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Postmortem human brain studies provide the molecular, cellular, and circuitry levels of resolution essential for the development of mechanistically-novel interventions for cognitive deficits in schizophrenia. However, the absence of measures of premortem cognitive aptitude in postmortem subjects has presented a major challenge to interpreting the relationship between the severity of neural alterations and cognitive deficits within the same subjects.
To begin addressing this challenge, proxy measures of cognitive aptitude were evaluated in postmortem subjects (N = 507) meeting criteria for schizophrenia, major depressive or bipolar disorder, and unaffected comparison subjects. Specifically, highest levels of educational and occupational attainment of the decedent and their parents were obtained during postmortem psychological autopsies.
Consistent with prior findings in living subjects, subjects with schizophrenia had the lowest educational and occupational attainment relative to all other subject groups, and they also failed to show the generational improvement in attainment observed in all other subject groups.
Educational and occupational attainment data obtained during postmortem psychological autopsies can be used as proxy measures of premortem cognitive function to interrogate the neural substrate of cognitive dysfunction in schizophrenia.
To determine the effect of mandatory and nonmandatory influenza vaccination policies on vaccination rates and symptomatic absenteeism among healthcare personnel (HCP).
Retrospective observational cohort study.
This study took place at 3 university medical centers with mandatory influenza vaccination policies and 4 Veterans Affairs (VA) healthcare systems with nonmandatory influenza vaccination policies.
The study included 2,304 outpatient HCP at mandatory vaccination sites and 1,759 outpatient HCP at nonmandatory vaccination sites.
To determine the incidence and duration of absenteeism in outpatient settings, HCP participating in the Respiratory Protection Effectiveness Clinical Trial at both mandatory and nonmandatory vaccination sites over 3 viral respiratory illness (VRI) seasons (2012–2015) reported their influenza vaccination status and symptomatic days absent from work weekly throughout a 12-week period during the peak VRI season each year. The adjusted effects of vaccination and other modulating factors on absenteeism rates were estimated using multivariable regression models.
The proportion of participants who received influenza vaccination was lower each year at nonmandatory than at mandatory vaccination sites (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.07–0.11). Among HCP who reported at least 1 sick day, vaccinated HCP had lower symptomatic days absent compared to unvaccinated HCP (OR for 2012–2013 and 2013–2014, 0.82; 95% CI, 0.72–0.93; OR for 2014–2015, 0.81; 95% CI, 0.69–0.95).
These data suggest that mandatory HCP influenza vaccination policies increase influenza vaccination rates and that HCP symptomatic absenteeism diminishes as rates of influenza vaccination increase. These findings should be considered in formulating HCP influenza vaccination policies.
OBJECTIVES/SPECIFIC AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the United States and increases risk for cirrhosis and liver cancer. Identifying modifiable risk factors for NAFLD could allow better targeting of prevention programs. Insulin resistance (IR) plays a significant role in the development and progression of NAFLD. IR is also an important precursor to the development of type 2 diabetes (T2DM). However, the development and duration of IR during young adulthood and its association with NAFLD and T2DM in midlife is unclear. To test whether trajectories of IR using homeostatic model assessment (HOMA-IR) change throughout early adulthood are associated with risk of prevalent NAFLD and T2DM among persons with NAFLD in midlife independent of current or baseline HOMA-IR. METHODS/STUDY POPULATION: Participants from the CARDIA study, a prospective multicenter population-based biracial cohort of adults (baseline age 18–30 years), underwent HOMA-IR measurement (≥8 h fasting and not pregnant) at baseline (1985–1986) and follow-up exam years 7, 10, 15, 20, and 25. At Year 25 (Y25, 2010–2011), liver fat was assessed by noncontrast computed tomography (CT). NAFLD was defined as CT liver attenuation <51 Hounsfield Units after exclusion of other causes of liver fat (alcohol/hepatitis/medications). Latent mixture modeling was used to identify 25-year trajectories in HOMA-IR over time. Multivariable logistic regression models were used to assess associations between HOMA-IR trajectory groups and prevalent NAFLD with adjustment for baseline or Y25 HOMA-IR. RESULTS/ANTICIPATED RESULTS: Among 3060 participants, we identified 3 distinct trajectory groups for HOMA-IR for individuals free from diabetes in middle adulthood: qualitatively low-stable (46.7% of the cohort), moderate-increasing (42.0%), and high-increasing (11.3%) with a NAFLD prevalence at Y25 of: 8.3%, 33.4%, and 63.5%, respectively (p-trend<0.0001). After adjustment for confounders (baseline smoking status, alcohol use, body mass index, physical activity score, systolic blood pressure, antihypertensive medication use, and total/HDL cholesterol ratio) and baseline HOMA-IR, increasing HOMA-IR trajectories were associated with greater NAFLD prevalence compared with the low-stable trajectory group [odds ratio (95% CI): 5.8 (4.3–7.9) and 22.3 (14.2–34.9) for moderate and high, respectively]. These associations were attenuated, but remained significant, even after controlling for current Y25 HOMA-IR [OR=3.6 (2.6–5.0) for moderate and 5.9 (3.4–10.3) for high (referent: low)]. Among participants with NAFLD (n=511), high-increasing HOMA-IR trajectory was associated with greater prevalent [OR=6.5 (1.6–25.7)] and incident [OR=8.7 (2.2–34.4)] T2DM at Y25 independent of confounders and Y25 HOMA-IR (referent: low-stable). DISCUSSION/SIGNIFICANCE OF IMPACT: In this community-based sample of individuals free from diabetes at baseline, an increasing HOMA-IR trajectory through young adulthood was associated with greater NAFLD prevalence in midlife. Knowledge of changes in IR throughout adulthood provides new information on the risk of T2DM among persons with NAFLD in midlife independent of current level of IR. These findings highlight early identification of increasing IR as a potential target for primary prevention of T2DM in the setting of NAFLD.
