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The recent FDA marketing authorizations granted for testing for mutations associated with hereditary breast and colon cancer, as well as pharmacogenomic susceptibilities, provide an opportunity to re-examine the medical as well as regulatory underpinnings of DTC genetic testing. In this chapter, we first examine the historical emergence of enabling technologies that have provided for the availability of DNA sequence information on a broad scale, the efforts by the medical community to incorporate these advances into models of “precision” or “personalized” medicine, and the risks and benefits of offering access to DNA germline sequence analysis outside of the traditional medical model. We then turn to the current and proposed regulatory schemes to provide oversight over DTC genetic testing, with a focus on the role of the FDA as an information regulator and guardian of public health and safety.
Hospital healthcare workers (HCWs) are at increased risk of contracting COVID-19 infection. We aimed to determine the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in HCWs in Ireland. Two tertiary referral hospitals in Irish cities with diverging community incidence and seroprevalence were identified; COVID-19 had been diagnosed in 10.2% and 1.8% of staff respectively by the time of the study (October 2020). All staff of both hospitals (N = 9038) were invited to participate in an online questionnaire and blood sampling for SARS-CoV-2 antibody testing. Frequencies and percentages for positive SARS-CoV-2 antibody were calculated and adjusted relative risks (aRR) for participant characteristics were calculated using multivariable regression analysis. In total, 5788 HCWs participated (64% response rate). Seroprevalence of antibodies to SARS-CoV-2 was 15% and 4.1% in hospitals 1 and 2, respectively. Thirty-nine percent of infections were previously undiagnosed. Risk for seropositivity was higher for healthcare assistants (aRR 2.0, 95% confidence interval (CI) 1.4–3.0), nurses (aRR: 1.6, 95% CI 1.1–2.2), daily exposure to patients with COVID-19 (aRR: 1.6, 95% CI 1.2–2.1), age 18–29 years (aRR: 1.4, 95% CI 1.1–1.9), living with other HCWs (aRR: 1.3, 95% CI 1.1–1.5), Asian background (aRR: 1.3, 95% CI 1.0–1.6) and male sex (aRR: 1.2, 95% CI 1.0–1.4). The HCW seroprevalence was six times higher than community seroprevalence. Risk was higher for those with close patient contact. The proportion of undiagnosed infections call for robust infection control guidance, easy access to testing and consideration of screening in asymptomatic HCWs. With emerging evidence of reduction in transmission from vaccinated individuals, the authors strongly endorse rapid vaccination of all HCWs.
To assess the relationship between food insecurity, sleep quality, and days with mental and physical health issues among college students.
An online survey was administered. Food insecurity was assessed using the ten-item Adult Food Security Survey Module. Sleep was measured using the nineteen-item Pittsburgh Sleep Quality Index (PSQI). Mental health and physical health were measured using three items from the Healthy Days Core Module. Multivariate logistic regression was conducted to assess the relationship between food insecurity, sleep quality, and days with poor mental and physical health.
Twenty-two higher education institutions.
College students (n 17 686) enrolled at one of twenty-two participating universities.
Compared with food-secure students, those classified as food insecure (43·4 %) had higher PSQI scores indicating poorer sleep quality (P < 0·0001) and reported more days with poor mental (P < 0·0001) and physical (P < 0·0001) health as well as days when mental and physical health prevented them from completing daily activities (P < 0·0001). Food-insecure students had higher adjusted odds of having poor sleep quality (adjusted OR (AOR): 1·13; 95 % CI 1·12, 1·14), days with poor physical health (AOR: 1·01; 95 % CI 1·01, 1·02), days with poor mental health (AOR: 1·03; 95 % CI 1·02, 1·03) and days when poor mental or physical health prevented them from completing daily activities (AOR: 1·03; 95 % CI 1·02, 1·04).
College students report high food insecurity which is associated with poor mental and physical health, and sleep quality. Multi-level policy changes and campus wellness programmes are needed to prevent food insecurity and improve student health-related outcomes.
The C677T polymorphism in the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) is associated with hypertension. Riboflavin acts as a cofactor for MTHFR in one-carbon metabolism which generates methyl groups for utilisation in important biological reactions such as DNA methylation. Supplementation with riboflavin has previously been shown to lower blood pressure in individuals with the MTHFR 677TT genotype. The mechanism regulating this gene-nutrient interaction is currently unknown but may involve aberrant DNA methylation which has been implicated hypertension.
