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Fractional flow reserve (FFR) or non-hyperaemic pressure ratios are recommended to assess functional relevance of intermediate coronary stenosis. Both diagnostic methods require the placement of a pressure wire in the coronary artery during invasive coronary angiography. Quantitative flow ratio (QFR) is an angiography-based computational method for the estimation of FFR that does not require the use of pressure wires. We aimed to investigate whether a QFR-based diagnostic strategy yields a non-inferior 12-month clinical outcome compared with an FFR-based strategy.

IMPORTANCE: Understanding of the genetics of accessory atrioventricular pathways (APs) and affiliated arrhythmias is limited. OBJECTIVE: To investigate the genetics of APs and affiliated arrhythmias. DESIGN, SETTING, AND PARTICIPANTS: This was a genome-wide association study (GWAS) of APs, defined by International Classification of Diseases (ICD) codes and/or confirmed by electrophysiology (EP) study. Genome-wide significant AP variants were tested for association with AP-affiliated arrhythmias: paroxysmal supraventricular tachycardia (PSVT), atrial fibrillation (AF), ventricular tachycardia, and cardiac arrest. AP variants were also tested in data on other heart diseases and measures of cardiac physiology. Individuals with APs and control individuals from Iceland (deCODE Genetics), Denmark (Copenhagen Hospital Biobank, Danish Blood Donor Study, and SupraGen/the Danish General Suburban Population Study [GESUS]), the US (Intermountain Healthcare), and the United Kingdom (UK Biobank) were included. Time of phenotype data collection ranged from January 1983 to December 2022. Data were analyzed from August 2022 to January 2024. EXPOSURES: Sequence variants. MAIN OUTCOMES AND MEASURES: Genome-wide significant association of sequence variants with APs. RESULTS: The GWAS included 2310 individuals with APs (median [IQR] age, 43 [28-57] years; 1252 [54.2%] male and 1058 [45.8%] female) and 1 206 977 control individuals (median [IQR] year of birth, 1955 [1945-1970]; 632 888 [52.4%] female and 574 089 [47.6%] male). Of the individuals with APs, 909 had been confirmed in EP study. Three common missense variants were associated with APs, in the genes CCDC141 (p.Arg935Trp: adjusted odds ratio [aOR], 1.37; 95% CI, 1.24-1.52, and p.Ala141Val: aOR, 1.55; 95% CI 1.34-1.80) and SCN10A (p.Ala1073Val: OR, 1.22; 95% CI, 1.15-1.30). The 3 variants associated with PSVT and the SCN10A variant associated with AF, supporting an effect on AP-affiliated arrhythmias. All 3 AP risk alleles were associated with higher heart rate and shorter PR interval, and have reported associations with chronotropic response. CONCLUSIONS AND RELEVANCE: Associations were found between sequence variants and APs that were also associated with risk of PSVT, and thus likely atrioventricular reentrant tachycardia, but had allele-specific associations with AF and conduction disorders. Genetic variation in the modulation of heart rate, chronotropic response, and atrial or atrioventricular node conduction velocity may play a role in the risk of AP-affiliated arrhythmias. Further research into CCDC141 could provide insights for antiarrhythmic therapeutic targeting in the presence of an AP.

Discovery of cancer risk variants in the sequence of the germline genome can shed light on carcinogenesis. Here we describe gene burden association analyses, aggregating rare missense and loss of function variants, at 22 cancer sites, including 130,991 cancer cases and 733,486 controls from Iceland, Norway and the United Kingdom. We identified four genes associated with increased cancer risk; the pro-apoptotic BIKfor prostate cancer, the autophagy involved ATG12for colorectal cancer, TGfor thyroid cancer and CMTR2for both lung cancer and cutaneous melanoma. Further, we found genes with rare variants that associate with decreased risk of cancer; AURKBfor any cancer, irrespective of site, and PPP1R15Afor breast cancer, suggesting that inhibition of PPP1R15A may be a preventive strategy for breast cancer. Our findings pinpoint several new cancer risk genes and emphasize autophagy, apoptosis and cell stress response as a focus point for developing new therapeutics.

Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn’s disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases.

AbstractEarly neurobehavioral outcomes among infants with abusive head trauma (AHT) have not been well characterized. Though there are standardized measures for assessing infants, the ability of these measures to detect deficits may be limited. The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale, Second Edition (NNNS-II) has been correlated with neurobehavioral outcomes as early as birth but has not been used with this clinical group. There is no strong evidence of the concurrent validity of this measure. The primary goal was to examine the concurrent validity of the NNNS-II in patients with suspected AHT by comparing it to the Mullen Scales of Early Learning, American Guidance Service (AGS) Edition (Mullen). A secondary goal was to characterize early neurobehavioral outcomes among infants with suspected AHT across two measures. This retrospective study included 11 infants who sustained a traumatic brain injury (TBI) around 40 days of age. The sample’s performance was variable and ranged from average to below average across measures. Participants experienced the most difficulty with visuospatial processing, attentional abilities, physiologic regulation, and asymmetric reflexes, and data suggested the NNNS-II may be more sensitive to deficits. There was evidence of concurrent validity of the NNNS-II based on strong to moderate correlations with the Mullen. Use of the NNNS-II shortly after the injury is more likely to showcase deficits, which may increase the likelihood that patients receive early intervention. Establishing concurrent validity of the NNNS-II further contributes to the evidence base regarding its criterion related validity, which may promote its more regular use.

Antimicrobial resistance (AMR) poses an important global health challenge in the 21st century. A previous study has quantified the global and regional burden of AMR for 2019, followed with additional publications that provided more detailed estimates for several WHO regions by country. To date, there have been no studies that produce comprehensive estimates of AMR burden across locations that encompass historical trends and future forecasts.

The increasing focus on patient centricity in the pharmaceutical industry over the past decade and the changing healthcare landscape, driven by factors such as increased access to information, social media, and evolving patient demands, has necessitated a shift toward greater connectivity and understanding of patients’ unique treatment needs. One pharmaceutical technology that has supported these efforts is long acting injectables (LAIs), which lower the administration frequency for the patient’s provided convenience, better compliance, and hence better therapeutical treatment for the patients. Furthermore, patients with conditions like the human immunodeficiency virus and schizophrenia have positively expressed the desire for less frequent dosing, such as that obtained through LAI formulations. In this work, a comprehensive analysis of marketed LAIs across therapeutic classes and technologies is conducted. The analysis demonstrated an increasing number of new LAIs being brought to the market, recently most as aqueous suspensions and one as a solution, but many other technology platforms were applied as well, in particular, polymeric microspheres and in situ forming gels. The analysis across the technologies provided an insight into to the physicochemical properties the compounds had per technology class as well as knowledge of the excipients typically used within the individual formulation technology. The principle behind the formulation technologies was discussed with respect to the release mechanism, manufacturing approaches, and the possibility of defining predictive in vitro release methods to obtain in vitro in vivo correlations with an industrial angle. The gaps in the field are still numerous, including better systematic formulation and manufacturing investigations to get a better understanding of potential innovations, but also development of new polymers could facilitate the development of additional compounds. The biggest and most important gaps, however, seem to be the development of predictive in vitro dissolution methods utilizing pharmacopoeia described equipment to enable their use for product development and later in the product cycle for quality-based purposes.

Periodontal diseases are associated with dysbiosis in the oral microbial communities. Managing oral biofilms is therefore key for preventing these diseases. Management protocols often include over‐the‐counter antimicrobial mouth rinses, which lack data on their effects on the oral microbiome's ecology, bacterial composition, metabolic activity, and dysbiosis resilience. This study examined the efficacy of antimicrobial mouth rinses to halt dysbiosis in in vitro oral biofilms under periodontitis‐simulating conditions. Multispecies oral biofilms were grown on hydroxyapatite discs (HADs) and rinsed daily with one of six mouth rinses. Positive and negative controls were included. After three rinses, biofilms were analyzed with viability quantitative polymerase chain reaction and visualized using scanning electron microscopy. Supernatants of rinsed biofilms were used for metabolic activity analysis. In addition, human oral keratinocytes were exposed to rinsed biofilms to assess their inflammatory response. All outputs were analyzed for correlation using Spearman coefficient. Product‐related changes were observed in the rinsed biofilms. Three of the six tested mouth rinses could significantly prevent dysbiosis with ≥30% reduction in pathobiont abundance relative to the control. These biofilms had lower metabolic activity, and the exposed human oral keratinocyte produced less interleukin‐8. Interleukin‐8 production correlated to both pathobiont quantity and the metabolic activity of the biofilms. Some mouth rinses could support biofilm resilience and stop dysbiosis evolution in the biofilm model, with a clear product‐related effect. Such mouth rinses can be considered for patients under maintenance/supportive periodontal therapy to prevent/delay disease recurrence. Others are more useful for different periodontal therapy stages.

