Developing Optimal Type 2 Diabetes Genetic Risk Communication Strategies for Physicians and Patients

Background: Currently, gestational diabetes (GDM) affects 13% of pregnancies; up to 70% of those women and their children will develop type 2 diabetes (T2D). GWAS have been successful at identifying T2D genetic risk variants. Physicians’ ability to effectively communicate T2D genetic risk is dependent on their patients’ genetic self-efficacy (GSE), genetic knowledge (GK), health literacy (HL), and numeracy.Methods: The Primordial Prevention Program has the overarching goal of examining the clinical utility of genetic testing for T2D prevention in high-risk families. Parents with a maternal history of GDM were interviewed to assess their preferences and understanding of their children’s T2D genetic risk reports. Results from these analyses were used to develop a more detailed survey to assess the correlation of GSE with GK, HL, and numeracy in an independent sample.Results: Interviews were conducted on 28 mothers and 21 fathers. Participants were 39±8 years old, 41% non-White, and reported high GSE levels (19.3±3.6), which positively correlated with HL (r=0.35, p=0.02) and GK (r=0.28, p=0.05). Adult participants from the follow up survey were 37±14 years old, 84% female, and 32% non-White. Participants’ GSE levels were positively correlated with GK (r=0.29, p=1.95x10-6), numeracy (r=0.30, p=9.31x10-7), and HL (r=0.14, p=0.02). In stratified analyses, those with a lower education level scored significantly lower compared to higher educated participants (GSE (8.6±2.8 vs.10.4±3.1, p=2.59 x 10-5), GK (12.9±1.7 vs. 13.7±1.5, p=1.37 x 10-4), numeracy (2.4±1.6 vs. 4.4±1.6, p=1.73 x 10-16), HL (31.5±8.9 vs. 36.5±5.4, p=1.22 x 10-7)).Conclusion and Potential Impact: In our study, parents and a higher educated adult population presented as genetically self-efficacious and had higher HL, numeracy and GK. Physicians’ assessment of their patients’ GSE, GK, HL, and numeracy will enable effective communication of genetic risk. Physicians should be aware that patients may demonstrate efficacy in their understanding of genetics, even though their understanding may not reflect their actual knowledge

H2A.Z Acidic Patch Couples Chromatin Dynamics to Regulation of Gene Expression Programs during ESC Differentiation

The histone H2A variant H2A.Z is essential for embryonic development and for proper control of developmental gene expression programs in embryonic stem cells (ESCs). Divergent regions of amino acid sequence of H2A.Z likely determine its functional specialization compared to core histone H2A. For example, H2A.Z contains three divergent residues in the essential C-terminal acidic patch that reside on the surface of the histone octamer as an uninterrupted acidic patch domain; however, we know little about how these residues contribute to chromatin structure and function. Here, we show that the divergent amino acids Gly92, Asp97, and Ser98 in the H2A.Z C-terminal acidic patch (H2A.Z[superscript AP3]) are critical for lineage commitment during ESC differentiation. H2A.Z is enriched at most H3K4me3 promoters in ESCs including poised, bivalent promoters that harbor both activating and repressive marks, H3K4me3 and H3K27me3 respectively. We found that while H2A.Z[superscript AP3] interacted with its deposition complex and displayed a highly similar distribution pattern compared to wild-type H2A.Z, its enrichment levels were reduced at target promoters. Further analysis revealed that H2A.Z[superscript AP3] was less tightly associated with chromatin, suggesting that the mutant is more dynamic. Notably, bivalent genes in H2A.Z[superscript AP3] ESCs displayed significant changes in expression compared to active genes. Moreover, bivalent genes in H2A.Z[superscript AP3] ESCs gained H3.3, a variant associated with higher nucleosome turnover, compared to wild-type H2A.Z. We next performed single cell imaging to measure H2A.Z dynamics. We found that H2A.Z[superscript AP3] displayed higher mobility in chromatin compared to wild-type H2A.Z by fluorescent recovery after photobleaching (FRAP). Moreover, ESCs treated with the transcriptional inhibitor flavopiridol resulted in a decrease in the H2A.Z[superscript AP3] mobile fraction and an increase in its occupancy at target genes indicating that the mutant can be properly incorporated into chromatin. Collectively, our work suggests that the divergent residues in the H2A.Z acidic patch comprise a unique domain that couples control of chromatin dynamics to the regulation of developmental gene expression patterns during lineage commitment.Massachusetts Life Sciences Center (David H. Koch Institute for Integrative Cancer Research at MIT Core Grant P30-CA14051)National Science Foundation (U.S.). Emergent Behaviors of Integrated Cellular Systems (Grant CBET-0939511)MIT Faculty Start-up FundMassachusetts Institute of Technology. Computational and Systems Biology Initiative (Merck & Co. Postdoctoral Fellowship

