Search

The resect-and-discard strategy allows endoscopists to replace post-polypectomy pathology with real-time prediction of polyp histology during colonoscopy (optical diagnosis). We aimed to investigate the benefits and harms of implementing computer-aided diagnosis (CADx) for polyp pathology into the resect-and-discard strategy.

High-throughput synthesis and screening (HTSS) methods were used to investigate the photophysical properties of 576 heteroleptic Rh(III) transition-metal complexes through measurement of the UV–visible absorption spectra, deaerated excited-state lifetime, and phosphorescent emission spectra. While 4d transition-metal photophysics are often highly influenced by deleterious metal-centered deactivation channels, the HTSS of structurally diverse cyclometalating and ancillary ligands attached to the metal center facilitated the discovery of photoactive complexes exhibiting long-lived charge-transfer phosphorescence (0.15–0.95 μs) spanning a substantial portion of the visible region (546–620 nm) at room temperature. Further photophysical and electrochemical investigations were then carried out on select complexes with favorable photophysics to understand the underlying features controlling these superior properties. Heteroleptic Ir(III) complexes with identical ligand morphology were also synthesized to compare these features to this family of well understood chromophores. A number of these Rh(III) complexes contained the requisite properties for photocatalytic activity and were consequently tested as photocatalysts (PCs) in a water reduction system using a Pd water reduction cocatalyst. Under certain conditions, the activity of the Rh(III) PC actually surpassed that of the Ir(III) PC, uncovering the potential of this often-overlooked class of transition metals as both efficient photoactive chromophores and PCs.

Black mothers and children experience significant health disparities in the USA. These health disparities have been attributed, in part, to experiencing racism in healthcare. This study aimed to explore how experiences of healthcare discrimination and mistreatment experienced by Black mothers may influence COVID-19 vaccine beliefs and decision-making for themselves and their families. From April 2021 to November 2021, we conducted 50 semi-structured interviews among Chicago residents. Ten participants self-identified as female and with reported children; these data were extracted from the larger sample for data analysis. Interview content included perceptions and experiences with the COVID-19 vaccine and experiences with healthcare discrimination, mistreatment, and medical mistrust. Interview transcripts were transcribed verbatim and coded using the MAXQDA 2022 qualitative software. Themes were identified using a team-based thematic analysis to understand how experiences of racism in healthcare may influence COVID-19 vaccine decision-making. Four themes were generated from the data: (1) experiences of healthcare discrimination and mistreatment, (2) distrust and fears of experimentation, (3) the influence of discrimination and distrust on COVID-19 vaccine decision-making, and (4) overcoming vaccine hesitancy. The results of this study highlight the current literature; Black mothers experience racism and discrimination in healthcare when seeking care for themselves and their children. It is evident in their stories that medical racism and historical medical abuse influence vaccine decision-making. Therefore, healthcare and public health initiatives should be intentional in addressing past and present racism in healthcare to improve vaccine distrust.

Over 4 million liters of mixed acidic (∼pH 2.5), high ionic strength (∼5 M nitrate) plutonium (Pu) processing waste were released into the 216-Z-9 (Z-9) trench at the Hanford Site, USA, and trace Pu has migrated 37 m below the trench. In this study, we used flowthrough columns to investigate Pu transport in simplified processing waste through uncontaminated Hanford sediments to determine the conditions that led to Pu migration. In low pH aqueous fluids, some Pu breakthrough is observed at pH < 4, and increased Pu transport (14% total Pu breakthrough) is observed at pH < 2. However, Pu migrates in organic processing solvents through low pH sediments virtually uninhibited with approximately 94 and 86% total Pu breakthrough observed at pH 1 and pH 3, respectively. This study demonstrates that Pu migration can occur both with and without organic solvents at pH < 4, but significantly more Pu can be transported when partitioned into organic processing solvents. Our data suggest that under acidic conditions (pH < 4) in the vadose zone beneath the Z-9 trench, Pu present in organic processing solvents moved relatively unhindered and may explain the historical downward migration of Pu tens of meters below the Z-9 trench.

Supplemental Digital Content is Available in the Text.

