We demonstrate a new type of analysis for the DRIFT-IId directional dark matter detector using a machine learning algorithm called a Random Forest Classifier. The analysis labels events as signal or ...background based on a series of selection parameters, rather than solely applying hard cuts. The analysis efficiency is shown to be comparable to our previous result at high energy but with increased efficiency at lower energies. This leads to a projected sensitivity enhancement of one order of magnitude below a WIMP mass of 15 GeV c\(^{-2}\) and a projected sensitivity limit that reaches down to a WIMP mass of 9 GeV c\(^{-2}\), which is a first for a directionally sensitive dark matter detector.
Soil organic matter (SOM) is considered to be key to sustainability of agriculture in the tropics. In southern Brazil, no-tillage has been adopted widely to control soil erosion, but its impact on ...the dynamics of SOM is not well established. We measured soil carbon (C) and delta13C in two crop rotations, one of which contained C4 maize (Zea mays L.), after 21 years of contrasting tillage (conventional tillage versus no-tillage). Adjacent sites that reflected historic land-uses were also sampled. In the tillage experiment there was no effect of tillage on the total amount of C in the 0-40 cm profile (even when contrasting bulk density was accounted for), and the concentration of C differed only in the 0-5 cm and 5-10 cm layers. However, the occasional input of C4 material in the maize rotation resulted in a significant effect of rotation on delta13C (P<0.001). Using 13C as a tracer for the SOM formed since the start of the experiment, we estimated the abundance of 'recent' and 'old' C within each depth interval. We found the main effect of tillage was to increase the medium-term turnover of SOM, particularly in the subsoil (i.e. below 20 cm depth). Compared with no-tillage, there was almost five times more recent C in the subsoil, and 20% more recent C in the 0-40 cm profile as a whole.
The implications of different adiposity measures on cardiovascular disease etiology remain unclear. In this article, we quantify and contrast causal associations of central adiposity (waist-to-hip ...ratio adjusted for body mass index WHRadjBMI) and general adiposity (body mass index BMI) with cardiometabolic disease.
Ninety-seven independent single-nucleotide polymorphisms for BMI and 49 single-nucleotide polymorphisms for WHRadjBMI were used to conduct Mendelian randomization analyses in 14 prospective studies supplemented with coronary heart disease (CHD) data from CARDIoGRAMplusC4D (Coronary Artery Disease Genome-wide Replication and Meta-analysis CARDIoGRAM plus The Coronary Artery Disease C4D Genetics; combined total 66 842 cases), stroke from METASTROKE (12 389 ischemic stroke cases), type 2 diabetes mellitus from DIAGRAM (Diabetes Genetics Replication and Meta-analysis; 34 840 cases), and lipids from GLGC (Global Lipids Genetic Consortium; 213 500 participants) consortia. Primary outcomes were CHD, type 2 diabetes mellitus, and major stroke subtypes; secondary analyses included 18 cardiometabolic traits.
Each one standard deviation (SD) higher WHRadjBMI (1 SD≈0.08 U) associated with a 48% excess risk of CHD (odds ratio OR for CHD, 1.48; 95% confidence interval CI, 1.28-1.71), similar to findings for BMI (1 SD≈4.6 kg/m
; OR for CHD, 1.36; 95% CI, 1.22-1.52). Only WHRadjBMI increased risk of ischemic stroke (OR, 1.32; 95% CI, 1.03-1.70). For type 2 diabetes mellitus, both measures had large effects: OR, 1.82 (95% CI, 1.38-2.42) and OR, 1.98 (95% CI, 1.41-2.78) per 1 SD higher WHRadjBMI and BMI, respectively. Both WHRadjBMI and BMI were associated with higher left ventricular hypertrophy, glycemic traits, interleukin 6, and circulating lipids. WHRadjBMI was also associated with higher carotid intima-media thickness (39%; 95% CI, 9%-77% per 1 SD).
Both general and central adiposity have causal effects on CHD and type 2 diabetes mellitus. Central adiposity may have a stronger effect on stroke risk. Future estimates of the burden of adiposity on health should include measures of central and general adiposity.
It is unclear whether C-reactive protein (CRP) is causally related to coronary heart disease (CHD). Genetic variants that are known to be associated with CRP levels can be used to provide causal ...inference of the effect of CRP on CHD. Our objective was to examine the association between CRP genetic variant +1444C>T (rs1130864) and CHD risk in the largest study to date of this association.