Mobile text-messaging smoking cessation interventions have demonstrated their efficacy in increasing cessation rates. These interventions tend to be multifaceted and there is a need to specify their building blocks. The purpose of this study was to use the Behavioural Change Techniques Taxonomy V1 (BCTTv1) to systematically analyse the behaviour change techniques present in the SmokefreeTXT (SFTXT) adult programme. The entire SFTXT library was coded using the BCTTv1. Frequencies were calculated to assess the presence of BCT groups and unique BCTs in the entire programme. The mix of BCTs was also examined by programme week and during periods of high user dropout. Of the 16 groups of behavioural techniques, 14 were present in SFTXT. Of the 93 distinct BCTs, 41 were present in the full SFTXT message library. The most prevalent BCT groups were Feedback and Monitoring, Natural Consequences, Social Support, and Shaping Knowledge. There were differences in the mix of BCTs across the duration of the intervention. The results will enable us to test how changes in the use of specific BCTs and their frequency of use over time, impact (1) engagement with the programme (particularly during the days with high dropout rates), and (2) smoking cessation outcomes over time.
Mental health research funding priorities in high-income countries must balance longer-term investment in identifying neurobiological mechanisms of disease with shorter-term funding of novel prevention and treatment strategies to alleviate the current burden of mental illness. Prioritising one area of science over others risks reduced returns on the entire scientific portfolio.
Following Hurricane Katrina and the 2009 H1N1 epidemic, pediatric critical care clinicians recognized the urgent need for a standardized pediatric triage/allocation system. This study collected regional provider opinion on issues of care allocation and pediatric triage in a disaster/pandemic setting.
This study was a cross-sectional survey of United States (US) health care providers and public health workers who demonstrated interest in critical care and/or disaster care medicine by attending a Northwest regional pediatric critical care symposium on disaster preparation, held in 2012 at Seattle Children's Hospital in Seattle, Washington (USA). The survey employed an electronic audience response system and included demographic, ethical, and logistical questions. Differences in opinions between respondents grouped by professions and work locations were evaluated using a chi-square test.
One hundred and twelve (97%) of 116 total attendees responded to at least one question; however, four of these responders failed to answer every question. Sixty-two (55%) responders were nurses, 29 (26%) physicians, and 21 (19%) other occupations. Fifty-five (51%) responders worked in pediatric hospitals vs 53 (49%) in other locations. Sixty-three (58%) of 108 successful responses prioritized children predicted to have a good neuro-cognitive outcome. Seventy-one (68%) agreed that no pediatric age group should be prioritized. Twenty-two (43%) of providers working in non-pediatric hospital locations preferred a triage system based on an objective score alone vs 14 (26%) of those in pediatric hospitals (P = .038).
JohnsonEM, DiekemaDS, Lewis-NewbyM, KingMA. Pediatric Triage and Allocation of Critical Care Resources During Disaster: Northwest Provider Opinion. Prehosp Disaster Med. 2014;29(5):1-6.
We compare forests dominated by Gilbertiodendron dewevrei at the Dja Biosphere Reserve (Cameroon) with adjacent high-diversity mixed forests in terms of tree-species composition and stand structure, in order to understand the co-occurrence of mixed forest tree species in the monodominant forest. A total of 18 1-ha permanent plots were established in the two forest types. In each plot, all trees with dbh ≥10 cm were identified as were those <10 cm dbh within a subsample of 300 m2. Species richness was significantly different between the two forest types. Mixed forest had an average of 109 species ha−1 for trees ≥10 cm dbh and 137 species for trees <10 cm dbh. By contrast, G. dewevrei-dominated forest had an average of 47 species ha−1 (≥10 cm dbh) and 92 species (<10 cm dbh). There was no significant difference in terms of stem density of the trees with dbh <10 cm between the two forests (mixed: 3.7 stems m−2; monodominant: 3.1 stems m−2). As G. dewevrei is a shade-tolerant species that can regenerate under its own shade, its higher stem density and basal area can reduce species richness of an area.
