bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preventing deaths and injuries from house fires: an outcome evaluation of a community-based smoke alarm installation programme
Authors: Istre Gregory R , McCoy Mary A , Moore Billy J , Roper Carey , Stephens-Stidham Shelli , Barnard Jeffrey J , Carlin Debra K , Stowe Martha , Anderson Ron J 
Published: July 2013

BackgroundFew studies have examined the impact of community-based smoke alarm (SA) distribution programmes on the occurrence of house fire-related deaths and injuries (HF-D/I).ObjectiveTo determine whether the rate of HF-D/I differed for programme houses that had a SA installed through a community-based programme called Operation Installation, versus non-programme houses in the same census tracts that had not received such a SA.MethodsTeams of volunteers and firefighters canvassed houses in 36 high-risk target census tracts in Dallas, TX, between April 2001 and April 2011, and installed lithium-powered SAs in houses where residents were present and gave permission. We then followed incidence of HF-D/I among residents of the 8134 programme houses versus the 24 346 non-programme houses.ResultsAfter a mean of 5.2 years of follow-up, the unadjusted HF-D/I rate was 68% lower among residents of programme houses versus non-programme houses (3.1 vs 9.6 per 100 000 population, respectively; rate ratio, 0.32; 95% CI 0.10 to 0.84). Multivariate analysis including several demographic variables showed that the adjusted HF-D/I rate in programme houses was 63% lower than non-programme houses. The programme was most effective in the first 5 years after SA installation, with declining difference in rates after the 6th year, probably due to SAs becoming non-functional during that time.ConclusionsThis collaborative, community-based SA installation programme was effective at preventing deaths and injuries from house fires, but the duration of effectiveness was less than 10 years.
How long do smoke alarms function? A cross-sectional follow-up survey of a smoke alarm installation programme
Authors: McCoy Mary A , Roper Carey , Campa Emily , Stephens-Stidham Shelli , Carlin Debra K , Istre Gregory R 
Published: July 2013

ObjectiveTo assess the functionality of lithium-powered smoke alarms that had been installed through a community-based programme called Operation Installation (OI).MethodsA random sample was chosen of homes that had received smoke alarms through OI, 2, 4, 6, 8 and 10 years previously. Sampled homes were visited, and information collected included functional status of smoke alarms. For homes in the 6-, 8- and 10-year sample, smoke alarms were removed and tested for battery and alarm function.Results800 homes were included in the survey results; 1884 smoke alarms had been installed through OI. The proportion of homes that had at least one functioning OI smoke alarm ranged from 91.8% for year 2 sample to 19.8% for year 10. Of the originally installed smoke alarms in year 10 sample, 45.5% had been removed and 59% (64/108) of those that were still installed were not functioning. Multivariate analysis showed that the presence of at least one working alarm in the home was associated positively with the number of smoke alarms that were originally installed and whether the original occupant was still living in the home, and negatively with the length of time since the smoke alarm was installed, and whether there was a smoker in the home. Testing of the smoke alarms revealed that most non-functioning alarms had missing or dead batteries.ConclusionsLess than a quarter of the originally installed smoke alarms were still present and functioning by year 10. These findings have important implications for smoke alarm installation programmes.
Sex differences in neonatal mortality in Sarlahi, Nepal: the role of biology and environment
Authors: Rosenstock Summer , Katz Joanne , Mullany Luke C , Khatry Subarna K , LeClerq Steven C , Darmstadt Gary L , Tielsch James M 
Published: July 2013

BackgroundStudies in South Asia have documented increased risk of neonatal mortality among girls, despite evidence of a biological survival advantage. Associations between gender preference and mortality are cited as reasons for excess mortality among girls. This has not, however, been tested in statistical models.MethodsA secondary analysis of data from a population-based randomised controlled trial of newborn infection prevention conducted in rural southern Nepal was used to estimate sex differences in early and late neonatal mortality, with girls as the reference group. The analysis investigated which underlying biological factors (immutable factors specific to the newborn or his/her mother) and environmental factors (mutable external factors) might explain observed sex differences in mortality.ResultsNeonatal mortality was comparable by sex (Ref=girls; OR 1.06, 95% CI 0.92 to 1.22). When stratified by neonatal period, boys were at 20% (OR 1.20, 95% CI 1.02% to 1.42%) greater risk of early and girls at 43% (OR 0.70, 95% CI 0.51% to 0.94%) greater risk of late neonatal mortality. Biological factors, primarily respiratory depression and unconsciousness at birth, explained excess early neonatal mortality among boys. Increased late neonatal mortality among girls was explained by a three-way environmental interaction between ethnicity, sex and prior sibling composition (categorised as primiparous newborns, infants born to families with prior living boys or boys and girls, and infants born to families with only prior living girls).ConclusionsRisk of neonatal mortality inverted between the early and late neonatal periods. Excess risk of early neonatal death among boys was consistent with biological expectations. Excess risk for late neonatal death among girls was not explained by overarching gender preference or preferential care-seeking for boys as hypothesised, but was driven by increased risk among Madeshi girls born to families with only prior girls.
Deployed antimicrobial stewardship: an audit of antimicrobial use at Role 3
Authors: Fletcher Tom E , Hutley E , Adcock C J , Martin N , Wilson D R 
Published: July 2013

