Optimum spectral window for imaging of art with optical coherence tomography

Optical Coherence Tomography (OCT) has been shown to have potential for important applications in the field of art conservation and archaeology due to its ability to image subsurface microstructures non-invasively. However, its depth of penetration in painted objects is limited due to the strong scattering properties of artists’ paints. VIS-NIR (400 nm – 2400 nm) reflectance spectra of a wide variety of paints made with historic artists’ pigments have been measured. The best spectral window with which to use optical coherence tomography (OCT) for the imaging of subsurface structure of paintings was found to be around 2.2 μm. The same spectral window would also be most suitable for direct infrared imaging of preparatory sketches under the paint layers. The reflectance spectra from a large sample of chemically verified pigments provide information on the spectral transparency of historic artists’ pigments/paints as well as a reference set of spectra for pigment identification. The results of the paper suggest that broadband sources at ~2 microns are highly desirable for OCT applications in art and potentially material science in general

Prenatal Household Air Pollution Exposure and Childhood Blood Pressure in Rural Ghana.

BACKGROUND: The association between prenatal household air pollution (HAP) exposure and childhood blood pressure (BP) is unknown. OBJECTIVE: Within the Ghana Randomized Air Pollution and Health Study (GRAPHS) we examined time-varying associations between a) maternal prenatal and b) first-year-of-life HAP exposure with BP at 4 years of age and, separately, whether a stove intervention delivered prenatally and continued through the first year of life could improve BP at 4 years of age. METHODS: GRAPHS was a cluster-randomized cookstove intervention trial wherein n=1,414 pregnant women were randomized to one of two stove interventions: a) a liquefied petroleum gas (LPG) stove or improved biomass stove, or b) control (open fire cooking). Maternal HAP exposure over pregnancy and child HAP exposure over the first year of life was quantified by repeated carbon monoxide (CO) measurements; a subset of women (n=368) also performed one prenatal and one postnatal personal fine particulate matter (PM2.5) measurement. Systolic and diastolic BP (SBP and DBP) were measured in n=667 4-y-old children along with their PM2.5 exposure (n=692). We examined the effect of the intervention on resting BP z-scores. We also employed reverse distributed lag models to examine time-varying associations between a) maternal prenatal and b) first-year-of-life HAP exposure and resting BP z-scores. Among those with PM2.5 measures, we examined associations between PM2.5 and resting BP z-scores. Sex-specific effects were considered. RESULTS: Intention-to-treat analyses identified that DBP z-score at 4 years of age was lower among children born in the LPG arm (LPG β=-0.20; 95% CI: -0.36, -0.03) as compared with those in the control arm, and females were most susceptible to the intervention. Higher CO exposure in late gestation was associated with higher SBP and DBP z-score at 4 years of age, whereas higher late-first-year-of-life CO exposure was associated with higher DBP z-score. In the subset with PM2.5 measurements, higher maternal postnatal PM2.5 exposure was associated with higher SBP z-scores. DISCUSSION: These findings suggest that prenatal and first-year-of-life HAP exposure are associated with child BP and support the need for reductions in exposure to HAP, with interventions such as cleaner cooking beginning in pregnancy. https://doi.org/10.1289/EHP13225

Synthesis and functionalization of azetidine‐containing small macrocyclic peptides

Cyclic peptides are increasingly important structures in drugs but their development can be impeded by difficulties associated with their synthesis. Here, we introduce the 3-aminoazetidine (3-AAz) subunit as a new turn-inducing element for the efficient synthesis of small head-to-tail cyclic peptides. Greatly improved cyclizations of tetra-, penta- and hexapeptides (28 examples) under standard reaction conditions are achieved by introduction of this element within the linear peptide precursor. Post-cyclization deprotection of the amino acid side chains with strong acid is realized without degradation of the strained four-membered azetidine. An special feature of this chemistry is that further late-stage modification of the resultant macrocyclic peptides can be achieved via the 3-AAz unit. This is done by: (i) chemoselective deprotection and substitution at the azetidine nitrogen, or by (ii) a click-based approach employing a 2-propynyl carbamate on the azetidine nitrogen. In this way, a range of dye and biotin tagged macrocycles are readily produced. Structural insights gained by XRD analysis of a cyclic tetrapeptide indicate that the azetidine ring encourages access to the less stable, all-trans conformation. Moreover, introduction of a 3-AAz into a representative cyclohexapeptide improves stability towards proteases compared to the homodetic macrocycle

