Optical and physical properties of annealed amorphous niobium oxide thin films.

The physical and optical properties of coatings deposited using physical vapor deposition techniques exhibit changes during post deposition annealing. Optical properties including the index of refraction and spectral transmission vary when coatings are annealed. Physical and mechanical properties such as thickness, density, and stress are also impacted by annealing. In this paper, we study the source of these changes by examining the impact of 150-500°C annealing on N b 2 O 5 films deposited using thermal evaporation and reactive magnetron sputtering. Models based on the Lorentz-Lorenz equation and potential energy considerations explain the data, and rationalize conflicts between previously reported results.

Tenant-Based Housing Voucher Programs: A Community Guide Systematic Review.

CONTEXT: Unaffordable or insecure housing is associated with poor health in children and adults. Tenant-based housing voucher programs (voucher programs) limit rent to 30% or less of household income to help households with low income obtain safe and affordable housing. OBJECTIVE: To determine the effectiveness of voucher programs in improving housing, health, and other health-related outcomes for households with low income. DESIGN: Community Guide systematic review methods were used to assess intervention effectiveness and threats to validity. An updated systematic search based on a previous Community Guide review was conducted for literature published from 1999 to July 2019 using electronic databases. Reference lists of included studies were also searched. ELIGIBILITY CRITERIA: Studies were included if they assessed voucher programs in the United States, had concurrent comparison populations, assessed outcomes of interest, were written in English, and published in peer-reviewed journals or government reports. MAIN OUTCOME MEASURES: Housing quality and stability, neighborhood opportunity (safety and poverty), education, income, employment, physical and mental health, health care use, and risky health behavior. RESULTS: Seven studies met inclusion criteria. Compared with low-income households not offered vouchers, voucher-using households reported increased housing quality (7.9 percentage points [pct pts]), decreased housing insecurity or homelessness (-22.4 pct pts), and decreased neighborhood poverty (-5.2 pct pts).Adults in voucher-using households had improved health care access and physical and mental health. Female youth experienced better physical and mental health but not male youth. Children who entered the voucher programs under 13 years of age had improved educational attainment, employment, and income in their adulthood; children's gains in these outcomes were inversely related to their age at program entry. CONCLUSION: Voucher programs improved health and several health-related outcomes for voucher-using households, particularly young children. Research is still needed to better understand household's experiences and contextual factors that influence achievement of desired outcomes.

Permanent Supportive Housing With Housing First to Reduce Homelessness and Promote Health Among Homeless Populations With Disability: A Community Guide Systematic Review.

CONTEXT: Poor physical and mental health and substance use disorder can be causes and consequences of homelessness. Approximately 2.1 million persons per year in the United States experience homelessness. People experiencing homelessness have high rates of emergency department use, hospitalization, substance use treatment, social services use, arrest, and incarceration. OBJECTIVES: A standard approach to treating homeless persons with a disability is called Treatment First, requiring clients be "housing ready"-that is, in psychiatric treatment and substance-free-before and while receiving permanent housing. A more recent approach, Housing First, provides permanent housing and health, mental health, and other supportive services without requiring clients to be housing ready. To determine the relative effectiveness of these approaches, this systematic review compared the effects of both approaches on housing stability, health outcomes, and health care utilization among persons with disabilities experiencing homelessness. DESIGN: A systematic search (database inception to February 2018) was conducted using 8 databases with terms such as "housing first," "treatment first," and "supportive housing." Reference lists of included studies were also searched. Study design and threats to validity were assessed using Community Guide methods. Medians were calculated when appropriate. ELIGIBILITY CRITERIA: Studies were included if they assessed Housing First programs in high-income nations, had concurrent comparison populations, assessed outcomes of interest, and were written in English and published in peer-reviewed journals or government reports. MAIN OUTCOME MEASURES: Housing stability, physical and mental health outcomes, and health care utilization. RESULTS: Twenty-six studies in the United States and Canada met inclusion criteria. Compared with Treatment First, Housing First programs decreased homelessness by 88% and improved housing stability by 41%. For clients living with HIV infection, Housing First programs reduced homelessness by 37%, viral load by 22%, depression by 13%, emergency departments use by 41%, hospitalization by 36%, and mortality by 37%. CONCLUSIONS: Housing First programs improved housing stability and reduced homelessness more effectively than Treatment First programs. In addition, Housing First programs showed health benefits and reduced health services use. Health care systems that serve homeless patients may promote their health and well-being by linking them with effective housing services.

