Predicting state level suicide fatalities in the united states with realtime data and machine learning.

Digital trace data and machine learning techniques are increasingly being adopted to predict suicide-related outcomes at the individual level; however, there is also considerable public health need for timely data about suicide trends at the population level. Although significant geographic variation in suicide rates exist by state within the United States, national systems for reporting state suicide trends typically lag by one or more years. We developed and validated a deep learning based approach to utilize real-time, state-level online (Mental Health America web-based depression screenings; Google and YouTube Search Trends), social media (Twitter), and health administrative data (National Syndromic Surveillance Program emergency department visits) to estimate weekly suicide counts in four participating states. Specifically, per state, we built a long short-term memory (LSTM) neural network model to combine signals from the real-time data sources and compared predicted values of suicide deaths from our model to observed values in the same state. Our LSTM model produced accurate estimates of state-specific suicide rates in all four states (percentage error in suicide rate of -2.768% for Utah, -2.823% for Louisiana, -3.449% for New York, and -5.323% for Colorado). Furthermore, our deep learning based approach outperformed current gold-standard baseline autoregressive models that use historical death data alone. We demonstrate an approach to incorporate signals from multiple proxy real-time data sources that can potentially provide more timely estimates of suicide trends at the state level. Timely suicide data at the state level has the potential to improve suicide prevention planning and response tailored to the needs of specific geographic communities.

Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1.

Despite the unique ability of pioneer transcription factors (PFs) to target nucleosomal sites in closed chromatin, they only bind a small fraction of their genomic motifs. The underlying mechanism of this selectivity is not well understood. Here, we design a high-throughput assay called ChIP-ISO to systematically dissect sequence features affecting the binding specificity of a classic PF, FOXA1. Combining ChIP-ISO with in vitro and neural network analyses, we find that 1) FOXA1 binding is strongly affected by co-binding TFs AP-1 and CEBPB, 2) FOXA1 and AP-1 show binding cooperativity in vitro, 3) FOXA1's binding is determined more by local sequences than chromatin context, including eu-/heterochromatin, and 4) AP-1 is partially responsible for differential binding of FOXA1 in different cell types. Our study presents a framework for elucidating genetic rules underlying PF binding specificity and reveals a mechanism for context-specific regulation of its binding.

Community-Based Outbreak Investigation And Response: Enhancing Preparedness, Public Health Capacity, And Equity.

Throughout the COVID-19 pandemic, the US has struggled with many aspects of the public health response, from determining where transmission is occurring to building trust with communities and implementing interventions. Three factors have contributed to these challenges: insufficient local public health capacity, siloed interventions, and underuse of a cluster-based approach to outbreak response. In this article we introduce Community-based Outbreak Investigation and Response (COIR), a local public health strategy developed during the COVID-19 pandemic that addresses these shortcomings. COIR can help local public health entities conduct disease surveillance more effectively, take a more proactive and efficient approach to mitigating transmission, coordinate response efforts, build community trust, and advance equity. We offer a practitioner's lens, informed through on-the-ground experience and engagement with policy makers, to highlight the financing, workforce, data system, and information-sharing policy changes needed to scale up COIR throughout the country. COIR can enable the US public health system to develop effective solutions to many of today's public health challenges and improve the nation's preparedness for public health crises in the years to come.

Recent Incarceration Among Individuals Infected With Hepatitis A Virus During Person-to-Person Community Outbreaks, United States, 2016-2020.

OBJECTIVES: Although many people who are incarcerated have risk factors for hepatitis A virus (HAV) infection, the proportion of hepatitis A cases among people with a recent incarceration is unknown. We examined the relationship between recent incarceration and HAV infection during community-based, person-to-person outbreaks to inform public health recommendations. METHODS: The Centers for Disease Control and Prevention surveyed health departments in 33 jurisdictions reporting person-to-person HAV outbreaks during 2016-2020 on the number of outbreak-associated cases, HAV-infected people recently incarcerated, and HAV-associated hospitalizations and deaths. RESULTS: Twenty-five health departments reported 18 327 outbreak-associated hepatitis A cases during January 11, 2016-January 24, 2020. In total, 2093 (11.4%) HAV-infected people had been recently incarcerated. Of those with complete data, 1402 of 1462 (95.9%) had been held in a local jail, and 1513 of 1896 (79.8.%) disclosed hepatitis A risk factors. Eighteen jurisdictions reported incarceration timing relative to the exposure period. Of 9707 cases in these jurisdictions, 991 (10.2%) were among recently incarcerated people; 451 of 688 (65.6%) people with complete data had been incarcerated during all (n = 55) or part (n = 396) of their exposure period. CONCLUSIONS: Correctional facilities are important settings for reaching people with risk factors for HAV infection and can also be venues where transmission occurs. Providing HAV vaccination to incarcerated people, particularly people housed in jails, can be an effective component of community-wide outbreak response.