The aims of this study were to examine DNA methylation of hypertension-related genes in adults stratified by MTHFR C677T genotype and the effect of riboflavin supplementation on DNA methylation of these genes in individuals with the MTHFR 677TT genotype.
Materials and Methods:
We measured DNA methylation using pyrosequencing in a set of candidate genes associated with hypertension including angiotensin II receptor type 1 (AGTR1), G nucleotide binding protein subunit alpha 12 (GNA12), insulin-like growth factor 2 (IGF2) and nitric oxide synthase 3 (NOS3). Stored peripheral blood leukocyte samples from participants previously screened for the MTHFR C677T genotype who participated in targeted randomised controlled trials (1.6mg/d riboflavin or placebo for 16 weeks) at Ulster University were accessed for this analysis (n = 120).
There were significant differences in baseline average methylation between MTHFR CC and TT genotypes at NOS3 (p = 0.026) and AGTR1 (p = 0.045) loci. Riboflavin supplementation in the TT genotype group resulted in altered average methylation at IGF2 (p = 0.025) and CpG site-specific alterations at the AGTR1 and GNA12 loci.
DNA methylation at genes related to hypertension were significantly different in individuals stratified by MTHFR genotype group. Furthermore, in MTHFR 677TT genotype individuals, there were concurrent alterations in DNA methylation at genes linked to hypertension in response to riboflavin supplementation. This is the largest study to date to demonstrate an interaction between DNA methylation of hypertension-related genes and riboflavin supplementation in adults with the MTHFR 677TT genotype. Further work using a genome-wide approach is required to better understand the role of riboflavin in altering DNA methylation in these genetically at-risk individuals.
Resolved emission from gas-phase methanol can reveal the abundance and distribution of the comet-forming ice reservoir in protoplanetary disks. ALMA Cycle 4 observations of four transitions of gas-phase methanol in TW Hya allow the first model-independent determination of the rotational temperature of methanol in a prototoplanetary disk. The data confirm that the methanol is rotationally cold (Trot < 50 K), and well constrain the column density to 2 × 1012 cm−2. Astrochemical models will constrain the chemical origin of methanol in TW Hya.
The Earth is dramatically carbon poor comparing to the interstellar medium and the proto-sun. The carbon to silicon ratios in inner solar system objects show a correlation with heliocentric distance, which suggests that the destruction of carbon grains has occurred before planet formation. To examine this hypothesis, we perform model calculations using a chemical reaction network under the physical conditions typical of protoplanetary disks. Our results show that, when carbonaceous grains are destroyed and converted into the gas phase and the gas becomes carbon-rich, the abundances of carbon-bearing species such as HCN and carbon-chain molecules, increase dramatically near the midplane, while oxygen-bearing species such as H2O and CO2 are depleted. The carbon to silicon ratios obtained by our model calculations qualitatively reproduce the observed gradient with disk radius, but there are some quantitative discrepancies from the observed values of the solar system objects. We adopted the model of a disk around a Herbig Ae star and performed line radiative transfer calculations to examine the effect of carbon grain destruction through observations with ALMA. The results indicate that HCN, H13 CN and c-C3 H2 may be good tracers of this process.
Observationally locating the position of the H2O snowline in protoplanetary disks is crucial for understanding planetesimal and planet formation processes, and the origin of water on the Earth. In our studies, we conducted calculations of chemical reactions and water line profiles in protoplanetary disks, and identified that ortho/para-H216O, H218O lines with small Einstein A coefficients and relatively high upper state energies are dominated by emission from the hot midplane region inside the H2O snowline. Therefore, through analyzing their line profiles the position of the H2O snowline can be located. Moreover, because the number density of the H218O is much smaller than that of H216O, the H218O lines can trace deeper into the disk and thus they are potentially better probes of the exact position of the H2O snowline in disk midplane.
Gas-phase methanol was recently detected in a protoplanetary disk for the first time with ALMA. The peak abundance and distribution of methanol observed in TW Hya differed from that predicted by chemical models. Here, the chemistry of methanol gas and ice is calculated using a physical model tailored for TW Hya with the aim to contrast the results with the recent detection in this source. New pathways for the formation of larger complex molecules (e.g., ethylene glycol) are included in an updated chemical model, as well as the fragmentation of methanol ice upon photodesorption. It is found that including fragmentation upon photodesorption improves the agreement between the peak abundance reached in the chemical models with that observed in TW Hya (∼10−11 with respect to H2); however, the model predicts that the peak in emission resides a factor of 2 − 3 farther out in the disk than the ALMA images. Reasons for the persistent differences in the gas-phase methanol distribution between models and the observations of TW Hya are discussed. These include the location of the ice reservoir which may coincide with the compact mm-dust disk (≲ 60 au) and sources of gas-phase methanol which have not yet been considered in models. The possibility of detecting larger molecules with ALMA is also explored. Calculations of the rotational spectra of complex molecules other than methanol using a parametric model constrained by the TW Hya observations suggest that the detection of individual emission lines of complex molecules with ALMA remains challenging. However, the signal-to-noise ratio can be enhanced via stacking of multiple transitions which have similar upper energy levels.
