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Background The current childhood obesity pandemic is likely to result in an increased risk of chronic kidney disease (CKD) later in life. Correlations between obesity-related comorbidities and kidney function can be found, but it is unclear to what extent this is caused by bias due to different mathematical forms of the estimated glomerular filtration rate (eGFR) equations. The present study aimed to analyze correlations between obesity-related comorbidities and different eGFR equations and to investigate whether rescaled serum creatinine (SCr/Q) for sex and age or height might be an alternative biomarker for kidney function estimation. Methods This cross-sectional cohort study included 600 children with overweight and obesity. Mean age was 12.20 ± 3.28 years, 53.5% were female, and mean BMI z-score was 3.31 ± 0.75. All children underwent a comprehensive assessment that included anthropometrical and blood pressure measurements, laboratory examination, air displacement plethysmography, and polysomnography. Qage and Qheight polynomials were used to rescale SCr and multiple creatinine-based eGFR equations were compared. Results SCr/Q and almost all GFR estimations significantly correlated with a waist-to-hip ratio, fat mass, homeostasis model assessment for insulin resistance, and triacylglyceride, HDL cholesterol, alanine transaminase, and serum uric acid concentrations. Multiple correlations, however, were not confirmed by all equations, which suggests dependency on the mathematical form of the different eGFR equations. Conclusions Correlations between obesity-related comorbidities and creatinine-based eGFR are present in children with overweight and obesity, but depend to a large extent on the eGFR equation of choice. SCr/Q might be an alternative biomarker for assessing correlations between obesity-related comorbidities and kidney function in children with overweight and obesity. Graphical Abstract

Aims There is considerable controversy regarding optimal management of patients with paraesophageal hiatus hernia (pHH). This survey aims at identifying recommended strategies for work-up, surgical therapy, and postoperative follow-up using Delphi methodology. Methods We conducted a 2-round, 33-question, web-based Delphi survey on perioperative management (preoperative work-up, surgical procedure and follow-up) of non-revisional, elective pHH among European surgeons with expertise in upper-GI. Responses were graded on a 5-point Likert scale and analyzed using descriptive statistics. Items from the questionnaire were defined as “recommended” or “discouraged” if positive or negative concordance among participants was > 75%. Items with lower concordance levels were labelled “acceptable” (neither recommended nor discouraged). Results Seventy-two surgeons with a median (IQR) experience of 23 (14–30) years from 17 European countries participated (response rate 60%). The annual median (IQR) individual and institutional caseload was 25 (15–36) and 40 (28–60) pHH-surgeries, respectively. After Delphi round 2, “recommended” strategies were defined for preoperative work-up (endoscopy), indication for surgery (typical symptoms and/or chronic anemia), surgical dissection (hernia sac dissection and resection, preservation of the vagal nerves, crural fascia and pleura, resection of retrocardial lipoma) and reconstruction (posterior crurorrhaphy with single stitches, lower esophageal sphincter augmentation (Nissen or Toupet), and postoperative follow-up (contrast radiography). In addition, we identified “discouraged” strategies for preoperative work-up (endosonography), and surgical reconstruction (crurorrhaphy with running sutures, tension-free hiatus repair with mesh only). In contrast, many items from the questionnaire including most details of mesh augmentation (indication, material, shape, placement, and fixation technique) were “acceptable”. Conclusions This multinational European Delphi survey represents the first expert-led process to identify recommended strategies for the management of pHH. Our work may be useful in clinical practice to guide the diagnostic process, increase procedural consistency and standardization, and to foster collaborative research.

BACKGROUND: There is a lack of evidence on acute kidney injury (AKI) and new-onset chronic kidney disease (CKD) after surgery for localised renal masses (LRMs) in patients with two kidneys and preserved baseline renal function. OBJECTIVE: To evaluate the prevalence and risk of AKI and new-onset clinically significant CKD (csCKD) in patients with a single renal mass and preserved renal function after being treated with partial (PN) or radical (RN) nephrectomy. DESIGN SETTING AND PARTICIPANTS: We queried our prospectively maintained databases to identify patients with a preoperative estimated glomerular filtration rate (eGFR) of ≥60 ml/min/1.73 m2 and a normal contralateral kidney who underwent PN or RN for a single LRM (cT1-T2N0M0) between January 2015 and December 2021 at four high-volume academic institutions. INTERVENTION: PN or RN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcomes of this study were AKI at hospital discharge and the risk of new-onset csCKD, defined as eGFR

After the Portuguese Colonial War (PCW), some research was conducted to examine PCW veterans' combat exposure, as well as their report of mental and physical health problems. Research revealed that the PCW left, and still presents, deep psychological and physical marks for many veterans. However, after 47 years, there is no available information regarding the most frequently used, as well as the most reliable and valid tools that measure these outcomes. This information is essential for researchers and clinicians to help them choose the most feasible measures to assess current and potential future veterans. To address this issue, this scoping review synthesizes information on preference and psychometric robustness of measures that assess combat exposure, mental and physical health problems in PCW veterans. Following PRISMA-ScR guidelines, searches were conducted, in May 2021; in five electronic databases for the inclusion of Portuguese or English quantitative, qualitative, or mixed-method peer reviewed studies or gray literature. Fifty-six studies were identified; 40 were considered eligible. Of the identified measures, only three were validated for PCW veterans, namely, the Exposure to Combat Severity Scale, Combat Distress Scale, and Posttraumatic Stress Disorder Checklist-Military Version. Currently, these reveal to be the most valid and reliable measures to assess combat exposure, emotional distress, and posttraumatic stress symptoms. However, findings also revealed a need for further development, adaptation or validation of self-report measures, especially regarding physical health problems. These will help clinicians and researchers to enhance their quality of assessment., The authors thank the Ministry of National Defense for partially funding this project. The authors declare that they have no conflicts of interest. This study was conducted at the Psychology Research Centre (CIPsi/UM) School of Psychology, University of Minho, and supported partially by the Portuguese Ministry of National Defense and partially by the Foundation for Science and Technology (FCT) through the Portuguese State Budget (UIDB/01662/2020). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article.