Expanded In-School Instructional Time and the Advancement of Health Equity: A Community Guide Systematic Review.

Expanded in-school instructional time (EISIT) may reduce racial/ethnic educational achievement gaps, leading to improved employment, and decreased social and health risks. When targeted to low-income and racial/ethnic minority populations, EISIT may thus promote health equity. Community Guide systematic review methods were used to search for qualified studies (through February 2015, 11 included studies) and summarize evidence of the effectiveness of EISIT on educational outcomes. Compared with schools with no time change, schools with expanded days improved students' test scores by a median of 0.05 standard deviation units (range, 0.0-0.25). Two studies found that schools with expanded day and year improved students' standardized test scores (0.04 and 0.15 standard deviation units). Remaining studies were inconclusive. Given the small effect sizes and a lack of information about the use of added time, there is insufficient evidence to determine the effectiveness of EISIT on academic achievement and thus health equity.

Examining the Effectiveness of Year-Round School Calendars on Improving Educational Attainment Outcomes Within the Context of Advancement of Health Equity: A Community Guide Systematic Review.

Students may lose knowledge and skills achieved in the school year during the summer break, with losses greatest for students from low-income families. Community Guide systematic review methods were used to summarize evaluations (published 1965-2015) of the effectiveness of year-round school calendars (YRSCs) on academic achievement, a determinant of long-term health. In single-track YRSCs, all students participate in the same school calendar; summer breaks are replaced by short "intersessions" distributed evenly throughout the year. In multi-track YRSCs, cohorts of students follow separate calendar tracks, with breaks at different times throughout the year. An earlier systematic review reported modest gains with single-track calendars and no gains with multi-track calendars. Three studies reported positive and negative effects for single-track programs and potential harm with multi-track programs when low-income students were assigned poorly resourced tracks. Lack of clarity about the role of intersessions as simple school breaks or as additional schooling opportunities in YRSCs leaves the evidence on single-track programs insufficient. Evidence on multi-track YRSCs is also insufficient.

Chronic Hyperphosphatemia and Vascular Calcification Are Reduced by Stable Delivery of Soluble Klotho.

αKlotho (αKL) regulates mineral metabolism, and diseases associated with αKL deficiency are characterized by hyperphosphatemia and vascular calcification (VC). αKL is expressed as a membrane-bound protein (mKL) and recognized as the coreceptor for fibroblast growth factor-23 (FGF23) and a circulating soluble form (cKL) created by endoproteolytic cleavage of mKL. The functions of cKL with regard to phosphate metabolism are unclear. We tested the ability of cKL to regulate pathways and phenotypes associated with hyperphosphatemia in a mouse model of CKD-mineral bone disorder and αKL-null mice. Stable delivery of adeno-associated virus (AAV) expressing cKL to diabetic endothelial nitric oxide synthase-deficient mice or αKL-null mice reduced serum phosphate levels. Acute injection of recombinant cKL downregulated the renal sodium-phosphate cotransporter Npt2a in αKL-null mice supporting direct actions of cKL in the absence of mKL. αKL-null mice with sustained AAV-cKL expression had a 74%-78% reduction in aorta mineral content and a 72%-77% reduction in mineral volume compared with control-treated counterparts (P<0.01). Treatment of UMR-106 osteoblastic cells with cKL + FGF23 increased the phosphorylation of extracellular signal-regulated kinase 1/2 and induced Fgf23 expression. CRISPR/Cas9-mediated deletion of fibroblast growth factor receptor 1 (FGFR1) or pretreatment with inhibitors of mitogen-activated kinase kinase 1 or FGFR ablated these responses. In summary, sustained cKL treatment reduced hyperphosphatemia in a mouse model of CKD-mineral bone disorder, and it reduced hyperphosphatemia and prevented VC in mice without endogenous αKL. Furthermore, cKL stimulated Fgf23 in an FGFR1-dependent manner in bone cells. Collectively, these findings indicate that cKL has mKL-independent activity and suggest the potential for enhancing cKL activity in diseases of hyperphosphatemia with associated VC.

