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Abstract Aims Parameters derived from reservoir‐excess pressure analysis have been demonstrated to predict cardiovascular events. Thus, altered reservoir‐excess pressure parameters could have a detrimental effect on highly‐perfused organs like the heart. We aimed to cross‐sectionally determine whether reservoir‐excess pressure parameters were associated with N‐terminal pro‐brain‐type natriuretic peptide (NT‐proBNP) in older adults. Methods We studied 868 older adults with diverse cardiovascular risk. Reservoir‐excess pressure parameters were obtained through radial artery tonometry including reservoir pressure integral, peak reservoir pressure, excess pressure integral (INTXSP), systolic rate constant (SRC) and diastolic rate constant (DRC). Plasma levels of NT‐proBNP, as a biomarker of cardiac overload, were analysed by the Proximity Extension Assay technology. Results Multivariable linear regression analyses revealed that all reservoir‐excess pressure parameters studied were associated with NT‐proBNP after adjusting for age and sex. After further adjustments for conventional cardiovascular risk factors, INTXSP [β = 0.191 (95% confidence interval, CI: 0.099, 0.283), P

Abstract Background The Vakinankaratra region of Madagascar has a high burden of child undernutrition which, in addition to poor psychosocial stimulation, is a strong risk factor of poor child development. However, there are limited studies evaluating the relations between developmental deficits, child nutrition outcomes, and home stimulation in the region. The purpose of this study was to assess the development of children aged 11–13 months in relation to their nutritional status and to examine parental home stimulation attitudes and practices in the Vakinankaratra region. Methods Cognitive (n = 36), language (n = 36), motor (n = 36), and socioemotional (n = 76) development were assessed using the Bayley Scales of Infant and Toddler Development III. Household stimulation environment was evaluated using the family care indicators survey. Stunting (length-for-age z-score 69%) were observed in this subsample. Limited time and tiredness were the major barriers to home stimulation mentioned by parents and confirmed by key informants. Children had a very limited variety of play materials, and most of the mothers used household objects (75%) and materials from outside the house (71%) as children’s toys. Composite cognitive [mean (SD): 60 (10.3)], motor [61.9 (13.4)], language [62 (13.2)], and socioemotional [85.1 (17.9]) scores were low. Fine motor, cognitive, and receptive and expressive language scores were correlated [0.4

[1.1.1]Propellane, a compound whose structure includes two saturated carbons in which all four bonds are directed into a single hemisphere, is of theoretical interest, but has also seen recent practical applications. Mono-, di-, and trisubstituted derivatives of this propellane (by substitution of its CH2 bridges with O, S, NH, CF2, CO, SO, and SO2) remain unknown despite several computational studies that have suggested some may be stable. In this study, we show that, in several cases, substituted propellanes are spontaneously formed upon the attempted computational optimization of the geometries of anionic bridgehead bromide precursors using the ωB97X-D/aug-cc-pVDZ DFT method. Spontaneous formation suggests that these propellanes are at lower energy relative to the precursors and, therefore, are promising synthetic targets. The success or failure to spontaneously form the propellane is considered in relation to the length and strain energy of the central bridgehead-bridgehead bond, as well as the total strain energy of each propellane.

Triple-negative breast cancer (TNBC) lacks targeted therapies, leaving cytotoxic chemotherapy as the current standard treatment. However, chemotherapy resistance remains a major clinical challenge. Increased insulin-like growth factor 1 signaling can potently blunt chemotherapy response, and lysosomal processes including the nutrient scavenging pathway autophagy can enable cancer cells to evade chemotherapy-mediated cell death. Thus, we tested whether inhibition of insulin receptor/insulin-like growth factor 1 receptor with the drug BMS-754807 and/or lysosomal disruption with hydroxychloroquine (HCQ) could sensitize TNBC cells to the chemotherapy drug carboplatin. Using in vitro studies in multiple TNBC cell lines, in concert with in vivo studies employing a murine syngeneic orthotopic transplant model of TNBC, we show that BMS-754807 and HCQ each sensitized TNBC cells and tumors to carboplatin and reveal that exogenous metabolic modulators may work synergistically with carboplatin as indicated by Bliss analysis. Additionally, we demonstrate the lack of overt in vivo toxicity with our combination regimens and, therefore, propose that metabolic targeting of TNBC may be a safe and effective strategy to increase sensitivity to chemotherapy. Thus, we conclude that the use of exogenous metabolic modulators, such as BMS-754807 or HCQ, in combination with chemotherapy warrants additional study as a strategy to improve therapeutic responses in women with TNBC.

