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Introduction: Cardiovascular disease (CVD) is the leading cause of mortality and disability in the United States. Spatiotemporal modeling of disease incidence may guide prevention efforts toward regions most at risk in the future. Methods: We examined spatiotemporal trends in composite CVD events, defined as myocardial infarction, ischemic stroke, atrial fibrillation, heart failure, coronary artery disease, or cardiovascular death, using electronic health records from 9,718,107 U.S. Veterans who used VA healthcare facilities from 2003-2018. Age-standardized annual incidence by state was modeled using the Bernardinelli model, a Bayesian Poisson regression with linear temporal trends for the US and individual states. Results: There were 626,271 CVD events over 16 years of follow up and annual incidence fell gradually from 11.5% in 2003 to 6.6% in 2018. Incidence among all US veterans decreased an estimated 3.1% [95% CI: -3.3%, -2.9%] per year (RR year = 0.969). State-level incidences also decreased monotonically over the follow-up period (Figure panel A ), ranging from an absolute decrease 5.0% (RI) to 1.7% (OR). Estimated incidence for the five states most above (RI, FL, NC, MT, LA) and most below (OR, NV, CT, OK, MI) the national trend are plotted against the US average in Figure panel B . These outlying states differed significantly from the overall trend (posterior probabilities ≥ 99.7%), and the magnitude of trend was loosely correlated with initial incidence rate (in 2003). Notably, four states crossed the national average over the study period: CT and OK started below average in 2003 but ended above in 2018, whereas RI and NC started with high incidence and ended with below average incidence in 2018. Conclusions: Among US veterans, there was significant geographic variation in the rate of decline of incident CVD from 2003-2018. Future research will investigate the mechanisms underpinning the observed trends, particularly prevalence and control of risk factors.

Background: Although recent large randomized clinical trials showed an increased risk of atrial fibrillation (AF) with marine omega-3 fatty acids supplements, it is unclear whether dietary marine omega-3 fatty acids assessed through food frequency questionnaires are associated with AF risk. Hence, we sought to test the hypothesis that dietary eicosapentaenoic acid/docosahexaenoic acid/docosapentaecnoic acid (EPA/DHA/DPA) is associated with a higher risk of AF in a large prospective cohort of US Veterans. Methods: We analyzed data from Million Veteran Program participants who completed self-reported food frequency questionnaires. We used multivariable Cox regression to estimate hazard ratios of AF across quintiles of omega-3 fatty acids consumption and a cubic spline analysis to assess the dose-response relationship between omega-3 fatty acids and AF. Results: Of the 301,294 Veterans studied, the mean intake of omega-3 fatty acids (EPA/DHA/DPA) was 0.39 g/day (SD 0.38), the mean age was 64.9 (SD 12.0) years; 91.2% (274,881 of 301,294) male and 84.0% (253,144 of 301,294) White. Consumption of EPA/DHA/DPA exhibited a non-linear inverse relation with incident AF characterized by an initial decline to 11% at 0.75 g/day of marine omega-3 fatty acids intake followed by a plateau. Conclusions: Contrary to our hypothesis, dietary EPA/DHA/DPA was not associated with a higher risk of AF but was inversely related to AF risk in a non-linear manner.

Introduction: Familial hypercholesterolemia (FH), defined as LDL-C ≥190mg/dL, is a strong cardiovascular disease (CVD) risk factor. The AHA/ACC guidelines recommend high intensity statins for primary prevention irrespective of global risk assessment. We sought to characterize trends and predictors of statin initiation among Veterans with FH in the Veterans Health Administration (VHA). Methods: Inclusion criteria consisted of care at the VHA (2002-2014), age ≥21 years, baseline LDL-C ≥190 mg/dL, no prevalent CVD, no prior statin use, and statin initiation within 90 days of LDL-C measurement. We defined baseline LDL-C in quartiles: Q1=190-195, Q2=196-202, Q3=203-215, and Q4 >215 (mg/dL). Statin intensity was defined as average intensity over one year following baseline LDL-C measurement. Multivariable logistic regression models were constructed to determine the odds of any statin initiation and high intensity statin initiation. Results: Over 12 years, 165,110 Veterans (age=52.9±11.9, men=91%; white race=74%) were included. Statins were initiated in 88,878 patients (overall 54%, 62% in 2014). Overall, 29,533 Veterans were on high intensity statins (overall 33%, 20% in 2002, 50% in 2014). In multivariable-adjusted logistic regression models, significant predictors of statin initiation were age, white race, diabetes hypertension, smoking, baseline LDL-C, and recent calendar year. Among those initiated on high intensity statins, the same predictors were significant; however, African Americans were more likely to be started on a high intensity statin (Table). Conclusions: Among Veterans with FH, the odds of statin initiation are higher among older, Caucasian, hypertensive, diabetic, and smoking veterans. The odds of statin prescription have increased over time with a higher proportion receiving high intensity statins more recently. These data reflect the VHA changes in clinical practice concordant with ACC/AHA guidelines.

High dimensional predictive models of Major Adverse Cardiac Events (MACE), which includes heart attack (AMI), stroke, and death caused by cardiovascular disease (CVD), were built using four longitudinal cohorts of Veterans Administration (VA) patients created from VA medical records. We considered 247 variables / risk factors measured across 7.5 years for millions of patients in order to compare predictions for the first reported MACE event using six distinct modelling methodologies. The best-performing methodology varied across the four cohorts. Model coefficients related to disease pathophysiology and treatment were relatively constant across cohorts, while coefficients dependent upon the confounding variables of age and healthcare utilization varied considerably across cohorts. In particular, models trained on a retrospective case-control (Rcc) cohort (where controls are matched to cases by date of birth cohort and overall level of healthcare utilization) emphasize variables describing pathophysiology and treatment, while predictions based on the cohort of all active patients at the start of 2017 (C-17) rely much more on age and variables reflecting healthcare utilization. In consequence, directly using an Rcc-trained model to evaluate the C-17 cohort resulted in poor performance (C-statistic = 0.65). However, a simple reoptimization of model dependence on age, demographics, and five other variables improved the C-statistic to 0.74, nearly matching the 0.76 obtained on C-17 by a C-17-trained model. Dependence of MACE risk on biomarkers for hypertension, cholesterol, diabetes, body mass index, and renal function in our models was consistent with the literature. At the same time, including medications and procedures provided important indications of both disease severity and the level of treatment. More detailed study designs will be required to disentangle these effects.

The 2011 Tohoku earthquake and subsequent tsunami had a catastrophic effect on the aquaculture industry of the North-East Japanese coast. Ten years on, this paper examines the environmental and economic impacts of this disaster within the context of the Fukushima nuclear meltdown. Following structural damage to the Tokyo Electric Power Company Fukushima Daiichi plant, fisheries and aquaculture industries were suspended, given the initially high radio caesium output into the coastal water column. Daily radiation testing began on all fisheries products, with tentative industry resuming within the Fukushima prefecture once radiation had dropped below the 50 Bq/kg, as stipulated by the Fukushima Fisheries Association. Routine testing continues biweekly (at least until March 2021). As of May 2016, 73 fish species were passed for consumption. The rapid functional recovery of the fisheries industry has been mediated by two factors, the sedimentation characteristics of the caesium isotopes and deposition of isotopes out to sea in an Easterly direction, given the interaction of oceanic currents. While the aquaculture industry may have recovered and food reduced to safe radiation levels, the disaster continues to exert a domestic and international economic impact given the stigma of Fukushima radiation.

This report outlines a study undertaken at Minamisanriku, a small coastal village on the East Coast of Honshu, Japan, in late 2018. The area relies heavily on fisheries and aquaculture for economic stability. While there, scientists, community leaders and individuals involved in the fisheries and aquaculture industry were interviewed to gain a qualitative understanding of the impacts of the 2011 tsunami caused by the Great East Japan Earthquake, particularly on the oyster industry and aquaculture in general in the region. The tsunami completely disrupted aquaculture operations, with a 93% loss of infrastructure. Consequently, stakeholders were presented with an opportunity to restructure in some way as they rebuilt the industry. The resulting 66% reduction in some species densities within aquaculture lots has subsequently led to increased sustainability and increased product quality. Those gains, paired with reduced material cost and efforts, have together resulted in a more socio-ecologically responsible aquaculture operation. This operation now generates at least same amount of revenue as pre-tsunami.