Effects of the Veterinary Pharmaceutical Ivermectin in Indoor Aquatic Microcosms

The effects of the parasiticide ivermectin were assessed in plankton-dominated indoor microcosms. Ivermectin was applied once at concentrations of 30, 100, 300, 1000, 3000, and 10,000 ng/l. The half-life (dissipation time 50%; DT50) of ivermectin in the water phase ranged from 1.1 to 8.3 days. The lowest NOECcommunity that could be derived on an isolated sampling from the microcosm study by means of multivariate techniques was 100 ng/l. The most sensitive species in the microcosm study were the cladocerans Ceriodaphnia sp. (no observed effect concentration, NOEC = 30 ng/l) and Chydorus sphaericus (NOEC = 100 ng/l). The amphipod Gammarus pulex was less sensitive to ivermectin, showing consistent statistically significant reductions at the 1000-ng/l treatment level. Copepoda taxa decreased directly after application of ivermectin in the highest treatment but had already recovered at day 20 posttreatment. Indirect effects (e.g., increase of rotifers, increased primary production) were observed at the highest treatment level starting only on day 13 of the exposure phase. Cladocera showed the highest sensitivity to ivermectin in both standard laboratory toxicity tests as well as in the microcosm study. This study demonstrates that simple plankton-dominated test systems for assessing the effects of ivermectin can produce results similar to those obtained with large complex outdoor systems

Neutrality and the Response of Rare Species to Environmental Variance

Neutral models and differential responses of species to environmental heterogeneity offer complementary explanations of species abundance distribution and dynamics. Under what circumstances one model prevails over the other is still a matter of debate. We show that the decay of similarity over time in rocky seashore assemblages of algae and invertebrates sampled over a period of 16 years was consistent with the predictions of a stochastic model of ecological drift at time scales larger than 2 years, but not at time scales between 3 and 24 months when similarity was quantified with an index that reflected changes in abundance of rare species. A field experiment was performed to examine whether assemblages responded neutrally or non-neutrally to changes in temporal variance of disturbance. The experimental results did not reject neutrality, but identified a positive effect of intermediate levels of environmental heterogeneity on the abundance of rare species. This effect translated into a marked decrease in the characteristic time scale of species turnover, highlighting the role of rare species in driving assemblage dynamics in fluctuating environments

Seasonal variations of the digestive tract of the Eurasian beaver castor fiber.

Forage availability for wild rodents varies with season. In turn, the composition of food can affect morphometric parameters of the digestive tract. This study was performed in Eurasian beavers (Castor fiber) whose population was close to extinction in most Eurasian countries, but has now increased. Due to the previous low number of studies, information about the effect of forage availability on the digestive tract morphology has previously been lacking. This study was performed using beavers captured from the natural environment during three seasons of different forage availability: winter, summer and autumn. It was found that the diet of the beaver varied during the year; in winter it was dominated by woody material consisting of willow shoots, whereas in summer the diet was primarily herbs, grass and leaves. Season also affected the mass of digested contents of the digestive tract. The digestive content increased in the caecum and colon in winter and autumn, when poor-quality food dominated the beaver's diet. The results indicated that the digestive tract parameters of beavers varied based on the composition of available forage

Pandemic-related ability and willingness in home healthcare workers

Objective: To assess pandemic-related attitudes and behavioral intentions of home healthcare workers (HHCWs).Design: Cross-sectional survey.Setting: New York City.Participants: A convenience sample of 384 HHCWs.Main Outcome Variables: Ability and willingness to report to work during a pandemic influenza outbreak.Results: A large proportion of HHCWs reported that they would be either unable or unwilling (or both) to provide care to their current (83 percent) or new (91 percent) patients during a pandemic. Ability was significantly associated with not having children living at home, having alternatives to mass transportation, not having a spouse/partner employed as a first responder or healthcare worker, and having longer tenure (ie, six or more years) in homecare. During an outbreak, 43 percent of HHCWs said they would be willing to take care of current patients and only 27 percent were willing to take care of new patients.Willingness to care for both current and new patients was inversely associated with fear for personal safety (p 0.01). Provision of key elements of a respiratory protection program was associated with decreased fear (p 0.05). Most participants (86 percent) had not received any work-based, pandemic- related training, and only 5 percent reported that their employer had an influenza pandemic plan.Conclusions: Given that a large majority of the participating HHCWs would either be unable or unwilling to report to duty during a pandemic, potential shortfalls in this workforce may occur. To counter this, organizations should focus on strategies targeting intervenable barriers to ability and to willingness (ie, the provision of a vaccine and respiratory protection programs).</jats:p

Electroweak parameters of the z0 resonance and the standard model

Contains fulltext : 124399.pdf (publisher's version ) (Open Access

GENERAL OVERGROWTH IN THE FRAGILE-X SYNDROME - VARIABILITY IN THE PHENOTYPIC-EXPRESSION OF THE FMR1 GENE MUTATION

The fragile X syndrome, which often presents in childhood with overgrowth, may in some cases show some diagnostic overlap with classical Sotos syndrome. We describe four fragile X patients with general overgrowth, all of whom are from families with other affected relatives who show the classic Martin-Bell phenotype. Molecular studies of the FMR1 gene in all cases showed the typical full mutation as seen in males affected by the fragile X syndrome. Endocrine studies were unremarkable, except in one case where there were raised levels of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3). These cases illustrate the clinical variability of the fragile X syndrome and the necessity of performing analysis of the FMR1 gene in mentally retarded patients presenting with general overgrowth