Abstract Quantifying variation in the ability to fight infection among free-living hosts is challenging and often constrained to one or a few measures of immune activity. While such measures are typically taken to reflect host resistance, they can also be shaped by pathogen effects, for example, if more virulent strains trigger more robust immune responses. Here, we test the extent to which pathogen-specific antibody levels, a commonly used measure of immunocompetence, reflect variation in host resistance versus pathogen virulence, and whether these antibodies effectively clear infection. House finches (Haemorhous mexicanus) from resistant and susceptible populations were inoculated with > 50 isolates of their novel Mycoplasma gallisepticum pathogen collected over a 20-year period during which virulence increased. Serum antibody levels were higher in finches from resistant populations and increased with year of pathogen sampling. Higher antibody levels, however, did not subsequently give rise to greater reductions in pathogen load. Our results show that antibody responses can be shaped by levels of host resistance and pathogen virulence, and do not necessarily signal immune clearance ability. While the generality of this novel finding remains unclear, particularly outside of mycoplasmas, it cautions against using antibody levels as implicit proxies for immunocompetence and/or host resistance.

Increasing academic participation among students from ethnic-racial underrepresented groups in STEM yields societal benefits including ameliorating economic ramifications of the labor shortages in STEM, improving scientific innovation, and providing opportunity, access, and participation in high-status STEM fields. Two longitudinal studies with students from underrepresented groups investigated the role of active learning interventions in the development of STEM self-efficacy and intentions to pursue STEM in the future. Study 1 longitudinally tracked high school students participating in a 4-week geoscience program that applied active learning techniques ranging from hands on experiments to peer discussion. High school student participants displayed increases in self-efficacy and STEM intentions from the start to completion of the program, an effect that was observed exclusively among those who reported strong program quality. Study 2 examined the role of mentorship effectiveness with a sample of community college STEM students interested in transferring to a 4-year college. Students’ relatively strong self-efficacy and STEM intentions at the start of the semester remained stable through the end of the semester. Altogether, the present research highlights the role of positive, inclusive educational climates in promoting STEM success among students from underrepresented group members.

The Garden State-LSAMP (GSLSAMP) alliance works collaboratively with the Northern New Jersey-Bridges to the Baccalaureate (NNJB2B) to greatly improve the graduation of community college students from underrepresented minority (URM) groups in STEM and their transfer rate to 4-years STEM programs. This is accomplished through several areas of enrichment. The two alliances sponsor joint activities to encourage a supportive community of 2-years and 4-years students. Community college students conduct research in the labs of mentoring faculty at 4-years programs where they interact with 4-years college students. A cross-campus near-peer mentoring program pairs recently transferred GSLSAMP mentors with mentees from the mentor’s community college of origin that eases and facilitates the graduation and transfer of mentees. In addition, the NNJB2B has adopted five proven high impact practices from GSLSAMP for their students. The results are that the graduation rate of the NNJB2B increased an average of 24.0% annually over the first 5 years of the program and the transfer rate improved 151.0% over the 2012 baseline. Four GSLSAMP 4-years institutions were especially active in the program and experienced an average increase of 62.9% over the 2012 baseline transfers from NNJB2B community colleges.