Synthesis and Functionalization of Azetidine‐Containing Small Macrocyclic Peptides

Cyclic peptides are increasingly important structures in drugs but their development can be impeded by difficulties associated with their synthesis. Here, we introduce the 3-aminoazetidine (3-AAz) subunit as a new turn-inducing element for the efficient synthesis of small head-to-tail cyclic peptides. Greatly improved cyclizations of tetra-, penta- and hexapeptides (28 examples) under standard reaction conditions are achieved by introduction of this element within the linear peptide precursor. Post-cyclization deprotection of the amino acid side chains with strong acid is realized without degradation of the strained four-membered azetidine. A special feature of this chemistry is that further late-stage modification of the resultant macrocyclic peptides can be achieved via the 3-AAz unit. This is done by: (i) chemoselective deprotection and substitution at the azetidine nitrogen, or by (ii) a click-based approach employing a 2-propynyl carbamate on the azetidine nitrogen. In this way, a range of dye and biotin tagged macrocycles are readily produced. Structural insights gained by XRD analysis of a cyclic tetrapeptide indicate that the azetidine ring encourages access to the less stable, all-trans conformation. Moreover, introduction of a 3-AAz into a representative cyclohexapeptide improves stability towards proteases compared to the homodetic macrocycle

TAME 2.0: expanding and improving online data science training for environmental health research

IntroductionData science training has the potential to propel environmental health research efforts into territories that remain untapped and holds immense promise to change our understanding of human health and the environment. Though data science training resources are expanding, they are still limited in terms of public accessibility, user friendliness, breadth of content, tangibility through real-world examples, and applicability to the field of environmental health science.MethodsTo fill this gap, we developed an environmental health data science training resource, the inTelligence And Machine lEarning (TAME) Toolkit, version 2.0 (TAME 2.0).ResultsTAME 2.0 is a publicly available website that includes training modules organized into seven chapters. Training topics were prioritized based upon ongoing engagement with trainees, professional colleague feedback, and emerging topics in the field of environmental health research (e.g., artificial intelligence and machine learning). TAME 2.0 is a significant expansion upon the original TAME training resource pilot. TAME 2.0 specifically includes training organized into the following chapters: (1) Data management to enable scientific collaborations; (2) Coding in R; (3) Basics of data analysis and visualizations; (4) Converting wet lab data into dry lab analyses; (5) Machine learning; (6) Applications in toxicology and exposure science; and (7) Environmental health database mining. Also new to TAME 2.0 are “Test Your Knowledge” activities at the end of each training module, in which participants are asked additional module-specific questions about the example datasets and apply skills introduced in the module to answer them. TAME 2.0 effectiveness was evaluated via participant surveys during graduate-level workshops and coursework, as well as undergraduate-level summer research training events, and suggested edits were incorporated while overall metrics of effectiveness were quantified.DiscussionCollectively, TAME 2.0 now serves as a valuable resource to address the growing demand of increased data science training in environmental health research. TAME 2.0 is publicly available at: https://uncsrp.github.io/TAME2/

Sex differences in oncogenic mutational processes.

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.

OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies. PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Surplus Food and the Rise of Charitable Food Provision

Many wealthy but unequal countries have seen a significant expansion in systematized charitable food provision, usually in the form of food banks and food pantries. The use of food charity as a way to manage both food surplus and household food insecurity was pioneered in the United States at a time of cuts to cash-based welfare entitlements. It has expanded to Canada, Europe, Australia, and a growing number of middle-income countries, often in the wake of socio-ecological crisis including recession and pandemic, but also ideological shifts around effective and just solutions to poverty and inequality. While food charity is often presented as a “win-win” solution to food waste and hunger, it has been criticized from numerous perspectives that are explored in the article, including the argument that corporate-backed food charity in its currently expanding form masks structural causes and thus fails to resolve either problem, while offering a largely inadequate and undignified food offer to marginalized people. Alternative solutions include rights-based policies to ensure people’s access to basic needs, mutual aid in the face of systemic precarity, and movements for food sovereignty as means to address both ecological and social harms caused by existing food production and distribution systems