bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Proinflammatory CD68
+
Mannose Receptor
−
Macrophages in Peroxiredoxin-1 Expression and in Abdominal Aortic Aneurysms in Humans
Authors: Boytard Ludovic , Spear Rafaelle , Chinetti-Gbaguidi Giulia , Acosta-Martin Adelina E. , Vanhoutte Jonathan , Lamblin Nicolas , Staels Bart , Amouyel Philippe , Haulon Stephan , Pinet Florence 
Published: December 2012

Objective—
Abdominal aortic aneurysms (AAAs), dilations of the infrarenal aorta, are characterized by inflammation and oxidative stress. We previously showed increased levels of peroxiredoxin-1 (PRDX-1) in macrophages cultured from AAA patients. The purpose of the study was to determine which subpopulation of macrophages is present in AAAs and is involved in upregulation of PRDX-1 in aneurysmal disease.

Methods and Results—

This study used immunohistochemistry with antibodies against CD68 and mannose receptor (MR) to determine the subtype of macrophages in AAA tissue samples (n=33); laser capture microdissection to isolate each subtype; and quantitative–reverse transcriptase-polymerase chain reaction, Western blot, and ELISA to assess
PRDX-1
mRNA and PRDX-1protein levels in both types. Proinflammatory CD68
+
MR
−
macrophages predominated in adventitial tissue, whereas the intraluminal thrombus contained CD68
+
MR
+
macrophages. The presence of lipids and iron-containing deposits confirmed their phagocytic phenotype. Laser capture microdissection-isolated CD68
+
MR
−
and CD68
+
MR
+
macrophages, characterized by quantitative–reverse transcriptase-polymerase chain reaction (
TNF
,
IL1B
,
MRC1
, and
CCL18
) and Western blot (stabilin and hemoglobin), validated the microdissected subtypes. PRDX-1 expression was colocalized with CD68
+
MR
−
macrophages.
PRDX-1
mRNA and PRDX-1 protein were both more abundant in CD68
+
MR
−
than CD68
+
MR
+
macrophages in AAA.

Conclusion—

These findings suggest that the proteins or mRNAs expressed by the proinflammatory CD68
+
MR
−
macrophages may contribute to aneurysmal pathology.
Association of Arginine Vasopressin Levels With Outcomes and the Effect of V2 Blockade in Patients Hospitalized for Heart Failure With Reduced Ejection Fraction
Authors: Lanfear David E. , Sabbah Hani N. , Goldsmith Steven R. , Greene Stephen J. , Ambrosy Andrew P. , Fought Angela J. , Kwasny Mary J. , Swedberg Karl , Yancy Clyde W. , Konstam Marvin A. , Maggioni Aldo P. , Zannad Faiez , Gheorghiade Mihai 
Published: December 2012

Background—
Arginine vasopressin (AVP) levels are elevated in proportion to heart failure severity and are associated with higher cardiovascular mortality in ambulatory patients. However, the relationship between baseline and trends in AVP with outcomes in patients hospitalized for worsening heart failure with reduced ejection fraction is unclear.

Methods and Results—

The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial investigated the effects of tolvaptan in patients with worsening heart failure and ejection fraction ≤40%. The present analysis examined baseline and follow-up AVP levels in 3196 EVEREST patients with valid AVP measurements. Coprimary end points included all-cause mortality, and the composite of cardiovascular mortality or heart failure hospitalization. Median follow-up was 9.9 months. Times to events were compared with univariate log-rank tests and multivariable Cox regression models, adjusted for baseline risk factors. After adjusting for baseline covariates, elevated AVP levels were associated with increased all-cause mortality (hazard ratio, 1.33; 95% confidence interval, 1.13–1.55) and cardiovascular mortality or heart failure hospitalization (hazard ratio, 1.23; 95% confidence interval, 1.08–1.39). There was no interaction of baseline AVP with treatment assignment in terms of survival (
P
=0.515). Tolvaptan therapy increased the proportion of patients with elevated AVP (
P
<0.001), but this had no effect on mortality (hazard ratio, 0.95; 95% confidence interval, 0.72–1.24).

