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Genetic studies of the metabolome can uncover enzymatic and transport processes shaping human metabolism. Using rare variant aggregation testing based on whole-exome sequencing data to detect genes associated with levels of 1,294 plasma and 1,396 urine metabolites, we discovered 235 gene–metabolite associations, many previously unreported. Complementary approaches (genetic, computational (in silico gene knockouts in whole-body models of human metabolism) and one experimental proof of principle) provided orthogonal evidence that studies of rare, damaging variants in the heterozygous state permit inferences concordant with those from inborn errors of metabolism. Allelic series of functional variants in transporters responsible for transcellular sulfate reabsorption (SLC13A1, SLC26A1) exhibited graded effects on plasma sulfate and human height and pinpointed alleles associated with increased odds of diverse musculoskeletal traits and diseases in the population. This integrative approach can identify new players in incompletely characterized human metabolic reactions and reveal metabolic readouts informative of human traits and diseases.

The ability of stony corals to thrive in the oligotrophic (low-nutrient, low-productivity) surface waters of the tropical ocean is commonly attributed to their symbiotic relationship with photosynthetic dinoflagellates1,2. The evolutionary history of this symbiosis might clarify its organismal and environmental roles3, but its prevalence through time, and across taxa, morphologies and oceanic settings, is currently unclear4, 5–6. Here we report measurements of the nitrogen isotope (15N/14N) ratio of coral-bound organic matter (CB-δ15N) in samples from Mid-Devonian reefs (Givetian, around 385 million years ago), which represent a constraint on the evolution of coral photosymbiosis. Colonial tabulate and fasciculate (dendroid) rugose corals have low CB-δ15N values (2.51 ± 0.97‰) in comparison with co-occurring solitary and (pseudo)colonial (cerioid or phaceloid) rugose corals (5.52 ± 1.63‰). The average of the isotopic difference per deposit (3.01 ± 0.58‰) is statistically indistinguishable from that observed between modern symbiont-barren and symbiont-bearing corals (3.38 ± 1.05‰). On the basis of this evidence, we infer that Mid-Devonian tabulate and some fasciculate (dendroid) rugose corals hosted active photosymbionts, while solitary and some (pseudo)colonial (cerioid or phaceloid) rugose corals did not. The low CB-δ15N values of the Devonian tabulate and fasciculate rugose corals relative to the modern range suggest that Mid-Devonian reefs formed in biogeochemical regimes analogous to the modern oligotrophic subtropical gyres. Widespread oligotrophy during the Devonian may have promoted coral photosymbiosis, the occurrence of which may explain why Devonian reefs were the most productive reef ecosystems of the Phanerozoic.

Background: Previous studies have repeatedly reported alcohol use disorders (AUDs) in patients after bariatric surgery (BS). This research field can benefit from studies combining health claims data with survey data. Methods: Based on a combined retrospective cohort and cross-sectional study, 2151 patients with BS identified in a large health claims database received a questionnaire, by which we assessed the presence of AUDs based on a validated instrument (AUDIT) as well as by ICD-10 codes from the health claims data. We described patients with vs. without AUDs regarding sex, time since surgery, satisfaction with weight loss and health care resource utilization (HCRU). Results: The majority of patients were female (80.7%) with a median time since surgery of 6 years (Interquartile range: 4–9 years). For the majority of patients, the bariatric intervention was either a RYGB-Bypass (50%) or sleeve gastrectomy (43%). Overall, 3% had at least one AUD diagnosis code in the claims data (men: 5.5%, women: 2.5%). Among men, 43.6% of diagnoses were coded after but not before the surgery (women: 52%). According to AUDIT (completed by 1496 patients), 9.4% of all patients showed at least hazardous/harmful alcohol consumption. Higher scores were associated with sex of the person, longer time since surgery, dissatisfaction with the weight loss and higher HCRU, with contradicting results regarding psychotherapeutic care. Conclusions: The proportion with AUDs in the study population gives rise to concern as alcohol consumption should be restricted after BS. The results suggest the necessity for close monitoring and post-surgical care.

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants with endocrine-disruptive properties. Their impact on puberty in boys is unclear. In this cross-sectional study, we investigated the association between PFAS exposure and pubertal timing in 300 Norwegian boys (9–16 years), enrolled in the Bergen Growth Study 2 during 2016. We measured 19 PFAS in serum samples and used objective pubertal markers, including ultrasound-measured testicular volume (USTV), Tanner staging of pubic hair development, and serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone. In addition to logistic regression of single pollutants and the sum of PFAS, Bayesian and elastic net regression were used to estimate the contribution of the individual PFAS. Higher levels of the sum of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS) were associated with later pubertal onset according to USTV (age-adjusted odds ratio (AOR): 2.20, 95% confidence interval (CI): 1.29, 3.93) and testosterone level (AOR: 2.35, 95% CI: 1.34, 4.36). Bayesian modeling showed that higher levels of PFNA and PFHxS were associated with later pubertal onset by USTV, while higher levels of PFNA and perfluoroundecanoic acid (PFUnDA) were associated with later pubertal onset by testosterone level. Our findings indicate that certain PFAS were associated with delay in male pubertal onset.

