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Abstract Background Collection of detailed dietary data is labor intensive and expensive, harmonization of existing data sets has been proposed as an effective tool for research questions in which individual studies are underpowered. Methods In this paper, we describe the methodology used to retrospectively harmonize nutritional data from multiple sources, based on the individual participant data of all available studies, which collected nutritional data in Israel between 1963 and 2014. This collaboration was established in order to study the association of red and processed meat with colorectal cancer. Two types of nutritional questionnaires, the Food Frequency Questionnaires (FFQ) and the 24-h dietary recall (24HR recall), and different food composition tables, were used by the participating studies. The main exposure of interest included type of meat (total meat, red meat, and poultry) and level of processing. Results A total of 29,560 Israeli men and women were enrolled. In studies using FFQ,the weighted mean intakes of total, red, processed meat, and poultry were 95, 27, 37 and 58 gr/day and 92, 25, 10, and 66 gr/day in studies using 24HR recall, respectively.. Despite several methodological challenges, we successfully harmonized nutritional data from the different studies. Conclusions This paper emphasizes the significance and feasibility of harmonization of previously collected nutritional data, offering an opportunity to examine associations between a range of dietary exposures and the outcome of interest, while minimizing costs and time in epidemiological studies.

Abstract Crohn disease (CD) burden has increased with globalization/urbanization, and the rapid rise is attributed to environmental changes rather than genetic drift. The Study Of Urban and Rural CD Evolution (SOURCE, n = 380) has considered diet-omics domains simultaneously to detect complex interactions and identify potential beneficial and pathogenic factors linked with rural-urban transition and CD. We characterize exposures, diet, ileal transcriptomics, metabolomics, and microbiome in newly diagnosed CD patients and controls in rural and urban China and Israel. We show that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which mirror those seen in CD. Ileal transcriptomics highlights personal metabolic and immune gene expression modules, that are directly linked to potential protective dietary exposures (coffee, manganese, vitamin D), fecal metabolites, and the microbiome. Bacteria-associated metabolites are primarily linked with host immune modules, whereas diet-linked metabolites are associated with host epithelial metabolic functions.

BackgroundDue to a high number of patients affected by long COVID or post-COVID condition, an essential step to address the long-term effects of COVID-19 lies in the development and implementation of flexible and accessible rehabilitation programs. Virtual reality (VR) technologies offer the potential to support traditional therapies with individualized at-home programs. ObjectiveThis study aims to provide an overview of existing scientific evidence on the development and implementation of VR-assisted respiratory rehabilitation programs for patients with long COVID and post-COVID condition and to synthesize the results. MethodsWe conducted a scoping review of studies from 6 databases. PubMed, CINAHL, Cochrane, ScienceDirect, Web of Science Social Sciences Citation Index, and PEDro were searched using an exploratory search strategy. The search, which was last updated in February 2024, included peer-reviewed studies on immersive VR applications providing respiratory rehabilitation programs for patients with chronic obstructive pulmonary disease and long COVID or post-COVID condition. Exclusion criteria were studies in clinical or inpatient settings, telemedicine, nonimmersive VR applications, and gray literature. Nine publications were included in this review. Findings were extracted and summarized from the studies according to the JBI (Joanna Briggs Institute) method and thematically categorized. Topics covered were study characteristics, physiotherapeutic concept, clinical parameters, as well as usability and acceptability. ResultsThe 9 publications included in the qualitative analysis were published in 2019-2023. Eight empirical studies were included: 4 followed a mixed methods design, 3 were qualitative studies, and 1 followed a quantitative method. One scoping review was included in the data analyses. Four of the included studies were on patients with chronic obstructive pulmonary disease. The 9 studies demonstrated that VR-supported respiratory rehabilitation programs result in positive initial outcomes in terms of physical as well as psychological parameters. Particularly noteworthy was the increased motivation and compliance of patients. However, adverse effects and lack of usability are the barriers to the implementation of this innovative approach. ConclusionsOverall, VR is a promising technology for the implementation of individualized and flexible respiratory rehabilitation programs for patients with long COVID and post-COVID condition. Nevertheless, corresponding approaches are still under development and need to be more closely adapted to the needs of users. Further, the evidence was limited to pilot studies or a small number of patients, and no randomized controlled trials or long-term studies were part of the study selection. The included studies were performed by 4 groups of researchers: 3 from Europe and 1 from the United States.

Background A significant percentage of patients with congenital heart disease surviving into adulthood will develop arrhythmias. These arrhythmias are associated with an increased risk of adverse events and death. We aimed to assess arrhythmia prevalence, risk factors, and associated health care usage in a large national cohort of patients with adult congenital heart disease. Methods and Results Adults with a documented diagnosis of congenital heart disease, insured by Clalit and Maccabi health services between January 2007 and December 2011, were included. We assessed the associations between arrhythmia and subsequent hospitalization rates and death with mixed negative binomial and Cox proportional hazard models, respectively. Among 11 653 patients with adult congenital heart disease (median age, 47 years [interquartile range, 31–62]), 8.7% had a tachyarrhythmia at baseline, 1.5% had a conduction disturbance, and 0.5% had both. Among those without a baseline arrhythmia, 9.2% developed tachyarrhythmias, 0.9% developed a conduction disturbance, and 0.3% developed both during the study period. Compared with no arrhythmia (reference group), arrhythmia in the previous 6 months was associated with a higher multivariable adjusted hospitalization rate, 1.33‐fold higher than the rate of the reference group (95% CI, 1.00–1.76) for ventricular arrhythmia, 1.27‐fold higher (95% CI, 1.17–1.38) for atrial arrhythmias, and 1.33‐fold higher (95% CI, 1.04–1.71) for atrioventricular block. Atrial tachyarrhythmias were associated with an adjusted mortality hazard ratio (HR) of 1.65 (95% CI, 1.44–2.94), and ventricular tachyarrhythmias with a >2‐fold increase in mortality risk (HR, 2.06 [95% CI, 1.44–2.94]). Conclusions Arrhythmias are significant comorbidities in the adult congenital heart disease population and have a significant impact on health care usage and survival.

