bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for REducing Anti-Psychotic use in residential care-Huntington Disease (REAP-HD): a pilot cluster randomised controlled trial of a multifaceted intervention for health professionals
Authors: Loy Clement T , Hayen Andrew , McKinnon Colleen 
Published: December 2014

IntroductionAntipsychotics are commonly used for management of behavioural symptoms in dementia, among people in residential care. This continues to occur despite their modest effectiveness, potential harms including increased risk of death and stroke, and absence of detrimental effect when people with dementia were randomised to antipsychotic withdrawal. This study aims to test the hypothesis that the multifaceted REducing Anti-Psychotic use in residential care-Huntington Disease (REAP-HD) programme is more effective than standard staff education (SSE) in reducing antipsychotic use for people with HD in residential care facilities (RCF).Methods and analysisthis is a cluster randomised controlled trial with blinded outcome assessment. The study population is healthcare professionals looking after people with HD in individual RCF, in the state of New South Wales. Each RCF will be centrally randomised to the REAP-HD programme or the comparator, SSE. Blinded outcome assessment will be performed by examining drug charts and using the Neuropsychiatric Inventory-Q (NPI-Q). Primary outcome is the proportion of people with HD who have had a reduction in antipsychotic use 4 months after the intervention. Secondary outcome measures are (1) change in severity of behavioural symptoms, as measured by the NPI-Q at 4 months (to ensure antipsychotic reduction has not lead to worsening behavioural symptoms), and (2) proportion of people with HD who have had a reduction in antipsychotic dosage at 4 months for each strategy, compared to 4 months prior to enrolment (to capture the possibility that both arms reduced antipsychotic use). Analysis will be by Intention-To-Treat and take into account the clustering. Recruitment is ongoing, as of July 2014.Ethics and disseminationThis protocol has been approved by the Western Sydney Local Health District Human Research Ethics Committee, trial registration ACTRN12614000083695. Study results will be disseminated through peer-reviewed publication in an anonymous manner.Trial registration numberACTRN12614000083695, the Australian New Zealand Clinical Trials Registry.
Assessment of equity in healthcare financing in Fiji and Timor-Leste: a study protocol
Authors: Asante Augustine D , Price Jennifer , Hayen Andrew , Irava Wayne , Martins Joao , Guinness Lorna , Ataguba John E , Limwattananon Supon , Mills Anne , Jan Stephen , Wiseman Virginia 
Published: December 2014

IntroductionEquitable health financing remains a key health policy objective worldwide. In low and middle-income countries (LMICs), there is evidence that many people are unable to access the health services they need due to financial and other barriers. There are growing calls for fairer health financing systems that will protect people from catastrophic and impoverishing health payments in times of illness. This study aims to assess equity in healthcare financing in Fiji and Timor-Leste in order to support government efforts to improve access to healthcare and move towards universal health coverage in the two countries.Methods and analysisThe study employs two standard measures of equity in health financing increasingly being applied in LMICs—benefit incidence analysis (BIA) and financing incidence analysis (FIA). In Fiji, we will use a combination of secondary and primary data including a Household Income and Expenditure Survey, National Health Accounts, and data from a cross-sectional household survey on healthcare utilisation. In Timor-Leste, the World Bank recently completed a health equity and financial protection analysis that incorporates BIA and FIA, and found that the distribution of benefits from healthcare financing is pro-rich. Building on this work, we will explore the factors that influence the pro-rich distribution.Ethics and disseminationThe study is approved by the Human Research Ethics Committee of University of New South Wales, Australia (Approval number: HC13269); the Fiji National Health Research Committee (Approval # 201371); and the Timor-Leste Ministry of Health (Ref MS/UNSW/VI/218).ResultsStudy outcomes will be disseminated through stakeholder meetings, targeted multidisciplinary seminars, peer-reviewed journal publications, policy briefs and the use of other web-based technologies including social media. A user-friendly toolkit on how to analyse healthcare financing equity will be developed for use by policymakers and development partners in the region.
Overview and biostratigraphy
Authors: Rees A. J. , Thomas A. T. , Lewis M. , Hughes H. E. , Turner P. 
Published: December 2014

Abstract

Excellent coastal exposures of strongly folded and faulted Cambrian rocks occur around the St David's Peninsula of SW Wales. The best sections occur in the St David's Anticline, in the vicinity of St David's itself, and these have been the subject of scientific study since the mid-Nineteenth Century. Based on this early work, a quadripartite lithostratigraphical scheme emerged, comprising the Caerfai, Solva and Menevian groups and the Lingula Flags Formation. However, this scheme is unnecessarily complex, and sometimes unworkable in practice. The Caerfai Group is here redefined to embrace much of the Solva Group of earlier authors, while the upper part of the Solva Group, the Menevian Group and Lingula Flags are combined in the new Porth-y-rhaw Group. Traditionally, all these Cambrian rocks have been thought of as being deposited on a stable cratonic platform, but there is substantial evidence of tectonic influences on sedimentation, particularly in the older part of the succession. The Cambrian was originally recognized and defined in North Wales. There, as in many other areas, it became common practice to divide the period into three parts, but more recent work favours a four-fold chronostratigraphical subdivision. The oldest part of the Cambrian is missing in South Wales, but rocks of Terreneuvian, C2, C3 and Furongian age are all represented. Age-diagnostic fossils are few in the older part of the local succession. Trace fossils low in the Caerfai Group indicate the
avalonensis
Ichnozone or
Teichichnus
Interval of the Terreneuvian, while a radiometric date of early C2 (CS3) age has been obtained higher up. Trilobite faunas occur more commonly in the higher parts of the Caerfai Group and in the Porth-y-rhaw Group, and these facilitate international correlation of the C3 (CS5) to Furongian (Paibian) parts of the succession. Trilobites characteristic of the
oelandicus
Biosuperzone and the
gibbus
,
fissus
,
parvifrons
,
punctuosus
,
pisiformis
and
Olenus
biozones all occur.
Quantification of Circulating miRNAs by Droplet Digital PCR: Comparison of EvaGreen- and TaqMan-Based Chemistries
Authors: Miotto Elena , Saccenti Elena , Lupini Laura , Callegari Elisa , Negrini Massimo , Ferracin Manuela 
Published: December 2014

Abstract
Droplet digital PCR (ddPCR) has been successfully used with TaqMan assays to assess gene expression through the quantification of mRNA and miRNA. Recently, a new ddPCR system that can also run DNA-binding dye-based assays has been developed but it has not yet been tested for miRNA. We tested and compared the feasibility of quantifying miRNA with the new QX200 Droplet Digital PCR system when used with EvaGreen dye– and TaqMan probe–based assays. RNA from plasma and serum of 28 patients with cancer and healthy persons was reverse-transcribed and quantified for two circulating miRNAs and one added exogenous miRNA, with both EvaGreen dye–based miRCURY LNA miRNA assays and TaqMan assays. Amplification and detection of target miRNAs were performed on the QX200 ddPCR system. Conditions required to run miRCURY LNA miRNA assays were optimized. The EvaGreen-based assay was precise, reproducible over a range of concentrations of four orders of magnitude, and sensitive, detecting a target miRNA at levels down to 1 copy/μL. When this assay was compared with TaqMan assays, high concordance was obtained for two endogenous miRNAs in serum and plasma (Pearson r &gt; 0.90). EvaGreen dye–based and TaqMan probe–based assays can be equally used with the ddPCR system to quantify circulating miRNAs in human plasma and serum. This study establishes the basis for using EvaGreen dye–based assays on a ddPCR system for quantifying circulating miRNA biomarkers and potentially other low-abundance RNA biomarkers in human biofluids.
See all the articles in this CEBP Focus section, “Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology.”
Cancer Epidemiol Biomarkers Prev; 23(12); 2638–42. ©2014 AACR.
Establishment of the Cancer Prevention Study II Nutrition Cohort Colorectal Tissue Repository
Authors: Campbell Peter T. , Deka Anusila , Briggs Peter , Cicek Mine , Farris Alton B. , Gaudet Mia M. , Jacobs Eric J. , Newton Christina C. , Patel Alpa V. , Teras Lauren R. , Thibodeau Stephen N. , Tillmans Lori , Gapstur Susan M. 
Published: December 2014

Abstract
Background: To better understand colorectal cancer etiology and prognosis, archived surgical tissues were collected from Cancer Prevention Study II (CPS-II) Nutrition Cohort participants who were diagnosed with colorectal cancer. Herein, the methodology for this collection is described to help inform other efforts to collect tissues.
Methods: The main components to accruing tissue were: (i) obtaining consent from participants or next-of-kin; (ii) contacting hospitals to request materials; and (iii) pathology review and laboratory processing.
Results: In CPS-II, we identified 3,643 participants diagnosed with colorectal cancer between 1992/1993 and 2009. Of these, tissue could not be sought from cases verified through state cancer registry linkage (N = 1,622), because of insufficient information on tissue location. We sought tissue from the 2,021 cases verified using medical records, and received tissue from 882. When hospitals were contacted within 10 years of diagnosis, we received 87% of tissue materials; beyond that 10-year mark, we received 32%. Compared with the 2,761 colorectal cancer cases without tissue, the 882 cases with tissue were more likely to be alive, diagnosed more recently during follow-up, and had less-advanced staged disease. Cases with and without tissues were similar with respect to age at diagnosis, smoking, body mass index, physical activity, and other epidemiologic factors.
Conclusions: Some of the most important elements in forming a tissue repository included having the cases' hospital contact and surgical accession information as well as contacting patients/next-of-kin and hospitals within 10 years of surgery.
Impact: This tissue repository will serve as an important resource for colorectal cancer studies.
See all the articles in this CEBP Focus section, “Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology.”
Cancer Epidemiol Biomarkers Prev; 23(12); 2694–702. ©2014 AACR.
DNA from Nails for Genetic Analyses in Large-Scale Epidemiologic Studies
Authors: Hogervorst Janneke G.F. , Godschalk Roger W.L. , van den Brandt Piet A. , Weijenberg Matty P. , Verhage Bas A.J. , Jonkers Leonie , Goessens Joy , Simons Colinda C.J.M. , Vermeesch Joris R. , van Schooten Frederik J. , Schouten Leo J. 
Published: December 2014

Abstract
Background: Nails contain genomic DNA that can be used for genetic analyses, which is attractive for large epidemiologic studies that have collected or are planning to collect nail clippings. Study participants will more readily participate in a study when asked to provide nail samples than when asked to provide a blood sample. In addition, nails are easy and cheap to obtain and store compared with other tissues.
Methods: We describe our findings on toenail DNA in terms of yield, quality, genotyping a limited set of SNPs with the Sequenom MassARRAY iPLEX platform and high-density genotyping with the Illumina HumanCytoSNP_FFPE-12 DNA array (&gt;262,000 markers). We discuss our findings together with other studies on nail DNA and we compare nails and other frequently used tissue samples as DNA sources.
Results: Although nail DNA is considerably degraded, genotyping a limited set of SNPs with the Sequenom MassARRAY iPLEX platform (average sample call rate, 97.1%) and high-density genotyping with the Illumina HumanCytoSNP_FFPE chip (average sample call rate, 93.8%) were successful.
Conclusions: Nails are a suitable source of DNA for genotyping in large-scale epidemiologic studies, provided that methods are used that are suitable or optimized for degraded DNA. For genotyping through (next generation) sequencing where DNA degradation is less of an issue, nails may be an even more attractive DNA source, because it surpasses other sources in terms of ease and costs of obtaining and storing the samples.
Impact: It is worthwhile to consider nails as a source of DNA for genotyping in large-scale epidemiologic studies.
See all the articles in this CEBP Focus section, “Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology.”
Cancer Epidemiol Biomarkers Prev; 23(12); 2703–12. ©2014 AACR.
Measurement of Telomere Length: A New Assay Using QuantiGene Chemistry on a Luminex Platform
Authors: Kibriya Muhammad G. , Jasmine Farzana , Roy Shantanu , Ahsan Habibul , Pierce Brandon 
Published: December 2014