Characterizing Substrate-Surface Interactions on Alumina-Supported Metal Catalysts by Dynamic Nuclear Polarization-Enhanced Double-Resonance NMR Spectroscopy.

The characterization of nanometer-scale interactions between carbon-containing substrates and alumina surfaces is of paramount importance to industrial and academic catalysis applications, but it is also very challenging. Here, we demonstrate that dynamic nuclear polarization surface-enhanced NMR spectroscopy (DNP SENS) allows the unambiguous description of the coordination geometries and conformations of the substrates at the alumina surface through high-resolution measurements of 13C-27Al distances. We apply this new technique to elucidate the molecular-level geometry of 13C-enriched methionine and natural abundance poly(vinyl alcohol) adsorbed on γ-Al2O3-supported Pd catalysts, and we support these results with element-specific X-ray absorption near-edge measurements. This work clearly demonstrates a surprising bimodal coordination of methionine at the Pd-Al2O3 interface.

An Inducible, Large-Intestine-Specific Transgenic Mouse Model for Colitis and Colitis-Induced Colon Cancer Research.

BACKGROUND: Animal models are an important tool to understand intestinal biology. Our laboratory previously generated C57BL/6-Tg(Car1-cre)5Flt transgenic mice (CAC) with large-intestine-specific Cre recombinase (Cre) expression as a model to study colon health. AIM: To expand the utility of the CAC mouse model by determining the impact of chemically induced colitis on CAC transgene expression. METHODS: CAC mice were crossed to Rosa reporter mice (Rosa26R (flox/flox) ) with a lox-STOP-lox signal controlling ß-galactosidase (ßgal) expression and then further crossed with Apc(CKO/CKO) mice in some experiments to delete Apc alleles (Apc (Δ580) ). Initially, 8-week-old CAC(Tg/WT);Rosa26R (flox/WT) ;Apc (Δ580/WT) mice were treated with dextran sulfate sodium (DSS) in drinking water (5 days, 0, 0.65, 1.35, or 2.0 %). Colon tissue damage and ßgal labeling were analyzed 10 day after stopping DSS. Next, 8-week-old CAC(Tg/WT);Rosa26R(flox/flox) mice were treated with 0 or 1.35 % DSS, and colonic ßgal labeling was assessed at 30 day post-DSS treatment. Finally, 10-week-old CAC(Tg/WT);Apc (Δ580/WT) mice were treated with DSS (0 or 2 %) for 5 days and colonic tumors were analyzed at 20 weeks. RESULTS: CAC(Tg/WT);Rosa26R (flox/WT) ;Apc (Δ580/WT) mice had a DSS dose-dependent increase in colon epithelial damage that correlated with increased epithelial ßgal labeling at 10 days (r (2) = 0.9, ß = 0.75). The ßgal labeling in CAC(Tg/WT);Rosa26R(flox/flox) mice colon remained high at 30 days, especially in the crypts of the healed ulcer. DSS also increased colon tumor incidence and multiplicity in CAC(Tg/WT);Apc (Δ580/WT) mice. CONCLUSIONS: DSS-mediated epithelial damage induces a persistent, Cre-mediated recombination of floxed alleles in CAC mice. This enables the examination of gene function in colon epithelium during experimental colitis and colitis-induced colon cancer.

Early Childhood Education to Promote Health Equity: A Community Guide Systematic Review.

CONTEXT: Children in low-income and racial and ethnic minority families often experience delays in development by 3 years of age and may benefit from center-based early childhood education. DESIGN: A meta-analysis on the effects of early childhood education by Kay and Pennucci best met Community Guide criteria and forms the basis of this review. RESULTS: There were increases in intervention compared with control children in standardized test scores (median = 0.29 SD) and high school graduation (median = 0.20 SD) and decreases in grade retention (median = 0.23 SD) and special education assignment (median = 0.28 SD). There were decreases in crime (median = 0.23 SD) and teen births (median = 0.46 SD) and increases in emotional self-regulation (median = 0.21 SD) and emotional development (median = 0.04 SD). All effects were favorable, but not all were statistically significant. Effects were also long-lasting. CONCLUSIONS: Because many programs are designed to increase enrollment for high-risk students and communities, they are likely to advance health equity.