Age at menopause (AOM) has a substantial impact on fertility and disease risk. While many loci with variants that associate with AOM have been identified through genome-wide association studies (GWAS) under an additive model, other genetic models are rarely considered1. Here through GWAS meta-analysis under the recessive model of 174,329 postmenopausal women from Iceland, Denmark, the United Kingdom (UK; UK Biobank) and Norway, we study low-frequency variants with a large effect on AOM. We discovered that women homozygous for the stop-gain variant rs117316434(A) in CCDC201(p.(Arg162Ter), minor allele frequency ~1%) reached menopause 9 years earlier than other women (P= 1.3 × 10−15). The genotype is present in one in 10,000 northern European women and leads to primary ovarian insufficiency in close to half of them. Consequently, homozygotes have fewer children, and the age at last childbirth is 5 years earlier (P= 3.8 × 10−5). The CCDC201gene was only found in humans in 2022 and is highly expressed in oocytes. Homozygosity for CCDC201loss-of-function has a substantial impact on female reproductive health, and homozygotes would benefit from reproductive counseling and treatment for symptoms of early menopause.

The most common cited cause of split-thickness skin graft failure is infection and due to the association between bacterial findings in wound beds an attempt to decrease the bacterial burden before skin-grafting evolved. Thus, preoperative microbiology swabs of the wound bed became routine at some institutions prior to grafting. This is not standard practice in the Pietermaritzburg Burn Service. Emphasis is instead placed on a strict protocol of intraoperative wound bed preparation to promote adequate graft take. This pilot study aims to evaluate whether preoperative wound swabs are appropriate. We performed a prospective observational study to determine if positive wound cultures were associated with graft failure. All patients with a burn surface area of less than 10%, where delayed grafting (later than 28 days from the time of burn injury) was performed, from March to December 2021 were analyzed. Patient demographics, days from burn to graft, %TBSA burn, %TBSA grafted, whether sharp debridement prior to grafting in the same procedure was performed or not, use of topical gentamicin intraoperatively, graft outcome (% graft loss), need for regraft, and organism grown were recorded into an excel spreadsheet for analysis. The sample included 52 patients. Of these, 17 (31.5%) were female. The median %TBSA grafted was 8% (IQR 4%-13%) and similar in both groups. The median days from burn to grafting were 35 days. Thirty-nine patients (75%) had graft Take and 13 (25%) had graft Failure. In the failed group, the median % graft failure was 50% (30%-70%). Of the group with successful graft take, 90% were noted to have had a positive wound culture prior to grafting. A positive wound culture was not found to be a risk factor for graft failure (P= .993). Despite the positive wound cultures graft take was more than 90% in 75% of grafts performed and only 2/52 patients required supplementary grafting. We believe that this demonstrates that our local protocol is reasonable in this setting and that waiting for negative wound swabs prior to grafting should not be a reason to delay grafting.

This scoping review was conducted to provide an overview of the evidence of point-of-care lung ultrasound (LUS) in emergency medicine. By emphasizing clinical topics, time trends, study designs, and the scope of the primary outcomes, a map is provided for physicians and researchers to guide their future initiatives.

The SCORE2 algorithm is recommended to estimate risk of cardiovascular disease (CVD). Coronary artery calcification (CAC) score is expensive but improves the risk prediction. This study aims to determine and compare the additive value of CAC-score and 19 biomarkers in risk prediction.