IntroductionInfections due to multidrug-resistant organisms are increasingly prevalent, and antimicrobial stewardship has become a priority for many healthcare organisations, including the Defence Medical Services. In military environments, infectious diseases remain a significant burden, and infections complicating the care of modern complex combat injuries are well recognised. A focus on infection prevention and control in the deployed environment is essential, and an important element of this is an antimicrobial formulary and stewardship programme. This audit analyses antimicrobial prescribing practices by military clinicians in patients admitted to UK/US Role 3 medical treatment facility in Camp Bastion, Afghanistan, relative to the UK published guidance.MethodsRetrospective case note review of all in-patient admissions during two time periods (October 2011 and October 2012). Notes were independently reviewed by an infection specialist not involved in the management of the patients.Results475 case notes were reviewed, of which 250 received antimicrobials. Coalition forces represented the most common patient group (131/250), with battle injury the most frequent indication (139/250) for antimicrobial prescription, followed by disease (100/250). A total of 302 antimicrobials were prescribed, with co-amoxiclav being the most frequently used antibiotic in 74% (185/250) of patients. 84.8% (212/250) were prescribed antimicrobials in line with the antimicrobial formulary. In battle injury, 93.5% (130/139) of antimicrobial prescriptions were in line with the formulary compared with 73.9% (82/111) in disease and non-battle injury patients.ConclusionsMaintaining a strong infection control effort in the deployed setting, even in a stabilised operational environment, is difficult, but our data show good compliance to the antimicrobial formulary superior to that reported in civilian hospitals. To improve this, further innovative strategies are required, combined with a continued focus on infection control basics across the full spectrum of care.
Geomorphological evidence of cold-based glacier activity in South Victoria Land, Antarctica
Authors: Atkins C. B. 
Published: July 2013

Abstract
Cold-based glaciers have long been recognized as capable of covering and protecting landscapes. However, recent studies of modern cold-based glaciers in Antarctica show that, in some situations, erosion, deformation and deposition can occur. Recognizing the dual ability of cold-based glaciers to protect and preserve surfaces on the one hand and erode and modify on the other is important for correctly interpreting the often-subtle imprint of cold-based glaciers on landscapes. A range of geomorphological features related to cold-based glacier activity has now been documented along with an improved understanding of cold-based glacier structure, processes and interaction with various substrates. Collectively, this provides an enhanced ability to understand the impact of cold-based glaciers on landscapes and reappraise the geomorphological record. Such insight allows recognition of previously unknown glacial events and better interpretations of the landscape exposure record. This is particularly important at the margins of the Antarctic Ice Sheets, where past fluctuations in ice sheet volume and its contributions to post glacial sea-level rise are poorly constrained. This paper reviews the known geomorphological evidence associated with cold-based glaciers in the South Victoria Land region of the Transantarctic Mountains. It aims to provide progress towards a set of criteria for recognizing cold-based glacier activity in other regions and to highlight the implications of cold-based glacial activity for surface exposure studies and interpreting glacial history.
Erlotinib Resistance in Lung Cancer Cells Mediated by Integrin β1/Src/Akt-Driven Bypass Signaling
Authors: Kanda Rina , Kawahara Akihiko , Watari Kosuke , Murakami Yuichi , Sonoda Kahori , Maeda Masashi , Fujita Hideaki , Kage Masayoshi , Uramoto Hidetaka , Costa Carlota , Kuwano Michihiko , Ono Mayumi 
Published: July 2013