With a constant push to shrink size and elevate power density, the heat flux in GaN-based devices is drastically intensified, requiring effective cooling to control junction temperature. This work presents an embedded manifold microchannel cooling (EMMC) arrangement targeted at mitigating junction temperature, in which microchannels are directly etched in the GaN substrate to extract heat generated due to self-heating. The single-phase laminar flow of deionized water through near-junction microchannels has been investigated in a unit-cell mimicking a recently reported GaN power converter with EMMC arrangement. The effects of geometrical parameters of the manifold and microchannel, heat flux and flow rate on the thermal-hydraulic performance of the unit-cell model are thoroughly studied. High heat transfer coefficients in the order of 10(5) W/(m(2).K) associated with the near-junction microfluidic single-phase flow are acquired, which demonstrates the excellent heat extraction capability of EMMC applied to GaN-based devices. The unit-cell model in the prediction of the thermal performance of a large-scale EMMC multifinger GaN device is in good agreement with experiment and capable of providing detailed fluid flow and temperature distributions for design optimization. Furthermore, a capped diamond heat spreader is integrated with the EMMC GaN device to reduce junction thermal spreading resistance. It is shown that high die heat flux in the range 0.86-3.01 kW/cm(2) can be effectively removed for the 10-mu m-thick diamond capped GaN-on-SiC EMMC device within a junction temperature range 48-110 degrees C. This new EMMC arrangement complemented with capped diamond holds promise as an ultimate near-junction cooling solution that facilitates the implementation and development of high-power compact GaN-based devices.

We consider the effect that an upstream cylinder has on the effective inertial collection efficiency of a downstream cylinder. We consider an initially uniform distribution of particles moving past a cylindrical fiber in a potential crossflow and numerically calculate the resulting particle distribution far downstream of the fiber using finite differences. We then investigate the effect that the downstream distribution of particles has on the effective inertial collision efficiency of a downstream test cylinder oriented parallel to the first. We show that the effective collision efficiency of the test cylinder depends on its relative offset in the transverse direction (normal to the flow) with respect to the upstream cylinder. For relatively small offsets there is complete shielding, and no particles collide with the test cylinder. As the offset increases, a growing effective collision efficiency is observed leading to a significant enhancement relative to the collision efficiency of an isolated cylinder for intermediate offsets and Stokes numbers close to unity. Importantly, we observe relative gains in effective collision efficiency above 100% for a range of Stokes number and offset values. For larger offsets and Stokes numbers, the effect of the upstream cylinder on the effective collision efficiency of the test cylinder decreases and eventually becomes negligible. Detailed results are provided for Stokes drag acting on the particles and we also show that a non-linear drag has negligible effect on the observed trends for the conditions relevant to filtration systems. These results suggest that the arrangement of fibers has a substantial effect on inertial particle impaction even when neighboring fibers do not alter the flow field around each individual collector. Moreover, periodic arrangements with specific orientations with respect of the flow could lead to a significant enhancement of the inertial collision of particles on an array of collectors, thus contributing towards a better filtration performance.

In this study, artificial neural network (ANN) was used to predict forced convection heat transfer enhancement from microscale pin fin heat sinks under various operating conditions and at different geometries. Experimental data acquired from the literature were employed to train the ANN model. Different numbers of training cycles, layers, and neurons in the network were investigated to design an effective neural network. The performance of the trained network was tested using the mean squared error and the most accurate one was selected to predict the average Nusselt number. Mean absolute percentage errors between the ANN output and the experimental datapoints were calculated and compared with the existing correlations. This machine learning method offers significant improvement for thermal performance prediction and could be a reliable tool for determining convective heat transfer in microscale pin fin heat sinks.

We report QDπ-v1.0 for modeling the internal energy of drug molecules containing H, C, N, and O atoms. The QDπ model is in the form of a quantum mechanical/machine learning potential correction (QM/Δ-MLP) that uses a fast third order self-consistent density-functional tight-binding (DFTB3/ 3OB) model that is corrected to a quantitatively high-level of accuracy through a deep-learning potential (DeepPot-SE). The model has the advantage that it is able to properly treat electrostatic interactions and handle changes in charge/protonation states. The model is trained against reference data computed at the ωB97X/6-31G* level (as in the ANI-1x data set) and compared to several other approximate semiempirical and machine learning potentials (ANI-1x, ANI-2x, DFTB3, MNDO/d, AM1, PM6, GFN1-xTB, and GFN2-xTB). The QDπ model is demonstrated to be accurate for a wide range of intra-and intermolecular interactions (despite its intended use as an internal energy model) and has shown to perform exceptionally well for relative protonation/deprotonation energies and tautomers. An example application to model reactions involved in RNA strand cleavage catalyzed by protein and nucleic acid enzymes illustrates QDπ has average errors less than 0.5 kcal/mol, whereas the other models compared have errors over an order of magnitude greater. Taken together, this makes QDπ highly attractive as a potential force field model for drug discovery., This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Chemical Theory and Computation, copyright © 2023 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.jctc.2c01172

Immunogenic cell death (ICD) refers to an immunologically distinct process of regulated cell death that activates, rather than suppresses, innate and adaptive immune responses. Such responses culminate into T cell-driven immunity against antigens derived from dying cancer cells. The potency of ICD is dependent on the immunogenicity of dying cells as defined by the antigenicity of these cells and their ability to expose immunostimulatory molecules like damage-associated molecular patterns (DAMPs) and cytokines like type I interferons (IFNs). Moreover, it is crucial that the host's immune system can adequately detect the antigenicity and adjuvanticity of these dying cells. Over the years, several well-known chemotherapies have been validated as potent ICD inducers, including (but not limited to) anthracyclines, paclitaxels, and oxaliplatin. Such ICD-inducing chemotherapeutic drugs can serve as important combinatorial partners for anti-cancer immunotherapies against highly immuno-resistant tumors. In this Trial Watch, we describe current trends in the preclinical and clinical integration of ICD-inducing chemotherapy in the existing immuno-oncological paradigms. ispartof: ONCOIMMUNOLOGY vol:12 issue:1 ispartof: location:United States status: accepted

Owing to growing uncontrolled land-use change and urban expansion, farmers in urban fringes are struggling to sustain their livelihood. Farmers have been expressing their dissatisfaction at different times. This study analyzes the stakeholders' perspectives on the causes and outcomes of farmers' resistance to land-use change and urban expansion processes by zooming in on Bahir Dar, Ethiopia. The paper is based on focus group discussions with farmers in the neighboring villages, local agricultural extension experts, and, subsequently, key informant interviews of local government officials. Juxtaposing farmers' and local experts' positions reveals that inadequate compensations during land expropriation, lack of good governance in the urban expansion process, and inaccessibility of infrastructures are primary reasons for the farmers' struggle against urban expansion in the urban fringes. This study provides insights into the consequences of unplanned urban development challenges and may inform research and policymaking on sustainable urban development in the area and beyond.