A cranial ultrasound (cUS) is an appropriate screening study in infants with congenital CMV (cCMV) infection. In addition to widely agreed-upon abnormalities that define central nervous system (CNS) involvement, subtle cUS findings may be noted, which may represent incidental findings of limited diagnostic and prognostic significance.

The short-chain fatty acids (SCFAs) butyrate, propionate and acetate are microbial metabolites and their availability in the gut and other organs is determined by environmental factors, such as diet and use of antibiotics, that shape the diversity and metabolism of the microbiota. SCFAs regulate epithelial barrier function as well as mucosal and systemic immunity via evolutionary conserved processes that involve G protein-coupled receptor signalling or histone deacetylase activity. Indicatively, the anti-inflammatory role of butyrate is mediated through direct effects on the differentiation of intestinal epithelial cells, phagocytes, B cells and plasma cells, and regulatory and effector T cells. Intestinally derived SCFAs also directly and indirectly affect immunity at extra-intestinal sites, such as the liver, the lungs, the reproductive tract and the brain, and have been implicated in a range of disorders, including infections, intestinal inflammation, autoimmunity, food allergies, asthma and responses to cancer therapies. An ecological understanding of microbial communities and their interrelated metabolic states, as well as the engineering of butyrogenic bacteria may support SCFA-focused interventions for the prevention and treatment of immune-mediated diseases.

Gene promoter and enhancer sequences are bound by transcription factors and are depleted of methylated CpG sites (cytosines preceding guanines in DNA). The absence of methylated CpGs in these sequences typically correlates with increased gene expression, indicating a regulatory role for methylation. We used nanopore sequencing to determine haplotype-specific methylation rates of 15.3 million CpG units in 7,179 whole-blood genomes. We identified 189,178 methylation depleted sequences where three or more proximal CpGs were unmethylated on at least one haplotype. A total of 77,789 methylation depleted sequences (~41%) associated with 80,503 cis-acting sequence variants, which we termed allele-specific methylation quantitative trait loci (ASM-QTLs). RNA sequencing of 896 samples from the same blood draws used to perform nanopore sequencing showed that the ASM-QTL, that is, DNA sequence variability, drives most of the correlation found between gene expression and CpG methylation. ASM-QTLs were enriched 40.2-fold (95% confidence interval 32.2, 49.9) among sequence variants associating with hematological traits, demonstrating that ASM-QTLs are important functional units in the noncoding genome.

Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, a 3-year prospective study, we evaluated a novel diagnostic concept based on multidisciplinary expertise in Germany. Here we present the systematic investigation of the phenotypic and molecular genetic data of 1,577 patients who had undergone exome sequencing and were partially analyzed with next-generation phenotyping approaches. Molecular genetic diagnoses were established in 32% of the patients totaling 370 distinct molecular genetic causes, most with prevalence below 1:50,000. During the diagnostic process, 34 novel and 23 candidate genotype–phenotype associations were identified, mainly in individuals with neurodevelopmental disorders. Sequencing data of the subcohort that consented to computer-assisted analysis of their facial images with GestaltMatcher could be prioritized more efficiently compared with approaches based solely on clinical features and molecular scores. Our study demonstrates the synergy of using next-generation sequencing and phenotyping for diagnosing ultrarare diseases in routine healthcare and discovering novel etiologies by multidisciplinary teams.

Nature-based climate solutions (NbCSs) could play an important role in meeting the goals of the Paris Agreement. The contribution approach offers an alternative model to carbon offsetting for funding NbCSs. This paper presents three crucial design principles to help ensure the contribution approach results in high-quality climate and other benefits and avoids harms.

