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Background: Training load is typically described in terms of internal and external load. Investigating the coupling of internal and external training load is relevant to many sports. Here, continuous kernel-density estimation (KDE) may be a valuable tool to capture and visualize this coupling. Aim: Using training load data in speed skating, we evaluated how well bivariate KDE plots describe the coupling of internal and external load and differentiate between specific training sessions, compared to training impulse scores or intensity distribution into training zones. Methods: On-ice training sessions of 18 young (sub)elite speed skaters were monitored for velocity and heart rate during 2 consecutive seasons. Training session types were obtained from the coach’s training scheme, including endurance, interval, tempo, and sprint sessions. Differences in training load between session types were assessed using Kruskal–Wallis or Kolmogorov–Smirnov tests for training impulse and KDE scores, respectively. Results: Training impulse scores were not different between training session types, except for extensive endurance sessions. However, all training session types differed when comparing KDEs for heart rate and velocity (both P Conclusion: 2D KDE plots provide a valuable tool to visualize and inform coaches on the (subtle differences in) coupling of internal and external training load for training sessions. This will help coaches design better training schemes aiming at desired training adaptations.

The EU agri-food sector, which is mainly composed of small and medium-sized enterprises has become more demanding in terms of technological inputs to reduce costs, improve the added value of food products, achieve sustainability issues, or address new market opportunities. The introduction of new technologies poses challenges for SMEs that lack the resources and time to cope with the technological transformation, which involves not only the assimilation of new technology in organizational processes but also business model innovation. In this context, this research aims to empirically explore the paths of agri-food SMEs engaged in the technological transformation process, based on the drivers and barriers, as well as the strategies used by these companies to overcome these barriers. In-depth semi-structured interviews with 14 EU agri-food SMEs were conducted and analysed using a combination of deductive pattern-matching and inductive approach. Based on similarities in terms of drivers, barriers, and strategies, seven main groups were identified to draw the paths of the technological transformation process for agri-food SMEs. Findings reveal that there is one common strategy that is adopted by all 14 companies, namely the employment of different types of partnerships and collaborations that allow companies to successfully enter new markets. The study contributes to the literature on technology transformation related to the agri-food sector, by proving insights into how EU agri-food SMEs cope with this process.

Objective: The aim of the study was to evaluate the oxygen saturation index (OSI) as an early predictor of clinical deterioration in infants with congenital diaphragmatic hernia (CDH). Methods: A single-center retrospective cohort study was conducted in consecutive infants with isolated CDH with continuous OSI measurements collected in the first 24 h after birth between June 2017 and July 2021. Outcomes of interest were pulmonary hypertension, extracorporeal membrane oxygenation (ECMO)-therapy, and mortality. We evaluated the discriminative values of the maximum OSI value and of mean OSI values with receiver operator characteristic (ROC) analysis and the area under the ROC curve. Results: In 42 infants with 49,473 OSI measurements, the median OSI was 5.0 (interquartile range 3.1–10.6). Twenty-seven infants developed pulmonary hypertension on a median of day 1 (1-1), of which 15 infants had an indication for ECMO-therapy, and 6 infants died. Maximum OSI values were associated with pulmonary hypertension, ECMO-therapy, and mortality. Mean OSI values had an acceptable discriminative ability for pulmonary hypertension and an excellent discriminative ability for ECMO-therapy and mortality. Although OSI measurements were not always present in the first hours after birth, we determined discriminative cut-offs for mean OSI values already in these first hours for pulmonary hypertension, the need for ECMO-therapy, and mortality. Conclusions: Continuous OSI evaluation is a promising modality to identify those infants at highest risk for clinical deterioration already in the first hours after birth. This provides an opportunity to tailor postnatal management based on the individual patient’s needs.

Background While patients with diffuse low-grade glioma (LGG) often survive for years, there is a risk of tumor progression which may impact patients’ long-term health-related quality of life (HRQOL) and neurocognitive functioning (NCF). We present a follow-up of LGG patients and their informal caregivers (T3) who took part in our previous HRQOL investigations (T1, M = 7 and T2 M = 13 years after diagnosis). Methods Participants completed HRQOL (short form-36 health survey [SF-36]; EORTC-BN20), fatigue (Checklist Individual Strength [CIS]), and depression (Center for Epidemiological Studies-Depression [CES-D]) questionnaires and underwent NCF assessments. T3 scores were compared with matched controls. Changes over time (T1–T2–T3) on group and participant level were assessed. Where available, histology of the initial tumor was revised and immunohistochemical staining for IDH1 R132H mutant protein was performed. Results Thirty patients and nineteen caregivers participated. Of N = 11 with tissue available, 3 patients had confirmed diffuse LGG. At T3, patients (M = 26 years after diagnosis) had HRQOL and NCF similar to, or better than controls, yet 23.3% and 53.3% scored above the cut-off for depression (≥16 CES-D) and fatigue (≥35 CIS), respectively. Caregivers’ HRQOL was similar to controls but reported high rates of fatigue (63.2%). Over time, patients’ mental health improved (P < .05). Minimal detectable change in HRQOL over time was observed in individual patients (30% improvement; 23.3% decline; 20% both improvement and decline) with 23.3% remaining stable. NCF remained stable or improved in 82.8% of patients. Conclusions While HRQOL and NCF do not appear greatly impacted during long-term survivorship in LGG, depressive symptoms and fatigue are persistent.