Full-area passivating contacts based on SiOx/poly-Si stacks are key for the new generation of industrial silicon solar cells substituting the passivated emitter and rear cell (PERC) technology. Demonstrating a potential efficiency increase of 1 to 2% compared to PERC, the utilization of n-type wafers with an n-type contact at the back and a p-type diffused boron emitter has become the industry standard in 2024. In this work, variations of this technology are explored, considering p-type passivating contacts on p-type Si wafers formed via a rapid thermal processing (RTP) step. These contacts could be useful in conjunction with n-type contacts for realizing solar cells with passivating contacts on both sides. Here, a particular focus is set on investigating the influence of the applied thermal treatment on the interfacial silicon oxide (SiOx) layer. Thin SiOxlayers formed via ultraviolet (UV)–O3exposure are compared with layers obtained through a plasma treatment with nitrous oxide (N2O). This process is performed in the same plasma enhanced chemical vapor deposition (PECVD) chamber used to grow the Si-based passivating layer, resulting in a streamlined process flow. For both oxide types, the influence of the RTP thermal budget on passivation quality and contact resistivity is investigated. Whereas the UV–O3oxide shows a pronounced degradation when using high thermal budget annealing (T> 860 °C), the N2O–plasma oxide exhibits instead an excellent passivation quality under these conditions. Simultaneously, the contact resistivity achieved with the N2O-plasma oxide layer is comparable to that yielded by UV–O3-grown oxides. To unravel the mechanisms behind the improved performance obtained with the N2O-plasma oxide at high thermal budget, characterization by high-resolution (scanning) transmission electron microscopy (HR-(S)TEM), X-ray reflectometry (XRR) and X-ray photoelectron spectroscopy (XPS) is conducted on layer stacks featuring both N2O and UV–O3oxides after RTP. A breakup of the UV–O3oxide at high thermal budget is observed, whereas the N2O oxide is found to maintain its structural integrity along the interface. Furthermore, chemical analysis reveals that the N2O oxide is richer in oxygen and contains a higher amount of nitrogen compared to the UV–O3oxide. These distinguishing characteristics can be directly linked to the enhanced stability exhibited by the N2O oxide under higher annealing temperatures and extended dwell times.

The role of the gut microbiota in human health calls for a better understanding of its determinants. In particular, the possible effects of chemicals with widespread exposure other than pharmaceuticals are little known. Our aim was to characterize the sensitivity of the early-life gut microbiota to specific chemicals with possible antimicrobial action. Within the SEPAGES French couple-child cohort, we assessed 12 phenols in repeated urine samples from 356 pregnant women and their offspring and 19 poly- and perfluoroalkyl substances (PFASs) in serum from the pregnant women. We collected stool samples from the children at one year of age, in which the V3–V4 region of the 16S rRNA gene was sequenced, allowing for gut bacterial profiling. Associations of each chemical with α- and β-diversity indices of the gut microbiota and with the relative abundance of the most abundant taxa were assessed using single-pollutant and mixture (BKMR) models. Perinatal exposure to certain parabens was associated with gut microbiota α- and β-diversity and with Firmicutes and Proteobacteria. Suggestive associations of certain phenols with genera of the Lachnospiraceaeand Enterobacteriaceaefamilies were observed, but these were not maintained after correction for multiple testing. Parabens, which have known antimicrobial properties, might disrupt the child gut microbiota, but larger studies are required to confirm these findings.

A higher number of births and a younger age at first birth are associated with a higher risk of cardiovascular disease. However, there is limited evidence on the associations between parity, age at first birth, and atrial fibrillation (AF). Moreover, the association between infertility and AF remains largely unexplored.We investigated the association between parity, infertility, age at first birth, and AF in a population-based cohort from Norway (the HUNT study) among women over 45 years old.Our findings reveal that women with four or more births, or a history of infertility, or younger age at first birth have approximately a 20% higher risk of AF.Graphical Abstract