Unmanned Aerial Systems in Occupational Hygiene-Learning from Allied Disciplines.

Unmanned Aerial System (UAS) technologies are rapidly developing, lowering cost, and technology barriers for their use in numerous applications. This review and commentary summarizes relevant literature in allied fields and evaluates potential application and utility of UAS technology in the discipline of occupational hygiene. Disciplines closely related to occupational hygiene are moving to investigate potential uses--and in some cases--already employing this technology for research or commercial purposes. The literature was reviewed to formulate a cross-sectional picture of how UAS technology is being used in these closely allied disciplines which could inform or guide potential use in occupational hygiene. Discussed are UAS applications in environmental monitoring, emergency response, epidemiology, safety, and process optimization. A rapidly developing state of the art indicates that there is potential utility for this technology in occupational hygiene. Benefits may include cost savings, time savings, and averting hazardous environments via remote sensing. The occupational hygiene community can look to allied fields to garner lessons and possible applications to their own practice.

Methionine bound to Pd/γ-Al2O3 catalysts studied by solid-state (13)C NMR.

The chemisorption and breakdown of methionine (Met) adsorbed on Pd/γ-Al2O3 catalysts were investigated by solid-state NMR. (13)C-enriched Met (ca. 0.4mg) impregnated onto γ-Al2O3 or Pd/γ-Al2O3 gives NMR spectra with characteristic features of binding to γ-Al2O3, to Pd nanoparticles, and oxidative or reductive breakdown of Met. The SCH3 groups of Met showed characteristic changes in chemical shift on γ-Al2O3 (13ppm) vs. Pd (19ppm), providing strong evidence for preferential binding to Pd, while the NC carbon generates a small resonance at 96ppm assigned to a distinct nonprotonated species bound to O or Pd. Additionally, NMR shows that the SCH3 groups of Met are mobile on γ-Al2O3 but immobilized by binding to Pd particles; on small Pd particles (ca. 4nm), the NCH groups undergo large-amplitude motions. In a reducing environment, Met breaks down by C-S bond cleavage followed by formation of C2-C4 organic acids. The SCH3 signal shifts to 22ppm, which is likely the signature of the principal species responsible for strong catalyst inhibition. These experiments demonstrate that solid-state magic-angle spinning NMR of (13)C-enriched Met can be a sensitive probe to investigate catalyst surfaces and characterize catalyst inhibition both before reaction and postmortem.

Out-of-School-Time Academic Programs to Improve School Achievement: A Community Guide Health Equity Systematic Review.

CONTEXT: Low-income and minority status in the United States are associated with poor educational outcomes, which, in turn, reduce the long-term health benefits of education. OBJECTIVE: This systematic review assessed the extent to which out-of-school-time academic (OSTA) programs for at-risk students, most of whom are from low-income and racial/ethnic minority families, can improve academic achievement. Because most OSTA programs serve low-income and ethnic/racial minority students, programs may improve health equity. DESIGN: Methods of the Guide to Community Preventive Services were used. An existing systematic review assessing the effects of OSTA programs on academic outcomes (Lauer et al 2006; search period 1985-2003) was supplemented with a Community Guide update (search period 2003-2011). MAIN OUTCOME MEASURE: Standardized mean difference. RESULTS: Thirty-two studies from the existing review and 25 studies from the update were combined and stratified by program focus (ie, reading-focused, math-focused, general academic programs, and programs with minimal academic focus). Focused programs were more effective than general or minimal academic programs. Reading-focused programs were effective only for students in grades K-3. There was insufficient evidence to determine effectiveness on behavioral outcomes and longer-term academic outcomes. CONCLUSIONS: OSTA programs, particularly focused programs, are effective in increasing academic achievement for at-risk students. Ongoing school and social environments that support learning and development may be essential to ensure the longer-term benefits of OSTA programs.

Animal models of colorectal cancer.

