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This is an obituary on Wolfgang Bartuschat (May 13, 1938 – August 10, 2022), an eminent Spinoza scholar at Universität Hamburg. As an interpreter, Bartuschat emphasized the human and individual perspective in Spinoza’s metaphysical and political thought. Bartuschat will also be remembered as an excellent translator and editor.

The present study analyzed trends in premature mortality from Noncommunicable diseases (NCDs) between 1990 and 2019, the projections up to 2030, and the risk factors (RFs) attributable to these diseases in the Community of Portuguese Language Countries (CPLP). Estimates from the Global Burden of Disease (GBD) study and the analysis of the burden of premature mortality due to NCDs were used for nine CPLP countries, applying age-standardized rates, using RStudio. Portugal, Brazil, Equatorial Guinea, Angola, and Guinea Bissau showed declining premature mortality rates caused by NCDs, while East Timor, Cape Verde, São Tomé and Príncipe, and Mozambique showed an increase in rates. Projections indicate that none of the countries is expected to achieve the goals of reducing premature mortality due to NCDs by one third by 2030. The attributable burden of disease showed that the most important RFs in 2019 were: high systolic blood pressure (SBP), tobacco, dietary risks, high body mass index (BMI), and air pollution. It can therefore be concluded that there are profound differences in the burden of NCDs among the countries, with better results in Portugal and Brazil, and that no CPLP country is likely to reach the NCD reduction target by 2030.

Introduction: Disaster Medicine (DM) requires skills, knowledge, and prior experience that are rarely put to test by health care providers. Pediatric DM presents unique challenges in terms of both knowledge and practice. Methods: An anonymous survey consisting of demographic and five-point Likert scale questions was administered to physicians, nurses, and other medical personnel from Israel’s major medical emergency teams who were deployed to respond to the refugee crisis in Ukraine. This included teams from the Hadassah and Tel Aviv Sourasky Medical Centers and the Israel Ministry of Health. Results: Of the 171 members of the medical teams deployed on the Ukraine border, a total of 105 responses were obtained (61.4%) from 61 physicians, 50 nurses, and 12 other health care providers. The teams were composed of pediatricians (31.6%), internal medicine physicians (21.6%), Emergency Medicine and intensive care physicians (18.0%), and 31.0% other specialties. For 60% of the participants, this was their first deployment, and 78% had received no training in DM. Members rated the need for DM training at 4/5 (IQR 3-5). Forty-nine (49) members (46.6%) were not briefed on situational awareness and 97 members (89.5%) were not trained in the recognition of acute stress reactions. The responders also rated their concerns about providing medical aid to children at 2/5 (IQR 1-3). A medical clown was part of the teams 42.8% of the time; the presence of clowns was rated at a median of 4/5 (IQR 4-5). The team members underscored the need for more targeted training in DM at 5/5 (IQR 3-5). Conclusion: The findings highlight the need for the formulation of a disaster education model that includes pediatric DM.

The construction industry has been evolving, embracing the delicate balance between the Fourth Industry Revolution and sustainable construction to create a sustainable and resilient built environment. Integrating digital tools and technologies in a renowned conventional construction industry is challenging, mainly due to the complex interaction between heterogeneous but heuristic construction processes, building systems, and workflows in achieving a common goal. This study took the initiative to review digital tool adoption and its role in the sustainable built environment by examining the impact of digital adoption in a sustainable built environment in terms of societal and industry impacts. A quantitative analysis is conducted, collecting 63 industry practitioners analysed through regression analysis. The result reveals that energy conservation is the most significant element in the sustainable built environment, which brought the greatest impact on both society and industry in Malaysia. Based on the results, it is found that the digital adoption level in the Malaysian construction industry is still at a minimal level. Through the introduction of Indutry4wrd, National 4IR and Construction 4.0 Strategic Plan (2021–2025), the importance of digital tools and technologies is slowly being acknowledged. The result of the study is significant to benchmark the current digital tools adoption in the Malaysian sustainable built environment. Moreover, the contribution could be made in terms of better understanding and facilitating, where relevant, greater usage of digital tools in the construction industry to promote efficiency.

Objective Studies of Australian health workforce demographics tend to be limited to single professions, a set geographic area, or based on incomplete data. This study aims to comprehensively describe changes to the demographic characteristics of Australia’s regulated health professions over 6 years. Methods Data were sourced from the Australian Health Practitioner Regulation Agency (Ahpra) registration database, and a retrospective analysis of 15 of the 16 regulated health professions between 1 July 2015 and 30 June 2021 was conducted. Variables including profession, age, gender and state/territory locations for the practitioners’ principal places of practice were analysed descriptively and via appropriate statistical tests. Results Changes in age, gender representation, and place of practice varied significantly and in different ways across the 15 professions. The total number of registered health practitioners increased by 141 161 (22%) from 2016 to 2021. The number of registered health practitioners per 100 000 population increased by 14% from 2016, with considerable variation across the professions. In 2021, women accounted for 76.3% of health practitioners across the 15 health professions, a significant increase of 0.5% points since 2016. Conclusions Changes to demographics, especially in ageing workforces and feminising professions, can have implications for workforce planning and sustainability. Future research could build on this demographic trend data by investigating causes or undertaking workforce supply or demand modelling.