Geriatric clinical screening tool for cervical spine injury after ground-level falls.

BACKGROUND: A consistent approach to cervical spine injury (CSI) clearance for patients 65 and older remains a challenge. Clinical clearance algorithms like the National Emergency X-Radiography Utilisation Study (NEXUS) criteria have variable accuracy and the Canadian C-spine rule excludes older patients. Routine CT of the cervical spine is performed to rule out CSI but at an increased cost and low yield. Herein, we aimed to identify predictive clinical variables to selectively screen older patients for CSI. METHODS: The University of Iowa's trauma registry was interrogated to retrospectively identify all patients 65 years and older who presented with trauma from a ground-level fall from January 2012 to July 2017. The relationship between predictive variables (demographics, NEXUS criteria and distracting injuries) and presence of CSI was examined using the generalised linear modelling (GLM) framework. A training set was used to build the statistical models to identify clinical variables that can be used to predict CSI and a validation set was used to assess the reliability and consistency of the model coefficients estimated from the training set. RESULTS: Overall, 2312 patients ≥65 admitted for ground-level falls were identified; 253 (10.9%) patients had a CSI. Using the GLM framework, the best predictive model for CSI included midline tenderness, focal neurological deficit and signs of trauma to the head/face, with midline tenderness highly predictive of CSI (OR=22.961 (15.178-34.737); p<0.001). The negative predictive value (NPV) for this model was 95.1% (93.9%-96.3%). In the absence of midline tenderness, the best model included focal neurological deficit (OR=2.601 (1.340-5.049); p=0.005) and signs of trauma to the head/face (OR=3.024 (1.898-4.815); p<0.001). The NPV was 94.3% (93.1%-95.5%). CONCLUSION: Midline tenderness, focal neurological deficit and signs of trauma to the head/face were significant in this older population. The absence of all three variables indicates lower likelihood of CSI for patients≥65. Future observational studies are warranted to prospectively validate this model.

Improving Communication by Standardizing Pediatric Rapid Response Team Documentation.

BACKGROUND: Rapid response teams (RRTs) have been used by multiple hospital systems to enhance patient care and safety. However, processes to document rapid response events (RRE) are often varied among providers and teams, which can lead to suboptimal communication of recommendations to both the primary medical team and family. METHODS: A preintervention chart review was conducted from January-March 2018 and revealed suboptimal baseline documentation following RREs. A literature review and survey of RRT team members led to the creation of a standardized document with an Epic SmartPhrase which included six key elements of RRE documentation: physical examination, intervention performed, response to intervention, plan of care, communication with care team, and communication with family. A postintervention chart review was completed from April-June 2019 to assess improvements in documentation with the use of this SmartPhrase. RESULTS: There were 23 RRE activations in the postintervention period, of which 60.8% were due to respiratory distress. The documentation of the six key elements improved (p < .05) after SmartPhrase creation and serial educational interventions. CONCLUSIONS: Standardized RRE documentation of six key elements significantly improved with the implementation of an Epic SmartPhrase. Improved quality of documentation enhances communication between team members and can contribute to safer patient care.

Evidence for Limited Early Spread of COVID-19 Within the United States, January-February 2020.

From January 21 through February 23, 2020, public health agencies detected 14 U.S. cases of coronavirus disease 2019 (COVID-19), all related to travel from China (1,2). The first nontravel-related U.S. case was confirmed on February 26 in a California resident who had become ill on February 13 (3). Two days later, on February 28, a second nontravel-related case was confirmed in the state of Washington (4,5). Examination of four lines of evidence provides insight into the timing of introduction and early transmission of SARS-CoV-2, the virus that causes COVID-19, into the United States before the detection of these two cases. First, syndromic surveillance based on emergency department records from counties affected early by the pandemic did not show an increase in visits for COVID-19-like illness before February 28. Second, retrospective SARS-CoV-2 testing of approximately 11,000 respiratory specimens from several U.S. locations beginning January 1 identified no positive results before February 20. Third, analysis of viral RNA sequences from early cases suggested that a single lineage of virus imported directly or indirectly from China began circulating in the United States between January 18 and February 9, followed by several SARS-CoV-2 importations from Europe. Finally, the occurrence of three cases, one in a California resident who died on February 6, a second in another resident of the same county who died February 17, and a third in an unidentified passenger or crew member aboard a Pacific cruise ship that left San Francisco on February 11, confirms cryptic circulation of the virus by early February. These data indicate that sustained, community transmission had begun before detection of the first two nontravel-related U.S. cases, likely resulting from the importation of a single lineage of virus from China in late January or early February, followed by several importations from Europe. The widespread emergence of COVID-19 throughout the United States after February highlights the importance of robust public health systems to respond rapidly to emerging infectious threats.

Programmed Death-1 Restrains the Germinal Center in Type 1 Diabetes.

Programmed death-1 (PD-1) inhibits T and B cell function upon ligand binding. PD-1 blockade revolutionized cancer treatment, and although numerous patients respond, some develop autoimmune-like symptoms or overt autoimmunity characterized by autoantibody production. PD-1 inhibition accelerates autoimmunity in mice, but its role in regulating germinal centers (GC) is controversial. To address the role of PD-1 in the GC reaction in type 1 diabetes, we used tetramers to phenotype insulin-specific CD4+ T and B cells in NOD mice. PD-1 or PD-L1 deficiency, and PD-1 but not PD-L2 blockade, unleashed insulin-specific T follicular helper CD4+ T cells and enhanced their survival. This was concomitant with an increase in GC B cells and augmented insulin autoantibody production. The effect of PD-1 blockade on the GC was reduced when mice were treated with a mAb targeting the insulin peptide:MHC class II complex. This work provides an explanation for autoimmune side effects following PD-1 pathway inhibition and suggests that targeting the self-peptide:MHC class II complex might limit autoimmunity arising from checkpoint blockade.

Identification of trophoblast-specific elements in the HLA-C core promoter.

There are several aspects of HLA-C gene expression that distinguish it from the HLA-A and HLA-B genes. First, HLA-C is expressed by extravillous trophoblasts, whereas HLA-A and HLA-B are not. Second, its cell-surface expression is much lower, which has been linked to changes in transcription and efficiency of peptide loading and export. Third, HLA-C possesses a NK cell-specific promoter and a complex alternative splicing system that regulates expression during NK cell development. In this study, we investigate the contribution of the HLA-C core promoter to trophoblast-specific expression. Analysis of transcription start sites showed the presence of a trophoblast-associated start site and additional upstream TATA and CCAAT-box elements in the HLA-C promoter, suggesting the presence of an overlapping trophoblast-specific promoter. A comparison of in vitro promoter activity showed that the HLA-C promoter was more active in trophoblast cell lines than either the HLA-A or HLA-B promoters. Enhanced trophoblast activity was mapped to the central enhanceosome region of the promoter, and mutational analysis identified changes in the RFX-binding region that generated a trophoblast-specific enhancer.

Current strategies exploiting NK-cell therapy to treat haematologic malignancies.