Darcy's law describes the flow of Newtonian fluids through bulk porous media as the product of the applied pressure difference, the fluid's viscosity and the medium's permeability. Brinkman extended Darcy's law with a viscous stress term, thereby enabling boundary conditions to the flow field at the surface of the medium. The validity of Brinkman's term, and the value of its effective viscosity, have been heavily debated since their introduction nearly 75 years ago. We use experiments and Multibody Dissipative Particle Dynamics (MDPD) simulations to study flows through ordered and disordered pillar arrays in microfluidic channels of limited height. We find that the simulated velocity profiles are well described by an expedient interpretation of Brinkman's theory. Depending on the solid volume fraction and pillar arrangement, the effective viscosity varies between two and three times the bulk fluid viscosity. The calculated effective permeabilities of the flow devices, combining the flow resistances due to the pillars and the walls by Brinkman's theory, agree well with the experimental data. This approach enables fast and accurate estimates of the effective permeability of micropillared chips. The simulated force distributions over the walls and pillars require an effective viscosity equal to the bulk viscosity and an elevation-dependent permeability of the pillar array.

Als Reaktion auf die neuen Herausforderungen von geänderten Nachhaltigkeitsanforderungen und Klimawandel im Agrarsektor sind nachhaltige Prozessinnovationen ein Weg die Produktion von Nahrungsmitteln mit vielfältigen Ökosystemdienstleistungen zu verbinden. Trotz ihrer seit längerem in der Forschung beschriebenen Vorteile sind die tatsächlichen Adoptionsraten dieser Innovationen in der landwirtschaftlichen Praxis in Deutschland eher gering. Um ihre weitere Verbreitung zu fördern, kommt der bislang in der Forschung kaum untersuchten Frage nach den Adoptionsfaktoren nachhaltiger Prozessinnovationen eine besondere Bedeutung zu. Das Ziel der vorliegenden Studie ist es, die Zugehörigkeit landwirtschaftlicher Entscheider*innen zu den verschiedenen Adoptionsstufen ‚Absichtslosigkeit‘, ‚Absichtsbildung‘, ‚Vorbereitung‘ und ‚Handlung‘ nachhaltiger Prozessinnovationen in der Landwirtschaft, am Beispiel von Agroforstsystemen, zu bestimmen und den Einfluss verschiedener Landwirt*innen- und Betriebscharakteristika als Adoptionsfaktoren auf die Stufenzugehörigkeit der Landwirt*innen darzustellen. Auf Basis quantitativer Befragungsdaten von 209 deutschen Landwirt*innen wird das transtheoretische Modell der Verhaltensänderung auf die Adoption von Innovationen mittels deskriptiver Statistiken, konfirmatorischer Faktorenanalyse und ordinal logistischer Regressionsanalyse angewendet. Die Ergebnisse zeigen, dass bei den aktuell primär vorherrschenden niedrigen Adoptionsstufen die Einstellung der Landwirt*innen zur Implementierung von Agroforstsystemen auf dem eigenen Betrieb als Adoptionsfaktor die Adoption am stärksten positiv beeinflusst. Während auch bestehende Erfahrungen mit erneuerbaren Energien einen positiven Einfluss auf die Adoption haben, trifft das Gegenteil auf vorherige Erfahrungen mit Kurzumtriebsplantagen (KUP) und Agroforstsystemen (AFS) zu. Regional betrachtet ist zudem eine höhere Adoptionswahrscheinlichkeit in Süddeutschland zu beobachten. Basierend auf den Ergebnissen werden die folgenden zielgerichteten Maßnahmen zur weiteren Verbreitung innovativer Landnutzungssysteme durch Verbesserung der Einstellung und die Etablierung einer Gruppe von Pionierlandwirt*innen entwickelt: Verbesserung der Kommunikation über Anforderungen und Potenziale von Innovationen, stärkere Ver­ankerung von nachhaltigen Prozessinnovationen in den Curricula der landwirtschaftlichen Berufsausbildungen und Studiengänge, Einrichtung eines permanenten Schulungs- und Weiterbildungsangebot, Auflage von langfristigen, niedrigschwelligen Förderprogrammen und regionale Ausdifferenzierung von Maßnahmen.

Polychlorinated dibenzo-p-dioxin and polychlorinated dibenzofuran (PCDD/F) are persistent, toxic, and bioaccumulative. Currently, PCDD/F monitoring programs primarily use fish and birds with potentially large home ranges to monitor temporal trends over broad spatial scales; sentinel organisms that provide targeted sediment contaminant information across small geographic areas have yet to be developed. Riparian orb-weaving spiders, which typically have small home ranges and consume primarily adult aquatic insects, are potential PCDD/F sentinels. Recent studies have demonstrated that spider tissue concentrations indicate the source and magnitude of dioxin-like chlorinated compounds in contaminated sediments, including polychlorinated biphenyls (PCBs). Our aim in the present study was to assess the utility of riparian spiders as sentinels for PCDD/F-contaminated sediments. We measured PCDD/F (total [Σ] and homologs) in surface sediments and spiders collected from three sites within the St. Louis River basin (Minnesota and Wisconsin, USA). We then compared (1) patterns in ΣPCDD/F concentrations between sediment and spiders, (2) the distribution of homologs within sediments and spiders when pooled across sites, and (3) the relationship between sediment and spider concentrations of PCDD/F homologs across 13 stations sampled across the three sites. The ΣPCDD/F concentrations in sediment (mean ± standard error 286 591 ± 97 614 pg/g) were significantly higher than those in riparian spiders (2463 ± 977 pg/g, p < 0.001), but the relative abundance of homologs in sediment and spiders were not significantly different. Spider homolog concentrations were significantly and positively correlated with sediment concentrations across a gradient of sediment PCDD/F contamination (R(2) = 0.47, p < 0.001). Our results indicate that, as has been shown for other legacy organic chemicals like PCBs, riparian spiders are suitable sentinels of PCDD/F in contaminated sediment.

