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Através dos conhecimentos adquiridos pelos alunos nas aulas de matemática e física no que diz respeito aos conteúdos de geometria plana, geometria espacial, força e momento, foi dada a proposta de construir uma ponte treliçada com palitos de churrasco na qual o sistema deveria suportar uma carga inúmeras vezes maior que o seu próprio peso. Os alunos, mesmo sendo do ensino médio, deveriam pesquisar a respeito do equilíbrio, dos esforços e das condições de construção para um sistema treliçado baseados em literaturas das disciplinas básicas dos cursos de arquitetura e engenharia. Os alunos que desenvolveram o projeto e fizeram a sua apresentação numa feira de matemática em uma universidade local fazem parte de um grupo de pesquisa em física aplicada. Este grupo é formado por alunos dos três anos do ensino médio.

Signals in the terahertz range are mainly wireless, waveguide-bound or on-chip signals. To measure their spectral power, linewidth and harmonics, usually spectrum analyzers are used. Here we present a photonic spectrum analyzer for waveguide-bound signals for the frequency range from 450 GHz to 1.05 THz with the possibility to extend its operation to on-chip signals. Therefore, a photonically generated local oscillator frequency is used to downconvert the signal under test within a photoconductor. A Vivaldi antenna feeds the signal from a dielectric waveguide to the photoconductor. This allows the measurement of any signal that can be transported via a dielectric waveguide. We show details on the transition from a rectangular metallic hollow waveguide to a dielectric waveguide and spectral measurements of a rectangular metallic hollow waveguide source. The same transition can also be used to attach metallic waveguide-coupled ground-source-ground probes in order to characterize on-chip sources.

We use the small scales of the Dark Energy Survey (DES) Year-3 cosmic shear measurements, which are excluded from the DES Year-3 cosmological analysis, to constrain the baryonic feedback. To model the baryonic feedback, we adopt a baryonic correction model and use the numerical package \texttt{Baccoemu} to accelerate the evaluation of the baryonic nonlinear matter power spectrum. We design our analysis pipeline to focus on the constraints of the baryonic suppression effects, utilizing the implication given by a principal component analysis on the Fisher forecasts. Our constraint on the baryonic effects can then be used to better model and ameliorate the effects of baryons in producing cosmological constraints from the next generation large-scale structure surveys. We detect the baryonic suppression on the cosmic shear measurements with a $\sim 2 \sigma$ significance. The characteristic halo mass for which half of the gas is ejected by baryonic feedback is constrained to be $M_c > 10^{13.2} h^{-1} M_{\odot}$ (95\% C.L.). The best-fit baryonic suppression is $\sim 5\%$ at $k=1.0 {\rm Mpc}\ h^{-1}$ and $\sim 15\%$ at $k=5.0 {\rm Mpc} \ h^{-1}$. Our findings are robust with respect to the assumptions about the cosmological parameters, specifics of the baryonic model, and intrinsic alignments., Comment: 20 pages, 10 figures. DES Collaboration, Year-3 analysis

This article proposes volatility as a term with which to approach some of the challenges that shape the current world. We develop this term as an analytical concept and perspective by thinking with people and ecologies from the margins, where uncertainty and rapid transformations have long been the order of the day. An approach focusing on volatility as a social and ecological condition provides an opportunity to consider what life in a radically uncertain world means and does to its inhabitants, which may offer useful lessons to those of us who are currently being forced to let go of their illusionary certainties. The article introduces a special issue elaborating volatility as a concept and perspective in various contexts and from different angles.Résumé : Cet article propose la volatilité comme un terme permettant d’aborder certains défis qui façonnent le monde actuel. Nous développons ce terme en tant que concept analytique et perspective en réfléchissant avec les populations et les écosystèmes en marge, où l’incertitude et les transformations rapides sont depuis longtemps à l’ordre du jour. Une approche axée sur la volatilité en tant que condition sociale et écologique permet d’examiner ce que signifie de vivre dans un monde radicalement incertain, notamment pour ses habitants - une approche qui peut donner des leçons utiles à ceux d’entre nous qui sont actuellement contraints de se défaire de leurs certitudes illusoires. L’article introduit un numéro spécial qui élabore la volatilité comme concept et perspective dans divers contextes et sous différents angles.

Abstract: Hydroxy-substituted anthraquinones are among the most important derivatives in organic synthesis. The attractive biological properties of these compounds are relevant to many therapeutic areas that are of use in clinical applications. In this study synthesized several amino-substituted anthraquinones were synthesized from 1,4-dihydroxyanthraquinone using a modified Marschalk reaction. Moreover, 1,4,5-trihydroxyanthraquinone was synthesized from anacardic acid, an agro-waste from the cashew industry. The in-vitro screening of the compounds against Trypanosoma brucei parasites revealed noteworthy activity with reasonable selectivity against human cell lines. A molecular docking study was performed to analyze the synthesized compounds' modes of interaction to the trypanothione reductase's active site. Visual inspections examined the docked poses, and test compounds displayed a good binding affinity with the receptor protein. This in vitro/ molecular docking evaluation suggests that substituted 1,4-dihydroxyanthraquinone derivative can be promising starting structures in the search for active drugs against trypanosomiasis.