ispartof: EXPERT REVIEW OF VACCINES vol:22 issue:1 pages:518-519 ispartof: location:England status: accepted

ispartof: ENERGY REPORTS vol:9 pages:2169-2184 status: accepted

Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative condition. Despite significant advances in pre-clinical models that enhance understanding of disease pathobiology, translation of candidate drugs to effective human therapies has been disappointing. There is increasing recognition of the need for a precision medicine approach toward drug development, as many failures in translation can be attributed in part to disease heterogeneity in humans. PRECISION-ALS is an academic industry collaboration between clinicians, Computer Scientists, Information engineers, technologists, data scientists and industry partners that will address the key clinical, computational, data science and technology associated research questions to generate a sustainable precision medicine based approach toward new drug development. Using extant and prospectively collected population based clinical data across nine European sites, PRECISION-ALS provides a General Data Protection Regulation (GDPR) compliant framework that seamlessly collects, processes and analyses research-quality multimodal and multi-sourced clinical, patient and caregiver journey, digitally acquired data through remote monitoring, imaging, neuro-electric-signaling, genomic and biomarker datasets using machine learning and artificial intelligence. PRECISION-ALS represents a first-in-kind modular transferable pan-European ICT framework for ALS that can be easily adapted to other regions that face similar precision medicine related challenges in multimodal data collection and analysis. ispartof: AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION vol:24 issue:5-6 ispartof: location:England status: Published online

What Is Known? In elderly inpatients, potential inappropriate medication (PIM) is a prominent prescription challenge. However, there is limited information available regarding PIM in patients with central nervous system (CNS) diseases in China. Objective. To evaluate and improve the rational use of drugs for the treatment of CNS diseases in elderly inpatients. Method. A retrospective, cross-sectional study was conducted among elderly inpatients (≥65 years) admitted to the Ninth People’s Hospital of Zhengzhou in China from March 2020 to March 2021. PIM was identified based on the 2019 Beers criteria at admission and discharge. The patients recruited in March 2020 were considered a baseline group, which was used as a comparison to evaluate PIM of CNS disease-related drugs in June 2020, September 2020, December 2020, and March 2021. Results. A total of 1500 patients were included in the evaluation. There was a statistically significant difference in the number of average hospitalization days, drug varieties used, and PIM detection ( p < 0.05 ), as determined by X2 test. A total of 332 cases of PIM were identified, and 226 cases were detected for the interaction with CNS disease dementia. Multifactor logistic regression analysis showed that male, length of stay ≥15 days, and >10 medication types were risk factors for the occurrence of PIM ( p < 0.05 ). After clinical supervision and training based on the High-Risk Drug Replacement Program for the Elderly, the rate of irrational medication under medical advice decreased from 34.67% in March 2020 to 14.0% ( p < 0.001 ) in March 2021. What Is New and Conclusion. There was certain rationality based on the High-Risk Drug Replacement Program for the Elderly, and the rates of selective serotonin reuptake inhibitor, 5-hydroxylamine/norepinephrine re-intake inhibitor, rotenone, quetiapine, and proton pump inhibitor use were improved. These results provide a reference for the continuous improvement of the PIM catalog for elderly patients.

The world's seas and oceans contain vast amounts of lithium, but the low concentration hereof renders solvent extraction impractical for its recovery. By contrast, seawater desalination brine, after treatment by nanofiltration, contains a roughly tenfold greater concentration of lithium than raw seawater. Hence, lithium can be effectively recovered from such streams using solvent extaction. Compared with other techniques to sequester lithium from dilute solutions, solvent extraction offers the advantages of simple operations, robust and well-established technology and high recovery yields. Thus, we propose a solvent-extraction based process to recover lithium from seawater desalination brine, treated by nanofiltration. The first step comprises the removal of magnesium and calcium using methyltrioctylammonium neodecanoate in p-cymene. This is followed by a lithium extraction step using the extractants Mextral 54–100 and Cyanex 923 in Shellsol D70 diluent. The lithium extract is then scrubbed with water and stripped with hydrochloric acid. Subsequently, residual alkaline earth metals are removed with sodium hydroxide in ethanol and finally lithium is precipitated using sodium carbonate. The solvent extraction, scrubbing and stripping steps were demonstrated on mini-pilot scale in continuous countercurrent mode (in mixer-settlers), while the precipitation steps were demonstrated in batch. The process was found to have an overall yield of 74%, affording a lithium carbonate product with a purity of 97 wt%.

Background There is evidence for a polygenic contribution to psychosis. One targetable mechanism through which polygenic variation may impact on individuals and interact with the social environment is stress sensitization, characterized by elevated reactivity to minor stressors in daily life. The current study aimed to investigate whether stress reactivity is modified by polygenic risk score for schizophrenia (PRS) in cases with enduring non-affective psychotic disorder, first-degree relatives of cases, and controls. Methods We used the experience sampling method to assess minor stressors, negative affect, positive affect and psychotic experiences in 96 cases, 79 first-degree relatives, i.e. siblings, and 73 controls at wave 3 of the Dutch Genetic Risk and Outcome of Psychosis (GROUP) study. Genome-wide data were collected at baseline to calculate PRS. Results We found that associations of momentary stress with psychotic experiences, but not with negative and positive affect, were modified by PRS and group (all pFWEv. low level of PRS. By contrast, controls with high PRS showed more intense psychotic experiences in response to stress compared to those with low PRS. Conclusions This tentatively suggests that polygenic risk may operate in different ways than previously assumed and amplify reactivity to stress in unaffected individuals but operate as a resilience factor in relatives by attenuating their stress reactivity.

Part of the appeal of attachment language is that it feels near to our everyday experience, as terms like 'attachment', 'security' or 'disorganisation' feel readily recognisable. Yet, not one of these terms is used by academic attachment researchers in line with ordinary language. This has hindered the evidence-based use of attachment in practice, the feedback loop from practice to research and the dialogue between attachment researchers in developmental psychology and in social psychology. This paper pinpoints the difficulties arising from the existence of multiple versions of 'attachment theory' that use exactly the same terms, held by communities that assume that they are referring to the same thing and with little infrastructure to help them discover otherwise. When we talk past one another, the different communities with a stake in knowledge of attachment are obstructed from genuinely learning from one another, drawing on their respective strengths and pursuing collaborations. One factor contributing to this situation has been the use of attachment terminology with technical meanings, but often without setting out clear definitions. We here introduce a guide to attachment terminology used by the academic community, which has recently been published on the website of the Society for Emotion and Attachment Studies. The guide is meant for researchers, clinicians and everyone concerned with attachment to increase understanding of the technical meaning of important terminology used by researchers, and support the quality of discussions between researchers, and between researchers and clinicians and other publics. ispartof: JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY vol:64 issue:5 pages:839-843 ispartof: location:England status: published

