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Birth weight and early growth have been associated with later blood pressure. However, not all studies consistently find a significant reduction in blood pressure with an increase in birth weight. In addition, the relative importance of birth weight and of other lifestyle and environmental factors is often overlooked and the association is rarely studied in adolescents. We investigated early life predictors, including birth weight, of adolescent blood pressure in the Gateshead Millennium Study (GMS). The GMS is a cohort of 1029 individuals born in 1999–2000 in Gateshead in Northern England. Throughout infancy and early childhood, detailed information were collected, including birth weight and measures of height and weight. Assessments of 491 returning participants at age 12 years included measures of body mass and blood pressure. Linear regression and path analysis were used to determine predictors and their relative importance on blood pressure. Birth weight was not directly associated with blood pressure at the age of 12. However, after adjustment for contemporaneous body mass index (BMI), an inverse association of standardized birth weight on systolic blood pressure was significant. The relative importance of birth weight on later systolic blood pressure was smaller than other contemporaneous body measures (height and BMI). There was no independent association of birth weight on blood pressure seen in this adolescent population. Contemporaneous body measures have an important role to play. Lifestyle factors that influence body mass or size, such as diet and physical activity, where interventions are directed at early prevention of hypertension should be targeted.
The Latino population in the United States is rapidly growing and faces profound health disparities; however, engagement of Latinos in biomedical research remains low. Our community-based participatory research partnership has recruited 2083 Spanish-speaking Latinos into 21 studies over 15 years. We sought to identify and describe the strategies we have used to successfully recruit and retain Spanish-speaking Latinos in research.
We abstracted and analyzed data from archived study notes, progress reports, team meeting minutes, and in-depth interviews conducted annually from community-based participatory research partnership members. We used a nominal group process to refine and prioritize strategies.
Overall, 13 recruitment strategies and 12 retention strategies emerged. These strategies relied on the creativity and perseverance of the study team and partners.
It is essential that we develop and disseminate effective recruitment and retention strategies that engage Latinos in biomedical research to reduce health disparities and promote health equity.
Recent cases of acute kidney injury due to Seoul hantavirus infection from exposure to wild or pet fancy rats suggest this infection is increasing in prevalence in the UK. We conducted a seroprevalence study in England to estimate cumulative exposure in at-risk groups with contact with domesticated and wild rats to assess risk and inform public health advice. From October 2013 to June 2014, 844 individual blood samples were collected. Hantavirus seroprevalence amongst the pet fancy rat owner group was 34.1% (95% CI 23·9–45·7%) compared with 3·3% (95% CI 1·6–6·0) in a baseline control group, 2·4% in those with occupational exposure to pet fancy rats (95% CI 0·6–5·9) and 1·7% with occupational exposure to wild rats (95% CI 0·2–5·9). Variation in seroprevalence across groups with different exposure suggests that occupational exposure to pet and wild rats carries a very low risk, if any. However incidence of hantavirus infection among pet fancy rat owners/breeders, whether asymptomatic, undiagnosed mild viral illness or more severe disease may be very common and public health advice needs to be targeted to this at-risk group.
The current project seeks to integrate literatures on personality risk for antisocial behavior (ASB) by examining how callous–unemotional traits relate to (a) the development of disinhibited traits and (b) the association between disinhibited traits and ASB. In Study 1, using a nationally representative sample of youth (N > 7,000), we examined whether conduct problems and lack of guilt assessed during ages 4–10 years predicted levels of and changes in disinhibited traits over the course of adolescence, and moderated associations between these traits and ASB. High levels of childhood conduct problems were associated with higher levels of impulsivity, sensation seeking, and ASB in early adolescence, whereas lack of guilt was associated with lower levels of sensation seeking. Neither conduct problems nor lack of guilt significantly predicted changes in impulsivity or sensation seeking, and associations among changes in sensation seeking, impulsivity, and ASB were also consistent across levels of conduct problems and lack of guilt. In Study 2, using a cross-sectional sample of adolescents (N = 970), we tested whether callous–unemotional traits moderated associations between disinhibited traits and ASB. Consistent with the results of Study 1, associations between disinhibited personality and ASB were consistent across a continuous range of callous–unemotional traits.