Short-, medium-, and long-chain chlorinated paraffins (CPs) (SCCPs, MCCPs, and LCCPs) and dechloranes are chemicals of emerging concern; however, little is known of their bioaccumulative potential compared to legacy contaminants in marine mammals. Here, we analyzed SCCPs, MCCPs, LCCPs, 7 dechloranes, 4 emerging brominated flame retardants, and 64 legacy contaminants, including polychlorinated biphenyls (PCBs), in the blubber of 46 individual marine mammals, representing 10 species, from Norway. Dietary niche was modeled based on stable isotopes of nitrogen and carbon in the skin/muscle to assess the contaminant accumulation in relation to diet. SCCPs and dechlorane-602 were strongly positively correlated with legacy contaminants and highest in killer (Orcinus orca) and sperm (Physeter macrocephalus) whales (median SCCPs: 160 ng/g lw; 230 ng/g lw and median dechlorane-602: 3.8 ng/g lw; 2.0 ng/g lw, respectively). In contrast, MCCPs and LCCPs were only weakly correlated to recalcitrant legacy contaminants and were highest in common minke whales (Balaenoptera acutorostrata; median MCCPs: 480 ng/g lw and LCCPs: 240 ng/g lw). The total contaminant load in all species was dominated by PCBs and legacy chlorinated pesticides (63–98%), and MCCPs dominated the total CP load (42–68%, except 11% in the long-finned pilot whale Globicephala melas). Surprisingly, we found no relation between contaminant concentrations and dietary niche, suggesting that other large species differences may be masking effects of diet such as lifespan or biotransformation and elimination capacities. CP and dechlorane concentrations were higher than in other marine mammals from the (sub)Arctic, and they were present in a killer whale neonate, indicating bioaccumulative properties and a potential for maternal transfer in these predominantly unregulated chemicals.

Introduction Cell-free DNA (cfDNA) screening for aneuploidy became available in the United States in 2011. Initially, it was offered as a screening option for women at increased risk of fetal [...]

AbstractThe purpose of this study is to assess the possible contribution of formalizing small-scale women entrepreneurs’ food processing enterprises in northern Ethiopia to their empowerment or disempowerment. The rationale for evaluating this contribution to (dis)empowerment is to provide updated and policy-relevant knowledge on the issue, including assessing if the critiques of the formalization agenda are still valid or whether the situation may have changed. The main finding suggests that formalization offers limited opportunities for empowering small-scale, resource-poor women entrepreneurs in northern Ethiopia. The contribution of formalization to women's (dis)empowerment varies among the various categories of participants in different ways and forms. Some better-off women entrepreneurs benefitted from formalization in some dimensions; however, this is not the case for most of the women entrepreneurs included in the study. Instead, for the poorer women entrepreneurs, formalization rather led to disempowerment. In conclusion, if formalization in Ethiopia harms or disempowers poor women entrepreneurs rather than benefits them, this paper suggests a need for a major change in policies and practices related to the formalization and women empowerment agenda.

Amblyopia, the most common visual impairment of childhood, is a public health concern. An extended period of optical treatment before patching is recommended by the clinical guidelines of several countries. The aim of this study was to compare an intensive patching regimen, with and without extended optical treatment (EOT), in a randomised controlled trial.

This article provides a summary of recent events and activities organized by various chapters of the American Guild of Organists (AGO) in different regions of the United States. The Central Iowa chapter hosted a diverse concert featuring compositions from nine countries and spanning five centuries. The Twin Cities chapter held an organ performance competition, with first place going to Evelyn Rohrbach. The Greater Kansas City chapter co-sponsored the 45th annual Bachathon, featuring performances by various musicians. The St. Louis chapter held its spring banquet and annual meeting, where new officers were installed and the Avis Blewett Award was presented. Lastly, the Madison chapter organized a hymn festival titled "Hymns of Victory." [Extracted from the article]

Congenital anomalies of the kidney and urinary tract (CAKUT) are the predominant cause for chronic kidney disease below age 30 years. Many monogenic forms have been discovered due to comprehensive genetic testing like exome sequencing. However, disease-causing variants in known disease-associated genes only explain a proportion of cases. Here, we aim to unravel underlying molecular mechanisms of syndromic CAKUT in three unrelated multiplex families with presumed autosomal recessive inheritance. Exome sequencing in the index individuals revealed three different rare homozygous variants in FOXD2, encoding a transcription factor not previously implicated in CAKUT in humans: a frameshift in the Arabic and a missense variant each in the Turkish and the Israeli family with segregation patterns consistent with autosomal recessive inheritance. CRISPR/Cas9-derived Foxd2knockout mice presented with a bilateral dilated kidney pelvis accompanied by atrophy of the kidney papilla and mandibular, ophthalmologic, and behavioral anomalies, recapitulating the human phenotype. In a complementary approach to study pathomechanisms of FOXD2-dysfunction–mediated developmental kidney defects, we generated CRISPR/Cas9-mediated knockout of Foxd2in ureteric bud–induced mouse metanephric mesenchyme cells. Transcriptomic analyses revealed enrichment of numerous differentially expressed genes important for kidney/urogenital development, including Pax2and Wnt4as well as gene expression changes indicating a shift toward a stromal cell identity. Histology of Foxd2 knockout mouse kidneys confirmed increased fibrosis. Further, genome-wide association studies suggest that FOXD2could play a role for maintenance of podocyte integrity during adulthood. Thus, our studies help in genetic diagnostics of monogenic CAKUT and in understanding of monogenic and multifactorial kidney diseases.