Available online 20 March 2023, Liquid properties, such as, surface tension and viscosity are important parameters as they control gas-liquid mass transfer in bioprocesses. An oscillatory flow reactor provided with smooth periodic constrictions (OFR-SPC) was considered to evaluate its potential for mass transfer performance in non-pure gas-liquid systems. The effect of surface tension and viscosity on the volumetric (kLa) and liquid-side mass transfer coefficients (kL), interfacial area, (a), gas holdup (G) and bubbles dynamics were investigated under different operational conditions (oscillation amplitude (x0) and frequency (f) and superficial gas velocity (ug)). Two liquid phases, ethanol and sucrose aqueous solutions covering a range of surface tension and viscosity values were used. For the bubble size distribution (BSD) measurements an image analysis technique was used. A Design of Experiment (DoE) methodology was implemented in this work to establish the relation of x0, f, ug, surface tension and viscosity with kLa. According to the results, changes in the liquid properties and operational conditions showed marked effects on bubbles size and mass transfer. However, surface tension and viscosity had no significant influence on G, contrary to the reported for common contactors, where G increased in the presence of ethanol and decreased at moderate/high viscosities. Moreover, it was found that increasing the oscillatory movement notably improved kL, and kLa (2 to 6-fold), either in ethanol or sucrose solutions, compared to common reactors, even with moderate power consumption (~105 W m-3). This improvement resulted from the bubbles breakage, which originates bubbles with small and approximately the same size (homogeneous regime) enhancing a, instead, lower oscillations resulted in large bubbles (heterogeneous regime). The results demonstrate that the OFR-SPC can ensure outstanding mass transfer rates, with potential and feasibility for use in gas-liquid bioprocesses, where mass transfer and liquid properties are important., This work was financially supported by: I) Project PTDC/QEQ-PRS/3787/2014 -POCI-01–0145-FEDER-016816 - funded by the European Regional Development Fund (ERDF) through COMPETE2020 -Programa Operacional Competitividade e Internacionalização (POCI) and by national funds through Fundaç ão para a Ciência e a Tecnologia.I.P. (FCT) - Project 9471 - Reforçar a Investigaç ão,o Desenvolvimento Tecnológico e a Inovaç ão; II) IF exploratory Project [IF/01087/2014] funded by FCT; III) LA/P/0045/2020 (ALiCE), UIDB/00511/2020 and UIDP/00511/2020 (LEPABE), funded by national funds through FCT/MCTES (PIDDAC); IV) the FCT under the scope of the strategic funding of UIDB/04469/2020 unit, and by LABBELS – Associate Laboratory in Biotechnology, Bioengineering and Microelectromechnaical Systems, LA/P/0029/2020. A. Ferreira is an Investigador FCT. F. Almeida would wish to thank to FCT for PhD scholarship 2020.05246. BD., info:eu-repo/semantics/publishedVersion

OBJECTIVES: In biomedical research, spin is the overinterpretation of findings, and it is a growing concern. To date, the presence of spin has not been evaluated in prognostic model research in oncology, including studies developing and validating models for individualized risk prediction. STUDY DESIGN AND SETTING: We conducted a systematic review, searching MEDLINE and EMBASE for oncology-related studies that developed and validated a prognostic model using machine learning published between 1st January, 2019, and 5th September, 2019. We used existing spin frameworks and described areas of highly suggestive spin practices. RESULTS: We included 62 publications (including 152 developed models; 37 validated models). Reporting was inconsistent between methods and the results in 27% of studies due to additional analysis and selective reporting. Thirty-two studies (out of 36 applicable studies) reported comparisons between developed models in their discussion and predominantly used discrimination measures to support their claims (78%). Thirty-five studies (56%) used an overly strong or leading word in their title, abstract, results, discussion, or conclusion. CONCLUSION: The potential for spin needs to be considered when reading, interpreting, and using studies that developed and validated prognostic models in oncology. Researchers should carefully report their prognostic model research using words that reflect their actual results and strength of evidence. ispartof: JOURNAL OF CLINICAL EPIDEMIOLOGY vol:157 pages:120-133 ispartof: location:United States status: published

Background The impact of extent of resection (EOR), residual tumor volume (RTV), and gross-total resection (GTR) in glioblastoma subgroups is currently unknown. This study aimed to analyze their impact on patient subgroups in relation to neurological and functional outcomes. Methods Patients with tumor resection for eloquent glioblastoma between 2010 and 2020 at 4 tertiary centers were recruited from a cohort of 3919 patients. Results One thousand and forty-seven (1047) patients were included. Higher EOR and lower RTV were significantly associated with improved overall survival (OS) and progression-free survival (PFS) across all subgroups, but RTV was a stronger prognostic factor. GTR based on RTV improved median OS in the overall cohort (19.0 months, P Conclusions Maximum resection was especially beneficial in the subgroups aged

BACKGROUND: Training the plantar intrinsic foot muscles (PIFMs) has the potential to benefit patients with lower extremity musculoskeletal conditions as well as the aged population. Isolated foot exercises, often standard in clinical practice, are difficult to perform, whereas functional exercises are much easier to accomplish. However, it is unclear whether functional exercises are comparable to isolated foot exercises in activating the PIFMs. OBJECTIVE: This study aims to compare the activation of PIFMs between functional exercises versus isolated foot exercises. METHODS: Using surface electromyography (EMG), muscle activation of three PIFMs was measured in four functional exercises (i.e. normal/unstable toe stance, toe walking, and hopping) versus a muscle-specific isolated foot exercise in 29 younger adults, resulting in 12 comparisons. RESULTS: Functional exercises showed larger mean EMG amplitudes than the isolated foot exercises in 25% of the 12 comparisons, while there was no difference in the remaining 75%. CONCLUSION: Functional exercises provoked comparable or even more activation of the PIFMs than isolated foot exercises. Given that functional exercises are easier to perform, this finding indicates the need to further investigate the effectiveness of functional exercises in physical therapy to improve muscle function and functional task performance in populations that suffer from PIFM weakness or dysfunction. ispartof: PHYSIOTHERAPY THEORY AND PRACTICE ispartof: location:England status: Published online

ACS omega 8(15), 13690 - 13701 (2023). doi:10.1021/acsomega.2c07869, L10-ordered FeNi, tetrataenite, found naturally in meteorites is a predilection for next-generation rare-earth free permanent magnetic materials. However, the synthesis of this phase remains unattainable in an industrially relevant time frame due to the sluggish diffusion of Fe and Ni near the order–disorder temperature (593 K) of L1$_0$ FeNi. The present work describes the synthesis of ordered L1$_0$ FeNi from elemental Fe and Ni powders by mechanical alloying up to 12 h and subsequent heat treatment at 623 K for 1000 h without a magnetic field and for 4 h in the presence of 1.5 T magnetic field. Also, to address the ambiguity of L1$_0$ phase identification caused by the low difference in the X-ray scattering factor of Fe and Ni, synchrotron-based X-ray diffraction is employed, which reveals that 6 h milling is sufficient to induce L1$_0$ FeNi formation. Further milling for 12 h is done to achieve a chemically homogeneous powder. The phase fraction of L1$_0$-ordered FeNi is quantified to ∼9 wt % for 12 h milled FeNi, which increases to ∼15 wt % after heat treatment. Heat treatment of the milled powder in a magnetic field increases the long-range order parameter (S) from 0.18 to 0.30. Further, the study of magnetic properties reveals a decrease in magnetic saturation and a slight increase in coercivity with the increase in milling duration. At the same time, heat treatment in the magnetic field shows a considerable increase in coercivity., Published by ACS Publications, Washington, DC

OBJECTIVE: This meta-analysis assesses cognitive functioning in children with acute lymphoblastic leukemia post-treatment who were treated with either chemotherapy-only (CT-only) or in combination with radiation therapy (CTRT). METHODS: The databases Pubmed and PsychInfo were searched between 1-1-2000 and 31-12-2021. Data were analyzed using Comprehensive Meta-Analysis (version 2). RESULTS: Mean weighted intelligence after treatment was 100.2 (number of studies n = 51, 95% CI: 98.8-101.5). For CT-only, it was 100.8 (95% CI: 99.5-102.2) and for CTRT 97.8 (95% CI: 95.9-100.2). Compared to recruited healthy controls, treated children had on average lower IQ scores (n = 23, mean difference -7.8, 95% CI: -10.7 to -5.0, p

BACKGROUND: Response rates of immune checkpoint inhibitor (ICI) therapy for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are low. PATIENTS AND METHODS: This retrospective multicentre cohort study evaluates the predictive and prognostic value of weight loss and changes in body composition prior and during therapy. Patient, tumor, and treatment characteristics of 98 patients were retrieved, including neutrophil and platelet-lymphocyte-ratio (NLR and PLR). Programmed death-ligand 1 (PD-L1) expression was determined on residual material. Cachexia was defined according to Fearon et al. (2011). Skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were evaluated on computed tomography scans at the third lumbar vertebrae level. Univariable and multivariable regression analyses were performed for 6 months progression free survival (PFS6m) and overall survival (OS). RESULTS: Significant early weight loss (>2%) during the first 6 weeks of therapy was shown in 34 patients (35%). This patient subgroup had a significantly higher NLR and PLR at baseline. NLR and PLR were inversely correlated with SM and VAT index. Independent predictors of PFS6m were lower World Health Organization performance status (HR 0.16 [0.04-0.54] p = 0.003), higher baseline SAT index (HR 1.045 [1.02-1.08] p = 0.003), and weight loss 2% early weight loss remained a predictor of OS, independent of PD-L1 expression (HR 2.09 [1.11-3.92] p = 0.02, HR 2.18 [1.13-4.21] p = 0.02). CONCLUSION: We conclude that the combination of cachexia at baseline and weight loss during ICI therapy is associated with worse OS in R/M HNSCC patients, independent of PD-L1 expression. ispartof: CANCER MEDICINE vol:12 issue:7 pages:7699-7712 ispartof: location:United States status: published

Background Drug eluting stents (DES) are associated with a 2% to 4% annual rate of target lesion failure through 5-to-10-year follow-up. The presence of a metallic protheses is a trigger for neo-atherosclerosis and very late stent thrombosis. A "leave nothing behind" strategy using Drug Coated Balloons has been suggested; however, paclitaxel coated balloons are only recommended in selected indications. Recently a novel sirolimus eluting balloon, the SELUTION SLR TM 014 PTCA balloon (SEB) (M.A. MedAlliance SA, Nyon, Switzerland) has been developed.Hypothesis A strategy of percutaneous coronary intervention (PCI) with SEB and provisional DES is non-inferior to a strategy of systematic DES on target vessel failure (TVF) at one and five years. If non-inferiority is met at 5 years, superiority will be tested.Design SELUTION DeNovo is a multi-center international open-label randomized trial. Subjects meeting eligibility criteria are randomized 1:1 to treatment of all lesions with either SEB and provisional DES or systematic DES. Major inclusion criteria are PCI indicated for >= 1 lesion considered suitable for treatment by either SEB or DES and clinical presentation with chronic coronary syndrome, unstable angina or non-ST segment elevation myocardial infarction (NSTEMI). There is no limitation in the number of lesions to be treated. Target lesions diameters are between 2 and 5 mm. Major exclusion criteria are lesions in the left main artery, chronic total occlusions, ST segment elevation myocardial infarction and unstable non-ST segment elevation myocardial infarction. Three thousand three hundred twenty six patients will be included in 50 sites in Europe and Asia. TVF rates and their components will be determined at 30 days, 6 months and annually up to 5 years post-intervention. Among secondary endpoints, bleeding events, cost-effectiveness data and net clinical benefits will be assessed.Summary SELUTION DeNovo trial is an open-label, multi-center international randomized trial comparing a strategy of PCI with SEB and provisional DES to a strategy of PCI with systematic DES on TVF at one and five years. Non-inferiority will be tested at one and five years. If non-inferiority is met at five years, superiority will be tested. (Am Heart J 2023;258:77-84.) The SELUTION DeNovo trial is funded by MedAlliance CardioVascular SA, Rue de Rive 5, 1260 Nyon, Switzerland.

The geochemical signature in alluvial soils is a witness of human activities that took place in a river catchment. Sampling of alluvial soils at depth, in combination with information on sedimentological history and age of samples, may even allow to reconstruct the pollution history of the river basin. In the present study, data on alluvial soils contaminated by a major pollution source were analyzed, with special attention for these soils as an archive for information on the pollution history of a river/river catchment, and on the postdepositional downward migration of metal(loid)s in the alluvial soils. Besides the lateral variation of soil properties and metal(loid) concentrations in the alluvial soils, the vertical distribution of metal(loid)s in soil profiles, as well as the evolution of soil composition in relation to the distance from the river, was addressed. The postdepositional mobilization of Cd was evaluated in a fine-scale sampled alluvial soil core, by comparing data from 137Cs dating with data about the Cd emissions through time and by using leaching tests to calculate the downward migration of Cd. A substantial amount of Cd could leach from superficial to deeper soil layers. Therefore, the low-resolution (cm-scale) sampling of the alluvial soil was not reliable to reconstruct the pollution history of the river catchment, because the elevated chloride-concentrations in the river water increased the downward leaching of Cd through the formation of chloro-complexes. Moreover, the variability in flooding and sedimentation regimes along the river resulted in a heterogeneous composition of the alluvial soils, allowing very large differences in metal(loid) concentrations in places only a few meters apart.