Introduction: Holistic rehabilitation approaches addressing the numerous complex challenges in young persons with acquired brain injury are required. The purpose of this study was to describe and evaluate the holistic person-centered youth mentoring intervention program, which is based on occupational therapy.Methods: Prospectively collected data were extracted from a national clinical quality database (n= 59). Proportions of young persons receiving different aspects of support and proportions rating the intervention as meaningful were calculated. One-year changes in occupation, work ability, and social interactions were calculated.Results: The young persons most frequently received support for energy management (75%) and structuring of everyday life (61%). Seventy-three percent rated the intervention as meaningful. One year post-inclusion, occupation and work ability had increased by 35% and 58%, respectively, and it had declined by 10% and 26%, respectively. The 1-year increase and decrease in social interactions were less clear (15% and 25%, respectively). One-year changes did not differ between those who entered the program early or late after injury indicating the potential beneficial effect of the program.Conclusion: The findings could indicate that the program has a unique value in supporting young persons with acquired brain injury to create a meaningful everyday life through occupation, work ability, and social interaction.

Health care is experiencing a drive towards digitisation, and many countries are implementing national health data resources. Although a range of cancer risk models exists, the utility on a population level for risk stratification across cancer types has not been fully explored. We aimed to close this gap by evaluating pan-cancer risk models built on electronic health records across the Danish population with validation in the UK Biobank.

The goals of this work are to: (i) investigate the dynamics of oceanic frontogenesis by taking advantage of the geometric mechanics underlying the class of Vertical Slice Models (VSMs) of ocean dynamics and (ii) illustrate the versatility and utility of deterministic and stochastic variational approaches by deriving several variants of wave–current interaction models which describe the effects of internal waves propagating within a vertical planar slice embedded in a 3D region of constant horizontal gradient of buoyancy in the direction transverse to the vertical plane.

The lay summary of trial results to be provided to participants should be written in plain language, use infographics and be concise — something that currently is almost never achieved.

The article titled "In Which I Try to Understand Spacetime and My Mother" by Melissa Holm Shoemake explores the author's personal experiences with religion, family, and self-discovery. The author reflects on their mother's reaction to a family tragedy and their own struggle to reconcile their past with their present. The article also touches on the concept of spacetime, which combines space and time to explain how events are perceived differently by observers. The author's writing delves into themes of faith, identity, and the complexities of familial relationships. [Extracted from the article]

Pediatric obesity is a progressive, chronic disease that can lead to serious cardiometabolic complications. Here we investigated the peripheral lipidome in 958 children and adolescents with overweight or obesity and 373 with normal weight, in a cross-sectional study. We also implemented a family-based, personalized program to assess the effects of obesity management on 186 children and adolescents in a clinical setting. Using mass spectrometry-based lipidomics, we report an increase in ceramides, alongside a decrease in lysophospholipids and omega-3 fatty acids with obesity metabolism. Ceramides, phosphatidylethanolamines and phosphatidylinositols were associated with insulin resistance and cardiometabolic risk, whereas sphingomyelins showed inverse associations. Additionally, a panel of three lipids predicted hepatic steatosis as effectively as liver enzymes. Lipids partially mediated the association between obesity and cardiometabolic traits. The nonpharmacological management reduced levels of ceramides, phospholipids and triglycerides, indicating that lowering the degree of obesity could partially restore a healthy lipid profile in children and adolescents.

Chemical ionization (CI) atmospheric pressure interface mass spectrometry is a unique analytical technique for its low detection limits, softness to preserve molecular information, and selectivity for particular classes of species. Here, we present a fast polarity switching approach for highly sensitive online analysis of a wide range of trace species in complex samples using selective CI chemistries and high-resolution mass spectrometry. It is achieved by successfully coupling a multischeme chemical ionization inlet (MION) and an Orbitrap Fourier transform mass spectrometer. The capability to flexibly combine ionization chemistries from both polarities effectively extends the detectability compared to using only one ionization chemistry, as commonly used positive and negative reagent ions tend to be sensitive to different classes of species. We tested the performance of the MION-Orbitrap using reactive gaseous organic species generated by α-pinene ozonolysis in an environmental chamber and a standard mixture of 71 pesticides. Diethylammonium and nitrate are used as reagent ions in positive and negative polarities. We show that with a mass resolving power of 280,000, the MION-Orbitrap can switch and measure both polarities within 1 min, which is sufficiently fast and stable to follow the temporal evolution of reactive organic species and the thermal desorption profile of pesticides. We detected 23 of the 71 pesticides in the mixture using only nitrate as the reagent ion. Facilitated by polarity switching, we also detected 47 pesticides using diethylammonium, improving the total number of detected species to 59. For reactive organic species generated by α-pinene ozonolysis, we show that combining diethylammonium and nitrate addresses the need to measure oxygenated molecules in atmospheric environments with a wide range of oxidation states. These results indicate that the polarity switching MION-Orbitrap can promisingly serve as a versatile tool for the nontargeted chemical analysis of trace species in various applications.

