bluuebunny/crossref_metadata_2025_split huggingface dataset:
Should identical CVD risks in young and old patients be managed identically? Results from two models
Authors: Liew Su May , Jackson Rod , Mant David , Glasziou Paul 
Published: March 2012

ObjectivesTo assess whether delaying risk reduction treatment has a different impact on potential life years lost in younger compared with older patients at the same baseline short-term cardiovascular risk.DesignModelling based on population data.MethodsPotential years of life lost from a 5-year treatment delay were estimated for patients of different ages but with the same cardiovascular risk (either 5% or 10% 5-year risk). Two models were used: an age-based residual life expectancy model and a Markov simulation model. Age-specific case fatality rates and time preferences were applied to both models, and competing mortality risks were incorporated into the Markov model.ResultsYounger patients had more potential life years to lose if untreated, but the maximum difference between 35 and 85 years was <1 year, when models were unadjusted for time preferences or competing risk. When these adjusters were included, the maximum difference fell to about 1 month, although the direction was reversed with older people having more to lose.ConclusionsSurprisingly, age at onset of treatment has little impact on the likely benefits of interventions that reduce cardiovascular risk because of the opposing effects of life expectancy, case fatality, time preferences and competing risks. These findings challenge the appropriateness of recommendations to use lower risk-based treatment thresholds in younger patients.
Comparison of screening strategies to improve the diagnosis of latent tuberculosis infection in the HIV-positive population: a cohort study
Authors: Pollock Katrina M , Tam Herman , Grass Lisa , Bowes Sharleen , Cooke Graham S , Pareek Manish , Montamat-Sicotte Damien , Kapembwa Moses , Taylor Graham P , Lalvani Ajit 
Published: March 2012

BackgroundHIV is the most important risk factor for progression of latent tuberculosis infection (LTBI) to active tuberculosis (TB). Detection and treatment of LTBI is necessary to reduce the increasing burden of TB in the UK, but a unified LTBI screening approach has not been adopted.ObjectiveTo compare the effectiveness of a TB risk-focused approach to LTBI screening in the HIV-positive population against current UK National Institute for Health and Clinical Excellence (NICE) guidance.DesignProspective cohort study.SettingTwo urban HIV treatment centres in London, UK.Participants114 HIV-infected individuals with defined TB risk factors were enrolled prospectively as part of ongoing studies into HIV and TB co-infection.Outcome measuresThe yield and case detection rate of LTBI cases within the research study were compared with those generated by the NICE criteria.Results17/114 (14.9%, 95% CI 8.3 to 21.5) had evidence of LTBI. Limiting screening to those meeting NICE criteria for the general population (n=43) would have detected just over half of these, 9/43 (20.9%, 95% CI 8.3 to 33.5) and those meeting criteria for HIV co-infection (n=74) would only have captured 8/74(10.8%, 95% CI 3.6 to 18.1) cases. The case detection rates from the study and NICE approaches were not significantly different. LTBI was associated with the presence of multiple TB risk factors (p=0.002).ConclusionAdoption of a TB risk-focused screening algorithm that does not use CD4 count stratification could prevent more cases of TB reactivation, without changing the case detection rate. These findings should be used to inform a large-scale study to create unified guidelines.
Public support for tobacco control policy extensions in Western Australia: a cross-sectional study
Authors: Rosenberg Michael , Pettigrew Simone , Wood Lisa , Ferguson Renee , Houghton Stephen 
Published: March 2012

ObjectivesPolicy makers seeking to introduce new tobacco control measures need to anticipate community support to assist them in planning appropriate implementation strategies. This study assessed community support for plain packaging and smoking bans in outdoor locations in Australia.DesignAnalytical cross-sectional survey.Setting and participants2005 Western Australian adults participated in a computer-assisted telephone interview. Random household telephone numbers were used to obtain a representative sample.Outcome measuresSupport for plain packaging of cigarettes and smoking bans at outdoor venues by demographic characteristics.ResultsAround half of the survey respondents supported plain packaging and almost a further quarter reported being neutral on the issue. Only one in three smokers disagreed with the introduction of a plain packaging policy. A majority of respondents supported smoking bans at five of the six nominated venues, with support being strongest among those with children under the age of 15 years. The venues with the highest levels of support were those where smoke-free policies had already been voluntarily introduced by the venue managers, where children were most likely to be in attendance, and that were more limited in size.ConclusionsThe study results demonstrate community support for new tobacco control policies. This evidence can be used by public policy makers in their deliberations relating to the introduction of more extensive tobacco control regulations.
Barriers to providing end-of-life care for people with dementia: a whole-system qualitative study
Authors: Dening Karen Harrison , Greenish Wendy , Jones Louise , Mandal Uttara , Sampson Elizabeth L 
Published: March 2012