BackgroundThe use of drones in the health care sector is increasingly being discussed against the background of the aging population and the growing shortage of skilled workers. In particular, the use of drones to provide medication in rural areas could bring advantages for the care of people with and without a need for care. However, there are hardly any data available that focus on the interaction between humans and drones. ObjectiveThis study aims to disclose and analyze factors associated with user acceptance of drone-based medication delivery to derive practice-relevant guidance points for participatory technology development (for apps and drones). MethodsA controlled mixed methods study was conducted that supports the technical development process of an app design for drone-assisted drug delivery based on a participatory research design. For the quantitative analysis, established and standardized survey instruments to capture technology acceptance, such as the System Usability Scale; Technology Usage Inventory (TUI); and the Motivation, Engagement, and Thriving in User Experience model, were used. To avoid possible biasing effects from a continuous user development (eg, response shifts and learning effects), an ad hoc group was formed at each of the 3 iterative development steps and was subsequently compared with the consisting core group, which went through all 3 iterations. ResultsThe study found a positive correlation between the usability of a pharmacy drone app and participants’ willingness to use it (r=0.833). Participants’ perception of usefulness positively influenced their willingness to use the app (r=0.487; TUI). Skepticism had a negative impact on perceived usability and willingness to use it (r=−0.542; System Usability Scale and r=−0.446; TUI). The study found that usefulness, skepticism, and curiosity explained most of the intention to use the app (F3,17=21.12; P

Abstract Background Reduction of Tanzania’s neonatal mortality rate has lagged behind that for all under-fives, and perinatal mortality has remained stagnant over the past two decades. We conducted a national verbal and social autopsy (VASA) study to estimate the causes and social determinants of stillbirths and neonatal deaths with the aim of identifying relevant health care and social interventions. Methods A VASA interview was conducted of all stillbirths and neonatal deaths in the prior 5 years identified by the 2015-16 Tanzania Demographic and Health Survey. We evaluated associations of maternal complications with antepartum and intrapartum stillbirth and leading causes of neonatal death; conducted descriptive analyses of antenatal (ANC) and delivery care and mothers’ careseeking for complications; and developed logistic regression models to examine factors associated with delivery place and mode. Results There were 204 stillbirths, with 185 able to be classified as antepartum (88 [47.5%]) or intrapartum (97 [52.5%]), and 228 neonatal deaths. Women with an intrapartum stillbirth were 6.5% (adjusted odds ratio (aOR) = 1.065, 95% confidence interval (CI) 1.002, 1.132) more likely to have a C-section for every additional hour before delivery after reaching the birth attendant. Antepartum hemorrhage (APH), maternal anemia, and premature rupture of membranes (PROM) were significantly positively associated with early neonatal mortality due to preterm delivery, intrapartum-related events and serious infection, respectively. While half to two-thirds of mothers made four or more ANC visits (ANC4+), a third or fewer received quality ANC (Q-ANC). Women with a complication were more likely to deliver at hospital only if they received Q-ANC (neonates: aOR = 4.5, 95% CI 1.6, 12.3) or ANC4+ (stillbirths: aOR = 11.8, 95% CI 3.6, 38.0). Nevertheless, urban residence was the strongest predictor of hospital delivery. Conclusions While Q-ANC and ANC4 + boosted hospital delivery among women with a complication, attendance was low and the quality of care is critical. Quality improvement efforts in urban and rural areas should focus on early detection and management of APH, maternal anemia, PROM, and prolonged labor, and on newborn resuscitation.

Abstract RAG2-SCID is a primary immunodeficiency caused by mutations in Recombination-activating gene 2 (RAG2), a gene intimately involved in the process of lymphocyte maturation and function. ex-vivo manipulation of a patient’s own hematopoietic stem and progenitor cells (HSPCs) using CRISPR-Cas9/rAAV6 gene editing could provide a therapeutic alternative to the only current treatment, allogeneic hematopoietic stem cell transplantation (HSCT). Here we show an innovative RAG2 correction strategy that replaces the entire endogenous coding sequence (CDS) for the purpose of preserving the critical endogenous spatiotemporal gene regulation and locus architecture. Expression of the corrective transgene leads to successful development into CD3+TCRαβ+ and CD3+TCRγδ+ T cells and promotes the establishment of highly diverse TRB and TRG repertoires in an in-vitro T-cell differentiation platform. Thus, our proof-of-concept study holds promise for safer gene therapy techniques of tightly regulated genes.