Item does not contain fulltext BACKGROUND: In VISION, the prostate-specific membrane antigen (PSMA)-targeted radioligand therapy lutetium-177 [(177)Lu]Lu-PSMA-617 (vipivotide tetraxetan) improved radiographic progression-free survival and overall survival when added to protocol-permitted standard of care in patients with metastatic castration-resistant prostate cancer. Here, we report additional health-related quality of life (HRQOL), pain, and symptomatic skeletal event results. METHODS: This multicentre, open-label, randomised, phase 3 trial was conducted at 84 cancer centres in nine countries in North America and Europe. Eligible patients were aged 18 years or older; had progressive PSMA-positive metastatic castration-resistant prostate cancer; an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; and had previously received of at least one androgen receptor pathway inhibitor and one or two taxane-containing regimens. Patients were randomly assigned (2:1) to receive either [(177)Lu]Lu-PSMA-617 plus protocol-permitted standard of care ([(177)Lu]Lu-PSMA-617 group) or standard of care alone (control group) using permuted blocks. Randomisation was stratified by baseline lactate dehydrogenase concentration, liver metastases, ECOG performance status, and androgen receptor pathway inhibitor inclusion in standard of care. Patients in the [(177)Lu]Lu-PSMA-617 group received intravenous infusions of 7·4 gigabecquerel (GBq; 200 millicurie [mCi]) [(177)Lu]Lu-PSMA-617 every 6 weeks for four cycles plus two optional additional cycles. Standard of care included approved hormonal treatments, bisphosphonates, and radiotherapy. The alternate primary endpoints were radiographic progression-free survival and overall survival, which have been reported. Here we report the key secondary endpoint of time to first symptomatic skeletal event, and other secondary endpoints of HRQOL assessed with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-5L, and pain assessed with the Brief Pain Inventory-Short Form (BPI-SF). Patient-reported outcomes and symptomatic skeletal events were analysed in all patients who were randomly assigned after implementation of measures designed to reduce the dropout rate in the control group (on or after March 5, 2019), and safety was analysed according to treatment received in all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov, NCT03511664, and is active but not recruiting. FINDINGS: Between June 4, 2018, and Oct 23, 2019, 831 patients were enrolled, of whom 581 were randomly assigned to the [(177)Lu]Lu-PSMA-617 group (n=385) or control group (n=196) on or after March 5, 2019, and were included in analyses of HRQOL, pain, and time to first symptomatic skeletal event. The median age of patients was 71 years (IQR 65-75) in the [(177)Lu]Lu-PSMA-617 group and 72·0 years (66-76) in the control group. Median time to first symptomatic skeletal event or death was 11·5 months (95% CI 10·3-13·2) in the [(177)Lu]Lu-PSMA-617 group and 6·8 months (5·2-8·5) in the control group (hazard ratio [HR] 0·50, 95% CI 0·40-0·62). Time to worsening was delayed in the [(177)Lu]Lu-PSMA-617 group versus the control group for FACT-P score (HR 0·54, 0·45-0·66) and subdomains, BPI-SF pain intensity score (0·52, 0·42-0·63), and EQ-5D-5L utility score (0·65, 0·54-0·78). Grade 3 or 4 haematological adverse events included decreased haemoglobin (80 [15%] of 529 assessable patients who received [(177)Lu]Lu-PSMA-617 plus standard of care vs 13 [6%] of 205 who received standard of care only), lymphocyte concentrations (269 [51%] vs 39 [19%]), and platelet counts (49 [9%] vs five [2%]). Treatment-related adverse events leading to death occurred in five (1%) patients who received [(177)Lu]Lu-PSMA-617 plus standard of care (pancytopenia [n=2], bone marrow failure [n=1], subdural haematoma [n=1], and intracranial haemorrhage [n=1]) and no patients who received standard of care only. INTERPRETATION: [(177)Lu]Lu-PSMA-617 plus standard of care delayed time to worsening in HRQOL and time to skeletal events compared with standard of care alone. These findings support the use of [(177)Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer who received previous androgen receptor pathway inhibitor and taxane treatment. FUNDING: Advanced Accelerator Applications (Novartis). 01 juni 2023

An oxygen-rich atmosphere is essential for complex animals. The early Earth had an anoxic atmosphere, and understanding the rise and maintenance of high O2 levels is critical for investigating what drove our own evolution and for assessing the likely habitability of exoplanets. A growing number of techniques aim to reproduce changes in O2 levels over the Phanerozoic Eon (the past 539 million years). We assess these methods and attempt to draw the reliable techniques together to form a consensus Phanerozoic O2 curve. We conclude that O2 probably made up around 5–10% of the atmosphere during the Cambrian and rose in pulses to ∼15–20% in the Devonian, reaching a further peak of greater than 25% in the Permo-Carboniferous before declining toward the present day. Evolutionary radiations in the Cambrian and Ordovician appear consistent with an oxygen driver, and the Devonian “Age of the Fishes” coincides with oxygen rising above 15% atm. ▪ An oxygen-rich atmosphere is essential for complex animals such as humans. ▪ We review the methods for reconstructing past variation in oxygen levels over the past 539 million years (the Phanerozoic Eon). ▪ We produce a consensus plot of the most likely evolution of atmospheric oxygen levels. ▪ Evolutionary radiations in the Cambrian, Ordovician, and Devonian periods may be linked to rises in oxygen concentration.