Natural killer (NK) cells recognize targets that have been changed via malignant transformation or infection. Previously, NK cells were thought to be short-lived, but we now know that NK cells can be long-lived and remember past exposures in response to CMV. NK cells use a plethora of activating and inhibitory receptors to recognize these changes and attack targets, but tumour cells often evade NK cells. Therefore, major efforts are being made to hone in on NK cell antitumour properties in immunotherapy. In the clinical setting, haploidentical NK cells can be adoptively transferred to help treat cancer. To expand NK cells in vivo and enhance tumour targeting, IL-15 is being tested in combination with a glycogen synthase kinase (GSK) 3 inhibitor (CHIR99021), an inhibitor that has been shown to expand mature, highly functional NK cells capable of killing multiple tumour targets. One major limitation to NK cell therapy is lack of specificity. To address this concern, bispecific or trispecific engagers that target NK cells to the tumour and an ADAM17 inhibitor that prevents CD16 shedding after NK cell activation are being tested. Additionally, monoclonal antibodies are being designed to redirect the inhibitory signals that limit NK cell functionality. Further understanding of the biology of NK cells will inform strategies to exploit NK cells for therapeutic purposes.

Identification of an elaborate NK-specific system regulating HLA-C expression.

The HLA-C gene appears to have evolved in higher primates to serve as a dominant source of ligands for the KIR2D family of inhibitory MHC class I receptors. The expression of NK cell-intrinsic MHC class I has been shown to regulate the murine Ly49 family of MHC class I receptors due to the interaction of these receptors with NK cell MHC in cis. However, cis interactions have not been demonstrated for the human KIR and HLA proteins. We report the discovery of an elaborate NK cell-specific system regulating HLA-C expression, indicating an important role for HLA-C in the development and function of NK cells. A large array of alternative transcripts with differences in intron/exon content are generated from an upstream NK-specific HLA-C promoter, and exon content varies between HLA-C alleles due to SNPs in splice donor/acceptor sites. Skipping of the first coding exon of HLA-C generates a subset of untranslatable mRNAs, and the proportion of untranslatable HLA-C mRNA decreases as NK cells mature, correlating with increased protein expression by mature NK cells. Polymorphism in a key Ets-binding site of the NK promoter has generated HLA-C alleles that lack significant promoter activity, resulting in reduced HLA-C expression and increased functional activity. The NK-intrinsic regulation of HLA-C thus represents a novel mechanism controlling the lytic activity of NK cells during development.

DNA binding drives the association of BRG1/hBRM bromodomains with nucleosomes.

BRG1 and BRM, central components of the BAF (mSWI/SNF) chromatin remodelling complex, are critical in chromatin structure regulation. Here, we show that the human BRM (hBRM) bromodomain (BRD) has moderate specificity for H3K14ac. Surprisingly, we also find that both BRG1 and hBRM BRDs have DNA-binding activity. We demonstrate that the BRDs associate with DNA through a surface basic patch and that the BRD and an adjacent AT-hook make multivalent contacts with DNA, leading to robust affinity and moderate specificity for AT-rich elements. Although we show that the BRDs can bind to both DNA and H3K14ac simultaneously, the histone-binding activity does not contribute substantially to nucleosome targeting in vitro. In addition, we find that neither BRD histone nor DNA binding contribute to the global chromatin affinity of BRG1 in mouse embryonic stem cells. Together, our results suggest that association of the BRG1/hBRM BRD with nucleosomes plays a regulatory rather than targeting role in BAF activity.

Hypoxia disrupts proteostasis in Caenorhabditis elegans.

Oxygen is fundamentally important for cell metabolism, and as a consequence, O2 deprivation (hypoxia) can impair many essential physiological processes. Here, we show that an active response to hypoxia disrupts cellular proteostasis - the coordination of protein synthesis, quality control, and degradation that maintains the functionality of the proteome. We have discovered that specific hypoxic conditions enhance the aggregation and toxicity of aggregation-prone proteins that are associated with neurodegenerative diseases. Our data indicate this is an active response to hypoxia, rather than a passive consequence of energy limitation. This response to hypoxia is partially antagonized by the conserved hypoxia-inducible transcription factor, hif-1. We further demonstrate that exposure to hydrogen sulfide (H2S) protects animals from hypoxia-induced disruption of proteostasis. H2S has been shown to protect against hypoxic damage in mammals and extends lifespan in nematodes. Remarkably, our data also show that H2S can reverse detrimental effects of hypoxia on proteostasis. Our data indicate that the protective effects of H2S in hypoxia are mechanistically distinct from the effect of H2S to increase lifespan and thermotolerance, suggesting that control of proteostasis and aging can be dissociated. Together, our studies reveal a novel effect of the hypoxia response in animals and provide a foundation to understand how the integrated proteostasis network is integrated with this stress response pathway.

