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It is easy to dismiss staying with a bad plan as foolish, but most people are at risk of falling into this trap under the right circumstances. Plan continuation bias and escalation of commitment are two traps that have doomed many a project and plan. Thoughtfully applying design thinking can help overcome these obstacles and lead to successful outcomes. [ABSTRACT FROM AUTHOR]

Fibrolamellar carcinoma (FLC) is a rare liver tumor driven by the DNAJ-PKAc fusion protein that affects healthy young patients. Little is known about the immune response to FLC, limiting rational design of immunotherapy. Multiplex immunohistochemistry and gene expression profiling were performed to characterize the FLC tumor immune microenvironment and adjacent non-tumor liver (NTL). Flow cytometry and T cell receptor (TCR) sequencing were performed to determine the phenotype of tumor-infiltrating immune cells and the extent of T cell clonal expansion. Fresh human FLC tumor slice cultures (TSCs) were treated with antibodies blocking programmed cell death protein-1 (PD-1) and interleukin-10 (IL-10), with results measured by cleaved caspase-3 immunohistochemistry. Immune cells were concentrated in fibrous stromal bands, rather than in the carcinoma cell compartment. In FLC, T cells demonstrated decreased activation and regulatory T cells in FLC had more frequent expression of PD-1 and CTLA-4 than in NTL. Furthermore, T cells had relatively low levels of clonal expansion despite high TCR conservation across individuals. Combination PD-1 and IL-10 blockade signficantly increased cell death in human FLC TSCs. Immunosuppresion in the FLC tumor microenvironment is characterized by T cell exclusion and exhaustion, which may be reversible with combination immunotherapy. [ABSTRACT FROM AUTHOR]

Background: We identified that Stanford Health Care had a significant number of patients who after discharge are found by the utilization review committee not to meet Center for Mediare and Medicaid Services (CMS) 2-midnight benchmark for inpatient status. Some of the charges incurred during the care of these patients are written-off and known as Medicare 1-day write-offs. This study which aims to evaluate the use of a Best Practice Alert (BPA) feature on the electronic medical record, EPIC, to ensure appropriate designation of a patient's hospitalization status as either inpatient or outpatient in accordance with Center for Medicare and Medicaid services (CMS) 2 midnight length of stay benchmark thereby reducing the number of associated write-offs. Method: We incorporated a best practice alert (BPA) into the Epic Electronic Medical Record (EMR) that would prompt the discharging provider and the case manager to review the patients' inpatient designation prior to discharge and change the patient's designation to observation when deemed appropriate. Patients who met the inclusion criteria (Patients must have Medicare fee-for-service insurance, inpatient length of stay (LOS) less than 2 midnights, inpatient designation as hospitalization status at time of discharge, was hospitalized to an acute level of care and belonged to one of 37 listed hospital services at the time of signing of the discharge order) were randomized to have the BPA either silent or active over a three-month period from July 18, 2019, to October 18, 2019. Result: A total of 88 patients were included in this study: 40 in the control arm and 48 in the intervention arm. In the intervention arm, 8 (8/48, 16.7%) had an inpatient status designation despite potentially meeting Medicare guidelines for an observation stay, comparing to 23 patients (23/40, 57.5%) patients in the control group (p = 0.001). The estimated number of write-offs in the control arm was 17 (73.9%, out of 23 inpatient patients) while in the intervention arm was 1 (12.5%, out of 8 inpatient patient) after accounting for patients who may have met inpatient criteria for other reasons based on case manager note review. Conclusion: This is the first time to our knowledge that a BPA has been used in this manner to reduce the number of Medicare 1-day write-offs. [ABSTRACT FROM AUTHOR]

Background: During deployment, veterans of the 1991 Gulf War (GW) were exposed to multiple war-related toxicants. Roughly a third of these veterans continue to exhibit neurotoxicant induced symptoms of Gulf War Illness (GWI), a multi-faceted condition that includes fatigue, pain and cognitive decrements. When studied empirically, both deployed veterans with exposures and those who meet the criteria for GWI are more likely to show deficits in the area of neuropsychological functioning. Although studies have shown cognitive impairments in small sample sizes, it is necessary to revisit these findings with larger samples and newer cohorts to see if other areas of deficit emerge with more power to detect such differences. A group of researchers and clinicians with expertise in the area of GWI have identified common data elements (CDE) for use in research samples to compare data sets. At the same time, a subgroup of researchers created a new repository to share these cognitive data and biospecimens within the GWI research community. Methods: The present study aimed to compare cognitive measures of attention, executive functioning, and verbal memory in a large sample of GWI cases and healthy GW veteran controls using neuropsychological tests recommended in the CDEs. We additionally subdivided samples based on the specific neurotoxicant exposures related to cognitive deficits and compared exposed versus non-exposed veterans regardless of case criteria status. The total sample utilized cognitive testing outcomes from the newly collated Boston, Biorepository, Recruitment, and Integrative Network (BBRAIN) for GWI. Results: Participants included 411 GW veterans, 312 GWI (cases) and 99 healthy veterans (controls). Veterans with GWI showed significantly poorer attention, executive functioning, learning, and short-and-long term verbal memory than those without GWI. Further, GW veterans with exposures to acetylcholinesterase inhibiting pesticides and nerve gas agents, had worse performance on executive function tasks. Veterans with exposure to oil well fires had worse performance on verbal memory and those with pyridostigmine bromide anti-nerve gas pill exposures had better verbal memory and worse performance on an attention task compared to unexposed veterans. Conclusions: This study replicates prior results regarding the utility of the currently recommended CDEs in determining impairments in cognitive functioning in veterans with GWI in a new widely-available repository cohort and provides further evidence of cognitive decrements in GW veterans related to war-related neurotoxicant exposures. [ABSTRACT FROM AUTHOR]