ObjectivesPeople with dementia may experience poor quality end-of-life care. The complex health and social care system may not meet their needs. The authors' objectives were to identify perceived and real barriers that prevent people with dementia and their carers receiving end-of-life care of acceptable quality.MethodsA whole-system qualitative study as part of a rapid participatory appraisal. The authors used semistructured interviews and focus groups with recently bereaved family carers of a person with dementia and a wide range of health and social care staff (50 participants). Thematic content analysis was used to analyse data and to identify barriers.ResultsFive areas were identified as barriers to providing good end-of-life care: impact of hospitalisation, care pathways, advance care planning, impact on carers, staff skills and training. A wide range of health and social professionals provided end-of-life care to people with dementia but with little coordination or knowledge of each other's activity or remit. Care was fragmented and ad hoc leading to crises and inappropriate hospital admissions. Staff lacked confidence and requested more training. Many of the identified barriers were underpinned by feelings of uncertainty regarding disease trajectory and the perceived futility of interventions. Areas of good practice were specialist nurse support to family carers and ‘in reach’ to nursing homes.ConclusionsQualitative methods of service evaluation facilitated a broader and deeper understanding of a range of perspectives, which, with other components of rapid participatory appraisal, generated potential solutions to improve care.
Long-term trends in reproductive and demographic parameters of female Northwest Atlantic hooded seals (Cystophora cristata): population responses to ecosystem change?
Authors: Frie Anne Kirstine , Stenson Garry B. , Haug Tore 
Published: March 2012

More than 2500 ovaries were collected from Northwest Atlantic hooded seals ( Cystophora cristata (Erxleben, 1777)) in the period 1956–2006 during moulting (data blocks: 1956–1960, 1970–1972, 1978), postmoulting (data blocks: 1990–1994, 1996–2006), and whelping (data blocks: 1967–1972, 1973–1976, 1979, 1983–1987, 1989–1995). Mean age at primiparity (MAP) was estimated as the mean age of females with a single corpus albicans or a corpus luteum from a postimplantation pregnancy. MAP was stable at 4.2–4.5 years during 1956–1978, increasing to 4.9–5.2 years in 1979 and to 6.1 years in 1989–1995 (later data insufficient). Patterns of corpus accumulation indicated occasional skipped pregnancies. This may have affected the accuracy of MAP estimates but not the main trends. Declining proportions of parae younger than 10 years after 1979 are consistent with effects of delayed maturation, reduced adult hunting mortality, and (or) increased juvenile mortality. From the 1990s, declining adult pregnancy rates are suggested by decreasing trends in proportions of older multiparae (8+) and other ovary-based proxies for pregnancy rates. Hooded seal abundance was largely stable from 1960 to the mid-1990s and changes in population parameters over this period are therefore more likely due to effects of ecosystem change on per-capita resource levels than population-mediated density dependence.
Assessment of the status and viability of a population of moose (Alces alces) at its southern range limit in Ontario
Authors: Murray Dennis L. , Hussey Karen F. , Finnegan Laura A. , Lowe Stacey J. , Price Glynis N. , Benson John , Loveless Karen M. , Middel Kevin R. , Mills Ken , Potter Derek , Silver Andrew , Fortin Marie-Josée , Patterson Brent R. , Wilson Paul J. 
Published: March 2012

Factors affecting the distribution and abundance of animals are of substantial interest, and across most of their southern range, populations of moose ( Alces alces (L., 1758)) are declining, presumably because of climate change. Conditions favouring moose population decline versus numerical increase in select areas of the range are not well understood. During 2006–2009, we tested the hypothesis that moose in southern Ontario formed a viable population near the species’ southern range limit, despite occurrence of climate patterns apparently deleterious for population growth. Our study upheld each of our predictions: (i) high pregnancy rate (83.0%) and annual female survival rate (0.899 (0.859, 0.941; 95% CI)), indicating that the population was increasing (λ = 1.16); (ii) female moose having blood-based condition indices within normal range, despite larger than expected home-range size; and (iii) levels of genetic differentiation indicating that the population was part of a larger metapopulation of moose in the region. We surmise that moose in southern Ontario currently are not subject to the prevalent continental decline, likely owing to favourable site-specific climatic conditions. Future research should elaborate on why select southern moose populations are increasing and whether they will ultimately succumb to die off as effects of climate change become increasingly pronounced.
When a beetle is too small to carry phoretic mites? A case of hydrophilid beetles (Coleoptera: Hydrophilidae) andUropoda orbicularis(Acari: Mesostigmata)
Authors: Bajerlein D. , Przewoźny M. 
Published: March 2012