Summary Whereas some studies have addressed the conditions and practices required to infuse critical notions into the organizational context of public social services, there is a paucity of knowledge on what a critical public service can look like in actual practice. This article explores the possibility of applying critical theory and practice at the organizational level of public social services. It focuses on one social services department in Israel that underwent a six-year process of learning and implementing the Poverty-Aware Paradigm. Findings Based on an in-depth case study that combines ethnographic and participatory methods, we outline how critical ideas are translated to four organizational principles: developing a critical learning culture, acknowledging services users’ knowledge and skills, leading a critical discourse in the community, and poverty-proofing services and allocating resources to tackle poverty. Each of these principles is presented with derivative organizational practices and a detailed account of their implementation. Applications By broadening the framing of critical practice as an individual, street-level endeavor, the findings offer policymakers and public social services professionals an organizational model that mitigates the negative consequences of current neoliberal and managerial policies around the world.

Patients with refractory or relapsed and refractory myeloid malignancies have a poor prognosis. Allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning (MAC) in patients with active, chemotherapy-refractory myeloid disease is historically associated with high rates of relapse and nonrelapse mortality (NRM). A MAC regimen combining clofarabine with busulfan (Clo/Bu4) has been reported to exhibit antileukemic activity with acceptable toxicity in patients age ≤70 years. Here we describe the clinical outcomes of a real-world population of patients with active myeloid malignancies undergoing allogeneic HCT with Clo/Bu4 MAC. In a single-center retrospective descriptive analysis, we identified patients who underwent HCT for myeloid malignancies not in remission using Clo/Bu4 MAC between 2012 and 2020. We report event-free survival (EFS) and overall survival (OS), cumulative incidences of relapse and NRM, and the incidence and severity of acute and chronic graft-versus-host disease (GVHD). We identified 69 patients with a median age of 60 years (range, 22 to 70 years). Most patients had relapsed/refractory or primary refractory acute myelogenous leukemia (AML; n = 55) or refractory myelodysplastic syndrome (MDS; n = 12); 1 patient had chronic myelogenous leukemia, and 1 patient had a blastic plasmacytoid dendritic cell neoplasm. Fifty patients (72.5%) had complete remission at day 100 post-transplantation. Two-year EFS and OS were 30% (95% confidence interval [CI], 20% to 44%) and 40% (95% CI, 29% to 54%), respectively. Patients with AML had a 2-year EFS and OS of 28% (95% CI, 18% to 44%) and 38% (95% CI, 27% to 54%), respectively; those with MDS had a 2-year EFS and OS of 47% (95% CI, 25% to 88%) and 56% (95% CI, 33% to 94%), respectively. The cumulative incidence of relapse at 2 years was 39% (95% CI, 27% to 51%) for all patients, including 45% (95% CI, 31% to 58%) in the patients with AML and 18% (95% CI, 2% to 45%) in those with MDS. NRM at 2 years was 31% (95% CI, 20% to 42%), including 27% (95% CI, 15% to 39%) in patients with AML and 35% (95% CI, 10% to 63%) in those with MDS. The total incidence of acute GVHD (aGVHD) of any severity was 80%, and the incidence of grade III-IV aGVHD was 22%. In patients who achieved remission, those who required systemic immunosuppression for aGVHD (58%) had poorer 2-year EFS (29% versus 54%; P = .05) and 2-year OS (39% versus 70%; P = .04) compared to those who did not. The 2-year cumulative incidence of chronic GVHD was 44% (95% CI, 28% to 58%). Clo/Bu4 MAC followed by allogeneic HCT for patients with active myeloid malignancies is an effective transplantation strategy for patients up to age 70, particularly those with advanced MDS. The high incidence of and poor outcomes associated with aGVHD highlight the importance of optimizing preventative strategies.

There is increasing recognition that pathogenic germ line variants drive the development of hematopoietic cancers in many individuals. Currently, patients with hereditary hematologic malignancies (HHMs) receive similar standard therapies and hematopoietic stem cell transplant (HSCT) approaches as those with sporadic disease. We hypothesize that patients with myeloid malignancies and deleterious germ line predisposition variants have different posttransplant outcomes than those without such alleles. We studied 472 patients with myeloid neoplasms, of whom 26% had deleterious germ line variants and 34% underwent HSCT. Deleterious germ line variants in CHEK2 and DDX41 were most commonly seen in American and Australian cohorts, respectively. Patients with deleterious germ line DDX41 variants had a higher incidence of severe (stage 3-4) acute graft-versus-host disease (GVHD) (38%) than recipients with deleterious CHEK2 variants (0%), other HHM variants (12%), or patients without such germ line variants (9%) (P = .002). Importantly, the use of posttransplant cyclophosphamide reduced the risk of severe acute GVHD in patients receiving HSCT for deleterious germ line DDX41-associated myeloid neoplasms (0% vs 53%, P = .03). Based on these results, we advocate the use of posttransplant cyclophosphamide when individuals with deleterious germ line DDX41 variants undergo allogeneic HSCT for myeloid malignancies, even when transplantation has been performed using wild-type donors.

