Constraining the temperature–density relation of the intergalactic medium with the Lyman-alpha and beta forests

The post-reionization thermal state of the intergalactic medium is characterized by a power-law relationship between temperature and density, with a slope determined by the parameter γ. We describe a new method to measure γ using the ratio of flux curvature in the Lyman α and β forests. At a given redshift, this curvature ratio incorporates information from the different gas densities traced by Lyman α and β absorption. It is relatively simple and fast to compute and appears robust against several observational uncertainties. We apply this technique to a sample of 27 high-resolution quasar spectra from the Very Large Telescope. While promising statistical errors on γ appear to be achievable with these spectra, to reach its full potential, the dependence of the curvature ratio on the thermal state of the gas in the foreground Lyman α forest will require further, detailed forward modelling

Hemodynamic Corelates of Abnormal Aortic Root Dimension in an Adult Population:The Strong Heart Study.

We evaluated the relationship of aortic root dimension (ARD) with flow output and both peripheral and central blood pressure, using multivariable equations predicting ideal sex-specific ARD at a given age and body height

A Case of Novel Coronavirus Disease 19 in a Chronic Hemodialysis Patient Presenting with Gastroenteritis and Developing Severe Pulmonary Disease.

Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease with an alarming case fatality rate up to 5%. The risk factors for severe presentations are concentrated in patients with chronic kidney disease, particularly patients with end-stage renal disease (ESRD) who are dialysis dependent. We report the first US case of a 56-year-old nondiabetic male with ESRD secondary to IgA nephropathy undergoing thrice-weekly maintenance hemodialysis for 3 years, who developed COVID-19 infection. He has hypertension controlled with angiotensin receptor blocker losartan 100 mg/day and coronary artery disease status-post stent placement. During the first 5 days of his febrile disease, he presented to an urgent care, 3 emergency rooms, 1 cardiology clinic, and 2 dialysis centers in California and Utah. During this interval, he reported nausea, vomiting, diarrhea, and low-grade fevers but was not suspected of COVID-19 infection until he developed respiratory symptoms and was admitted to the hospital. Imaging studies upon admission were consistent with bilateral interstitial pneumonia. He was placed in droplet-eye precautions while awaiting COVID-19 test results. Within the first 24 h, he deteriorated quickly and developed acute respiratory distress syndrome (ARDS), requiring intubation and increasing respiratory support. Losartan was withheld due to hypotension and septic shock. COVID-19 was reported positive on hospital day 3. He remained in critical condition being treated with hydroxychloroquine and tocilizumab in addition to the standard medical management for septic shock and ARDS. Our case is unique in its atypical initial presentation and highlights the importance of early testing

Using HbA1c to improve efficacy of the American Diabetes Association fasting plasma glucose criterion in screening for new type 2 diabetes in American Indians. The Strong Heart Study

