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Selfish genetic elements contribute to hybrid incompatibility and bias or drive their own transmission1,2. Chromosomal drive typically functions in asymmetric female meiosis, whereas gene drive is normally post-meiotic and typically found in males. Here, using single-molecule and single-pollen genome sequencing, we describe Teosinte Pollen Drive, an instance of gene drive in hybrids between maize (Zea mays ssp. mays) and teosinte mexicana (Z. mays ssp. mexicana) that depends on RNA interference (RNAi). 22-nucleotide small RNAs from a non-coding RNA hairpin in mexicana depend on Dicer-like 2 (Dcl2) and target Teosinte Drive Responder 1 (Tdr1), which encodes a lipase required for pollen viability. Dcl2, Tdr1 and the hairpin are in tight pseudolinkage on chromosome 5, but only when transmitted through the male. Introgression of mexicana into early cultivated maize is thought to have been critical to its geographical dispersal throughout the Americas3, and a tightly linked inversion in mexicana spans a major domestication sweep in modern maize4. A survey of maize traditional varieties and sympatric populations of teosinte mexicana reveals correlated patterns of admixture among unlinked genes required for RNAi on at least four chromosomes that are also subject to gene drive in pollen from synthetic hybrids. Teosinte Pollen Drive probably had a major role in maize domestication and diversification, and offers an explanation for the widespread abundance of self small RNAs in the germ lines of plants and animals.

To emphasize to learners how factors outside individual control impact health, scholars introduced the concept of structural competency. Structural competency refers to the development of analytical skills that reveal the larger societal context beyond the patient-clinician interaction that shapes health outcomes. The growing adoption of structural competency curricula, however, has revealed that prelicensure and early career health professionals can feel overwhelmed by the mismatch between the wide scale of entrenched problems and the limited scope of their therapeutic skills. In this Reflections paper, I draw on theories from Giddens, Bourdieu, and Foucault to restore a role for individual agency in promoting health. Conceiving of structure and agency as mutually constituting suggests that structures are human-made and can be vulnerable to challenge. Structures, however, disperse power to such an extent that people internalize their rules and discipline themselves to follow them without explicit enforcement. It is precisely in those local sites of power that health professions learners and educators can intervene to interrupt the reproduction of structures harmful to health. As I demonstrate with an example from a reproductive health emergency, being structurally competent may also include contesting agreed upon norms at the level of the learning and clinical environments rather than only macro-level societal forces. Rewriting norms within health professions education and clinical practice is not necessarily a simpler task, but it provides learners and educators with more accessible targets for action.

The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 2,717 new measurements from 869 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. Particle properties and search limits are listed in Summary Tables. We give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Most of the 120 reviews are updated, including many that are heavily revised. The Review is divided into two volumes. Volume 1 includes the Summary Tables and 97 review articles. Volume 2 consists of the Particle Listings and contains also 23 reviews that address specific aspects of the data presented in the Listings. The complete Review (both volumes) is published online on the website of the Particle Data Group (pdg.lbl.gov) and in a journal. Volume 1 is available in print as the PDG Book. A Particle Physics Booklet with the Summary Tables and essential tables, figures, and equations from selected review articles is available in print, as a web version optimized for use on phones, and as an Android app. The 2024 edition of the Review of Particle Physics should be cited as: S. Navas et al. (Particle Data Group), Phys. Rev. D 110, 030001 (2024)