We present here direct evidence for neutrons causing nucleation of supercooled water. Highly purified water (20 nm filtration) is cooled to well below freezing (as low as -20 degrees C) with a radioactive calibration source of neutrons / gamma-rays either present or removed during each of many control cooling runs for the same volume of water. When it is primarily neutrons irradiating the sample bulk, the non-equilibrium freezing point (also known as the "supercooling point") is, on average, +0.7 degrees C warmer than the control equivalent, with a statistical significance of greater than 5 sigma, with systematic uncertainty included. This effect is not observed with water in the presence of gamma-rays instead of neutrons. While these neutrons should have theoretically had sufficient energy to mount the energy barrier, corroborating our results, their raising of supercooling temperature has never been reported experimentally to the best of our knowledge. The potential to use deeply supercooled solutions, not only water, as metastable detectors for radiation and perhaps dark matter or neutrino physics presents now a new avenue for exploration., Comment: 14 pages, 7 figures; pre-print, pre-acceptance version

Decreased expression of chicken cholecystokinin A receptor (CCKAR) attenuates satiety, which contributes to increased food intake and growth for modern broilers. The study aims to define the core promoter of CCKAR, and to identify variants associated with expression activity. A 21 kb region around the CCKAR was re-sequenced to detect sequence variants. A series of 5′-deleted promoter plasmids were constructed to define the core promoter of CCKAR. The effects of sequence variants located in promoter (PSNP) and conserved (CSNP) regions on promoter activity were analyzed by comparing luciferase activity between haplotypes. A total of 182 variants were found in the 21 kb region. There were no large structural variants around CCKAR. pNL−328/+183, the one with the shortest insertion, showed the highest activity among the six promoter constructs, implying that the key cis elements regulating CCKAR expression are mainly distributed 328 bp upstream. We detected significant activity differences between high- and low-growth associated haplotypes in four of the six promoter constructs. The high-growth haplotypes of constructs pNL−1646/+183, pNL−799/+183 and pNL−528/+183 showed lower activities than the low-growth haplotypes, which is consistent with decreased expression of CCKAR in high-growth chickens. Lower expression of the high-growth allele was also detected for the CSNP5-containing construct. The data suggest that the core promoter of CCKAR is located the 328 bp region upstream from the transcription start site. Lower expression activities shown by the high-growth haplotypes in the reporter assay suggest that CSNP5 and variants located between 328 bp and 1646 bp upstream form a promising molecular basis for decreased expression of CCKAR and increased growth in chickens.

Gastrin and cholecystokinin peptides bind a common G-protein coupled receptor, cholecystokinin receptor B (CCKBR) whilst cholecystokinin receptor A (CCKAR) is preferentially bound by CCK. Gastrin and cholecystokinin mediate signalling from the gastrointestinal tract to regulate appetite and digestive function. In this study, expression of the cholecystokinin/gastrin family and distribution of their receptors expression was measured to understand the target organs for the peptides and how expression responds to changes in food intake. We confirmed the restricted expression of gastrin in the antrum and the abundant expression of cholecystokinin in the hypothalamus. The expression of gastrin in the antrum was significantly elevated in broiler breeders when released from feed restriction. CCKBR was most abundant in the hypothalamus and proventriculus. CCKAR was most abundant in the pancreas and crop, more than tenfold greater than the gastrointestinal tract. Cholecystokinin expression in the pancreas increased after removal of food restriction. CCKAR in the gastrointestinal tract peaks around the distal ileum, distal to the peak of cholecystokinin expression. There was virtually no cholecystokinin expression in the caecum but CCKAR expression was high. The CCKAR expression in the crop was unexpected, supporting a role of cholecystokinin in mediating crop emptying which was supported by the observation of in-vitro contraction after cholecystokinin administration. The response to changes in food intake and the expression pattern of the cholecystokinin/gastrin family and their receptors will stimulate and inform new hypotheses on their role in growth in poultry.