Introduction: Exposure to nerve agents, pyridostigmine bromide (PB), pesticides, and oil-well fires during the 1991 Gulf War (GW) are major contributors to the etiology of Gulf War Illness (GWI). Since the apolipoprotein E (APOE) ε4 allele is associated with the risk of cognitive decline with age, particularly in the presence of environmental exposures, and cognitive impairment is one of the most common symptoms experienced by veterans with GWI, we examined whether the ε4 allele was associated with GWI. Methods: Using a case-control design, we obtained data on APOE genotypes, demographics, and self-reported GW exposures and symptoms that were deposited in the Boston Biorepository and Integrative Network (BBRAIN) for veterans diagnosed with GWI (n = 220) and healthy GW control veterans (n = 131). Diagnosis of GWI was performed using the Kansas and/or Center for Disease Control (CDC) criteria. Results: Age- and sex-adjusted analyses showed a significantly higher odds ratio for meeting the GWI case criteria in the presence of the ε4 allele (Odds ratio [OR] = 1.84, 95% confidence interval [CI = 1.07–3.15], p ≤ 0.05) and with two copies of the ε4 allele (OR = 1.99, 95% CI [1.23–3.21], p ≤ 0.01). Combined exposure to pesticides and PB pills (OR = 4.10 [2.12–7.91], p ≤ 0.05) as well as chemical alarms and PB pills (OR = 3.30 [1.56–6.97] p ≤ 0.05) during the war were also associated with a higher odds ratio for meeting GWI case criteria. There was also an interaction between the ε4 allele and exposure to oil well fires (OR = 2.46, 95% CI [1.07–5.62], p ≤ 0.05) among those who met the GWI case criteria. Conclusion: These findings suggest that the presence of the ε4 allele was associated with meeting the GWI case criteria. Gulf War veterans who reported exposure to oil well fires and have an ε4 allele were more likely to meet GWI case criteria. Long-term surveillance of veterans with GWI, particularly those with oil well fire exposure, is required to better assess the future risk of cognitive decline among this vulnerable population. [ABSTRACT FROM AUTHOR]

In 2014, the Australian Government established the Teacher Education Ministerial Advisory Group (TEMAG) to advise on how teacher education programmes could ensure new teachers were adequately prepared for the classroom. Following this, the Australian Government endorsed a key recommendation of the TEMAG Action Now: Classroom Ready Teachers report, the inclusion of specialisations in primary Initial Teacher Education (ITE). This research was conducted at an Australian public university that, in 2016, had embedded specialisations in a revised primary teacher programme structure and was one of the first ITE institutions in Australia to graduate primary teachers with a specialisation. Using a mixed-methods case study design with convenience sampling, this study sought to investigate these primary graduates' perceptions of undertaking a specialisation in relation to the development of content knowledge and pedagogical knowledge in the specialist area, as well as perceived employment advantages. This research took place over 4 years with participants having completed a Bachelor of Education (Primary) at least three months prior to participating. The participants reported benefits to having completed a primary specialisation but expressed concerns about their preparedness to teach their specialisation and whether it would result in any advantages for employment. Recommendations from the participants included teaching practice in their area of specialisation, consideration of specialist skills and changing the timetabling of the specialisation in the programme. Ultimately, there is a need for ongoing research in this area to determine the extent to which primary specialisations deliver the intended outcomes and impacts at both the policy driver level and the university level. [ABSTRACT FROM AUTHOR]

Few studies have focused on the application of the Tl isotopic system for geochemical exploration. We report ε 205Tl values of rock samples from the TL Deposit, British Columbia, Canada – a sediment-hosted massive sulfide (SHMS) deposit with characteristics of a Broken Hill-type deposit – and investigate relationships with major and trace element geochemistry. Maps generated using Tl isotope and trace element data indicate that ε 205Tl values can potentially be used to fingerprint ore mineralization at the TL Deposit. The sources of Tl and other metals (Ag, Pb, Zn) are assessed using Tl isotope data. Measured ε 205Tl values exhibit positive correlations with Pb, sedimentary exhalative metal index (Zn + 100*Pb + 100*Tl), and the redox proxy, U/Th, and negative correlations with Be, Cd, Ce, La, Ni and Th. Individual lithologies have distinct Tl isotopic compositions. Metal-rich heavily altered samples have relatively high ε 205Tl values (−5.0 to −2.5 ε -units) reflecting the euxinic conditions of the global Paleoproterozoic ocean and hydrothermal influence. Samples with lower ε 205Tl values (−15 to −7.6 ε -units) reflect a combination of their mineralogy (phyllosilicate minerals such as biotite and clinochlore), Tl from sediments reflecting the Tl isotopic composition of modern seawater, and possible low-temperature alteration processes. Samples with high Pb and Ag contents have high ε 205Tl values, indicating a hydrothermal origin of these metals, whereas Zn is highest in samples with low ε 205Tl values, indicating a low-temperature or sedimentary origin. Thallium isotopes, paired with conventional geochemical data, show promise as a useful tool for exploration of SHMS deposits with Broken Hill-type characteristics. Supplementary material: Major, minor and trace element contents of samples and reference materials, blank values, correlation coefficient values, and XRD patterns are available at https://doi.org/10.6084/m9.figshare.c.6370671 Thematic collection: This article is part of the Geochemical processes related to mined, milled, or natural metal deposits collection available at: https://www.lyellcollection.org/topic/collections/geochemical-processes-related-to-mined-milled-or-natural-metal-deposits [ABSTRACT FROM AUTHOR]

Background The burden of influenza is mostly felt by employees and employers because of increased absenteeism rates, loss of productivity and associated direct costs. Even though interventions against influenza among working adults are effective, patronage and compliance to these measures especially vaccination are low compared to other risk groups. Aims This study was aimed to assess evidence of economic evaluations of interventions against influenza virus infection among workers or in the workplace setting. Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guideline for systematic reviews was followed. Three databases, PubMed, Web of Science and EconLit, were searched using keywords to identify relevant articles from inception till 25 October 2020. Original peer-reviewed papers that conducted economic evaluations of influenza interventions using cost–benefit, cost–effectiveness or cost–utility analysis methods focused on working-age adults or work settings were eligible for inclusion. Two independent teams of co-authors extracted and synthesized data from identified studies. Results Twenty-four articles were included: 21 were cost–benefit analyses and 3 examined cost–effectiveness analyses. Two papers also presented additional cost–utility analysis. Most of the studies were pharmaceutical interventions (n = 23) primarily focused on vaccination programs while one study was a non-pharmaceutical intervention examining the benefit of paid sick leave. All but two studies reported that interventions against influenza virus infection at the workplace were cost-saving and cost-effective regardless of the analytic approach. Conclusions Further cost–effectiveness research in non-pharmaceutical interventions against influenza in workplace settings is warranted. There is a need to develop standardized methods for reporting economic evaluation methods to ensure comparability and applicability of future research findings. [ABSTRACT FROM AUTHOR]

