Beyond the Walls: Conceptualizing Natural Environments as “Third Educators”

This research examined preservice early childhood educators’ perceptions of outdoor settings and their intentions to use outdoor settings in their teaching practice. Students enrolled in an early childhood education program (n = 110) at a university in the Great Lakes region completed surveys that assessed perceptions of natural settings, intentions to use natural settings in future teaching, knowledge of the benefits of nature for children, and personal nature relatedness. Participants reported relatively high intentions to use natural settings in future teaching, as well as knowledge of the benefits of nature for children, but moderate levels of personal nature relatedness. Participants were more likely to select “maintained” settings such as parks for educational purposes, and more “natural” settings, especially those with water, for personal purposes. Knowledge of the benefits of nature experiences, the perceived difficulty in using natural settings, and personal levels of nature relatedness each significantly predicted intention to use natural settings in future teaching. We recommend that teacher preparation programs provide: opportunities for students to observe and/or interact with children as they engage in unstructured play in natural environments; opportunities to engage in both structured and unstructured learning experiences in natural environments; and preparing students to provide appropriate supervision in natural environments

Changes in Physician Antipsychotic Prescribing Preferences, 2002–2007

Objective Physician antipsychotic prescribing behavior may be influenced by comparative effectiveness evidence, regulatory warnings, and formulary and other restrictions on these drugs. This study measured changes in the degree to which physicians are able to customize treatment choices and changes in physician preferences for specific agents after these events. Methods The study used 2002–2007 prescribing data from the IMS Health Xponent database and data on physician characteristics from the American Medical Association for a longitudinal cohort of 7,399 physicians. Descriptive and multivariable regression analyses were conducted of the concentration of prescribing (physician-level Herfindahl index) and preferences for and likelihood of prescribing two first-generation antipsychotics and six second-generation antipsychotics. Analyses adjusted for prescribing volume, specialty, demographic characteristics, practice setting, and education. Results Antipsychotic prescribing was highly concentrated at the physician level, with a mean unadjusted Herfindahl index of .33 in 2002 and .29 in 2007. Psychiatrists reduced the concentration of their prescribing more over time than did other physicians. High-volume psychiatrists had a Herfindahl index that was half that of low-volume physicians in other specialties (.18 versus .36), a difference that remained significant (p<.001) after adjustment for physician characteristics. The share of physicians preferring olanzapine dropped from 29.9% in 2002 to 10.3% in 2007 (p<.001) while the share favoring quetiapine increased from 9.4% to 44.5% (p<.001). Few physicians (<5%) preferred a first-generation antipsychotic in 2002 or 2007. Conclusions Preferences for specific antipsychotics changed dramatically during this period. Although physician prescribing remained heavily concentrated, the concentration decreased over time, particularly among psychiatrists.National Institute of Mental Health (U.S.) (Grant R01MH093359)National Institute of Mental Health (U.S.) (Grant P30 MH090333)National Institute of Mental Health (U.S.) (Grant R01MH087488)Agency for Healthcare Research and Quality (Grant R01HS017695)Robert Wood Johnson Foundation (Investigator Award in Health Policy Research

How Quickly Do Physicians Adopt New Drugs? The Case of Second-Generation Antipsychotics