Cortisol is the primary output of the hypothalamic–pituitary–adrenal (HPA) axis and is central to the biological stress response, with wide-ranging effects on psychiatric health. Despite well-studied biological pathways of glucocorticoid function, little attention has been paid to the role of genetic variation. Conventional salivary, urinary and serum measures are strongly influenced by diurnal variation and transient reactivity. Recently developed technology can be used to measure cortisol accumulation over several months in hair, thus indexing chronic HPA function.
In a socio-economically diverse sample of 1070 twins/multiples (ages 7.80–19.47 years) from the Texas Twin Project, we estimated effects of sex, age and socio-economic status (SES) on hair concentrations of cortisol and its inactive metabolite, cortisone, along with their interactions with genetic and environmental factors. This is the first genetic study of hair neuroendocrine concentrations and the largest twin study of neuroendocrine concentrations in any tissue type.
Glucocorticoid concentrations increased with age for females, but not males. Genetic factors accounted for approximately half of the variation in cortisol and cortisone. Shared environmental effects dissipated over adolescence. Higher SES was related to shallower increases in cortisol with age. SES was unrelated to cortisone, and did not significantly moderate genetic effects on either cortisol or cortisone.
Genetic factors account for sizable proportions of glucocorticoid variation across the entire age range examined, whereas shared environmental influences are modest, and only apparent at earlier ages. Chronic glucocorticoid output appears to be more consistently related to biological sex, age and genotype than to experiential factors that cluster within nuclear families.
Firestone & Scholl (F&S) rely on three problematic assumptions about the mind (modularity, reflexiveness, and context-insensitivity) to argue cognition does not fundamentally influence perception. We highlight evidence indicating that perception, cognition, and emotion are constructed through overlapping, distributed brain networks characterized by top-down activity and context-sensitivity. This evidence undermines F&S's ability to generalize from case studies to the nature of perception.
Medulloblastoma (MB) is the most common malignant pediatric brain tumour, and is categorized into four molecular subgroups, with Group 3 MB having the worst prognosis due to the highest rate of metastatic dissemination and relapse. In this work, we describe the epigenetic regulator Bmi1 as a novel therapeutic target for treatment of recurrent Group 3 MB. Through comparative profiling of primary and recurrent MB, we show that Bmi1 defines a treatment-refractory cell population that is uniquely targetable by a novel class of small molecule inhibitors. We have optimized an in vivo mouse-adapted therapy model that has the advantage of generating recurrent, human, treatment-refractory MBs. Our preliminary studies showed that although chemoradiotherapy administered to mice engrafted with human MB showed reduction in tumour size, Bmi1 expression was enriched in the post-treatment residual tumour. Furthermore, we found that knockdown of Bmi1 in human recurrent MB cells decreases proliferation and self-renewing capacities of MB cells in vitro as well as both tumour size and extent of spinal leptomeningeal metastases in vivo. Oral administration of a potent Bmi1 inhibitor, PTC 028, resulted in a marked reduction in tumour burden and an increased survival in treatment cohort. Bmi1 inhibitors showed high specificity for MB cells and spared normal human neural stem cells, when treated with doses relevant for MB cells. As Group 3 medulloblastoma is often metastatic and uniformly fatal at recurrence, with no current or planned trials of targeted therapy, an efficacious agent such as Bmi1 inhibitor could be rapidly transitioned to clinical trials.
It remains unclear whether the topological deficits of the white matter network documented in cross-sectional studies of chronic schizophrenia patients are due to chronic illness or to other factors such as antipsychotic treatment effects. To answer this question, we evaluated the white matter network in medication-naive first-episode schizophrenia patients (FESP) before and after a course of treatment.
We performed a longitudinal diffusion tensor imaging study in 42 drug-naive FESP at baseline and then after 8 weeks of risperidone monotherapy, and compared them with 38 healthy volunteers. Graph theory was utilized to calculate the topological characteristics of brain anatomical network. Patients’ clinical state was evaluated using the Positive and Negative Syndrome Scale (PANSS) before and after treatment.
Pretreatment, patients had relatively intact overall topological organizations, and deficient nodal topological properties primarily in prefrontal gyrus and limbic system components such as the bilateral anterior and posterior cingulate. Treatment with risperidone normalized topological parameters in the limbic system, and the enhancement positively correlated with the reduction in PANSS-positive symptoms. Prefrontal topological impairments persisted following treatment and negative symptoms did not improve.
During the early phase of antipsychotic medication treatment there are region-specific alterations in white matter topological measures. Limbic white matter topological dysfunction improves with positive symptom reduction. Prefrontal deficits and negative symptoms are unresponsive to medication intervention, and prefrontal deficits are potential trait biomarkers and targets for negative symptom treatment development.