Firefighters are exposed to high risks and hazards, such as flames and smoke, in their daily lives. To be protected against these risks, firefighters wear protective clothing. As an employer, it is the duty to provide firefighters with good protection according to DIN EN 469. To do so, it is necessary to select, procure and maintain suitable firefighters' protective clothing. In order to identify weaknesses in the above steps and to develop and present proposals for remedying the identified weak points, an empirical study was conducted. In preparation for this study, interviews were first conducted with members of fire brigades. Based on the interviews, the relevant standards and regulations for fire fighters´ clothing were classified and areas of tension between the standards and regulations as well as their design in everyday fire brigade life were identified. Based on this, a standardized quantitative survey was conducted and the answers of the respondents were empirically evaluated. The evaluation examined both the respondents' answering behavior and the dependency between the answering behavior for different questions due to demographic differences. A key finding is that women firefighters are less satisfied with their firefighting clothing compared to men firefighters. The firefighters' clothing fits them worse. They do not feel as safe and comfortable. Moreover, woman have less confidence in the protective clothing. There is a correlation between the fit of the clothing and the satisfaction, confidence and feeling of protection

The purpose of this article is to document an investigation into the unique book classification system developed by the Pacific Northwest Indian Center (PNIC), also known as the Museum of Native American Cultures (MONAC), which operated from the mid-1960s through the early 1990s in Spokane, Washington. The article will provide some background information on PNIC/MONAC and its library operation, describe the process of reviewing and evaluating the classification system, and offer analysis into the positive and problematic aspects of the classification system in relation to other classification systems developed for materials by and about indigenous peoples of North America.

The organic carbon (Corg) stored in seagrass meadows is globally significant and could be relevant in strategies to mitigate increasing CO2 concentration in the atmosphere. Most of that stored Corg is in the soils that underlie the seagrasses. We explored how seagrass and soil characteristics vary among seagrass meadows across the geographic range of turtlegrass (Thalassia testudinum) with a goal of illuminating the processes controlling soil organic carbon (Corg) storage spanning 23° of latitude. Seagrass abundance (percent cover, biomass, and canopy height) varied by over an order of magnitude across sites, and we found high variability in soil characteristics, with Corg ranging from 0.08 to 12.59% dry weight. Seagrass abundance was a good predictor of the Corg stocks in surficial soils, and the relative importance of seagrass-derived soil Corg increased as abundance increased. These relationships suggest that first-order estimates of surficial soil Corg stocks can be made by measuring seagrass abundance and applying a linear transfer function. The relative availability of the nutrients N and P to support plant growth was also correlated with soil Corg stocks. Stocks were lower at N-limited sites than at P-limited ones, but the importance of seagrass-derived organic matter to soil Corg stocks was not a function of nutrient limitation status. This finding seemed at odds with our observation that labile standard substrates decomposed more slowly at N-limited than at P-limited sites, since even though decomposition rates were 55% lower at N-limited sites, less Corg was accumulating in the soils. The dependence of Corg stocks and decomposition rates on nutrient availability suggests that eutrophication is likely to exert a strong influence on carbon storage in seagrass meadows.

Purpose: Tumor hypoxia is a paradigmatic negative prognosticator of treatment resistance in head and neck squamous cell carcinoma (HNSCC). The lack of robust and reliable hypoxia classifiers limits the adaptation of stratified therapies. We hypothesized that the tumor DNA methylation landscape might indicate epigenetic reprogramming induced by chronic intratumoral hypoxia. Experimental Design: A DNA-methylome–based tumor hypoxia classifier (Hypoxia-M) was trained in the TCGA (The Cancer Genome Atlas)-HNSCC cohort based on matched assignments using gene expression–based signatures of hypoxia (Hypoxia-GES). Hypoxia-M was validated in a multicenter DKTK-ROG trial consisting of human papillomavirus (HPV)–negative patients with HNSCC treated with primary radiochemotherapy (RCHT). Results: Although hypoxia-GES failed to stratify patients in the DKTK-ROG, Hypoxia-M was independently prognostic for local recurrence (HR, 4.3; P = 0.001) and overall survival (HR, 2.34; P = 0.03) but not distant metastasis after RCHT in both cohorts. Hypoxia-M status was inversely associated with CD8 T-cell infiltration in both cohorts. Hypoxia-M was further prognostic in the TCGA-PanCancer cohort (HR, 1.83; P = 0.04), underscoring the breadth of this classifier for predicting tumor hypoxia status. Conclusions: Our findings highlight an unexplored avenue for DNA methylation–based classifiers as biomarkers of tumoral hypoxia for identifying high-risk features in patients with HNSCC tumors.

