Quantifying the timescales of fluid-rock interaction on Mars using the nakhlite meteorites

Etch pits within olivine grains from the nakhlite meteorites reveal the magnitude and timescale of water-mediated alteration of the martian crust

The nakhlite meteorites provide evidence for mineralization of martian CO2 by carbonation of silicates

Evidence from the Lafayette meteorite shows that carbon dioxide could have been sequestered very effectively from the martian atmosphere by mineral carbonation

Associations between diabetes and both cardiovascular disease and all-cause mortality are modified by grip strength: evidence from UK Biobank, a prospective population-based cohort study

OBJECTIVE Grip strength and diabetes are predictors of mortality and cardiovascular disease (CVD), but whether these risk factors interact to predispose to adverse health outcomes is unknown. This study determined the interactions between diabetes and grip strength and their association with health outcomes. RESEARCH DESIGN AND METHODS We undertook a prospective, general population cohort study by using UK Biobank. Cox proportional hazards models were used to explore the associations between both grip strength and diabetes and the outcomes of all-cause mortality and CVD incidence/mortality as well as to test for interactions between diabetes and grip strength. RESULTS 347,130 UK Biobank participants with full data available (mean age 55.9 years, BMI 27.2 kg/m2, 54.2% women) were included in the analysis, of which 13,373 (4.0%) had diabetes. Over a median follow-up of 4.9 years (range 3.3–7.8 years), 6,209 died (594 as a result of CVD), and 4,301 developed CVD. Participants with diabetes were at higher risk of all-cause and CVD mortality and CVD incidence. Significant interactions (P < 0.05) existed whereby the risk of CVD mortality was higher in participants with diabetes with low (hazard ratio [HR] 4.05 [95% CI 2.72, 5.80]) versus high (HR 1.46 [0.87, 2.46]) grip strength. Similar results were observed for all-cause mortality and CVD incidence. CONCLUSIONS Risk of adverse health outcomes among people with diabetes is lower in those with high grip strength. Low grip strength may be useful to identify a higher-risk subgroup of patients with diabetes. Intervention studies are required to determine whether resistance exercise can reduce risk

The chronology and tectonic style of landscape evolution along the elevated Atlantic continental margin of South Africa resolved by joint apatite fission track and (U-Th-Sm)/He thermochronology

Atlantic-type continental margins have long been considered “passive” tectonic settings throughout the entire postrift phase. Recent studies question the long-term stability of these margins and have shown that postrift uplift and reactivation of preexisting structures may be a common feature of a continental margin’s evolution. The Namaqualand sector of the western continental margin of South Africa is characterized by a ubiquitously faulted basement but lacks preservation of younger geological strata to constrain postrift tectonic fault activity. Here we present the first systematic study using joint apatite fission track and apatite (U-Th-Sm)/He thermochronology to achieve a better understanding on the chronology and tectonic style of landscape evolution across this region. Apatite fission track ages range from 58.3 ± 2.6 to 132.2 ± 3.6Ma, with mean track lengths between 10.9 ± 0.19 and 14.35 ± 0.22 μm, and mean (U-Th-Sm)/He sample ages range from 55.8 ± 31.3 to 120.6 ± 31.4Ma. Joint inverse modeling of these data reveals two distinct episodes of cooling at approximately 150–130Ma and 110–90Ma with limited cooling during the Cenozoic. Estimates of denudation based on these thermal histories predict approximately 1–3 km of denudation coinciding with two major tectonic events. The first event, during the Early Cretaceous, was driven by continental rifting and the development and removal of synrift topography. The second event, during the Late Cretaceous, includes localized reactivation of basement structures as well as regional mantle-driven uplift. Relative tectonic stability prevailed during the Cenozoic, and regional denudation over this time is constrained to be less than 1 km

The impact of confounding on the associations of different adiposity measures with the incidence of cardiovascular disease: a cohort study of 296 535 adults of white European descent