Data-informed decision making in teachers’ practice, now recommended by different teacher inquiry models and policy documents, implies deep practice change for many teachers. However, not much is known how teachers perceive the different steps that analytics-informed teacher inquiry into their own practice entails. This paper presents the results of a study into developing an Analytics Model for Teacher Inquiry (AMTI), which was then used to understand how teachers (N=10) construe the steps in the model and to explore the possible constraints as well as incentives for Teaching and Learning Analytics (TLA)-informed teacher practices. In the final iteration experts (N=7) and teacher-researchers (N=2) tested and evaluated the developed model. Their feedback was used to improve the model and provide example cases with insights into possible scenarios for TLA-informed analyses of teaching.

To compare operative data and patient satisfaction between open and laparoscopic surgery for post-partum diagnosed uterine rupture.In this questionnaire-based cohort study we collected all cases of post-partum diagnosed uterine rupture after vaginal delivery, between 2016 and 2020 in a single academic tertiary center. The cohort was divided according to surgical method of repair; demographic, clinical, operative and post operative data were collected and compared between groups. A phone questionnaire on various satisfaction domains was conducted and satisfaction rates were compared between groups.Eight cases of uterine rupture following vaginal delivery were treated by laparoscopy, and eight were treated by laparotomy. The median operative time was 103 (IQR 86.3-129.0) minutes for the laparoscopy group and 61 (IQR 59.0-75.0) minutes for the laparotomy group (p=0.04). Blood transfusion was required in 25% of women who underwent laparoscopy, as compared to 88% of women who underwent laparotomy (p=0.010.05). Median hospitalization time was 3 (IQR 3-4) days in the laparoscopy group and 4 (IQR 4-4) days in the laparotomy group (p=0.2). Overall satisfaction, satisfaction from recovery, satisfaction from scars, satisfaction from ability to care for the neonate and post-operative pain and mood were all improved in the laparoscopy group, as compared to the laparotomy group.Minimally invasive surgery is a viable surgical option for patients with uterine rupture diagnosed after vaginal delivery, and may result in better patient recovery and satisfaction.

A hemoterapia é compreendida como o processo desde a captação do sangue doado, processamento dos hemocomponentes até à sua administração ao paciente ficando a cargo da enfermagem a realização da hemotransfusão e o acompanhamento junto ao paciente. O objetivo da pesquisa foi verificar o conhecimento de 95 profissionais dentre eles técnicos em enfermagem e enfermeiros inseridos nos setores de Unidades de Terapia Intensiva (UTIs) em relação aos procedimentos de transfusão e como se sentem em relação aos conhecimentos necessários à esta prática hemoterápica. Trata-se de uma pesquisa de campo, de caráter transversal descritivo, com abordagem quantiqualitativa em Unidades de Terapia Intensiva de um Hospital no norte do País sendo a coleta realizada no período de dezembro de 2021 a março de 2022. Os resultados obtidos apontam para um déficit no conhecimento em torno da terapêutica por parte da maioria dos profissionais corroborando com estudos anteriores sobre a prática, concluindo então a necessidade de planos estratégicos de mobilização profissional para realização e manutenção de medidas de educação continuada objetivando mais qualidade na assistência e minimização de erros por falta de conhecimento.

Linking genotype with phenotype is a fundamental goal in biology and requires robust data for both. Recent advances in plant-genome sequencing have expedited comparisons among multiple-related individuals. The abundance of structural genomic within-species variation that has been discovered indicates that a single reference genome cannot represent the complete sequence diversity of a species, leading to the expansion of the pan-genome concept. For high-resolution forward genetics, this unprecedented access to genomic variation should be paralleled and integrated with phenotypic characterization of genetic diversity. We developed a multi-parental framework for trait dissection in melon (Cucumis melo), leveraging a novel pan-genome constructed for this highly variable cucurbit crop. A core subset of 25 diverse founders (MelonCore25), consisting of 24 accessions from the two widely cultivated subspecies of C. melo, encompassing 12 horticultural groups, and 1 feral accession was sequenced using a combination of short- and long-read technologies, and their genomes were assembled de novo. The construction of this melon pan-genome exposed substantial variation in genome size and structure, including detection of ~300 000 structural variants and ~9 million SNPs. A half-diallel derived set of 300 F