Generally, fasting and refeeding confer anti- and proinflammatory effects, respectively. In humans, these caloric-load interventions function, in part, via regulation of CD4+T cell biology. However, mechanisms orchestrating this regulation remain incomplete. We employed integrative bioinformatics of RNA sequencing and high-performance liquid chromatography–mass spectrometry data to measure serum metabolites and gene expression of peripheral blood mononuclear cells isolated from fasting and refeeding in volunteers to identify nutrient-load metabolite-driven immunoregulation. Propionate, a short chain fatty acid (SCFA), and the SCFA-sensing G protein–coupled receptor 43 (ffar2) were coordinately and inversely regulated by fasting and refeeding. Propionate and free fatty acid receptor agonists decreased interferon-γ and interleukin-17 and significantly blunted histone deacetylase activity in CD4+T cells. Furthermore, propionate blunted nuclear factor κB activity and diminished interleukin-6 release. In parallel, propionate reduced phosphorylation of canonical T helper 1 (TH1) and TH17 regulators, STAT1 and STAT3, respectively. Conversely, knockdown of free fatty acid receptors significantly attenuated the anti-inflammatory role of propionate. Interestingly, propionate recapitulated the blunting of CD4+THcell activation in primary cells from obese individuals, extending the role of this metabolite to a disease associated with low-grade inflammation. Together, these data identify a nutrient-load responsive SCFA–G protein–coupled receptor linked pathway to regulate CD4+THcell immune responsiveness.Propionate blunts T helper cell responsiveness.

Supermartensitic stainless steels with 15Cr-6Ni-2Mo-1Cu and 135 ksi minimum yield strength (15Cr-135 SMSS) offer high strength and good toughness through a complex hierarchical microstructure of nanoscale precipitates, tempered martensite, and reverted austenite. Upon welding and postweld heat treatment, substantial changes to heat-affected zone microstructure and hardness may occur. Here, we reveal spatially heterogeneous microstructure and microhardness in the HAZ of 15Cr-135 SMSS; correlate these changes to measured phase transformation temperatures; and demonstrate that HAZ hardness changes depend strongly on postweld heat treatment (PWHT) temperatures. Furthermore, we demonstrate that PWHT may lead to undesired reductions in base metal yield strength and formulate a design guide for PWHT that quantifies the trade-offs in desired reductions of HAZ hardness with undesired changes to base metal yield strength. These findings have important practical implications for welding procedure design and qualification. [ABSTRACT FROM AUTHOR]

In anderen Ländern hat sich das Konzept der interprofessionellen Ausbildung seit mehreren Jahren bzw. Jahrzehnten bewährt und dient als Vorbild. Erfreulicherweise setzen auch in Deutschland erste Kliniken dieses Konzept um, wenn auch noch vereinzelt. Die bereits in der Ausbildung vermittelte ganzheitliche und interprofessionell aufeinander abgestimmte Zusammenarbeit trägt nicht nur zur Qualität der Patient*innenversorgung im Gesundheitswesen bei, sondern bedeutet auch einen erheblichen Mehrwert für den Gesundheitssektor. Am Universitätsklinikum Regensburg sind die unterschiedlichen interprofessionellen Lehrkonzepte nicht mehr wegzudenken. Die interprofessionelle Ausbildungsstation A-STAR entwickelte sich von einem Projekt zu einem festen Bestandteil einer innovativen und zeitgemäßen praktischen Ausbildung.