Background: Prevention of TB is paramount to achieving elimination targets as recommended by the World Health Organization's action framework for low incidence countries striving to eliminate TB. Although the rates of TB in Canada are low, understanding the latent TB infection (LTBI) cascade is paramount to identifying gaps in care and treatment barriers, thereby increasing the effectiveness of preventive strategies. The purpose of this study was to examine the LTBI cascade of care and identify barriers to treatment completion in adults referred from primary care to a regional tertiary care TB clinic in Ottawa, Canada.Methods: Electronic medical records between January 2010 and December 2016 were reviewed retrospectively and an LTBI cascade of care was constructed from The Ottawa Hospital TB clinic and surrounding primary care clinics. A cohort of 2207 patients with untreated LTBI was used to ascertain the associations between demographic and clinical factors for both treatment non-initiation and non-completion using log-binomial univariable and multivariable regression models.Results: Of 2207 patients with untreated LTBI who were seen in the clinic during the study period, 1771 (80.2%) were offered treatment, 1203 (67.9% of those offered) started treatment, and 795 (66.1% of those started) completed treatment. In multivariable analysis, non-initiation of treatment was associated with older age (adjusted risk ratio [aRR] 1.06 per 5-year increase, 95% CI: 1.03-1.08) and female gender (aRR 1.28, 95% CI: 1.11-1.47). Non completion of treatment was associated with referral from the TB Clinic back to the primary care team following initial consult (aRR 1.62, 95% CI: 1.35-1.94) and treatment with the standard of 9 months of Isoniazid (9H) compared to 4 months of Rifampin (4R) (aRR 1.45, 95% CI:1.20-1.74).Conclusions: LTBI treatment completion was significantly decreased among patients who were referred back to primary care from the TB clinic. The 4R regimen resulted in more people completing LTBI treatment compared to 9H in keeping with a recently published RCT. Improved education, communication, and collaboration between tertiary care TB clinics and primary care teams may improve treatment completion rates and address the TB burden in low incidence communities in Canada. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2019 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2019 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2019 article‐registration‐date‐month 3 article‐registration‐date‐day 9 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2019_Article_226.pdf target‐type OnlinePDF issue‐type Regular article‐type ReviewPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine --> Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with limited response to cytotoxic chemoradiotherapy, as well as newer immunotherapies. The PDA tumor microenvironment contains infiltrating immune cells including cytotoxic T cells; however, there is an overall immunosuppressive milieu. Hypoxia is a known element of the solid tumor microenvironment and may promote tumor survival. Through various mechanisms including, but not limited to, those mediated by HIF‐1α, hypoxia also leads to increased tumor proliferation and metabolic changes. Furthermore, epithelial to mesenchymal transition is promoted through several pathways, including NOTCH and c‐MET, regulated by hypoxia. Hypoxia‐promoted changes also contribute to the immunosuppressive phenotype seen in many different cell types within the microenvironment and thereby may inhibit an effective immune system response to PDA. Pancreatic stellate cells (PSCs) and myofibroblasts appear to contribute to the recruitment of myeloid derived suppressor cells (MDSCs) and B cells in PDA via cytokines increased due to hypoxia. PSCs also increase collagen secretion in response to HIF‐1α, which promotes a fibrotic stroma that alters T cell homing and migration. In hypoxic environments, B cells contribute to cytotoxic T cell exhaustion and produce chemokines to attract more immunosuppressive regulatory T cells. MDSCs inhibit T cell metabolism by hoarding key amino acids, modulate T cell homing by cleaving L‐selectin, and prevent T cell activation by increasing PD‐L1 expression. Immunosuppressive M2 phenotype macrophages promote T cell anergy via increased nitric oxide (NO) and decreased arginine in hypoxia. Increased numbers of regulatory T cells are seen in hypoxia which prevent effector T cell activation through cytokine production and increased CTLA‐4. Effective immunotherapy for pancreatic adenocarcinoma and other solid tumors will need to help counteract the immunosuppressive nature of hypoxia‐induced changes in the tumor microenvironment. Promising studies will look at combination therapies involving checkpoint inhibitors, chemokine inhibitors, and possible targeting of hypoxia. While no model is perfect, assuring that models incorporate the effects of hypoxia on cancer cells, stromal cells, and effector immune cells will be crucial in developing successful therapies. [ABSTRACT FROM AUTHOR]

Objectives To assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early rheumatoid arthritis (RA) inception cohorts with a focus on methotrexate (MTX) exposure. Design Multicentre prospective early RA inception cohort studies; the early RA study (ERAS) and the early RA network (ERAN). Setting Secondary care, ERAS nine centres, ERAN 23 centres in England, Wales and Ireland. Participants Patients with new diagnosis of RA, n=2701. Standardised data including demographics, drug therapies and clinical outcomes including the presence of RA-ILD were collected at baseline, within 3-6 months, at 12 months and annually thereafter. Primary and secondary outcome measures Primary outcome was the association of MTX exposure on RA-ILD diagnosis. Secondary outcomes were the association of demographic, comorbid and RA-specific factors on RA-ILD diagnosis and the association of MTX exposure on time to RA-ILD diagnosis. Results Of 92 eligible ILD cases, 39 occurred in 1578 (2.5%) MTX exposed and 53 in 1114 (4.8%) non-MTX exposed cases. The primary analysis of RA-ILD cases only developing after any conventional synthetic diseasemodifying antirheumatic drug treatment (n=67) showed MTX exposure not to be associated with incident RA-ILD (OR 0.85, 95% CI 0.49 to 1.49, p=0.578) and a nonsignificant trend for delayed ILD diagnosis (OR 0.54, 95% CI 0.28 to 1.06, p=0.072). In an extended analysis including RA-ILD cases present at RA diagnosis (n=92), MTX exposure was associated with a significantly reduced risk of incident RA-ILD (OR 0.48, 95% CI 0.3 to 0.79, p=0.004) and longer time to ILD diagnosis (OR 0.41, 95% CI 0.23 to 0.75, p=0.004). Other independent baseline associations with incident RA-ILD were higher age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first outpatient visit. Conclusions MTX treatment was not associated with an increased risk of RA-ILD diagnosis. On the contrary, evidence suggested that MTX may delay the onset of ILD. [ABSTRACT FROM AUTHOR]