Headache is a common complaint in children who present at the pediatric emergency department (PED). Serious conditions such as intracranial tumors and idiopathic intracranial hypertension (IIH) should be rapidly ruled out. Ophthalmoscopy for the presence of papilledema has long been considered critical to the assessment of headaches in children; however, the yield of this procedure is poorly validated. This retrospective study implemented a computerized search of the medical records of a single tertiary center to identify all children aged 2-18 years who presented at the PED complaining of headache between 2007 and 2017. The clinical, demographic, radiographic, and laboratory data were analyzed. Of the 948 children aged 2-18 years who presented at the PED complaining of headache, 536 had an ophthalmoscopy examination carried out by an ophthalmologist. Forty-one had papilledema, of whom 7 had an intracranial tumor, 15 had IIH, and 9 had optic nerve head drusen. Of the 495 children without papilledema, 3 had intracranial tumor, and 11 had IIH. The sensitivity and specificity of papilledema for the diagnosis of intracranial tumor were 70% and 93.5%, respectively, with an NPV and PPV of 99.4% and 17.1%, respectively. The sensitivity and specificity of papilledema for the diagnosis of intracranial pathology in general were 61.1% and 96.2%, respectively, with an NPV and PPV of 97.2% and 53.7%, respectively. Conclusion: Assessment by ophthalmoscopy for papilledema in children presenting to the PED with headache had high sensitivity and high specificity, thus reinforcing the importance of ophthalmoscopy as a screening tool in these children. What is Known: • Headache is a common complaint in children. Serious intracranial pathologies need to be rapidly excluded. • Ophthalmoscopy for the presence of papilledema is commonly used as a screening tool for intracranial pathology, but this procedure is poorly validated. What is New: • Ophthalmoscopy for the assessment of papilledema in children who present with headache to the pediatric emergency department is shown to exhibit sensitivity and specificity for the diagnosis of intracranial pathology.

Kui keeleliste osaoskuste õpetamine võõrkeeletunnis tavaliselt probleeme ei valmista, siis õpetajatele teeb muret õpilaste vähene suhtlusvalmidus. Probleemi aitavad vähendada suhtlussõbralik ja õppijaid motiveeriv keskkond, samuti loovust nõudvad õppijakesksed ning sihtkeele kultuuriruumi vastu huvi tekitavad ülesanded. Seda võimaldab simulatsioon fiktiivse identiteedi kasutamisega. Siinse sekkumisuuringu eesmärk oli välja selgitada, kuidas toetab fiktiivse identiteedi kui keeleõppemeetodi kasutamine üliõpilaste suhtlusvalmidust saksa keeles rääkimisel. Tulemustest järeldub, et meetod toetab üliõpilaste suhtlusvalmidust vaid osaliselt. Positiivsete külgedena märgiti, et fiktiivne identiteet aitab olla rohkem avatum ja spontaansem oma tegelaskujust rääkimisel. Ühtlasi paneb see otsima uusi väljendeid ja sõnu ning kiirendab sisseelamist saksakeelsesse maailma. Samas võivad selle meetodi ülesanded põhjustada rahulolematust. Osa üliõpilasi arvas, et ilma fiktiivse identiteedita oleksid nad tundides suhelnud sama palju. Negatiivset mõju avaldavate teguritena nimetati segadust erinevate identiteetide kasutamisel ja vähest huvi uue tegelaskuju väljamõtlemisel. Meetodis nähti eelkõige võimalust,kuidas keeleoskust aktiivselt arendada. Summary

An increased awareness concerning risks of algorithmic bias has driven a surge of efforts around bias mitigation strategies. A vast majority of the proposed approaches fall under one of two categories: (1) imposing algorithmic fairness constraints on predictive models, and (2) collecting additional training samples. Most recently and at the intersection of these two categories, methods that propose active learning under fairness constraints have been developed. However, proposed bias mitigation strategies typically overlook the bias presented in the observed labels. In this work, we study fairness considerations of active data collection strategies in the presence of label bias. We first present an overview of different types of label bias in the context of supervised learning systems. We then empirically show that, when overlooking label bias, collecting more data can aggravate bias, and imposing fairness constraints that rely on the observed labels in the data collection process may not address the problem. Our results illustrate the unintended consequences of deploying a model that attempts to mitigate a single type of bias while neglecting others, emphasizing the importance of explicitly differentiating between the types of bias that fairness-aware algorithms aim to address, and highlighting the risks of neglecting label bias during data collection.

This article aims to characterize physical violence by an intimate partner suffered by adult women treated in public urgency and emergency services in Brazil. This is a cross-sectional study using data from the VIVA Survey 2017. The proportions and 95% confidence intervals of the characteristics of the victim, violence, and perpetrator were calculated. The associations of characteristics were identified through Simple Correspondence Analysis (SCA). More than half of the assisted women self-declared their race/skin color to be black (70.2%) and were the victim of a male perpetrator (96.3%). Most violence occurred at home (71.1%) through physical force (74.1%). In the SCA, an association was found among the variables of age group, between 40 and 59 years; level of education, up to 08 years of study; alcohol consumption by the victim; and violence by weapons (Profile 2). An association was also found among the variables of age group, between 18 and 24 years; black race/skin color; lack of paid work; aggression on public places; and more serious injuries (Profile 4). There are different intimate partner violence (IPV) profiles for women in different contexts. Confronting IPV requires Public Policies that consider these differences in the construction of actions that focus on women and perpetrators of violence.

