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ObjectivesWe investigated how provider vaccine communication behaviors influence parental vaccination acceptance and visit experience.MethodsIn a cross-sectional observational study, we videotaped provider-parent vaccine discussions (n = 111). We coded visits for the format providers used for initiating the vaccine discussion (participatory vs presumptive), parental verbal resistance to vaccines after provider initiation (yes vs no), and provider pursuit of recommendations in the face of parental resistance (pursuit vs mitigated or no pursuit). Main outcomes were parental verbal acceptance of recommended vaccines at visit's end (all vs ≥ 1 refusal) and parental visit experience (highly vs lower rated).ResultsIn multivariable models, participatory (vs presumptive) initiation formats were associated with decreased odds of accepting all vaccines at visit's end (adjusted odds ratio [AOR] = 0.04; 95% confidence interval [CI] = 0.01, 0.15) and increased odds of a highly rated visit experience (AOR = 17.3; 95% CI = 1.5, 200.3).ConclusionsIn the context of 2 general communication formats used by providers to initiate vaccine discussions, there appears to be an inverse relationship between parental acceptance of vaccines and visit experience. Further exploration of this inverse relationship in longitudinal studies is needed.

BackgroundHypertension treatment reduces morbidity and mortality yet has not been broadly implemented in many low-resource settings, including sub-Saharan Africa (SSA). We hypothesized that a patient-centered integrated chronic disease model that included hypertension treatment and leveraged the HIV care system would reduce mortality among adults with uncontrolled hypertension in rural Kenya and Uganda.Methods and findingsThis is a secondary analysis of the SEARCH trial (NCT:01864603), in which 32 communities underwent baseline population-based multidisease testing, including hypertension screening, and were randomized to standard country-guided treatment or to a patient-centered integrated chronic care model including treatment for hypertension, diabetes, and HIV. Patient-centered care included on-site introduction to clinic staff at screening, nursing triage to expedite visits, reduced visit frequency, flexible clinic hours, and a welcoming clinic environment. The analytic population included nonpregnant adults (≥18 years) with baseline uncontrolled hypertension (blood pressure ≥140/90 mm Hg). The primary outcome was 3-year all-cause mortality with comprehensive population-level assessment. Secondary outcomes included hypertension control assessed at a population level at year 3 (defined per country guidelines as at least 1 blood pressure measure ConclusionsIn this cluster randomized comparison where both arms received population-level hypertension screening, implementation of a patient-centered hypertension care model was associated with a 21% reduction in all-cause mortality and a 22% improvement in hypertension control compared to standard care among adults with baseline uncontrolled hypertension. Patient-centered chronic care programs for HIV can be leveraged to reduce the overall burden of cardiovascular mortality in SSA.Trial registrationClinicalTrials.gov NCT01864603.

Carboxymethyl-dextran (CMD)-coated iron oxide nanoparticles (IONs) are of great interest in nanomedicine, especially for applications in drug delivery. To develop a magnetically controlled drug delivery system, many factors must be considered, including the composition, surface properties, size and agglomeration, magnetization, cytocompatibility, and drug activity. This study reveals how the CMD coating thickness can influence these particle properties. ION@CMD are synthesized by co-precipitation. A higher quantity of CMD leads to a thicker coating and a reduced superparamagnetic core size with decreasing magnetization. Above 12.5–25.0 g L−1 of CMD, the particles are colloidally stable. All the particles show hydrodynamic diameters < 100 nm and a good cell viability in contact with smooth muscle cells, fulfilling two of the most critical characteristics of drug delivery systems. New insights into the significant impact of agglomeration on the magnetophoretic behavior are shown. Remarkable drug loadings (62%) with the antimicrobial peptide lasioglossin and an excellent efficiency (82.3%) were obtained by covalent coupling with the EDC/NHS (N-ethyl-N′-(3-(dimethylamino)propyl)carbodiimide/N-hydroxysuccinimide) method in comparison with the adsorption method (24% drug loading, 28% efficiency). The systems showed high antimicrobial activity with a minimal inhibitory concentration of 1.13 µM (adsorption) and 1.70 µM (covalent). This system successfully combines an antimicrobial peptide with a magnetically controllable drug carrier.