Using confocal Raman microspectroscopy, we derive parameters for bilayer water transport across an isolated nanoliter aqueous droplet pair. For a bilayer formed with two osmotically imbalanced and adherent nanoliter aqueous droplets in a surrounding oil solvent, a droplet interface bilayer (DIB), the water permeability coefficient across the lipid bilayer was determined from monitoring the Raman scattering from the C≡N stretching mode of K3Fe(CN)6 as a measure of water uptake into the swelling droplet of a DIB pair. We also derive passive diffusional permeability coefficient for D2O transport across a droplet bilayer using O–D Raman signal. This method provides a significant methodological advance in determining water permeability coefficients in a convenient and reliable way. [ABSTRACT FROM AUTHOR]

Graphene-based nanomaterials (GBN) have many potential biomedical applications. However, information regarding their biological properties and interactions with cells and/or soluble factors within a complex tissue is limited. The objective of this study was to use the growing feather (GF) of chickens as a minimally invasive cutaneous test-site to assess and monitor leukocyte recruitment in response to intradermal GBN injection. Specifically, the dermis of 20 GFs per chicken was injected with 10 μl of phosphate-buffered saline (PBS)-vehicle or 10 μl of 300 μg ml−1 oxygen-functionalized (f) GBN (6 chickens/treatment). GFs were collected before- (0) and at 0.25, 1, 2, 3, 4, 5, and 7 days post-injection and used for leukocyte-population analysis of immunofluorescently stained pulp cell suspensions or histological examination. Based on flow-cytometric cell population analysis, lymphocytes and macrophages were the major leukocyte-populations infiltrating GFs in response to f-GBN presence. Compared with PBS-controls, levels of T cells (γδ-, αβ-, CD4- and CD8-T cells) were greatly elevated in f-GBN-injected GFs within 6 h and remained elevated throughout the 7-day examination period. f-GBN's effects on local tissue leukocyte recruitment were not reflected in the blood, except for a higher percentage of lymphocytes on 7 days. These observations together with a visual examination of f-GBN-injected GF tissue-sections suggest a delayed-type hypersensitivity-like, inflammatory cell-mediated response to the non-biodegradable f-GBN. The GF ' in vivo test-tube'system together with blood sampling provided unique insight into the time-course, qualitative, and quantitative aspects of immune system activities initiated by the presence of f-GBN in a complex tissue of a living animal. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Health service planners, administrators and providers need to understand the patients' perspective of health services related to osteoporosis to optimise health outcomes. The aims of this study were to systematically identify and review the literature regarding patients' perceived health service needs relating to osteoporosis and osteopenia. A systematic scoping review was performed of publications in MEDLINE, EMBASE, CINAHL and PsycINFO (1990-2016). Descriptive data regarding study design and methodology were extracted and risk of bias assessed. Aggregates of patients' perceived needs of osteoporosis health services were categorised. Thirty-three studies (19 quantitative and 14 qualitative) from 1027 were relevant. The following areas of perceived need emerged: (1) patients sought healthcare from doctors to obtain information and initiate management. They were dissatisfied with poor communication, lack of time and poor continuity of care. (2) Patients perceived a role for osteoporosis pharmacotherapy but were concerned about medication administration and adverse effects. (3) Patients believed that exercise and vitamin supplementation were important, but there is a lack of data examining the needs for other non-pharmacological measures such as smoking cessation and alcohol. (4) Patients wanted diagnostic evaluation and ongoing surveillance of their bone health. This review identified patients' needs for better communication with their healthcare providers. It also showed that a number of important cornerstones of therapy for osteoporosis, such as pharmacotherapy and exercise, are identified as important by patients, as well as ongoing surveillance of bone health. Understanding patients' perceived needs and aligning them with responsive and evidence-informed service models are likely to optimise patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Integration of oncology and palliative care (PC) should be the standard model of care for patients with advanced cancer. An expert panel developed criteria that constitute integration. This study determined whether the PC service within this Health Service, which is considered to be fully "integrated", could be benchmarked against these criteria.Methods: A survey was undertaken to determine the perceived level of integration of oncology and palliative care by all health care professionals (HCPs) within our cancer centre. An objective determination of integration was obtained from chart reviews of deceased patients. Integration was defined as >70% of all respondents answered "agree" or "strongly agree" to each indicator and >70% of patient charts supported each criteria.Results: Thirty-four HCPs participated in the survey (response rate 69%). Over 90% were aware of the outpatient PC clinic, interdisciplinary and consultation team, PC senior leadership, and the acceptance of concurrent anticancer therapy. None of the other criteria met the 70% agreement mark but many respondents lacked the necessary knowledge to respond. The chart review included 67 patients, 92% of whom were seen by the PC team prior to death. The median time from referral to death was 103 days (range 0-1347). The level of agreement across all criteria was below our predefined definition of integration.Conclusion: The integration criteria relating to service delivery are medically focused and do not lend themselves to interdisciplinary review. The objective criteria can be audited and serve both as a benchmark and a basis for improvement activities. [ABSTRACT FROM AUTHOR]