Abstract
EGF receptor (EGFR) kinase inhibitors, including gefitinib and erlotinib, exert potent therapeutic efficacy in non–small cell lung cancers harboring EGFR-activating mutations. However, most patients ultimately develop resistance to these drugs. Here, we report a novel mechanism of acquired resistance to EGFR tyrosine kinase inhibitors and the reversal of which could improve clinical outcomes. In erlotinib-resistant lung cancer cells harboring activating EGFR mutations that we established, there was increased expression of Src, integrin β1, α2, and α5 along with enhanced cell adhesion activity. Interestingly, RNAi-mediated silencing of integrin β1 restored erlotinib sensitivity and reduced activation of Src and Akt after erlotinib treatment. Furthermore, Src silencing inhibited Akt phosphorylation and cell growth, with this inhibitory effect further augmented by erlotinib treatment. Increased expression of integrin β1, α5, and/or α2 was also observed in refractory tumor samples from patients with lung cancer treated with erlotinib and/or gefitinib. Together, our findings identify the integrin β1/Src/Akt signaling pathway as a key mediator of acquired resistance to EGFR-targeted anticancer drugs. Cancer Res; 73(20); 6243–53. ©2013 AACR.
A Synthetic Lethality–Based Strategy to Treat Cancers Harboring a Genetic Deficiency in the Chromatin Remodeling Factor BRG1
Authors: Oike Takahiro , Ogiwara Hideaki , Tominaga Yuichi , Ito Kentaro , Ando Osamu , Tsuta Koji , Mizukami Tatsuji , Shimada Yoko , Isomura Hisanori , Komachi Mayumi , Furuta Koh , Watanabe Shun-Ichi , Nakano Takashi , Yokota Jun , Kohno Takashi 
Published: July 2013

Abstract
The occurrence of inactivating mutations in SWI/SNF chromatin-remodeling genes in common cancers has attracted a great deal of interest. However, mechanistic strategies to target tumor cells carrying such mutations are yet to be developed. This study proposes a synthetic-lethality therapy for treating cancers deficient in the SWI/SNF catalytic (ATPase) subunit, BRG1/SMARCA4. The strategy relies upon inhibition of BRM/SMARCA2, another catalytic SWI/SNF subunit with a BRG1-related activity. Immunohistochemical analysis of a cohort of non–small-cell lung carcinomas (NSCLC) indicated that 15.5% (16 of 103) of the cohort, corresponding to preferentially undifferentiated tumors, was deficient in BRG1 expression. All BRG1-deficient cases were negative for alterations in known therapeutic target genes, for example, EGFR and DDR2 gene mutations, ALK gene fusions, or FGFR1 gene amplifications. RNA interference (RNAi)–mediated silencing of BRM suppressed the growth of BRG1-deficient cancer cells relative to BRG1-proficient cancer cells, inducing senescence via activation of p21/CDKN1A. This growth suppression was reversed by transduction of wild-type but not ATPase-deficient BRG1. In support of these in vitro results, a conditional RNAi study conducted in vivo revealed that BRM depletion suppressed the growth of BRG1-deficient tumor xenografts. Our results offer a rationale to develop BRM-ATPase inhibitors as a strategy to treat BRG1/SMARCA4–deficient cancers, including NSCLCs that lack mutations in presently known therapeutic target genes. Cancer Res; 73(17); 5508–18. ©2013 AACR.
Racial Differences in the Incidence and Clearance of Human Papilloma Virus (HPV): The HPV in Men (HIM) Study
Authors: Schabath Matthew B. , Villa Luisa L. , Lin Hui-Yi , Fulp William J. , Akogbe Gabriel O. , Abrahamsen Martha E. , Papenfuss Mary R. , Lazcano-Ponce Eduardo , Salmerón Jorge , Quiterio Manuel , Giuliano Anna R. 
Published: July 2013