The article examines the myth of "U.S. National Environmental Policy Act (NEPA) delay" in the context of transitioning to a renewable energy economy, revealing that delays in clean energy implementation are often attributed to factors beyond the NEPA. It discusses the causes of project delays, highlighting insufficient resources, coordination challenges, and project-specific factors as contributors, challenging the notion that NEPA reviews are the cause of delays in policy implementation.

The field of machine learning potentials has experienced a rapid surge in progress, thanks to advances in machine learning theory, algorithms, and hardware capabilities. While the underlying methods are continuously evolving, the infrastructure for their deployment has lagged. The community, due to these rapid developments, frequently finds itself split into groups built around different implementations of machine-learned potentials. In this work, we introduce IPSuite, a Python-driven software package designed to connect different methods and algorithms from the comprehensive field of machine-learned potentials into a single platform while also providing a collaborative infrastructure, helping ensure reproducibility. Furthermore, the data management infrastructure of the IPSuitecode enables simple model sharing and deployment in simulations. Currently, IPSuitesupports six state-of-the-art machine learning approaches for the fitting of interatomic potentials as well as a variety of methods for the selection of training data, running of ab initiocalculations, learning-on-the-fly strategies, model evaluation, and simulation deployment.

A high genetic risk of elevated blood pressure (BP) is associated with increased BP from early childhood and throughout the lifespan.Inherited predispositions also affect the risk of cardiovascular morbidity and mortality, yet this appears to be modified by the absence or presence of hypertension, indicating that genetic hypertension risk is not deterministic, and that controlling BP can and should be done across the polygenic risk distribution.Given that differences in BP emerge early in life as a function of genetic risk, polygenic risk scores have the potential to reduce the duration of exposure to high BP by identifying high-risk individuals from birth, and thereby attenuate lifelong disease risk.Graphical Abstract

Two-thirds of all human conceptions are lost, in most cases before clinical detection. The lack of detailed understanding of the causes of pregnancy losses constrains focused counseling for future pregnancies. We have previously shown that a missense variant in synaptonemal complex central element protein 2 (SYCE2), in a key residue for the assembly of the synaptonemal complex backbone, associates with recombination traits. Here we show that it also increases risk of pregnancy loss in a genome-wide association analysis on 114,761 women with reported pregnancy loss. We further show that the variant associates with more random placement of crossovers and lower recombination rate in longer chromosomes but higher in the shorter ones. These results support the hypothesis that some pregnancy losses are due to failures in recombination. They further demonstrate that variants with a substantial effect on the quality of recombination can be maintained in the population.

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Solid-phase peptide synthesis (SPPS) is an efficient platform technology for synthesizing synthetic peptides but has an environmental downside due to the use of vast amounts of toxic solvents. In recent years, a big effort has been made to replace these solvents with more environmentally benign alternatives; however, this work has not had a significant effect on reducing the PMI and carbon footprint of SPPS. Herein, we demonstrate that by adding a low concentration of Oxyma Pure to the waste stream after Fmoc-removal, a simple real-time online UV–vis monitoring system can quantify piperidine with the needed sensitivity. In addition to the potential for reducing washing volumes after Fmoc-removal, this inexpensive and easy-to-implement process analytical tool allows the determination of completed washing by visual inspection due to the yellow color of Oxyma Pure in the presence of piperidine. Moreover, manual sampling of the waste stream is not needed, which reduces the overall process time. Importantly, the methodology was found to be compatible with green SPPS performed in 10–50% DMSO in the EtOAc mixtures.