Introduction To determine the association of fruit and vegetable consumption with overall sleep duration among pregnant women. Methods Data from the 2011 and 2012 Behavioral Risk Factors Surveillance System (BRFSS) were used. All women (n = 2951) of childbearing age (18-44 years) who were pregnant and responded to all fruit and vegetable consumption and sleep duration questions were included. Covariates included age, race, education level, exercise, and marital status. Data were analyzed using linear and ordinal logistic regression. Results Total daily fruit and vegetable consumption was not associated with sleep duration among pregnant women, controlling for confounders [β = −0.03, (−0.07, 0.00)]. Orange and green vegetable consumption were both inversely associated with sleep duration [β = −0.19, (−0.38, −0.01) and β = −0.20, (−0.33, −0.08) respectively]. Ordinal logistic regression found that the odds of meeting or exceeding sleep time recommendations increased slightly with each unit increase in total fruit and vegetable consumption [OR = 1.05 (1.003, 1.092)] and for every unit increase in fruit consumption [OR = 1.12 (1.038, 1.208)]. Women who exercised within the past 30 days reported approximately 20 min of additional sleep compared to those who did not [β = 0.32 (0.16, 0.49)]. Age, employment status, and marital status were also independently associated with sleep duration. Discussion Sleep duration in pregnant women was associated with exercise and other demographic factors, but only mildly associated with fruit and vegetable consumption. Future research should investigate the effects of additional factors including sleep quality, gestational age, family status and other medications as potential confounders. [ABSTRACT FROM AUTHOR]

Plant secondary compounds are diverse structurally, and associated biological effects can vary depending on multiple factors including chemical structure and reaction conditions. Phenolic compounds such as tannins can chelate dietary iron, and supplementation of animal species sensitive to iron overload with tannins may prevent/treat iron overload disorder. We assessed the nutrient and phenolic composition and iron-binding capacity of Carolina willow (Salix caroliniana), a plant fed to zoo-managed browsing herbivores. Based on studies in other plant species and the chemical structures of phenolic compounds, we hypothesized that the concentration of condensed tannins in willow would be inversely related to the concentration of phenolic glycosides and directly related to iron-binding capacity. Our results indicated that willow nutrient composition varied by year, season, and plant part, which could be taken into consideration when formulating animal diets. We also found that the predominant plant secondary compounds were condensed tannins with minimal phenolic glycosides. Instead of binding to iron, the willow leaf extracts reduced iron from the ferric to ferrous form, which may have prooxidative effects and increase the bioavailability of iron depending on animal species, gastrointestinal conditions, and whole animal processes. We recommend identifying alternative compounds that effectively chelate iron in vitro and conducting chelation therapy trials in vivo to assess potential effects on iron balance and overall animal health. Zoo Biol. [ABSTRACT FROM AUTHOR]

The article discusses situations in which both indemnitors and indemnitees have opinions to support for or go against finding a waiver for the attorney-client privilege. It mentions that the consensus regarding subject-matter waiver issues is very difficult to achieve. It adds that a joint-defense agreement which clearly mentions the party's expectation may help and indemnitors and indemnitees are required to follow developments in law cases which are decided and moved forward with care.

Freeze tolerance is a critical winter survival strategy for the wood frog, Rana sylvatica. In response to freezing, a number of genes are upregulated to facilitate the survival response. This includes fr10, a novel freeze-responsive gene first identified in R. sylvatica. This study analyzes the transcriptional expression of fr10 in seven tissues in response to freezing, anoxia, and dehydration stress, and throughout the Gosner stages of tadpole development. Transcription of fr10 increased overall in response to 24 h of freezing, with significant increases in expression detected in testes, heart, brain, and lung when compared to control tissues. When exposed to anoxia; heart, lung, and kidney tissues experienced a significant increase, while the transcription of fr10 in response to 40 % dehydration was found to significantly increase in both heart and brain tissues. An analysis of the transcription of fr10 throughout the development of the wood frog showed a relatively constant expression; with slightly lower transcription levels observed in two of the seven Gosner stages. Based on these results, it is predicted that fr10 has multiple roles depending on the needs and stresses experienced by the wood frog. It has conclusively been shown to act as a cryoprotectant, with possible additional roles in anoxia, dehydration, and development. In the future, it is hoped that further knowledge of the mechanism of action of FR10 will allow for increased stress tolerance in human cells and tissues. [ABSTRACT FROM AUTHOR]

The article offers suggestions for insurance policyholder attorneys on insurance coverage issues. The suggestions include policyholder attorneys informing their clients about the importance of complying with the conditions found in virtually all liability policies, altering policyholders to the adverse consequences of failing to build a solid foundation to support their coverage claim, and preparing a well thought out risk management and insurance program.

Background/objectives: Vitamin D deficiency in children remains a global concern. Although literature exists on the vitamin D status and its risk factors among children in the Middle East, findings have yielded mixed results, and large, representative community studies are lacking.Subjects/methods: In a nationally representative survey of 1077 Jordanian children of preschool age (12-59 months) in Spring 2010, we measured 25(OH)D3 concentrations by liquid chromatography-tandem mass spectrometry and calculated prevalence ratios for deficiency associated with various factors.Results: RESULTS showed 19.8% (95% confidence interval (CI): 16.4-23.3%) deficiency (<12 ng/ml) and 56.5% (95% CI: 52.0-61.0%) insufficiency (<20 ng/ml). In adjusted models, prevalence of deficiency was higher for females compared with males (prevalence ratio (PR)=1.74, 95% CI: 1.22-2.47, P=0.002) and lower for children 24-35 months of age (PR=0.64, 95% CI: 0.44-0.92, P=0.018) compared with children 12-23 months of age. In rural areas, there was no difference in prevalence of vitamin D deficiency between those whose mothers had/did not have vitamin D deficiency (P=0.312); however, in urban areas, prevalence of vitamin D deficiency was 3.18 times greater among those whose mothers were vitamin D deficient compared with those whose mothers were not deficient (P=0.000).Conclusions: Vitamin D deficiency and insufficiency pose significant public health problems in Jordanian children with female children disproportionately affected. Strong associations between vitamin D status in children and urban residency and maternal vitamin D status suggest that the behaviors related to sun exposure in urban mothers likely also affect the sun exposure and thus vitamin D status of their children. [ABSTRACT FROM AUTHOR]