The diagnosis of cardiac amyloidosis can be established non-invasively by scintigraphy using bone-avid tracers, but visual assessment is subjective and can lead to misdiagnosis. We aimed to develop and validate an artificial intelligence (AI) system for standardised and reliable screening of cardiac amyloidosis-suggestive uptake and assess its prognostic value, using a multinational database of 99mTc-scintigraphy data across multiple tracers and scanners.

Tricomponent cobalt(salen)-catalyzed carbofunctionalization of unsaturated substrates by radical–polar crossover has the potential to streamline access to broad classes of heteroatom-functionalized synthetic targets, yet the reaction platform has remained elusive, despite the well-developed analogous hydrofunctionalizations mediated by high-valent alkylcobalt intermediates. We report herein the development of a cobalt(salen) catalytic system that enables carbofunctionalization. The reaction entails a tricomponent decarboxylative 1,4-carboamination of dienes and provides a direct route to aromatic allylic amines by obviating preformed allylation reagents and protection of oxidation-sensitive aromatic amines. The catalytic system merges acridine photocatalysis with cobalt(salen)-catalyzed regioselective 1,4-carbofunctionalization that facilitates the crossover of the radical and polar phases of the tricomponent coupling process, revealing critical roles of the reactants, as well as ligand effects and the nature of the formal high-valent alkylcobalt species on the chemo- and regioselectivity.

The article presents the discussion on effect of soil additives on improving water retention capacity in the soil and thus enhancing water availability for plants. Topics include experiments was to reduce soil evaporation and thereby contribute to improved soil moisture; and materials included organic mulches such as wood chips, bark mulch, and straw, as well as synthetic mulches like plastic film and non-woven fabrics.

Seabirds transfer nutrients from the ocean to their nesting island, potentially altering nitrogen (N) cycling within adjacent terrestrial and marine ecosystems. Yet, the processes involved in seabird‐N transfer along the land–sea continuum remain elusive. Using δ15N and δ18O measurements of groundwater nitrate, we demonstrate the role of brackish groundwater located within a coral island's landmass as a major reservoir of nitrate (at millimolar levels). Nearly all of the total dissolved seabird‐derived N leaching into the groundwater (mostly ammonium and uric acid) is converted to nitrate by nitrification, as supported by the relatively low δ18O of the groundwater nitrate (3.97‰ ± 0.30‰). Comparison of nitrate δ15N and δ18O suggests that little denitrification takes place within the groundwater lens, implying that the high δ15N of groundwater nitrate (13.73‰ ± 0.05‰) derives from the high trophic position of seabirds and postdepositional processes that increase the δ15N of seabird excreta. Seawater and coral skeleton samples from a reef flat exposed to groundwater had higher δ15N values than at sites devoid of groundwater influence, indicating that the main source of N at the latter site was the Subtropical Upper Water, while the groundwater nitrate dominated the exposed reef flat N pool up to 200 m from shore. In addition, these results indicate that coral‐bound δ15N can detect seabird‐derived nitrate δ15N, raising opportunities to reconstruct historical seabird‐N inputs to coral reefs in relation to climatic and other changes, such as the introduction of invasive species.

Introduction: Comparing antibiotic prescribing between countries can provide important insights into potential needs of improving antibiotic stewardship programs. We aimed to compare outpatient antibiotic prescribing in early life between children born in Denmark and Germany. Methods: Using the Danish nationwide healthcare registries and a German claims database (GePaRD, ~ 20% population coverage), we included children born between 2004 and 2016, and followed them regarding outpatient antibiotic prescriptions until end of enrollment or the end of 2018. We then determined the median time to first antibiotic prescription. Based on all prescriptions in the first 2 years of life, we calculated the rate of antibiotic treatment episodes and for the children’s first prescriptions in this period, we determined established quality indicators. All analyses were stratified by birth year and country. Results: In the 2016 birth cohorts, the median time to first antibiotic prescription was ~ 21 months in Denmark and ~ 28 in Germany; the rate of antibiotic treatment episodes per 1000 person-years was 537 in Denmark and 433 in Germany; the percentage of prescribed antibiotics with higher concerns regarding side effects and/or resistance potential was 6.2% in Denmark and 44.2% in Germany. In the 2016 birth cohorts, the age at first antibiotic prescription was 50–59% higher compared to the 2004 birth cohorts; the rate of antibiotic treatment episodes was 43–44% lower. Conclusions: Infants in Denmark received antibiotics markedly earlier and more frequently than in Germany, while quality indicators of antibiotic prescribing were more favorable in Denmark. Although both countries experienced positive changes towards more rational antibiotic prescribing in early life, our findings suggest potential for further improvement. This particularly applies to prescribing antibiotics with a lower potential for side effects and/or resistance in Germany.

