First look at the Fomalhaut debris disk with the Spitzer Space Telescope

We present Spitzer Space Telescope early release observations of Fomalhaut, a nearby A-type star with dusty circumstellar debris. The disk is spatially resolved at 24, 70, and 160 � m using the Multiband Imaging Photometer for Spitzer (MIPS). While the disk orientation and outer radius are comparable to values measured in the submillimeter, the disk inner radius cannot be precisely defined: the central hole in the submillimeter ring is at least partially filled with emission from warm dust, seen inSpitzerInfrared Spectrograph (IRS) 17.5‐34 � m spectra and MIPS 24 � m images. The disk surface brightness becomes increasingly asymmetric toward shorter wavelengths, with the south-southeast ansa always brighter than the north-northwest one. This asymmetry may reflect perturbations on the disk by an unseen interior planet. Subject headingg circumstellar matter — infrared: stars — planetary systems — stars: individual (Fomalhaut

Generalized Connective Tissue Disease in Crtap-/- Mouse

Mutations in CRTAP (coding for cartilage-associated protein), LEPRE1 (coding for prolyl 3-hydroxylase 1 [P3H1]) or PPIB (coding for Cyclophilin B [CYPB]) cause recessive forms of osteogenesis imperfecta and loss or decrease of type I collagen prolyl 3-hydroxylation. A comprehensive analysis of the phenotype of the Crtap-/- mice revealed multiple abnormalities of connective tissue, including in the lungs, kidneys, and skin, consistent with systemic dysregulation of collagen homeostasis within the extracellular matrix. Both Crtap-/- lung and kidney glomeruli showed increased cellular proliferation. Histologically, the lungs showed increased alveolar spacing, while the kidneys showed evidence of segmental glomerulosclerosis, with abnormal collagen deposition. The Crtap-/- skin had decreased mechanical integrity. In addition to the expected loss of proline 986 3-hydroxylation in α1(I) and α1(II) chains, there was also loss of 3Hyp at proline 986 in α2(V) chains. In contrast, at two of the known 3Hyp sites in α1(IV) chains from Crtap-/- kidneys there were normal levels of 3-hydroxylation. On a cellular level, loss of CRTAP in human OI fibroblasts led to a secondary loss of P3H1, and vice versa. These data suggest that both CRTAP and P3H1 are required to maintain a stable complex that 3-hydroxylates canonical proline sites within clade A (types I, II, and V) collagen chains. Loss of this activity leads to a multi-systemic connective tissue disease that affects bone, cartilage, lung, kidney, and skin

International collaborative study to assess cardiovascular risk and evaluate long-term health in cats with preclinical hypertrophic cardiomyopathy and apparently healthy cats:The REVEAL Study

Background: Hypertrophic cardiomyopathy is the most prevalent heart disorder in cats and principal cause of cardiovascular morbidity and mortality. Yet, the impact of preclinical disease is unresolved. Hypothesis/Objectives: Observational study to characterize cardiovascular morbidity and survival in cats with preclinical nonobstructive (HCM) and obstructive (HOCM) hypertrophic cardiomyopathy and in apparently healthy cats (AH). Animals: One thousand seven hundred and thirty client-owned cats (430 preclinical HCM; 578 preclinical HOCM; 722 AH). Methods: Retrospective multicenter, longitudinal, cohort study. Cats from 21 countries were followed through medical record review and owner or referring veterinarian interviews. Data were analyzed to compare long-term outcomes, incidence, and risk for congestive heart failure (CHF), arterial thromboembolism (ATE), and cardiovascular death. Results: During the study period, CHF, ATE, or both occurred in 30.5% and cardiovascular death in 27.9% of 1008 HCM/HOCM cats. Risk assessed at 1, 5, and 10 years after study entry was 7.0%/3.5%, 19.9%/9.7%, and 23.9%/11.3% for CHF/ATE, and 6.7%, 22.8%, and 28.3% for cardiovascular death, respectively. There were no statistically significant differences between HOCM compared with HCM for cardiovascular morbidity or mortality, time from diagnosis to development of morbidity, or cardiovascular survival. Cats that developed cardiovascular morbidity had short survival (mean \ub1 standard deviation, 1.3 \ub1 1.7 years). Overall, prolonged longevity was recorded in a minority of preclinical HCM/HOCM cats with 10% reaching 9-15 years. Conclusions and Clinical Importance: Preclinical HCM/HOCM is a global health problem of cats that carries substantial risk for CHF, ATE, and cardiovascular death. This finding underscores the need to identify therapies and monitoring strategies that decrease morbidity and mortality