Background. As cancer survivorship continues to improve, the perioperative morbidity and mortality following surgical treatment of metastatic bone disease become an increasingly important consideration. The objective of this study is to identify risk factors for early postoperative complications and mortality following extremity prophylactic fixation and pathologic fracture stabilization. Methods. A single-centre retrospective review of 185 patients (226 total surgeries) who underwent prophylactic fixation or pathologic fracture stabilization for extremity metastatic bone disease between 2005 and 2020 was performed. Skull, spine, pelvic, and revision surgeries along with diagnosis of primary bone neoplasm were excluded. Univariate, multivariate, and subgroup analyses were performed to identify predictors and independent risk factors for 30-day postoperative morbidity and mortality. Results. Primary cancers included lung (n = 41), breast (n = 36), multiple myeloma (n = 35), prostate (n = 16), lymphoma (n = 11), renal cell carcinoma (n = 10), and other (n = 36). The 30-day postoperative complication and mortality rates were 32.30% (n = 73) and 17.26% (n = 39), respectively. The most common complications were pulmonary-related, cardiac events, surgical site infection, sepsis, and thromboembolism. Pathologic fracture, presence of extra-skeletal metastases, longer surgical duration, and blood transfusion requirements were associated with 30-day postoperative complications overall. A past medical history for cardiac disease was also associated with systemic but not local surgical complications. Pathologic fracture, presence of extra-skeletal metastases, lung cancer, blood transfusion requirements, and increasing pack-year smoking history were predictors for 30-day mortality. In the multivariate analysis, pathologic fracture (p=0.016) and presence of extra-skeletal metastases (p=0.029) were independent predictors of complications. For mortality, pathologic fracture (p=0.014), presence of extra-skeletal metastases (p=0.0085), and increased blood transfusion requirements (p=0.048) were independent risk factors. Conclusions. The findings of this study provide additional guidance for perioperative risk assessment and patient counselling. Additionally, improving clinical assessment tools to identify and quantify patients at risk of pathologic fractures becomes increasingly important given the significant morbidity and mortality associated with pathologic fracture treatment.

Abstract Cryogenic liquids such as liquid nitrogen are of relevance for numerous processes in engineering, and the food and pharmaceutical industries. However, as a result of its strong evaporation at ambient conditions, its handling for laboratory purposes and experimentation is so far cumbersome. In the present work an original design approach for a supply device for liquid nitrogen is developed and characterized in detail. With the device pure liquid nitrogen is supplied from a pressurized dewar flask to a hypodermic needle without contamination of the liquid with its own vapor or frost, finally enabling to generate a free liquid jet or single droplets in a way comparable to the handling of non-cryogenic liquids using a syringe and a hypodermic needle. Compared to previous approaches for the generation of liquid nitrogen droplets in scientific studies which mostly rely on a reservoir for liquid nitrogen from which droplets form at a bottom outlet due to gravity, the present design allows generation of droplets and free liquid jets in a significantly better controlled and more flexible way. The device is experimentally characterized for varying operational conditions during generation of a free liquid jet, and its versatility for laboratory research purposes is further briefly demonstrated.

Introduction: Hyperhemolysis syndrome (HHS) is a rare complication of repeat blood transfusions in sickle cell disease (SCD). This can occur acutely or have a delayed presentation and often goes unrecognized in the emergency department (ED) due to its rapid progression and similarity to acute chest syndrome and other common complications of SCD. Case Report: We present a case of a 20-year-old male with SCD who presented to the ED with pain and tenderness in his lower extremities one day after discharge for a crisis. Unbeknownst to the ED team, during his admission he had received a blood transfusion. On presentation he was noted to have hyperkalemia, hyperbilirubinemia, anemia, and uncontrolled pain, and was admitted for sickle cell pain crisis. Over the next 36 hours, his hemoglobin dropped precipitously from 8.9 grams per deciliter (g/dL) to 4.2 g/dL (reference range: 11.5-14.5 g/dL), reticulocyte count from 11.7 % to 3.8% (0.4-2.2%), and platelets from 318,000 per cubic centimeter (K/cm3) to 65 K/cm3 (140-350 K/cm3). He also developed a fever, hypoxia, transaminitis, a deteriorating mental status, and severe lactic acidosis. Hematology was consulted and he was treated with methylprednisolone, intravenous immunoglobulin, two units of antigen-matched red blood cells, fresh frozen plasma, and cryoprecipitate. He was transferred to an outside hospital for exchange transfusion and remained hospitalized for 26 days with acute liver failure, bone marrow necrosis, and a fever of unknown origin. Conclusion: Because of the untoward outcomes associated with delay in HHS diagnosis and the need for early initiation of steroids, it is important for emergency providers to screen patients with hemoglobinopathies for recent transfusion at ED presentation. Asking the simple question about when a patient’s last transfusion occurred can lead an emergency physician to include HHS in the differential and work-up of patients with sickle cell disease complications.

The European Cooperation in Science and Technology (COST) is an intergovernmental organization dedicated to funding and coordinating scientific and technological research in Europe, fostering collaboration among researchers and institutions across countries. Recently, COST Action funded the ''Genome Editing to treat Human Diseases'' (GenE-HumDi) network, uniting various stakeholders such as pharmaceutical companies, academic institutions, regulatory agencies, biotech firms, and patient advocacy groups. GenE-HumDi’s primary objective is to expedite the application of genome editing for therapeutic purposes in treating human diseases. To achieve this goal, GenE-HumDi is organized in several working groups, each focusing on specific aspects. These groups aim to enhance genome editing technologies, assess delivery systems, address safety concerns, promote clinical translation, and develop regulatory guidelines. The network seeks to establish standard procedures and guidelines for these areas to standardize scientific practices and facilitate knowledge sharing. Furthermore, GenE-HumDi aims to communicate its findings to the public in accessible yet rigorous language, emphasizing genome editing’s potential to revolutionize the treatment of many human diseases. The inaugural GenE-HumDi meeting, held in Granada, Spain, in March 2023, featured presentations from experts in the field, discussing recent breakthroughs in delivery methods, safety measures, clinical translation, and regulatory aspects related to gene editing.