Background: Influenza vaccines have been demonstrated to effectively reduce the incidence of influenza infection and potentially associated risks of cardiovascular events in patients with cardiovascular disease (CVD). Despite strong guideline and public health endorsements, global influenza vaccination rates in patients with CVD are highly variable. This prespecified analysis of NUDGE-FLU (Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake) examined the effect of digital behavioral nudges on influenza vaccine uptake based on the presence of CVD. Methods: NUDGE-FLU was a randomized, pragmatic, nationwide, register-based trial that included Danish citizens 65 years of age or older during the 2022 to 2023 influenza season. Households were randomized in a 9:1:1:1:1:1:1:1:1:1 ratio to usual care or 9 electronic letters with designs based on behavioral concepts. Danish nationwide registers were used to collect baseline and outcome data. The primary end point was receipt of an influenza vaccine on or before January 1, 2023. The effects of the intervention letters were examined according to the presence of CVD and across cardiovascular subgroups that included heart failure, ischemic heart disease, and atrial fibrillation. Results: Of 964 870 NUDGE-FLU participants from 691 820 households, 264 392 (27.4%) had CVD. During follow-up, 83.1% of participants with CVD versus 79.2% of participants without CVD received an influenza vaccination ( P P for interaction=0.41). A repeated letter strategy with a reminder follow-up letter 14 days later was also effective in increasing influenza vaccination, irrespective of CVD (CVD: absolute difference, +0.80 percentage points [99.55% CI, –0.27 to 1.86]; no CVD: +0.67 percentage points [99.55% CI, –0.06 to 1.40]; P for interaction=0.77). Effectiveness of both nudging strategies was consistent across all major CVD subgroups. None of the other 7 nudging strategies were effective, regardless of CVD status. Conclusions: Electronic letter interventions emphasizing the potential cardiovascular benefits of influenza vaccination and using a reminder letter strategy were similarly beneficial in increasing influenza vaccination rates among older adults with and without CVD and across cardiovascular subgroups. Electronic nudges may improve influenza vaccine uptake in individuals with CVD. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05542004.

Abstract: Research into the effects of social media on well-being often distinguishes “active” and “passive” use, with passive use supposedly more harmful to well-being (i.e., the passive use hypothesis). Recently, several studies and reviews have begun to question this hypothesis and its conceptual basis, the active/passive dichotomy. As this dichotomy has become a staple of social media research but evidence challenging its validity is mounting, a comprehensive debate on its pros, cons, and potential future is needed. This adversarial review brings together two voices – one more supportive, and the other more critical – toward the active/passive model. In constructive dialogue, we summarize and contrast our two opposing positions: The first position argues that the active/passive dichotomy is a useful framework because it adequately describes how and why passive use is (more) harmful for well-being. The second position challenges the validity of the dichotomy and the passive use hypothesis specifically. Arguments are presented alongside (a) the empirical basis, (b) conceptualization, and (c) operationalization of active and passive use, with particular focus on the passive use hypothesis. Rather than offering a conciliatory summary of the status quo, the goal of this review is to carve out key points of friction in the literature on the effects of social media through fruitful debate. We summarize our main agreements and unresolved disagreements on the merits and shortcomings of the active/passive dichotomy. In doing so, this review paves the way for researchers to decide whether and how they want to continue applying this lens in their future work.

Mit Einführung des ersten bundesrechtlich geregelten Gesetzes der Anästhesietechnischen und Operationstechnischen Assistenz und der nachfolgenden Ausbildungs- und Prüfungsverordnung treten verbindliche und ausdifferenzierte Regelungen bezüglich Praxisanleitung und -begleitung in Kraft. Der Beitrag erläutert die Termini Praxisanleitung und -begleitung sowie die einzelnen relevanten Regelungen der praktischen Ausbildung.

O hálux varo é um acometimento infrequente na rotina ortopédica e consiste no desvio medial do hálux em relação ao primeiro metatarso. No presente artigo, relatamos o caso de uma paciente, do sexo feminino, com 45 anos, que chegou ao serviço de saúde após sofrer um trauma na região do pé direito. A paciente evoluiu com uma deformidade, ao apresentar um hálux varo pós-traumático, que necessitará de posterior intervenção cirúrgica. Para tanto, foi aplicada a técnica Mini TightRope, a qual apresentou vantagens em relação a outras estratégias cirúrgicas, já que pode promover a reabilitação funcional e estética do paciente.