The aim of our study was to determine the limit of a beetle’s body size below which it is not able to carry phoretic mites. We tested the hypothesis that body size of the carrier is the vital factor in selecting a host in mites with facultative and nonspecific phoresy. The study was conducted on beetles of the family Hydrophilidae and deutonymphs of the mite Uropoda orbicularis (Müller, 1776). Among 20 species of hydrophilids collected, only 7 carried deutonymphs. The smallest hydrophilids with body lengths below 2.32 mm did not carry deutonymphs. These were Cercyon analis (Paykull, 1798), Cercyon nigriceps (Marsham, 1802), Cercyon pygmaeus (Illiger, 1801), Cercyon terminatus (Marsham, 1802), Cryptopleurum crenatum (Kugelann, 1794), Cryptopleurum minutum (Fabricius, 1775), Cryptopleurum subtile Sharp, 1884, and Megasternum concinnum (Marsham, 1802). On the contrary, the largest beetles, of the genus Sphaeridium Fabricius, 1775, were most heavily and frequently occupied by phoretic deutonymphs. Most representatives of the genus Cercyon Leach, 1817 did not carry mites or had a very low mite burden. Our study indicates that beetle infestation by nonspecific phoretic mites is strongly influenced by beetle body size.
Comparing body condition of moose (Alces alces) selected by wolves (Canis lupus) and human hunters: consequences for the extent of compensatory mortality
Authors: Sand H. , Wikenros C. , Ahlqvist P. , Strømseth T.H. , Wabakken P. 
Published: March 2012

Predators commonly select prey of inferior quality compared with the average animals found in the population. Consequently, predation may often be compensatory to other sources of mortality. We tested whether wolves ( Canis lupus L., 1758) in Scandinavia selected moose in poor body condition by comparing mandibular marrow fat (MMF) of wolf-killed moose ( Alces alces (L., 1758)) with harvested moose. Model selection analyses indicated that MMF levels were lower for wolf-killed moose compared with harvested moose, but an unbalanced sample design between years for the two causes of death (wolves and harvest) may have confounded a clear interpretation of the results. Nevertheless, corrected MMF levels (to 1 April) showed that a significantly (p = 0.006) higher proportion of the wolf-killed calves (18.5%) were below the level often assumed to reflect acute malnutrition (<20% MMF) compared with harvested moose calves (3.3%). For wolf-killed yearlings and adult females, 5.6% and 8.3%, respectively, had MMF below this level compared with 0% for harvested individuals. As a result, 15.1% of the total number of wolf-killed moose and 1.6% of the harvested moose during winter appear to be compensatory to mortality from starvation. Differences in body condition, and thus levels of compensatory mortality, found between wolf-killed and harvested moose in this study may reflect a stronger selection for individuals in poor body condition by wolves.
Free-ranging eastern chipmunks (Tamias striatus) infected with bot fly (Cuterebra emasculator) larvae have higher resting but lower maximum metabolism
Authors: Careau V. , Garant D. , Humphries M.M. 
Published: March 2012

Given the ubiquity and evolutionary importance of parasites, their effect on the energy budget of mammals remains surprisingly unclear. The eastern chipmunk ( Tamias striatus (L., 1758)) is a burrowing rodent that is commonly infected by cuterebrid bot fly ( Cuterebra emasculator Fitch, 1856) larvae. We measured resting metabolic rate (RMR) and cold-induced Vo2-max (under heliox atmosphere) in 20 free-ranging individuals, of which 4 individuals were infected by one or two larva. We found that RMR was significantly higher in chipmunks infected by bot fly larvae (mean ± SE = 0.88 ± 0.05 W) than in uninfected individuals (0.74 ± 0.02 W). In contrast, Vo2-max was significantly lower in chipmunks infected by bot fly larvae (4.96 ± 0.70 W) than in uninfected individuals (6.37 ± 0.16 W). Consequently, the aerobic scope (ratio of Vo2-max to RMR) was negatively correlated with the number of bot fly larvae (infected individuals = 5.74 ± 1.03 W; noninfected individuals = 8.67 ± 0.26 W). Finally, after accounting for the effects of body mass and bot fly parasitism on RMR and Vo2-max, there was no correlation between the two variables among individuals within our population. In addition to providing the first estimate of Vo2-max in T. striatus, these results offer additional evidence that bot fly parasitism has significant impacts on the metabolic ecology of this host species.
Prognostic and Predictive Significance of Plasma HGF and IL-8 in a Phase III Trial of Chemoradiation with or without Tirapazamine in Locoregionally Advanced Head and Neck Cancer
Authors: Le Quynh-Thu , Fisher Richard , Oliner Kelly S. , Young Richard J. , Cao Hongbin , Kong Christina , Graves Edward , Hicks Rodney J. , McArthur Grant A. , Peters Lester , O'Sullivan Brian , Giaccia Amato , Rischin Danny 
Published: March 2012