AimsThis is a sub-analysis of a randomized controlled trial on heart failure (HF) disease management (DM) in which patients with HF (N = 1,360; 27.5% women) were assigned randomly to DM (N = 682) or usual care (UC) (N = 678). Study intervention did not significantly affect the rate of hospital admissions or mortality. This study evaluates sex-related differences in baseline characteristics, clinical manifestations, adherence to treatment and outcomes among the study cohort.MethodsAssociation between sex and hospital admissions and mortality was tested in multivariable models adjusted for the patients’ baseline characteristics. The primary composite outcome of the study included time to first HF hospitalization or all-cause mortality. Secondary composite outcome included number of hospital admissions and days of hospitalization, for HF and all other causes.ResultsCompared to males, females recruited in the study were on average 3 years older [median age 72 (62, 78) vs. 75 (65, 82), p = 0.001], with higher prevalence of preserved left ventricular function (LVEF ≥50%) and lower frequency of ischemic heart disease (IHD) (p ≤ 0.001). Females had shorter 6-min walking distance and worse quality of life and depression scores at baseline (p < 0.001). The proportion of patients receiving HF recommended medical treatment was similar among females and males. During a median follow-up of 2.7 years (range: 0–5), there were no significant differences between females and males with respect to the time elapsed until the study primary endpoint and its components in univariate analysis [557 (56.5%) males and 218 (58.3%) females were hospitalized for HF or died for any cause; p > 0.05]. Multivariable analysis showed that females were significantly less likely than males to experience the primary outcome [adjusted hazard ratio (HR) = 0.835, 95% CI: 0.699, 0.998] or to die from any cause [adjusted HR = 0.712; 95%CI: 0.560, 0.901]. The sex-related mortality differences were especially significant among patients with non-preserved EF, with IHD or with recent HF hospitalization. Females also had lower rates of all-cause hospital admissions [adjusted rate ratio = 0.798; 95%CI: 0.705, 0.904] and were more likely to adhere to HF medical therapy compared to males.ConclusionFemales with HF fare better than men. Sex related differences were not explained by baseline and morbidity-related characteristics or adherence to medical treatment.

Upwelling of nutrient-rich deep waters make eastern boundary upwelling systems (EBUSs), such as the Humboldt Current system, hot spots of marine productivity. Associated settling of organic matter to depth and consecutive aerobic decomposition results in large subsurface water volumes being oxygen depleted. Under these circumstances, organic matter remineralisation can continue via denitrification, which represents a major loss pathway for bioavailable nitrogen. Additionally, anaerobic ammonium oxidation can remove significant amounts of nitrogen in these areas. Here we assess the interplay of suboxic water upwelling and nitrogen cycling in a manipulative offshore mesocosm experiment. Measured denitrification rates in incubations with water from the oxygen-depleted bottom layer of the mesocosms (via 15N label incubations) mostly ranged between 5.5 and 20 nmol N2 L−1 h−1 (interquartile range), reaching up to 80 nmol N2 L−1 h−1. However, actual in situ rates in the mesocosms, estimated via Michaelis–Menten kinetic scaling, did most likely not exceed 0.2–4.2 nmol N2 L−1 h−1 (interquartile range) due to substrate limitation. In the surrounding Pacific, measured denitrification rates were similar, although indications of substrate limitation were detected only once. In contrast, anammox (anaerobic ammonium oxidation) made only a minor contribution to the overall nitrogen loss when encountered in both the mesocosms and the Pacific Ocean. This was potentially related to organic matter C / N stoichiometry and/or process-specific oxygen and hydrogen sulfide sensitivities. Over the first 38 d of the experiment, total nitrogen loss calculated from in situ rates of denitrification and anammox was comparable to estimates from a full nitrogen budget in the mesocosms and ranged between ∼ 1 and 5.5 µmol N L−1. This represents up to ∼ 20 % of the initially bioavailable inorganic and organic nitrogen standing stocks. Interestingly, this loss is comparable to the total amount of particulate organic nitrogen that was exported into the sediment traps at the bottom of the mesocosms at about 20 m depth. Altogether, this suggests that a significant portion, if not the majority of nitrogen that could be exported to depth, is already lost, i.e. converted to N2 in a relatively shallow layer of the surface ocean, provided that there are oxygen-deficient conditions like those during coastal upwelling in our study. Published data for primary productivity and nitrogen loss in all EBUSs reinforce such conclusion.

Genome engineering via targeted nucleases, specifically CRISPR-Cas9, has revolutionized the field of gene therapy research, providing a potential treatment for diseases of the blood and immune system. While numerous genome editing techniques have been used, CRISPR-Cas9 homology-directed repair (HDR)-mediated editing represents a promising method for the site-specific insertion of large transgenes for gene knock-in or gene correction. Alternative methods, such as lentiviral/gammaretroviral gene addition, gene knock-out via non-homologous end joining (NHEJ)-mediated editing, and base or prime editing, have shown great promise for clinical applications, yet all possess significant drawbacks when applied in the treatment of patients suffering from inborn errors of immunity or blood system disorders. This review aims to highlight the transformational benefits of HDR-mediated gene therapy and possible solutions for the existing problems holding the methodology back. Together, we aim to help bring HDR-based gene therapy in CD34+ hematopoietic stem progenitor cells (HSPCs) from the lab bench to the bedside.

