2,427 research outputs found
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
Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes the strong heart study
AbstractObjectivesThe goal of this study was to determine if the haptoglobin phenotype was predictive of cardiovascular disease (CVD) in diabetic mellitus (DM).BackgroundCardiovascular disease is the most frequent, severe, and costly complication of type 2 DM. There are clear geographic and ethnic differences in the risk of CVD among diabetic patients that cannot be fully explained by differences in conventional CVD risk factors. We have demonstrated that a functional allelic polymorphism in the haptoglobin gene acts as a major determinant of susceptibility for the development of diabetic microvascular complications.MethodsWe sought to determine if this paradigm concerning the haptoglobin gene could be extended to CVD in DM. We tested this hypothesis in a case-control sample from the Strong Heart study, a population-based longitudinal study of CVD in American Indians. Haptoglobin phenotype was determined by polyacrylamide gel electrophoresis in 206 CVD cases and 206 matched controls age 45 to 74 years. Median follow-up was six years.ResultsIn multivariate analyses controlling for conventional CVD risk factors, haptoglobin phenotype was a highly statistically significant, independent predictor of CVD in DM. The odds ratio of having CVD in DM with the haptoglobin 2-2 phenotype was 5.0 times greater than in DM with the haptoglobin 1-1 phenotype (p = 0.002). An intermediate risk of CVD was associated with the haptoglobin 2-1 phenotype.ConclusionsThis study suggests that determination of haptoglobin phenotype may contribute to the algorithm used in CVD risk stratification, and in evaluation of new therapies to prevent CVD in the diabetic patient
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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
Risk Factors for Arterial Hypertension in Adults With Initial Optimal Blood Pressure
Whether metabolic factors and their change over time influence development of arterial hypertension in adults with initially optimal blood pressure (BP) is unknown. We analyzed associations of BP in the optimal range (<120/80 mm Hg), metabolic risk factors, and their changes over 4-year follow-up, with 8-year incident hypertension, in a cohort of American Indians with a high prevalence of obesity. At baseline, 967 participants with optimal BP and no prevalent cardiovascular disease (69.5% women; mean age, 54±7 years) were evaluated and reexamined after 4 (second examination) and 8 years to evaluate predictors of 8-year incident arterial hypertension. In participants with normal glucose tolerance, baseline BP and decrease in high-density lipoprotein cholesterol from baseline to the second examination were the most potent predictors of 8-year arterial hypertension (both
P
<0.0001), with additional effects of baseline waist circumference and its increase, increase in BP, and presence of diabetes at the second examination (all
P
<0.04). In participants with impaired glucose tolerance or diabetes, the most potent predictor of 8-year incident hypertension was diabetes at the second examination (
P
<0.0001) followed by a increase in BP and LDL cholesterol over the first 4 years (both
P
<0.001). Thus, incident arterial hypertension can be predicted by initial metabolic profile and unfavorable metabolic variations over time, in addition to initial BP. At optimal levels of initial BP, increasing abdominal obesity, and abnormal lipid profile are major predictors of development of arterial hypertension. Possible implications of these findings for primary cardiovascular prevention should be tested in prospective studies
Depressed Myocardial Energetic Efficiency Increases Risk of Incident Heart Failure: The Strong Heart Study
An estimation of myocardial mechano-energetic efficiency (MEE) per unit of left ventricular (LV) mass (MEEi) can significantly predict composite cardiovascular (CV) events in treated hypertensive patients with normal ejection fraction (EF), after adjustment for LV hypertrophy (LVH). We have tested whether MEEi predicts incident heart failure (HF), after adjustment for LVH, in the population-based cohort of a "Strong Heart Study" (SHS) with normal EF. We included 1,912 SHS participants (age 59 ± 8 years; 64% women) with preserved EF (≥50%) and without prevalent CV disease. MEE was estimated as the ratio of stroke work to the "double product" of heart rate times systolic blood pressure. MEEi was calculated as MEE/LV mass, and analyzed in quartiles. During a follow-up study of 9.2 ± 2.3 years, 126 participants developed HF (7%). HF was preceded by acute myocardial infarction (AMI) in 94 participants. A Kaplan-Meier plot, in quartiles of MEEi, demonstrated significant differences, substantially due to the deviation of the lowest quartile (p < 0.0001). Using AMI as a competing risk event, sequential models of Cox regression for incident HF (including significant confounders), demonstrated that low MEEi predicted incident HF not due to AMI (p = 0.026), after adjustment for significant effect of age, LVH, prolonged LV relaxation, diabetes, and smoking habits with negligible effects for sex, hypertension, antihypertensive therapy, obesity, and hyperlipemia. Low LV mechano-energetic efficiency per unit of LVM, is a predictor of incident, non-AMI related, HF in subjects with initially normal EF
Assessing the Use of GEE Methods for Analyzing Continuous Outcomes from Family Studies: Strong Heart Family Study
Background: Because of its convenience and robustness, the generalized estimating equations (GEE) method has been commonly used to fit marginal models of continuous outcomes in family studies. However, unbalanced family sizes and complex pedigree structures within each family may challenge the GEE method, which treats families as clusters with the same correlation structure. The appropriateness of using the GEE method to analyze continuous outcomes in family studies remains unclear. In this paper, we performed simulation studies to evaluate the performance of GEE in the analysis of family study data.
Methods: In simulation studies, we generated data from a linear mixed effects model with individual random effects. The random effects covariance matrix is specified as twice that of the pedigree matrix from the Strong Heart Family Study (SHFS) and other hypothetical pedigree structures. A Bayesian approach that utilizes the pedigree matrix was also conducted as a benchmark to compare with GEE methods with either independent or exchangeable correlation structures. Finally, analysis with a real data example was included.
Results: Our simulation results showed that GEE with independent correlation structure worked well for family data with continuous outcomes. Real data analysis revealed that all GEE and Bayesian approaches produced similar results.
Conclusion: GEE model performs well on continuous outcome in family studies, and it yields estimated coefficients similar to a Bayesian model, which takes genetic relationship into account. Overall, GEE is robust to misspecification of genetic relationships among family members
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 45–74 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 £ 126 mg/dl or 2hPG
≥ 200 mg/dl, as having IFG if they had 110 £ 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 ≥ 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 ≥ 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 ≥ 126 and 2hPG ≥ 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 ≥ 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
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