Characteristics of People with Hip or Knee Osteoarthritis Deemed Not Yet Ready for Total Joint Arthroplasty at Triage.

PURPOSE: To identify the characteristics of people with hip or knee osteoarthritis (OA) attending a regional triage centre for an initial consult who are deemed not yet ready for total joint arthroplasty (TJA). METHODS: Initial consultation notes (n=482) were reviewed retrospectively. Predictive variables were derived from the literature a priori, and 14 of these variables were suitable for inclusion in stepwise multiple logistic regression analyses. RESULTS: Of the 222 eligible people, 131 (59%) were deemed not yet ready for TJA. Five variables entered into the model ([Formula: see text]=133.19, p<0.001) for an overall success rate of 81.1%. Those deemed not yet ready for TJA were more likely to have knee OA (vs. hip OA; odds ratio [OR]=0.352, p=0.018), to have less severe OA (OR=0.246 for each category increase in severity, p<0.001), to use no gait aid (vs. cane; OR=0.390, p=0.033), and to have a higher Lower Extremity Functional Scale score (OR=1.050 for each 1-point increase, p=0.003) and better joint status as measured by the Knee Society Scale or Hip Harris Scale (OR=3.946 for each category increase, p=0.007). CONCLUSION: Considering these characteristics will help clinicians to identify individuals likely to require interventions other than TJA.

Objectif : Identifier les caractéristiques des personnes souffrant d'arthrose du genou ou de la hanche qui se rendent à un centre de triage régional pour une première consultation et sont considérées comme n'étant pas prêtes pour une arthroplastie totale des articulations (ATA). Méthodes : Des notes de première consultation (n=482) ont été examinées de manière rétrospective. Des variables prédictives ont d'abord été tirées de la recension des écrits à ce sujet, puis 14 de ces variables se sont avérées convenables pour une inclusion dans des analyses de régression logistique multiple par étapes. Résultats : Sur les 222 personnes admissibles, 131 (59 %) ont été considérées comme n'étant pas prêtes pour une ATA. Cinq variables ont été entrées dans le modèle ([Formula: see text]=133,19, p<0,001) pour un taux global de réussite de 81,1 %. Les personnes considérées comme n'étant pas prêtes pour une ATA étaient plus susceptibles de souffrir d'arthrose du genou (hanche et genou; rapport de cotes [RC]=0,352, p=0,018), de souffrir d'arthrose moins grave (RC=0,246 pour chaque augmentation de catégorie de gravité, p<0,001), de n'utiliser aucune aide à la marche (canne et aucune aide à la marche; RC=0,390, p=0,033) et d'avoir des résultats plus élevés à l'échelle fonctionnelle des membres inférieurs (RC=1,050 pour chaque augmentation d'un point, p=0,003) et des articulations en meilleur état selon le score des échelles de hanche Harris et de la Knee Society (RC=3,946 pour chaque augmentation de catégorie, p=0,007). Conclusion : Le fait de tenir compte des caractéristiques énumérées ci-dessus aidera les cliniciens à identifier les personnes qui pourraient avoir besoin d'une intervention autre que l'ATA.

Severe Acute Respiratory Illness (SARI) Surveillance in Louisiana, 2013-2014.

The objectives of this article are to describe the severe acute respiratory illness (SARI) surveillance implemented in Louisiana during the 2013-2014 influenza season, present the epidemiology of reported SARI cases, and identify ways to improve this system by incorporating formal SARI surveillance into the influenza surveillance program. Of the 212 SARI cases, 181 (85%) had at least one underlying medical condition, 54 (25.7%) had two conditions, 43 (20.3%) had three conditions, and 25 (11.8%) reported four or more. The most common four underlying conditions were: obesity (43.4%), chronic cardiac conditions (39.6%), diabetes (29.7%), and chronic pulmonary conditions (26.9%). While obesity was the most reported underlying condition, it was three times more likely to be reported in less than 65 years old rather than those >65. Continuation of SARI data collection in future seasons will allow comparisons regarding severity, populations affected, and identify risk factors most commonly associated with severe illness. Reporting of SARI cases also increased influenza-associated adult mortality reporting to the Office of Public Health's Office of Infectious Diseases Epidemiology (ID Epi). Though all influenza-associated mortality is reportable in Louisiana, adult mortality was reported rarely prior to the 2013-2014 season.