Objective The authors examined physician adoption of second-generation antipsychotic medications and identified physician-level factors associated with early adoption. Methods The authors estimated Cox proportional-hazards models of time to adoption of nine second-generation antipsychotics by 30,369 physicians who prescribed antipsychotics between 1996 and 2008, when the drugs were first introduced, and analyzed the total number of agents prescribed during that time. The models were adjusted for physicians’ specialty, demographic characteristics, education and training, practice setting, and prescribing volume. Data were from IMS Xponent, which captures over 70% of all prescriptions filled in the United States, and the American Medical Association Physician Masterfile. Results On average, physicians waited two or more years before prescribing new second-generation antipsychotics, but there was substantial heterogeneity across products in time to adoption. General practitioners were much slower than psychiatrists to adopt second-generation antipsychotics (hazard ratios (HRs) range .10−.35), and solo practitioners were slower than group practitioners to adopt most products (HR range .77−.89). Physicians with the highest antipsychotic-prescribing volume adopted second-generation antipsychotics much faster than physicians with the lowest volume (HR range .15−.39). Psychiatrists tended to prescribe a broader set of antipsychotics (median=6) than general practitioners and neurologists (median=2) and pediatricians (median=1). Conclusions As policy makers search for ways to control rapid health spending growth, understanding the factors that influence physician adoption of new medications will be crucial in the efforts to maximize the value of care received by individuals with mental disorders as well as to improve medication safety.National Institute of Mental Health (U.S.) (R01 MH093359)Robert Wood Johnson Foundation (Investigator Award in Health Policy Research)Agency for Healthcare Research and Quality (R01HS017695)National Institute of Mental Health (U.S.) ((NIMH) R34 MH082682)National Institute of Mental Health (U.S.) ((NIMH) P30 MH090333)National Institute of Mental Health (U.S.) ((NIMH) R01 MH087488)National Science Foundation (U.S.) (0915674

Regional Variation in Physician Adoption of Antipsychotics: Impact on US Medicare expenditures

Background—Regional variation in US Medicare prescription drug spending is driven by higher prescribing of costly brand-name drugs in some regions. This variation likely arises from differences in the speed of diffusion of newly-approved medications. Second-generation antipsychotics were widely adopted for treatment of severe mental illness and for several off-label uses. Rapid diffusion of new psychiatric drugs likely increases drug spending but its relationship to non-drug spending is unclear. The impact of antipsychotic diffusion on drug and medical spending is of great interest to public payers like Medicare, which finance a majority of mental health spending in the U.S.National Institute of Mental Health (U.S.) (R01 MH093359

Estimating the economic impact of canine rabies to Viet Nam 2005–2014

The global economic impact of canine rabies has been estimated by several studies. Asia bears a disproportionate burden of this zoonosis due to high levels of human deaths and rates of post-exposure prophylaxis (PEP), but low investment in preventative dog vaccination. The same factors that cause rabies to burden much of Asia are also present in Viet Nam. This study estimated the economic burden of canine rabies in a societal perspective including direct and indirect cost of rabies in dogs, livestock, and humans. Using data collected from personal interviews, published literature, published and supplementary reports, and primary data collection, we estimated the economic impact of canine rabies in Viet Nam over a ten year period (2005–2014). We incorporated the direct and indirect costs for PEP, dog vaccination efforts, livestock losses, and disability adjusted life years (DALYs) into the analysis. General findings from this analysis indicated that over the 10 year study period, the total economic impact of canine rabies was over $719 million USD. The largest portion of impacts (92$1.75 USD. Our results indicate that canine rabies impacts in Viet Nam are consistent with the burden elsewhere reported in Asia, with large expenditures on PEP and very small investments in dog vaccination

Structure of a putative NTP pyrophosphohydrolase: YP_001813558.1 from Exiguobacterium sibiricum 255-15.

The crystal structure of a putative NTPase, YP_001813558.1 from Exiguobacterium sibiricum 255-15 (PF09934, DUF2166) was determined to 1.78 Å resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-α-helical NTP pyrophosphatases. In dimeric dUTPase-like proteins, a central four-helix bundle forms the active site. However, in YP_001813558.1, an unexpected intertwined swapping of two of the helices that compose the conserved helix bundle results in a `linked dimer' that has not previously been observed for this family. Interestingly, despite this novel mode of dimerization, the metal-binding site for divalent cations, such as magnesium, that are essential for NTPase activity is still conserved. Furthermore, the active-site residues that are involved in sugar binding of the NTPs are also conserved when compared with other α-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity

The structure of BVU2987 from Bacteroides vulgatus reveals a superfamily of bacterial periplasmic proteins with possible inhibitory function.