INTRODUCTION: Worldwide, polypharmacy and medication appropriateness-related outcomes (MARO) are growing public health concerns associated with potentially inappropriate prescribing, adverse health effects, and avoidable costs to health systems. Continuity of care (COC) is a cornerstone of high-quality care that has been shown to improve patient-relevant outcomes. However, the relationship between COC and polypharmacy/MARO has not been systematically explored. OBJECTIVE: The aim of this systematic review was to investigate the operationalization of COC, polypharmacy, and MARO as well as the relationship between COC and polypharmacy/MARO. METHODS: We performed a systematic literature search in PubMed, Embase, and CINAHL. Quantitative observational studies investigating the associations between COC and polypharmacy and/or COC and MARO by applying multivariate regression analysis techniques were eligible. Qualitative or experimental studies were not included. Information on the definition and operationalization of COC, polypharmacy, and MARO and reported associations was extracted. COC measures were assigned to the relational, informational, or management dimension of COC and further classified as objective standard, objective non-standard, or subjective. Risk of bias was assessed by using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS: Twenty-seven studies were included. Overall, substantial differences existed in terms of the COC dimensions and related COC measures. Relational COC was investigated in each study, while informational and management COC were only covered among three studies. The most frequent type of COC measure was objective non-standard (n = 16), followed by objective standard (n = 11) and subjective measures (n = 3). The majority of studies indicated that COC is strongly associated with both polypharmacy and MARO, such as potentially inappropriate medication (PIM), potentially inappropriate drug combination (PIDC), drug-drug interaction (DDI), adverse drug events (ADE), unnecessary drug use, duplicated medication, and overdose. More than half of the included studies (n = 15) had a low risk of bias, while five studies had an intermediate and seven studies a high risk of bias. CONCLUSIONS: Differences regarding the methodological quality of included studies as well as the heterogeneity in terms of the operationalization and measurement of COC, polypharmacy, and MARO need to be considered when interpreting the results. Yet, our findings suggest that optimizing COC may be helpful in reducing polypharmacy and MARO. Therefore, COC should be acknowledged as an important risk factor for polypharmacy and MARO, and the importance of COC should be considered when designing future interventions targeting these outcomes. ispartof: DRUGS & AGING vol:40 issue:6 pages:473-497 ispartof: location:New Zealand status: published

Aims To investigate whether the elevation in postprandial concentrations of the gut hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM) and peptide YY (PYY) accounts for the beneficial changes in food preferences, sweet taste function and eating behaviour after Roux-en-Y gastric bypass (RYGB). Materials and methods This was a secondary analysis of a randomized single-blind study in which we infused GLP-1, OXM, PYY (GOP) or 0.9% saline subcutaneously for 4 weeks in 24 subjects with obesity and prediabetes/diabetes, to replicate their peak postprandial concentrations, as measured at 1 month in a matched RYGB cohort (ClinicalTrials.gov NCT01945840). A 4-day food diary and validated eating behaviour questionnaires were completed. Sweet taste detection was measured using the method of constant stimuli. Correct sucrose identification (corrected hit rates) was recorded, and sweet taste detection thresholds (EC50s: half maximum effective concencration values) were derived from concentration curves. The intensity and consummatory reward value of sweet taste were assessed using the generalized Labelled Magnitude Scale. Results Mean daily energy intake was reduced by 27% with GOP but no significant changes in food preferences were observed, whereas a reduction in fat and increase in protein intake were seen post-RYGB. There was no change in corrected hit rates or detection thresholds for sucrose detection following GOP infusion. Additionally, GOP did not alter the intensity or consummatory reward value of sweet taste. A significant reduction in restraint eating, comparable to the RYGB group was observed with GOP. Conclusion The elevation in plasma GOP concentrations after RYGB is unlikely to mediate changes in food preferences and sweet taste function after surgery but may promote restraint eating.

Background: A growing body of empirical research shows that suicidal behaviors are prevalent in childhood. Yet, few studies have examined risk factors related to suicidal ideation (SI) among children aged 12 and younger. Aims: The current study addresses this gap. Method: A questionnaire was filled out by 1,350 Flemish primary caregivers (94.7% mothers) of 9-year-old children (50.4% boys, Mage = 9.45). Their responses were analyzed using logistic regression and independent samples t tests. Results: The presence of passive SI was reported in 10.5% of the children. A psychiatric, developmental, or behavioral condition (or multiple conditions), a learning disorder, impulsivity, aggression, and experiencing multiple stressful family life events were discovered as potential risk factors of passive SI in childhood. Limitations: The cross-sectional nature of this study meant that causality could not be inferred. In addition, it was based on reports of primary caregivers, rather than on reports from the children themselves. Conclusion: These new empirical findings can be used for the development of prevention programs and be taken into account in risk assessments of SI in clinical practice. Confirmation of our findings in a longitudinal child-reported study is needed. ispartof: CRISIS-THE JOURNAL OF CRISIS INTERVENTION AND SUICIDE PREVENTION vol:44 issue:2 ispartof: location:Canada status: published

An anal fissure is a painful tear of the sensitive anoderm, distally from the dentate line. It is a prevalent disorder and impairs quality of life dramatically. Typical or primary fissures are associated with constipation and mostly located at the posterior midline. About 1% of fissures are atypical in appearance and are generally secondary in nature. These secondary fissures should arouse attention and require further exploration for underlying conditions, such as Crohn's disease, malignancy, trauma or venereal infections. The aim of this manuscript is to provide a comprehensive review on the clinical aspects, evaluation and treatment of secondary anal fissures. (Acta gastroenterol. belg., 2023, 86, 58-67).

Electronic cigarette usage has significantly expanded among young people and pregnant women in the last decade. Although there are already some data regarding the short- and long-term consequences of e-cigarettes on human health, their effect on embryo and lung development still needs to be fully disclosed. In this sense, this study describes, for the first time, the impact of electronic cigarette aerosol on early lung development. For this purpose, ex vivo chick (Gallus gallus) embryonic lungs were cultured in vitro for 48h in e-cigarette aerosol exposed-medium or unexposed medium. Chick lung explants were also cultured in a cigarette smoke-exposed medium for comparison purposes. Lung explants were morphologically analyzed to assess the impact on lung growth. Additionally, TNF- levels were determined in the supernatant as a marker of pro-inflammatory response. The results suggest that electronic cigarette aerosol impairs lung growth and promotes lung inflammation. However, its impact on early lung growth seems less detrimental than conventional cigarette smoke. This work provides significant data regarding the impact of e-cig aerosol, adding to the efforts to fully understand its effect on embryo development. The validation of these effects may eventually lead to new tobacco control recommendations for pregnant women., This work has been funded by National funds, through the Foundation for Science and Technology (FCT) - project UIDB/50026/2020, UIDP/50026/2020, UIDB/04469/2020 and UIDB/04050/2020. Funding bodies did not play any role in the study design, data collection, and analysis, publication decisions or preparation of the manuscript., info:eu-repo/semantics/publishedVersion