Proceedings of the Sixth Caldwell Conference, St. Catherines Island, Georgia, May 20-22, 2011.

494 pages : illustrations (some color), maps (some color) ; 26 cm. Conference sponsored by the American Museum of Natural History and the St. Catherines Island Foundation.Although this volume covers a broad range of temporal and methodological topics, the chapters are unified by a geographic focus on the archaeology of the Georgia Bight. The various research projects span multiple time periods (including Archaic, Woodland, Mississippian, and contact periods) and many incorporate specialized analyses (such as petrographic point counting, shallow geophysics, and so forth). The 26 contributors conducting this cutting-edge work represent the full spectrum of the archaeological community, including museum, academic, student, and contract archaeologists. Despite the diversity in professional and theoretical backgrounds, temporal periods examined, and methodological approaches pursued, the volume is unified by four distinct, yet interrelated, themes. Contributions in Part I discuss a range of analytical approaches for understanding time, exchange, and site layout. Chapters in Part II model coastal landscapes from both environmental and social perspectives. The third section addresses site-specific studies of late prehistoric architecture and village layout throughout the Georgia Bight. Part IV presents new and ongoing research into the Spanish mission period of this area. These papers were initially presented and discussed at the Sixth Caldwell Conference, cosponsored by the American Museum of Natural History and the St. Catherines Island Foundation, held on St. Catherines Island, Georgia, May 20-22, 2011. TABLE OF CONTENTS: Revising the ¹⁴C reservoir correction for St. Catherines Island, Georgia / David Hurst Thomas, Matthew C. Sanger, and Royce H. Hayes -- An assessment of coastal faunal data from Georgia and northeast Florida / Alexandra L. Parsons and Rochelle A. Marrinan -- Archaeological geophysics on St. Catherines Island : beyond prospection / Ginessa J. Mahar -- Paste variability and clay resource utilization at the Fountain of Youth site, St. Augustine, 8SJ31 / Ann S. Cordell and Kathleen A. Deagan -- Petrographic analysis of pottery and clay samples from the Georgia Bight : evidence of regional social interactions / Neill J. Wallis and Ann S. Cordell -- Past shorelines of the Georgia coast / Chester B. DePratter and Victor D. Thompson -- Coastal landscapes and their relationship to human settlement on the Georgia coast / John A. Turck and Clark R. Alexander -- The role of small islands in foraging economies of St. Catherines Island / Matthew F. Napolitano -- Ever-shifting landscapes : tracking changing spatial usage along coastal Georgia / Matthew C. Sanger -- A paleoeconomic model of the Georgia coast (4500-300 B.P.) / Thomas G. Whitley -- A survey of Irene phase architecture on the Georgia coast / Deborah A. Keene and Ervan G. Garrison -- Life and death on the Ogeechee : a view from the Redbird Creek village / Ryan O. Sipe -- Mission San Joseph de Sapala : mission-period archaeological research on Sapelo Island / Richard W. Jefferies and Christopher R. Moore -- The Guale landscape of Mission Santa Catalina de Guale : 30 years of geophysics at a Spanish colonial mission / Elliot H. Blair -- Missions San Buenaventura and Santa Cruz de Guadalquini : retreat from the Georgia coast / Keith H. Ashley, Vicki L. Rolland, and Robert L. Thunen -- Entangling events : the Guale coastal landscape and the Spanish missions / Victor D. Thompson, John A. Turck, Amanda D. Roberts Thompson, and Chester B. DePratter -- Island and coastal archaeology on the Georgia Bight / Scott M. Fitzpatrick

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Long-term Incidence and risk of noncardiovascular and all-cause mortality in apparently healthy cats and cats with preclinical hypertrophic cardiomyopathy

Background Epidemiologic knowledge regarding noncardiovascular and all‐cause mortality in apparently healthy cats (AH) and cats with preclinical hypertrophic cardiomyopathy (pHCM) is limited, hindering development of evidence‐based healthcare guidelines. Objectives To characterize/compare incidence rates, risk, and survival associated with noncardiovascular and all‐cause mortality in AH and pHCM cats. Animals A total of 1730 client‐owned cats (722 AH, 1008 pHCM) from 21 countries. Methods Retrospective, multicenter, longitudinal, cohort study. Long‐term health data were extracted by medical record review and owner/referring veterinarian interviews. Results Noncardiovascular death occurred in 534 (30.9%) of 1730 cats observed up to 15.2 years. Proportion of noncardiovascular death did not differ significantly between cats that at study enrollment were AH or had pHCM (P = .48). Cancer, chronic kidney disease, and conditions characterized by chronic weight‐loss‐vomiting‐diarrhea‐anorexia were the most frequently recorded noncardiovascular causes of death. Incidence rates/risk of noncardiac death increased with age in AH and pHCM. All‐cause death proportions were greater in pHCM than AH (65% versus 40%, respectively; P &lt; .001) because of higher cardiovascular mortality in pHCM cats. Comparing AH with pHCM, median survival (study entry to noncardiovascular death) did not differ (AH, 9.8 years; pHCM, 8.6 years; P = .10), but all‐cause survival was significantly shorter in pHCM (P = .0001). Conclusions and Clinical Importance All‐cause mortality was significantly greater in pHCM cats due to disease burden contributed by increased cardiovascular death superimposed upon noncardiovascular death

On-orbit performance of the MIPS instrument

The Multiband Imaging Photometer for Spitzer (MIPS) provides long wavelength capability for the mission, in imaging bands at 24, 70, and 160 microns and measurements of spectral energy distributions between 52 and 100 microns at a spectral resolution of about 7%. By using true detector arrays in each band, it provides both critical sampling of the Spitzer point spread function and relatively large imaging fields of view, allowing for substantial advances in sensitivity, angular resolution, and efficiency of areal coverage compared with previous space far-infrared capabilities. The Si:As BIB 24 micron array has excellent photometric properties, and measurements with rms relative errors of 1% or better can be obtained. The two longer wavelength arrays use Ge:Ga detectors with poor photometric stability. However, the use of 1.) a scan mirror to modulate the signals rapidly on these arrays, 2.) a system of on-board stimulators used for a relative calibration approximately every two minutes, and 3.) specialized reduction software result in good photometry with these arrays also, with rms relative errors of less than 10%

The Effect of Numbered Jerseys on Directed Commands, Teamwork, and Clinical Performance During Simulated Emergencies

Communication and teamwork are essential during inpatient emergencies such as cardiac arrest and rapid response (RR) codes. We investigated whether wearing numbered jerseys affect directed commands, teamwork, and performance during simulated codes. Eight teams of 6 residents participated in 64 simulations. Four teams were randomized to the experimental group wearing numbered jerseys, and four to the control group wearing work attire. The experimental group used more directed commands (49% vs. 31%, p < .001) and had higher teamwork score (25 vs. 18, p < .001) compared with control group. There was no difference in time to initiation of chest compression, bag-valve-mask ventilation, and correct medications. Time to defibrillation was longer in the experimental group (190 vs. 140 seconds, p = .035). Using numbered jerseys during simulations was associated with increased use of directed commands and better teamwork. Time to performance of clinical actions was similar except for longer time to defibrillation in the jersey group