Background/Objectives:Vitamin D deficiency in children remains a global concern. Although literature exists on the vitamin D status and its risk factors among children in the Middle East, findings have yielded mixed results, and large, representative community studies are lacking.Subjects/Methods:In a nationally representative survey of 1077 Jordanian children of preschool age (12-59 months) in Spring 2010, we measured 25(OH)D3 concentrations by liquid chromatography-tandem mass spectrometry and calculated prevalence ratios for deficiency associated with various factors.Results:Results showed 19.8% (95% confidence interval (CI): 16.4-23.3%) deficiency (<12 ng/ml) and 56.5% (95% CI: 52.0-61.0%) insufficiency (<20 ng/ml). In adjusted models, prevalence of deficiency was higher for females compared with males (prevalence ratio (PR)=1.74, 95% CI: 1.22-2.47, P=0.002) and lower for children 24-35 months of age (PR=0.64, 95% CI: 0.44-0.92, P=0.018) compared with children 12-23 months of age. In rural areas, there was no difference in prevalence of vitamin D deficiency between those whose mothers had/did not have vitamin D deficiency (P=0.312); however, in urban areas, prevalence of vitamin D deficiency was 3.18 times greater among those whose mothers were vitamin D deficient compared with those whose mothers were not deficient (P=0.000).Conclusions:Vitamin D deficiency and insufficiency pose significant public health problems in Jordanian children with female children disproportionately affected. Strong associations between vitamin D status in children and urban residency and maternal vitamin D status suggest that the behaviors related to sun exposure in urban mothers likely also affect the sun exposure and thus vitamin D status of their children. [ABSTRACT FROM AUTHOR]

Objective:To characterize the population and short-term outcomes in preterm infants with surgical necrotizing enterocolitis (NEC).Study Design:Preterm infants with surgical NEC were identified from 27 hospitals over 3 years using the Children's Hospitals Neonatal Database; infants with gastroschisis, volvulus, major congenital heart disease or surgical NEC that resolved prior to referral were excluded. Patient characteristics and pre-discharge morbidities were stratified by gestational age (<28 vs 280/7 to 366/7 weeks' gestation).Result:Of the 753 eligible infants, 60% were born at <28 weeks' gestation. The median age at referral was 14 days; only 2 infants were inborn. Male gender (61%) was overrepresented, whereas antenatal steroid exposure was low (46%). Although only 11% had NEC totalis, hospital mortality (<28 weeks' gestation: 41%; 280/7 to 366/7 weeks' gestation: 32%, P=0.02), short bowel syndrome (SBS)/intestinal failure (IF) (20% vs 26%, P=0.06) and the composite of mortality or SBS/IF (50% vs 49%, P=0.7) were prevalent. Also, white matter injury (11.7% vs 6.6%, P=0.02) and grade 3 to 4 intraventricular hemorrhages (23% vs 2.7%, P<0.01) were commonly diagnosed. After referral, the median length of hospitalization was longer for survivors (106 days; interquartile range (IQR) 79, 152) relative to non-survivors (2 days; IQR 1,17; P<0.001). These survivors were prescribed parenteral nutrition infrequently after hospital discharge (<28 weeks': 5.2%; 280/7 to 366/7 weeks': 9.9%, P=0.048).Conclusion:After referral for surgical NEC, the short-term outcomes are grave, particularly for infants born <28 weeks' gestation. Although analyses to predict outcomes are urgently needed, these data suggest that affected infants are at a high risk for lengthy hospitalizations and adverse medical and neuro-developmental abnormalities. [ABSTRACT FROM AUTHOR]

Objective:To characterize the population and short-term outcomes in preterm infants with surgical necrotizing enterocolitis (NEC).Study Design:Preterm infants with surgical NEC were identified from 27 hospitals over 3 years using the Children's Hospitals Neonatal Database; infants with gastroschisis, volvulus, major congenital heart disease or surgical NEC that resolved prior to referral were excluded. Patient characteristics and pre-discharge morbidities were stratified by gestational age (<28 vs 280/7 to 366/7 weeks' gestation).Result:Of the 753 eligible infants, 60% were born at <28 weeks' gestation. The median age at referral was 14 days; only 2 infants were inborn. Male gender (61%) was overrepresented, whereas antenatal steroid exposure was low (46%). Although only 11% had NEC totalis, hospital mortality (<28 weeks' gestation: 41%; 280/7 to 366/7 weeks' gestation: 32%, P=0.02), short bowel syndrome (SBS)/intestinal failure (IF) (20% vs 26%, P=0.06) and the composite of mortality or SBS/IF (50% vs 49%, P=0.7) were prevalent. Also, white matter injury (11.7% vs 6.6%, P=0.02) and grade 3 to 4 intraventricular hemorrhages (23% vs 2.7%, P<0.01) were commonly diagnosed. After referral, the median length of hospitalization was longer for survivors (106 days; interquartile range (IQR) 79, 152) relative to non-survivors (2 days; IQR 1,17; P<0.001). These survivors were prescribed parenteral nutrition infrequently after hospital discharge (<28 weeks': 5.2%; 280/7 to 366/7 weeks': 9.9%, P=0.048).Conclusion:After referral for surgical NEC, the short-term outcomes are grave, particularly for infants born <28 weeks' gestation. Although analyses to predict outcomes are urgently needed, these data suggest that affected infants are at a high risk for lengthy hospitalizations and adverse medical and neuro-developmental abnormalities. [ABSTRACT FROM AUTHOR]

Background/objectives:Two national surveys were conducted in Jordan in 2002 and 2010 to investigate the micronutrient status in women and children. To determine the prevalence of anemia, iron and folate deficiency among women and children in 2010 and compare with the prevalence of anemia and iron deficiency in 2002.Subjects/methods:A nationally representative survey was conducted in 2002 (1023 women, 15-49 years of age; 1059 children, 12-59 months of age) and a second survey in 2010 (2035 women; 940 children). Venous blood samples were used to measure hemoglobin, ferritin and red blood cell folate (the latter on a subsample of 393 women).Results:Among women in 2010, the prevalence of folate deficiency and insufficiency was 13.6% and 82.9%, respectively. Geometric mean serum ferritin was higher in 2010 compared with 2002 (21.3 ng/ml vs 18.3, P=0.01); there was no significant change in the prevalence of iron deficiency (35.1% vs 38.7%, P=0.17), iron deficiency anemia (19.1% vs 20.0%, P=0.61) or anemia (29.2% vs 29.3%, P=0.96). Among children, a significantly lower prevalence was observed in 2010 compared with 2002 for iron deficiency (13.7% vs 26.2% P<0.001) and iron deficiency anemia (4.8% vs 10.1%, P<0.001); a nonsignificant lower prevalence was observed for anemia (16.6% vs 20.2%, P=0.09).Conclusions:In 2010, approximately one of seven women was folate deficient and six out of seven were folate insufficient for the prevention of neural tube defects. Between 2002 and 2010, significant improvement was observed in the prevalence of iron deficiency in children, but not in women. [ABSTRACT FROM AUTHOR]