Resumo O objetivo deste artigo é caracterizar a violência física por parceiro íntimo sofrida por mulheres adultas atendidas nos serviços públicos de urgência e emergência do Brasil. Estudo transversal utilizando dados do VIVA Inquérito 2017. Foram calculados as frequências e os intervalos de confiança das características da vítima, da violência e do agressor. As associações das características foram identificadas por meio da análise de correspondência simples (ACS). A maioria das mulheres atendidas se autodeclarou da raça/cor da pele negra (70,2%) e foi vítima de agressor do sexo masculino (96,3%). A maioria das violências ocorreu em residência (71,1%) por meio de força corporal (74,1%). Na ACS, destaca-se a associação entre a faixa etária de 40 a 59 anos, escolaridade de até 08 anos de estudo, consumo de álcool pela vítima e violência por meio de armas (perfil 2); e a associação da faixa etária de 18 a 24 anos, raça/cor da pele negra, ausência de atividade remunerada, agressão em via pública e lesões de maior gravidade (perfil 4). Existem diferentes perfis de VPI para mulheres em diferentes contextos. O enfrentamento à VPI necessita de Políticas Públicas que considerem essas diferenças na construção de ações que foquem as mulheres e os perpetradores da violência. Abstract This article aims to characterize physical violence by an intimate partner suffered by adult women treated in public urgency and emergency services in Brazil. This is a cross-sectional study using data from the VIVA Survey 2017. The proportions and 95% confidence intervals of the characteristics of the victim, violence, and perpetrator were calculated. The associations of characteristics were identified through Simple Correspondence Analysis (SCA). More than half of the assisted women self-declared their race/skin color to be black (70.2%) and were the victim of a male perpetrator (96.3%). Most violence occurred at home (71.1%) through physical force (74.1%). In the SCA, an association was found among the variables of age group, between 40 and 59 years; level of education, up to 08 years of study; alcohol consumption by the victim; and violence by weapons (Profile 2). An association was also found among the variables of age group, between 18 and 24 years; black race/skin color; lack of paid work; aggression on public places; and more serious injuries (Profile 4). There are different intimate partner violence (IPV) profiles for women in different contexts. Confronting IPV requires Public Policies that consider these differences in the construction of actions that focus on women and perpetrators of violence.

The Hebrew Bible and other ancient Near Eastern texts describe Egyptian, Aramean, Assyrian, and Babylonian military campaigns to the Southern Levant during the 10th to sixth centuries BCE. Indeed, many destruction layers dated to this period have been unearthed in archaeological excavations. Several of these layers are securely linked to specific campaigns and are widely accepted as chronological anchors. However, the dating of many other destruction layers is often debated, challenging the ability to accurately reconstruct the different military campaigns and raising questions regarding the historicity of the biblical narrative. Here, we present a synchronization of the historically dated chronological anchors and other destruction layers and artifacts using the direction and/or intensity of the ancient geomagnetic field recorded in mud bricks from 20 burnt destruction layers and in two ceramic assemblages. During the period in question, the geomagnetic field in this region was extremely anomalous with rapid changes and high-intensity values, including spikes of more than twice the intensity of today’s field. The data are useful in the effort to pinpoint these short-term variations on the timescale, and they resolve chronological debates regarding the campaigns against the kingdoms of Israel and Judah, the relationship between the two kingdoms, and their administrations.

Funder: Please see main manuscript file., The detection of proteins is of central importance to biomolecular analysis and diagnostics. Typical immunosensing assays rely on surface-capture of target molecules, but this constraint can limit specificity, sensitivity, and the ability to obtain information beyond simple concentration measurements. Here we present a surface-free, single-molecule microfluidic sensing platform for direct digital protein biomarker detection in solution, termed digital immunosensor assay (DigitISA). DigitISA is based on microchip electrophoretic separation combined with single-molecule detection and enables absolute number/concentration quantification of proteins in a single, solution-phase step. Applying DigitISA to a range of targets including amyloid aggregates, exosomes, and biomolecular condensates, we demonstrate that the assay provides information beyond stoichiometric interactions, and enables characterization of immunochemistry, binding affinity, and protein biomarker abundance. Taken together, our results suggest a experimental paradigm for the sensing of protein biomarkers, which enables analyses of targets that are challenging to address using conventional immunosensing approaches.

Postcrisis bank regulations raised market-making costs for bank-affiliated dealers. We show that this can, somewhat surprisingly, improve overall investor welfare and reduce average transaction costs despite the increased cost of immediacy. Bank dealers in OTC markets optimize between two parallel trading mechanisms: market making and matchmaking. Bank regulations that increase market-making costs change the market structure by intensifying competitive pressure from nonbank dealers and incentivizing bank dealers to shift their business activities toward matchmaking. Thus, postcrisis bank regulations have the (unintended) benefit of replacing costly bank balance sheets with a more efficient form of financial intermediation.