Few studies have investigated fathers' roles in child care in Madagascar. This study explored the perceptions, attitudes, and practices regarding fathers' involvement in child care using qualitative methods. Ten focus group discussions were conducted among parents of children aged 6-23 months; seven were among mothers, and three among fathers. In-depth semi-structured interviews (n = 8) were also conducted with key informants. Discussions and interviews were audio-recorded and the verbatim transcripts in Malagasy were translated into English. Data were analyzed using the thematic analysis approach. Provision of financial and material support as well as teaching and playing with the child were the main perceived roles of fathers. In practice, fathers spent their time alone with their children playing and holding them when the mother was unavailable. Busy schedules and separation due to work were major barriers to fathers' involvement. Traditional gender roles for child care in which the mother is seen as primarily responsible for the child were salient across the data. Consequently, men involved in child care activities and their wives were often criticized by the community. Nevertheless, there was self-reported interest from both mothers and fathers in involving men more in child care. Interventions aimed to increase fathers' involvement in child care may be more successful when they focus on shifting the community perceptions on the division of responsibilities between fathers and mothers.

Abstract Background Studies evaluating child feeding in Madagascar are scarce despite its importance in child growth during the first two years of life. This study assessed the associations between the WHO infant and young child feeding (IYCF) indicators and stunting and identified determinants of inappropriate child feeding practices. Methods The most recent Demographic and Health Survey was used including a total of 1956 infants aged 0–23 months. Logistic regressions were performed for the association between IYCF indicators and stunting and for the determination of risk factors for inappropriate feeding practices. Results The rates of initiation of breastfeeding within one hour after birth (77.2%), continued breastfeeding at one year (99.6%) and timely introduction of solid, semi-solid or soft foods at 6–8 months (88.3%) were high. Exclusive breastfeeding under 6 months (48.8%), attaining minimum dietary diversity (22.2%) and consumption of iron-rich foods (19.6%) were relatively low. Higher length-for-age was associated with achieving minimum dietary diversity (p

Abstract Background Good glycaemic control in type 2 diabetes (T2DM) protects the microcirculation. Current guidelines suggest glycaemic targets be relaxed in advanced diabetes. We explored whether disease duration or pre-existing macrovascular complications attenuated the association between hyperglycaemia and microvascular function. Methods 743 participants with T2DM (n = 222), cardiovascular disease (CVD = 183), both (n = 177) or neither (controls = 161) from two centres in the UK, underwent standard clinical measures and endothelial dependent (ACh) and independent (SNP) microvascular function assessment using laser Doppler imaging. Results People with T2DM and CVD had attenuated ACh and SNP responses compared to controls. This was additive in those with both (ANOVA p

Background: Central haemodynamic parameters derived from reservoir pressure analysis (RPA-parameters) exhibit prognostic utility. Alterations in reservoir function could have an unfavourable influence on target organs, such as the kidneys. We determined in older adults whether these RPA-parameters would be associated with the reduction in estimated glomerular filtration rate (eGFR) during a 3-year follow-up period. Methods: We studied 544 individuals (69.4 ± 7.9 yrs, 195F, 235CVD) at baseline and after 3 years. RPA-parameters including reservoir pressure integral (INTPR), peak reservoir pressure, excess pressure integral, systolic and diastolic rate constants were obtained by radial artery tonometry. Results: After 3 years, 95 individuals (72.4 ± 7.6 yrs, 26F) had an eGFR reduction of more than 5 ml/min/1.73 m2/year. A multivariate logistic regression analysis revealed that baseline INTPR was independently associated with the eGFR reduction after adjusting for conventional risk factors and baseline renal function [odds ratio 0.975 (95% CI, 0.958–0.993), p < 0.01]. When the eGFR reduction was expressed as a continuous variable, baseline INTPR was also independently associated with changes in eGFR (β = 0.115, p < 0.01; multivariate linear regression with adjustment for conventional risk factors and baseline renal function). These associations remained unchanged after further adjustments for central artery stiffness or traditional central haemodynamic parameters. No other RPA-parameters exhibited significant associations. Conclusions: These findings demonstrate that baseline INTPR is independently associated with the eGFR reduction in older adults, suggesting that INTPR may play a role in the functional decline of the kidneys.