Purpose Many consumer packaged goods (CPG) companies have increased the visibility of their corporate brand to consumers by adding a corporate logo (e.g. Unilever “U”) on the packaging of their product brands (e.g. Dove, Domestos, Lipton, Knorr) and showcasing their product-brand portfolio in additional corporate-brand advertising. This paper aims to investigate consumer needs and product-brand familiarity as moderators of the impact of such a strong form of corporate-brand endorsement on the evaluation of established CPG product brands. Design/methodology/approach Two experiments with n = 670 and n = 118 respondents compare consumer evaluations of eight (Study 2: ten) product brands of a major German (Study 2: Anglo-Dutch) CPG company with versus without corporate-brand endorsement. The authors measure (Study 2: manipulate) the importance a consumer attaches to symbolic, experiential, relational and functional needs in brand choice. Findings Corporate-brand endorsement improves (decreases) the evaluation of established CGP product brands among consumer segments who base their brand choice in a CPG category predominantly on functional or relational (experiential or symbolic) needs. Furthermore, it exerts a negative effect on product brands among heavy category users due to their higher product-brand familiarity. Practical implications Rather than endorsing all its product brands with the corporate brand, a CPG company should do so selectively, depending on the positioning and target audience of each product brand. Originality/value To the best of the authors’ knowledge, this paper is the first to demonstrate the importance of consumer needs and product-brand familiarity in corporate-brand endorsement.

Athlete development depends on many factors that need to be balanced by the coach. The amount of data collected grows with the development of sensor technology. To make data-informed decisions for training prescription of their athletes, coaches could be supported by feedback through a coach dashboard. The aim of this paper is to describe the design of a coach dashboard based on scientific knowledge, user requirements, and (sensor) data to support decision making of coaches for athlete development in cyclic sports. The design process involved collaboration with coaches, embedded scientists, researchers, and IT professionals. A classic design thinking process was used to structure the research activities in five phases: empathise, define, ideate, prototype, and test phases. To understand the user requirements of coaches, a survey (n = 38), interviews (n = 8) and focus-group sessions (n = 4) were held. Design principles were adopted into mock-ups, prototypes, and the final coach dashboard. Designing a coach dashboard using the co-operative research design helped to gain deep insights into the specific user requirements of coaches in their daily training practice. Integrating these requirements, scientific knowledge, and functionalities in the final coach dashboard allows the coach to make data-informed decisions on training prescription and optimise athlete development.Keywords: dashboard; training load; coach; feedback; athlete development; performance; overreaching; overtraining

Relapse after first-episode psychosis (FEP) is a major clinical challenge for specialized early intervention services. Understanding patient perspectives on factors contributing to relapse can inform the development of risk assessments and preventive interventions. The objective of this study was to identify factors that may contribute to and prevent relapse from the perspectives of patients receiving services for FEP. Data from 25 participants across four focus groups in Canada were analyzed with a descriptive content analysis approach. Twelve factors were identified, of which four (social environment, technology use, medication, and lifestyle behaviors) had both contributory and preventive roles. In descending order of frequency, risk factors for relapse included substance use; unsupportive social environment; technology use; taking and not taking medication; lack of sleep; work, career, or school stress; significant life events; symptoms of depression or mania; generalized worry; and financial stress. Preventive factors consisted of having a supportive social environment, using technology, taking medication, using coping strategies, and engaging in healthy lifestyle behaviors and meaningful activities. These findings extend the literature on relapse vulnerability and protective factors. Importantly, the factors identified in this study are modifiable, and thereby provide insights for the development and optimization of relapse risk assessments and preventive interventions.

Human habitat disturbances can promote hybridization between closely related, but typically reproductively isolated, species. We explored whether human habitat disturbances are related to hybridization between two closely related songbirds, black-capped and mountain chickadees, using both genomic and citizen science data sets. First, we genotyped 409 individuals from across both species' ranges using reduced-representation genome sequencing and compared measures of genetic admixture to a composite measure of human landscape disturbance. Then, using eBird observations, we compared human landscape disturbance values for sites where phenotypically diagnosed hybrids were observed to locations where either parental species was observed to determine whether hybrid chickadees are reported in more disturbed areas. We found that hybridization between black-capped and mountain chickadees positively correlates with human habitat disturbances. From genomic data, we found that (1) hybrid index (HI) significantly increased with habitat disturbance, (2) more hybrids were sampled in disturbed habitats, (3) mean HIs were higher in disturbed habitats versus wild habitats, and (4) hybrids were detected in habitats with significantly higher disturbance values than parentals. Using eBird data, we found that both hybrid and black-capped chickadees were significantly more disturbance-associated than mountain chickadees. Surprisingly, we found that nearly every black-capped chickadee we sampled contained some proportion of hybrid ancestry, while we detected very few mountain chickadee backcrosses. Our results highlight that hybridization between black-capped and mountain chickadees is widespread, but initial hybridization is rare (few F1s were detected). We conclude that human habitat disturbances can erode pre-zygotic reproductive barriers between chickadees and that post-zygotic isolation is incomplete. Understanding what becomes of recently hybridizing species following large-scale habitat disturbances is a new, but pressing, consideration for successfully preserving genetic biodiversity in a rapidly changing world.

Triple X syndrome is a sex chromosomal aneuploidy characterized by the presence of a supernumerary X chromosome, resulting in a karyotype of 47,XXX in affected females. It has been associated with a variable cognitive, behavioral, and psychiatric phenotype, but little is known about its effects on brain function. We therefore conducted 7 T resting-state functional magnetic resonance imaging and compared data of 19 adult individuals with 47,XXX and 21 age-matched healthy control women using independent component analysis and dual regression. Additionally, we examined potential relationships between social cognition and social functioning scores, and IQ, and mean functional connectivity values. The 47,XXX group showed significantly increased functional connectivity of the fronto-parietal resting-state network with the right postcentral gyrus. Resting-state functional connectivity (rsFC) variability was not associated with IQ and social cognition and social functioning deficits in the participants with 47,XXX. We thus observed an effect of a supernumerary X chromosome in adult women on fronto-parietal rsFC. These findings provide additional insight into the role of the X chromosome on functional connectivity of the brain. Further research is needed to understand the clinical implications of altered rsFC in 47,XXX.

Scholarly interest in the technosphere is exploding. Most analyses define the technosphere as massive, modern, and autonomous. This article constructively critiques these claims, focusing on scale, time, and power. First, it suggests that the technosphere exists at multiple scales that intersect in myriad ways. Second, it shows that the technosphere has a three-million-year history, meaning that Homo sapiens and the technosphere coevolved. This coevolution implies that the technosphere is a profoundly social entity. Third, its history is about how human groups (usually white, male ones) have used technology to build a physical world that works to their advantage and is thus also an issue of power. As histories of pollution, climate change, and many other things show, the technosphere does not exist outside a powerless, undifferentiated humanity. Social and technological formations are thoroughly interwoven. Clark and Szerszynski have urged scholars to "socialize the Anthropocene." This article urges scholars to "socialize" the technosphere, to interrogate and explore its social dimensions.

Cultural evolution of birdsong occurs when songs change over generations and such changes can spread directionally or via drift within populations. We describe the emergence and directional spread of a novel song variant within a population of White-throated Sparrows in central British Columbia, Canada. Birds in this population have been singing a doublet-ending song since the early 2000s. In 2015, we detected a novel variant, consisting of a doublet-ending song with a distinctive amplitude modulation in the first note (Modulated-Doublet). We banded and recorded birds from 2015 to 2020 and classified songs using both audio and spectrographic analysis. The proportion of birds singing the Modulated-Doublet increased, replacing the Unmodulated-Doublet over time. Additionally, the modulation became more pronounced, both across the population and within individual birds, over successive years. The rapid spread suggests there may be several transmission biases driving the adoption of this novel song over the older established variant.

Le traité de Roubo en quatre chapitres sur l’art de la menuiserie, L’Art du menuisier, publié entre 1769 et 1774 par l’Académie royale des Sciences, est considéré comme une source de premier ordre sur les matériaux, les outils et les techniques utilisés par les menuisiers au xviiie siècle. Bien que souvent cité par les historiens d’art et les spécialistes du mobilier, l’ouvrage n’a jamais fait l’objet, dans son intégralité, d’un examen approfondi ou d’une expertise. Cet essai va tenter de déterminer, grâce aux recherches historiographiques actuelles, dans quelle mesure le contenu des travaux de Roubo renvoie aux pratiques actuelles du métier. Il apparaît ainsi indispensable que le lecteur de Roubo ait connaissance d’un certain nombre de parutions en liaison avec le contexte et la destination de l’ouvrage pour que son contenu puisse être correctement évalué. Roubo’s four-part treatise on joinery, L’Art du menuisier, published between 1769 and 1774 by the Académie Royale des Sciences, stands as the prime source on materials, tools and techniques used by 18th century joiners. Although often quoted as such by art historians and furniture conservators, the book as a whole has never been the subject of in-depth study or evaluation. In this article, an attempt is made to establish to what extent the content of Roubo’s texts reflects actual working practices, by applying standard historiographical criteria. It appears that the Roubo student should be aware of a number of issues relating to the background and purpose of the work, to be able to appreciate its content correctly.

OBJECTIVES To longitudinally evaluate self-reported health status (HS) and quality of life (QoL) in 8- and 12-year-old survivors of congenital diaphragmatic hernia (CDH). We hypothesized that HS would improve with age—as associated health problems tend to decline—whereas QoL would decrease, as the children start to compare themselves with peers. METHODS Self-reported HS and QoL of 133 children born between 1999 and 2013 who had joined our standardized follow-up program were routinely assessed at the ages of 8 and 12 with generic, internationally validated, standardized instruments. Longitudinal evaluation of total and subscale scores was performed using general linear model analyses. In addition, we compared these scores to sex- and age-specific normative data. RESULTS Between ages 8 and 12, boys born with CDH perceived a decline in HS (mean difference −7.15, P < .001). Self-reported QoL did not change over time in both boys and girls. At both ages, HS was significantly lower than that of healthy peers (effect size = 0.71, P = .001 for boys, and effect size = 0.69, P = .003 for girls), whereas differences in QoL were small. CONCLUSIONS Children born with CDH are at risk for declining HS between 8 and 12 years, but not QoL, compared with healthy peers. Given that children born with CDH tend to grow into deficits, our findings highlight the need for continued somatic and psychological assessments in adolescent and adult CDH survivors.