Das Adenokarzinom des Ösophagus zeigt weltweit steigende Fallzahlen, es ist hauptsächlich im distalen Ösophagus lokalisiert. Der Barrett-Ösophagus stellt den wichtigsten Risikofaktor dar. Definitionskriterien sind histologisch nachgewiesene Barrett-Metaplasie und eine minimale Länge von 1 cm. Die Ösophagogastroduodenoskopie (ÖGD) mit hochauflösender Videoqualität und (virtueller) Chromoendoskopie stellt die wichtigste Diagnostik dar. Neue Technologien wie z. B. künstliche Intelligenz zur Detektion, Charakterisierung und Biopsieplanung suspekter Läsionen werden intensiv untersucht. Die ersten Publikationen zeigen vielversprechende Ergebnisse. Ein kommerziell erhältliches System ist noch nicht verfügbar. Die Therapie des Barrett-Ösophagus orientiert sich an der vorliegenden Histologie. Ein Barrett-Ösophagus ohne Dysplasie soll nur endoskopisch überwacht werden. Im Fall einer LGIN („low-grade intraepithelial neoplasia“) können endoskopische Kontrollen wie auch eine Ablation (Radiofrequenzablation, RFA/Argon-Plasma-Koagulation, APC) der Barrett-Schleimhaut durchgeführt werden. Im Fall einer HGIN („high-grade intraepithelial neoplasia“) oder eines Frühkarzinoms mit visuell detektierbarer Läsion soll eine endoskopische Therapie (endoskopische Mukosaresektion, EMR/endoskopische Submukosadissektion, ESD) mit anschließender thermischer Ablation (RFA/APC) erfolgen. Dieses zweistufige Therapiekonzept hat sich in den letzten Jahren als Standard etabliert. Es ist auch bei submukosalen Karzinomen T1b (sm1 < 500ym, L0, V0, G1/G2, VM0-R0) sicher (sm1: limitiert auf Mukosa oder Submukosa, L0: keine Infiltration lymphatischer Gefäße, V0: keine Infiltration venöser Gefäße, VM: vertikale Tumorausdehnung).

This article has supplementary material on the web site: www.jdbp.org.

Pediatric Moyamoya Angiopathy (MMA) is a progressive intracranial occlusive arteriopathy that represents a leading cause of transient ischemic attacks and strokes in childhood. Despite this, up to now no large, exclusively pediatric MMA cohort has been subjected to systematic genetic investigation. In this study, we performed molecular karyotyping, exome sequencing and automated structural assessment of missense variants on a series of 88 pediatric MMA patients and correlated genetic, angiographic and clinical (stroke burden) findings. The two largest subgroups in our cohort consisted of RNF213and neurofibromatosis type 1 (NF1) patients. While deleterious RNF213variants were associated with a severe MMA clinical course with early symptom onset, frequent posterior cerebral artery involvement and higher stroke rates in multiple territories, NF1 patients had a similar infarct burden compared to non-NF1 individuals and were often diagnosed incidentally during routine MRIs. Additionally, we found that MMA-associated RNF213variants have lower predicted functional impact compared to those associated with aortic disease. We also raise the question of MMA as a feature of recurrent as well as rare chromosomal imbalances and further support the possible association of MMA with STAT3deficiency. In conclusion, we provide a comprehensive characterization at the genetic and clinical level of a large exclusively pediatric MMA population. Due to the clinical differences found across genetic subgroups, we propose genetic testing for risk stratification as part of the routine assessment of pediatric MMA patients.

This article has supplementary material on the web site: www.jdbp.org.

Parallel career tracks have become more prevalent today, especially in Brazil, where more than a quarter of all postgrads have one. Despite its growing popularity, little research has tapped into this new career phenomenon. This study examines whether having a parallel career track leads to negative work outcomes related to sustainable careers, such as higher absenteeism and lower engagement, in comparison to a single career track. Cross-sectional and longitudinal data were gathered from 380 and 102 Brazilian professionals respectively, who filled out an online survey. A normal and a repeated-measures multivariate analysis of variance were used to examine whether work outcomes differed between those with parallel career tracks versus single career tracks. The findings indicate that parallel career tracks do not have different effects on individual sustainable employability outcomes when compared to single career tracks, including employability, engagement, absenteeism, presenteeism, and burnout. Therefore, organizations can face this new career trend without reluctance as it does not harm individual work outcomes related to sustainable careers. This study contributes significantly to improving the understanding of this new career format by examining the impact of parallel career tracks on individual work outcomes through a longitudinal design.

In the paper, synthesis process of the TiO2particles was discussed, from the fluoride solution, through TiO2·nH2O gel thermal precipitation and decomposition, and its impact on the further sintering of the obtained powders. It was demonstrated that the main phase of the obtained titania was anatase. Morphology of the obtained TiO2can be controlled through variations of the precipitation temperature and the emulsifier concentration. It was found that the addition of the chloride ions during gel formation caused crystallization of the (NH4)2TiOF4phase. When it underwent decomposition under heating, agglomerated particles in form of rods several micrometers long were synthesized. Obtained powders were sintered, and both the sintering process and the final bulk structures were examined. The results indicated the lowest microhardness of 540 kg/mm2in the specimens prepared out of the powders synthesized without emulsifier, while the highest hardness of 1450 kg/mm2was reached when the TiO2particles had been precipitated at room temperature with emulsifier proportion С(Ti):C(OР9) = 1:0.5. However, further increase of the emulsifier concentration led to the decrease of hardness.