Abstract
Purpose: Hepatocyte growth factor (HGF) is a hypoxia-induced secreted protein that binds to cMet and regulates interleukin (IL)-8 expression. We evaluated the role of circulating HGF and IL-8 as prognostic and predictive factors for efficacy of tirapazamine (TPZ), a hypoxic cell cytotoxin.
Experimental Design: Patients with stages III to IV head and neck cancer were randomized to receive radiotherapy with cisplatin (CIS) or CIS plus TPZ (TPZ/CIS). Eligibility for the substudy included plasma sample availability for HGF and IL-8 assay by ELISA and no major radiation deviations (N = 498). Analyses included adjustment for major prognostic factors. p16INK4A staining (human papillomavirus surrogate) was carried out on available tumors. Thirty-nine patients had hypoxia imaging with 18F-fluoroazomycin arabinoside (18FAZA)–positron emission tomography.
Results: Elevated IL-8 level was associated with worse overall survival (OS) irrespective of treatment. There was an interaction between HGF and treatment arm (P = 0.053); elevated HGF was associated with worse OS in the control but not in the TPZ/CIS arm. Similar trends were observed in analyses restricted to p16INK4A-negative patients. Four subgroups defined by high and low HGF/IL-8 levels were examined for TPZ effect; the test for interaction with arm was P = 0.099. TPZ/CIS seemed to be beneficial for patients with high HGF and IL-8 but adverse for low HGF and high IL-8. Only HGF correlated with 18FAZA tumor standard uptake value.
Conclusions: IL-8 is an independent prognostic factor irrespective of treatment. There is an interaction between HGF and treatment arm. Certain subgroups based on IL-8/HGF levels seemed to do better with TPZ/CIS while others did worse, highlighting the complexity of hypoxia targeting in unselected patients. Clin Cancer Res; 18(6); 1798–807. ©2012 AACR.
Interleukin-27 Inhibits the Growth of Pediatric Acute Myeloid Leukemia in NOD/SCID/Il2rg−/− Mice
Authors: Zorzoli Alessia , Di Carlo Emma , Cocco Claudia , Ognio Emanuela , Ribatti Domenico , Ferretti Elisa , Dufour Carlo , Locatelli Franco , Montagna Daniela , Airoldi Irma 
Published: March 2012

Abstract
Purpose: Acute myeloid leukemia (AML) accounts for more than half of fatal cases in all pediatric leukemia patients; this observation highlights the need of more effective therapies. Thus, we investigated whether interleukin (IL)-27, an immunomodulatory cytokine, functions as an antitumor agent against pediatric AML cells.
Experimental Design: Expression of WSX-1 and gp130 on AML cells from 16 pediatric patients was studied by flow cytometry. Modulation of leukemia cell proliferation or apoptosis upon IL-27 treatment in vitro was tested by bromodeoxyuridine/propidium iodide (PI) and Ki67, or Annexin V/PI staining and flow cytometric analysis. The angiogenic potential of AML cells treated or not with IL-27 was studied by chorioallantoic membrane assay and PCR array. In vivo studies were carried out using nonobese diabetic/severe combined immunodeficient (NOD/SCID)/Il2rg−/− mice injected intravenously with five pediatric AML cell samples. Leukemic cells engrafted in PBS and IL-27–treated animals were studied by immunohistochemical/morphologic analysis and by PCR array for expression angiogenic/dissemination-related genes.
Results: We provided the first demonstration that (i) AML cells injected into NOD/SCID/Il2rg−/− mice gave rise to leukemia dissemination that was severely hampered by IL-27, (ii) compared with controls, leukemia cells harvested from IL-27–treated mice showed significant reduction of their angiogenic and spreading related genes, and (iii) similarly to what was observed in vivo, IL-27 reduced in vitro AML cell proliferation and modulated the expression of different genes involved in the angiogenic/spreading process.
Conclusion: These results provide an experimental rationale for the development of future clinical trials aimed at evaluating the toxicity and efficacy of IL-27. Clin Cancer Res; 18(6); 1630–40. ©2012 AACR.
A High-Throughput Panel for Identifying Clinically Relevant Mutation Profiles in Melanoma
Authors: Dutton-Regester Ken , Irwin Darryl , Hunt Priscilla , Aoude Lauren G. , Tembe Varsha , Pupo Gulietta M. , Lanagan Cathy , Carter Candace D. , O'Connor Linda , O'Rourke Michael , Scolyer Richard A. , Mann Graham J. , Schmidt Christopher W. , Herington Adrian , Hayward Nicholas K. 
Published: March 2012