Abstract
Background: This analysis assessed the acquisition (incidence) and persistence (clearance) of human papilloma virus (HPV) infection by self-reported race among men in The HPV in Men (HIM) Study, a multinational prospective study of the natural history of genital HPV infections.
Methods: Self-reported race was categorized as White, Black, Asian/Pacific Islander (PI), or multiple and mixed race. Genital samples were combined for HPV DNA testing and categorized by any, oncogenic, and non-oncogenic HPV infections.
Results: Asian/PI race had significantly the lowest incidence of any, oncogenic, and non-oncogenic HPV infection (P &lt; 0.001). In multivariable analyses, Asian/PI race was associated with a lower probability of acquiring any [HR = 0.63; 95% confidence interval (CI), 0.42–0.95] and non-oncogenic HPV infection (HR = 0.61; 95% CI, 0.40–0.93) when compared to Whites. No significant associations were evident for Asian/PI race for clearance. Multiple and mixed race was significantly associated with lower probability of acquiring non-oncogenic HPV infection (HR = 0.83; 95% CI, 0.69–0.99) and borderline significant associations were observed for any HPV (HR = 0.91) and oncogenic infections (HR = 0.92). Multiple and mixed race was associated with a lower probability of clearing any (HR = 0.92; 95% CI, 0.84–1.00) and oncogenic HPV infections (HR = 0.85; 95% CI, 0.75–0.95).
Conclusion: Asian/PI race had the lowest incidence of HPV and exhibited a lower probability of acquiring new HPV infections. Multiple and mixed race had the second lowest incidence of infection and was associated with a lower probability of acquiring and clearing an HPV infection.
Impact: Race-specific differences in HPV infection could be due to behavior, innate genetic differences, or circulating intratypic HPV variants. Cancer Epidemiol Biomarkers Prev; 22(10); 1762–70. ©2013 AACR.
Multiple Myeloma Patients Have a Specific Serum Metabolomic Profile That Changes after Achieving Complete Remission
Authors: Puchades-Carrasco Leonor , Lecumberri Ramón , Martínez-López Joaquín , Lahuerta Juan-José , Mateos María-Victoria , Prósper Felipe , San-Miguel Jesús F. , Pineda-Lucena Antonio 
Published: July 2013

Abstract
Purpose: Multiple myeloma remains an incurable disease. New approaches to develop better tools for improving patient prognostication and monitoring treatment efficacy are very much needed. In this study, we aimed to evaluate the potential of metabolomics by 1H-NMR to provide information on metabolic profiles that could be useful in the management of multiple myeloma.
Experimental Design: Serum samples were collected from multiple myeloma patients at the time of diagnosis and after achieving complete remission. A matched control set of samples was also included in the study. The 1H-NMR measurements used to obtain the metabolic profile for each patient were followed by the application of univariate and multivariate statistical analyses to determine significant differences.
Results: Metabolic profiles of multiple myeloma patients at diagnosis exhibited higher levels of isoleucine, arginine, acetate, phenylalanine, and tyrosine, and decreased levels of 3-hydroxybutyrate, lysine, glutamine, and some lipids compared with the control set. A similar analysis conducted in multiple myeloma patients after achieving complete remission indicated that some of the metabolic changes (i.e., glutamine, cholesterol, lysine) observed at diagnosis displayed a variation in the opposite direction upon responding to treatment, thus contributing to multiple myeloma patients having a closer metabolic profile to those of healthy individuals after the disappearance of major disease manifestations.
Conclusions: The results highlight the potential of metabolic profiles obtained by 1H-NMR in identifying multiple myeloma biomarkers that may be useful to objectively discriminate individuals with and without multiple myeloma, and monitor response to treatment. Clin Cancer Res; 19(17); 4770–9. ©2013 AACR.
Downregulation of Hematopoietic MUC1 during Experimental Colitis Increases Tumor-Promoting Myeloid-Derived Suppressor Cells
Authors: Poh Tze Wei , Madsen Cathy S. , Gorman Jessica E. , Marler Ronald J. , Leighton Jonathan A. , Cohen Peter A. , Gendler Sandra J. 
Published: July 2013

Abstract
Purpose: MUC1 is a tumor-associated antigen that is aberrantly expressed in cancer and inflammatory bowel disease (IBD). Even though immune cells express low MUC1 levels, their modulations of MUC1 are important in tumor progression. Consistent with previous clinical data that show increased myeloid-derived suppressor cells (MDSCs) in IBD, we now show that downregulation of MUC1 on hematopoietic cells increases MDSCs in IBD, similar to our data in tumor-bearing mice. We hypothesize that MDSC expansion in IBD is critical for tumor progression.
Experimental Design: To mechanistically confirm the linkage between Muc1 downregulation and MDSC expansion, we generated chimeric mice that did not express Muc1 in the hematopoietic compartment (KO→WT). These mice were used in two models of colitis and colitis-associated cancer (CAC) and their responses were compared with wild-type (WT) chimeras (WT→WT).
Results: KO→WT mice show increased levels of MDSCs during colitis and increased protumorigenic signaling in the colon during CAC, resulting in larger colon tumors. RNA and protein analysis show increased upregulation of metalloproteinases, collagenases, defensins, complements, growth factors, cytokines, and chemokines in KO→WT mice as compared with WT→WT mice. Antibody-mediated depletion of MDSCs in mice during colitis reduced colon tumor formation during CAC.
Conclusion: Development of CAC is a serious complication of colitis and our data highlight MDSCs as a targetable link between inflammation and cancer. In addition, the lack of MUC1 expression on MDSCs can be a novel marker for MDSCs, given that MDSCs are still not well characterized in human cancers. Clin Cancer Res; 19(18); 5039–52. ©2013 AACR.
Anti-PD-1 Antibody Therapy Potently Enhances the Eradication of Established Tumors By Gene-Modified T Cells
Authors: John Liza B. , Devaud Christel , Duong Connie P.M. , Yong Carmen S. , Beavis Paul A. , Haynes Nicole M. , Chow Melvyn T. , Smyth Mark J. , Kershaw Michael H. , Darcy Phillip K. 
Published: July 2013