Background. As cancer survivorship continues to improve, the perioperative morbidity and mortality following surgical treatment of metastatic bone disease become an increasingly important consideration. The objective of this study is to identify risk factors for early postoperative complications and mortality following extremity prophylactic fixation and pathologic fracture stabilization. Methods. A single‐centre retrospective review of 185 patients (226 total surgeries) who underwent prophylactic fixation or pathologic fracture stabilization for extremity metastatic bone disease between 2005 and 2020 was performed. Skull, spine, pelvic, and revision surgeries along with diagnosis of primary bone neoplasm were excluded. Univariate, multivariate, and subgroup analyses were performed to identify predictors and independent risk factors for 30‐day postoperative morbidity and mortality. Results. Primary cancers included lung (n = 41), breast (n = 36), multiple myeloma (n = 35), prostate (n = 16), lymphoma (n = 11), renal cell carcinoma (n = 10), and other (n = 36). The 30‐day postoperative complication and mortality rates were 32.30% (n = 73) and 17.26% (n = 39), respectively. The most common complications were pulmonary‐related, cardiac events, surgical site infection, sepsis, and thromboembolism. Pathologic fracture, presence of extra‐skeletal metastases, longer surgical duration, and blood transfusion requirements were associated with 30‐day postoperative complications overall. A past medical history for cardiac disease was also associated with systemic but not local surgical complications. Pathologic fracture, presence of extra‐skeletal metastases, lung cancer, blood transfusion requirements, and increasing pack‐year smoking history were predictors for 30‐day mortality. In the multivariate analysis, pathologic fracture (p = 0.016) and presence of extra‐skeletal metastases (p = 0.029) were independent predictors of complications. For mortality, pathologic fracture (p = 0.014), presence of extra‐skeletal metastases (p = 0.0085), and increased blood transfusion requirements (p = 0.048) were independent risk factors. Conclusions. The findings of this study provide additional guidance for perioperative risk assessment and patient counselling. Additionally, improving clinical assessment tools to identify and quantify patients at risk of pathologic fractures becomes increasingly important given the significant morbidity and mortality associated with pathologic fracture treatment. [ABSTRACT FROM AUTHOR]

Eastern boundary upwelling systems (EBUS) are among the most productive marine ecosystems on Earth. The production of organic material is fueled by upwelling of nutrient-rich deep waters and high incident light at the sea surface. However, biotic and abiotic factors can modify surface production and related biogeochemical processes. Determining these factors is important because EBUS are considered hotspots of climate change, and reliable predictions of their future functioning requires understanding of the mechanisms driving the biogeochemical cycles therein. In this field experiment, we used in situ mesocosms as tools to improve our mechanistic understanding of processes controlling organic matter cycling in the coastal Peruvian upwelling system. Eight mesocosms, each with a volume of ∼55 m3, were deployed for 50 d ∼6 km off Callao (12∘ S) during austral summer 2017, coinciding with a coastal El Niño phase. After mesocosm deployment, we collected subsurface waters at two different locations in the regional oxygen minimum zone (OMZ) and injected these into four mesocosms (mixing ratio ≈1.5 : 1 mesocosm: OMZ water). The focus of this paper is on temporal developments of organic matter production, export, and stoichiometry in the individual mesocosms. The mesocosm phytoplankton communities were initially dominated by diatoms but shifted towards a pronounced dominance of the mixotrophic dinoflagellate (Akashiwo sanguinea) when inorganic nitrogen was exhausted in surface layers. The community shift coincided with a short-term increase in production during the A. sanguinea bloom, which left a pronounced imprint on organic matter C : N : P stoichiometry. However, C, N, and P export fluxes did not increase because A. sanguinea persisted in the water column and did not sink out during the experiment. Accordingly, export fluxes during the study were decoupled from surface production and sustained by the remaining plankton community. Overall, biogeochemical pools and fluxes were surprisingly constant for most of the experiment. We explain this constancy by light limitation through self-shading by phytoplankton and by inorganic nitrogen limitation which constrained phytoplankton growth. Thus, gain and loss processes remained balanced and there were few opportunities for blooms, which represents an event where the system becomes unbalanced. Overall, our mesocosm study revealed some key links between ecological and biogeochemical processes for one of the most economically important regions in the oceans.

Abstract Background Nigeria is the largest country in sub-Saharan Africa, with one of the highest neonatal mortality rates and the second highest number of neonatal deaths in the world. There is broad international consensus on which interventions can most effectively reduce neonatal mortality, however, there is little direct evidence on what interventions are effective in the Nigerian setting. Methods We used the 2013 Nigeria Demographic and Health Survey (NDHS) and the follow-up 2014 Verbal and Social Autopsy study of neonatal deaths to estimate the association between neonatal survival and mothers’ and neonates’ receipt of 18 resources and interventions along the continuum of care with information available in the NDHS. We formed propensity scores to predict the probability of receiving the intervention or resource and then weighted the observations by the inverse of the propensity score to estimate the association with mortality. We examined all-cause mortality as well as mortality due to infectious causes and intrapartum related events. Results Among 19,685 livebirths and 538 neonatal deaths, we achieved adequate balance for population characteristics and maternal and neonatal health care received for 10 of 18 resources and interventions, although inference for most antenatal interventions was not possible. Of ten resources and interventions that met our criteria for balance of potential confounders, only early breastfeeding was related to decreased all-cause neonatal mortality (relative risk 0.42, 95% CI 0.32–0.52, p