Colorectal cancer is a heterogeneous disease that afflicts a large number of people in the USA. The use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on colon biology. In addition, animal models with features of specific human colorectal cancers can be used to test strategies for cancer prevention and treatment. In this review, we provide an overview of the mechanisms driving human cancer, we discuss the approaches one can take to model colon cancer in animals, and we describe a number of specific animal models that have been developed for the study of colon cancer. We believe that there are many valuable animal models to study various aspects of human colorectal cancer. However, opportunities for improving upon these models exist.

Generation and activity of a humanized monoclonal antibody that selectively neutralizes the epidermal growth factor receptor ligands transforming growth factor-α and epiregulin.

At least seven distinct epidermal growth factor (EGF) ligands bind to and activate the EGF receptor (EGFR). This activation plays an important role in the embryo and in the maintenance of adult tissues. Importantly, pharmacologic EGFR inhibition also plays a critical role in the pathophysiology of diverse disease states, especially cancer. The roles of specific EGFR ligands are poorly defined in these disease states. Accumulating evidence suggests a role for transforming growth factor α (TGFα) in skin, lung, and kidney disease. To explore the role of Tgfa, we generated a monoclonal antibody (mAb41) that binds to and neutralizes human Tgfa with high affinity (KD = 36.5 pM). The antibody also binds human epiregulin (Ereg) (KD = 346.6 pM) and inhibits ligand induced myofibroblast cell proliferation (IC50 values of 0.52 and 1.12 nM for human Tgfa and Ereg, respectively). In vivo, a single administration of the antibody to pregnant mice (30 mg/kg s.c. at day 14 after plug) or weekly administration to neonate mice (20 mg/kg s.c. for 4 weeks) phenocopy Tgfa knockout mice with curly whiskers, stunted growth, and expansion of the hypertrophic zone of growth plate cartilage. Humanization of this monoclonal antibody to a human IgG4 antibody (LY3016859) enables clinical development. Importantly, administration of the humanized antibody to cynomolgus monkeys is absent of the skin toxicity observed with current EGFR inhibitors used clinically and no other pathologies were noted, indicating that neutralization of Tgfa could provide a relatively safe profile as it advances in clinical development.

Engineering catalyst microenvironments for metal-catalyzed hydrogenation of biologically derived platform chemicals.

It is shown that microenvironments formed around catalytically active sites mitigate catalyst deactivation by biogenic impurities that are present during the production of biorenewable chemicals from biologically derived species. Palladium and ruthenium catalysts are inhibited by the presence of sulfur-containing amino acids; however, these supported metal catalysts are stabilized by overcoating with poly(vinyl alcohol) (PVA), which creates a microenvironment unfavorable for biogenic impurities. Moreover, deactivation of Pd catalysts by carbon deposition from the decomposition of highly reactive species is suppressed by the formation of bimetallic PdAu nanoparticles. Thus, a PVA-overcoated PdAu catalyst was an order of magnitude more stable than a simple Pd catalyst in the hydrogenation of triacetic acid lactone, which is the first step in the production of biobased sorbic acid. A PVA-overcoated Ru catalyst showed a similar improvement in stability during lactic acid hydrogenation to propylene glycol in the presence of methionine.

A systems approach reveals species differences in hepatic stress response capacity.

To minimize the occurrence of unexpected toxicities in early phase preclinical studies of new drugs, it is vital to understand fundamental similarities and differences between preclinical species and humans. Species differences in sensitivity to acetaminophen (APAP) liver injury have been related to differences in the fraction of the drug that is bioactivated to the reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI). We have used physiologically based pharmacokinetic modeling to identify oral doses of APAP (300 and 1000 mg/kg in mice and rats, respectively) yielding similar hepatic burdens of NAPQI to enable the comparison of temporal liver tissue responses under conditions of equivalent chemical insult. Despite pharmacokinetic and biochemical verification of the equivalent NAPQI insult, serum biomarker and tissue histopathology analyses revealed that mice still exhibited a greater degree of liver injury than rats. Transcriptomic and proteomic analyses highlighted the stronger activation of stress response pathways (including the Nrf2 oxidative stress response and autophagy) in the livers of rats, indicative of a more robust transcriptional adaptation to the equivalent insult. Components of these pathways were also found to be expressed at a higher basal level in the livers of rats compared with both mice and humans. Our findings exemplify a systems approach to understanding differential species sensitivity to hepatotoxicity. Multiomics analysis indicated that rats possess a greater basal and adaptive capacity for hepatic stress responses than mice and humans, with important implications for species selection and human translation in the safety testing of new drug candidates associated with reactive metabolite formation.