Proteins that contain the DUF2874 domain constitute a new Pfam family PF11396. Members of this family have predominantly been identified in microbes found in the human gut and oral cavity. The crystal structure of one member of this family, BVU2987 from Bacteroides vulgatus, has been determined, revealing a β-lactamase inhibitor protein-like structure with a tandem repeat of domains. Sequence analysis and structural comparisons reveal that BVU2987 and other DUF2874 proteins are related to β-lactamase inhibitor protein, PepSY and SmpA_OmlA proteins and hence are likely to function as inhibitory proteins

Promotion of Prescription Drugs to Consumers and Providers, 2001–2010

Background: Pharmaceutical firms heavily promote their products and may have changed marketing strategies in response to reductions in new product approvals, restrictions on some forms of promotion, and the expanding role of biologic therapies. Methods: We used descriptive analyses of annual cross-sectional data from 2001 through 2010 to examine direct-to-consumer advertising (DTCA) (Kantar Media) and provider-targeted promotion (IMS Health and SDI), including: (1) inflation-adjusted total promotion spending ($and percent of sales); (2) distribution by channel (consumer v. provider); and (3) provider specialty both for the industry as a whole and for top-selling biologic and small molecule therapies. Results: Total promotion peaked in 2004 at US$36.1 billion (13.4% of sales). By 2010 it had declined to $27.7B (9.0$370 million (8.8% of sales) spent on promotion, top biologics were promoted less, with only $33 million (1.4% of sales) spent per product. Little change occurred in the composition of promotion between primary care physicians and specialists from 2001–2010. Conclusions: These findings suggest that pharmaceutical companies have reduced promotion following changes in the pharmaceutical pipeline and patent expiry for several blockbuster drugs. Promotional strategies for biologic drugs differ substantially from small molecule therapies

Hypoxic oligodendrocyte precursor cell-derived VEGFA is associated with blood–brain barrier impairment

Abstract Cerebral small vessel disease is characterised by decreased cerebral blood flow and blood–brain barrier impairments which play a key role in the development of white matter lesions. We hypothesised that cerebral hypoperfusion causes local hypoxia, affecting oligodendrocyte precursor cell—endothelial cell signalling leading to blood–brain barrier dysfunction as an early mechanism for the development of white matter lesions. Bilateral carotid artery stenosis was used as a mouse model for cerebral hypoperfusion. Pimonidazole, a hypoxic cell marker, was injected prior to humane sacrifice at day 7. Myelin content, vascular density, blood–brain barrier leakages, and hypoxic cell density were quantified. Primary mouse oligodendrocyte precursor cells were exposed to hypoxia and RNA sequencing was performed. Vegfa gene expression and protein secretion was examined in an oligodendrocyte precursor cell line exposed to hypoxia. Additionally, human blood plasma VEGFA levels were measured and correlated to blood–brain barrier permeability in normal-appearing white matter and white matter lesions of cerebral small vessel disease patients and controls. Cerebral blood flow was reduced in the stenosis mice, with an increase in hypoxic cell number and blood–brain barrier leakages in the cortical areas but no changes in myelin content or vascular density. Vegfa upregulation was identified in hypoxic oligodendrocyte precursor cells, which was mediated via Hif1α and Epas1. In humans, VEGFA plasma levels were increased in patients versus controls. VEGFA plasma levels were associated with increased blood–brain barrier permeability in normal appearing white matter of patients. Cerebral hypoperfusion mediates hypoxia induced VEGFA expression in oligodendrocyte precursor cells through Hif1α/Epas1 signalling. VEGFA could in turn increase BBB permeability. In humans, increased VEGFA plasma levels in cerebral small vessel disease patients were associated with increased blood–brain barrier permeability in the normal appearing white matter. Our results support a role of VEGFA expression in cerebral hypoperfusion as seen in cerebral small vessel disease

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P &lt; 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms