à manutenção rotineira, sem mudanças significativas. A pesquisa levantou pontos de interesse para estudos preliminares e apresentou uma síntese que consiste na correção da congruência das ruas do acesso à trincheira da Rua Aviador Paulo Lepinski, na ampliação da mesma para mais uma pista e uma faixa de desaceleração vinda da BR-376 para entrar no Aeroporto. É necessária uma solução compatível com o porte do Aeroporto, dado os atuais investimentos, as sugestões de correção do projeto geométrico aqui propostas consistem em faixas de desaceleração e alargamento de vias, contudo necessitam de compatibilização com as interferências do local.

Supplemental material, sj-pdf-1-smm-10.1177_09622802231163331 for A multistate approach for the study of interventions on an intermediate time-to-event in health disparities research by Linda Valeri, Cecile Proust-Lima, Weijia Fan, Jarvis T. Chen and Helene Jacqmin-Gadda in Statistical Methods in Medical Research

Additional file 1.

Objetivo: O presente estudo discute a influência de áreas verdes urbanas nos preços dos imóveis – casas e apartamentos – com a segurança urbana na cidade de Curitiba. Métodos: Pesquisa exploratória com levantamento bibliográfico no Portal Brasileiro de Periódicos da CAPES, a fim de conceituar a definição de segurança urbana para compreender as correlações existentes entre as áreas verdes e o valor dos imóveis. Resultados: Os resultados apontam que os indivíduos sentem-se mais seguros na localização dos imóveis próximos à Reserva Particular do Patrimônio Natural (RPPN) Airumã em comparação àqueles da Estação Ecológica Campos Naturais de Curitiba “Teresa Urban” e Refinaria Getúlio Vargas – REPAR. A partir da concepção de segurança urbana, percebe-se uma variação do sentimento de pertencimento de lugar entre os indivíduos. Isso porque, há maior coesão social na área verde localizada ao norte, em contrapartida ao irrisório sentimento de pertencimento dos indivíduos das áreas ao sul de Curitiba. Conclusão: O resultado da análise elucida que o preço dos imóveis no entorno de áreas verdes públicas estão diretamente atrelados ao planejamento de cada região, que reflete, ou não, a segurança urbana. Com isso, compreender a heterogeneidade do espaço urbano é crucial para a aplicar instrumentos econômicos e/ou políticas públicas em territórios dinâmicos.

Background: The treatment of endocrinopathies in haemoglobinopathies is a continually expanding research area; therefore, recommendations supporting the appropriateness of treatments are a pressing need for the medical community. Methods: The Management Committee of SITE selected and gathered a multidisciplinary and multi-professional team, including experts in haemoglobinopathies and experts in endocrinopathies, who have been flanked by experts with methodological and organizational expertise, in order to formulate recommendations based on the available scientific evidence integrated by personal clinical experience. The project followed the systematic approach for the production of clinical practice guidelines according to the methodology suggested by the National Center for Clinical Excellence, Quality and Safety of Care (CNEC). Results: Out of 14 topics, 100 clinical questions were addressed, and 206 recommendations were elaborated on. The strength of recommendations, panel agreement, a short general description of the topic, and the interpretation of evidence were reported. Conclusions: Good Practice Recommendations are the final outcome of translational research and allow one to transfer to the daily clinical practice of endocrine complications in haemoglobinopathies.

The progression of dementia prevalence over the years and the lack of efficient treatments to stop or reverse the cognitive decline make dementia a major public health challenge in the developed world. Identifying people at high risk of developing dementia could improve the treatment of these patients and help select the target population for preventive clinical trials. We used joint modeling to build a dynamic prediction tool of dementia based on the change over time of 2 neurocognitive tests (the Mini-Mental State Examination and the Isaacs Set Tests) as well as an autonomy scale (the Instrumental Activities of Daily Living). The model was estimated with data from the French cohort Personnes Agées QUID (1988–2015) and validated both by cross-validation and externally with data from the French Three City cohort (1999–2018). We evaluated its predictive abilities through area under the receiver operating characteristics curve and Brier score, accounting for right censoring and competing risk of death, and obtained an average area under the curve value of 0.95 for the risk of dementia in the next 5 or 10 years. This tool is able to discriminate a high-risk group of people from the rest of the population. This could be of help in clinical practice and research.

Multi-scale calcium (Ca2+ ) dynamics, exhibiting wide-ranging temporal kinetics, constitutes a ubiquitous mode of signal transduction. We report a novel endoplasmic-reticulum (ER)-targeted Ca2+ indicator, R-CatchER, which showed superior kinetics in vitro (koff ≥2×103 s-1 , kon ≥7×106 M-1 s-1 ) and in multiple cell types. R-CatchER captured spatiotemporal ER Ca2+ dynamics in neurons and hotspots at dendritic branchpoints, enabled the first report of ER Ca2+ oscillations mediated by calcium sensing receptors (CaSRs), and revealed ER Ca2+ -based functional cooperativity of CaSR. We elucidate the mechanism of R-CatchER and propose a principle to rationally design genetically encoded Ca2+ indicators with a single Ca2+ -binding site and fast kinetics by tuning rapid fluorescent-protein dynamics and the electrostatic potential around the chromophore. The design principle is supported by the development of G-CatchER2, an upgrade of our previous (G-)CatchER with improved dynamic range. Our work may facilitate protein design, visualizing Ca2+ dynamics, and drug discovery.

In this study, we analyzed the performance of the morphological features (MF) and morphological distance-related features (MDRF) in the classification of autism spectrum disorder (ASD) and typical development (TD). Initially, we pre-processed the structural magnetic resonance images (sMRI) of ASD and TD from seven sites publicly available in the autism brain imaging data exchange (ABIDE-I and ABIDE-II) database using the standard pipeline. Further, sMRI images were parcellated into different regions using the Destrieux atlas. Moreover, MF (surface area) and MDRF were calculated from each region. We tested the performance of the MF and MDRF on each site by feeding them to classifiers such as random forest (RF), support vector machines (SVM), and multi-layer perceptron (MLP). Our results suggest that the MDRF were able to classify the ASD and TD better than the MF. Furthermore, the RF gives a single-site average classification accuracy of 91.78% and 95.27% using MF and MDRF respectively. We achieved the average classification accuracy of 69.08% and 82.91% between the sites using MF and MDRF respectively. Our results suggest that the frontal lobe and right hemisphere contribute more MDRF to the machine learning model. Furthermore, many features were found within the frontal lobe (15 distance features) and frontal-parietal (11 distance features) lobes of the top features in the USM site. The results suggest that the MDRF can be used as a valuable feature metric to classify ASD-like neurodevelopmental disorders.

This is a repository of files related to the ReproducibiliTea Journal Club at the University of Portsmouth.

Semicontinuous data, characterized by an excess of zeros followed by a non-negative and right-skewed distribution, are frequently observed in biomedical research. Different statistical models have been proposed to investigate the association of covariates with such outcome. Motivated by the search of genetic factors associated with Neutrophil Extracellular Traps (NETs), a semicontinuous biomarker involved in thrombosis, we here investigated the impact of the selected model for semicontinuous traits in the context of a Genome Wide Association Study (GWAS). We compared three models that jointly model zero and positive values while allowing the estimation of a single association parameter of covariates with the global mean: Tobit, Negative Binomial and Compound Poisson-Gamma. We assessed the fit of these models to a sample of 657 participants of the FARIVE study measured for NETs plasma levels. For each of these three models, we performed a GWAS on NETs in FARIVE participants and results were compared. A simulation study was also conducted to evaluate the control of the type I error. Compound Poisson-Gamma and Negative Binomial models fitted NETs data observed in FARIVE better than the Tobit model. However, the Negative Binomial model suffered from an inflation of its type I error, attributable to extreme positive values of the NETs and low frequency variants. Conversely, the Compound Poisson-Gamma model was robust to both phenomena. Using the latter model, a GWAS identified a genome wide significant locus on chr21q21.3. The lead variant was rs57502213, a deletion of two nucleotides located ∼40kb upstream the non-coding RNA (miR155HG) hosting the miR-155 that was recently highlighted to have a role in NETs formation. This work indicates that the modeling strategy for a semicontinuous outcome in the framework of GWAS studies is crucial. The choice of the model should take into account the nature of the process generating zero values and the presence of extreme values. Our work also suggests that the Compound Poisson-Gamma model, while still marginally employed, can be a robust modeling strategy for GWAS analysis on a semicontinuous trait.

iLOV is an engineered flavin-binding fluorescent protein (FbFP) with applications for in vivo cellular imaging. To expand the range of applications of FbFPs for multicolor imaging and FRET-based biosensing, it is desirable to understand how to modify their absorption and emission wavelengths (i.e., through spectral tuning). There is particular interest in developing FbFPs that absorb and emit light at longer wavelengths, which has proven challenging thus far. Existing spectral tuning strategies that do not involve chemical modification of the flavin cofactor have focused on placing positively charged amino acids near flavin’s C4a and N5 atoms. Guided by previously reported electrostatic spectral tunning maps (ESTMs) of the flavin cofactor and by quantum mechanical/molecular mechanical (QM/MM) calculations reported in this work, we suggest an alternative strategy: placing a negatively charged amino acid near flavin’s N1 atom. We predict that a single-point mutant, iLOV-Q430E, has a slightly red-shifted absorption and fluorescence maximum wavelength relative to iLOV. To validate our theoretical prediction, we experimentally expressed and purified iLOV-Q430E and measured its spectral properties. We found that the Q430E mutation in iLOV results in a slight change in absorption and a 4-8 nm redshift in the fluorescence relative to iLOV, in good agreement with the computational prediction. Molecular dynamics simulations showed that the carboxylate side chain of the glutamate in iLOV-Q430E points away from the flavin cofactor, which leads to a future expectation that further red-shifting may be achieved by bringing the side chain closer to the cofactor.

Background: A significant number of patients who require surgery for benign prostatic hyperplasia are under either anticoagulation (AC) or antiplatelet (AP) therapy. Objective: To assess the efficacy and morbidity of holmium laser enucleation of the prostate (HoLEP) and bipolar transurethral enucleation of the prostate (B-TUEP) in patients who required AC/AP therapy. Design, setting, and participants: This study included 296 (67.6%) and 142 (32.4%) patients who underwent HoLEP and B-TUEP, respectively. The AC/AP group included patients whose AP therapy was not interrupted pre-, peri-, and/or postoperatively, and patients who underwent perioperative AC therapy bridging with low-molecular-weight heparin. Intervention: HoLEP and B-TUEP. Outcome measurements and statistical analysis: We tested the hypothesis that AC/AP therapy had a limited impact on the efficacy of HoLEP and B-TUEP. To adjust for potential baseline confounders, propensity-score matching was performed. Clinical characteristics were compared among groups using the Kruskal-Wallis or chi-square test. Logistic regression analyses tested the association between clinical variables and the odds of Clavien-Dindo ≥2 complications after surgery. Results and limitations: Overall, 28 (9.5%) and 46 (15.5%) patients in the HoLEP group and 15 (10.5%) and 24 (16.9%) men in the B-TUEP group had AC and AP therapy, respectively (p = 0.9). HoLEP patients under either AC or AP therapy deserved longer catheter maintenance and a longer hospital stay (HS) than those without AC/AP therapy (all p ≤ 0.01). Operative time, rates of postoperative complications, and 2-mo International Prostate Symptoms Score (IPSS) were similar between patients with and without AC/CP. Among B-TUEP patients, HS was longer (p = 0.03) and the rate of complications was higher (p < 0.001) in patients under AC or AP therapy. Postoperative haemoglobin drop and 2-mo IPSS were similar among groups and surgical techniques. Limitations are the retrospective nature of the study, and the lack of long-term complications and functional outcomes. Conclusions: HoLEP and B-TUEP can safely be performed in patients deserving continuous AP/AC therapy with only a slight increase in HS and catheterisation time. Patient summary: We assessed the safety and efficacy of holmium laser enucleation of the prostate (HoLEP) and bipolar transurethral enucleation of the prostate (B-TUEP) in men under chronic anticoagulation/antiplatelet therapy. Both HoLEP and B-TUEP could safely be performed as minimally invasive treatment options in this subset of patients at a high risk of bleeding from benign prostatic hyperplasia surgery.

Accurate and reproducible measurement of blood flow profile is very important in many clinical investigations for diagnosing cardiovascular disorders. Given that many factors could affect human circulation, and several parameters must be set to properly evaluate blood flows with phase-contrast techniques, we developed an MRI-compatible hydrodynamic phantom to simulate different physiological blood flows. The phantom included a programmable hydraulic pump connected to a series of pipes immersed in a solution mimicking human soft tissues, with a blood-mimicking fluid flowing in the pipes. The pump is able to shape and control the flow by driving a piston through a dedicated software. Periodic waveforms are used as input to the pump to move the fluid into the pipes, with synchronization of the MRI sequences to the flow waveforms. A dedicated software is used to extract and analyze flow data from magnitude and phase images. The match between the nominal and the measured flows was assessed, and the scope of phantom variables useful for a reliable calibration of an MRI system was accordingly defined. Results showed that the NO-HYPE phantom is a valuable tool for the assessment of MRI scanners and sequence design for the MR evaluation of blood flows. Graphical abstract Overview of the NOvel HYdrodynamic Phantom for the Evaluation of MRI flow measurements (NO-HYPE). Left: internal of the CompuFlow 1000 MR pump unit. Right: Setting of the NO-HYPE before a MRI acquisition session. Soft tissue mimicking material is hosted in the central part of the phantom (light blue chamber). Glass pipes pass through the chamber carrying the blood mimicking fluid.

Background and purpose In patients with acute ischemic stroke treated with reperfusion therapy we aimed to evaluate whether pretreatment blood-brain barrier (BBB) leakage is associated with subsequent hemorrhagic transformation (HT). Methods We prospectively screened patients with acute ischemic stroke treated with intravenous thrombolysis and/or endovascular treatment. Before treatment, each patient received computed tomography (CT), CT angiography, and CT perfusion. We assessed pretreatment BBB leakage within the ischemic area using the volume transfer constant (Ktrans ) value. Our primary outcome was relevant HT, defined as hemorrhagic infarction type 2 or parenchymal hemorrhage type 1 or 2. We evaluated independent associations between BBB leakage and HT using logistic regression, adjusting for age, sex, baseline stroke severity, Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6, treatment type, and onset-to-treatment time. Results We enrolled 171 patients with available assessment of BBB leakage. The patients' mean (±SD) age was 75.5 (±11.8) years, 86 (50%) were men, and the median (interquartile range) National Institutes of Health Stroke Scale score was 18 (12-23). A total of 32 patients (18%) received intravenous thrombolysis, 102 (60%) underwent direct endovascular treatment, and 37 (22%) underwent both. Patients with relevant HT (N = 31;18%) had greater mean BBB leakage (Ktrans 0.77 vs. 0.60; p = 0.027). After adjustment in the logistic regression model, we found that BBB leakage was associated both with a more than twofold risk of relevant HT (odds ratio [OR] 2.50; 95% confidence interval [CI] 1.03-6.03 per Ktrans point increase; OR 2.34; 95% CI 1.06-5.17 for Ktrans values > 0.63 [mean BBB leakage value]) and with symptomatic intracerebral hemorrhage (OR 4.30; 95% CI 1.13-13.77 per Ktrans point increase). Conclusion Pretreatment BBB leakage before reperfusion therapy was associated with HT, and may help to identify patients at risk of HT.

The full nonlinear evolution of a gravitational perturbation around a Schwarzschild anti-de Sitter black hole in Einstein-Gauss-Bonnet gravity is investigated. It is shown that the time evolution of the system is governed by a Schröedinger-type equation where the effective potential is found to be dependent on the EGB coupling constant. Under specific limits, our results recover Regge-wheeler and Zerilli equations describing massless scalar fields in Schwarzschild space-time. Our results suggest an equivalence between dispersion relation of QNMs in Gauss-Bonnet AdS black holes and AdS-waves system. Using a simple ansatz, we study the final stages of a massive scalar field in the presence of EGB gravity out of which a sonic horizon is emerged.

Purpose Glioblastoma (GBM) is associated with a poorer prognosis when leptomeningeal dissemination (LMD) occurs. Recently, the role of both ventricular entry (VE) during surgery and subventricular zone localization of tumors in promoting LMD in GBM patients has been debated. This article investigates the role of VE in causing LMD in GBM patients. Methods We conducted a retrospective analysis of GBMs operated on at our Institution between March 2018 and December 2020. We collected pre- and post-surgical images, anamnestic information, and surgical reports. Results Two hundred cases were collected. The GBM localization was periventricular in 69.5% of cases, and there was a VE during the surgical procedure in 51% of cases. The risk of post-surgical LMD in the case of VE was 16%. The rate of LMD was higher in the case of VE than not-VE (27.4% vs. 4%, p Conclusion According to our data, VE is an independent factor associated with a higher rate of post-surgical LMD, and the periventricular localization is not independently correlated to this negative outcome. Neurosurgeons should avoid VE when possible. The correct surgical strategy should be founded on balancing the need for maximal EOR and the risks associated with VE.

The proposed study has been designed to investigate the effectiveness of Truth-Lies Discussions (TLDs) (see Achieving Best Evidence Guidance, Ministry of Justice [MoJ], 2022) as an investigative interviewing strategy that promotes honesty with child victims and witnesses. The main aim is to explore whether varying the mode of presentation and the role of the protagonist in a TLD scenario promotes honesty in child witnesses. This study will also investigate the relationship between children’s conceptual understanding of truths and lies and their subsequent lie- and truth-telling behaviour.

Using a qualitative approach, this study aimed to undertake an in-depth exploration of the experiences of COVID-19 patients and their significant others among the economically weaker sections in Kashmir. The study was conducted on 18 participants of different households solely from rural Kashmir while using the purposive sampling technique to recruit the participants and the principle of data saturation to determine the sample size. Data were collected using semi-structured in-depth interviews and analyzed through Braun and Clarke’s thematic analysis framework. From the data analysis, six overarching themes of diagnosis, healthcare, treatment, survival thereof, social support and stigma were arrived at, which delineated the direct or indirect experiences of participants with COVID-19. The findings of the study revealed that the economically weaker sections of rural Kashmir are deprived of requisite healthcare facilities, which further intensifies their vulnerabilities to COVID-19 and associated health issues. They lie at the core of acute health disadvantage amid the COVID-19 crisis, and are hence drifted toward extreme marginality and socioeconomic adversity.

The non-enhancing peritumoral area (NEPA) is defined as the hyperintense region in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images surrounding a brain tumor. The NEPA corresponds to different pathological processes, including vasogenic edema and infiltrative edema. The analysis of the NEPA with conventional and advanced magnetic resonance imaging (MRI) was proposed in the differential diagnosis of solid brain tumors, showing higher accuracy than MRI evaluation of the enhancing part of the tumor. In particular, MRI assessment of the NEPA was demonstrated to be a promising tool for distinguishing high-grade gliomas from primary lymphoma and brain metastases. Additionally, the MRI characteristics of the NEPA were found to correlate with prognosis and treatment response. The purpose of this narrative review was to describe MRI features of the NEPA obtained with conventional and advanced MRI techniques to better understand their potential in identifying the different characteristics of high-grade gliomas, primary lymphoma and brain metastases and in predicting clinical outcome and response to surgery and chemo-irradiation. Diffusion and perfusion techniques, such as diffusion tensor imaging (DTI), diffusional kurtosis imaging (DKI), dynamic susceptibility contrast-enhanced (DSC) perfusion imaging, dynamic contrast-enhanced (DCE) perfusion imaging, arterial spin labeling (ASL), spectroscopy and amide proton transfer (APT), were the advanced MRI procedures we reviewed.

We propose a novel methodology to quantify the effect of stochastic interventions for a non-terminal intermediate time-to-event on a terminal time-to-event outcome. Investigating these effects is particularly important in health disparities research when we seek to quantify inequities in the timely delivery of treatment and its impact on patients’ survival time. Current approaches fail to account for time-to-event intermediates and semi-competing risks arising in this setting. Under the potential outcome framework, we define causal contrasts relevant in health disparities research and provide identifiability conditions when stochastic interventions on an intermediate non-terminal time-to-event are of interest. Causal contrasts are estimated in continuous time within a multistate modeling framework and analytic formulae for the estimators of the causal contrasts are developed. We show via simulations that ignoring censoring in intermediate and/or terminal time-to-event processes or ignoring semi-competing risks may give misleading results. This work demonstrates that a rigorous definition of the causal effects and joint estimation of the terminal outcome and intermediate non-terminal time-to-event distributions are crucial for valid investigation of interventions and mechanisms in continuous time. We employ this novel methodology to investigate the role of delaying treatment uptake in explaining racial disparities in cancer survival in a cohort study of colon cancer patients.

Despite improved outcomes of modern continuous-flow left ventricular assist devices (CF-LVADs), device exchange is still needed for various indications. While the majority of CF-LVADs are exchanged to the same model, exchange to a different pump model is occasionally warranted. In this meta-analysis, we sought to consolidate the existing evidence to better elucidate the indications and outcomes in these cases. A comprehensive systematic search of adult patient cohorts who underwent CF-LVAD exchange to a different CF-LVAD model was performed. Study-level data from 10 studies comprising 98 patients were extracted and pooled for analysis. Mean patient age was 58 (95% CI: 48-65) and 81% were male. Indication for initial CF-LVAD was ischemic cardiomyopathy in 45% (34-57). Initial device was HeartMate II LVAD (HMII) in 93 (94.9%) and HeartWare HVAD (HW) in 5 (5.1%) patients. After mean CF-LVAD support time of 18.8 (15.2-22.4) months, exchange indications included thrombosis in 71% (43-89), infection in 21% (8-47) and device malfunction in 12% (7-21). HMII to HW exchange occurred in 53 (54.1%) patients, HMII to HeartMate III (HM3) in 32 (32.7%), and HM II to either HW or HM3 in 13 (13.2%) patients. Postoperatively, right ventricular assist device was required in 16% (8-32). Overall, 20% (8-40) of patients experienced a stroke, while HW patients had a significantly higher stroke incidence than HM3 patients (HW: 21% (8-47) vs. HM3: 5% (1-24), P < .01). Overall 30-day mortality was 10% (6-17), while HW had a significantly worse 30-day mortality than HM3 (HW: 13% (7-24) vs. HM3: 5% (1-24), P = .03). Following device exchange from a different CF-LVAD model, HM3 is associated with lower stroke and higher survival when compared to HW.

d-2-Hydroxyglutarate dehydrogenase from Pseudomonas aeruginosa PAO1 (PaD2HGDH) catalyzes the oxidation of d-2-hydroxyglutarate to 2-ketoglutarate, which is a necessary step in the serine biosynthetic pathway. The dependence of P. aeruginosa on PaD2HGDH makes the enzyme a potential therapeutic target against P. aeruginosa. In this study, recombinant His-tagged PaD2HGDH was expressed and purified to high levels from gene PA0317, which was previously annotated as an FAD-binding PCMH-type domain-containing protein. The enzyme cofactor was identified as FAD with fluorescence emission after phosphodiesterase treatment and with mass spectrometry analysis. PaD2HGDH had a kcat value of 11 s-1 and a Km value of 60 μM with d-2-hydroxyglutarate at pH 7.4 and 25 °C. The enzyme was also active with d-malate but did not react with molecular oxygen. Steady-state kinetics with d-malate and phenazine methosulfate as an electron acceptor established a mechanism that was consistent with ping-pong bi-bi steady-state kinetics at pH 7.4. A comparison of the kcat/Km values with d-2-hydroxyglutarate and d-malate suggested that the C5 carboxylate of d-2-hydroxyglutarate is important for the substrate specificity of the enzyme. Other homologues of the enzyme have been previously grouped in the VAO/PMCH family of flavoproteins. PaD2HGDH shares fully conserved residues with other α-hydroxy acid oxidizing enzymes, and these conserved residues are found in the active site of the PaD2HDGH homology model. An Enzyme Function Initiative-Enzyme Similarity Tool Sequence Similarity Network analysis suggests a functional difference between PaD2HGDH and human D2HGDH, and no relationship with VAO. A phylogenetic tree analysis of PaD2HGDH, VAO, and human D2HGDH establishes genetic diversity among these enzymes.