Abstract Background Socioeconomic differences in oral health and dental care utilization are a persistent problem in many high-income countries. We evaluated demographic, geographic and socioeconomic factors associated with disparities in households’ out-of-pocket expenditure (OOPE) on dental care, and the effect of ongoing dental health reform on these disparities. Methods This cross-sectional analysis used data collected in two Israeli Household Expenditure Surveys conducted in 2014 and 2018. OOPE for dental care was estimated using a two-part multivariable model. A logistic regression was used to examine the likelihood of reporting any OOPE, and a log-transformed linear regression model examined the level of expenditure among those who reported any OOPE. Results In 2018, OOPE on dental care accounted for 22% of total health expenditure for all households, whereas among those who reported dental OOPE it reached 43%. Households with children up to age 14 years reported lower OOPE, regardless of ownership of supplementary health insurance. Owning supplementary health insurance had a heterogeneous effect on the level of OOPE, with a significant increase among those with 0–8 years of education, compared to households without such insurance, but not among those of higher educational level. In 2014, Arab ethnic minority and residence in the country periphery were associated with a greater likelihood for any OOPE and higher amounts of OOPE on dental care. While the gaps between Jewish and Arab households persisted into 2018, those between peripheral and non-peripheral localities seem to have narrowed. Conclusions The burden of dental OOPE on Israeli households remains heavy and some disparities still exist, even after the implementation of the dental health reform. Expanding the dental health reform and addressing barriers to preventive dental care, especially among Arabs and those of lower educational level, may help in reducing households’ private expenses on dental care.

Abstract Background Verbal autopsy is the main method used in countries with weak civil registration systems for estimating community causes of neonatal and 1–59-month-old deaths. However, validation studies of verbal autopsy methods are limited and assessment has been dependent on hospital-based studies, with uncertain implications for its validity in community settings. If the distribution of community deaths by cause was similar to that of facility deaths, or could be adjusted according to related demographic factors, then the causes of facility deaths could be used to estimate population causes. Methods Causes of neonatal and 1–59-month-old deaths from verbal/social autopsy (VASA) surveys in four African countries were estimated using expert algorithms (EAVA) and physician coding (PCVA). Differences between facility and community deaths in individual causes and cause distributions were examined using chi-square and cause-specific mortality fractions (CSMF) accuracy, respectively. Multinomial logistic regression and random forest models including factors from the VASA studies that are commonly available in Demographic and Health Surveys were built to predict population causes from facility deaths. Results Levels of facility and community deaths in the four countries differed for one to four of 10 EAVA or PCVA neonatal causes and zero to three of 12 child causes. CSMF accuracy for facility compared to community deaths in the four countries ranged from 0.74 to 0.87 for neonates and 0.85 to 0.95 for 1–59-month-olds. Crude CSMF accuracy in the prediction models averaged 0.86 to 0.88 for neonates and 0.93 for 1–59-month-olds. Adjusted random forest prediction models increased average CSMF accuracy for neonates to, at most, 0.90, based on small increases in all countries. Conclusions There were few differences in facility and community causes of neonatal and 1–59-month-old deaths in the four countries, and it was possible to project the population CSMF from facility deaths with accuracy greater than the validity of verbal autopsy diagnoses. Confirmation of these findings in additional settings would warrant research into how medical causes of deaths in a representative sample of health facilities can be utilized to estimate the population causes of child death.

Multiple methodologies have been developed to identify and predict adverse events (AEs); however, many of these methods do not consider how patient population characteristics, such as diseases, age, and gender, affect AEs seen. In this study, we evaluated the utility of collecting and analyzing AE data related to hydroxychloroquine (HCQ) and chloroquine (CQ) from US Prescribing Information (USPIs, also called drug product labels or package inserts), the FDA Adverse Event Reporting System (FAERS), and peer-reviewed literature from PubMed/EMBASE, followed by AE classification and modeling using the Ontology of Adverse Events (OAE). Our USPI analysis showed that CQ and HCQ AE profiles were similar, although HCQ was reported to be associated with fewer types of cardiovascular, nervous system, and musculoskeletal AEs. According to EMBASE literature mining, CQ and HCQ were associated with QT prolongation (primarily when treating COVID-19), heart arrhythmias, development of Torsade des Pointes, and retinopathy (primarily when treating lupus). The FAERS data was analyzed by proportional ratio reporting, Chi-square test, and minimal case number filtering, followed by OAE classification. HCQ was associated with 63 significant AEs (including 21 cardiovascular AEs) for COVID-19 patients and 120 significant AEs (including 12 cardiovascular AEs) for lupus patients, supporting the hypothesis that the disease being treated affects the type and number of certain CQ/HCQ AEs that are manifested. Using an HCQ AE patient example reported in the literature, we also ontologically modeled how an AE occurs and what factors (e.g., age, biological sex, and medical history) are involved in the AE formation. The methodology developed in this study can be used for other drugs and indications to better identify patient populations that are particularly vulnerable to AEs.

