Impact of Obesity on Mortality in Hospitalized Patients with Pneumonia Due to 2009 H1N1 Influenza A Virus Versus Other Etiologies

Background: Reports from the 2009 H1N1 influenza A virus (2009 H1N1) pandemic indicate increased mortality in obese patients hospitalized with pneumonia. However, articles published prior to the pandemic have suggested that obesity may be a protective factor for mortality in these patients. The objective of this study was to compare the impact of obesity on mortality in hospitalized patients with pneumonia due to the 2009 H1N1 versus pneumonia due to other etiologies. Methods: This was a secondary analysis of the CAPO international cohort study. Study groups were defined as follows: Group One, pneumonia due to 2009 H1N1: Patients hospitalized with pneumonia after March 2009 with a positive RT-PCR for 2009 H1N1 and Group Two, pneumonia due to other etiologies: Patients hospitalized with pneumonia before March 2009. Body Mass Index (BMI) was used to predict the influence of obesity on mortality. The effect of BMI on mortality was analyzed using a propensity-adjusted logistic regression model. Results: From the total of 897 patients, 215 (24%) had pneumonia due to 2009 H1N1. After adjustment, increased BMI was associated with increased mortality in patients with pneumonia due to 2009 H1N1 and with decreased mortality in patients with pneumonia due to other etiologies. Conclusions: Obesity is associated with poor outcomes in patients with pneumonia due to 2009 H1N1 but is protective in patients with pneumonia due to other etiologies. Defining the molecular mechanisms by which obesity influences outcomes in patients with pneumonia may help to develop novel therapeutic strategies. Funding: US Department of Homeland Security

Healthcare Workers Hospitalized with COVID-19: Outcomes from the Burden of COVID-19 study at the University of Louisville Center of Excellence for Research in Infectious Diseases [CERID]

Introduction: On March 6, 2020, the current ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also known as COVID-19 reached the commonwealth of Kentucky. Within days the first cases of infection and hospitalization were identified among healthcare workers (HCW) in Kentucky, other states in the U.S., and around the world. There is little information available regarding the impact of COVID-19 on the HCW population within this area. The objective of this study is to describe the baseline characteristics of hospitalized HCWs infected with COVID-19. Methods: Data collection was performed as part of a retrospective study of patients hospitalized with COVID-19 in any of nine acute care hospitals in Louisville. COVID-19 infection was confirmed using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Descriptive statistics were performed on clinical and epidemiological characteristics of hospitalized patients with COVID-19 who had indicated healthcare as their occupation. Results: Of the 700 adults hospitalized with COVID-19 from March 7 through July 1, 2020, 23 were HCWs. The mean age was 51 years and 78% were female. The majority of hospitalized HCWs had comorbidities including obesity (70%), hypertension (57%), hyperlipidemia (35%) and diabetes (26%). Common symptoms reported were fever (70%), dyspnea (78%), cough (78%) and fatigue (57%). Nine HCWs (39%) were admitted to the intensive care unit (ICU) and 6 (26%) developed acute respiratory distress syndrome (ARDS). Two (9%) patients developed a new, serious arrhythmia, two sustained cardiac arrest (9%), and two (9%) died in-hospital. Conclusions: Older adult HCWs with underlying health conditions such as obesity and hypertension were more likely to be hospitalized and have severe in-hospital complications. One HCW death due to COVID-19 was identified in this small population. These findings can help to identify and strengthen approaches to protect HCWs from SARS-CoV-2 infection and from long term effects of COVID-19

Epidemiology and Outcomes of Hospitalized Adults with SARS-CoV-2 Community-Acquired Pneumonia in Louisville, Kentucky