Connecting the observed composition of exoplanets to their formation sites often involves comparing the atmospheric C/O ratio to a disk midplane model with a fixed chemical composition. In this scenario chemistry during the planet formation era is not considered. However, kinetic chemical evolution during the lifetime of the gaseous disk can change the relative abundances of volatile species, thus altering the C/O ratios of planetary building blocks. In our chemical evolition models we utilize a large network of gas-phase, grain-surface and gas-grain interaction reactions, thus providing a comprehensive treatment of chemistry. The results show that, if sufficient ionisation is present, then chemistry does alter the C/O ratios of gas and ice during the epoch of planet(esimal) formation. This modifies the picture of C/O ratios in disk midplanes defined simply by volatile ice lines in a midplane of fixed chemical composition. Chemical evolution thus needs to be addressed when predicting the makeup of planets and their atmospheres.
Observationally measuring the location of the H2O snowline is crucial for understanding the planetesimal and planet formation processes, and the origin of water on Earth. The velocity profiles of emission lines from protoplanetary disks are usually affected by Doppler shift due to Keplerian rotation and thermal broadening. Therefore, the velocity profiles are sensitive to the radial distribution of the line-emitting regions. In our work (Notsu et al. 2016, 2017), we found candidate water lines to locate the position of the H2O snowline through future high-dispersion spectroscopic observations. First, we calculated the chemical composition of the disks around a T Tauri star and a Herbig Ae star using chemical kinetics. We confirmed that the abundance of H2O gas is high not only in the hot midplane region inside the H2O snowline but also in the hot surface layer and the photodesorption region of the outer disk. The position of the H2O snowline in the Herbig Ae disk exists at a larger radius from the central star than that in the T Tauri disk. Second, we calculated the H2O line profiles and identified that H2O emission lines with small Einstein A coefficients (∼10−6 − 10−3 s−1) and relatively high upper state energies (∼ 1000K) are dominated by emission from the hot midplane region inside the H2O snowline, and therefore their profiles potentially contain information which can be used to locate the position of the H2O snowline. The wavelengths of the H2O lines which are the best candidates to locate the position of the H2O snowline range from mid-infrared to sub-millimeter, and the total line fluxes tend to increase with decreasing wavelengths. We investigated the possibility of future observations using the ALMA and mid-infrared high-dispersion spectrographs (e.g., SPICA/SMI-HRS). Since the fluxes of those identified lines from a Herbig Ae disk are stronger than those of a T Tauri disk, the possibility of a successful detection is expected to increase for a Herbig Ae disk.
Molecular oxygen, O2, was recently detected in comet 67P by the ROSINA instrument on board the Rosetta spacecraft with a surprisingly high abundance of 4% relative to H2O, making O2 the fourth most abundant in comet 67P. Other volatile species with similar volatility, such as molecular nitrogen N2, were also detected by Rosetta, but with much lower abundances and much weaker correlations with water. Here, we investigate the chemical and physical origin of O2 and other volatile species using the new constraints provided by Rosetta. We follow the chemical evolution during star formation with state-of-the-art astrochemical models applied to dynamical physical models by considering three origins: i) in dark clouds, ii) during forming protostellar disks, and iii) during luminosity outbursts in disks. The models presented here favour a dark cloud (or “primordial”) grain surface chemistry origin for volatile species in comets, albeit for dark clouds which are slightly warmer and denser than those usually considered as solar system progenitors.
The Protoplanetary Discussions conference—held in Edinburgh, UK, from 2016 March 7th–11th—included several open sessions led by participants. This paper reports on the discussions collectively concerned with the multi-physics modelling of protoplanetary discs, including the self-consistent calculation of gas and dust dynamics, radiative transfer, and chemistry. After a short introduction to each of these disciplines in isolation, we identify a series of burning questions and grand challenges associated with their continuing development and integration. We then discuss potential pathways towards solving these challenges, grouped by strategical, technical, and collaborative developments. This paper is not intended to be a review, but rather to motivate and direct future research and collaboration across typically distinct fields based on community-driven input, to encourage further progress in our understanding of circumstellar and protoplanetary discs.