Objective To assess the most frequent clinical features of Multisystem Inflammatory Syndrome in children (MIS-C) at presentation to the Emergency Department (ED) in a large multicenter cohort of patients, in order to define useful tools for a timely diagnosis.MethodsClinical and laboratory characteristics were retrospectively reviewed for 210 MIS-C patients from 18 Italian pediatric EDs. We assessed correlations between clinical and laboratory parameters and compared features of patients of different age (≤5 years and >5 years). ResultsFever was the main presenting symptom (100%), followed by conjunctivitis (46%), abdominal pain (44%), vomit (41%) and diarrhea (39%). Forty-nine percent of children presented to the ED in critical or nearly critical conditions. A higher prevalence of mucocutaneous involvement was found in younger children (69% versus 47%, p5 years (62% versus 85%, ppConclusionsApart from fever, most common MIS-C manifestations at presentation to the ED are conjunctivitis, abdominal pain, vomit and diarrhea. Younger children more frequently present with mucocutaneous involvement, while gastrointestinal manifestations are more common in older patients. These findings should be considered when MIS-C is suspected in the ED, in order to achieve a timely recognition of the condition.

Com o barateamento e a instalação de dispositivos IoT, embarcados, sensores e GPS em ônibus públicos, uma grande quantidade de dados pode se gerada e utilizada como base para tomadas de decisão. Entretanto se os dados forem afetados por erros e incertezas tais análises podem ser inválidas. Este trabalho apresenta um protótipo com um método de Map Matching para detectar e extrair dados de Streaming de trajetórias GPS em uma rede de transporte e seus pontos de ônibus. O artigo utiliza conceitos de Sistemas de Informações Geográficas, Map Matching,Sistemas de Transportes Inteligentes e Cidades Inteligentes. Testes realizados em dados de Streaming de trajetórias de GPS de transporte público de Curitiba ilustraram a eficiência da metodologia do algoritmo de Map Matching (usando as trajetórias de GPS de veículos e seus pontos de ônibus), além de indicar fatores para melhoria dos dados.

A cada uma hora cinco pessoas são vítimas fatais de acidentes de trânsito no Brasil. Entre os anos de 2008 e 2016, mais de 350 mil pessoas morreram vítimas de acidentes nas estradas e ruas no país. Nesta direção este artigo propõe um protótipo para sugerir itinerários seguros, baseado em dados abertos, com a finalidade de reduzir a probabilidade do usuário se envolver em um acidente em uma rodovia federal. Para isso, a aplicação utiliza uma plataforma web paravisualizar informações sobre rotas seguras e rotas mais rápidas.

Many forms of love, from intimate friendships to obsessive attachment, are characterized by a pattern of synchronous and increased behavioral activity and increased neural activity in the mesolimbic dopamine system. This suggests that dopamine neurons may play an important role in mediating and rewarding behaviors that are contingent on the presence of a social partner. This hypothesis is based on the fact that dopamine neurons are responsive to social stimuli and reward stimuli associated with social behavior and are altered by social experience. Importantly, there is increasing evidence that dopamine plays a key role in mediating many forms of social behavior. The dopamine system has a high density of dopamine receptors in regions involved with reward processing and reinforcement learning, such as the striatum. These regions may mediate the reinforcing effects of social interaction and possibly mediate some forms of social attachment, such as those involved in pair bonding. Future research that tests this hypothesis will have important implications for understanding the neural substrates of the natural rewards associated with the formation and maintenance of attachments to other individuals , which could provide important insights into the neural mechanisms involved in psychiatric disorders.