BackgroundInfants with a congenital diaphragmatic hernia (CDH) and expected mild pulmonary hypoplasia have an estimated survival rate of 90%. Current guidelines for delivery room management do not consider the individual patient's disease severity, but an individualized approach with spontaneous breathing instead of routine mechanical ventilation could be beneficial for the mildest cases. We developed a resuscitation algorithm for this individualized approach serving two purposes: improving the success rate by structuring the approach and providing a guideline for other centers.MethodsAn initial algorithm was discussed with all local stakeholders. Afterwards, the resulting algorithm was refined using input from international experts.ResultsEligible CDH infants: left-sided defect, observed to expected lung-to-head ratio ≥50%, gestational age at birth ≥37.0 weeks, and no major associated structural or genetic abnormalities. To facilitate fetal-to-neonatal transition, we propose to start stabilization with non-invasive respiratory support and to adjust this individually.ConclusionsInfants with mild CDH might benefit from an individualized approach for neonatal resuscitation. Herein, we present an algorithm that could serve as guidance for centers implementing this.

Roete, AJ, Stoter, IK, Lamberts, RP, Elferink-Gemser, MT, and Otter, RTA. Introducing a method to quantify the specificity of training for races in speed skating. J Strength Cond Res 36(7): 1998-2004, 2022-The specificity of training for races is believed to be important for performance development. However, measuring specificity is challenging. This study aimed to develop a method to quantify the specificity of speed skating training for sprint races (i.e., 500 and 1,000 m), and explore the amount of training specificity with a pilot study. On-ice training and races of 10 subelite-to-elite speed skaters were analyzed during 1 season (i.e., 26 weeks). Intensity was mapped using 5 equal zones, between 4 m center dot s(-1) to peak velocity and 50% to peak heart rate. Training specificity was defined as skating in the intensity zone most representative for the race for a similar period as during the race. During the season, eight 500 m races, seven 1,000 m races, and 509 training sessions were analyzed, of which 414 contained heart rate and 375 sessions contained velocity measures. Within-subject analyses were performed. During races, most time was spent in the highest intensity zone (Vz5 and HRz5). In training, the highest velocity zone Vz5 was reached 107 +/- 28 times, with 9 +/- 3 efforts (0.3 +/- 0.1% training) long enough to be considered 500 m specific, 6 +/- 5 efforts (0.3 +/- 0.3% training) were considered 1,000 m specific. For heart rate, HRz5 was reached 151 +/- 89 times in training, 43 +/- 33 efforts (1.3 +/- 0.9% training) were considered 500 m specific, and 36 +/- 23 efforts (3.2 +/- 1.7% training) were considered 1,000 m specific. This newly developed method enables the examination of training specificity so that coaches can control whether their intended specificity was reached. It also opens doors to further explore the impact of training specificity on performance development.

Funder: Medical Research Council, Funder: National Institute for Health Research (NIHR), Funder: Wellcome Trust, Funder: UK Health Security Agency, Funder: Cancer Research UK, OBJECTIVES: To investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection. METHODS: We performed a case-control study, comparing reinfection cases with singly infected individuals pre-vaccination, matched by gender, age, region and timing of first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), anti-SARS-CoV-2 nucleocapsid (anti-N), live virus microneutralisation (LV-N) and pseudovirus microneutralisation (PV-N). Results were analysed using fixed effect linear regression and fitted into conditional logistic regression models. RESULTS: We identified 23 cases and 92 controls. First infections occurred before November 2020; reinfections occurred before February 2021, pre-vaccination. Anti-S levels, LV-N and PV-N titres were significantly lower among cases; no difference was found for anti-N levels. Increasing anti-S levels were associated with reduced risk of reinfection (OR 0·63, CI 0·47-0·85), but no association for anti-N levels (OR 0·88, CI 0·73-1·05). Titres >40 were correlated with protection against reinfection for LV-N Wuhan (OR 0·02, CI 0·001-0·31) and LV-N Alpha (OR 0·07, CI 0·009-0·62). For PV-N, titres >100 were associated with protection against Wuhan (OR 0·14, CI 0·03-0·64) and Alpha (0·06, CI 0·008-0·40). CONCLUSIONS: Before vaccination, protection against SARS-CoV-2 reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels. Detectable LV-N titres were sufficient for protection, whilst PV-N titres >100 were required for a protective effect. TRIAL REGISTRATION NUMBER: ISRCTN11041050.

The rates of syphilis among pregnant women and infants have increased in recent years, particularly in the U.S. South. Although state policies require prenatal syphilis testing, recent screening rates comparable across Southern states are not known. The purpose of this study is to measure syphilis screening among Medicaid enrollees with delivery in states in the U.S. South.A total of 6 state-university research partnerships in the U.S. South developed a distributed research network to analyze Medicaid claims data using a common analytic approach for enrollees with delivery in fiscal years 2017-2018 and 2018-2019 (combined N=504,943). In 2020-2021, each state calculated the percentage of enrollees with delivery with a syphilis screen test during the first trimester, third trimester, and at any point during pregnancy. Percentages for those with first-trimester enrollment were compared with the percentages of those who enrolled in Medicaid later in pregnancy.Prenatal syphilis screening during pregnancy ranged from 56% to 91%. Screening was higher among those enrolled in Medicaid during the first trimester than in those enrolled later in pregnancy.Despite state laws requiring syphilis screening during pregnancy, screening was much lower than 100%, and states varied in syphilis screening rates among Medicaid enrollees. Findings indicate that access to Medicaid in the first trimester is associated with higher rates of syphilis screening and that efforts to improve access to screening in practice settings are needed.