Por meio de estudo retrospectivo, do período de janeiro de 2017 a maio de 2019, 289 animais foram testados para FIV e FeLV e os resultados foram destinados a análises de alterações hematológicas apresentadas. O teste estatístico utilizado para a associação foi o teste do qui-quadrado ao nível de 5% de significância. Desta amostra total, 208 (71,97%) animais foram negativos ao teste imunocromatográfico, enquanto 81 (28,03%) foram positivos. Destes positivos 14 (17,28%) eram apenas FIV positivos, 51 (62,96%) eram apenas FeLV e 16 (19,75%) eram FIV e FeLV positivos. Os resultados estatísticos revelaram que o perfil de risco na FeLV está relacionado à idade, principalmente animais de 0 a 3 anos de idade, enquanto que no perfil de risco do FIV prevaleceram machos não castrados. Nos achados hematológicos, estatisticamente houve relação entre FeLV e baixa contagem de hemácias e concentração de hemoglobina, enquanto infecções concomitantes de FIV e FeLV apresentaram relação com baixa contagem de hemácias. Valores dentro dos limites de referência, mas com diferença estatística, foram observados para leucócitos totais em animais FeLV positivos. Conclui-se que gatos acometidos por FIV são principalmente machos inteiros, enquanto pelo FeLV são animais jovens, de até 3 anos de idade, que se apresentam anêmicos e níveis normais de leucócitos, enquanto nos coinfectados a anemia é a principal alteração.

ZusammenfassungMusikspielstätten sind ein integraler Teil der Musikwirtschaft und leisten durch ihre Aktivitäten auch einen sozialen und kulturellen Mehrwert in den Städten und Regionen. Sie dienen als Orte für künstlerische Experimente, für neue Talente und für Begegnungen und Austausch. Das trifft in besonderem Maße auf kleine Musikspielstätten zu, die in einem Spannungsfeld aus musikalisch-ästhetischem Anspruch und den ökonomischen Notwendigkeiten eines Gewerbebetriebs operieren. Insbesondere in prosperierenden Städten stehen sie oftmals unter Druck.Vor diesem Hintergrund untersucht der vorliegende Beitrag verschiedene Determinanten der Umsatzrentabilität von Musikspielstätten. Dabei betrachten wir kulturelle und räumliche Aspekte, um zu klären, ob und in welchem Maße diese den Umsatz beeinflussen. Die Ergebnisse der quantitativen Auswertung stammen aus zwei Analysen: (1) eine deskriptive Bestandsaufnahme kultureller und ökonomischer Kennzahlen und (2) eine multivariate Regressionsanalyse, um Zusammenhänge zwischen strukturellen, kulturellen und ökonomischen Merkmalen zu untersuchen.Unsere Befunde zeigen, dass neben dem zu erwartenden positiven Einfluss von Kapazität und Anzahl der Veranstaltungen auch verschiedene Aspekte der Programmgestaltung (z. B. Genrevielfalt und Vielfalt der Veranstaltungsformate) signifikant mit der Umsatzhöhe zusammenhängen. Die Ergebnisse liefern wichtige Hinweise für politische Entscheidungsträger:innen, die die kulturelle Vielfalt und Lebendigkeit ihrer lokalen Musik-Ökosysteme fördern möchten.

The article presents the problems of assumptions of inclusive education. Some of the assumptions appear hypocritical, where declarations of inclusion are accompanied by an exclusionary discourse. These discourses are analyzed in the light of the development of the theory of special education and in the actions of educational officials and politicians. Particular attention was paid to the Education for All project. The author points out that this project, despite valuable declarations, contains in the executive part a traditional, clinical image of person with disabilities. This image is not conductive to the inclusion of children in joint education.

Inland ships are an important source of NOx, especially for cities along busy waterways. The amount and effect of such emissions depend on the traffic density and NOx emission rates of individual vessels. Ship emission rates are typically derived using in situ land measurements in relation to NOx emission factors (e.g. the number of pollutants emitted by ships per unit of burnt fuel). In this study, a different approach is taken, and NOx emission rates are obtained (in g s−1). Within the EU LIFE project, CLean INland SHipping (CLINSH), a new approach to calculating the NOx emission rates from data of in situ measurement stations has been developed and is presented in this study. Peaks (i.e. elevated concentrations) of NOx were assigned to the corresponding source ships, using the AIS (automated identification system) signals they transmit. Each ship passage was simulated, using a Gaussian puff model, in order to derive the emission rate of the respective source ship. In total, over 32 900 ship passages have been monitored over the course of 4 years. The emission rates of NOx were investigated with respect to ship speed, ship size, and direction of travel. Comparisons of the onshore-derived emission rates and those on board for selected CLINSH ships show good agreement. The derived emission rates are of a similar magnitude to emission factors from previous studies. Most ships comply with existing limits due to grandfathering. The emission rates (in g s−1) can be directly used to investigate the effect of ship traffic on air quality, as the absolute emitted number of pollutants per unit of time is known. In contrast, for relative emission factors (in g kg−1 fuel), further knowledge about the fuel consumption of the individual ships is needed to calculate the number of pollutants emitted per unit of time.