There have been many reports that a metastable form of ice can exist in the atmosphere and that it transitions rapidly to stable, hexagonal ice at temperatures above about 200 K. Although this often-called cubic ice has also been created in laboratories over the years, we present here a method for the simple formation of this metastable phase in the laboratory, at one atmosphere, in relatively large volumes and at higher temperatures than previously reported. Evidence for this phase is found during the monitoring of optical transmission through bulk samples of quenched aqueous solutions. In our experiments, frozen samples were created by quenching 0.2 ml aqueous volumes in glass tubes to 195 K which are then warmed to and held at 267 K. Results show an unusual drop in optical transmission occurring in the first few minutes. Such a change is best explained by the transition of a metastable phase to hexagonal ice, rather than by any freeze concentration effects. In the minutes following nucleation and freezing of the sample, the average size of the poly-crystals forming the frozen matrix would be typically expected to increase due to recrystallization, causing lower side and back-scatter of the traversing light and so a subsequent increased optical transmission. However, the drop in transmission we see with samples nucleated at such a low temperature cannot be explained by recrystallisation but rather by a re-ordering of the ice, the grain boundaries, and the interstitial water.

Background: Decreased expression of chicken CCKAR gene attenuates satiety, which contributes to increased food intake and growth of modern broilers. The study aims to define the core promoter of CCKAR, and to identify variants associated with expression activity.Methods and results: The 21-kb region around the CCKAR was re-sequenced to detect sequence variants. A series of 5’-deleted promoter plasmids were constructed to define the core promoter of CCKAR. Effect of sequence variants located in promoter (PSNP) and conserved (CSNP) regions on promoter activity was analyzed by comparing luciferase activity between haplotypes. A total of 182 variants were found in the 21-kb region. But no large structural variants were found. The pNL-328/+183, the one with the shortest insertion, showed the highest activity among six promoter constructs. To find out variants associated with CCKAR expression, this study compared promoter activities between haplotypes on each construct. We detected significant difference of promoter activities between haplotypes on four of six promoter constructs. The high-growth haplotype of pNL-1646/+183, pNL-799/+183 and pNL-528/+183 showed lower activities than the low-growth haplotype, which is in the direct with decreased expression of CCKAR in high-growth chickens. The expected difference was also detected on the CSNP5-containing construct.Conclusions: The data reveals the core promoter of CCKAR located within the 328-bp region upstream from the transcription start site. Low promoter activities shown the high-growth haplotypes in the reporter assay suggest that CSNP5 and promoter variants form promising molecular basis for decreased expression of CCKAR and high growth of chickens.

Background: Familial hypercholesterolemia (FH) genetic variants confer risk for coronary artery disease independent of LDL-C (low-density lipoprotein cholesterol) when considering a single measurement. In real clinical settings, longitudinal LDL-C data are often available through the electronic health record. It is unknown whether genetic testing for FH variants provides additional risk-stratifying information once longitudinal LDL-C is considered. Methods: We used the extensive electronic health record data available through the Million Veteran Program to conduct a nested case-control study. The primary outcome was coronary artery disease, derived from electronic health record codes for acute myocardial infarction and coronary revascularization. Incidence density sampling was used to match case/control exposure windows, defined by the date of the first LDL-C measurement to the date of the first coronary artery disease code of the index case. Adjustments for the first, maximum, or mean LDL-C were analyzed. FH variants in LDLR , APOB , and PCSK9 (Proprotein convertase subtilisin/kexin type 9) were assessed by custom genotype array. Results: In a cohort of 23 091 predominantly prevalent cases at enrollment and 230 910 matched controls, FH variant carriers had an increased risk for coronary artery disease (odds ratio [OR], 1.53 [95% CI, 1.24–1.89]). Adjusting for mean LDL-C led to the greatest attenuation of the risk estimate, but significant risk remained (odds ratio, 1.33 [95% CI, 1.08–1.64]). The degree of attenuation was not affected by the number and the spread of LDL-C measures available. Conclusions: The risk associated with carrying an FH variant cannot be fully captured by the LDL-C data available in the electronic health record, even when considering multiple LDL-C measurements spanning more than a decade.