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

BACKGROUND: Schizophrenia is associated with an increased risk of aggressive behaviour, which may partly be explained by illness-related changes in brain structure. However, previous studies have been limited by group-level analyses, small and selective samples of inpatients and long time lags between exposure and outcome. METHODS: This cross-sectional study pooled data from 20 sites participating in the international ENIGMA-Schizophrenia Working Group. Sites acquired T1-weighted and diffusion-weighted magnetic resonance imaging scans in a total of 2095 patients with schizophrenia and 2861 healthy controls. Measures of grey matter volume and white matter microstructural integrity were extracted from the scans using harmonised protocols. For each measure, normative modelling was used to calculate how much patients deviated (in z-scores) from healthy controls at the individual level. Ordinal regression models were used to estimate the associations of these deviations with concurrent aggressive behaviour (as odds ratios [ORs] with 99% confidence intervals [CIs]). Mediation analyses were performed for positive symptoms (i.e., delusions, hallucinations and disorganised thinking), impulse control and illness insight. Aggression and potential mediators were assessed with the Positive and Negative Syndrome Scale, Scale for the Assessment of Positive Symptoms or Brief Psychiatric Rating Scale. RESULTS: Aggressive behaviour was significantly associated with reductions in total cortical volume (OR [99% CI] = 0.88 [0.78, 0.98], p = .003) and global white matter integrity (OR [99% CI] = 0.72 [0.59, 0.88], p = 3.50 × 10-5) and additional reductions in dorsolateral prefrontal cortex volume (OR [99% CI] = 0.85 [0.74, 0.97], p =.002), inferior parietal lobule volume (OR [99% CI] = 0.76 [0.66, 0.87], p = 2.20 × 10-7) and internal capsule integrity (OR [99% CI] = 0.76 [0.63, 0.92], p = 2.90 × 10-4). Except for inferior parietal lobule volume, these associations were largely mediated by increased severity of positive symptoms and reduced impulse control. CONCLUSIONS: This study provides evidence that the co-occurrence of positive symptoms, poor impulse control and aggressive behaviour in schizophrenia has a neurobiological basis, which may inform the development of therapeutic interventions.

This article explores the implementation of Radically Open Dialectical Behavior Therapy (RO DBT) in a University or College Counseling Setting (UCCS). The authors review the rationale for including RO DBT in a UCCS and the process of implementing the treatment at their center. This paper evaluates this newly implemented treatment by examining clinician experience, feasibility, and adaptability of RO DBT including Words of Wisdom regarding future implementations of RO DBT in a UCCS.

BackgroundSevere and sustained emotional stress creates a physiological burden through increased sympathetic activity and higher energy demand. This may lead to increased oxidative stress and development of the metabolic syndrome. Emotional stress has been shown to contribute to the onset, progression, and control of type 2 diabetes (T2D). Stress management and biofeedback assisted relaxation have been shown to improve glycemic control. Use of a mobile app for stress management may enhance the scalability of such an approach. ObjectiveThe aim of this study was to assess the effect of using a mobile app of biofeedback-assisted relaxation on weight, blood pressure (BP), and glycemic measures of patients with T2D. MethodsAdult patients with T2D and inadequate glycemic control (hemoglobin A1c [HbA1c]>7.5%) were recruited from the outpatient diabetes clinic. Baseline weight, BP, HbA1c, fasting plasma glucose (FPG), triglycerides (TG), and 7-point self-monitoring of blood glucose were measured. Patients were provided with a stress reducing biofeedback mobile app and instructed to use it 3 times a day. The mobile app—Serenita—is an interactive relaxation app based on acquiring a photoplethysmography signal from the mobile phone’s camera lens, where the user places his finger. The app collects information regarding the user’s blood flow, heart rate, and heart rate variability and provides real-time feedback and individualized breathing instructions in order to modulate the stress level. All clinical and biochemical measures were repeated at 8 and 16 weeks of the study. The primary outcome was changes in measures at 8 weeks. ResultsSeven patients completed 8 weeks of the study and 4 completed 16 weeks. At week 8, weight dropped by an average of 4.0 Kg (SD 4.3), systolic BP by 8.6 mmHg (SD 18.6), HbA1c by 1.3% (SD 1.6), FPG by 4.3 mmol/l (4.2), and serum TG were unchanged. ConclusionsStress reduction using a mobile app based on biofeedback may improve glycemic control, weight, and BP.