Circular economy (CE) has emerged as a strong contender for illuminating the path toward sustainability. Although companies are seen as the most important agents of change, the definition of goals and indicators for assessing the adoption of CE at the company level is still in the early phases. A company that wants to contribute to the CE, whether due to the ambition of the stakeholders or legal requirements, needs to understand what is really within its responsibilities and sphere of influence. However, measuring and evaluating the performance of circularity is still not a common practice in companies. In this context, this paper presents the development of the Overall Circularity Effectiveness (OCE) index to assess the circularity level of manufacturing companies by analyzing inputs and outputs. The index was developed following the design research methodology (DRM) with interactions between theory and practice, based on literature review, survey with companies, development, testing, and evaluation with companies. The paper also presents an application of the proposed index into a case study and discusses its usability and usefulness, comparing it with the existing company-level CE measurement approaches. The OCE was constructed to be simple to understand, practical to calculate through quantitative measures, relevant to the CE context, and generic to be applied in any type or size of manufacturing company. Although the index was developed to be used by any manufacturing company, it was applied in only four companies and all with material from the technical cycle.

Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community. The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan. NDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS. This review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade. This review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy.

Mechanisms explaining the link between psoriasis, a proinflammatory condition, and cardiovascular disease are not fully known. PCSK9 is predominantly expressed in hepatocytes as a critical regulator of lipid metabolism, and clinical trials targeting PCSK9 reduce cardiovascular disease. Independent of its role in lipid metabolism, PCSK9 levels associate with endothelial dysfunction and predict cardiovascular events. We used two separate human psoriasis cohorts and the K14-Rac1V12−/+murine model of psoriasis to investigate PCSK9 and cardiovascular risk in psoriasis. In both psoriasis cohorts (n = 88 and n = 20), PCSK9 levels were 20% and 13% higher than in age-, sex-, and cholesterol-matched controls, respectively (P< 0.05 for each comparison) and correlated with PASI (r = 0.43, P< 0.05). Despite no difference in hepatocyte expression, K14-Rac1V12−/+mice demonstrated skin-specific PCSK9 staining, which was confirmed in human psoriatic lesional skin. In patients with psoriasis, PCSK9 levels correlated with impaired endothelial vascular health (e.g., early atherosclerosis, β = 4.5, P< 0.01) and log converted coronary artery calcium score (β = 0.30, P = 0.01), which remained significant after adjustment for Framingham risk, body mass index, and active biologic use. Taken together, these findings suggest, independent of cholesterol, an association between circulating PCSK9 and early as well as advanced stages of atherosclerosis in psoriasis.