WSTĘP. Celem badania jest określenie optymalnej krytycznej linii FPG-HbA1c, umożliwiającej rozpoznanie cukrzycy w grupie chorych z nieprawidłowym stężeniem glukozy na czczo (IFG, impaired fasting glucose) i poprawa skuteczności oznaczenia glikemii na czczo (FPG, fasting plasma glucose), stosowanego jako samodzielne badanie przesiewowe w kierunku cukrzycy u Indian amerykańskich. MATERIAŁ I METODY. Analizowano oznaczenia stężenia glukozy na czczo i 2 godziny po doustnym obciążeniu glukozą (2hPG) oraz HbA1c w grupie 2389 Indian amerykańskich w wieku 45-74 lat, którzy dotychczas nie byli leczeni z powodu cukrzycy, u których wcześniej nie rozpoznawano cukrzycy, a których poddano wyjściowej i powtórnej ocenie w ramach badania SHS (Strong Heart Study). Zgodnie z kryteriami American Diabetes Association cukrzycę rozpoznawano, gdy stężenie glukozy na czczo było równe lub wyższe niż 126 mg/dl lub gdy wartość 2hPG wynosiła 200 mg/dl lub więcej. Nieprawidłowe stężenie glukozy na czczo rozpoznawano, gdy mieściło się ono w przedziale 110 Ł FPG < 126 mg/dl, a jako wartość prawidłową (NFG, normal fasting glucose) przyjęto stężenie glukozy na czczo niższe niż 110 mg/dl. Do rozpoznawania cukrzycy w grupie badanych z IFG (2hPG ł 200 mg/dl) zastosowano modele regresji logistycznej. Najlepszy model wybrano na podstawie porównania pól pod krzywymi ROC (receiver operating characteristic) utworzonymi w oparciu o różne modele regresji logistycznej. Do wyznaczenia optymalnych wartości krytycznych użyto funkcji przydatności opartej na najlepszym modelu oraz współczynniku koszt/korzyść. Dane z drugiego badania wykorzystano do oceny wpływu czasu, jaki upłynął pomiędzy dwoma kolejnymi badaniami przesiewowymi, zarówno na kryterium FPG, jak i na optymalną krytyczną linię FPG-HbA1c. WYNIKI. W grupie chorych z nowo rozpoznaną cukrzycą, u 37% w badaniu wyjściowym oraz u 55,2% w badaniu powtórnym stwierdzono wartości 2hPG większe bądź równe 200 mg/dl, przy wartościach FPG mniejszych niż 126 mg/dl. Zarówno w wyjściowym, jak i w drugim oznaczeniu u znacznej części pacjentów z IFG rozpoznano cukrzycę (odpowiednio: 19,3 i 22,9%). Porównanie pól pod krzywymi ROC dla poszczególnych modeli regresji logistycznej wykazało, że największa wartość pola odpowiada łącznemu oznaczeniu FPG i HbA1c. Wartość ta była znamiennie wyższa od wartości pola dla oznaczenia FPG (p = 0,0008). Dla współczynnika koszt/korzyść = 0,23888 optymalna linia krytyczna o największej użyteczności miała wartość równą 0,89 × HbA1c + 0,11 × FPG = 17,92. U chorych, u których wartości FPG i HbA1c znajdowały się na tej linii lub powyżej, zalecano wykonanie doustnego testu tolerancji glukozy (OGTT, oral glucose tolerance test) w celu rozpoznania lub wykluczenia cukrzycy. Optymalne wartości krytyczne w badaniu powtórzonym po 4 latach były mniejsze. WNIOSKI. Według kryteriów American Diabetes Association cukrzycę rozpoznaje się, gdy wartość FPG jest większa lub równa 126 mg/dl albo gdy wartość 2hPG wynosi 200 mg/dl lub więcej. Wykonanie badania FPG jest proste i zaleca się je jako badanie przesiewowe. Natomiast stosowanie w praktyce OGTT w celu uzyskania wartości 2hPG jest kłopotliwe, szczególnie u chorych, u których stwierdza się wartość FPG poniżej 126 mg/dl. Wykonywanie OGTT jako badania przesiewowego u każdego pacjenta również jest niepraktyczne. Uzyskane dane wskazują, że u 37% osób z nowo wykrytą cukrzycą w badaniu wyjściowym i u 55,2% w oznaczeniu drugim stężenie glukozy w OGTT wynosiło 200 mg/dl lub więcej, podczas gdy wartość FPG była niższa niż 126 mg/dl. W takich wypadkach, na podstawie oznaczenia wyłącznie FPG jako badania przesiewowego, cukrzyca nie zostałaby rozpoznana. Mimo że odsetek chorych na cukrzycę w grupie NFG jest mały i może zostać zignorowany (4,7% w pierwszym i 6,5% w drugim oznaczeniu), to częstość przypadków cukrzycy stwierdzonych w grupie IFG w trakcie niniejszego badania (ok. 20%) wymaga uwzględnienia w dyskusji na temat metody badań przesiewowych. Wydaje się, że u części chorych z nieprawidłowym stężeniem glukozy na czczo, wybranych na podstawie optymalnych krytycznych wartości FPG-HbA1c, warto wykonać OGTT. Wyznaczenie optymalnej linii krytycznej i odstępu między kolejnymi testami przesiewowymi wymaga dalszych badań.INTRODUCTION. To find an optimal critical line in the fasting plasma glucose (FPG)-HbA1c plane for identifying diabetes in participants with impaired fasting glucose (IFG) and thereby improve the efficacy of using FPG alone in diabetes screening among American Indians. RESEARCH DESIGN AND METHODS. We used FPG, 2-h postload glucose (2hPG), and HbA1c measured in the 2,389 American Indians (aged 45&#8211;74 years, without diabetes treatment or prior history of diabetes) in the Strong Heart Study (SHS) baseline (second) examination. Participants were classified as having diabetes if they had either FPG &#163; 126 mg/dl or 2hPG &#8805; 200 mg/dl, as having IFG if they had 110 &#163; FPG < 126 mg/dl, and as having normal fasting glucose (NFG) if they had FPG < 110, according to the American Diabetes Association (ADA) definition. Logistic regression models were used for identifying diabetes (2hPG &#8805; 200 mg/dl) in IFG participants. The areas under the receiver operating characteristic (ROC) curves generated by different logistic regression models were evaluated and compared to select the best model. A utility function based on the best model and the cost-to-benefit ratio was used to find the optimal critical line. The data from the second examination were used to study the effect of the time interval between the successive diabetes screenings on both the FPG criterion and the optimal critical line. RESULTS. A total of 37% of all subjects with new diabetes at baseline and 55.2% of those in the second exam had 2hPG &#8805; 200 but FPG < 126. There was a very large portion of IFG participants with diabetes (19.3 and 22.9% in the baseline and second exam, respectively). Among the areas under the ROC curves, the area generated by the logistic regression model on FPG plus HbA1c is the largest and is significantly larger than that based on FPG (P = = 0.0008). For a cost-to-benefit ratio of 0.23888, the optimal critical line that has the highest utility is: 0.89 × HbA1c + 0.11 × FPG = 17.92. Those IFG participants whose FPG and HbA1c were above or on the line were referred to take an oral glucose tolerance test (OGTT) to diagnose diabetes. The optimal critical line is lower if a successive diabetes screening will be conducted 4 years after the previous screening. CONCLUSIONS. FPG &#8805; 126 and 2hPG &#8805; 200, as suggested by the ADA, are used in-dependently to define diabetes. The FPG level is easy to obtain, and using FPG alone is suggested for diabetes screening. It is difficult to get physicians and patients to perform an OGTT to get a 2hPG level because of the many drawbacks of the OGTT, especially in those patients who already have FPG < 126. It is also impractical to conduct an OGTT for everyone in a diabetes screening. Our data show that 37% of all subjects with new diabetes in the SHS baseline exam and 55.2% of those in the second exam have 2hPG &#8805; 200 but FPG < 126. These cases of diabetes cannot be detected if FPG is used alone in a diabetes screening. Therefore, although the small portion of diabetes in the NFG group (4.7% in the base-line and 6.9% in the second exam) may be ignored, those cases of diabetes among IFG participants (~20% in our data) need further consideration in a diabetes screening. It may be worthwhile for those IFG participants identified by the optimal critical line to take an OGTT. The optimal critical line and time interval between successive diabetes screenings need further study