Firms use aggregate data from data brokers (e.g., Acxiom, Experian) and external data sources (e.g., Census) to infer the likely characteristics of consumers in a target list and thus better predict consumers’ profiles and needs unobtrusively. The authors demonstrate that the simple count method most commonly used in this effort relies implicitly on an assumption of conditional independence that fails to hold in many settings of managerial interest. They develop a Bayesian profiling introducing different conditional independence assumptions. They also show how to introduce additional observed covariates into this model. They use simulations to demonstrate that in managerially relevant settings, the Bayesian method will outperform the simple count method, often by an order of magnitude. The authors then compare different conditional independence assumptions in two case studies. The first example estimates customers’ age on the basis of their first names; prediction errors decrease substantially. In the second example, the authors infer the income, occupation, and education of online visitors of a marketing analytic software company based exclusively on their IP addresses. The face validity of the predictions improves dramatically and reveals an interesting (and more complex) endogenous list-selection mechanism than the one suggested by the simple count method.

We present a study of the structure and differential capacitance of electric double layers of aqueous electrolytes. We consider electric double layer capacitors (EDLC) composed of spherical cations and anions in a dielectric continuum confined between a planar cathode and anode. The model system includes steric as well as Coulombic ion-ion and ion-electrode interactions. We compare results of computationally expensive, but “exact” , Brownian Dynamics (BD) simulations with approximate, but cheap, calculations based on classical Density Functional Theory (DFT). Excellent overall agreement is found for a large set of system parameters, including variations in concentration, ionic size- and valency-asymmetries, applied voltages and electrode separation, provided the differences between the canonical ensemble of the BD simulations and the grand-canonical ensemble of DFT are properly taken into account. In particular, a careful distinction is made between the differential capacitance $$C_N$$ C N at fixed number of ions and $$C_\mu $$ C μ at fixed ionic chemical potential. Furthermore, we derive and exploit their thermodynamic relations. In the future these relations will also be useful for comparing and contrasting experimental data with theories for supercapactitors and other systems. The quantitative agreement between simulation and theory indicates that the presented DFT is capable of accounting accurately for coupled Coulombic and packing effects. Hence it is a promising candidate to cheaply study room temperature ionic liquids at much lower dielectric constants than that of water.

Rabies causes approximately 20,000 human deaths in India each year. Nearly all of these occur following dog bites. Large-scale, high-coverage dog rabies vaccination campaigns are the cornerstone of rabies elimination strategies in both human and dog populations, although this is particularly challenging to achieve in India as a large proportion of the dog population are free-roaming and unowned. Further, little is known about free-roaming dog ecology in India which makes defining optimum vaccination strategies difficult. In this study, data collected using a mobile phone application during three annual mass vaccination and neutering (surgical sterilisation of both males and females) campaigns of free-roaming dogs in Ranchi, India (during which a total of 43,847 vaccinations, 26,213 neuter surgeries and 28,172 re-sight observations were made) were interrogated, using two novel approaches to estimate the proportion of neutered dogs that were lost from the city (assumed due to mortality or migration) between campaign years. Analysis revealed high losses of neutered dogs each year, ranging from 25.3% (28.2-22.8) to 55.8% (57.0-54.6). We also estimated that the total population declined by 12.58% (9.89-15.03) over the three-year period. This demonstrates that there is a high turnover of free-roaming dogs and that despite neutering a large number of dogs in an annual sterilisation campaign, the decline in population size was modest over a three-year time period. These findings have significant implications for the planning of rabies vaccination campaigns and population management programmes as well as highlighting the need for further research into the demographics of free-roaming, unowned dogs in India.

India has a large, free-roaming dog population, encompassing both owned and stray dogs. Canine surgical neutering is often a central component of dog population management and rabies control initiatives. The provision of practical, surgical training opportunities remains a major challenge for veterinary educational establishments worldwide to ensure competency in this routine procedure. A 12-day educational programme, focusing on surgical neutering skills, was developed to address this need. A questionnaire comprising 26 questions covering surgical and clinical topics, and a self-assessment of confidence in undertaking five common surgical procedures, was completed immediately before and after finishing the programme. A total of 296 participants attended, with 228 achieving the inclusion criteria for the study. Total knowledge scores increased significantly after the training programme (mean score pre-18.94, 95% CI 18.13–19.74; post-28.11, 95% CI 27.44–28.77, p

The Deposit, Evaluate and Lookup Predictive Healthcare Information (DELPHI) library provides a centralised location for the depositing, exploring and analysing of patient-level prediction models that are compatible with data mapped to the observational medical outcomes partnership common data model.

The Deposit, Evaluate and Lookup Predictive Healthcare Information (DELPHI) library provides a centralised location for the depositing, exploring and analysing of patient-level prediction models that are compatible with data mapped to the observational medical outcomes partnership common data model.

Biominerals, such as nacreous bivalve shells, are important archives of environmental information. Most marine calcifiers form their shells from amorphous calcium carbonate, hypothesised to occur via particle attachment and stepwise crystallisation of metastable precursor phases. However, the mechanism of this transformation, including the incorporation of trace elements used for environmental reconstructions, are poorly constrained. Here, using shells of the Mediterranean mussel, we explore the formation of nacre from the meso- to the atomic scale. We use a combination of strontium pulse-chase labelling experiments in aquaculture and correlated micro- to sub-nanoscale analysis to show that nacre grows in a dynamic two-step process with extensional and space-filling growth components. Furthermore, we show that nacre crystallizes via localised dissolution and reprecipitation within nanogranules. Our findings elucidate how stepwise crystallization pathways affect trace element incorporation in natural biominerals, while preserving their intricate hierarchical ultrastructure.