Conclusions—
Elevated baseline AVP level was independently predictive of mortality, but did not identify a group of patients who had improved outcomes with tolvaptan treatment. Tolvaptan treatment increased AVP levels during follow-up, but this incremental increase was not associated with worsened outcomes.
Global Increasing Trends in Annual Maximum Daily Precipitation
Authors: Westra Seth , Alexander Lisa V. , Zwiers Francis W. 
Published: December 2012

AbstractThis study investigates the presence of trends in annual maximum daily precipitation time series obtained from a global dataset of 8326 high-quality land-based observing stations with more than 30 years of record over the period from 1900 to 2009. Two complementary statistical techniques were adopted to evaluate the possible nonstationary behavior of these precipitation data. The first was a Mann–Kendall nonparametric trend test, and it was used to evaluate the existence of monotonic trends. The second was a nonstationary generalized extreme value analysis, and it was used to determine the strength of association between the precipitation extremes and globally averaged near-surface temperature. The outcomes are that statistically significant increasing trends can be detected at the global scale, with close to two-thirds of stations showing increases. Furthermore, there is a statistically significant association with globally averaged near-surface temperature, with the median intensity of extreme precipitation changing in proportion with changes in global mean temperature at a rate of between 5.9% and 7.7% K−1, depending on the method of analysis. This ratio was robust irrespective of record length or time period considered and was not strongly biased by the uneven global coverage of precipitation data. Finally, there is a distinct meridional variation, with the greatest sensitivity occurring in the tropics and higher latitudes and the minima around 13°S and 11°N. The greatest uncertainty was near the equator because of the limited number of sufficiently long precipitation records, and there remains an urgent need to improve data collection in this region to better constrain future changes in tropical precipitation.
Data Centre Energy Efficiency Analysis to minimize total cost of ownership
Authors: Flucker Sophia , Tozer Robert 
Published: December 2012

The data centre industry grows with our increasing demand for IT services; energy forms a large part of data centre operating costs. Operators face increasing pressure to reduce their environmental impact and deliver competitively priced services to support users. However, many existing data centres were designed without a ‘green’ design brief; priorities were focussed around infrastructure redundancy. There are significant opportunities to implement modifications to design and operation and reduce operating costs, particularly to cooling systems, including managing data hall air, operating at higher temperatures, using free cooling and optimising for part load operation. Energy analysis can identify areas for improvement, often with short payback periods. This enables operators to realise massive reductions in energy (and sometimes capital) costs, whilst still delivering a reliable service. Practical application: The paper describes the challenges of reducing energy consumption and operating cost faced by those working in the data centre industry, along with tools and solutions. Details on where and how to achieve energy savings are presented, whilst maintaining the required availability for both new build and legacy facilities. Practical examples of how to put theory into practice are explained, including case studies where real clients have implemented improvements.
Prostate Effect in Dogs with the Aldosterone Receptor Blocker Eplerenone
Authors: Levin Stuart , McMahon Ellen , John-Baptiste Annette , Bell Rosonald R. 
Published: December 2012

Eplerenone (Inspra®) is an aldosterone receptor antagonist approved for the treatment of hypertension and heart failure after a myocardial infarction. In vitro receptor binding and transactivation studies showed eplerenone had high selectivity for the mineralocorticoid receptor over other steroid receptors (glucocorticoid, androgen, and progesterone). The most sensitive off-target effect of orally administered eplerenone preclinically was prostate atrophy in dogs. Dose-related prostate atrophy was observed at eplerenone dosages ≥15 mg/kg/day for 13 weeks or longer. The no observed adverse effect level (NOAEL) for the prostate effect in dogs was 5 mg/kg/day. The maximal effect was seen by 13 weeks and the atrophy was reversible even after 1 year of daily treatment. An additional study demonstrated dogs with eplerenone-induced prostate atrophy (confirmed by intrarectal ultrasound) had slightly decreased semen volume but no compound-related effects on libido, semen protein content, sperm motility, daily sperm production, or epididymal sperm transit time. Four possible mechanisms for prostate effect were investigated: (1) inhibition of testosterone synthesis and secretion; (2) inhibition of 5α-reductase, the enzyme within the prostate that converts testosterone into the more active growth factor dihydrotestosterone (DHT); (3) competitive antagonism of the androgen receptor; and (4) inhibition of 5α-reductase or competitive antagonism of the androgen receptor by aldosterone, which increased in dogs treated with eplerenone. Data from these studies supported blockade of androgen receptors at suprapharmacological concentrations of eplerenone. Another mineralocorticoid blocker, spironolactone, had greater antiandrogenic activity than eplerenone both in vivo and in vitro, and it has well known clinically significant antiandrogenic effects in humans, whereas eplerenone does not.
Clinical Practice Guideline Development Manual, Third Edition
Authors: Rosenfeld Richard M. , Shiffman Richard N. , Robertson Peter 
Published: December 2012