Abstract Individuals with psychotic disorders often lead sedentary lives, heightening the risk of developing forward head posture. Forward head posture affects upper cervical vertebrae, raising the likelihood of daily discomforts like skeletal misalignment, neck pain, and reduced cardiorespiratory fitness. Improving cardiorespiratory fitness in psychotic disorders is relevant, given its proven benefits in enhancing physical and mental health. This study investigates forward head posture by measuring craniovertebral angles in psychotic disorders and the relationship with reduced cardiorespiratory fitness. To determine whether forward head posture is specific to psychotic disorders, we also included individuals with autism spectrum disorder and healthy controls. Among 85 participants (32 psychotic disorders, 26 autism spectrum disorder, 27 healthy controls), photogrammetric quantification revealed a significantly lower mean craniocervical angle in psychotic disorders compared to autism spectrum disorder (p =

Isotropic functions of positions r 1 , r 2 , … , r N , i.e. functions invariant under simultaneous rotations of all the coordinates, are conveniently formed using spherical harmonics and Clebsch-Gordan coefficients. An orthonormal basis of such functions provides a formalism suitable for analyzing isotropic distributions such as those that arise in cosmology, for instance in the clustering of galaxies as revealed by large-scale structure surveys. The algebraic properties of the basis functions are conveniently expressed in terms of 6-j and 9-j symbols. The calculation of relations among the basis functions is facilitated by ‘Yutsis’ diagrams for the addition and recoupling of angular momenta.

We show how the galaxy four-point correlation function can test for cosmological parity violation. The detection of cosmological parity violation would reflect previously unknown forces present at the earliest moments of the Universe. Recent developments both in rapidly evaluating galaxy N-point correlation functions and in determining the corresponding covariance matrices make the search for parity violation in the four-point correlation function possible in current and upcoming surveys such as those undertaken by Dark Energy Spectroscopic Instrument, the Euclid satellite, and the Vera C. Rubin Observatory. We estimate the limits on cosmic parity violation that could be set with these data.

We present an analytic treatment of the self-similar collapse of a uniform density ellipsoid to linear order in the deviations from sphericity. First we obtain a self-consistent closed-form solution for the evolution of an isolated ellipsoid and then impose the effects of an external forcing. This model describes the evolution under gravity of a pre-stellar core of molecular gas embedded in a much larger and lower-density filament. We compare with numerical solutions for the collapse without the limitation of small deviations. These show how the external perturbing force producing the initial deviation from sphericity is eventually surpassed by the anisotropic forces generated by the collapsing ellipsoid itself. This model should be useful in interpreting the way in which environment shapes the evolution of pre-stellar cores.

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

ObjectiveBroca's aphasia is a syndrome of impaired fluency with retained comprehension. The authors used an unbiased algorithm to examine which neuroanatomical areas are most likely to result in Broca's aphasia following surgical lesions.MethodsPatients were prospectively evaluated with standardized language batteries before and after surgery. Broca's area was defined anatomically as the pars opercularis and triangularis of the inferior frontal gyrus. Broca's aphasia was defined by the Western Aphasia Battery language assessment. Resections were outlined from MRI scans to construct 3D volumes of interest. These were aligned using a nonlinear transformation to Montreal Neurological Institute brain space. A voxel-based lesion-symptom mapping (VLSM) algorithm was used to test for areas statistically associated with Broca's aphasia when incorporated into a resection, as well as areas associated with deficits in fluency independent of Western Aphasia Battery classification. Postoperative MRI scans were reviewed in blinded fashion to estimate the percentage resection of Broca's area compared to areas identified using the VLSM algorithm.ResultsA total of 289 patients had early language evaluations, of whom 19 had postoperative Broca's aphasia. VLSM analysis revealed an area that was highly correlated (p < 0.001) with Broca's aphasia, spanning ventral sensorimotor cortex and supramarginal gyri, as well as extending into subcortical white matter tracts. Reduced fluency scores were significantly associated with an overlapping region of interest. The fluency score was negatively correlated with fraction of resected precentral, postcentral, and supramarginal components of the VLSM area.ConclusionsBroca's aphasia does not typically arise from neurosurgical resections in Broca's area. When Broca's aphasia does occur after surgery, it is typically in the early postoperative period, improves by 1 month, and is associated with resections of ventral sensorimotor cortex and supramarginal gyri.