IMPORTANCE: Psoriasis, a chronic inflammatory skin disease associated with accelerated noncalcified coronary burden (NCB) by coronary computed tomography angiography (CCTA), accelerates lipoprotein oxidation in the form of oxidized modified lipoproteins. A transmembrane scavenger receptor for these oxidized modified lipoproteins is lectinlike oxidized low-density lipoprotein receptor-1 (LOX-1), which has been reported to be associated with coronary artery disease. It is unknown whether this receptor is associated with coronary artery disease in psoriasis. OBJECTIVE: To assess the association between soluble LOX-1 (sLOX-1) and NCB in psoriasis over time. DESIGN, SETTING, AND PARTICIPANTS: In a cohort study at the National Institutes of Health, 175 consecutive patients with psoriasis were referred from outpatient dermatology practices between January 1, 2013, and October 1, 2017. A total of 138 consecutively recruited patients with psoriasis were followed up at 1 year. EXPOSURES: Circulating soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were measured blindly by field scientists running undiluted serum using an enzyme-linked immunosorbent assay. MAIN OUTCOMES AND MEASURES: Coronary computed tomography angiography scans were performed to quantify NCB in all 3 major epicardial coronary arteries by a reader blinded to patient demographics, visit, and treatment status. RESULTS: Among the 175 patients with psoriasis, the mean (SD) age was 49.7 (12.6) years and 91 were men (55%). The cohort had relatively low median cardiovascular risk by Framingham risk score (median, 2.0 [interquartile range (IQR), 1.0-6.0]) and had a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) suggestive of overweight profiles (29.6 [6.0]). Elevated sLOX-1 levels were found in patients with psoriasis compared with age- and sex-matched controls (median, 210.3 [IQR, 110.9-336.2] vs 83.7 [IQR, 40.1-151.0]; P &lt; .001), and were associated with Psoriasis Area Severity Index (PASI) score (β = 0.23; 95% CI, 0.082-0.374; P = .003). Moreover, sLOX-1 was associated with NCB independent of hyperlipidemia status (β = 0.11; 95% CI, 0.016-0.200; P = .023), an association which persisted after adjusting for traditional cardiovascular risk factors, statin use, and biologic psoriasis treatment (β = 0.10; 95% CI, 0.014-0.193; P = .03). At 1 year, in those who had clinical improvement in PASI (eg, >50% improvement), a reduction in sLOX-1 (median, 311.1 [IQR, 160.0-648.8] vs median, 224.2 [IQR, 149.1 - 427.4]; P = .01) was associated with a reduction in NCB (β = 0.14; 95% CI, 0.028-0.246; P = .02). CONCLUSIONS AND RELEVANCE: Soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were elevated in patients with psoriasis and were associated with severity of skin disease. Moreover, sLOX-1 associated with NCB independent of hyperlipidemia status, suggesting that inflammatory sLOX-1 induction may modulate lipid-rich NCB in psoriasis. Improvement of skin disease was associated with a reduction of sLOX-1 at 1 year, demonstrating the potential role of sLOX-1 in inflammatory atherogenesis in psoriasis.

Physical activity and sleep are critical to the pain experience, and bidirectional relations between physical activity and pain and between sleep and pain have been identified. Methodologies typically used to assess physical activity and sleep, however, are subject to bias (i.e., self-report), costly and invasive hospital implementation (i.e., PSG), and lack of recent technological advancement (i.e., actigraphy). Fitbits may represent a cost-effective, reliable, and valid methodology for measurement of these constructs, though their feasibility and acceptability have not been investigated in pediatric pain populations. The current study aimed to assess feasibility and acceptability of Fitbits for assessment of physical activity and sleep in youth with acute and chronic pain. We investigated three samples of youth with pain (ages=11-17): those undergoing cardiac (N=14) or orthopedic surgery (N=7) and those in a multidisciplinary pain rehabilitation program (N=15). Results indicated the majority of youth demonstrated adequate compliance with Fitbit wearing (cardiac: 63.4%; orthopedic: 87.2%; rehabilitation: 82.4%). Self-report results indicated high mean levels of comfort and satisfaction and low mean levels of burden on 0-10 scales (cardiac: comfort M=8.6, SD=1.4; satisfaction M=8.5, SD=1.1; burden M=0.6, SD=0.9;; orthopedic: comfort M=8.9, SD=1.2; satisfaction M=9.4, SD=0.8; burden M=0.3, SD=0.5; rehabilitation: comfort M=8.5, SD=1.3; satisfaction M=7.9, SD=1.5; burden M=1.3, SD=1.4). Findings support the feasibility and acceptability of Fitbits for assessing physical activity and sleep in pediatric pain populations. Considerations related to a data collection pipeline and patient-related implementation are discussed. Future clinical research in pediatric pain may benefit from leveraging Fitbits for assessment and intervention. Funding: NIH K01DA057374.