Broiler breeder chickens are commercially feed restricted to slow their growth and improve their health and production, however, there is research demonstrating that this leads to chronic hunger resulting in poor welfare. A challenge in these studies is to account for possible daily rhythms or the effects of time since last meal on measures relating hunger. To address this, we used 3 feed treatments: AL (ad libitum fed), Ram (restricted, fed in the morning) and Rpm (restricted, fed in the afternoon) to control for diurnal effects. We then conducted foraging motivation tests and collected home pen behavior and physiological samples at 4 times relative to feeding throughout a 24 h period. The feed treatment had the largest influence on the data, with AL birds weighing more, having lower concentrations of plasma NEFA, and mRNA expression of AGRP and NPY alongside higher expression of POMC in the basal hypothalamus than Ram or Rpm birds (P0.05) but AGRP expression was highest in the basal hypothalamus shortly after a meal (P

Introduction: Heart failure (HF) increases morbidity, mortality, and costs, with complex pathogenic mechanisms. Interleukin-6 (IL-6) is a key cytokine and immune regulator with broad impact on inflammation – a critical component of HF pathophysiology. Circulating levels of IL-6 receptor (IL-6R) determines the activity of the IL-6 signaling pathway. We aim to estimate the causal effect of the IL-6R on HF and two clinical subtypes: HF with reduced (HFrEF) and preserved ejection fraction (HFpEF) in a Mendelian Randomization (MR) framework including mediators. Hypothesis: Plausible causal associations between IL-6R and HF, HFrEF and HFpEF are mediated by body mass index (BMI) or coronary artery disease (CAD). Methods: Two-sample MR analyses were conducted using genetic association results for composite HF, HFrEF and HFpEF among >300,000 MVP participants of European ancestry. Thirty-four independent genetic variants within 250 kb from the IL6R gene associated with plasma IL-6R levels were used as genetic instrumental variables. We estimated the direct effect of IL-6R levels on HF and subtypes, and the indirect effect mediated through BMI and CAD. Results: Causal effects of IL-6R on composite HF, HFrEF and HFpEF were estimated as odds ratios (OR): 0.97 (CI 0.96-0.99, p=0.02), 0.96 (CI 0.93-0.98, p=0.003) and 1.00 (CI 0.97-1.03, p=0.89), respectively. Mediation analyses for composite HF and HFrEF showed significant mediation effects by CAD, with ORs 0.98 (CI 0.97-0.99) and 0.98 (CI 0.96-1.00), respectively. No mediation effect of BMI was identified. Conclusions: These findings support a causal role of IL-6 signaling in composite HF and HFrEF, but not HFpEF. Although the IL-6 signaling pathway plays a role in both BMI and CAD, the effect of IL-6 signaling on composite HF and HFrEF may be mediated through by CAD. Our findings demonstrate the role of IL-6 signaling in HF and its difference between HF subtypes, which may lead to more specific therapeutic targets for HF.

The prediction of myocardial infarction (MI), acute ischemic stroke (AIS), cardiovascular (CVD) death, and 3-point MACE (MI, AIS, or CVD death) in Million Veteran Program (MVP) participants over 8 years of follow up was evaluated using environmental/traditional risk factors (“E”), polygenic risk scores (“G”), and a combination of both approaches (“GxE”). Individuals free of atherosclerotic cardiovascular disease (ASCVD) at baseline were included. Risk factor levels for the participants close to the time of MVP enrollment for age, sex, systolic blood pressure, cholesterol, HDL cholesterol, smoking status, and diabetes status were analyzed. Outcomes were determined from VA electronic record data, Medicare/Medicaid data, and the National Death Index. Analyses were undertaken separately for non-Hispanic European (EUR), African American (AFR), and Hispanic (HIS) participants. There were 157,941 veterans at risk with 8,157 MI events, 2,024 AIS events, 1,778 CVD deaths, and 9,350 3-pt MACE events over 8 years of follow-up. The overall results showed good performance with the environmental model for all three racial-ethnic groups, with C-statistics ranging from 0.69 to 0.77. The G models showed very modest prediction capabilities and similarly modest improvement in the combined GxE models. In conclusion, traditional risk factor modeling has been shown to be highly effective and, in the MVP experience, the additional impact of genetic or genetic interaction information was small.