The observation of 8B solar Neutrinos in the Kamiokande-II detector is presented. Based on 450 days of data in the time period of January 1987 through May 1988, the measured flux obtained with Ee ≥ 9.3 MeV was 0.46 ± 0.13 (stat) ± 0.08 (sys) of the value predicted by the standard solar model. The detector and analysis methods were improved since June 1988 and the background level has been decreased by a factor of about three since then.
Surveys with ISO (Kessler et al 1996), in particular with the CAM (Cesarsky et al 1996) and PHOT (Lemke et al 1996) instruments, will greatly extend our understanding of extra-galactic populations and their cosmological evolution. The main advantages that ISO surveys have over e.g IRAS are increased sensitivity/depth and wavelength coverage. Within the Guaranteed and Open Time programmes there are many field surveys which will efficiently map the limits in these parameters. In this talk I will briefly overview those surveys before concentrating in more detail on one survey in particular, the ISO survey of the Hubble Deep Field (HDF), to illustrate the kind of results that can be expected.
Restoration in Mediterranean-climate grasslands is strongly impeded by lack of native propagules and competition with exotic grasses and forbs. We report on a study testing several methods for exotic plant control combined with planting native grasses to restore prairies in former agricultural land in coastal California. Specifically we compared tarping (shading out recently germinated seedlings with black plastic) once, tarping twice, topsoil removal, herbicide (glyphosate), and a control treatment in factorial combinations with or without wood mulch. Into each treatment we planted three native grass species (Elymus glaucus, Hordeum brachyantherum, and Stipa pulchra) and monitored plant survival and cover for three growing seasons. Survival of native grass species was high in all treatments, but was slightly lower in unmulched soil removal and control treatments in the first 2 yr. Mulching, tarping, and herbicide were all effective in reducing exotic grass cover and enhancing native grass cover for the first 2 yr, but by the third growing season cover of the plant guilds and bare ground had mostly converged, primarily because of the declining effects of the initial treatments. Mulching and tarping were both considerably more expensive than herbicide treatment. Topsoil removal was less effective in increasing native grass cover likely because soil removal altered the surface hydrology in this system. Our results show that several treatments were effective in enhancing native grass establishment, but that longer term monitoring is needed to evaluate the efficacy of restoration efforts. The most appropriate approach to controlling exotics to restore specific grassland sites will depend not only on the effectiveness, but also on relative costs and site constraints.
The ability to discriminate biogenic from abiogenic calcium carbonate (CaCO3) would be useful in the search for extant or extinct life, since CaCO3 can be produced by both biotic and abiotic processes on Earth. Bioprecipitated CaCO3 material was produced during the growth of heterotrophic microbial isolates on medium enriched with calcium acetate or calcium citrate. These biologically produced CaCO3, along with natural and synthetic non-biologically produced CaCO3 samples, were analysed by reflectance spectroscopy (0.35–2.5 μm), Raman spectroscopy (532 and 785 nm), and laser-induced fluorescence spectroscopy (365 and 405 nm excitation). Optimal instruments for the discrimination of biogenic from abiogenic CaCO3 were determined to be reflectance spectroscopy, and laser-induced fluorescence spectroscopy. Multiple absorption features in the visible light region occurred in reflectance spectra for most biogenic CaCO3 samples, which are likely due to organic pigments. Multiple fluorescence peaks occurred in emission spectra (405 nm excitation) of biogenic CaCO3 samples, which also are best attributed to the presence of organic compounds; however, further analyses must be performed in order to better determine the cause of these features to establish criteria for confirming the origin of a given CaCO3 sample. Raman spectroscopy was not useful for discrimination since any potential Raman peaks in spectra of biogenic carbonates collected by both the 532 and 785 nm lasers were overwhelmed by fluorescence. However, this also suggests that biogenic carbonates may be identified by the presence of this organic-associated fluorescence. No reliable spectroscopic differences in terms of parameters such as positions or widths of carbonate-associated absorption bands were found between the biogenic and abiogenic carbonate samples. These results indicate that the presence or absence of organic matter intimately associated with carbonate minerals is the only potentially useful spectral discriminator for the techniques that were examined, and that multiple spectroscopic techniques are capable of detecting the presence of associated organic materials. However, the presence or absence of intimately associated organic matter is not, in itself, an indicator of biogenicity.