Background: Congenital tibial dysplasia is a severe pediatric condition that classically results in a persistent pseudarthrosis. A majority of these cases are associated with neurofibromatosis type I (NF1), a genetic disorder in which inactivation of the NF1 gene leads to overactivity of the Ras-MEK-MAPK (mitogen-activated protein kinase) signaling pathway. We therefore hypothesized that pharmaceutical inhibition of MEK-MAPK may be a beneficial therapeutic strategy. Methods: In vitro methods were used to demonstrate a role for the MEK inhibitor PD0325901 in promoting osteogenic differentiation in Nf1-/- calvarial osteoblasts. Local applications of rhBMP-2 and/or PD0325901 were then tested in a mouse model of NF1 tibial pseudarthrosis featuring localized double inactivation of the Nf1 gene in a fracture. Mice received no treatment, PD0325901 (10 mg/kg/day from two days before fracture to ten days after fracture), rhBMP-2 (10 µg), or a combination of rhBMP-2 and PD0325901. Results: Animals treated with the delivery vehicle alone, PD0325901, rhBMP-2, or the PD0325901 + rhBMP-2 combination showed union rates of 0%, 8%, 69% (p < 0.01), or 80% (p < 0.01), respectively, at twenty-one days after fracture. Mice treated with the rhBMP-2 + PD0325901 combination displayed a callus volume sixfold greater than the vehicle controls and twofold greater than the group receiving rhBMP-2 alone. Although MEK inhibition combined with rhBMP-2 led to increases in bone formation and union, the proportion of fibrous tissue in the callus was not significantly reduced. Conclusions: The data suggest that MEK inhibition can promote bone formation in combination with rhBMP-2 in the context of an NF1 pseudarthrosis. However, PD0325901 did not promote substantive bone anabolism in the absence of an exogenous anabolic stimulus and did not suppress fibrosis. Clinical Relevance: This study examines a signaling pathway-based approach to treating poor bone healing in a model of NF1 pseudarthrosis. [ABSTRACT FROM AUTHOR]

The aims of this study were to examine differences in self-schemas between persons living with HIV/AIDS with and without depressive symptoms, and the degree to which these self-schemas predict depressive symptoms in this population. Self-schemas are beliefs about oneself and include self-esteem, HIV symptom management self-efficacy, and self-compassion. Beck's cognitive theory of depression guided the analysis of data from a sample of 1766 PLHIV from the USA and Puerto Rico. Sixty-five percent of the sample reported depressive symptoms. These symptoms were significantly (p≤ 0.05), negatively correlated with age (r= −0.154), education (r= −0.106), work status (r= −0.132), income adequacy (r= −0.204, self-esteem (r= −0.617), HIV symptom self-efficacy (r= − 0.408), and self-kindness (r= − 0.284); they were significantly, positively correlated with gender (female/transgender) (r= 0.061), white or Hispanic race/ethnicity (r= 0.047) and self-judgment (r= 0.600). Fifty-one percent of the variance (F= 177.530 (df = 1524);p< 0.001) in depressive symptoms was predicted by the combination of age, education, work status, income adequacy, self-esteem, HIV symptom self-efficacy, and self-judgment. The strongest predictor of depressive symptoms was self-judgment. Results lend support to Beck's theory that those with negative self-schemas are more vulnerable to depression and suggest that clinicians should evaluate PLHIV for negative self-schemas. Tailored interventions for the treatment of depressive symptoms in PLHIV should be tested and future studies should evaluate whether alterations in negative self-schemas are the mechanism of action of these interventions and establish causality in the treatment of depressive symptoms in PLHIV. [ABSTRACT FROM AUTHOR]

An experiment was conducted to define the lysine requirement of neonatal pigs fed a liquid diet up to 5.5 kg bodyweight (BW). Neonatal pigs, 1-2 days old, with an initial bodyweight of 1.63 ± 0.04 kg, were randomly allotted to 10 isocaloric diets varying in lysine concentration from 0.76 to 1.62 g lysine/MJ gross energy (GE). Diets were formulated using whey protein concentrate and casein as protein sources and contained similar balance of indispensable amino acids. On day 1 of the experiment, pigs were fed 350 g liquid diet/kg metabolic bodyweight (BW0.75) according to the average BW of all pigs. On day 2, feeding rate was increased to 400 g/kg BW0.75. Increments were 100 g/kg BW0.75 per day for the subsequent 3 days until pigs reached 700 g/kg BW0.75 on day 5. Thereafter, feed was offered to pigs at a common feeding level of 700 g/kg BW0.75 each day until they reached 5.5 kg BW. Feed intake and BW were measured daily. Concentration of fat in the carcass decreased (P < 0.05) and the ratio of crude protein (CP) to fat in the carcass increased (P < 0.05) linearly as lysine inclusion increased. Both average daily gain and CP accretion increased (quadratic, P < 0.05), whereas fat accretion decreased (quadratic, P < 0.05) as lysine inclusion increased. Using the maximum point of the quadratic function, the estimated dietary lysine required for maximal growth (271 g/day) and CP accretion (45.2 g/day) was 1.41 and 1.32 g lysine/MJ GE, respectively. The dietary lysine required, estimating the requirement at the lower limit of the 95% confidence interval for CP accretion of 42.9 g/day, was 1.12 g lysine/MJ GE. Gross efficiency of CP deposition (CP deposition/CP intake) achieved a maximum of 0.85 at 1.01 g lysine/MJ GE. Low birthweight pigs tend to have a much lower chance of survival than their larger litter mates due to competition for milk which can lead to starvation. This study determined the lysine requirement of pigs weaned at 1-2 days of age and fed a liquid diet. Definition of nutrient requirements will lead to improved formulation of liquid diets for rearing low birthweight pigs to increase piglet survival and promote rapid growth rate to weaning. [ABSTRACT FROM AUTHOR]