Ice- and organic-rich deposits of late Pleistocene age, known as Yedoma Ice Complex (IC), are widespread across large permafrost regions in Northeast Siberia. To reconstruct Yedoma IC formation in Central Yakutia, we analyzed the geochemistry, sedimentology, and stratigraphy of thawed and frozen deposits below two thermokarst lakes in different evolutionary stages (a mature alas lake and a initial Yedoma lake) from the Yukechi site in the Lena-Aldan interfluve. We focused on inorganic geochemical characteristics and mineral weathering in two ∼17 m long sediment cores to trace syngenetic permafrost aggradation and degradation over time. Geochemical properties, element ratios, and specific weathering indices reflect varying sedimentation processes and seasonal thaw depths under variable environmental conditions. Deeper thaw during the interstadial Marine Isotope Stage (MIS) 3 enabled increasing mineral weathering and initial thermokarst processes. Sedimentological proxies reflect high transport energy and short transport paths and mainly terrestrial sediment supply. The Yedoma formation resulted from fluvial, alluvial and aeolian processes. Low mean TOC contents in both cores contrast with Yedoma deposits elsewhere. Likely, this is a result of the very low organic matter content of the source material of the Yukechi Yedoma. Pronounced cryostructures and strongly depleted pore water stable isotopes show a perennially frozen state and preserved organic matter for the lower part of the Yedoma lake core, while changing permafrost conditions, conditions promoting weathering, and strong organic matter decomposition are suggested by our proxies for its middle and upper parts. For the alas lake core, less depleted water stable isotopes reflect the influence of recent precipitation, i.e. the infiltration of rain and lake water into the unfrozen ground. The FENG, MIA(R), and ICV weathering indices have proven to be promising proxies for the identification of conditions that promote mineral weathering to different degrees in the stratigraphy of the thawed and frozen Yedoma deposits, for which we assume a rather homogeneous chemical composition of the parent material. Our study highlights that the understanding of environmental conditions during Yedoma formation and degradation processes by specific geochemical proxies is crucial for assessing the potential decomposition and preservation of the frozen and unfrozen Yedoma inventories.

We conducted a qualitative study from 2018 to 2019 to update the reasons why US parents’ refuse or delay vaccines. Four focus groups and 4 semi-structured interviews involving 33 primary care pediatric providers were conducted in Washington and Colorado. A thematic analysis was conducted to identify themes related to reasons for parental refusal or delay. Five predominant themes were identified: (1) vaccine safety, (2) relative influence of information sources, decision-makers, and timing, (3) low perceived risk of contracting vaccine-preventable disease, (4) lack of trust, and (5) religious objection. Vaccine safety was the theme mentioned most frequently by providers (N = 45 times by 26 providers) and religious objection to vaccination was referred to the least (N = 6 times by 6 providers). Provider-reported reasons for parental refusal or delay of childhood vaccines in 2018 to 2019 remain similar to those reported in previous studies.

In this paper, we enumerate Dumont permutations of the fourth kind avoiding or containing certain permutations of length 4. We also conjecture a Wilf-equivalence of two 4-letter patterns on Dumont permutations of the first kind.

Abstract This paper uses multimedia to showcase the narratives and lived experiences of those who live and work in tropical Asian mega‐deltas, and as such is the first journal article of its kind in the field of Regional Geography. Using videos, photography and audio this paper describes the characteristics of ponds and their place in the intrinsically connected human‐environmental fabric of these delta regions. The aim is to bring to life descriptive inventories and provide greater weight in support of our conclusion that tropical Asian mega‐delta ponds are important and threatened systems. River deltas comprise just 1% of land cover worldwide but support the livelihoods of more than 500 million people. Delta research has historically focused on the major river channels and the socio‐ecological role of ponds has been overlooked despite their large number and surface area. Ponds are intrinsically linked to daily life (potable water, sanitation, bathing, washing), industry (aquaculture, agriculture) and the natural‐cultural heritage (religion, folklore) of deltas. In contrast to the larger river channels, ponds are likely to be significant stores and processors of nutrients, including carbon, and pollutants at annual to decadal scales, on account of their heavy anthropogenic use and smaller individual sizes. Consequently, they are severely polluted water sources and pose significant public health risks. In this review, we use case studies from three Asian mega‐deltas (the Red River Delta and the Mekong River Delta, Vietnam, and the Ganges‐Brahmaputra‐Meghna Delta, India and Bangladesh) to highlight the importance of Asian mega‐delta ponds as important socio‐ecological systems in their own right. We discuss future environmental challenges, knowledge gaps on the ecological function and biodiversity of these habitats, management and policy practices, and the capacity of ponds to achieve the UN Sustainable Development Goals.