The migration of low levels of plutonium has been observed at the Nevada National Security Site (NNSS) and attributed to colloids. To better understand the mechanism(s) of colloid-facilitated transport at this site, we performed flow cell desorption experiments with mineral colloid suspensions produced by hydrothermal alteration of NNSS nuclear melt glass, residual material left behind from nuclear testing. Three different colloid suspensions were used: (1) colloidal material from hydrothermal alteration of nuclear melt glass at 140 °C; (2) at 200 °C; and (3) plutonium sorbed to SWy-1 montmorillonite at room temperature. The 140 °C sample contained only montmorillonite, while zeolite and other phases were present in the 200 °C sample. Overall, more plutonium was desorbed from the 140 °C colloids (ca. 9–16%) than from the 200 °C colloids (ca. 4–8%). Furthermore, at the end of the 4.5 day flow cell experiments, the desorption rates for the 140 °C colloids and the Pu–montmorillonite colloids were similar while the desorption rates from the 200 °C colloids were up to an order of magnitude lower. We posit that the formation of zeolites and clays hydrothermally altered at 200 °C may lead to a more stable association of plutonium with colloids, resulting in lower desorption rates. This may give rise to more extensive colloid-facilitated transport and help explain why trace levels of plutonium are found downgradient from their original source decades after a nuclear detonation. Interestingly, in the case of cesium (a co-contaminant of plutonium), no difference was observed between the 140 and 200 °C colloids. This reflects intrinsic differences between cesium and plutonium sorption/desorption behavior (charge, cation size) and suggests that the Cs sorption mechanism (cation exchange) is not similarly affected by colloid formation temperature.

ABSTRACTFinishing treatments applied to cabinetwork are an important aspect of historical decorative interiors. Veneers and solid woods were treated with transparent varnishes to highlight the grain and enhance the intrinsic colour of the wood, with modifications to tone and wood grain often undertaken before the varnish was applied. The intention was not to obscure the surface as with polychrome coatings, but rather to embellish the natural wood prior to varnishing. Ageing processes and losses of original layers, e.g. due to removal during restoration treatments, mean that very little evidence of these finishing layers remains and their significance has therefore largely been forgotten. Literary sources refer in particular to staining with a mordant to adjust and/or modify the hue of wood. But some historical treatises also describe the application of black-brown washes or glazes to enhance the textural appearance of the wood. One organic colourant used for washes is bistre (or bister), a finely dispersed, organic pigment of a warm, deep, transparent brown hue that contains characteristic hardwood pyrolysis products. In order to clarify the nature of bistre as discussed in this article, reconstruction processes carried out according to historical sources are described. Gas chromatography–mass spectrometry analysis is suggested as a possible analytical method to identify typical marker compounds in both reference materials and historical samples dating from the sixteenth to nineteenth centuries.

ABSTRACTIn recent decades, there have been more and more chemical analyses of aged and degraded lacquers, and the quality of identification of components has steadily improved. Despite this progress, a number of questions still remain open. This paper studied historical sources written in German in a bid to enhance and diversify the identification of natural resins in European lacquers, with special emphasis placed on resins of the Pinaceaefamily, which includes species of larch, fir, spruce and pine. The authors show that careful interpretation of the written sources, whilst unavoidable, enables important information on the composition of lacquers to be obtained. Chemical analysis of lacquers alone, without accompanying study of the sources, is problematic due to the considerable changes that occur in the resins during processing and ageing. Although the most important resins – mastic, larch turpentine and sandarac – can be easily identified, it was not possible to differentiate between fir, spruce and pine resins in aged lacquers. This can be explained by the properties of their diterpenoid constituents. Given that many commercial products are adulterated or even mislabelled to this day, it seems that discerning a product’s quality by evaluating colour, transparency and consistency, as described in the sources, is a method that is still very valuable today.

Name of the disease (Synonyms):: Simpson-Golabi-Behmel syndrome (SGBS). OMIM# of the disease:: 312870. Name of the analysed genes or DNA/chromosome segments:: GPC3. OMIM# of the gene(s):: 300037.

Early-onset epileptic encephalopathy (EE) and combined developmental and epileptic encephalopathies (DEE) are clinically and genetically heterogeneous severely devastating conditions. Recent studies emphasized de novo variants as major underlying cause suggesting a generally low-recurrence risk. In order to better understand the full genetic landscape of EE and DEE, we performed high-resolution chromosomal microarray analysis in combination with whole-exome sequencing in 63 deeply phenotyped independent patients. After bioinformatic filtering for rare variants, diagnostic yield was improved for recessive disorders by manual data curation as well as molecular modeling of missense variants and untargeted plasma-metabolomics in selected patients. In total, we yielded a diagnosis in ∼42% of cases with causative copy number variants in 6 patients (∼10%) and causative sequence variants in 16 established disease genes in 20 patients (∼32%), including compound heterozygosity for causative sequence and copy number variants in one patient. In total, 38% of diagnosed cases were caused by recessive genes, of which two cases escaped automatic calling due to one allele occurring de novo. Notably, we found the recessive gene SPATA5causative in as much as 3% of our cohort, indicating that it may have been underdiagnosed in previous studies. We further support candidacy for neurodevelopmental disorders of four previously described genes (PIK3AP1, GTF3C3, UFC1, and WRAP53), three of which also followed a recessive inheritance pattern. Our results therefore confirm the importance of de novo causative gene variants in EE/DEE, but additionally illustrate the major role of mostly compound heterozygous or hemizygous recessive inheritance and consequently high-recurrence risk.

