Until treatment and vaccine for coronavirus disease-2019 (COVID-19) becomes widely available, other methods of reducing infection rates should be explored. This study used a retrospective, observational analysis of deidentified tests performed at a national clinical laboratory to determine if circulating 25-hydroxyvitamin D (25(OH)D) levels are associated with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) positivity rates. Over 190,000 patients from all 50 states with SARS-CoV-2 results performed mid-March through mid-June, 2020 and matching 25(OH)D results from the preceding 12 months were included. Residential zip code data was required to match with US Census data and perform analyses of race/ethnicity proportions and latitude. A total of 191,779 patients were included (median age, 54 years [interquartile range 40.4-64.7]; 68% female. The SARS-CoV-2 positivity rate was 9.3% (95% C.I. 9.2-9.5%) and the mean seasonally adjusted 25(OH)D was 31.7 (SD 11.7). The SARS-CoV-2 positivity rate was higher in the 39,190 patients with "deficient" 25(OH)D values (<20 ng/mL) (12.5%, 95% C.I. 12.2-12.8%) than in the 27,870 patients with "adequate" values (30-34 ng/mL) (8.1%, 95% C.I. 7.8-8.4%) and the 12,321 patients with values �55 ng/mL (5.9%, 95% C.I. 5.5-6.4%). The association between 25 (OH)D levels and SARS-CoV-2 positivity was best fitted by the weighted second-order polynomial regression, which indicated strong correlation in the total population (R 2 = 0.96) and in analyses stratified by all studied demographic factors. The association between lower SARS-CoV-2 positivity rates and higher circulating 25(OH)D levels remained significant in a multivariable logistic model adjusting for all included demographic factors (adjusted odds ratio 0.984 per ng/mL increment, 95% C.I. 0.983-0.986; p<0.001). SARS-CoV-2 positivity is strongly and inversely associated with circulating 25(OH)D levels, a relationship that persists across latitudes, races/ethnicities, both sexes, and age ranges. Our findings provide impetus to explore the role of vitamin D supplementation in reducing the risk for SARS-CoV-2 infection and COVID-19 disease.
BackgroundInterpretation of parathyroid hormone (iPTH) requires knowledge of vitamin D status that is influenced by season.ObjectiveCharacterize the temporal relationship between 25-hydroxyvitamin D3 levels [25(OH)D3] and intact iPTH for several seasons, by gender and latitude in the U.S. and relate 25-hydrovitamin D2 [25(OH)D2] levels with PTH levels and total 25(OH)D levels.MethodWe retrospectively determined population weekly-mean concentrations of unpaired [25(OH)D2 and 25(OH)D3] and iPTH using 3.8 million laboratory results of adults. The 25(OH)D3 and iPTH distributions were normalized and the means fit with a sinusoidal function for both gender and latitudes: North >40, Central 32–40 and South <32 degrees. We analyzed PTH and total 25(OH)D separately in samples with detectable 25(OH)D2 (≥4 ng/mL).FindingsSeasonal variation was observed for all genders and latitudes. 25(OH)D3 peaks occurred in September and troughs in March. iPTH levels showed an inverted pattern of peaks and troughs relative to 25(OH)D3, with a delay of 4 weeks. Vitamin D deficiency and insufficiency was common (33% <20 ng/mL; 60% <30 ng/mL) as was elevated iPTH levels (33%>65 pg/mL). The percentage of patients deficient in 25(OH)D3 seasonally varied from 21% to 48% and the percentage with elevated iPTH reciprocally varied from 28% to 38%. Patients with detectable 25(OH)D2 had higher PTH levels and 57% of the samples with a total 25(OH)D > 50 ng/mL had detectable 25(OH)D2.Interpretation25(OH)D3 and iPTH levels vary in a sinusoidal pattern throughout the year, even in vitamin D2 treated patients; 25(OH)D3, being higher in the summer and lower in the winter months, with iPTH showing the reverse pattern. A large percentage of the tested population showed vitamin D deficiency and secondary hyperparathyroidism. These observations held across three latitudinal regions, both genders, multiple-years, and in the presence or absence of detectable 25(OH)D2, and thus are applicable for patient care.