The brewing industry is regarded as a fiercely competitive and insatiable sector of activity, driven by the significant technological improvements observed in recent years and the most recent consumer trends pointing to a sharp demand for sensory enhanced beers. Some emergent and sustainable technologies regarding food processing such as pulsed electric fields (PEF), ultrasound (US), thermosonication (TS), high-pressure processing (HPP), and ohmic heating (OH) have shown the potential to contribute to the development of currently employed brewing methodologies by both enhancing the quality of beer and contributing to processing efficiency with a promise of being more environmentally friendly. Some of these technologies have not yet found their way into the industrial brewing process but already show potential to be embedded in continuous thermal and non-thermal unit operations such as pasteurization, boiling and sterilization, resulting in beer with improved organoleptic properties. This review article aims to explore the potential of different advanced processing technologies for industrial application in several key stages of brewing, with particular emphasis on continuous beer production., This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and by LABBELS—Associate Laboratory in Biotechnology, Bioengineering and Microelectromechnaical Systems, LA/P/0029/2020. Ricardo N. Pereira acknowledges FCT for its Assistant Research program under the scope of Scientific Stimulus Employment with reference CEECIND/02903/2017., info:eu-repo/semantics/publishedVersion

Indoor positioning based on IEEE 802.11 wireless LAN (Wi-Fi) fingerprinting needs a reference data set, also known as a radio map, in order to match the incoming fingerprint in the operational phase with the most similar fingerprint in the data set and then estimate the device position indoors. Scalability problems may arise when the radio map is large, e.g., providing positioning in large geographical areas or involving crowdsourced data collection. Some researchers divide the radio map into smaller independent clusters, such that the search area is reduced to less dense groups than the initial database with similar features. Thus, the computational load in the operational stage is reduced both at the user devices and on servers. Nevertheless, the clustering models are machine-learning algorithms without specific domain knowledge on indoor positioning or signal propagation. This work proposes several clustering variants to optimize the coarse and fine-grained search and evaluates them over different clustering models and data sets. Moreover, we provide guidelines to obtain efficient and accurate positioning depending on the data set features. Finally, we show that the proposed new clustering variants reduce the execution time by half and the positioning error by approximate to 7% with respect to fingerprinting with the traditional clustering models., This work was supported by the European Union's H2020 Research and Innovation Programme under the Marie Sklodowska-Curie under Agreement 813278 (A-WEAR, http://www.a-wear.eu/) and Agreement 101023072 (ORIENTATE,http://orientate.dsi.uminho.pt).

ispartof: AMERICAN JOURNAL OF MEDICAL GENETICS PART A status: Published online

Statistical and dynamical modeling techniques are used to downscale global climate model (GCM) outputs to practical resolutions for local- or regional-scale applications. Current techniques do not incorporate the effects of land-use and land-cover changes, although research has shown that such changes can substantially affect climate locally. Here, we explore a new downscaling technique that uses tile-level GCM outputs provided under phase 6 of the Coupled Model Intercomparison Project (CMIP6). The method, land-cover tile downscaling (LTD), spatially locates the tile-level GCM outputs by mapping them to corresponding classes in high-resolution land-cover maps. Furthermore, it applies an elevation-based correction to account for the effect of topography on the local climate. LTD is applied to near-surface temperature outputs from the Community Earth System Model, version 2 (CESM2) and U.K. Earth System Model, version 1 (UKESM1), and surface temperature output from CESM2 and evaluated against observations. In comparison with grid-averaged control data, LTD outputs show an overall bias reduction that is not spatially consistent. Moreover, LTD performs better on air temperature data than on surface temperature and better on areas dominated by primary/secondary land and crops than on urban land. This could arise from simplifications in methods, like land-cover reclassification and simplified lapse rate estimates. However, the difference in response between the two variables and land-cover types implies that biases also stem from model structural features involved in estimating their tile-level outputs. This is supported by the differences between grid average data provided by the models and the same data reconstructed from tile-level outputs. Therefore, a thorough evaluation and quality control of tile-level outputs is recommended.

BACKGROUND: Gastroparesis and functional dyspepsia are disorders characterized by upper gastrointestinal symptoms and multifaceted etiologies. One of the main therapeutic approaches is accelerating gastric emptying (GE) by means of prokinetic agents. Their efficacy has been demonstrated, although the association between symptom improvement and acceleration of emptying is less clear. Meta-analyses have found contradictory results. Differences in applied methodology and included trials might drive these contradictions. OBJECTIVE: To provide a transparent meta-analysis update to elucidate the association between symptom improvement and acceleration of GE due to gastroprokinetic agents available for long-term use in patients with gastroparesis. DESIGN: Two approaches from earlier meta-analyses were executed and compared. One analyzed the relative changes on active treatment versus baseline, the other compared the change from baseline on active treatment versus the change from baseline on placebo. Papers that reported sufficient numerical data for both analyses were selected. Both analyses included the same trials. RESULTS: Overall, both approaches yield the same positive direction of association between symptom improvement and acceleration of emptying (0.291 (-0.391, 0.972), p = 0.4 and 0.453 (0.123, 0.782), p = 0.007 for the active-only and placebo-controlled analysis respectively). The association between symptom improvement and GE acceleration for studies using optimal GE tests was either 0.028 (p > 0.9) or 0.463 (p = 0.007), and for sub-optimal GE tests was either 0.370 (p = 0.4) or 0.052 (p > 0.9) depending on the used meta-analysis methodology. CONCLUSIONS: The applied methodology for GE testing, and the meta-analysis substantially impacts the conclusion. When considering the clinically relevant outcome of improvement from baseline, symptoms and emptying improve with prokinetics, but no correlation is found between both aspects. When the change over placebo is considered, limiting the analysis to scientifically more rigorous study approaches, changes in emptying rate and symptom improvement are positively associated. ispartof: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL vol:11 issue:2 ispartof: location:England status: Published online

This study aimed to improve the performance and mode of administration of a glass-reinforced hydroxyapatite synthetic bone substitute, Bonelike by Biosckin® (BL®), by association with a dextrin-based hydrogel, DEXGEL, to achieve an injectable and moldable device named DEXGEL Bone., Open access funding provided by FCT|FCCN (b-on). The authors were funded by FEDER and NORTE 2020 through project no. 003262 titled “iBONE therapies: advanced solutions for bone regen eration.” This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of the UID/BIO/04469 unit and COMPETE 2020 (POCI-01–0145- FEDER-006684) and BioTecNorte operation (NORTE-01–0145- FEDER-000004) funded by the European Regional Development Fund under the scope of Norte 2020—Programa Operacional Regional do Norte. The authors were granted a scholarship (SFRH/BD/132000/2017) by Portuguese FCT. This work was also funded by project UIDB/CVT/00772/2020 supported by FCT., info:eu-repo/semantics/publishedVersion