Abstract General practitioners (GPs) are often unaware of antipsychotic (AP)-induced cardiovascular risk (CVR) and therefore patients using atypical APs are not systematically monitored. We evaluated the feasibility of a complex intervention designed to review the use of APs and advise on CVR-lowering strategies in a transmural collaboration. A mixed methods prospective cohort study in three general practices in the Netherlands was conducted in 2021. The intervention comprised three steps: a digital information meeting, a multidisciplinary meeting, and a shared decision-making visit to the GP. We assessed patient recruitment and retention rates, advice given and adopted, and CVR with QRISK3 score and mental state with MHI-5 at baseline and three months post-intervention. GPs invited 57 of 146 eligible patients (39%), of whom 28 (19%) participated. The intervention was completed by 23 (82%) and follow-up by 18 participants (64%). At the multidisciplinary meeting, 22 (78%) patients were advised to change AP use. Other advice concerned medication (other than APs), lifestyle, monitoring, and psychotherapy. At 3-months post-intervention, 41% (28/68) of this advice was adopted. Our findings suggest that this complex intervention is feasible for evaluating health improvement in patients using AP in a trial.

Abstract Background As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (

Abstract Acute myeloid leukemia (AML) is a highly aggressive hematologic cancer with poor survival across a broad range of molecular subtypes. Development of efficacious and well-tolerable therapies encompassing the range of mutations that can arise in AML remains an unmet need. The bromo- and extra-terminal domain (BET) family of proteins represents an attractive therapeutic target in AML due to their crucial roles in many cellular functions, regardless of any specific mutation. Many BET inhibitors (BETi) are currently in pre-clinical and early clinical development, but acquisition of resistance continues to remain an obstacle for the drug class. Novel methods to circumvent this development of resistance could be instrumental for the future use of BET inhibitors in AML, both as monotherapy and in combination. To date, many investigations into possible drug combinations of BETi with CDK inhibitors have focused on CDK9, which has a known physical and functional interaction with the BET protein BRD4. Therefore, we wished to investigate possible synergy and additive effects between inhibitors of these targets in AML. Here, we describe combination therapy with the multi-CDK inhibitor dinaciclib and the BETi PLX51107 in pre-clinical models of AML. Dinaciclib and PLX51107 demonstrate additive effects in AML cell lines, primary AML samples, and in vivo. Further, we demonstrate novel activity of dinaciclib through inhibition of the canonical/β-catenin dependent Wnt signaling pathway, a known resistance mechanism to BETi in AML. We show dinaciclib inhibits Wnt signaling at multiple levels, including downregulation of β-catenin, the Wnt co-receptor LRP6, as well as many Wnt pathway components and targets. Moreover, dinaciclib sensitivity remains unaffected in a setting of BET resistance, demonstrating similar inhibitory effects on Wnt signaling when compared to BET-sensitive cells. Ultimately, our results demonstrate rationale for combination CDKi and BETi in AML. In addition, our novel finding of Wnt signaling inhibition could have potential implications in other cancers where Wnt signaling is dysregulated and demonstrates one possible approach to circumvent development of BET resistance in AML.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of COVID-19. METHODS: In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18-79 years (Part 1) or ≥70 years (Part 2) with severe COVID-19, respiratory failure and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90 mg (human anti-GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28. RESULTS: In Part 1 (n=806 randomised 1:1 otilimab:placebo), 71% of otilimab-treated patients were alive and free of respiratory failure at Day 28 versus 67% who received placebo; the model-adjusted difference of 5.3% was not statistically significant (95% CI -0.8-11.4%, p=0.09). A nominally significant model-adjusted difference of 19.1% (95% CI 5.2-33.1%, p=0.009) was observed in the predefined 70-79 years subgroup, but this was not confirmed in Part 2 (n=350 randomised) where the model-adjusted difference was 0.9% (95% CI -9.3-11.2%, p=0.86). Compared with placebo, otilimab resulted in lower serum concentrations of key inflammatory markers, including the putative pharmacodynamic biomarker CC chemokine ligand 17, indicative of GM-CSF pathway blockade. Adverse events were comparable between groups and consistent with severe COVID-19. CONCLUSIONS: There was no significant difference in the proportion of patients alive and free of respiratory failure at Day 28. However, despite the lack of clinical benefit, a reduction in inflammatory markers was observed with otilimab, in addition to an acceptable safety profile.