Interstellar methanol is thought to be the precursor of larger, more complex organic molecules. It holds a central role in many astrochemical models (e.g., Garrod & Herbst 2006). Methanol has also been the focus of several laboratory studies (e.g., Watanabe et al. 2004, Fuchs et al. 2009), in an effort to gain insight into grain-surface chemistry, which potentially builds chemical complexity already in the cold, dark prestellar phase. The case of methanol is a prime example of experimental work having implications on astronomical scales. Drozdovskaya et al. (2014) unified physical and chemical models to simulate infalling material during the birth of a low-mass protostar. An axisymmetric 2D semi-analytic collapse model (Visser et al. 2009), wavelength-dependent radiative transfer calculations with RADMC3D (Dullemond & Dominik 2004) and a comprehensive gas-grain chemical network (Walsh et al. 2014) were used to study two modes of protoplanetary disk formation.
We present observations of the first 10° of longitude in the Mopra CO survey of the southern Galactic plane, covering Galactic longitude l = 320–330° and latitude b = ±0.5°, and l = 327–330°, b = +0.5–1.0°. These data have been taken at 35-arcsec spatial resolution and 0.1 km s−1 spectral resolution, providing an unprecedented view of the molecular clouds and gas of the southern Galactic plane in the 109–115 GHz J = 1–0 transitions of 12CO, 13CO, C18O, and C17O. Together with information about the noise statistics from the Mopra telescope, these data can be retrieved from the Mopra CO website and the CSIRO-ATNF data archive.
The application of metabolomics in multi-centre studies is increasing. The aim of the present study was to assess the effects of geographical location on the metabolic profiles of individuals with the metabolic syndrome. Blood and urine samples were collected from 219 adults from seven European centres participating in the LIPGENE project (Diet, genomics and the metabolic syndrome: an integrated nutrition, agro-food, social and economic analysis). Nutrient intakes, BMI, waist:hip ratio, blood pressure, and plasma glucose, insulin and blood lipid levels were assessed. Plasma fatty acid levels and urine were assessed using a metabolomic technique. The separation of three European geographical groups (NW, northwest; NE, northeast; SW, southwest) was identified using partial least-squares discriminant analysis models for urine (R2X: 0·33, Q2: 0·39) and plasma fatty acid (R2X: 0·32, Q2: 0·60) data. The NW group was characterised by higher levels of urinary hippurate and N-methylnicotinate. The NE group was characterised by higher levels of urinary creatine and citrate and plasma EPA (20 : 5 n-3). The SW group was characterised by higher levels of urinary trimethylamine oxide and lower levels of plasma EPA. The indicators of metabolic health appeared to be consistent across the groups. The SW group had higher intakes of total fat and MUFA compared with both the NW and NE groups (P≤ 0·001). The NE group had higher intakes of fibre and n-3 and n-6 fatty acids compared with both the NW and SW groups (all P< 0·001). It is likely that differences in dietary intakes contributed to the separation of the three groups. Evaluation of geographical factors including diet should be considered in the interpretation of metabolomic data from multi-centre studies.
Cosmic ray ionization has been found to be a dominant mechanism for the formation of ions in dense interstellar environments. Cosmic rays are further known to initiate the highly efficient ion-neutral chemistry within star forming regions. In this talk we explore the effect of both cosmic rays and UV photons on a model hot Jupiter atmosphere using a non-equlibrium chemical network that combines reactions from the UMIST Database for Astrochemistry, the KIDA database for interstellar and protoplanetary environments and three-body and combustion reactions from the NIST database and from various irradiated gas planet networks. The physical parameters for our model atmosphere are based on HD 189733 b (Effective Temperature of 1000 K, log g = 3.3, solar metallicity, at a distance 0.03 AU from a K dwarf). The active UV photochemistry high in our model hot Jupiter atmosphere tends to destroy these hydrocarbons, but on a time-scale sufficiently slow that PAH formation could already have taken place. In most cases, carbon-bearing species formed by cosmic rays are destroyed by UV photons (e.g. C2H2, C2H4, HC3N). Conversely, carbon-bearing species enhanced by an active photochemistry are depleted when cosmic ray ionization is significant (e.g. CN, HCN and CH4). Ammonia is an interesting exception to this trend, enhanced both by an active photochemistry and a high cosmic ray ionization rate.