Two blood-based brain biomarker tests such as the combination of glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 (GFAP+UCH-L1) or S100B have potential to reduce the need for head computed tomography (CT) scanning in patients with mild traumatic brain injury (mTBI). We assessed the clinical and economic impact of using GFAP+UCH-L1 versus CT scan and GFAP+UCH-L1 versus S100B to screen adults with suspected mTBI presenting to an emergency department (ED). A decision model was developed to estimate costs and health outcomes of GFAP+UCH-L1, CT scan, and S100B associated with these screening protocols. Model parameters were extracted from peer-reviewed articles, clinical guidelines, and expert opinion. Analysis was performed from a French health care system perspective (costs in 2020 euros). In the model, patients with a positive biomarker receive a CT scan to confirm the presence of intracranial lesions (ICLs). Depending on clinical state and biomarker and CT results, patients were discharged immediately, kept for observation in the ED, admitted for in-hospital stay and observation, or admitted for surgical management. Incorrect test results may lead to delayed treatment and poor outcomes or overtreatment. GFAP+UCH-L1 use was associated with an overall decrease in CT scans when compared with CT screening or S100B use (325.42 and 46.43 CTs per 1000 patients, respectively). The use of GFAP+UCH-L1 resulted in modest cost savings when compared with CT scanning and with S100B. In all cases, use of GFAP+UCH-L1 marginally improved quality-adjusted life-years (QALYs) and outcomes. Thus, screening with GFAP+UCH-L1 reduced the need for CT scans when compared with systematic CT scan screening or use of S100B while maintaining similar costs and health outcomes.

Galena is treated as the most important silver ore in antiquity and especially in Roman mining history, but many other silver mineralisation and phases occur in the Earth's crust that also contain valuable amounts of silver for exploitation. This study addresses the silver-containing sulfosalts and how to decide between the alternative ores when only metallurgical remains are preserved and the mining context is not evident. Numerous samples of ore minerals, slags, lead metal and stones were collected by one of us (C. Domergue) over several years in the Spanish Sierra Morena, including two Roman foundry sites: Cerro del Plomo and Fuente Espi, both in the mining district of Linares-La Carolina. Cerro del Plomo is closely associated with lead-bearing ore veins near the foundry, while the mines that supplied Fuente Espi with lead ore have not yet been archaeologically explored. The metallurgical remains from the two foundries were analysed for their microstructure, mineralogy and phase composition using microscopy, electron microprobe analysis and X-ray diffraction. It was hoped that the litharge in particular would provide information about the ores used. Metal inclusions of copper and lead were identified, both still containing some silver. The cooling history and stratigraphy of the litharge cakes were developed and parallels drawn with earlier cupellation models. The litharge cakes from Cerro del Plomo and Fuente Espi are comparable in terms of microstructure and phase composition. Chemical and isotope analysis will follow and be the subject of a separate publication.

Purpose: This study evaluated the impact of 1-day workshops on teachers’ knowledge, practices, and dispositions using known characteristics of quality professional development and Guskey’s five levels of professional development evaluation. Method: Eight workshops were evaluated over a 2-year period using pre/post surveys, end-of-workshop surveys, observations, interviews, and artifacts. Results: Participants reported high levels of satisfaction and trainer effectiveness scores at the end of workshops. Statistical analyses revealed improvements in four of six outcome variables 4 weeks after workshop completion: self-reported knowledge, utilization of implementation strategies, presence of a community of continued learning, and teacher efficacy. Qualitative data corroborated these results but offered mixed evidence of teacher implementation and improved student outcomes. Discussion/Conclusion: Findings confirm that 1-day workshops aligned with characteristics of quality professional development are highly valued by participants and can improve teachers’ knowledge and efficacy, but teacher practice and student learning may be more difficult to influence and document.

Study Design Systematic review. Objective The aim of this study was to conduct a systematic overview of the pathogenesis and the treatment options of combined odontoid and atlas fractures in geriatric patients. Methods This review is based on articles retrieved by a systematic search in the PubMed and Web of Science databases for articles published until February 2021 dealing with combination fractures of C1 and C2 in geriatric patients. Results Altogether, 438 articles were retrieved from the literature search. A total of 430 articles were excluded. The remaining eight original articles were included in this systematic review depicting the topics pathogenesis, non-operative treatment, posterior approach, and anterior approach. The overall level of evidence of the studies is low. Conclusion Combined odontoid and atlas fractures in the geriatric population are commonly caused by simple falls and seem to be associated with atlanto-odontoid osteoarthritis. Non-operative treatment with a cervical orthosis is a feasible treatment option in the majority of patients with stable C2 fractures. In case of surgery posterior C1 and C 2 stabilization and anterior triple or quadruple screw fixation are possible techniques. Some patients may also deserve an occipito-cervical fusion. A possible treatment algorithm is proposed.

To understand current and prevent future measles mortality burden, it is critical to have robust estimates of measles case fatality. Dynamic estimates of measles case fatality ratios (CFR) that are age-, location-, and time-specific are essential to capture variation in underlying population-level factors that contribute systematically to increases or decreases in case fatality, such as vaccination coverage and measles incidence. In this study, we updated estimates of measles CFR by expanding upon previous systematic reviews and implementing a meta-regression model.