The objective of this study was to extend the psychometric evaluation of a brief version of the Self-Compassion Scale (SCS). A secondary analysis of data from an international sample of 1967 English-speaking persons living with HIV disease was used to examine the factor structure, and reliability of the 12-item Brief Version Self-Compassion Inventory (BVSCI). A Maximum Likelihood factor analysis and Oblimin with Kaiser Normalization confirmed a two-factor solution, accounting for 42.58% of the variance. The BVSCI supported acceptable internal consistencies, with 0.714 for the total scale and 0.822 for Factor I and 0.774 for Factor II. Factor I (lower self-compassion) demonstrated strongly positive correlations with measures of anxiety and depression, while Factor II (high self-compassion) was inversely correlated with the measures. No significant differences were found in the BVSCI scores for gender, age, or having children. Levels of self-compassion were significantly higher in persons with HIV disease and other physical and psychological health conditions. The scale shows promise for the assessment of self-compassion in persons with HIV without taxing participants, and may prove essential in investigating future research aimed at examining correlates of self-compassion, as well as providing data for tailoring self-compassion interventions for persons with HIV. [ABSTRACT FROM PUBLISHER]

Background/Objectives:To combat iron and other micronutrient deficiencies, the Ministry of Health of the Kyrgyz Republic launched a regional Infant and Young Child Nutrition (IYCN) program in 2009, which included promotion of home fortification with micronutrient powder (MNP) containing iron (12.5 mg elemental iron), vitamin A (300 μg) and other micronutrients. Every 2 months children aged 6-24 months were provided 30 sachets to be taken on a flexible schedule. The objective was to assess biochemical indicators of iron and vitamin A status among children aged 6-24 months at the baseline and follow-up surveys.Subjects/Methods:Cross-sectional representative cluster surveys were conducted in 2008 (n=571 children) and 2010 (n=541). Data collected included measurement of hemoglobin, serum ferritin, soluble transferrin receptor (sTfR), retinol-binding protein, C-reactive protein (CRP) and α1-glycoprotein acid (AGP).Results:Among all children, declines were observed in the prevalence of: anemia, 50.6% versus 43.8% (P=0.05); total iron deficiency (either low ferritin or high sTfR), 77.3% versus 63.7% (P<0.01); and iron deficiency anemia, 45.5% versus 33.4% (P<0.01). Among children without inflammation as measured by CRP and AGP, similar declines were observed, but only declines in total iron deficiency and iron deficiency anemia reached statistical significance. Among all children and those without inflammation, the prevalence of vitamin A deficiency remained the same.Conclusions:One year after the introduction of home fortification with MNP, within a larger IYCN program, the prevalence of anemia, iron deficiency and iron deficiency anemia declined, but vitamin A deficiency remained unchanged. [ABSTRACT FROM AUTHOR]

High fevers and/or rashes prior to neutrophil engraftment are frequently observed after umbilical cord blood (UCB) transplantation, and the condition is referred to as pre-engraftment syndrome (PES). Few studies have evaluated the risk factors for and treatment response to PES. Therefore, we retrospectively characterized PES in 57 consecutive engrafted patients (12 years old) who received myeloablative dual UCB transplantation. All patients received TBI (13.2 Gy)-based myeloablative conditioning. Tacrolimus (n=35) or CYA (n=22) combined with mycophenolate mofetil was used as GVHD prophylaxis. PES was defined as the presence of non-infectious fever (38.5 °C) and/or rash prior to or on the day of neutrophil engraftment. The incidence (95% confidence interval) of PES was 77% (66-88%). The incidence of PES was significantly higher in patients who received CYA as a GVHD prophylaxis than those who received tacrolimus (P<0.001), and this association was confirmed in the multivariate analysis. The occurrence of PES did not impact OS or tumor relapse, although it may have increased non-relapse mortality (P=0.071). The incidence of acute GHVD or treatment-related mortality was not influenced by the choice to use corticosteroids to treat PES. This study suggests that use of CYA for GVHD prophylaxis increases the risk of PES following dual UCB transplantation. [ABSTRACT FROM AUTHOR]

Urolith formation has been documented in giraffes and goats. As research in giraffes poses logistical challenges, 16 buck goats were used as a model. The impact of two commercially available, pelleted feeds used for giraffes, ADF-16 and Wild Herbivore (WH), as well as the impact of alfalfa hay and pellet proportions (20% hay:80% pellets, 80P or 80% hay:20% pellet, 20P) on the formation of urolithogenic precursors in goat urine was accomplished in a 2 × 2 factorial balance study. Complete diets contained 0.60, 0.32, 0.35 and 0.26% phosphorus (P) with calcium:P ratios of 1.60, 4.16, 3.06 and 5.23, for 80P-ADF-16, 20P-ADF-16, 80P-WH and 20P-WH respectively. Total faeces and urine were collected over two 5-day periods to assess N and mineral balance. Fresh urine samples were collected and evaluated microscopically for urolithic crystal content. Urinary nitrogen (N) was lower and N retention was higher in goats fed 80P diets (p < 0.05). Intake of P was greatest for goats fed 80P-ADF-16; however, urinary P excretion and P retention were not affected by treatment. Crystal scores were higher in animals receiving 80P diets (p = 0.08), with crystals being composed predominantly of calcium phosphate. Urine pH was alkaline (>8) for all treatments. Urinary P concentration, a risk factor for urolithiasis, was highest (p ≤ 0.06) in the 80P-ADF-16 treatment (0.38 vs. 0.01, 0.02 and 0.04 mg/dl for 20P-ADF-16, 80P-WH and 20P-WH respectively), reflecting its highest dietary P level. Further investigation is recommended to determine the long-term effects of these diets on urolithogenic compound formation. [ABSTRACT FROM AUTHOR]