We estimated the association of CRP genetic variant +1444C>T (rs1130864) with CRP levels and with CHD in five studies and then pooled these analyses (N = 18,637 participants amongst whom there were 4,610 cases). CRP was associated with potential confounding factors (socioeconomic position, physical activity, smoking and body mass) whereas genotype (rs1130864) was not associated with these confounders. The pooled odds ratio of CHD per doubling of circulating CRP level after adjustment for age and sex was 1.13 (95%CI: 1.06, 1.21), and after further adjustment for confounding factors it was 1.07 (95%CI: 1.02, 1.13). Genotype (rs1130864) was associated with circulating CRP; the pooled ratio of geometric means of CRP level among individuals with the TT genotype compared to those with the CT/CC genotype was 1.21 (95%CI: 1.15, 1.28) and the pooled ratio of geometric means of CRP level per additional T allele was 1.14 (95%CI: 1.11, 1.18), with no strong evidence in either analyses of between study heterogeneity (I(2) = 0%, p>0.9 for both analyses). There was no association of genotype (rs1130864) with CHD: pooled odds ratio 1.01 (95%CI: 0.88, 1.16) comparing individuals with TT genotype to those with CT/CC genotype and 0.96 (95%CI: 0.90, 1.03) per additional T allele (I(2)<7.5%, p>0.6 for both meta-analyses). An instrumental variables analysis (in which the proportion of CRP levels explained by rs1130864 was related to CHD) suggested that circulating CRP was not associated with CHD: the odds ratio for a doubling of CRP level was 1.04 (95%CI: 0.61, 1.80).
We found no association of a genetic variant, which is known to be related to CRP levels, (rs1130864) and having CHD. These findings do not support a causal association between circulating CRP and CHD risk, but very large, extended, genetic association studies would be required to rule this out.
In January to February 2014, 16 hand, foot and mouth disease (HFMD) cases were identified in Edinburgh, United Kingdom. All presented with atypical features, with most (n=13) resembling eczema ...herpeticum or chickenpox. Coxsackievirus A6 (CV-A6) was identified in all the typed cases (n=11). As atypical forms of HFMD associated with CV-A6 are likely to emerge throughout Europe, clinicians should be alert to unusual clinical presentations of HFMD and virologists aware of effective diagnostic testing and enterovirus typing methods.
Abstract
Study question
Is extended oocyte cryostorage period associated with decreased post-warm survival rate?
Summary answer
There is a weak inverse correlation between oocyte cryostorage duration ...and post-warm survival (r = 0.09, p = 0.01). This equates clinically to a reduction of 0.0003% survival/day.
What is known already
It is widely reported that extended embryo storage is not associated with reduced post-warm survival rates, however there are no such studies in the literature relating to the effect of extended cryostorage duration on oocytes.
Successful outcomes from oocyte vitrification are related to reduced patient age however UK government regulations only permit those with a medical indication to store and use their gametes over 10 years.
With the intended extension of this 10-year limit, it is therefore fair for clinics to expect an increasing population of younger patients choosing to store their oocytes for longer periods.
Study design, size, duration
A retrospective audit of all vitrified/warmed oocyte cycles at a single centre from 2014-2021. A total of 5208 oocytes were included in the study, from 602 treatment cycles.
Participants/materials, setting, methods
Patients of all ages were included in the study. Data was obtained retrospectively from IDEAS V6.0 at CRGH, UK. All oocytes were vitrified/warmed according to the Irvine Scientific/Kitazato media protocols, with all other protocols excluded. Data was analysed using IBM® SPSS® Statistics V24. Kendall’s tau-b and Spearman’s Rho correlation coefficients measured the strength and direction of association between variables. A linear regression model was used to establish the effect of duration on survival per day.
Main results and the role of chance
The median age at oocyte vitrification was 31 years (range 18-45 years, LQR=25 years, UQR=37 years). There was a median of 8 oocytes thawed per case (LQR=6, UQR 11 oocytes) with a median of 6 oocytes surviving (LQR=3, UQR=9 oocytes). The median survival rate across all ages was 81% (LQR=58%, UQR=100%). There was no significant difference in oocyte survival rate between age categories (<35 years vs > 35 years; p = 0.137, n = 414 & 188 respectively). Increasing age was however, significantly correlated with fewer oocytes vitrified (r = 0.283, p = 0.001).
There is a weak inverse correlation between oocyte cryostorage duration and post-warm survival (r = 0.09). This correlation reaches statistical significance (p = 0.01), however this equates clinically to a reduction of 0.0003% survival rate per day.
No significant difference was observed in post-warm oocyte survival rate across duration of vitrification categories (≤3 years vs 4-5 years vs > 5 years; p = 0.154, n = 416, 141 & 45 cases respectively).
The median duration for which oocytes remained in cryostorage was 565 days (1.6 years) (LQR & UQR=233 days (0.64 years) and 1390 days (3.8 years) respectively).
Limitations, reasons for caution
Although retrospective, the study benefits from many cycles, all of which were carried out at the same unit, using the same vitrification/warming media protocol. Limitations of this study include a relatively short median cryostorage duration time which could be masking the true effect of duration on post-warm oocyte survival.
Wider implications of the findings
Following a public consultation in 2020 regarding the 10-year storage limit for gametes and embryos, the UK Government proposed changes the current legislation which will allow patients to extend cryostorage beyond 10 years without a medical indication. To our knowledge, this is the first study to lend support this movement.
Trial registration number
IRB-001C03-01-22
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