Though his dance criticism constitutes no more than a few pages, the nineteenth-century poet Stéphane Mallarmé has come to be considered an important dance theorist. His dance essays set forth a complex and original view of dance as a poetry of the body and prefigure contemporary efforts to study dance as a system of signs. Mallarmé's prose style is, however, notoriously obscure and resistant to translation. Thus despite the power and beauty of their literary expression, his ideas on dance remain largely inaccessible without critical examination. Through a close reading and translation of several of his key passages on dance, this essay will seek to clarify his theory of the aesthetico-metaphysical function of dance and his concept of its relationship to his own art, poetry.
Weaning is associated with a major shift in the microbial community of the intestine, and this instability may make it more acquiescent than the adult microbiota to long-term changes. Modulation achieved through dietary interventions may have potentially beneficial effects on the developing immune system, which is driven primarily by the microbiota. The specific aim of the present study was to determine whether immune development could be modified by dietary supplementation with the human probiotic Bifidobacterium lactis NCC2818 in a tractable model of weaning in infants. Piglets were reared by their mothers before being weaned onto a solid diet supplemented with B. lactis NCC2818, while sibling controls did not receive supplementation. Probiotic supplementation resulted in a reduction in IgA (P< 0·0005) and IgM (P< 0·009) production by mucosal tissues but had no effect on IgG production (P>0·05). Probiotic-supplemented pigs had more mast cells than unsupplemented littermates (P< 0·0001), although numbers in both groups were low. In addition, the supplemented piglets made stronger serum IgG responses to fed and injected antigens (P< 0·05). The present findings are consistent with B. lactis NCC2818 reducing intestinal permeability induced by weaning, and suggest that the piglet is a valuable intermediate between rodent models and human infants. The results also strongly suggest that measures of the effect of probiotic supplementation on the immune system need to be interpreted carefully as proxy measures of health benefit. However, they are useful in developing an understanding of the mechanism of action of probiotic strains, an important factor in predicting favourable health outcomes of nutritional intervention.
Excavations at Tinney's Lane, Sherborne in 2002 uncovered extensive evidence for Late Bronze Age settlement and pottery production, dating from a short time period probably within the 12th or 11th century cal bc. Well-preserved deposits of burnt stone, broken vessels, and burnt sherds, together with resulting debris redeposited in associated pits, were accompanied by a series of post-hole structures interpreted as round-houses and four-post settings. Environmental evidence in the form of charcoal, charred plant remains, and molluscs has provided important information concerning sources of fuel and water for pottery production as well as allowing a reconstruction of the local vegetation. Finds of fired clay, metal, stone, shale, flint, and bone include items from distant sources, informing topics such as site status and exchange, and include many categories of tools and equipment that would have been used within the pottery-making processes. Analysis of the spatial distribution of these finds amongst the structures and surviving layers of burning has allowed the definition of a series of industrial activity areas, each comprising one or more round-houses, a four-post structure, bonfire bases or pits used for firing, and other pits with specific related functions. Altogether the site has provided some of the best evidence for pottery production within prehistoric Britain.
The present randomised parallel study assessed the impact of adding MUFA to a dietary portfolio of cholesterol-lowering foods on the intravascular kinetics of apoAI- and apoB-containing lipoproteins in subjects with dyslipidaemia. A sample of sixteen men and postmenopausal women consumed a run-in stabilisation diet for 4 weeks. Subjects were then randomly assigned to an experimental dietary portfolio either high or low in MUFA for another 4 weeks. MUFA substituted 13·0 % of total energy from carbohydrate (CHO) in the high-MUFA dietary portfolio. Lipoprotein kinetics were assessed after the run-in and portfolio diets using a primed, constant infusion of [2H3]leucine and multicompartmental modelling. The high-MUFA dietary portfolio resulted in higher apoAI pool size (PS) compared with the low-MUFA dietary portfolio (15·9 % between-diet difference, P= 0·03). This difference appeared to be mainly attributable to a reduction in apoAI fractional catabolic rate (FCR) after the high-MUFA diet ( − 5·6 %, P= 0·02 v. pre-diet values), with no significant change in production rate. The high-MUFA dietary portfolio tended to reduce LDL apoB100 PS compared with the low-MUFA dietary portfolio ( − 28·5 % between-diet difference, P= 0·09), predominantly through an increase in LDL apoB100 FCR (23·2 % between-diet difference, P= 0·04). These data suggest that adding MUFA to a dietary portfolio of cholesterol-lowering foods provides the added advantage of raising HDL primarily through a reduction in HDL clearance rate. Replacing CHO with MUFA in a dietary portfolio may also lead to reductions in LDL apoB100 concentrations primarily by increasing LDL clearance rate, thus potentiating further the well-known cholesterol-lowering effect of this diet.