Aims: The data regarding the associations of body mass index (BMI) with cardiovascular (CVD) risk, especially for those at the low categories of BMI, are conflicting. The aim of our study was to examine the associations of body composition (assessed by five different measures) with incident CVD outcomes in healthy individuals. Methods and results: A total of 296 535 participants (57.8% women) of white European descent without CVD at baseline from the UK biobank were included. Exposures were five different measures of adiposity. Fatal and non-fatal CVD events were the primary outcome. Low BMI (≤18.5 kg m−2) was associated with higher incidence of CVD and the lowest CVD risk was exhibited at BMI of 22–23 kg m−2 beyond, which the risk of CVD increased. This J-shaped association attenuated substantially in subgroup analyses, when we excluded participants with comorbidities. In contrast, the associations for the remaining adiposity measures were more linear; 1 SD increase in waist circumference was associated with a hazard ratio of 1.16 [95% confidence interval (CI) 1.13–1.19] for women and 1.10 (95% CI 1.08–1.13) for men with similar magnitude of associations for 1 SD increase in waist-to-hip ratio, waist-to-height ratio, and percentage body fat mass. Conclusion: Increasing adiposity has a detrimental association with CVD health in middle-aged men and women. The association of BMI with CVD appears more susceptible to confounding due to pre-existing comorbidities when compared with other adiposity measures. Any public misconception of a potential ‘protective’ effect of fat on CVD risk should be challenged

Dietary fat and total energy intake modifies the association of genetic profile risk score on obesity: evidence from 48 170 UK Biobank participants

Background: Obesity is a multifactorial condition influenced by both genetics and lifestyle. The aim of this study was to investigate whether the association between a validated genetic profile risk score for obesity (GPRS-obesity) and body mass index (BMI) or waist circumference (WC) was modified by macronutrient intake in a large general population study. Methods: This study included cross-sectional data from 48 170 white European adults, aged 37–73 years, participating on the UK Biobank. Interactions between GPRS-obesity, and macronutrient intake (including total energy, protein, fat, carbohydrate and dietary fibre intake) and its effects on BMI and WC were investigated. Results: The 93-SNPs genetic profile risk score was associated with a higher BMI (β:0.57 kg.m−2 per standard deviation (s.d.) increase in GPRS, [95%CI:0.53–0.60]; P=1.9 × 10−183) independent of major confounding factors. There was a significant interaction between GPRS and total fat intake (P[interaction]=0.007). Among high fat intake individuals, BMI was higher by 0.60 [0.52, 0.67] kg.m−2 per s.d. increase in GPRS-obesity; the change in BMI with GPRS was lower among low fat intake individuals (β:0.50 [0.44, 0.57] kg.m-2). Significant interactions with similar patterns were observed for saturated fat intake (High β:0.66 [0.59, 0.73] versus Low β:0.49 [0.42, 0.55] kg.m-2, P-interaction=2 × 10-4), and total energy intake (High β:0.58 [0.51, 0.64] versus Low β:0.49 [0.42, 0.56] kg.m−2, P-interaction=0.019), but not for protein intake, carbohydrate intake and fiber intake (P-interaction >0.05). The findings were broadly similar using WC as the outcome. Conclusions: These data suggest that the benefits of reducing the intake of fats and total energy intake, may be more important in individuals with high genetic risk for obesity

Associations of grip strength with cardiovascular, respiratory, and cancer outcomes and all cause mortality: prospective cohort study of half a million UK Biobank participants

