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Prior to COVID-19, few hospitals had fully tested emergency surge plans. Uncertainty in the timing and degree of surge complicates planning efforts, putting hospitals at risk of being overwhelmed. Many lack access to hospital-specific, data-driven projections of future patient demand to guide operational planning. Our hospital experienced one of the largest surges in New England. We developed statistical models to project hospitalizations during the first wave of the pandemic. We describe how we used these models to meet key planning objectives. To build the models successfully, we emphasize the criticality of having a team that combines data scientists with frontline operational and clinical leadership. While modeling was a cornerstone of our response, models currently available to most hospitals are built outside of their institution and are difficult to translate to their environment for operational planning. Creating data-driven, hospital-specific, and operationally relevant surge targets and activation triggers should be a major objective of all health systems.
This chapter examines the western reception of the creed and canons of the 325 Council of Nicaea. The Nicene–Constantinopolitan Creed appeared in the eucharistic liturgy towards the end of the sixth century, controversially with the insertion of filioque possibly at the Third Synod of Toledo in 589, although the creed was not used in Rome until 1014 under Benedict VIII, despite efforts by Charlemagne with Leo III early in the ninth century. The theological dispute over filioque resulted in the schism between East and West in 1054. The reception of the twenty canons of Nicaea as disciplinary law can be traced through letters of Roman bishops from the end of the fourth century onwards preserved mainly in what would become known as decretal collections. In the middle of the fourth century in Rome the canons from the 343 Synod of Serdica were conflated with the canons from Nicaea and early in the fifth century under Zosimus they were significant in the dispute between Rome and Carthage over questions of Rome’s authority. The questions examined are the degree to which the Catholic Church has considered the canons from Nicaea to be infallible and their status today.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
This article provides an overview of selected ongoing international efforts that have been inspired by Edward Zigler's vision to improve programs and policies for young children and families in the United States. The efforts presented are in close alignment with three strategies articulated by Edward Zigler: (a) conduct research that will inform policy advocacy; (b) design, implement, and revise quality early childhood development (ECD) programs; and (c) invest in building the next generation of scholars and advocates in child development. The intergenerational legacy left by Edward Zigler has had an impact on young children not only in the United States, but also across the globe. More needs to be done. We need to work together with a full commitment to ensure the optimal development of each child.
Dunn identifies two foundational types of motivating experiences in earliest Christianity: postmortem appearances of Jesus and the first disciples’ Pentecost experiences. He regards the experiences of the apostle Paul as particularly illustrative of early Christianity, featuring the liberating power of the Spirit and of being “in Christ,” experiencing the Spirit of God as the Spirit of Jesus, and the shared experience of believers as members of the body of Christ.
OBJECTIVES/GOALS: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatologic disease childhood and a cause of pain and potential disability. JIA has a strong genetic component and no known cure. The goal of this study is to evaluate allele-dependent effects of a novel JIA risk variant at 1q24.3. METHODS/STUDY POPULATION: JIA patients meeting criteria for the two most common disease subtypes (oligoarticular and RF neg polyarthritis) were genotyped using the Immunochip, an Illumina array with dense coverage of the HLA region and 186 other loci previously reported in autoimmune diseases. Phase I association findings (Hinks, 2013) and Phase II analysis (unpublished) of an expanded cohort (4,271 JIA and 14,390 controls) identified new risk loci, including rs78037977 at 1q24.3. We prioritized rs78037977 and predicted possible impacted mechanisms based on Bayesian predictions of attributable risk, the surrounding chromatin landscape, and transcription factor binding data. A luciferase reporter assay was used to assess allele-dependent enhancer activity. RESULTS/ANTICIPATED RESULTS: rs78037977 is located between FASLG and TNFSF18 at chromosome 1q24.3 is associated with JIA (p = 6.3x10−09), and explains 94% of the posterior probability at this locus; no other SNPs in linkage disequilibrium (r2>0.6). The chromatin landscape around rs78037977 contains H3K4Me1 and H3K27Ac marks, which are indicative of enhancer activity. Further, >160 transcription factors have chromatin immunoprecipitation followed by sequencing (ChIP-seq) peaks overlapping rs78037977 in various cellular contexts. In luciferase reporter assays, the region around rs78037977 containing the reference A allele had ~2-fold increased enhancer activity compared to the non-reference allele. DISCUSSION/SIGNIFICANCE OF IMPACT: This work provides in vitro evidence to support allele-dependent enhancer activity of a novel JIA-risk variant at 1q24.3. Our ongoing work investigates the effect of the DNA-containing region of rs78037977 on gene expression and differential transcription factor binding at rs78037977.