As the use of the messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) Coronavirus disease 2019 vaccine has grown, reports on menstrual changes have arisen. We aimed to examine menstrual bleeding patterns and endometriosis-associated symptoms after receiving the mRNA BNT162b2 SARS-CoV-2 vaccine in women with endometriosis, as compared to the control group.This is a questionnaire-based cross-sectional study including a total of 174 women. The study group included 86 women with a confirmed diagnosis of endometriosis and the control group included 88 women with no diagnosis or suspected diagnosis of endometriosis. Each woman completed a questionnaire on menstrual bleeding patterns and endometriosis-associated symptoms before and after receiving two doses of the BNT162b2 vaccine. Primary outcomes were changes in amount or length of menstrual bleeding, rates of intermenstrual bleeding and worsening in dysmenorrhea in the endometriosis patient group, as compared to the control group. Secondary outcomes included changes in all endometriosis-associated symptoms.In our cohort, women with endometriosis were more likely to experience changes in bleeding patterns (women with endometriosis: 39.5%, control group: 31.0%, p = 0.02), and a significant worsening in endometriosis-associated symptoms with an almost 4.3-fold worsening in dysmenorrhea [95% CI 1.9-9.9, p 0.01] and 5.5-fold odds for any worsening in symptoms in endometriosis patients, as compared to the control group [95% CI 2.7-11.1, p 0.01].In our cohort, endometriosis was shown to be a significant risk factor for worsening of menstrual symptoms, after receiving the SARS-CoV-2 BNT162b2 mRNA vaccine. Further research is needed to confirm these findings.

Allogeneic hematopoietic cell transplantation (alloHCT) is indicated for patients with intermediate-risk or high-risk myelofibrosis (MF) and remains the sole potential cure. Reduced-intensity conditioning (RIC) is commonly used because of older patient age, comorbidities, and a high incidence of transplantation-related mortality. Patients with MF are at increased risk of graft failure (GF), which is more common with RIC regimens, and is associated with shortened overall survival (OS). Owing to the high rate of GF with conventional fludarabine (Flu) and busulfan (Bu) RIC, we added low-dose total body irradiation (TBI; 200 cGy) for patients with MF. We retrospectively compared alloHCT outcomes in adult patients with MF who received RIC with Flu/Bu/TBI and those who received RIC with Flu/Bu. The primary endpoint was the incidence of GF. Secondary endpoints included time to engraftment, acute and chronic graft-versus-host disease (GVHD), hepatic sinusoidal obstruction syndrome (SOS), nonrelapse mortality, overall response rate, progression-free survival, and OS. Of 33 patients who underwent alloHCT, 8 received Flu/Bu RIC and 25 received Flu/Bu/TBI RIC. GF occurred in 50% of the Flu/Bu recipients (all secondary GF) and in 4% of the Flu/Bu/TBI recipients (1 case of primary GF; relative risk, .08; 95% confidence interval [CI], .01 to .62; P = .0016). GF incidence was similar with related or unrelated donors and in patients who did and did not receive Janus-associated kinase inhibitors prior to alloHCT. Molecular remission and donor chimerism ≥99% were significantly more common with Flu/Bu/TBI. No significant differences in acute GVHD, chronic GVHD, or time to engraftment were observed. SOS occurred in none of the 8 patients who received Flu/Bu and in 6 of the 25 patients who received Flu/Bu/TBI, but this difference did not reach statistical significance. Progression or relapse at 1 year was less common with Flu/Bu/TBI (0% versus 63%; P.001). The median OS was 49 months for Flu/Bu/TBI recipients and 30.8 months for Flu/Bu recipients (hazard ratio, .98; 95% CI, .33 to 2.88; P = .97). Flu/Bu/TBI resulted in a significant reduction in GF and a significant improvement in the frequency of molecular remission and full donor chimerism compared with Flu/Bu. The addition of low-dose TBI to Flu/Bu successfully mitigates against GF in patients with MF without increased rates of complications.

This article addresses a unique program involving international collaboration between gifted students from Israel and Croatia. The COVID-19 pandemic opened an opportunity for effective synchronous communication that enabled an unmediated connection between the participants. During the program the children researched the moon from various aspects: scientific, emotional-behavioral and artistic, via theater and creative writing. There were 35 gifted students, 20 from Israel and 15 from Croatia. Five teachers of gifted students, an educational counselor, an educational psychologist and the writers of this article participated in the program and provided the students with academic accompaniment in giftedness and creativity.

To investigate the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA BNT162b2 vaccine on women's menstrual cycle.In this questionnaire-based cross-sectional study, we assessed menstrual pattern and changes in women who completed the SARS-CoV-2 mRNA BNT162b2 vaccine 3 months before and after receiving the vaccine. Included were women aged 18-50 years without known gynecologic comorbidities who regularly monitor their menstruation through electronic calendars. All participants competed a detailed questionnaire on their menstrual symptoms including information on any irregular bleeding. To minimize bias, each woman served as a self-control before and after vaccination. Primary outcome was rate of irregular bleeding following vaccination and secondary outcome was presence of any menstrual change, including irregular bleeding, mood changes, or dysmenorrhea following the vaccine.A total of 219 women met the inclusion critieria. Of them, 51 (23.3%) experienced irregular bleeding following the vaccine. Almost 40% (n = 83) of study participants reported any menstrual change following vaccination. Parity was positively asssociated with irregular bleeding with 26 (50%) of those suffering from irregular bleeding being multiparous compared with only 53 (31.5%) of women with no irregular bleeding (nulliparous 46% vs 60%, multiparous 50% vs 31%, rest 4% vs 8%, P = 0.049). The presence of medical comorbidities was also significantly higher among patients who experienced irregular bleeding (20.0% vs 6.0%, P = 0.003).Our study shows relatively high rates of irregular bleeding and menstrual changes after receiving the SARS-CoV-2 mRNA BNT162b2 vaccine. Further research is needed to confirm our findings and to better characterize the magnitude of change and any possible long-term implications.

Femoral fractures are among the most common reasons for orthopedic-related hospital admissions in children. While spica cast is recommended for most children younger than 5 years, in the last decades, Pavlik harness was proven to be a safe alternative for young children. The objective is to assess the safety, outcomes and complications of a hip abduction brace (HAB) for the treatment of femoral fractures in children under the age of 3 years. This 7-year retrospective study was conducted in a single tertiary hospital. Children aged 6-36 months diagnosed with a femoral fracture, which did not necessitate operative treatment, were included. HAB has been used as the treatment of choice for nondisplaced or minimally displaced fractures of the proximal femur as well as for both displaced and nondisplaced femoral shaft fractures. The database was composed of a total of 102 children under the age of 3 with femoral fractures. Twenty-nine (28.4%) patients were treated with HAB and the others with a spica cast. The average age (±SD) at presentation was 21.5 ± 6.1 months. The length of stay was 0.96 ± 1 day. The complication rate was 6.9%. A satisfactory outcome in terms of fracture alignment and union was reported in 100% of the patients treated with HAB. When compared with patients treated with a spica cast, the HAB group were younger, had less severe injuries, shorter lengths of stay, lower complication rates and no need for surgical intervention. HAB can be considered a safe and comfortable alternative in selected children aged 6-36 months with nondisplaced/mildly displaced proximal and diaphyseal femoral fractures.

CPX-351 and venetoclax and azacitidine (ven/aza) are both indicated as initial therapy for acute myeloid leukemia (AML) in older adults. In the absence of prospective randomized comparisons of these regimens, we used retrospective observational data to evaluate various outcomes for patients with newly diagnosed AML receiving either CPX-351 (n = 217) or ven/aza (n = 439). This study used both a nationwide electronic health record (EHR)-derived de-identified database and the University of Pennsylvania EHR. Our study includes 217 patients who received CPX-351 and 439 who received ven/aza. Paitents receiving ven/aza were older, more likely to be treated in the community, and more likely to have a diagnosis of de novo acute myeloid leukemia. Other baseline covariates were not statistically significantly different between the groups. Median overall survival (OS) for all patients was 12 months and did not differ based on therapy (13 months for CPX-351 vs 11 months for ven/aza; hazard ratio, 0.88; 95% confidence interval, 0.71-1.08; P = .22). OS was similar across multiple sensitivity analyses. Regarding safety outcomes, early mortality was similar (10% vs 13% at 60 days). However, documented infections were higher with CPX-351 as were rates of febrile neutropenia. Hospital length of stay, including any admission before the next cycle of therapy, was more than twice as long for CPX-351. In this large multicenter real-world dataset, there was no statistically significant difference in OS. Prospective randomized studies with careful attention to side effects, quality of life, and impact on transplant outcomes are needed in these populations.

This is the event report on the 2nd Regenerative Medicine workshop "From project to market" that took place on October 12, 2022 in Prague, Czech Republic. Regenerative medicine aims to transform the current practice of medicine by treating the root causes of disease and disorders, through gene/cell therapies, and tissue-engineered products. As a consultancy active in various regenerative medicine related research project on a European scale, AMIRES organized the 2nd edition of the regenerative medicine workshop to exchange outcomes and experiences in the development of novel technologies and solutions in this field by EU-fundedinitiatives and European companies. The event featured individual presentations of EU-funded research and innovation projects in addition to a round table with all speakers, where challenges and hurdles of practical deployment of the new technologies in regenerative medicine were discussed.