Abstract
Success with molecular-based targeted drugs in the treatment of cancer has ignited extensive research efforts within the field of personalized therapeutics. However, successful application of such therapies is dependent on the presence or absence of mutations within the patient's tumor that can confer clinical efficacy or drug resistance. Building on these findings, we developed a high-throughput mutation panel for the identification of frequently occurring and clinically relevant mutations in melanoma. An extensive literature search and interrogation of the Catalogue of Somatic Mutations in Cancer database identified more than 1,000 melanoma mutations. Applying a filtering strategy to focus on mutations amenable to the development of targeted drugs, we initially screened 120 known mutations in 271 samples using the Sequenom MassARRAY system. A total of 252 mutations were detected in 17 genes, the highest frequency occurred in BRAF (n = 154, 57%), NRAS (n = 55, 20%), CDK4 (n = 8, 3%), PTK2B (n = 7, 2.5%), and ERBB4 (n = 5, 2%). Based on this initial discovery screen, a total of 46 assays interrogating 39 mutations in 20 genes were designed to develop a melanoma-specific panel. These assays were distributed in multiplexes over 8 wells using strict assay design parameters optimized for sensitive mutation detection. The final melanoma-specific mutation panel is a cost effective, sensitive, high-throughput approach for identifying mutations of clinical relevance to molecular-based therapeutics for the treatment of melanoma. When used in a clinical research setting, the panel may rapidly and accurately identify potentially effective treatment strategies using novel or existing molecularly targeted drugs. Mol Cancer Ther; 11(4); 888–97. ©2012 AACR.
Bcl-x Inactivation in Macrophages Accelerates Progression of Advanced Atherosclerotic Lesions in Apoe
−/−
Mice
Authors: Shearn Andrew I.U. , Deswaerte Virginie , Gautier Emmanuel L. , Saint-Charles Flora , Pirault John , Bouchareychas Laura , Rucker Edmund B. , Beliard Sophie , Chapman John , Jessup Wendy , Huby Thierry , Lesnik Philippe 
Published: March 2012

Objective—
Bcl-x is the most abundantly expressed member of the Bcl-2 gene family in macrophages, but its role in macrophage apoptosis during atherogenesis is unknown.

Methods and Results—

We previously reported dual pro- and antiatherogenic effects of macrophage survival in early versus advanced atherosclerotic lesions, respectively, potentially reflecting growing impairment of efferocytosis during plaque progression. Here, we specifically inactivated Bcl-x in macrophages and evaluated its impact on atherosclerotic lesion formation in Apoe
−/−
mice at various stages of the disease. Bcl-x deficiency in macrophages increased their susceptibility to apoptosis, resulting in the depletion of tissue macrophages in vivo, including its major pool, Küppfer cells in the liver. We also observed increased cholesterol levels that were, however, not associated with any acceleration of early atherosclerotic plaque progression. This observation suggests that the atheroprotective effect of macrophage apoptosis at that stage of disease was counterbalanced by enhanced cholesterol levels. Bcl-x KO
mac
/Apoe
−/−
mice exhibited significantly larger advanced lesions than control mice. These lesions showed vulnerable traits. Such enhanced lesion size may occur as a result not only of apoptotic cell accumulation but also of elevated cholesterol levels.

Conclusion—
Modulation of macrophage resistance to apoptosis through targeted deletion of Bcl-x has a major impact on the entire macrophage cell population in the body, including Küpffer cells. Macrophage survival may, therefore, not only influence atherosclerotic plaque development and vulnerability but also cholesterol metabolism.