In this paper, we study the deployment potential of automated minibuses (AmBs) on the first-mile part of public transport (PT) trips or short (sub)urban commutes by comparing “regular” (fixed route and fixed schedule) and “flexible” (door-to-door and on-demand) service types. For reaching that goal, we run a stated choice experiment in the Netherlands. The participants have assessed the referred two AmB alternatives compared to their current travel mode (car, PT, or active modes (AM) – bicycle and walking) used as the main mode for unimodal travellers or as access travel mode to transit lines for multimodal travellers. The results of a joint mixed logit model estimation based on data obtained from Dutch travellers show that there are similarities and differences in the preferences for the AmBs service type within and between the segments of travellers (car, PT, and AM) and that these are mostly in instrumental variables (cost and time) and attitudes. Current PT users prefer the flexible service to regular service based on their perception of in-vehicle travel time and waiting time, while current users of car and AM do not show a difference in preference between the two services concerning these variables. Moreover, their perception of in-vehicle travel time and waiting time is not significantly different from PT users’ perception of those variables in the regular service. This may mean that for non-PT users (car and AM), AmB’s flexibility of door-to-door transport is not seen as offering a significant advantage over what they think about public transport. When looking at the preferences of potential users explained by underlying psychological factors, we conclude that a positive attitude towards riding in AmBs is a significant factor in all three segments of travellers. Trust, usefulness, and enjoyment in using AmBs are important prerequisites for car and PT users to choose either service type. The experience with technology positively influences the preferences of current PT users for both AmB services.

Background The Government of Indonesia is determined to follow global commitments to reduce the neonatal mortality rate. Yet, there is a paucity of information on contributing factors and causes of neonatal deaths, particularly at the sub-national level. This study describes care-seeking during neonates’ fatal illnesses and their causes of death. Methods We conducted a cross-sectional community-based study to identify all neonatal deaths in Serang and Jember Districts, Indonesia. Follow-up interviews were conducted with the families of deceased neonates using an adapted verbal and social autopsy instrument. Cause of death was determined using the InSilicoVA algorithm. Results The main causes of death of 259 neonates were prematurity (44%) and intrapartum-related events (IPRE)-mainly birth asphyxia (39%). About 83% and 74% of the 259 neonates were born and died at a health facility, respectively; 79% died within the first week after birth. Of 70 neonates whose fatal illness began at home, 59 (84%) sought care during the fatal illness. Forty-eight of those 59 neonates went to a formal care provider; 36 of those 48 neonates (75%) were moderately or severely ill when the family decided to seek care. One hundred fifteen of 189 neonates (61%) whose fatal illnesses began at health facilities were born at a hospital. Among those 115, only 24 (21%) left the hospital alive–of whom 16 (67%) were referred by the hospital. Conclusions The high proportion of deaths due to prematurity and IPRE suggests the need for improved management of small and asphyxiated newborns. The moderate to severe condition of neonates at the time when care was sought from home highlights the importance of early illness recognition and appropriate management for sick neonates. Among deceased neonates whose fatal illness began at their delivery hospital, the high proportion of referrals may indicate issues with hospital capability, capacity, and/or cost.

Background Despite the increased access to facility-based delivery in Indonesia, the country’s maternal mortality remains unacceptably high. Reducing maternal mortality requires a good understanding of the care-seeking pathways for maternal complications, especially with the government moving toward universal health coverage. This study examined care-seeking practices and health insurance in instances of pregnancy-related deaths in Jember District, East Java, Indonesia. Methods This was a community-based cross-sectional study to identify all pregnancy-related deaths in the district from January 2017 to December 2018. Follow-up verbal and social autopsy interviews were conducted to collect information on care-seeking behavior, health insurance, causes of death, and other factors. Findings Among 103 pregnancy-related deaths, 40% occurred after 24 hours postpartum, 36% during delivery or within the first 24 hours postpartum, and 24% occurred while pregnant. The leading causes of deaths were hemorrhage (38.8%), pregnancy-induced hypertension (20.4%), and sepsis (16.5%). Most deaths occurred in health facilities (81.6%), primarily hospitals (74.8%). Nearly all the deceased sought care from a formal health provider during their fatal illness (93.2%). Seeking any care from an informal provider during the fatal illness was more likely among women who died after 24 hours postpartum (41.0%, OR 7.4, 95% CI 1.9, 28.5, p = 0.049) or during pregnancy (29.2%, OR 4.4, 95% CI 1.0, 19.2, p = 0.003) than among those who died during delivery or within 24 hours postpartum (8.6%). There was no difference in care-seeking patterns between insured and uninsured groups. Conclusions The fact that women sought care and reached health facilities regardless of their insurance status provides opportunities to prevent deaths by ensuring that every woman receives timely and quality care. Accordingly, the increasing demand should be met with balanced readiness of both primary care and hospitals to provide quality care, supported by an effective referral system.

In this paper, we study the deployment potential of automated minibuses (AmBs) on the first-mile part of public transport (PT) trips or short (sub)urban commutes by comparing 'regular' (fixed route and fixed schedule) and 'flexible' (door-to-door and on-demand) service types. For reaching that goal, we run a stated choice experiment in the Netherlands. The participants have assessed the referred two AmB alternatives compared to their current travel mode (car, PT, or active modes (AM) - bicycle and walking) used as the main mode for unimodal travellers or as access travel mode to transit lines for multimodal travellers. The results of a joint mixed logit model estimation based on data obtained from Dutch travellers show that there are similarities and differences in the preferences for the AmBs service type within and between the segments of travellers (car, PT, and AM) and that these are mostly in instrumental variables (cost and time) and attitudes. Current PT users prefer the flexible service to regular service based on their perception of in-vehicle travel time and waiting time, while current users of car and AM do not show a difference in preference between the two services concerning these variables. Moreover, their perception of in-vehicle travel time and waiting time is not significantly different from PT users' perception of those variables in the regular service. This may mean that for non-PT users (car and AM), AmB's flexibility of door-to-door transport is not seen as offering a significant advantage over what they think about public transport. When looking at the preferences of potential users explained by underlying psychological factors, we conclude that a positive attitude towards riding in AmBs is a significant factor in all three segments of travellers. Trust, usefulness, and enjoyment in using AmBs are important prerequisites for car and PT users to choose either service type. The experience with technology positively influences the preferences of current PT users for both AmB services., Author(s): Maryna Öztürker (corresponding author) [1]; Gonçalo Homem de Almeida Correia [1]; Arthur Scheltes [2]; Marie-José Olde Kalter [2]; Bart van Arem [1] 1. Introduction In the last several decades, [...]