Reliable delivery of economic well performance of geothermal projects is affected to a high degree by uncertain reservoir quality. Construction of multilateral wells is well known as an effective concept to overcome the challenges of reservoir heterogeneity or low permeability by increasing the reservoir contact. However, the drilling costs for these structures are currently very high and multilateral well construction with standard rotary steerable systems is complex. Canopus’ directional steel shot drilling system (DSSD) has the potential to enable the construction of short-radius multilaterals at rates attractive for geothermal applications.As part of the European GEOTHERMICA project ‘DEPLOI the HEAT’, the operational performance and economic impact of Canopus’ DSSD system will be investigated. Full-scale tests at TNO’s Rijswijk Centre for Sustainable Geo-Energy (RCSG) and a field trial at the Hagerbach underground test facility (VSH) are planned for the first project year. The RCSG drilling rig enables full factory acceptance testing (FAT) of the drilling assembly before the trial at the VSH site is executed. The geology at the VSH site reflects conditions of typical mid-depth fractured limestone reservoirs in Switzerland and elsewhere. At VSH, a complete set of operational parameters and system longevity will be tested with a full-scale trial to prepare for live well deployment.Further, a techno-economic assessment of multilateral structures drilled with Canopus’ DSSD system will highlight the potential for increasing or safe-guarding well productivity and economically de-risking geothermal projects. Several operators are involved in this project and the techno-economic assessment of the drilling technology will be based on several site-specific data sets provided by them. Stochastic modeling approaches will be implemented to generate an ensemble of equally probable realizations of permeable structures in the subsurface. Then, the performance and costs of different well geometries and multilateral configurations in different subsurface model realizations will be evaluated and compared.The current status of this project will be presented with a focus on the factory acceptance testing at TNO, the VSH trial preparations and the workflow developed for the techno-economic assessment of this innovative multilateral drilling technology.

Active continental rifting in Ethiopia has led to formation of numerous volcanoes and geothermal systems with associated socio-economic potential for generating clean energy.Aluto and Corbetti are two silicic volcanoes in the Central Main Ethiopian Rift (CMER) that have been closely examined. Past studies provided insights into their formation in the extensional magma-tectonic context of the CMER, into causes of volcanic unrest and surface deformation and seismic activity, as well as their geothermal systems. However, many aspects about the structure of the volcanoes’ underlying transcrustal magmatic system remained unanswered.Here, we present new 3-D electrical conductivity models of these volcanoes, obtained from inversions of magnetotelluric (MT) data, providing the most detailed images of the associated magmatic and geothermal systems across multiple scales so far.The models from Aluto and Corbetti provide evidence for several hypothesized properties of the associated magmatic systems. The cross-rift model, enclosing Aluto, shows that the volcano’s lower crustal melt source, west of the rift axis, also feeds volcanos in the western part of the rift, which has been debated in the past. Our Corbetti model confirms the existence of a shallow magmatic intrusion, as it has been modelled from InSAR and gravimetry studies.We estimate thermodynamically constrained melt fractions and interpret geothermal flow structures. The inferred melt fractions indicate crystalline magmatic mush systems in rheological lock-up, where melt is extracted slowly through buoyancy processes, while mechanical trapping explains the observed compositional gaps.

Many patients with hematologic malignancies are not curable with chemotherapy and require novel therapeutic approaches. Chimeric antigen receptor (CAR) T cell therapy is one such approach that involves the transfer of T cells engineered to express CARs for a specific cell-surface antigen. CD38 is a validated tumor antigen in multiple myeloma (MM) and in T-cell acute lymphoblastic leukemia (T-ALL) and is also overexpressed in acute myeloid leukemia (AML). Here, we developed human CD38-redirected T cells (CART-38) as a unified approach to treat three different hematologic malignancies that occur across the pediatric-to-adult age spectrum. Importantly, CD38 expression on activated T cells did not impair CART-38 cells expansion or in vitro function. In xenografted mice, CART-38-mediated rejection of AML, T-ALL, and MM cell lines and primary samples and prolonged survival. In a xenograft model of normal human hematopoiesis, CART-38 resulted in the expected reduction of hematopoietic progenitors, which warrants caution and careful monitoring of this potential toxicity when translating this new immunotherapy into the clinic. Deploying CART-38 against multiple CD38-expressing malignancies is significant, as it expands the potential for this novel therapy to impact diverse patient populations.

Acute and chronic coronary syndromes (ACS and CCS) are leading causes of mortality. Inflammation is considered to be a key pathogenic driver, but immune states in humans and their clinical implications remain poorly understood. We hypothesized that Multi-Omic blood analysis combined with Multi-Omic Factor Analysis (MOFA) might uncover hidden sources of variance providing pathophysiological insights linked to clinical needs. Here, we compile a single cell longitudinal dataset of the circulating immune states in ACS & CCS (13x103clinical & Multi-Omic variables, n=117 subjects, n=838 analyzed samples) from two independent cohorts. Using MOFA, we identify multilayered factors, characterized by distinct classical monocyte and CD4+& CD8+T cell states that explain a large proportion of inter-patient variance. Three factors either reflect disease course or predict outcome in coronary syndromes. The diagnostic performance of these factors reaches beyond established biomarkers highlighting the potential use of MOFA as a novel tool for multilayered patient risk stratification.