Decreased insulin availability and high blood glucose levels, the hallmark features of poorly controlled diabetes, drive disease progression and are associated with decreased skeletal muscle mass. We have shown that mice with β‐cell dysfunction and normal insulin sensitivity have decreased skeletal muscle mass. This project asks how insulin deficiency impacts on the structure and function of the remaining skeletal muscle in these animals. Skeletal muscle function was determined by measuring exercise capacity and specific muscle strength prior to and after insulin supplementation for 28 days in 12‐week‐old mice with conditional β‐cell deletion of the ATP binding cassette transporters ABCA1 and ABCG1 (β‐DKO mice). Abca1and Abcg1floxed (fl/fl) mice were used as controls. RNAseq was used to quantify changes in transcripts in soleus and extensor digitorum longus muscles. Skeletal muscle and mitochondrial morphology were assessed by transmission electron microscopy. Myofibrillar Ca2+sensitivity and maximum isometric single muscle fibre force were assessed using MyoRobotbiomechatronics technology. RNA transcripts were significantly altered in β‐DKO mice compared with fl/fl controls (32 in extensor digitorum longus and 412 in soleus). Exercise capacity and muscle strength were significantly decreased in β‐DKO mice compared with fl/fl controls (P =0.012), and a loss of structural integrity was also observed in skeletal muscle from the β‐DKO mice. Supplementation of β‐DKO mice with insulin restored muscle integrity, strength and expression of 13 and 16 of the dysregulated transcripts in and extensor digitorum longus and soleus muscles, respectively. Insulin insufficiency due to β‐cell dysfunction perturbs the structure and function of skeletal muscle. These adverse effects are rectified by insulin supplementation.

Modifying the optical and electronic properties of crystalline organic thin films is of great interest for improving the performance of modern organic semiconductor devices. Therein, the statistical mixing of molecules to form a solid solution provides an opportunity to fine-tune optical and electronic properties. Unfortunately, the diversity of intermolecular interactions renders mixed organic crystals highly complex, and a holistic picture is still lacking. Here, we report a study of the optical absorption properties in solid solutions of pentacene and tetracene, two prototypical organic semiconductors. In the mixtures, the optical properties can be continuously modified by statistical mixing at the molecular level. Comparison with time-dependent density functional theory calculations on occupationally disordered clusters unravels the electronic origin of the low energy optical transitions. The disorder partially relaxes the selection rules, leading to additional optical transitions that manifest as optical broadening. Furthermore, the contribution of diabatic charge-transfer states is modified in the mixtures, reducing the observed splitting in the 0–0 vibronic transition. Additional comparisons with other blended systems generalize our results and indicate that changes in the polarizability of the molecular environment in organic thin-film blends induce shifts in the absorption spectrum.

The article focuses on preventive water management in orchards, addressing the challenges posed by changing precipitation patterns and emphasizing the need for efficient water utilization. It summarizes a three-year project conducted at four different locations in Germany, exploring ways to enhance water availability in orchards and optimize the utilization of natural rainfall.

The phenomenon of migration has received a considerable amount of scholarly attention in recent years. This article presents and elaborates on how contemporary missiological research addresses and discusses migration processes. It approached the theme of migration from various perspectives, including how migration phenomena influence individual and communal expressions of faith; how migration experiences are and can be reflected on theologically; and challenges and opportunities of migration to mission thinking and practice. Further, based on the presentation of themes and approaches in the field, the article discusses how migration might challenge and develop the research agenda within missiology. It is argued that migration and migration processes do not only challenge the idea of easily identifiable contexts, but that they also blur and destabilise the whole idea of fixed borders. This challenges missiology to rethink its basic theories related to contextualization and inter-religious encounters, as well as the understanding of mission thinking and practice. Keywords migration, missiology, mission, religion, theology, missiological research, Christianity., Migration is a phenomenon that has received a considerable amount of attention in recent years. It is addressed, discussed, and debated in media, in politics, and not least in academia. [...]