Understanding how we can age healthily is a challenge at the heart of biogerontological interest. Whereas myriad genes are known to affect the lifespan of model organisms, effects of such interventions on healthspan-the period of life where an animal is considered healthy, rather than merely alive-are less clear. To understand relationships between life- and healthspan, in recent years several platforms were developed with the purpose of assessing both readouts simultaneously. We here relied on one such platform, the WorMotel, to study effects of adulthood-restricted knock-down of 130 Caenorhabditis elegans genes on the locomotive health of the animals along their lifespans. We found that knock-down of six genes affected healthspan while lifespan remained unchanged. For two of these, F26A3.4 and chn-1, knock-down resulted in an improvement of healthspan. In follow-up experiments we showed that knockdown of F26A3.4 indeed improves locomotive health and muscle structure at old age. ispartof: Biogerontology vol:24 issue:2 ispartof: location:Netherlands status: Published online

Social insects display extreme phenotypic differences between sexes and castes even though the underlying genome can be almost identical. Epigenetic processes have been proposed as a possible mechanism for mediating these phenotypic differences. Using whole genome bisulfite sequencing of queens, males, and reproductive female workers we have characterised the sex- and caste-specific methylome of the bumblebee Bombus terrestris. We have identified a potential role for DNA methylation in histone modification processes which may influence sex and caste phenotypic differences. We also find differentially methylated genes generally show low levels of DNA methylation which may suggest a separate function for lowly methylated genes in mediating transcriptional plasticity, unlike highly methylated genes which are usually involved in housekeeping functions. We also examined the relationship between the underlying genome and the methylome using whole genome re-sequencing of the same queens and males. We find DNA methylation is enriched at zero-fold degenerate sites. We suggest DNA methylation may be acting as a targeted mutagen at these sites, providing substrate for selection via non-synonymous changes in the underlying genome. However, we did not see any relationship between DNA methylation and rates of positive selection in our samples. In order to fully assess a possible role for DNA methylation in adaptive processes a specifically designed study using natural population data is needed. ispartof: HEREDITY vol:130 issue:4 pages:188-195 ispartof: location:England status: published

Aims Multinomial logistic regression models allow one to predict the risk of a categorical outcome with > 2 categories. When developing such a model, researchers should ensure the number of participants ([Formula: see text]) is appropriate relative to the number of events ([Formula: see text]) and the number of predictor parameters ([Formula: see text]) for each category k. We propose three criteria to determine the minimum n required in light of existing criteria developed for binary outcomes. Proposed criteria The first criterion aims to minimise the model overfitting. The second aims to minimise the difference between the observed and adjusted [Formula: see text] Nagelkerke. The third criterion aims to ensure the overall risk is estimated precisely. For criterion (i), we show the sample size must be based on the anticipated Cox-snell [Formula: see text] of distinct ‘one-to-one’ logistic regression models corresponding to the sub-models of the multinomial logistic regression, rather than on the overall Cox-snell [Formula: see text] of the multinomial logistic regression. Evaluation of criteria We tested the performance of the proposed criteria (i) through a simulation study and found that it resulted in the desired level of overfitting. Criterion (ii) and (iii) were natural extensions from previously proposed criteria for binary outcomes and did not require evaluation through simulation. Summary We illustrated how to implement the sample size criteria through a worked example considering the development of a multinomial risk prediction model for tumour type when presented with an ovarian mass. Code is provided for the simulation and worked example. We will embed our proposed criteria within the pmsampsize R library and Stata modules.

Public transport network design deals with finding efficient network solution(s) from a set of alternatives that best satisfies the often-conflicting objectives of stakeholders like passengers and operators. This work presents a simulation-based optimization (SBO) model for designing public transport networks. The work’s novelty is in developing such a network design model that fully accounts for the stochastic behavior of commuters on the transit network. The SBO discipline solves decision-based problems like the transit network design problem (TNDP) by combining simulation and optimization models. The proposed model integrates a disaggregated activity-based travel demand simulation with a multi-objective network optimization algorithm. Trip-based travel demand models are commonly used to represent traveler behavior in the literature. The approach limits its ability to accommodate the stochastic realities of traveler behavior in a transit network design solution. Using activity-based simulation instead makes it possible to account for a more realistic traveler behavior, especially real-time decisions made in response to changing network dynamics which ultimately affect the distribution of demand over time on the network. The proposed model is applied to the improved design of the integrated public transport network in the City of Cape Town, South Africa. The results show SBO can design efficient network solutions that reflect the objectives of network stakeholders.

BACKGROUND: While prior Micra trials demonstrated a high implant success rate and favorable safety and efficacy results, changes in implant populations and safety over time is not well studied. The objective of this analysis was to report the performance of Micra in European and Middle Eastern patients and compare to the Micra Investigational Device Exemption (IDE) and Micra Post Approval Registry (PAR) studies. METHODS: The prospective, single-arm Micra Acute Performance European and Middle Eastern (MAP EMEA) registry was designed to further study the performance of Micra in patients from EMEA. The primary endpoint was to characterize acute (30-day) major complications. Electrical performance was analyzed. The major complication rate through 12 months was compared with the IDE and PAR studies. RESULTS: The MAP EMEA cohort (n = 928 patients) had an implant success rate of 99.9% and were followed for an average of 9.7 ± 6.5 months. Compared to prior studies, MAP EMEA patients were more likely to have undergone dialysis and have a condition which precluded the use of a transvenous pacemaker (p

The combination of ethyl (hydroxyimino)cyanoacetate (Oxyma) and diisopropylcarbodiimide (DIC) has demonstrated superior performance in amino acid activation for peptide synthesis. However, it was recently reported that Oxyma and DIC could react to generate undesired hydrogen cyanide (HCN) at 20 °C, raising safety concerns for the practical use of this activation strategy. To help minimize the risks, there is a need for a comprehensive investigation of the mechanism and kinetics of the generation of HCN. Here we show the results of the first systematic computational study of the underpinning mechanism, including comparisons with experimental data. Two pathways for the decomposition of the Oxyma/DIC adduct are derived to account for the generation of HCN and its accompanying cyclic product. These two mechanisms differ in the electrophilic carbon atom attacked by the nucleophilic sp2-nitrogen in the cyclization step and in the cyclic product generated. On the basis of computed “observed” activation energies, ΔGobs⧧, the mechanism that proceeds via the attack of the sp2-nitrogen at the oxime carbon is identified as the most kinetically favorable one, a conclusion that is supported by closer agreement between predicted and experimental 13C NMR data. These results can provide a theoretical basis to develop a design strategy for suppressing HCN generation when using Oxyma/DIC for amino acid activation.