The nasal epithelium is the initial entry portal and primary barrier to infection by all human coronaviruses (HCoVs). We utilize primary human nasal epithelial cells grown at air–liquid interface, which recapitulate the heterogeneous cellular population as well as mucociliary clearance functions of the in vivo nasal epithelium, to compare lethal [Severe acute respiratory syndrome (SARS)-CoV-2 and Middle East respiratory syndrome-CoV (MERS-CoV)] and seasonal (HCoV-NL63 and HCoV-229E) HCoVs. All four HCoVs replicate productively in nasal cultures, though replication is differentially modulated by temperature. Infections conducted at 33 °C vs. 37 °C (reflective of temperatures in the upper and lower airway, respectively) revealed that replication of both seasonal HCoVs (HCoV-NL63 and -229E) is significantly attenuated at 37 °C. In contrast, SARS-CoV-2 and MERS-CoV replicate at both temperatures, though SARS-CoV-2 replication is enhanced at 33 °C late in infection. These HCoVs also diverge significantly in terms of cytotoxicity induced following infection, as the seasonal HCoVs as well as SARS-CoV-2 cause cellular cytotoxicity as well as epithelial barrier disruption, while MERS-CoV does not. Treatment of nasal cultures with type 2 cytokine IL-13 to mimic asthmatic airways differentially impacts HCoV receptor availability as well as replication. MERS-CoV receptor DPP4 expression increases with IL-13 treatment, whereas ACE2, the receptor used by SARS-CoV-2 and HCoV-NL63, is down-regulated. IL-13 treatment enhances MERS-CoV and HCoV-229E replication but reduces that of SARS-CoV-2 and HCoV-NL63, reflecting the impact of IL-13 on HCoV receptor availability. This study highlights diversity among HCoVs during infection of the nasal epithelium, which is likely to influence downstream infection outcomes such as disease severity and transmissibility.

Supplemental Fig 1,2,3. Tumor growth rates, overall survival and single agent GDC-0973 in vitro response

Activating mutations in the KRAS oncogene occur in approximately 90% of pancreatic cancers, resulting in aberrant activation of the MAPK and the PI3K pathways, driving malignant progression. Significant efforts to develop targeted inhibitors of nodes within these pathways are underway and several are currently in clinical trials for patients with KRAS-mutant tumors, including patients with pancreatic cancer. To model MEK and PI3K inhibition in late-stage pancreatic cancer, we conducted preclinical trials with a mutant Kras-driven genetically engineered mouse model that faithfully recapitulates human pancreatic ductal adenocarcinoma development. Treatment of advanced disease with either a MEK (GDC-0973) or PI3K inhibitor (GDC-0941) alone showed modest tumor growth inhibition and did not significantly enhance overall survival. However, combination of the two agents resulted in a significant survival advantage as compared with control tumor-bearing mice. To model the clinical scenario, we also evaluated the combination of these targeted agents with gemcitabine, the current standard-of-care chemotherapy for pancreatic cancer. The addition of MEK or PI3K inhibition to gemcitabine, or the triple combination regimen, incrementally enhanced overall survival as compared with gemcitabine alone. These results are reminiscent of the survival advantage conferred in this model and in patients by the combination of gemcitabine and erlotinib, an approved therapeutic regimen for advanced nonresectable pancreatic cancer. Taken together, these data indicate that inhibition of MEK and PI3K alone or in combination with chemotherapy do not confer a dramatic improvement as compared with currently available therapies for patients with pancreatic cancer. Mol Cancer Ther; 14(1); 40–47. ©2014 AACR.

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Background: The CoVid-19 pandemic has impacted many aspects of everyday life, including the (mental) health care system. An increase in depression and anxiety symptoms has been reported worldwide, which is particularly pronounced in females and young people. We aimed at evaluating changes in patient rates of those receiving psychopharmacological medication, often used in treating depression and anxiety. Method: Based on data of the Austrian public health insurance institutions, we conducted an interrupted time series analysis of antidepressants, antipsychotics and benzodiazepines comparing patient rate developments before and throughout the Covid19 pandemic (2013 to 2021), with a special focus on adolescents in comparison to the general population. Age- and sex specific ARIMA models were fitted to the pre Corona period (2013 Q1 – 2020 Q2), used to generate forecasts for the period from 2020 Q3 to 2021 Q4 and then compared to observed developments in the same period to assess significant deviations from the forecasted expactable development paths. Results: A significant excess of patients receiving antidepressants both among male and female adolescents (10-14 and 15-19 years) in comparison to the expectable development path was found in most of the evaluated period (2020 Q3 – 2021 Q4), while the general population was found to be mostly within 97.5% confidence bands of the forecasts. With regards to antipsychotics, the interrupted time series analysis showed a significant excess of patients in the group of female adolescents in almost all quarters, which was especially pronounced in the age group 15-19. Antipsychotics patient rates within the general population only showed significant excess in two quarters. No significant uptake beyond the expactable development paths were found in regard to prescriptions of benzodiazepines in any group. Conclusion: Increased rates of patients receiving antidepressants and antipsychotics, which were especially pronounced in female adolescents, echo epidemiological evidence from multiple studies worldwide reporting an increase in depression and anxiety. Whereas the increasing rates of adolescent patients receiving antidepressants correspond with the use of this medication class as proposed in treatment guidelines for the respective disorders, the increased patient rates in antipsychotics might be understood as a signal for the off-label use of these compounds.