Feasibility study of walking for exercise in individuals living in assisted living settings.

BACKGROUND AND PURPOSE: Decreased physical activity levels are an increasing concern, specifically for the aging population. Older adults (>65 years) are able to achieve health benefits from participating in a regular exercise program based on studies done in younger community-dwelling older adults. There is less research investigating the efficacy of exercise for improving physical function among the older adult population in assisted living settings. This study investigated using a treadmill with a harness system, to engage older adults in aerobic exercise. The primary objective of the study was to assess the feasibility of a large trial by evaluating the recruitment and short-term retention rate of older adults with limited mobility. Secondary objectives were to determine whether older adults could achieve the frequency, intensity, and duration of aerobic exercise recommended by the American College of Sports Medicine. METHODS: A feasibility study of residents of an assisted living facility who had care needs ranging from retirement home to palliative care. The feasibility of recruitment and retention was determined by recording the number of older adults who consented to participate in treadmill walking for 3 weeks, declined treadmill participation including reasons why, and completed the 6 treadmill sessions. All participating residents completed a baseline assessment, including a medical chart review, and had the choice to walk on the treadmill or not. To determine whether participants could achieve what is recommended in physical activity guidelines, exercise, frequency, intensity, and duration achieved after the final treadmill sessions were reported. RESULTS: Among eligible residents, 30% consented to participate in the study. There were no significant differences between treadmill participants and those who chose not to walk on the treadmill. The average compliance to treadmill sessions was 94.4% ± 10.8%. Treadmill participants achieved an average intensity of 50.3% heart rate reserve (SD = 30.2%) and an average frequency of 3 sessions in 1 week. Average duration of the final session was 14 minutes 53 seconds ± 6 minutes 43 seconds. CONCLUSION: This study provides preliminary evidence that it is feasible to recruit and retain older adults in assisted living facilities to participate in a short-term treadmill walking study; however, it may be difficult to recruit a large number of individuals. Treadmill participants were able to achieve the American College of Sports Medicine's recommended intensity and frequency for aerobic exercise. For older adults in assisted living settings to achieve 20 minutes a day, they may need more than 3 weeks of progression or multiple sessions per day.

Respiratory syncytial virus-associated hospitalizations in Louisiana.

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and pneumonia in children under one year of age worldwide. Records indicative of RSV cases were pulled from The Louisiana Inpatient Hospital Discharge Data based on RSV diagnosis codes to describe the burden of RSV infections in Louisiana from 1999 to 2010. Two thousand to three thousand hospitalized RSV cases occurred each year, with rates ranging from 37.2 to 71.4 hospitalizations per 100,000 population and the majority of cases (79%) being diagnosed with bronchiolitis. The vast majority of cases occurred in children under one year of age, and within that group, 44% of the cases occurred in children ages 0 to 3 months. The RSV season was found to occur from November to March, and immunoprophylaxis for high-risk infants should be given according to that season. Hospital-acquired versus community-acquired infections were also examined and most (96.1%) cases were community-acquired.

Faithfully fit forever: a holistic exercise and wellness program for faith communities.

Older adults are at risk for numerous acute and chronic health conditions. Many of these conditions can be prevented or better managed by participation in health promotion and wellness programming. The social support found through involvement in a faith community makes this setting an ideal place for offering health promotion and wellness programming. This article includes a description of an innovative, faith-based, community-based wellness program titled Faithfully Fit Forever (FFF). The Cardiac Rehabilitation and Parish Nursing Departments at MeritCare Health System, Fargo, North Dakota, developed FFF in 2000. FFF is a holistic health improvement program that embraces the interconnection between mind, body, and spirit. It is led by laypeople (many are parish nurses) who are members of the individual religious community. The program includes 30 to 40 minutes of exercise, health education time, and devotional time promoting spiritual and emotional health.