Individuals with personality disorders (especially paranoid personality disorder) tend to be reluctant to engage in treatment. This paper aimed to elucidate the role of personality disorder in predicting engagement with psychological treatment for depression. The Outcomes of Depression International Network (ODIN) involves six urban and three rural study sites throughout Europe at which cases of depression were identified through a two-stage community survey. One patient in seven who was offered psychological treatment for depression had a comorbid diagnosis of personality disorder (most commonly paranoid personality disorder). Forty-five percent of patients who were offered psychological treatment for depression did not complete treatment. The odds of completion were higher for patients with a comorbid diagnosis of personality disorder, especially paranoid, anxious or dependent personality disorder. The relatively low number of cases with some specific personality disorders (e.g. schizoid personality disorder) limited the study's power to reach conclusions about these specific disorders. This study focused on a community-based sample which may lead to apparently lower rates of engagement when compared to studies based on treatment-seeking populations. Episodes of depression in the context of personality disorder may represent a valuable opportunity to engage with patients who might otherwise resist engagement.
Capacity legislation in Ireland is evolving. The Assisted Decision-Making (Capacity) Act 2015 has been passed into law, but its main provisions are yet to be commenced. This paper compares the law and its practical implications currently and under the new legislation. Quick reference algorithms for frontline clinicians are proposed.
The objective of this systematic review was to evaluate the efficacy of antibiotics to prevent or control colibacillosis in broilers. Studies found eligible were conducted controlled trials in broilers that evaluated an antibiotic intervention, with at least one of the following outcomes: mortality, feed conversion ratio (FCR), condemnations at slaughter, or total antibiotic use. Four electronic databases plus the gray literature were searched. Abstracts were screened for eligibility and data were extracted from eligible trials. Risk of bias was evaluated.
Seven trials reported eligible outcomes in a format that allowed data extraction; all reported results for FCR and one also reported mortality. Due to the heterogeneity in the interventions and outcomes evaluated, it was not feasible to conduct meta-analysis.
Qualitatively, for FCR, comparisons between an antibiotic and an alternative product did not show a significant benefit for either. Some of the comparisons between an antibiotic and a no-treatment placebo showed a numerical benefit to antibiotics, but with wide confidence intervals. The risk-of-bias assessment revealed concerns with reporting of key trial features.
The results of this review do not provide compelling evidence for or against the efficacy of antibiotics for the control of colibacillosis.
A systematic review and network meta-analysis (NMA) were conducted to address the question, ‘What is the efficacy of litter management strategies to reduce morbidity, mortality, condemnation at slaughter, or total antibiotic use in broilers?’ Eligible studies were clinical trials published in English evaluating the efficacy of litter management in broilers on morbidity, condemnations at slaughter, mortality, or total antibiotic use. Multiple databases and two conference proceedings were searched for relevant literature. After relevance screening and data extraction, there were 50 trials evaluating litter type, 22 trials evaluating litter additives, 10 trials comparing fresh to re-used litter, and six trials evaluating floor type. NMAs were conducted for mortality (61 trials) and for the presence or absence of footpad lesions (15 trials). There were no differences in mortality among the litter types, floor types, or additives. For footpad lesions, peat moss appeared beneficial compared to straw, based on a small number of comparisons. In a pairwise meta-analysis, there was no association between fresh versus used litter on the risk of mortality, although there was considerable heterogeneity among studies (I2 = 66%). There was poor reporting of key design features in many studies, and analyses rarely accounted for non-independence of observations within flocks.
A systematic review and network meta-analysis were conducted to assess the relative efficacy of internal or external teat sealants given at dry-off in dairy cattle. Controlled trials were eligible if they assessed the use of internal or external teat sealants, with or without concurrent antimicrobial therapy, compared to no treatment or an alternative treatment, and measured one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, IMI during the first 30 days in milk (DIM), or clinical mastitis during the first 30 DIM. Risk of bias was based on the Cochrane Risk of Bias 2.0 tool with modified signaling questions. From 2280 initially identified records, 32 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. Use of an internal teat sealant (bismuth subnitrate) significantly reduced the risk of new IMI at calving compared to non-treated controls (RR = 0.36, 95% CI 0.25–0.72). For comparisons between antimicrobial and teat sealant groups, concerns regarding precision were seen. Synthesis of the primary research identified important challenges related to the comparability of outcomes, replication and connection of interventions, and quality of reporting of study conduct.
A systematic review and meta-analysis were conducted to determine the efficacy of selective dry-cow antimicrobial therapy compared to blanket therapy (all quarters/all cows). Controlled trials were eligible if any of the following were assessed: incidence of clinical mastitis during the first 30 DIM, frequency of intramammary infection (IMI) at calving, or frequency of IMI during the first 30 DIM. From 3480 identified records, nine trials were data extracted for IMI at calving. There was an insufficient number of trials to conduct meta-analysis for the other outcomes. Risk of IMI at calving in selectively treated cows was higher than blanket therapy (RR = 1.34, 95% CI = 1.13, 1.16), but substantial heterogeneity was present (I2 = 58%). Subgroup analysis showed that, for trials using internal teat sealants, there was no difference in IMI risk at calving between groups, and no heterogeneity was present. For trials not using internal teat sealants, there was an increased risk in cows assigned to a selective dry-cow therapy protocol, compared to blanket treatment, with substantial heterogeneity in this subgroup. However, the small number of trials and heterogeneity in the subgroup without internal teat sealants suggests that the relative risk between treatments may differ from the determined point estimates based on other unmeasured factors.
A systematic review and network meta-analysis were conducted to assess the relative efficacy of antimicrobial therapy given to dairy cows at dry-off. Eligible studies were controlled trials assessing the use of antimicrobials compared to no treatment or an alternative treatment, and assessed one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, incidence of IMI during the first 30 days in milk (DIM), or incidence of clinical mastitis during the first 30 DIM. Databases and conference proceedings were searched for relevant articles. The potential for bias was assessed using the Cochrane Risk of Bias 2.0 algorithm. From 3480 initially identified records, 45 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. The use of cephalosporins, cloxacillin, or penicillin with aminoglycoside significantly reduced the risk of new IMI at calving compared to non-treated controls (cephalosporins, RR = 0.37, 95% CI 0.23–0.65; cloxacillin, RR = 0.55, 95% CI 0.38–0.79; penicillin with aminoglycoside, RR = 0.42, 95% CI 0.26–0.72). Synthesis revealed challenges with a comparability of outcomes, replication of interventions, definitions of outcomes, and quality of reporting. The use of reporting guidelines, replication among interventions, and standardization of outcome definitions would increase the utility of primary research in this area.
Prevention and control of respiratory disease is a major contributor to antibiotic use in swine. A systematic review was conducted to address the question, ‘What is the comparative efficacy of antimicrobials for the prevention of swine respiratory disease?’ Eligible studies were controlled trials published in English evaluating prophylactic antibiotics in swine, where clinical morbidity, mortality, or total antibiotic use was assessed. Four databases and the gray literature were searched for relevant articles. Two reviewers working independently screened titles and abstracts for eligibility followed by full-text articles, and then extracted data and evaluated risk of bias for eligible trials. There were 44 eligible trials from 36 publications. Clinical morbidity was evaluated in eight trials where antibiotics were used in nursery pigs and 10 trials where antibiotics were used in grower pigs. Mortality was measured in 22 trials in nursery pigs and 12 trials in grower pigs. There was heterogeneity in the antibiotic interventions and comparisons published in the literature; thus, there was insufficient evidence to allow quantification of the efficacy, or relative efficacy, of antibiotic interventions. Concerns related to statistical non-independence and quality of reporting were noted in the included trials.
A systematic review and network meta-analysis (MA) was conducted to address the question, ‘What is the efficacy of bacterial vaccines to prevent respiratory disease in swine?’ Four electronic databases and the grey literature were searched to identify clinical trials in healthy swine where at least one intervention arm was a commercially available vaccine for one or more bacterial pathogens associated with respiratory disease in swine, including Mycoplasma hyopneumoniae, Actinobacillus pleuropneumonia, Actinobacillus suis, Bordetella bronchiseptica, Pasteurella multocida, Stretococcus suis, Haemophils parasuis, and Mycoplasma hyorhinis. To be eligible, trials had to measure at least one of the following outcomes: incidence of clinical morbidity, mortality, lung lesions, or total antibiotic use. There were 179 eligible trials identified in 146 publications. Network MA was undertaken for morbidity, mortality, and the presence or absence of non-specific lung lesions. However, there was not a sufficient body of research evaluating the same interventions and outcomes to allow a meaningful synthesis of the comparative efficacy of the vaccines. To build this body of research, additional rigor in trial design and analysis, and detailed reporting of trial methods and results are warranted.
Invasive species drive biodiversity loss and lead to changes in parasite–host associations. Parasites are linked to invasions and can mediate invasion success and outcomes. We review theoretical and empirical research into parasites in biological invasions, focusing on a freshwater invertebrate study system. We focus on the effects of parasitic infection on host traits (behaviour and life history) that can mediate native/invader trophic interactions. We review evidence from the field and laboratory of parasite-driven changes in predation, intraguild predation and cannibalism. Theoretical work shows that the trait-mediated effects of parasites can be as strong as classical density effects and their impact on the host’s trophic interactions merits more consideration. We also report on evidence of broader cascading effects warranting deeper study. Biological invasion can lead to altered parasite–host associations. Focusing on amphipod invasions, we find patterns of parasite introduction and loss that mirror host invasion pathways, but also highlight the risks of introducing invasive parasites. Horizon scanning and impact predictions are vital in identifying future disease risks, potential pathways of introduction and suitable management measures for mitigation.
Anxiety disorders are among the most prevalent psychiatric conditions. Despite many proven pharmacological and non-pharmacological treatments available, high rates of partial response and low rates of long-term remission remain. Ketamine has been receiving increasing attention as an interventional treatment modality in psychiatry, especially among refractory conditions, including major depressive disorder. There is limited yet growing evidence to support the use of ketamine in anxiety disorders. In this review of the literature, we present case reports, case series, and controlled trials demonstrating proof-of-concept for its potential role in the treatment of anxiety and anxiety spectrum disorders. Its unique mechanism of action, rapid onset, and high rate of response have driven its use in clinical practice. Ketamine is generally well tolerated by patients and has a limited side effect profile; however, the effects of long-term use are unknown. While there is a growing body of research and increasing clinical experience to suggest ketamine may have clinical applications in the treatment of refractory anxiety disorders, further research to determine long-term safety and tolerability is indicated.