BackgroundGuidelines translate best evidence into best practice. A well‐crafted guideline promotes quality by reducing health care variations, improving diagnostic accuracy, promoting effective therapy, and discouraging ineffective—or potentially harmful—interventions. Despite a plethora of published guidelines, methodology is often poorly defined and varies greatly within and among organizations.PurposeThe third edition of this manual describes the principles and practices used successfully by the American Academy of Otolaryngology—Head and Neck Surgery Foundation to produce quality‐driven, evidence‐based guidelines using efficient and transparent methodology for actionable recommendations with multidisciplinary applicability. The development process emphasizes a logical sequence of key action statements supported by amplifying text, action statement profiles, and recommendation grades linking action to evidence. New material in this edition includes standards for trustworthy guidelines, updated classification of evidence levels, increased patient and public involvement, assessing confidence in the evidence, documenting differences of opinion, expanded discussion of conflict of interest, and use of computerized decision support for crafting actionable recommendations.ConclusionAs clinical practice guidelines become more prominent as a key metric of quality health care, organizations must develop efficient production strategies that balance rigor and pragmatism. Equally important, clinicians must become savvy in understanding what guidelines are—and are not—and how they are best used to improve care. The information in this manual should help clinicians and organizations achieve these goals.
Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection
Authors: Leeansyah Edwin , Ganesh Anupama , Quigley Máire F. , Sönnerborg Anders , Andersson Jan , Hunt Peter W. , Somsouk Ma , Deeks Steven G. , Martin Jeffrey N. , Moll Markus , Shacklett Barbara L. , Sandberg Johan K. 
Published: December 2012

Key Points
Antimicrobial CD8+ MAIT cells are activated, exhausted, and progressively and persistently depleted during chronic HIV-1 infection. This decline in MAIT cell level and function may seriously impair the ability to mount immune responses to bacterial and fungal pathogens.
Protocol for ADDITION-PRO: a longitudinal cohort study of the cardiovascular experience of individuals at high risk for diabetes recruited from Danish primary care
Authors: Johansen Nanna B , Hansen Anne-Louise S , Jensen Troels M , Philipsen Annelotte , Rasmussen Signe S , Jørgensen Marit E , Simmons Rebecca K , Lauritzen Torsten , Sandbæk Annelli , Witte Daniel R 
Published: December 2012

Abstract

Background
Screening programmes for type 2 diabetes inevitably find more individuals at high risk for diabetes than people with undiagnosed prevalent disease. While well established guidelines for the treatment of diabetes exist, less is known about treatment or prevention strategies for individuals found at high risk following screening. In order to make better use of the opportunities for primary prevention of diabetes and its complications among this high risk group, it is important to quantify diabetes progression rates and to examine the development of early markers of cardiovascular disease and microvascular diabetic complications. We also require a better understanding of the mechanisms that underlie and drive early changes in cardiometabolic physiology. The ADDITION-PRO study was designed to address these issues among individuals at different levels of diabetes risk recruited from Danish primary care.

Methods/Design

ADDITION-PRO is a population-based, longitudinal cohort study of individuals at high risk for diabetes. 16,136 eligible individuals were identified at high risk following participation in a stepwise screening programme in Danish general practice between 2001 and 2006. All individuals with impaired glucose regulation at screening, those who developed diabetes following screening, and a random sub-sample of those at lower levels of diabetes risk were invited to attend a follow-up health assessment in 2009–2011 (n = 4,188), of whom 2,082 (50%) attended. The health assessment included detailed measurement of anthropometry, body composition, biochemistry, physical activity and cardiovascular risk factors including aortic stiffness and central blood pressure. All ADDITION-PRO participants are being followed for incident cardiovascular disease and death.

Discussion
The ADDITION-PRO study is designed to increase understanding of cardiovascular risk and its underlying mechanisms among individuals at high risk of diabetes. Key features of this study include (i) a carefully characterised cohort at different levels of diabetes risk; (ii) detailed measurement of cardiovascular and metabolic risk factors; (iii) objective measurement of physical activity behaviour; and (iv) long-term follow-up of hard clinical outcomes including mortality and cardiovascular disease. Results will inform policy recommendations concerning cardiovascular risk reduction and treatment among individuals at high risk for diabetes. The detailed phenotyping of this cohort will also allow a number of research questions concerning early changes in cardiometabolic physiology to be addressed.
Participant experiences from chronic administration of a multivitamin versus placebo on subjective health and wellbeing: a double-blind qualitative analysis of a randomised controlled trial
Authors: Sarris Jerome , Cox Katherine H M , Camfield David A , Scholey Andrew , Stough Con , Fogg Erin , Kras Marni , White David J , Sali Avni , Pipingas Andrew 
Published: December 2012

Abstract

Background
While many randomised controlled trials have been conducted on multivitamins, to our knowledge no qualitative research exploring the subjective experience of taking a multivitamin during a clinical trial has been reported.

Methods
Semi-structured and open-ended written questions were incorporated into a 16-week double-blind, randomised, placebo-controlled, parallel groups trial of once-daily multivitamin administration. At the final study visit (week 16), three open-ended questions were posed to elucidate any positive, negative or unusual experiences from taking either the multivitamin or matched placebo. Qualitative thematic analysis was undertaken by researchers who were blind as to treatment condition of participants, and triangulation (independent analysis from three researchers) was employed to ensure methodological rigour. Participant’s experiences were categorised as “positive” or “negative” and a Chi Square analysis was then applied to each of the experiential themes, to compare experiences between the multivitamin and placebo groups, (subdividing the groups by gender). Usual experiences were categorised and discussed separately.

Results
Of the 182 participants enrolled, 116 completed the study and qualitative data were available from 114 participants. Thematic analysis revealed significant effects in favour of the multivitamin over placebo for participants experiencing increased energy levels (p=.022) and enhanced mood (p=.027). The beneficial effect on energy levels was particularly evident among female participants. A trend was found for participants reporting better sleep in the multivitamin over placebo. The multivitamin and placebo groups did not significantly differ in perceived positive or negative effects in areas relating to other aspects of mental function or physical health. No significant negative effects were revealed, although there was a non-significant trend for more people in the multivitamin group having minor digestive complaints.

Conclusion
This represents the first documented qualitative investigation of participants’ experience of chronic administration of a multivitamin. Results uncovered a range of subjective beneficial effects that are consistent with quantitative data from previously published randomised controlled trials examining the effects of multivitamins and B vitamin complexes on mood and well-being.

Trial registration

Prior to commencement this trial was registered with the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au) ACTRN12611000092998
Enhanced CD8 T-cell anti-viral function and clinical disease in B7-H1-deficient mice requires CD4 T cells during encephalomyelitis
Authors: Phares Timothy W , Stohlman Stephen A , Hinton David R , Bergmann Cornelia C 
Published: December 2012

AbstractBackgroundAnti-viral CD8 T-cell activity is enhanced and prolonged by CD4 T-cell-mediated help, but negatively regulated by inhibitory B7-H1 interactions. During viral encephalomyelitis, the absence of CD4 T cells decreases CD8 T cell activity and impedes viral control in the central nervous system (CNS). By contrast, the absence of B7-H1 enhances CD8 T-cell function and accelerates viral control, but increases morbidity. However, the relative contribution of CD4 T cells to CD8 function in the CNS, in the absence of B7-H1, remains unclear.MethodsWild-type (WT) and B7-H1−/−mice were infected with a gliatropic coronavirus and CD4 T cells depleted to specifically block T helper function in the CNS. Flow cytometry and gene expression analysis of purified T-cell populations from lymph nodes and the CNS was used to directly monitorex vivoT-cell effector function. The biological affects of altered T-cell responses were evaluated by analysis of viral control and spinal-cord pathology.ResultsIncreased anti-viral activity by CD8 T cells in the CNS of B7-H1−/−mice was lost upon depletion of CD4 T cells; however, despite concomitant loss of viral control, the clinical disease was less severe. CD4 depletion in B7-H1−/−mice also decreased inducible nitric oxide synthase expression by microglia and macrophages, consistent with decreased microglia/macrophage activation and reduced interferon (IFN)-γ. Enhanced production of IFN-γ, interleukin (IL)-10 and IL-21 mRNA was seen in CD4 T cells from infected B7-H1−/−compared with WT mice, suggesting that over-activated CD4 T cells primarily contribute to the increased pathology.ConclusionsThe local requirement of CD4 T-cell help for CD8 T-cell function is not overcome if B7-H1 inhibitory signals are lost. Moreover, the increased effector activity by CD8 T cells in the CNS of B7-H1−/−mice is attributable not only to the absence of B7-H1 upregulation on major histocompatibility complex class I-presenting resident target cells, but also to enhanced local CD4 T-cell function. B7-H1-mediated restraint of CD4 T-cell activity is thus crucial to dampen both CD8 T-cell function and microglia/macrophage activation, thereby providing protection from T-cell-mediated bystander damage.
Does TomoDirect 3DCRT represent a suitable option for post-operative whole breast irradiation? A hypothesis-generating pilot study
Authors: Borca Valeria Casanova , Franco Pierfrancesco , Catuzzo Paola , Migliaccio Fernanda , Zenone Flora , Aimonetto Stefania , Peruzzo Andrea , Pasquino Massimo , Russo Giuliana , La Porta Maria Rosa , Cante Domenico , Sciacero Piera , Girelli Giuseppe , Ricardi Umberto , Tofani Santi 
Published: December 2012

Abstract

Background
This study investigates the use of TomoDirectTM 3DCRT for whole breast adjuvant radiotherapy (AWBRT) that represents a very attractive treatment opportunity, mainly for radiotherapy departments without conventional Linacs and only equipped with helical tomotherapy units.

Methods
Plans were created for 17 breast cancer patients using TomoDirect in 3DCRT and IMRT modality and field-in-field 3DCRT planning (FIF) and compared in terms of PTV coverage, overdosage, homogeneity, conformality and dose to OARs. The possibility to define patient-class solutions for TD-3DCRT employment was investigated, correlating OARs dose constraints to patient specific anatomic parameters.

Results
TD-3DCRT showed PTV coverage and homogeneity significantly higher than TD-IMRT and FIF. PTV conformality was significantly better for FIF, while no differences were found between TD-3DCRT and TD-IMRT. TD-3DCRT showed mean values of the OARs dosimetric endpoints significantly higher than TD-IMRT; with respect to FIF, TD-3DCRT showed values significantly higher for lung V20Gy, mean heart dose and V25Gy, while contralateral lung maximum dose and contralateral breast mean dose resulted significantly lower. The Central Lung Distance (CLD) and the maximal Heart Distance (HD) resulted as useful clinical tools to predict the opportunity to employ TD-3DCRT: positive correlations were found between CLD and both V20Gy and mean lung dose and between HD and both V25Gy and the mean heart dose. TD-3DCRT showed a significantly shorter mean beam-on time than TD-IMRT.

Conclusions
The present study showed that TD-3DCRT and TD-IMRT are two feasible and dosimetrically acceptable treatment approach for AWBRT, with an optimal PTV coverage and adequate OARs sparing. Some concerns might be raised in terms of dose to organs at risks if TD-3DCRT is applied to a general population. A correct patients clusterization according to simple quantitative anatomic measures, would help to correctly allocate patients to the appropriate treatment planning strategy in terms of target coverage, but also of normal tissue sparing.