Background: During the ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV-2 community-acquired pneumonia (CAP) has been the primary cause of hospitalization. The objective of this study was to evaluate the clinical characteristics and outcomes of 1,013 patients hospitalized with SARS-CoV-2 CAP from September 2020 through March 2021 in Louisville, Kentucky. Methods: This was a retrospective observational study of 1,013 patients hospitalized with SARS-CoV-2 CAP at eight of the adult hospitals in the city of Louisville from September 2020 through March 2021. Patients with 1) a positive reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2, 2) fever, cough, or shortness of breath, and 3) an infiltrate on chest imaging were defined as having SARS-CoV-2 CAP. Data were abstracted from each hospital’s electronic health record. Descriptive statistics were performed on clinical and epidemiological characteristics of hospitalized patients with SARS-CoV-2 CAP. Demographic characteristics of the study population were compared with census data from the city of Louisville. Data were analyzed by descriptive and inferential statistics using R version 3.4.0. Results: Of the 1,013 patients hospitalized with SARS-CoV-2 CAP, the median age was 65 years, 53% were males, 24% reported their race as African American or Black, and 6% identified as Hispanic. The most frequent comorbidities were hypertension (73%), obesity (56%), and diabetes (43%). At the time of admission, 60% required supplemental oxygen. The mortality rate was 19% for the total population and 45% for the 359 patients admitted to the intensive care unit (ICU). For each comorbidity, the proportion of hospitalized patients with SARS-CoV-2 CAP was significantly different from the Louisville population (P Conclusions: The elderly, males, and patients with a history of coronary artery disease, cerebrovascular disease, chronic obstructive pulmonary disease, hypertension, diabetes, renal disease, or obesity are overrepresented among hospitalized patients with SARS-CoV-2 CAP compared to the Louisville population. These patients are also more likely to require ICU care and experience worse clinical outcomes, with death occurring in approximately one in every five hospitalizations

Using Y-chromosome capture enrichment to resolve haplogroup H2 shows new evidence for a two-Path Neolithic expansion to Western Europe

Uniparentally-inherited markers on mitochondrial DNA (mtDNA) and the non-recombining regions of the Y chromosome (NRY), have been used for the past 30 years to investigate the history of humans from a maternal and paternal perspective.Researchers have preferred mtDNA due to its abundance in the cells, and comparatively high substitution rate. Conversely, the NRY is less susceptible to back mutations and saturation, and is potentially more informative than mtDNA owing to its longer sequence length. However, due to comparatively poor NRY coverage via shotgun sequencing, and the relatively low and biased representation of Y-chromosome variants on capture arrays such as the 1240K, ancient DNA studies often fail to utilize the unique perspective that the NRY can yield.Here we introduce a new DNA enrichment assay, coined YMCA (Y-mappable capture assay), that targets the “mappable” regions of the NRY. We show that compared to low-coverage shotgun sequencing and 1240K capture, YMCA significantly improves the coverage and number of sites hit on the NRY, increasing the number of Y-haplogroup informative SNPs, and allowing for the identification of previously undiscovered variants.To illustrate the power of YMCA, we show that the analysis of ancient Y-chromosome lineages can help to resolve Y-chromosomal haplogroups. As a case study, we focus on H2, a haplogroup associated with a critical event in European human history: the Neolithic transition. By disentangling the evolutionary history of this haplogroup, we further elucidate the two separate paths by which early farmers expanded from Anatolia and the Near East to western Europe.Competing Interest StatementThe authors have declared no competing interest.Introduction Results and Discussion - Validating the performance of YMCA - Application of YMCA to YHG H2 as a case study - Identifying diagnostic SNPs for improved YHG H2 resolution Discussion Materials and Methods - Data - Contamination quality filtering - Method of Y Haplogroup Assignment - Comparing the Performance of our Y-capture Array Phylogenetic Tree Reconstructio

Full production cycle performance of gene-edited, sterile Atlantic salmon - growth, smoltification, welfare indicators and fillet composition

Using germ cell-free (GCF), sterile, dnd-knockout salmon for farming could solve the problems associated with precocious maturation and genetic introgression of farmed breeds into wild populations. However, prior to using GCF fish in the salmon farming industry, it is crucial to understand if, or how, the GCF phenotype differs from wild type (WT) counterparts in terms of growth and welfare. To characterize the GCF phenotype throughout a production cycle, we reared GCF and WT salmon in indoor common garden tanks for 3 years, until harvest size. Regarding body size, smoltification markers (mRNA levels of gill Na+/K+-ATPase [NKA] subunits), plasma stress indicators (pH, glucose, sodium, chloride, calcium), relative heart size, prevalence of vertebra deformities and fillet proximate composition, GCF fish could not be distinguished from WTs. Transient differences were detected in plasma concentrations of lactate and osmolality, and only a few genes were differentially expressed in WT and GCF transcriptomes of muscle and pituitary. At harvest, fillets from GCF and WT salmon contained the same amount of omega-3 fatty acids, however the relative content of omega-3 fatty acids was higher in GCF compared to WT males. Towards harvest size, body growth rate, condition factor and relative liver size were significantly higher in WT than in GCF fish, probably relating to initiation of puberty in WTs. Since GCF salmon never become sexually mature, it is possible to postpone the time of harvest to exploit the growth potential uninhibited by sexual maturation. In conclusion, GCF salmon performed to a large extent similarly to their WT counterparts but had the clear advantage of never maturing

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362