Although affecting different arterial territories, the related atherosclerotic vascular diseases coronary artery disease (CAD) and peripheral artery disease (PAD) share similar risk factors and have shared pathobiology. To identify novel pleiotropic loci associated with atherosclerosis, we performed a joint analysis of their shared genetic architecture, along with that of common risk factors. Using summary statistics from genome-wide association studies of nine known atherosclerotic (CAD, PAD) and atherosclerosis risk factors (body mass index, smoking initiation, type 2 diabetes, low density lipoprotein, high density lipoprotein, total cholesterol, and triglycerides), we perform 15 separate multi-trait genetic association scans which resulted in 25 novel pleiotropic loci not yet reported as genome-wide significant for their respective traits. Colocalization with single-tissue eQTLs identified candidate causal genes at 14 of the detected signals. Notably, the signal between PAD and LDL-C at the PCSK6 locus affects PCSK6 splicing in human liver tissue and induced pluripotent derived hepatocyte-like cells. These results show that joint analysis of related atherosclerotic disease traits and their risk factors allowed identification of unified biology that may offer the opportunity for therapeutic manipulation. The signal at PCSK6 represent possible shared causal biology where existing inhibitors may be able to be leveraged for novel therapies.

XSP25, previously shown to be the most abundant hydrophilic protein in xylem sap of Populus nigra in winter, belongs to a secretory protein family in which the arrangement of basic and acidic amino acids is conserved between dicotyledonous and monocotyledonous species. Its gene expression was observed at the same level in roots and shoots under long-day conditions, but highly induced under short-day conditions and at low temperatures in roots, especially in endodermis and xylem parenchyma in the root hair region of Populus trichocarpa, and its protein level was high in dormant buds, but not in roots or branches. Addition of recombinant PtXSP25 protein mitigated the denaturation of lactate dehydrogenase by drying, but showed only a slight effect on that caused by freeze–thaw cycling. Recombinant PtXSP25 protein also showed ice recrystallization inhibition activity to reduce the size of ice crystals, but had no antifreezing activity. We suggest that PtXSP25 protein produced in shoots and/or in roots under short-day conditions and at non-freezing low temperatures followed by translocation via xylem sap to shoot apoplast may protect the integrity of the plasma membrane and cell wall functions from freezing and drying damage in winter environmental conditions.

Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic elevation of alanine aminotransferase (cALT) levels without other liver diseases, we performed a multiancestry genome-wide association study (GWAS) in the Million Veteran Program (MVP) including 90,408 cALT cases and 128,187 controls. Seventy-seven loci exceeded genome-wide significance, including 25 without prior NAFLD or alanine aminotransferase associations, with one additional locus identified in European American-only and two in African American-only analyses (P < 5 × 10(−8)). External replication in histology-defined NAFLD cohorts (7,397 cases and 56,785 controls) or radiologic imaging cohorts (n = 44,289) replicated 17 single-nucleotide polymorphisms (SNPs) (P < 6.5 × 10(−4)), of which 9 were new (TRIB1, PPARG, MTTP, SERPINA1, FTO, IL1RN, COBLL1, APOH and IFI30). Pleiotropy analysis showed that 61 of 77 multiancestry and all 17 replicated SNPs were jointly associated with metabolic and/or inflammatory traits, revealing a complex model of genetic architecture. Our approach integrating cALT, histology and imaging reveals new insights into genetic liability to NAFLD.