Acknowledgements: The authors thank G. Marciani and O. Jöris for comments on archaeology; C. Jeong, M. Spyrou and K. Prüfer for comments on genetics; M. O’Reilly for graphical support for Fig. 5 and Extended Data Fig. 9; the entire IT and laboratory teams at the Department of Archaeogenetics of MPI-SHH for technical assistance; M. Meyer and S. Nagel for support with single-stranded library preparation; K. Post, P. van Es, J. Glimmerveen, M. Medendorp, M. Sier, S. Dikstra, M. Dikstra, R. van Eerden, D. Duineveld and A. Hoekman for providing access to human specimens from the North Sea (The Netherlands); M. D. Garralda and A. Estalrrich for providing access to human specimens from La Riera (Spain); J. Górski and M. Zając for providing access to human specimens from Maszycka cave; C. Di Patti for providing access to human specimens from San Teodoro 2 (Italy); P. Blaževičius for providing access to the Donkalnis human remains and the new radiocarbon dates; the Italian Ministry of Culture and Soprintendenza Archeologia Belle Arti e Paesaggio for the Provinces of Verona, Rovigo, and Vicenza for granting access to the human remains of Tagliente 2; F. Fontana, who carries out investigations of the Riparo Tagliente site (Italy); the Friuli Venezia Giulia Superintendency for providing access to the human tooth Pradis 1; and the Soprintendenza Archeologia Belle Arti e Paesaggio for the Provinces of Barletta-Andria-Trani and Foggia for providing access to the Paglicci human remains. This project has received funding by the European Research Council under the European Union’s Horizon 2020 research and innovation programme under grant agreements no. 803147-RESOLUTION (to S.T.), no. 771234-PALEoRIDER (to W.H.), no. 864358 (to K.M.), no. 724703 and no. 101019659 (to K.H.). K.H. is also supported by the Deutsche Forschungsgemeinschaft (DFG FOR 2237). E.A. has received funding from the Van de Kamp fonds. PACEA co-authors of this research benefited from the scientific framework of the University of Bordeaux’s IdEx Investments for the Future programme/GPR Human Past. A.G.-O. is supported by a Ramón y Cajal fellowship (RYC-2017-22558). L. Sineo, M.L. and D.C. have received funding from the Italian Ministry of University and Research (MUR) PRIN 2017 grants 20177PJ9XF and 20174BTC4R_002. H. Rougier received support from the College of Social and Behavioral Sciences of CSUN and the CSUN Competition for RSCA Awards. C.L.S. and T. Saupe received support from the European Union through the European Regional Development Fund (project no. 2014-2020.4.01.16-0030) and C.L.S. received support from the Estonian Research Council grant PUT (PRG243). S. Shnaider received support from the Russian Science Foundation (no. 19-78-10053)., Modern humans have populated Europe for more than 45,000 years1,2. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period3. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago. We identify a genetic ancestry profile in individuals associated with Upper Palaeolithic Gravettian assemblages from western Europe that is distinct from contemporaneous groups related to this archaeological culture in central and southern Europe4, but resembles that of preceding individuals associated with the Aurignacian culture. This ancestry profile survived during the Last Glacial Maximum (25,000 to 19,000 years ago) in human populations from southwestern Europe associated with the Solutrean culture, and with the following Magdalenian culture that re-expanded northeastward after the Last Glacial Maximum. Conversely, we reveal a genetic turnover in southern Europe suggesting a local replacement of human groups around the time of the Last Glacial Maximum, accompanied by a north-to-south dispersal of populations associated with the Epigravettian culture. From at least 14,000 years ago, an ancestry related to this culture spread from the south across the rest of Europe, largely replacing the Magdalenian-associated gene pool. After a period of limited admixture that spanned the beginning of the Mesolithic, we find genetic interactions between western and eastern European hunter-gatherers, who were also characterized by marked differences in phenotypically relevant variants.

Leukemia cells reciprocally interact with their surrounding bone marrow microenvironment (BMM), rendering it hospitable to leukemia cell survival, for instance through the release of small extracellular vesicles (sEVs). In contrast, we show here that BMM deficiency of pleckstrin homology domain family M member 1 (PLEKHM1), which serves as a hub between fusion and secretion of intracellular vesicles and is important for vesicular secretion in osteoclasts, accelerates murine BCR-ABL1+ B-cell acute lymphoblastic leukemia (B-ALL) via regulation of the cargo of sEVs released by BMM-derived mesenchymal stromal cells (MSCs). PLEKHM1-deficient MSCs and their sEVs carry increased amounts of syntenin and syndecan-1, resulting in a more immature B-cell phenotype and an increased number/function of leukemia-initiating cells (LICs) via focal adhesion kinase and AKT signaling in B-ALL cells. Ex vivo pretreatment of LICs with sEVs derived from PLEKHM1-deficient MSCs led to a strong trend toward acceleration of murine and human BCR-ABL1+ B-ALL. In turn, inflammatory mediators such as recombinant or B-ALL cell–derived tumor necrosis factor α or interleukin-1β condition murine and human MSCs in vitro, decreasing PLEKHM1, while increasing syntenin and syndecan-1 in MSCs, thereby perpetuating the sEV-associated circuit. Consistently, human trephine biopsies of patients with B-ALL showed a reduced percentage of PLEKHM1+ MSCs. In summary, our data reveal an important role of BMM-derived sEVs for driving specifically BCR-ABL1+ B-ALL, possibly contributing to its worse prognosis compared with BCR-ABL1− B-ALL, and suggest that secretion of inflammatory cytokines by cancer cells in general may similarly modulate the tumor microenvironment.