While there is still a debate on what a 15-Minute city is, this vision raised unseen attention for local accessibility. Accessibility measures for decades aim to express the potential of our transport and land-use system. Also, the number of scholars developing indicators to measure the 15-Minute city is increasing fast. When measuring accessibility, numerous practical and methodological open questions are inherited or further complicated when measuring 15-Minute city readiness. Among them are: Should accessibility be measured normative or positive? Accessibility to which destinations should be measured? Is the indicator flexible enough to answer diverse planning questions? Should a composite indicator or several indicators be used? What is the acceptable travel time to certain destination types, and what is a suitable travel time cutoff? On which spatial resolution should the indicators be computed? While the list is incomplete, this work does not aim to find exact answers to them. Instead, it proposes a flexible set of cumulative and gravity-based accessibility measures as a toolkit that reacts to the described challenges when analyzing the 15-Minute city readiness. It follows the understanding that one single composite indicator falls short when concrete weaknesses in accessibility (e.g., lack of grocery supply) need to be identified or interventions (e.g., new supermarket) are assessed. Meanwhile, the power of composite indicators is the seeming clarity of communication. The presented work is part of the co-creative development of the dynamic accessibility instrument GOAT, which is carried out by a group of scientists, software developers, GIS experts, designers,and planning practitioners. Based on a literature review, expert interviews, and planning workshops, the requirements for the software are iteratively derived. As a geographical study context, the Region of Munich, Freiburg, Aachen, and Görlitz was chosen, which covers urban, suburban, and rural areas. The basis of the accessibility measures, which are visualized as heatmaps,aregeneric matrices that map the travel time for the modes of walking and cycling from a hexagonal raster to diverse opportunity data sets. As opportunity data sets, various daily services from the groups: education, leisure, public transport, health, living, and shopping are integrated. A cumulative, modified gaussian, and cumulative gaussian are implemented as impedance functions. The sensitivity parameters can be adjusted for the modified gaussian and cumulative gaussian functions. For all three functions, the cutoff travel time can be between 1-20 minutes.Furthermore, a weight can be specified for each category to build composite indicators. While the sensitivity can be adjusted, an online survey with approximately 800 participants in Germany provides a suggested calibration. The analyses are presented in web maps that can react to land-use scenarios (e.g., opening/closing of a supermarket). Predecessors of the indicators are currently used in the planning software GOAT in practice, and the described improved version of the indicators is currently integrated. Meanwhile, the indicators were computed for the study context, and comparisons show their strengths. Upcoming studies aim to compute the indicators in international case studies and apply them to different planning questions. &nbsp

While there is still a debate on what a 15-Minute city is, this vision raised unseen attention for local accessibility. Accessibility measures for decades aim to express the potential of our transport and land-use system. Also, the number of scholars developing indicators to measure the 15-Minute city is increasing fast. When measuring accessibility, numerous practical and methodological open questions are inherited or further complicated when measuring 15-Minute city readiness. Among them are: Should accessibility be measured normative or positive? Accessibility to which destinations should be measured? Is the indicator flexible enough to answer diverse planning questions? Should a composite indicator or several indicators be used? What is the acceptable travel time to certain destination types, and what is a suitable travel time cutoff? On which spatial resolution should the indicators be computed? While the list is incomplete, this work does not aim to find exact answers to them. Instead, it proposes a flexible set of cumulative and gravity-based accessibility measures as a toolkit that reacts to the described challenges when analyzing the 15-Minute city readiness. It follows the understanding that one single composite indicator falls short when concrete weaknesses in accessibility (e.g., lack of grocery supply) need to be identified or interventions (e.g., new supermarket) are assessed. Meanwhile, the power of composite indicators is the seeming clarity of communication. The presented work is part of the co-creative development of the dynamic accessibility instrument GOAT, which is carried out by a group of scientists, software developers, GIS experts, designers,and planning practitioners. Based on a literature review, expert interviews, and planning workshops, the requirements for the software are iteratively derived. As a geographical study context, the Region of Munich, Freiburg, Aachen, and Görlitz was chosen, which covers urban, suburban, and rural areas. The basis of the accessibility measures, which are visualized as heatmaps,aregeneric matrices that map the travel time for the modes of walking and cycling from a hexagonal raster to diverse opportunity data sets. As opportunity data sets, various daily services from the groups: education, leisure, public transport, health, living, and shopping are integrated. A cumulative, modified gaussian, and cumulative gaussian are implemented as impedance functions. The sensitivity parameters can be adjusted for the modified gaussian and cumulative gaussian functions. For all three functions, the cutoff travel time can be between 1-20 minutes.Furthermore, a weight can be specified for each category to build composite indicators. While the sensitivity can be adjusted, an online survey with approximately 800 participants in Germany provides a suggested calibration. The analyses are presented in web maps that can react to land-use scenarios (e.g., opening/closing of a supermarket). Predecessors of the indicators are currently used in the planning software GOAT in practice, and the described improved version of the indicators is currently integrated. Meanwhile, the indicators were computed for the study context, and comparisons show their strengths. Upcoming studies aim to compute the indicators in international case studies and apply them to different planning questions. &nbsp

The emergence of carbapenem-resistant organisms (CROs) is a significant global threat. Reduction of carbapenem consumption can decrease CROs. In the global endemic era of ESBL-producing bacteria, carbapenems are considered the treatment of choice, leading to challenge in limiting carbapenem use. This review describes the role of precision prescribing for prevention of CROs. This involves improving antibiotic selection, dosing and shortening duration. The effect of different antibiotics, dosing and duration on CRO development are explored. Available options for precision prescribing, gaps in the scientific evidence, and areas for future research are also presented.