Genetic Variants Related to Cardiometabolic Traits Are Associated to B Cell Function, Insulin Resistance, and Diabetes Among AmeriCan Indians: The Strong Heart Family Study

Background: Genetic research may inform underlying mechanisms for disparities in the burden of type 2 diabetes mellitus among American Indians. Our objective was to assess the association of genetic variants in cardiometabolic candidate genes with B cell dysfunction via HOMA-B, insulin resistance via HOMA-IR, and type 2 diabetes mellitus in the Strong Heart Family Study (SHFS). Methods and Results: We examined the association of variants, previously associated with cardiometabolic traits (∼200,000 from Illumina Cardio MetaboChip), using mixed models of HOMA-B residuals corrected for HOMA-IR (cHOMA-B), log transformed HOMA-IR, and incident diabetes, adjusted for age, sex, population stratification, and familial relatedness. Center-specific estimates were combined using fixed effect meta-analyses. We used Bonferroni correction to account for multiple testing (P \u3c 4.13 × 10−7). We also assessed the association between variants in candidate diabetes genes with these metabolic traits. We explored the top SNPs in an independent, replication sample from Southwestern Arizona. We identified significant associations with cHOMA-B for common variants at 26 loci of which 8 were novel (PRSS7, FCRL5, PEL1, LRP12, IGLL1, ARHGEF10, PARVA, FLJ16686). The most significant variant association with cHOMA-B was observed on chromosome 5 for an intergenic variant near PARP8 (rs2961831, P = 6.39 × 10−9). In the replication study, we found a signal at rs4607517 near GCK/YKT6 (P = 0.01). Variants near candidate diabetes genes (especially GCK and KCNQ1) were also nominally associated with HOMA-IR and cHOMA-B. Conclusion: We identified variants at novel loci and confirmed those at known candidate diabetes loci associations for cHOMA-B. This study also provided evidence for association of variants at KCNQ2, CTNAA2, and KCNQ1with cHOMA-B among American Indians. Further studies are needed to account for the high heritability of diabetes among the American Indian participants of the SHFS cohort