Improved hydrothermal stability of mesoporous oxides for reactions in the aqueous phase.

A simple and inexpensive approach is used to coat metal oxide surfaces (SBA-15) with thin films of carbon. These carbon films provide improved hydrothermal stability to oxides, such as silica and alumina, which are not otherwise stable at elevated temperatures in the presence of liquid water. Furthermore, the carbon film changes the surface chemistry of the support.

Use of Herbarium Voucher Specimens To Investigate Phytochemical Composition in Poisonous Plant Research.

Poisonous plants cause large losses to the livestock industry through death, reduced production efficiency, reproductive dysfunction, and compromised harvesting of rangeland and pasture forages. Research investigating poisonous plants is complex because there are hundreds of genera of toxic plants representing thousands of species. To investigate the effects of poisonous plants on livestock, a clear understanding of the taxonomic identity of the plant and the ability to collect the plant in sufficient quantities for scientific studies is required. Subsequently, the active principles must be defined and investigated in the taxa of interest to better predict risk and make recommendations to reduce losses. Herbaria are collections of preserved plant specimens and are an important resource in poisonous plant research. Voucher specimens have often been used in the identification of the plant for the experimental reproduction of suspected livestock poisoning associated with a spontaneous case. More recently, herbarium specimens have been used to investigate the chemical composition of toxic plants as well as the distribution of different chemotypes over the landscape. The primary purpose of this review is to highlight the chemical analysis of herbarium specimens in poisonous plant research.

Intercostal Cryo Nerve Block in Minimally Invasive Cardiac Surgery: The Prospective Randomized FROST Trial.

INTRODUCTION: Intercostal cryo nerve block has been shown to enhance pulmonary function recovery and pain management in post-thoracotomy procedures. However, its benefit have never been demonstrated in minimal invasive thoracotomy heart valve surgery (Mini-HVS). The purpose of the study was to determine whether intraoperative intercostal cryo nerve block in conjunction with standard of care (collectively referred to hereafter as CryoNB) provided superior analgesic efficacy in patients undergoing Mini-HVS compared to standard-of-care (SOC). METHODS: FROST was a prospective, 3:1 randomized (CryoNB vs. SOC), multicenter trial in patients undergoing Mini-HVS. The primary endpoint was the 48-h postoperative forced expiratory volume in 1 s (FEV1) result. Secondary endpoints were visual analog scale (VAS) scores for pain at the surgical site and general pain, intensive care unit and hospital length-of-stay, total opioid consumption, and allodynia at 6 months postoperatively. RESULTS: A total of 84 patients were randomized to the two arms of the trial CryoNB (n = 65) and SOC (n = 19). Baseline Society of Thoracic Surgeons Predictive Risk of Mortality (STS PROM) score, ejection fraction, and FEV1 were similar between cohorts. A higher 48-h postoperative FEV1 result was demonstrated in the CryoNB cohort versus the SOC cohort (1.20 ± 0.46 vs. 0.93 ± 0.43 L; P = 0.02, one-sided two-sample t test). Surgical site VAS scores were similar between the CryoNB and SOC cohorts at all postoperative timepoints evaluated, but VAS scores not related to the surgical site were lower in the SOC group at 72, 94, and 120 h postoperatively. The SOC cohort had a 13% higher opioid consumption than the CryoNB cohort. One of 64 CryoNB patients reported allodynia that did not require pain medication at 10 months. CONCLUSIONS: The results of FROST demonstrated that intercostal CryoNB provided enhanced FEV1 score at 48 h postoperatively with optimized analgesic effectiveness versus SOC. Future larger prospective randomized trials are warranted to determine whether intercostal CryoNB has an opioid-sparing effect in patients undergoing Mini-HVS. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02922153.