Wildlife professionals lack a framework and process for incorporating ethical considerations in a systematic and transparent way, along with ecological and social science, to support wildlife management decision‐making. We provide such a framework and process based on 3 of the major theoretical branches ethicists have developed in Western culture: consequentialist moral theory, which focuses on consequences and outcomes; principle‐ and rule‐based approaches that deal with what is considered right or wrong; and virtue ethical theory, which considers factors such as character, virtue, and aesthetics. The framework can be used to anticipate the ethical consequences of alternative courses of action or taking no action. If wildlife professionals use this framework as an assessment tool to provide input into decision‐making, resulting decisions will be more transparent, better understood by stakeholders, and more consistent with public trust responsibilities. Ethics, along with biological and social science, play a role in wildlife management decision making. This paper provides a practical framework and process that can be used to make assessment of ethical considerations explicit and transparent. Use of the framework will contribute to more fully informed decision making, consistent with public trust responsibilities.

Right heart catheterization (RHC) is a common diagnostic tool and of special importance in the diagnosis of pulmonary hypertension (PH). Until today there are no clear instructions or guidelines on which venous access to prefer.

o Vaccine confidence is a belief that vaccines work, are safe, and are part of a trustworthy medical system. The COVID-19 pandemic exposed the fragility of the public's confidence in vaccines and the vaccine enterprise, limiting the public health impact of vaccination. In this review, we examine the critical nature of vaccine confidence to pandemic preparedness and response.

Individuals with Down syndrome (DS) or Autism Spectrum Disorder (ASD), and especially those with both DS and co‐occurring ASD (DS + ASD) commonly display behavioral and psychiatric symptoms that can impact quality of life and places increased burden on caregivers. While the mainstay of treatment in DS and ASD is focused on educational and behavioral therapies, pharmacological treatments can be used to reduce symptom burden. There is a paucity of evidence and limited clinical trials in DS and DS + ASD. Some scientific evidence is available, primarily in open label studies and case series that can guide treatment choices. Additionally, clinical decisions are often extrapolated from evidence and experience from those with ASD, or intellectual disability in those without DS. This article reviews current research in pharmacological treatment in DS, ASD, and DS + ASD, reviews co‐occurring neurodevelopmental and mental health diagnoses in individuals with DS + ASD across the lifespan, and describes practical approaches to psychopharmacological management.

Individuals with Down syndrome (DS) experience a range of medical and neurodevelopmental conditions, necessitating systematic study of their occurrence and impact on neurodevelopmental outcomes. We describe the prevalence and relationships of medical, neurodevelopmental (ND), and mental health (MH) conditions in children with DS. We created a prospective clinical database of individuals with DS, integrated into the workflow of a specialty Down Syndrome Program at a specialty pediatric referral hospital. Conditions were collected through caregiver‐ and clinician report at clinical visits (N= 599). We calculated frequencies of medical, ND, and MH conditions and then assessed the relationship between medical, ND, and MH conditions using frequencies and comparative statistics. The most frequent co‐occurring conditions were vision (72.5%), ear/hearing (71.0%), gastrointestinal (61.3%), respiratory (45.6%), and feeding (33.6%) problems, with variation in frequency by age. ND and MH conditions were reported in one quarter, most commonly autism spectrum disorder and attention‐deficit/hyperactivity disorder. Those with ND and MH conditions had greater frequency of medical conditions, with highest rates of vision, ear/hearing, and gastrointestinal issues, and CHD. Systematically collected clinical data in a large cohort of children with DS reveals high prevalence of several co‐occurring medical, ND, and MH conditions. Clinical care requires an understanding of the complex relationship between medical conditions and neurodevelopment.