Diabetes-specific genetic effects on obesity traits in American Indian populations: the Strong Heart Family Study

<p>Abstract</p> <p>Background</p> <p>Body fat mass distribution and deposition are determined by multiple environmental and genetic factors. Obesity is associated with insulin resistance, hyperinsulinemia, and type 2 diabetes. We previously identified evidence for genotype-by-diabetes interaction on obesity traits in Strong Heart Family Study (SHFS) participants. To localize these genetic effects, we conducted genome-wide linkage scans of obesity traits in individuals with and without type 2 diabetes, and in the combined sample while modeling interaction with diabetes using maximum likelihood methods (SOLAR 2.1.4).</p> <p>Methods</p> <p>SHFS recruited American Indians from Arizona, North and South Dakota, and Oklahoma. Anthropometric measures and diabetes status were obtained during a clinic visit. Marker allele frequencies were derived using maximum likelihood methods estimated from all individuals and multipoint identity by descent sharing was estimated using Loki. We used variance component linkage analysis to localize quantitative trait loci (QTLs) influencing obesity traits. We tested for evidence of additive and QTL-specific genotype-by-diabetes interactions using the regions identified in the diabetes-stratified analyses.</p> <p>Results</p> <p>Among 245 diabetic and 704 non-diabetic American Indian individuals, we detected significant additive gene-by-diabetes interaction for weight and BMI (<it>P </it>< 0.02). In analysis accounting for QTL-specific interaction (<it>P </it>< 0.001), we detected a QTL for weight on chromosome 1 at 242 cM (LOD = 3.7). This chromosome region harbors the adiponectin receptor 1 gene, which has been previously associated with obesity.</p> <p>Conclusion</p> <p>These results suggest distinct genetic effects on body mass in individuals with diabetes compared to those without diabetes, and a possible role for one or more genes on chromosome 1 in the pathogenesis of obesity.</p

Stop Atherosclerosis in Native Diabetics Study (SANDS): Baseline Characteristics of the Randomized Cohort

Objectives: To present baseline characteristics of American Indians in the Stop Atherosclerosis in Native Diabetics Study (SANDS) and compare them with population-based data from American Indians and other ethnic groups. Design: 499 people with type 2 diabetes ≥ age 40, without known CVD, were recruited for a randomized 3-year trial to evaluate treatment targets for LDL-C (70 vs. 100 mg/dL) and systolic blood pressure (BP) (115 vs. 130 mmHg). Baseline evaluations included physical exam, collection of blood and urine samples, and carotid ultrasound and echocardiographic measures. Results: Mean age was 56 years; 66% were female. Average BMI was 33 kg/m2. Average duration of both hypertension and diabetes was 10 years, average A1c was 8.0 %, and mean LDL-C was 104 mg/dL. Participants in the conventional treatment group had slightly higher systolic BPs than participants in the aggressive treatment group (133 mm Hg vs. 128 mm Hg, p \u3c 0.002). Compared with the population-based cohorts of the Strong Heart Study (SHS), NHANES, and the TRIAD registry, SANDS participants had similar values for lipids, BP, and CRP, as well as degree of obesity, smoking rates, and renal function as indicated by estimated glomerular filtration rate. Conclusions: The baseline characteristics of the SANDS cohort are similar to those of a population-based sample of American Indian diabetic men and women and closely resemble diabetic men and women of other ethnic groups. Results from this study can be used to identify appropriate targets for LDL-C and BP lowering in diabetic American Indians and diabetic patients in other ethnic groups