Previous meta-analyses have shown reduced risks of composite adverse events with intravascular imaging-guided percutaneous coronary intervention (PCI) compared with angiography guidance alone. However, these studies have been insufficiently powered to show whether all-cause death or all myocardial infarction are reduced with intravascular imaging guidance, and most previous intravascular imaging studies were done with intravascular ultrasound rather than optical coherence tomography (OCT), a newer imaging modality. We aimed to assess the comparative performance of intravascular imaging-guided PCI and angiography-guided PCI with drug-eluting stents.

AbstractPostirradiation examination of nuclear fuel is routinely performed to characterize the important properties of current and future fuel. Gamma emission tomography is a proven noninvasive technique for this purpose. Among various measurement elements of the technique, a gamma-ray detector is an important element whose spectroscopic abilities and detection efficiency affect the overall results. Finding a combination of high detection efficiency and excellent energy resolution in a single detector is often a challenge. We have designed a novel planar segmented high-purity germanium detector that offers simultaneous measurement in six lines of sight with excellent energy resolution. The simultaneous detection ability enables faster data acquisition in a tomographic measurement, which may facilitate achieving higher spatial resolution. In this work, we have demonstrated the first use of the detector by performing a full tomographic measurement of mockup fuel rods. Two methods of detector data analysis were used to make spectra, and the images (tomograms) were reconstructed using the filtered back projection algorithm. The reconstructed images validate the successful use of the detector for tomographic measurement. The use of the detector for real fuel measurement is being planned and will be performed in the near future.

Study design: Controlled pragmatic intervention with follow-up. Objectives: To describe cardiometabolic risk outcomes after a pragmatic intervention implemented into standard spinal cord injury (SCI) rehabilitation. Setting: Inpatient SCI rehabilitation in East-Denmark. Participants: Inpatients, >18 years, having sustained a SCI within the last 12 months at admission to rehabilitation, regardless of etiology, neurological level or completeness of the lesion or mobility status. Methods: Patient education on health promotion was guided by evidence and included feedback on peak oxygen uptake (VO2peak) (primary outcome measure), body mass index (BMI), Dual energy X-ray absorptiometry and metabolic profile (secondary outcome measures). Paired t-tests, non-parametric tests and Analysis of Variance (ANOVA) were used for analyzes. VO2peak and BMI were compared to historical data. Results: VO2peak increased significantly from admission to discharge but did not exceed historical data despite a minimal clinical important difference. BMI decreased significantly during rehabilitation (p< 0.001) followed by a significant increase after discharge (p= 0.006). There was a trend that people with American Spinal Injury Association Impairment Scale (AIS) D SCI increased lean mass to nearly normal values. Criteria for pre-diabetes or diabetes were present in 28.5% and dyslipidemia in 45% of the participants 44.2 days after time of injury. Conclusions: Despite improvements during rehabilitation, outcome measures were worse than recommended, and most outcome measures worsened at follow up, even in people with an AIS D SCI. Meaningful support regarding exercise and diet when tackling altered life circumstances is needed after discharge.

IMPORTANCE: Since bilateral simultaneous postoperative endophthalmitis (BSPOE) after immediate sequential bilateral cataract surgery (ISBCS) can be devastating for the patient, evaluating such cases in depth is important to maintaining patient safety. OBJECTIVE: To evaluate whether a systemic breach of sterility was associated with an outbreak of BSPOE after ISBCSs performed on the same day at a single community-based eye clinic. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series included all patients diagnosed with BSPOE at ophthalmology departments in Denmark following an infectious outbreak after ISBCSs performed at a single community-based eye clinic in December 2022. EXPOSURE: Bilateral simultaneous postoperative endophthalmitis acquired after ISBCS. MAIN OUTCOME AND MEASURES: Patient recovery from BSPOE after ISBCS was evaluated based on clinical and microbiological reports. RESULTS: A woman aged 71 years, a man aged 84 years, and a woman aged 79 years consecutively presented with symptoms of endophthalmitis at regional eye departments 4 to 8 days after ISBCS performed on the same date at the same eye clinic. Five of 6 infected eyes underwent vitrectomy, and all eyes received an intravitreous injection of antibiotics. The same strain of Staphylococcus epidermidis was isolated in 4 of 5 eyes that underwent vitrectomy. Contamination of viscoelastics was ruled out with repeated cultures. One eye was eviscerated due to phthisis. In another patient, the final visual acuity of the eye most severely affected was 20/63 Snellen equivalents. Visual acuity of the remaining eyes recovered to 20/25 (3 eyes in 2 patients) and 20/20 (1 eye) Snellen equivalents. CONCLUSIONS AND RELEVANCE: The finding of the same strain of S epidermidis in all patient cultures suggests a systemic breach of sterility at the clinic on the day of ISBCS. The outcome of these cases emphasizes the need to adhere to a strict surgical methodology and sterile principles during ISBCS.