BackgroundEmpirically driven personalized diagnostic applications and treatment stratification is widely perceived as a major hallmark in psychiatry. However, databased personalized decision making requires standardized data acquisition and data access, which are currently absent in psychiatric clinical routine. ObjectiveHere, we describe the informatics infrastructure implemented at the psychiatric Münster University Hospital, which allows standardized acquisition, transfer, storage, and export of clinical data for future real-time predictive modelling in psychiatric routine. MethodsWe designed and implemented a technical architecture that includes an extension of the electronic health record (EHR) via scalable standardized data collection and data transfer between EHRs and research databases, thus allowing the pooling of EHRs and research data in a unified database and technical solutions for the visual presentation of collected data and analyses results in the EHR. The Single-source Metadata ARchitecture Transformation (SMA:T) was used as the software architecture. SMA:T is an extension of the EHR system and uses module-driven engineering to generate standardized applications and interfaces. The operational data model was used as the standard. Standardized data were entered on iPads via the Mobile Patient Survey (MoPat) and the web application Mopat@home, and the standardized transmission, processing, display, and export of data were realized via SMA:T. ResultsThe technical feasibility of the informatics infrastructure was demonstrated in the course of this study. We created 19 standardized documentation forms with 241 items. For 317 patients, 6451 instances were automatically transferred to the EHR system without errors. Moreover, 96,323 instances were automatically transferred from the EHR system to the research database for further analyses. ConclusionsIn this study, we present the successful implementation of the informatics infrastructure enabling standardized data acquisition and data access for future real-time predictive modelling in clinical routine in psychiatry. The technical solution presented here might guide similar initiatives at other sites and thus help to pave the way toward future application of predictive models in psychiatric clinical routine.

A significant advantage of a graphene biosensor is that it inherently represents a continuum of independent and aligned sensor-units. We demonstrate a nanoscale version of a micro-physiometer - a device that measures cellular metabolic activity from the local acidification rate. Graphene functions as a matrix of independent pH sensors enabling subcellular detection of proton excretion. Raman spectroscopy shows that aqueous protons p-dope graphene - in agreement with established doping trajectories, and that graphene displays two distinct pKa values (2.9 and 14.2), corresponding to dopants physi- and chemisorbing to graphene respectively. The graphene physiometer allows micron spatial resolution and can differentiate immunoglobulin (IgG)-producing human embryonic kidney (HEK) cells from non-IgG-producing control cells. Population-based analyses allow mapping of phenotypic diversity, variances in metabolic activity, and cellular adhesion. Finally we show this platform can be extended to the detection of other analytes, e.g. dopamine. This work motivates the application of graphene as a unique biosensor for (sub)cellular interrogation.

BackgroundApproximately 150 women annually become pregnant while taking isotretinoin despite participation in the iPLEDGE program. Noncompliance with the requirement to be abstinent or use 2 contraceptive methods may be a contributing factor.ObjectiveWe sought to determine the degree of adherence to contraception or abstinence among women taking isotretinoin.MethodsWe conducted an anonymous survey of women of childbearing potential taking isotretinoin for at least 2 months.ResultsAmong 75 participants, 21 (28%) chose abstinence as their primary means of pregnancy prevention, of whom 4 (19%) were sexually active during treatment. The most commonly chosen contraceptive methods among the 39 women who were sexually active were condoms (35, 90%) and oral contraceptive pills (18, 46%). Twelve women (31%) admitted to having intercourse at least once using 1 or fewer forms of contraception; 10 failed to use condoms, and 1 reported completely unprotected intercourse. Among sexually active oral contraceptive pill users, 7 (39%) reported missing 1 or more pills in the previous month.LimitationsData were self-reported, thus participants may have inaccurately reported contraception use.ConclusionsEncouraging the use of highly effective, patient-independent contraception and limiting abstinence to women who have never been sexually active may further reduce the rate of isotretinoin-exposed pregnancies.