This study examines the changes in teleworking during the lockdown in April 2020 and the intention to change commuting behaviour after COVID-19 in the Netherlands. Survey data of 1,515 Dutch employees and large-scale smartphone-based GPS-data of the same participants before and during COVID-19 is used. The probability of increasing teleworking during COVID-19 is estimated using an ordinal logistic regression model, considering sociodemographic characteristics, the initial travel behaviour and the initial work situation as determining factors. Two binary logistic regression models are developed to analyse whether employees expect to continue teleworking after the COVID-19 pandemic and whether they will decrease car use for commuting. Both models consider teleworking and car use intentions in the context of behavioural changes during COVID-19. The main factors that influenced teleworking during the lockdown are job characteristics. Office workers and teaching staff were more likely to increase the amount of time spent working from home and showed a higher chance of changes in daily commuting routines. After COVID-19, office workers expect to increase teleworking. The results suggest that employees with a relatively large change in teleworking during the early lockdown expect to work from home more frequently after COVID-19. This effect is strengthened further by positive experiences with teleworking (i.e. more pleasure and higher productivity) and supporting policy measures by the employer, such as sufficient ICT facilities. The main conclusion related to intended changes in mode choice is that car use for commuting is expected to decrease after COVID-19, mostly because of an increase in teleworking.

It has been shown that anti-Muslim sentiment is more pronounced in East Germany than in West Germany. In this paper, we discuss existing explanations and add to them. We argue that some East Germans see themselves as a disadvantaged group in competition with other minorities, such as Muslims, for social recognition by West Germans; they are in what we call a “race for second place”. Based on social identity theory, we expect that this might be particularly true for those who explicitly self-identify as East Germans. The theoretical discussion carves out the role of “perceived non-recognition” and “outgroup mobility threat” as important concepts within the conflicts of belonging. We use unique data from the survey “Postmigrant Societies: East-Migrant Analogies” for a comprehensive empirical analysis. We find that factors related to pre-existing arguments – such as socioeconomic and demographic variables, personality traits, or contact – can capture much of the group differences in anti-Muslim sentiment, but that they do not fully apply to those who were born and still live in the East and who explicitly self-identify as East Germans. For this subgroup, perceived non-recognition adds to the empirical models and outgroup mobility threat has a stronger effect.

Background Dalbavancin has been used off-label to treat invasive bacterial infections in vulnerable populations like people who use drugs (PWUD) because of its broad gram-positive coverage and unique pharmacological properties. This retrospective, multisite study examined clinical outcomes at 90 days in PWUD versus non-PWUD after secondary treatment with dalbavancin for bacteremia, endocarditis, osteomyelitis, septic arthritis, and epidural abscesses. Methods Patients at 3 teaching hospitals who received dalbavancin for an invasive infection between March 2016 and May 2022 were included. Characteristics of PWUD and non-PWUD, infection highlights, hospital stay and treatment, and outcomes were compared using χ2 for categorical variables, t test for continuous variables, and nonparametric tests where appropriate. Results There were a total of 176 patients; 78 were PWUD and 98 were non-PWUD. PWUD were more likely to have a patient-directed discharge (26.9% vs 3.1%; P <.001) and be lost to follow-up (20.5% vs 7.14%; P <.01). Assuming loss to follow-up did not achieve clinical cure, 73.1% of PWUD and 74.5% of non-PWUD achieved clinical cure at 90 days (P =.08). Conclusions Dalbavancin was an effective treatment option for invasive gram-positive infections in our patient population. Despite higher rates of patient-directed discharge and loss to follow-up, PWUD had similar rates of clinical cure at 90 days compared to non-PWUD. [ABSTRACT FROM AUTHOR]

Abstract Objective Harmonizing individual patient data (IPD) for meta-analysis has clinical and statistical advantages. Harmonizing IPD from multiple studies may benefit from a flexible data harmonization platform (DHP) that allows harmonization of IPD already during data collection. This paper describes the development and use of a flexible DHP that was initially developed for the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study. Results The DHP that we developed (I) allows IPD harmonization with a flexible approach, (II) has the ability to store data in a centralized and secured database server with large capacity, (III) is transparent and easy in use, and (IV) has the ability to export harmonized IPD and corresponding data dictionary to a statistical program. The DHP uses Microsoft Access as front-end application and requires a relational database management system such as Microsoft Structured Query Language (SQL) Server or MySQL as back-end application. The DHP consists of five user friendly interfaces which support the user to import original study data, to harmonize the data with a master data dictionary, and to export the harmonized data into a statistical software program of choice for further analyses. The DHP is now also adopted in two other studies.