The article provides a summary of recent events and activities organized by various chapters of the American Organist Magazine. These events include recitals, masterclasses, workshops, and social gatherings held in different locations across the North Central region of the United States. The article highlights the participation of renowned musicians, such as James Kibbie, the King's Singers, and Katie Webb, as well as the collaboration with local churches and organizations. The events covered a range of topics, including musical rhetoric, liturgy, organ renovation, and birdsong. Overall, the article showcases the diverse and vibrant organ music community in the North Central region. [Extracted from the article]

Heterochrony is an elegant concept linking evolutionary changes and ontogeny. It basically describes changes in the growth trajectories of organisms. Although heterochrony is therefore, in principle, tied to quantitative aspects of morphology, many examples involving heterochrony use qualitative character states and also lack a strict phylogenetic frame. Here we look at the group of lacewings, Neuroptera, and explore the possibility of identifying heterochronic events based on quantitative shape data in combination with a conflict-free core tree derived from several conflicting phylogenetic reconstructions. We used the shape of the head in three life stages, larva stage 1, larva stage 3 and adult, for most major lineages of Neuroptera, in total 88 specimens. We used Elliptic Fourier Transformation and Principal Component Analysis to recognise changes of the head outlines. We could identify several heterochronic shifts within Neuroptera. Most lineages show no strong differentiation between stage 1 larvae and stage 3 larvae and a strong change towards the adult, but no real indirect pattern. Yet, a strictly indirect pattern is apparent in two lineages, Sisyridae and Mantispidae. The group Ithonidae is unique in showing almost no quantitative change throughout the post-embryonic ontogeny. The unusual patterns in Sisyridae and Mantispidae are best understood as heterochronic shifts affecting the stage 3 larvae. Less expressed heterochronic shifts affected, for example, the lineage towards Myrmeleontiformia. Heterochrony overall appears to have strongly influenced the diversification of lacewings.

Background: Investigate retinal fluid changes via a novel deep-learning algorithm in real-world patients receiving faricimab for the treatment of neovascular age-related macular degeneration (nAMD). Methods: Multicenter, retrospective chart review and optical coherence tomography (OCT) image upload from participating sites was conducted on patients treated with faricimab for nAMD from February 2022 to January 2024. The Notal OCT Analyzer (NOA) algorithm provided intraretinal, subretinal and total retinal fluid for each scan. Results were segregated based on treatment history and fluid compartments, allowing for multiple cross-sections of evaluation. Results: A total of 521 eyes were included at baseline. The previous treatments prior to faricimab were aflibercept, ranibizumab, bevacizumab, or treatment-naive for 52.3%, 21.0%, 13.3%, and 11.2% of the eyes, respectively. Of all 521 eyes, 49.9% demonstrated fluid reduction after one injection of faricimab. The mean fluid reduction after one injection was −60.7nL. The proportion of eyes that saw reduction in fluid compared to baseline after second, third, fourth and fifth faricimab injections were 54.4%, 51.9%, 51.4% and 52.2%, respectively. The mean (SD) retreatment interval after second, third, fourth and fifth faricimab injection were 53.4 (34.3), 56.6 (36.0), 57.1 (35.3) and 61.5 (40.2) days, respectively. Conclusion: Deep-learning algorithms provide a novel tool for evaluating precise quantification of retinal fluid after treatment of nAMD with faricimab. Faricimab demonstrates reduction of retinal fluid in multiple groups after just one injection and sustains this response after multiple treatments, along with providing increases in treatment intervals between subsequent injections.

Heterogeneous tabular data are the most commonly used form of data and are essential for numerous critical and computationally demanding applications. On homogeneous datasets, deep neural networks have repeatedly shown excellent performance and have therefore been widely adopted. However, their adaptation to tabular data for inference or data generation tasks remains highly challenging. To facilitate further progress in the field, this work provides an overview of state-of-the-art deep learning methods for tabular data. We categorize these methods into three groups: data transformations, specialized architectures, and regularization models. For each of these groups, our work offers a comprehensive overview of the main approaches. Moreover, we discuss deep learning approaches for generating tabular data and also provide an overview over strategies for explaining deep models on tabular data. Thus, our first contribution is to address the main research streams and existing methodologies in the mentioned areas while highlighting relevant challenges and open research questions. Our second contribution is to provide an empirical comparison of traditional machine learning methods with 11 deep learning approaches across five popular real-world tabular datasets of different sizes and with different learning objectives. Our results, which we have made publicly available as competitive benchmarks, indicate that algorithms based on gradient-boosted tree ensembles still mostly outperform deep learning models on supervised learning tasks, suggesting that the research progress on competitive deep learning models for tabular data is stagnating. To the best of our knowledge, this is the first in-depth overview of deep learning approaches for tabular data; as such, this work can serve as a valuable starting point to guide researchers and practitioners interested in deep learning with tabular data.