La actividad física y ejercicio físico durante la gestación entregan beneficios tanto para la madre, al disminuir el riesgo de desarrollar condiciones como preeclampsia y diabetes gestacional, como para el feto, disminuyendo condiciones como la macrosomía y morbilidad respiratoria llevando a mejorar el resultado perinatal. Del mismo modo, una mejor condición física se asocia a resultados perinatales favorables. A nivel mundial, existen una serie de recomendaciones sobre los niveles de actividad física necesarios para obtener estos beneficios. La mayoría coincide en que se deben alcanzar al menos 150 minutos de actividad física moderada a la semana. A pesar de esto, la actividad física, el ejercicio y la condición física durante la gestación han sido poco explorados en Chile, existiendo una brecha en el conocimiento respecto a este tema. El objetivo de esta revisión es recopilar la evidencia disponible en Chile sobre actividad física, ejercicio y condición física durante la gestación, identificando las principales brechas de conocimiento respecto a este tema. Palabras clave: Actividad física, gestación, condición física. Abstract. Physical activity and exercise during pregnancy are beneficial for the mother, reducing the risk of developing conditions such as preeclampsia and gestational diabetes, as well as for the fetus by decreasing complications such as fetal macrosomia and respiratory outcomes, leading to an improved perinatal outcome. In the same way, a better physical fitness is associated to better perinatal outcomes. Worldwide, there are several recommendations regarding the appropriate physical activity levels necessary to obtain these benefits. Most agree that at least 150 minutes of moderate physical activity per week should be achieved. Despite this, physical activity, exercise, and physical fitness during pregnancy have been poorly explored in Chile, and thus there is a gap in knowledge on this subject. This review aims to compile the evidence available in Chile on physical activity, exercise, and physical fitness during pregnancy, identifying the main knowledge gaps on this topic. Keywords: Physical activity, pregnancy, fitness.

O artigo parte da experiência dolorosa da perda dos entes queridos em tempos de pandemia para iluminar a questão do sentido da vida e da morte. O objetivo é relacionar essas experiências com situações dramáticas. Na comunidade cristã de Tessalônica pelo ano 51 da era cristã a preocupação era o destino dos mortos por ocasião da vinda do Senhor. No século III, Cipriano na obra “De mortalitate” em meio à epidemia exorta os cristãos a não temer a morte, pois morrer era encontrar-se com o Senhor. O estudo oferece um significado teológico da morte à luz da ressurreição de Cristo. A morte possui um significado, pois viver em Cristo é viver vida nova, e morrer é estar com Cristo ressuscitado. Conclui-se que a esperança cristã na vida eterna não é alienação num futuro celestial. Nas situações de morte quem vive como ressuscitado é solidário com os que sofrem e comprometido em promover vida. Portanto, a vida presente espelha a realidade futura. No entanto, quando o presente não apresenta sinais de esperança, coloca-se mais ênfase no futuro em Deus.

Kurzfassung Trotz des Fehlschlags seiner „Spezialoperation“ in der Ukraine setzt der russische Präsident Putin unvermindert auf Sieg. Russlands Ende 2022 erkennbare Strategie für die vierte Kriegsphase zielt auf Ermattung des ukrainischen Widerstands durch strategische Bombardierungen auf zivile Ziele und Infrastruktur sowie auf Wiedererlangung der militärischen Initiative durch Einziehen von Hundertausenden Reservisten und Ankurbeln der Rüstungsindustrie. Erfolg oder Nichterfolg dieser Strategie hängen davon ab, ob die westlichen Staaten die Ukraine weiterhin mit Waffen und Wirtschaftshilfe unterstützen. Entscheidend ist aber auch, ob Russland seine Strategie überhaupt implementieren kann, ohne in gravierende Schwierigkeiten zu geraten. Die wirtschaftliche Leistungsfähigkeit Russlands ist begrenzt und wird durch die Folgen der westlichen Sanktionen weiter eingeschränkt. Zudem ist unklar, wie sich dieser Krieg auf Russland auswirkt, sollte er nach Putins Vorstellungen fortgesetzt werden. Viele Experten sehen schon einen Kollaps Russlands voraus.