We examined the effect of renal dysfunction on B-natriuretic peptide (BNP), N-terminal (NT)-proBNP, and their molar ratio at varying severities of cardiac function in 94 Thai patients with chest pain (52 men; 32 women), also measuring creatinine and left ventricular ejection fraction (LVEF). Renal function was classified into 5 stages by estimated glomerular filtration rate. The molar NT-proBNP/BNP ratio was calculated. Cardiac status was classified by LVEF (normal, >50%; moderate, 35%-50%; severe, <35%). BNP, NT-proBNP, and their ratio corresponded to renal disease stage exponential (0.51, 1.05, and 0.54, respectively; correlation coefficients, >or=0.95). BNP and the ratio are affected less than NT-proBNP by renal dysfunction, starting in stage III; NT-proBNP expresses effects starting in stage II. NT-proBNP is more sensitive than BNP to renal disease stage. For log of geometric means vs stage of renal disease, the BNP slopes and correlation coefficients vary considerably (slopes, 0.036-0.531; r(2), 0.017-0.99). The NT-proBNP slopes and regression coefficients vary considerably (slopes, 0.18-0.71; r(2), 0.33-0.99). For the ratio, the slopes show low variation (0.148-0.337), r(2) greater than 0.96, women differing from men (P = .012). The effect of renal disease differs by gender. BNP and NT-proBNP increase by stage III for women but not for men. One must consider renal function, gender, and LVEF when using BNP or NT-proBNP as cardiac biomarkers. The ratio of the 2 peptides is the most consistent marker across LVEFs.
Interference by endogenous and exogenous substances with assays for clinical analytes is a common problem in laboratory medicine. For this review, we defined interference as "the effect of a substance present in the sample that alters the correct value of the result, usually expressed as concentration or activity, for an analyte." There are four major endogenous compounds that consistently interfere with laboratory results: hemoglobin, bilirubin, lipids, and paraproteins. The major exogenous sources of interference are drugs prescribed for the patient; and there are several excellent compendia of the effect of drugs on clinical laboratory tests. We recommend determining whether the interference is dependent or independent of the analyte for the assay. Further, we propose an approach to the identification and resolution of an interference problem for the clinical laboratory and make recommendations to manufacturers.
Metal halide perovskites are the first solution processed semiconductors that can compete in their functionality with conventional semiconductors, such as silicon. Over the past several years, perovskite semiconductors have reported breakthroughs in various optoelectronic devices, such as solar cells, photodetectors, light emitting and memory devices, and so on. Until now, perovskite semiconductors face challenges regarding their stability, reproducibility, and toxicity. In this Roadmap, we combine the expertise of chemistry, physics, and device engineering from leading experts in the perovskite research community to focus on the fundamental material properties, the fabrication methods, characterization and photophysical properties, perovskite devices, and current challenges in this field. We develop a comprehensive overview of the current state-of-the-art and offer readers an informed perspective of where this field is heading and what challenges we have to overcome to get to successful commercialization.
We determined concentrations of magnesium, total protein, albumin, and globulin in more than 74 000 serum specimens from patients and noted a direct linear relationship between the concentration of magnesium in serum and the concentrations of total protein, albumin, and globulin in serum. Albumin and magnesium concentrations are linearly related at high and low albumin concentrations; within the reference interval, however, the magnesium concentration is independent of the albumin concentration. Linear regression analysis suggests that 25% of the total serum magnesium is bound to albumin and 8% to globulins.
Bloom filter encoded identifiers are increasingly used for privacy preserving record linkage applications, because they allow for errors in encrypted identifiers. However, little research on the security of Bloom filters has been published so far. In this paper, we formalize a successful attack on Bloom filters composed of bigrams. It has previously been assumed in the literature that an attacker knows the global data set from which a sample is drawn. In contrast, we suppose that an attacker does not know this global data set. Instead, we assume the adversary knows a publicly available list of the most frequent attributes. The attack is based on subtle filtering and elementary statistical analysis of encrypted bigrams. The attack described in this paper can be used for the deciphering of a whole database instead of only a small subset of the most frequent names, as in previous research. We illustrate our proposed method with an attack on a database of encrypted surnames. Finally, we describe modifications of the Bloom filters for preventing similar attacks.
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