Objective: To investigate the association of grip strength with disease specific incidence and mortality and whether grip strength enhances the prediction ability of an established office based risk score. Design: Prospective population based study. Setting: UK Biobank. Participants: 502 293 participants (54% women) aged 40-69 years. Main outcome measures: All cause mortality as well as incidence of and mortality from cardiovascular disease, respiratory disease, chronic obstructive pulmonary disease, and cancer (all cancer, colorectal, lung, breast, and prostate). Results: Of the participants included in analyses, 13 322 (2.7%) died over a mean of 7.1 (range 5.3-9.9) years’ follow-up. In women and men, respectively, hazard ratios per 5 kg lower grip strength were higher (all at P<0.05) for all cause mortality (1.20, 95% confidence interval 1.17 to 1.23, and 1.16, 1.15 to 1.17) and cause specific mortality from cardiovascular disease (1.19, 1.13 to 1.25, and 1.22, 1.18 to 1.26), all respiratory disease (1.31, 1.22 to 1.40, and 1.24, 1.20 to 1.28), chronic obstructive pulmonary disease (1.24, 1.05 to 1.47, and 1.19, 1.09 to 1.30), all cancer (1.17, 1.13 to 1.21, 1.10, 1.07 to 1.13), colorectal cancer (1.17, 1.04 to 1.32, and 1.18, 1.09 to 1.27), lung cancer (1.17, 1.07 to 1.27, and 1.08, 1.03 to 1.13), and breast cancer (1.24, 1.10 to 1.39) but not prostate cancer (1.05, 0.96 to 1.15). Several of these relations had higher hazard ratios in the younger age group. Muscle weakness (defined as grip strength <26 kg for men and <16 kg for women) was associated with a higher hazard for all health outcomes, except colon cancer in women and prostate cancer and lung cancer in both men and women. The addition of handgrip strength improved the prediction ability, based on C index change, of an office based risk score (age, sex, diabetes diagnosed, body mass index, systolic blood pressure, and smoking) for all cause (0.013) and cardiovascular mortality (0.012) and incidence of cardiovascular disease (0.009). Conclusion: Higher grip strength was associated with a range of health outcomes and improved prediction of an office based risk score. Further work on the use of grip strength in risk scores or risk screening is needed to establish its potential clinical utility

Optimization of combined temozolomide and peptide receptor radionuclide therapy (PRRT) in mice after multimodality molecular imaging studies

Background: Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine tumours (NET) comprise somatostatin-analogue lutetium-177-labelled octreotate (177Lu-TATE) treatment, also referred to as peptide receptor radionuclide therapy (PRRT), and temozolomide (TMZ) treatment. Their combination might result in additive effects. Using MRI and SPECT/CT, we studied tumour characteristics and therapeutic responses after different (combined) administration schemes in a murine tumour model in order to identify the optimal treatment schedule for PRRT plus TMZ. Methods: We performed molecular imaging studies in mice bearing SSTR-expressing H69 (humane small cell lung cancer) tumours after single intravenous (i.v.) administration of 30 MBq 177Lu-TATE or

The nakhlite meteorites provide evidence for mineralization of martian CO2 by carbonation of silicates

Evidence from the Lafayette meteorite shows that carbon dioxide could have been sequestered very effectively from the martian atmosphere by mineral carbonation

Hydrophobic and ionic-interactions in bulk and confined water with implications for collapse and folding of proteins

Water and water-mediated interactions determine thermodynamic and kinetics of protein folding, protein aggregation and self-assembly in confined spaces. To obtain insights into the role of water in the context of folding problems, we describe computer simulations of a few related model systems. The dynamics of collapse of eicosane shows that upon expulsion of water the linear hydrocarbon chain adopts an ordered helical hairpin structure with 1.5 turns. The structure of dimer of eicosane molecules has two well ordered helical hairpins that are stacked perpendicular to each other. As a prelude to studying folding in confined spaces we used simulations to understand changes in hydrophobic and ionic interactions in nano droplets. Solvation of hydrophobic and charged species change drastically in nano water droplets. Hydrophobic species are localized at the boundary. The tendency of ions to be at the boundary where water density is low increases as the charge density decreases. Interaction between hydrophobic, polar, and charged residue are also profoundly altered in confined spaces. Using the results of computer simulations and accounting for loss of chain entropy upon confinement we argue and then demonstrate, using simulations in explicit water, that ordered states of generic amphiphilic peptide sequences should be stabilized in cylindrical nanopores