Several species of polar microalgae are able to live and thrive in the extreme environment found within sea ice, where ice crystals may reduce the organisms' living space and cause mechanical damage to the cells. Among the strategies adopted by these organisms to cope with the harsh conditions in their environment, ice-binding proteins (IBPs) seem to play a key role and possibly contribute to the success of microalgae in sea ice. Indeed, IBPs from microalgae predominantly belong to the so-called "DUF 3494-IBP" family, which today represents the most widespread IBP family. Since IBPs have the ability to control ice crystal growth, their mechanism of function is of interest for many potential applications. Here, we describe methods for a classical determination of the IBP activity (thermal hysteresis, recrystallization inhibition) and further methods for protein activity characterization (ice pitting assay, determination of the nucleating temperature).

Recent published results and a re-analysis of existing measurements of the Workman–Reynolds Freezing Potential allow a redefinition the electric potential created when ice grows into a dilute salt solution. The entire process is largely determined by the solubility and diffusivity of the ion species being incorporated differentially into the ice lattice. This new look at the Workman–Reynolds effect shows that the voltage itself is of secondary interest, and rather it is the time to reach peak voltage, which is of paramount interest in the study of the mechanism.

When water-ice grows into salt solutions ion species are excluded by the ice differentially due to non-identical solubility in the ice lattice. This causes an electrical potential across the interface during the ice growth process, initially named the Workman Reynolds Freezing Potential, and may be one of the causes for lightning. However, by measuring the voltage between the ice and water, we have found that when tetrahydrofuran hydrate crystals are grown into salt solutions all ion species are excluded equally and the potential does not manifest. When considered together, this marked difference in ion exclusion scenarios may have ramifications for hydrate exploration because of the chlorine anomaly, which is often used as an indicator of the presence of hydrate reserves.

The development of anti-icing, anti-frosting transparent plates is important for many reasons, such as poor visibility through the ice-covered windshields of vehicles. We have fabricated new glass surfaces coated with polypeptides which mimic a part of winter flounder antifreeze protein. We adopted glutaraldehyde and polyethylene glycol as linkers between these polypeptides and silane coupling agents applied to the glass surfaces. We have measured the contact angle, the temperature of water droplets on the cooling surfaces, and the frost weight. In addition, we have conducted surface roughness observation and surface elemental analysis. It was found that peaks in the height profile, obtained with the atomic force microscope for the polypeptide-coated surface with polyethylene glycol, were much higher than those for the surface without the polypeptide. This shows the adhesion of many polypeptide aggregates to the polyethylene glycol locally. The average supercooling temperature of the droplet for the polypeptide-coated surface with the polyethylene glycol was lower than for the polypeptide-coated surface with glutaraldehyde and the polyethylene-glycol-coated surface without the polypeptide. In addition, the average weight of frost cover on the specimen was lowest for the polypeptide-coated surface with the polyethylene glycol. These results argue for the effects of combined polyethylene glycol and polypeptide aggregates on the locations of ice nuclei and condensation droplets. Thus, this polypeptide-coating with the polyethylene glycol is a potential contender to improve the anti-icing and anti-frosting of glasses.

We investigated type 2 diabetes (T2D) genetic susceptibility via multi-ancestry meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP), DIAMANTE, Biobank Japan and other studies. We report 568 associations, including 286 autosomal, 7 X-chromosomal and 25 identified in ancestry-specific analyses that were previously unreported. Transcriptome-wide association analysis detected 3,568 T2D associations with genetically predicted gene expression in 687 novel genes; of these, 54 are known to interact with FDA-approved drugs. A polygenic risk score (PRS) was strongly associated with increased risk of T2D-related retinopathy and modestly associated with chronic kidney disease (CKD), peripheral artery disease (PAD) and neuropathy. We investigated the genetic etiology of T2D-related vascular outcomes in the MVP and observed statistical SNP-T2D interactions at 13 variants, including coronary heart disease (CHD), CKD, PAD and neuropathy. These findings may help to identify potential therapeutic targets for T2D and genomic pathways that link T2D to vascular outcomes.