AbstractPurpose: To determine the antitumor efficacy and toxicity of a novel combination approach involving adoptive T-cell immunotherapy using chimeric antigen receptor (CAR) T cells with an immunomodulatory reagent for blocking immunosuppression.Experimental Design: We examined whether administration of a PD-1 blocking antibody could increase the therapeutic activity of CAR T cells against two different Her-2+ tumors. The use of a self-antigen mouse model enabled investigation into the efficacy, mechanism, and toxicity of this combination approach.Results: In this study, we first showed a significant increase in the level of PD-1 expressed on transduced anti-Her-2 CD8+ T cells following antigen-specific stimulation with PD-L1+ tumor cells and that markers of activation and proliferation were increased in anti-Her-2 T cells in the presence of anti-PD-1 antibody. In adoptive transfer studies in Her-2 transgenic recipient mice, we showed a significant improvement in growth inhibition of two different Her-2+ tumors treated with anti-Her-2 T cells in combination with anti-PD-1 antibody. The therapeutic effects observed correlated with increased function of anti-Her-2 T cells following PD-1 blockade. Strikingly, a significant decrease in the percentage of Gr1+ CD11b+ myeloid-derived suppressor cells (MDSC) was observed in the tumor microenvironment of mice treated with the combination therapy. Importantly, increased antitumor effects were not associated with any autoimmune pathology in normal tissue expressing Her-2 antigen.Conclusion: This study shows that specifically blocking PD-1 immunosuppression can potently enhance CAR T-cell therapy that has significant implications for potentially improving therapeutic outcomes of this approach in patients with cancer. Clin Cancer Res; 19(20); 5636–46. ©2013 AACR.
Phase I Study of BIIB028, a Selective Heat Shock Protein 90 Inhibitor, in Patients with Refractory Metastatic or Locally Advanced Solid Tumors
Authors: Hong David , Said Rabih , Falchook Gerald , Naing Aung , Moulder Stacy , Tsimberidou Apostolia-Maria , Galluppi Gerald , Dakappagari Naveen , Storgard Chris , Kurzrock Razelle , Rosen Lee S. 
Published: July 2013

Abstract
Purpose: Heat shot protein 90 (Hsp90) is a ubiquitous molecular chaperone involved in protein folding, activation, and assembly, including key mediators of signal transduction, cell-cycle control, and transcriptional regulation. We conducted a phase I dose-finding and pharmacokinetic/pharmacodynamic study of BIIB028, a prodrug designed to inhibit Hsp90 activity.
Experimental Design: Patients with advanced solid tumors were enrolled and received escalating doses of BIIB028 intravenously twice a week in 21-day cycles (3 + 3 design). Response was evaluated after two cycles.
Results: Forty-one patients received doses of 6 to 192 mg/m2. The maximum tolerated dose was 144 mg/m2. Dose-limiting toxicities were syncope (n = 1) and fatigue (n = 1). Common toxicities at least possibly related to drug were grades 1 to 2, including fatigue (46%), diarrhea (44%), nausea (44%), vomiting (29%), hot flushes (29%), and abnormal dreams (17%). The concentration–time curves for day 1 and day 18 for both prodrug and active metabolite (CF2772) showed a negligible difference. There was a dose-dependent increase in plasma exposure for BIIB028 (CF3647) and CF2772 with plasma half-life of 0.5 and 2.1 hours, respectively. Pharmacodynamic analyses showed significant increases in Hsp70 in peripheral blood mononuclear cells and significantly decreased circulating human EGF receptor-2 extracellular domain in all patients who received BIIB028 at dose levels of 48 mg/m2 or more. Stable disease for at least eight cycles (24 weeks) was achieved in 5 (12%) patients (for durations of 6, 6, 8, 12.5, and 19 months).
Conclusion: BIIB028 is a well-tolerated molecule that showed target impact and was associated with prolonged stable disease in two patients. Clin Cancer Res; 19(17); 4824–31. ©2013 AACR.