Background: The University of Washington (UW) Center for Stewardship in Medicine (CSiM) supports a tele-antimicrobial stewardship (AMS) program (TASP) using the ECHO approach (Extension for Community Healthcare Outcomes) in small, rural, and Critical Access Hospitals (primarily in the western U.S.) with education, mentoring, organizational capacity building, and a community of peers. To evaluate the continuing education (CE) component of UW-TASP ECHO, CSiM surveyed individuals receiving CE credits as part of the program. This survey was designed to track individuals’ satisfaction with the program and to assess the impact of UW-TASP ECHO on AMS in participating facilities. Methods: The CE participants’ survey was completed annually by individuals participating in UW TASP ECHO using online survey software. The survey included closed-ended and open-ended questions. Responses to open-ended questions were entered into Atlas.ti qualitative analysis software and coded iteratively according to themes that emerged. When a new code emerged partway through the coding process, earlier surveys were re-coded for the new code. Final codes were grouped into themes and sub-themes and quotes from each theme identified were summarized and attached to the theme and reported. Results: Data from three administrations of this survey were available: 2018-2019 (n=66); 2020-2021 (n=27); and 2021-2022 (n=30). These surveys were completed by a total of 95 individuals from 53 hospitals. Seven of these individuals completed a survey in each year, 14 completed a survey in two years, and 74 completed only one survey. Themes identified were COVID-19 support (including procedures and policies, being kept up-to-date, research summaries, and peer support), the antibiotic pocket guide developed by UW, strength in community, staff education, role of CSiM in developing/strengthening the AMS program at the facility, change in use of antibiotics, UW imprimatur, learning/growing as a healthcare provider, and importance for small, rural hospitals (see examples in Table 1). Conclusions: This qualitative analysis provides evidence from surveys of individuals participating in CE that UW TASP ECHO has had a meaningful impact in such domains as building a strong community among small, rural and critical access hospitals, educating staff, changing antibiotic use and providing peer support, among others.

Background: Inappropriate diagnosis and treatment of urinary tract infections (UTI) contributes to antibiotic overuse. The Inappropriate Diagnosis of UTI (ID-UTI) measure—which quantifies the percentage of treated bacteriuria that is asymptomatic (ASB) using a standard definition of UTI—has been validated in acute care hospitals, but not in critical access hospitals (CAHs) where resources differ. Methods: From October 2022-July 2023, ten CAHs participated in a program to reduce ASB treatment, including education, coaching, and hospital feedback using the ID-UTI measure. Our primary aim was to assess performance characteristics of the ID-UTI standard definition and measure in CAHs (Figure 1). Non-physician abstractors from each CAH submitted clinical data (e.g., signs/symptoms) via REDCap for consecutive adult patients who were admitted or discharged from the emergency department and received antibiotics for bacteriuria. The case abstraction goal for each CAH was 5-6 cases/month. To assess feasibility, we evaluated the ability of each CAH to achieve goal case abstractions. To assess validity and reliability of the ID-UTI standard definition, two physicians reviewed 10% of submitted cases using deidentified patient notes and assessed agreement with the standard ID-UTI definition and consensus clinical opinion. Based on submitted data, we provided bi-monthly feedback reports to CAHs including the hospital-level ID-UTI measure to benchmark progress and for peer comparison. We measured monthly change in the ID-UTI measure using a mixed-effects logistic regression model (Figure 1, Figure 2). Results: Among 10 CAHs, 4 (40%) submitted >59 cases over 10 months (goal) while 3 (30%) submitted >35 cases (secondary goal). Physician reviewers assessed 9.5% (58/608) of cases. Utilizing the ID-UTI standard definition, there was high agreement (93%) in ASB vs UTI designation between each physician reviewer and the CAH’s REDCap assessment (Figure 3). Compared to clinical opinion, the ID-UTI standard definition identified 48% (16/33) of ASB cases and 100% (25/25) of UTI cases (Figure 4). Over the program, the percentage of cases treated for UTI that were ASB decreased from 28.4% (range 0-63%) to 18.6% (range, 0-33%; p=0.055) (Figure 5). Conclusions: Case abstraction with use of the ID-UTI measure was feasible and reliable to implement with modifications for CAHs. Data collection by untrained staff was as reliable as physician adjudication. Though the ID-UTI standard definition undercounted ASB cases (low sensitivity), cases reported as ASB were always ASB when adjudicated (high specificity). The program, including performance feedback using the ID-UTI measure, was associated with a trend toward lower treatment of ASB.