Key Points: Question: Can multivariate machine learning approaches identify the neural signature of major depressive disorder in individual patients? Findings: In this case-control neuroimaging study that included 1801 patients with depression and healthy controls, the best machine learning algorithm only achieved a diagnostic classification accuracy of 62% across major neuroimaging modalities. Meaning: Although multivariate neuroimaging markers increase predictive power compared with univariate analyses, no depression biomarker could be uncovered that is able to identify individual patients. This case-control study evaluates whether machine learning can identify a multivariate biomarker for major depressive disorder. Importance: Biological psychiatry aims to understand mental disorders in terms of altered neurobiological pathways. However, for one of the most prevalent and disabling mental disorders, major depressive disorder (MDD), no informative biomarkers have been identified. Objective: To evaluate whether machine learning (ML) can identify a multivariate biomarker for MDD. Design, Setting, and Participants: This study used data from the Marburg-Münster Affective Disorders Cohort Study, a case-control clinical neuroimaging study. Patients with acute or lifetime MDD and healthy controls aged 18 to 65 years were recruited from primary care and the general population in Münster and Marburg, Germany, from September 11, 2014, to September 26, 2018. The Münster Neuroimaging Cohort (MNC) was used as an independent partial replication sample. Data were analyzed from April 2022 to June 2023. Exposure: Patients with MDD and healthy controls. Main Outcome and Measure: Diagnostic classification accuracy was quantified on an individual level using an extensive ML-based multivariate approach across a comprehensive range of neuroimaging modalities, including structural and functional magnetic resonance imaging and diffusion tensor imaging as well as a polygenic risk score for depression. Results: Of 1801 included participants, 1162 (64.5%) were female, and the mean (SD) age was 36.1 (13.1) years. There were a total of 856 patients with MDD (47.5%) and 945 healthy controls (52.5%). The MNC replication sample included 1198 individuals (362 with MDD [30.1%] and 836 healthy controls [69.9%]). Training and testing a total of 4 million ML models, mean (SD) accuracies for diagnostic classification ranged between 48.1% (3.6%) and 62.0% (4.8%). Integrating neuroimaging modalities and stratifying individuals based on age, sex, treatment, or remission status does not enhance model performance. Findings were replicated within study sites and also observed in structural magnetic resonance imaging within MNC. Under simulated conditions of perfect reliability, performance did not significantly improve. Analyzing model errors suggests that symptom severity could be a potential focus for identifying MDD subgroups. Conclusion and Relevance: Despite the improved predictive capability of multivariate compared with univariate neuroimaging markers, no informative individual-level MDD biomarker—even under extensive ML optimization in a large sample of diagnosed patients—could be identified. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) studies on major depressive disorder (MDD) have predominantly found short-term electroconvulsive therapy (ECT)-related gray matter volume (GMV) increases, but research on the long-term stability of such changes is missing. Our aim was to investigate long-term GMV changes over a 2-year period after ECT administration and their associations with clinical outcome. Methods: In this nonrandomized longitudinal study, patients with MDD undergoing ECT (n = 17) are assessed three times by structural MRI: Before ECT (t 0), after ECT (t 1) and 2 years later (t 2). A healthy (n = 21) and MDD non-ECT (n = 33) control group are also measured three times within an equivalent time interval. A 3(group) × 3(time) ANOVA on whole-brain level and correlation analyses with clinical outcome variables is performed. Results: Analyses yield a significant group × time interaction (pFWE < 0.001) resulting from significant volume increases from t 0 to t 1 and decreases from t 1 to t 2 in the ECT group, e.g., in limbic areas. There are no effects of time in both control groups. Volume increases from t 0 to t 1 correlate with immediate and delayed symptom increase, while volume decreases from t 1 to t 2 correlate with long-term depressive outcome (all p ⩽ 0.049). Conclusions: Volume increases induced by ECT appear to be a transient phenomenon as volume strongly decreased 2 years after ECT. Short-term volume increases are associated with less symptom improvement suggesting that the antidepressant effect of ECT is not due to volume changes. Larger volume decreases are associated with poorer long-term outcome highlighting the interplay between disease progression and structural changes. [ABSTRACT FROM AUTHOR]

Holocene permafrost from ice wedge polygons in the vicinity of large seabird breeding colonies in the Thule District, NW Greenland, was drilled to explore the relation between permafrost aggradation and seabird presence. The latter is reliant on the presence of the North Water Polynya (NOW) in the northern Baffin Bay. The onset of peat accumulation associated with the arrival of little auks (Alle alle) in a breeding colony at Annikitisoq, north of Cape York, is radiocarbon-dated to 4400 cal BP. A thick-billed murre (Uria lomvia) colony on Appat (Saunders Island) in the mouth of the Wolstenholme Fjord started 5650 cal BP. Both species provide marine-derived nutrients (MDNs) that fertilize vegetation and promote peat growth. The geochemical signature of organic matter left by the birds is traceable in the frozen Holocene peat. The peat accumulation rates at both sites are highest after the onset, decrease over time, and were about 2-times faster at the little auk site than at the thick-billed murre site. High accumulation rates induce shorter periods of organic matter (OM) decomposition before it enters the perennially frozen state. This is seen in comparably high C∕N ratios and less depleted δ13C, pointing to a lower degree of OM decomposition at the little auk site, while the opposite pattern can be discerned at the thick-billed murre site. Peat accumulation rates correspond to δ15N trends, where decreasing accumulation led to increasing depletion in δ15N as seen in the little-auk-related data. In contrast, the more decomposed OM of the thick-billed murre site shows almost stable δ15N. Late Holocene wedge ice fed by cold season precipitation was studied at the little auk site and provides the first stable-water isotopic record from Greenland with mean δ18O of -18.0±0.8 ‰, mean δD of -136.2±5.7 ‰, mean d excess of 7.7±0.7 ‰, and a δ18O-δD slope of 7.27, which is close to those of the modern Thule meteoric water line. The syngenetic ice wedge polygon development is mirrored in testacean records of the little auk site and delineates polygon low-center, dry-out, and polygon-high-center stages. The syngenetic permafrost formation directly depending on peat growth (controlled by bird activity) falls within the period of neoglacial cooling and the establishment of the NOW, thus indirectly following the Holocene climate trends.