The control of ice growth in ice slurry is important for many fields, including (a) the cooling of the brain during cardiac arrest, (b) the storage and transportation of fresh fish and fruits, and (c) the development of distributed air-conditioning systems. One of the promising methods for the control is to use a substance such as antifreeze protein. We have observed and report here growth states of ice particles in both quiescent and flowing aqueous solutions of winter flounder antifreeze proteins in mini-channels with a microscope. We also measured ice growth rates. Our aim was to improve the levels of ice growth inhibition by subjecting the antifreeze protein solution both to preheating and to concentrating by ultrafiltration. We have found that the ice growth inhibition by the antifreeze protein decreased in flowing solutions compared with that in quiescent solutions. In addition, unlike unidirectional freezing experiments, the preheating of the antifreeze protein solution reduced the ice growth inhibition properties. This is because the direction of flow, containing HPLC6 and its aggregates, to the ice particle surfaces can change as the ice particle grows, and thus the probability of interaction between HPLC6 and ice surfaces does not increase. In contrast to this, ultrafiltration after preheating the solution improved the ice growth inhibition. This may be due to the interaction between ice surfaces and many aggregates in the concentrates.

Introduction: Severe elevations of LDL-Cholesterol (LDL-C) ≥190mg/dl in adults, representing the familial hypercholesterolemia (FH) phenotype, have been associated with increased risk of cardiovascular disease (CVD). The 2013 AHA/ACC guidelines recommend high intensity statin therapy to reduce LDL-C by ≥50%. We identified patients with FH phenotype in the Veterans Health Administration (VHA) who were statin-naive and determined the degree of LDL-C reduction over one year after statin initiation and the efficacy of statin intensity on ≥50% reduction. Methods: Patients receiving care at the VHA from 2002-2007, ≥21 years of age, with baseline LDL-C measurement of ≥190 mg/dl (LDL-C 0 ), and statin-naïve were included. Statin initiation was required within 90 days of LDL-C 0 , and a follow up level (LDL-C 1 ) had to be collected within one year ± 90 days. All participants were free of clinical CVD at baseline. Baseline characteristics were ascertained from patient charts. LDL-C reduction was defined as the difference between LDL-C 0 and LDL-C 1 . Multivariable logistic regression models, adjusted for age, sex, race, diabetes, kidney disease, hypertension, and hypertension treatment were constructed to determine the odds of goal LDL-C (≥50%) reduction by statin intensity. We defined statin intensity per the 2013 AHA/ACC guidelines. High intensity statins included Simvastatin 80mg, Atorvastatin 40-80mg, and Rosuvastatin 20-40mg. Results: We included 35,894 Veterans (Men: N= 33,049 (92.1%), Age=55±10 years; Women: N=2845 (7.9%), Age=50±11 years). The mean duration between LDL-C 0 and LDL-C 1 was 52±7 weeks. The population was predominantly white (78.1%). Mean LDL-C 0 was 210±22 mg/dl, triglycerides were 175±126 mg/dl. At baseline, 0.3% had kidney disease, 14.1% diabetes, and 52.8% hypertension. Mean absolute LDL-C reduction in the population was 70.2±41.9 mg/dl. A total of 6718 (18.7%) patients achieved an LDL-C reduction of ≥50%. Among these patients, 5.2% were on low, 62.2% were on moderate, and 32.6% were on high intensity statins. In multivariable-adjusted logistic regression models using moderate intensity statins as the comparator, high intensity therapy resulted in 97% higher odds of achieving goal LDL-C reduction (Odds ratio [OR]=1.97; 95% Confidence Interval [CI]=1.85-2.09), and low intensity statins resulted in 42% lower odds of achieving goal LDL-C reduction (OR= 0.58; 95%CI= 0.52-0.65). Conclusions: In a large veteran population with the FH phenotype, though there was a marked reduction in LDL-C with statin therapy, most patients did not achieve goal LDL-C reduction of ≥50%. This may be related to statin intensity, individual response to statin therapy, or lack of adherence to treatment. In multivariable-adjusted logistic regression models, patients on high intensity statins had 2-fold odds of goal LDL-C reduction compared to moderate intensity statins.