BackgroundBronchiolitis is a respiratory infection of viral origin and is often linked to syncytial respiratory virus. It is the most frequent cause of hospitalisation in children aged under 2 years and sometimes requires transfer to intensive care. Infectious complications may also arise in the short term, and longer-term progression towards asthma is also possible. The occurrence of bronchiolitis in children may affect families in different ways, and may have psychological, organisational, employment-related, and possibly financial consequences.ObjectiveThe aim of the study was to determine the familial and socioeconomic repercussions of bronchiolitis in infants.SettingParents with a child with bronchiolitis between January 2021 and May 2022, who were registered at the site of the Association Française de Pédiatrie Ambulatoire (Mpedia site) or at the site of the Malin Programme, which serves families experiencing financial difficulties, were included in the study.ParticipantsAll parents consenting to participate in the study.ResultsA total of 2,059 valid questionnaires were retrieved: 1,318 (64%) were obtained from parents through the Mpedia website and 741 (36%) were obtained through the Malin Programme. Parents associated with the Malin Programme had more children, as well as higher rates of unemployment and financial difficulties, and required greater medical assistance. Hospitalisation was necessary in 37% of cases and was comparable between groups. During the illness, moderate to severe anxiety was present in 73% of parents; this percentage rose to 87% if the child required hospitalisation. Many parents reported effects on daily home (84%) and work life (90%), and 60% had taken a leave of absence from work.ConclusionBeyond the immediate or longer-term medical consequences of bronchiolitis in infants, the illness affects families in multiple ways and can lead to anxiety, as well as changes in day-to-day home and work life. Physicians should have greater awareness of these consequences and should strive to decrease their impact.

Summary: Here, we present a protocol for the development of mRNA-loaded lipid nanoparticle (LNP) vaccines for target antigen sequences of interest. We describe key steps required to design and synthesize mRNA constructs, their LNP encapsulation, and mouse immunization. We then detail quality control assays to determine RNA purity, guidelines to measure RNA immunogenicity using in vitro reporter systems, and a technique to evaluate antigen-specific T cell responses following immunization. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The Dark Energy Spectroscopic Instrument (DESI) embarked on an ambitious 5 yr survey in 2021 May to explore the nature of dark energy with spectroscopic measurements of 40 million galaxies and quasars. DESI will determine precise redshifts and employ the baryon acoustic oscillation method to measure distances from the nearby universe to beyond redshift z > 3.5, and employ redshift space distortions to measure the growth of structure and probe potential modifications to general relativity. We describe the significant instrumentation we developed to conduct the DESI survey. This includes: a wide-field, 3.°2 diameter prime-focus corrector; a focal plane system with 5020 fiber positioners on the 0.812 m diameter, aspheric focal surface; 10 continuous, high-efficiency fiber cable bundles that connect the focal plane to the spectrographs; and 10 identical spectrographs. Each spectrograph employs a pair of dichroics to split the light into three channels that together record the light from 360-980 nm with a spectral resolution that ranges from 2000-5000. We describe the science requirements, their connection to the technical requirements, the management of the project, and interfaces between subsystems. DESI was installed at the 4 m Mayall Telescope at Kitt Peak National Observatory and has achieved all of its performance goals. Some performance highlights include an rms positioner accuracy of better than 0.″1 and a median signal-to-noise ratio of 7 of the [O ii] doublet at 8 × 10-17 erg s-1 cm-2 in 1000 s for galaxies at z = 1.4-1.6. We conclude with additional highlights from the on-sky validation and commissioning, key successes, and lessons learned.