In the fractional quantum Hall effect, quasiparticles are collective excitations that have a fractional charge and show fractional statistics as they interchange positions. While the fractional charge affects semi-classical characteristics such as shot noise and charging energies, fractional statistics is most notable through quantum interference. Here we study fractional statistics in a bilayer graphene Fabry–Pérot interferometer. We tune the interferometer from the Coulomb-dominated regime to the Aharonov–Bohm regime, both for integer and fractional quantum Hall states. Focusing on the fractional quantum Hall state with a filling factor ν= 1/3, we follow the evolution of the Aharonov–Bohm interference of quasiparticles while varying the magnetic flux through an interference loop and the charge density within the loop independently. When their combined variation is such that the Landau filling remains 1/3, the charge density in the loop varies continuously. We then observe pristine Aharonov–Bohm oscillations with a period of three flux quanta, as expected for quasiparticles of one-third of the electron charge. Yet, when the combined variation leads to discrete events of quasiparticle addition or removal, phase jumps emerge and alter the phase evolution. Notably, across all cases with discrete and continuous charge variation, the average phase consistently increases by 2π with each addition of one electron to the loop, as expected for quasiparticles, obeying fractional statistics.

Representatives of Schizomida, known as short-tailed whip scorpions, are an understudied group within Megoperculata. They are found subterraneanly in tropical and sub-tropical regions. They lack eyes, have superior mobility, and possess a flagellum which is relevant to their mating, but in general little is known about their general biology. Fossil representatives of Schizomida from a variety of time periods are available for study. Using 23 fossil specimens (14 of which are described here for the first time) and 86 extant individuals from the literature, changes in both body size and flagella shape in Schizomida were compared over time. Measurements of prosoma length and leg length were used as a proxy for body size, and a comparative size analysis was carried out. Individuals from the Cretaceous period were found to be significantly smaller than extant individuals, contrary to our expectations. For flagellum shape, images were used to create reconstructions, which were then analysed using an elliptic Fourier analysis followed by a principal component analysis. The morphological diversity of the male flagellum shape was found to have decreased significantly between the Cretaceous and modern fauna. We discuss potential explanations for our findings, although a greater understanding of the general biology of Schizomida is required to properly interpret our results.

At the beginning of the COVID-19 pandemic, with a lack of knowledge about the novel virus and a lack of widely available tests, getting first feedback about being infected was not easy. To support all citizens in this respect, we developed the mobile health app Corona Check. Based on a self-reported questionnaire about symptoms and contact history, users get first feedback about a possible corona infection and advice on what to do. We developed Corona Check based on our existing software framework and released the app on Google Play and the Apple App Store on April 4, 2020. Until October 30, 2021, we collected 51,323 assessments from 35,118 users with explicit agreement of the users that their anonymized data may be used for research purposes. For 70.6% of the assessments, the users additionally shared their coarse geolocation with us. To the best of our knowledge, we are the first to report about such a large-scale study in this context of COVID-19 mHealth systems. Although users from some countries reported more symptoms on average than users from other countries, we did not find any statistically significant differences between symptom distributions (regarding country, age, and sex). Overall, the Corona Check app provided easily accessible information on corona symptoms and showed the potential to help overburdened corona telephone hotlines, especially during the beginning of the pandemic. Corona Check thus was able to support fighting the spread of the novel coronavirus. mHealth apps further prove to be valuable tools for longitudinal health data collection.

Geographic atrophy is a leading cause of progressive, irreversible vision loss. The objectives of OAKS and DERBY were to assess the efficacy and safety of pegcetacoplan compared with sham treatment in patients with geographic atrophy.

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The importance of early diagnosis of 5q-Spinal muscular atrophy (5q-SMA) has heightened as early intervention can significantly improve clinical outcomes. In 96% of cases, 5q-SMA is caused by a homozygous deletion of SMN1. Around 4 % of patients carry a SMN1deletion and a single-nucleotide variant (SNV) on the other allele. Traditionally, diagnosis is based on multiplex ligation probe amplification (MLPA) to detect homozygous or heterozygous exon 7 deletions in SMN1. Due to high homologies within the SMN1/SMN2locus, sequence analysis to identify SNVs of the SMN1gene is unreliable by standard Sanger or short-read next-generation sequencing (srNGS) methods. The objective was to overcome the limitations in high-throughput srNGS with the aim of providing SMA patients with a fast and reliable diagnosis to enable their timely therapy. A bioinformatics workflow to detect homozygous SMN1deletions and SMN1SNVs on srNGS analysis was applied to diagnostic whole exome and panel testing for suggested neuromuscular disorders (1684 patients) and to fetal samples in prenatal diagnostics (260 patients). SNVs were detected by aligning sequencing reads from SMN1and SMN2to an SMN1reference sequence. Homozygous SMN1deletions were identified by filtering sequence reads for the ,, gene-determining variant“ (GDV). 10 patients were diagnosed with 5q-SMA based on (i) SMN1deletion and hemizygous SNV (2 patients), (ii) homozygous SMN1deletion (6 patients), and (iii) compound heterozygous SNVs in SMN1(2 patients). Applying our workflow in srNGS-based panel and whole exome sequencing (WES) is crucial in a clinical laboratory, as otherwise patients with an atypical clinical presentation initially not suspected to suffer from SMA remain undiagnosed.