This work explores the bandwidth limits of connected slot arrays, focusing on their low-frequency bound. We show how the ground plane, present in this structure to ensure unidirectional radiation, places a limit on their operation in terms of active reflection coefficient at lower frequencies. In particular, a low-frequency approximation of the active reflection coefficient of a representative connected slot array is derived based on a Green’s function formulation and an equivalent circuit model of the array. The design parameters of the array unit-cell are taken into account and their influence on the proposed limit is analyzed. Finally, the low-frequency approximation reveals the impact of surface waves when scanning over the E-plane of the array. A solution to overcome such an issue is proposed. It considers the introduction of vertical metallic walls within the substrate supporting the slots of the array. The proposed low-frequency bound is modified accordingly to further highlight the benefits of this solution.

IMPORTANCE: Recurrent pericarditis is a treatment challenge and often a debilitating condition. Drugs inhibiting interleukin 1 cytokines are a promising new treatment option, but their use is based on scarce biological evidence and clinical trials of modest sizes, and the contributions of innate and adaptive immune processes to the pathophysiology are incompletely understood. OBJECTIVE: To use human genomics, transcriptomics, and proteomics to shed light on the pathogenesis of pericarditis. DESIGN, SETTING, AND PARTICIPANTS: This was a meta-analysis of genome-wide association studies of pericarditis from 5 countries. Associations were examined between the pericarditis-associated variants and pericarditis subtypes (including recurrent pericarditis) and secondary phenotypes. To explore mechanisms, associations with messenger RNA expression (cis-eQTL), plasma protein levels (pQTL), and CpG methylation of DNA (ASM-QTL) were assessed. Data from Iceland (deCODE genetics, 1983-2020), Denmark (Copenhagen Hospital Biobank/Danish Blood Donor Study, 1977-2022), the UK (UK Biobank, 1953-2021), the US (Intermountain, 1996-2022), and Finland (FinnGen, 1970-2022) were included. Data were analyzed from September 2022 to August 2023. EXPOSURE: Genotype. MAIN OUTCOMES AND MEASURES: Pericarditis. RESULTS: In this genome-wide association study of 4894 individuals with pericarditis (mean [SD] age at diagnosis, 51.4 [17.9] years, 2734 [67.6%] male, excluding the FinnGen cohort), associations were identified with 2 independent common intergenic variants at the interleukin 1 locus on chromosome 2q14. The lead variant was rs12992780 (T) (effect allele frequency [EAF], 31%-40%; odds ratio [OR], 0.83; 95% CI, 0.79-0.87; P = 6.67 × 10−16), downstream of IL1B and the secondary variant rs7575402 (A or T) (EAF, 45%-55%; adjusted OR, 0.89; 95% CI, 0.85-0.93; adjusted P = 9.6 × 10−8). The lead variant rs12992780 had a smaller odds ratio for recurrent pericarditis (0.76) than the acute form (0.86) (P for heterogeneity = .03) and rs7575402 was associated with CpG methylation overlapping binding sites of 4 transcription factors known to regulate interleukin 1 production: PU.1 (encoded by SPI1), STAT1, STAT3, and CCAAT/enhancer-binding protein β (encoded by CEBPB). CONCLUSIONS AND RELEVANCE: This study found an association between pericarditis and 2 independent sequence variants at the interleukin 1 gene locus. This finding has the potential to contribute to development of more targeted and personalized therapy of pericarditis with interleukin 1–blocking drugs.