Anthropogenic climate change is predicted to severely impact the global hydrological cycle1, particularly in tropical regions where agriculture-based economies depend on monsoon rainfall2. In the Horn of Africa, more frequent drought conditions in recent decades3,4contrast with climate models projecting precipitation to increase with rising temperature5. Here we use organic geochemical climate-proxy data from the sediment record of Lake Chala (Kenya and Tanzania) to probe the stability of the link between hydroclimate and temperature over approximately the past 75,000 years, hence encompassing a sufficiently wide range of temperatures to test the ‘dry gets drier, wet gets wetter’ paradigm6of anthropogenic climate change in the time domain. We show that the positive relationship between effective moisture and temperature in easternmost Africa during the cooler last glacial period shifted to negative around the onset of the Holocene 11,700 years ago, when the atmospheric carbon dioxide concentration exceeded 250 parts per million and mean annual temperature approached modern-day values. Thus, at that time, the budget between monsoonal precipitation and continental evaporation7crossed a tipping point such that the positive influence of temperature on evaporation became greater than its positive influence on precipitation. Our results imply that under continued anthropogenic warming, the Horn of Africa will probably experience further drying, and they highlight the need for improved simulation of both dynamic and thermodynamic processes in the tropical hydrological cycle.

The program included several interviews with organbuilder and Appleton resident Ron Wahl, Lawrence University organ student Victor Sandberg, and Micah Zuelke, who also gave a short performance. Unique to the program was a performance of sub-dean Karel Suchy's Way of the Cross, played by the Milwaukee Handbell Ensemble (Kaethe Grabenhofer, director) with Suchy at the organ. Karen Haslag Bob and Gloria Taylor (left) hosted a program and dinner to close out Central Missouri's program year. [Extracted from the article]

Introduction A common dc-to-dc converter problem is generating a regulated voltage when the input voltage can be above, below, or equal to the output--that is, the converter must perform both [...]

Large-scale quantum networks require the implementation of long-lived quantum memories as stationary nodes interacting with qubits of light. Epitaxially grown quantum dots hold great potential for the on-demand generation of single and entangled photons with high purity and indistinguishability. Coupling these emitters to memories with long coherence times enables the development of hybrid nanophotonic devices that incorporate the advantages of both systems. Here we report the first GaAs/AlGaAs quantum dots grown by the droplet etching and nanohole infilling method, emitting single photons with a narrow wavelength distribution (736.2 ± 1.7 nm) close to the zero-phonon line of silicon-vacancy centers. Polarization entangled photons are generated via the biexciton–exciton cascade with a fidelity of (0.73 ± 0.09). High single photon purity is maintained from 4 K (g(2)(0) = 0.07 ± 0.02) up to 80 K (g(2)(0) = 0.11 ± 0.01), therefore making this hybrid system technologically attractive for real-world quantum photonic applications.

ABSTRACTThis article assesses the reliability and validity of the Self-Efficacy in Client-Centredness questionnaire (SECCQ). SECCQ assesses social worker students’ subjective belief in their ability to provide client-centered care in their daily interaction with children or families. Self-efficacy is defined as an individual’s judgments concerning their capability to perform certain skills necessary to attain a desired outcome of behavior. Client-centeredness, on the other hand, relates to how social workers treat clients, not only from a clinical perspective, but also from an emotional, mental, and social perspective. Overall findings demonstrate that this questionnaire has satisfying psychometric properties and high reliability. Hence, the SECCQ may be a valuable tool for raising students’ awareness of their self-efficacy and the evaluation of student learning outcomes.

Als häufig erste Ansprechpartner*innen und Vertrauenspersonen für pflegebedürftige Menschen können Pflegefachpersonen einen wichtigen Beitrag zur Einordnung und zum Verständnis von Sterbewünschen und Wünschen nach einer Suizidassistenz leisten. Sie übernehmen dabei eine umfassende moralische Verantwortung. Wenn dieser nicht entsprochen werden kann, steigt das Risiko für moralisches Belastungserleben. Dies kann sich unter anderem negativ auf die im Rahmen dieser Thematik bedeutsame (moralische) Sensibilität und Empathiefähigkeit, aber auch auf die pflegerische Versorgungsqualität, das Berufsleben sowie die Gesundheit von Pflegefachpersonen auswirken. Um professionell auf diese neuen moralischen und ethischen Herausforderungen reagieren zu können, müssen seitens der Bildungs- und Versorgungseinrichtungen entsprechende Strukturen und Prozesse implementiert bzw. optimiert werden. Es braucht einen Handlungsrahmen für den Umgang mit Wünschen nach einer Suizidassistenz, in dem eine klare Haltung sowie definierte Aufgaben- und Kompetenzbereiche festgelegt sind.