Abstract
Background: Telomeres are tandem repeats of sequences present at the end of the chromosomes that maintain chromosomal integrity. After repeated cell division, telomeres shorten to a critical level, triggering replicative senescence or apoptosis, which is a key determinant of cellular aging. Short telomeres also contribute to genome instability and are a hallmark of many cancers. There are several methods for estimating telomere length (TL) from extracted DNA samples. Southern blot is accurate but requires a large quantity of DNA and is expensive. qPCR is cost-effective and requires a small quantity of DNA and is therefore widely used for large-scale epidemiologic studies; however, it typically requires triplicates. We describe a novel multiplexed probe-based non-PCR method for TL measurement.
Methods: A small amount of DNA (∼50 ng) is hybridized to telomere repeat sequence–specific probes (T) and a reference single gene probes (R). T and R signals are detected from a single reaction well containing the same input DNA. Branching DNA technology is used to amplify the signal, which is detected by Luminex technology.
Results: The intra- and interassay CV (∼3% and ∼5%, respectively) shows the precision of the new assay and the measurements from single well correlated well with traditional single-plex qPCR run in triplicate (r = 0.7 to 0.8). The assay was also validated in an independent set of samples using Southern blot (r = 0.74).
Conclusion: We describe a novel assay for TL assessment using the Luminex platform.
Impact: This may offer an alternative cost-efficient way to study TL in extracted DNA samples.
See all the articles in this CEBP Focus section, “Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology.”
Cancer Epidemiol Biomarkers Prev; 23(12); 2667–72. ©2014 AACR.
Tumor Intrinsic Subtype Is Reflected in Cancer-Adjacent Tissue
Authors: Casbas-Hernandez Patricia , Sun Xuezheng , Roman-Perez Erick , D'Arcy Monica , Sandhu Rupninder , Hishida Asahi , McNaughton Kirk K. , Yang Xiaohong R. , Makowski Liza , Sherman Mark E. , Figueroa Jonine D. , Troester Melissa A. 
Published: December 2014

Abstract
Introduction: Overall survival of early-stage breast cancer patients is similar for those who undergo breast-conserving therapy (BCT) and mastectomy; however, 10% to 15% of women undergoing BCT suffer ipsilateral breast tumor recurrence. The risk of recurrence may vary with breast cancer subtype. Understanding the gene expression of the cancer-adjacent tissue and the stromal response to specific tumor subtypes is important for developing clinical strategies to reduce recurrence risk.
Methods: We utilized two independent datasets to study gene expression data in cancer-adjacent tissue from invasive breast cancer patients. Complementary in vitro cocultures were used to study cell–cell communication between fibroblasts and specific breast cancer subtypes.
Results: Our results suggest that intrinsic tumor subtypes are reflected in histologically normal cancer-adjacent tissue. Gene expression of cancer-adjacent tissues shows that triple-negative (Claudin-low or basal-like) tumors exhibit increased expression of genes involved in inflammation and immune response. Although such changes could reflect distinct immune populations present in the microenvironment, altered immune response gene expression was also observed in cocultures in the absence of immune cell infiltrates, emphasizing that these inflammatory mediators are secreted by breast-specific cells. In addition, although triple-negative breast cancers are associated with upregulated immune response genes, luminal breast cancers are more commonly associated with estrogen-response pathways in adjacent tissues.
Conclusions: Specific characteristics of breast cancers are reflected in the surrounding histologically normal tissue. This commonality between tumor and cancer-adjacent tissue may underlie second primaries and local recurrences.
Impact: Biomarkers derived from cancer-adjacent tissue may be helpful in defining personalized surgical strategies or in predicting recurrence risk. Cancer Epidemiol Biomarkers Prev; 24(2); 406–14. ©2014 AACR.
The Rise of HPV-Positive Oropharyngeal Cancers in the United States
Authors: Fakhry Carole , Cohen Ezra 
Published: December 2014

Abstract
This perspective highlights a study that reports an increasing proportion of human papillomavirus–positive oropharyngeal cancer among blacks in recent calendar periods. The results are discussed in the context of other studies which evaluated racial differences in the distribution of human papillomavirus–positive oropharyngeal cancer and survival. Cancer Prev Res; 8(1); 9–11. ©2014 AACR.
See related article by Zandberg et al., p. 12
Paradoxical Muscle Sympathetic Reflex Activation in Human Heart Failure
Authors: Millar Philip J. , Murai Hisayoshi , Floras John S. 
Published: December 2014

Background—
Muscle sympathetic activation in heart failure with reduced ejection fraction (HFrEF) has been attributed, on the basis of multiunit recordings, to attenuated inhibitory feedback from stretch-sensitive cardiopulmonary mechanoreceptors. However, such preparations integrate 2 populations of single units exhibiting directionally opposite firing when atrial pressure is perturbed. We tested the hypothesis that the proportion of single units firing paradoxically when filling pressure increases is augmented in HFrEF.

Methods and Results—

Muscle sympathetic nerve activity and estimated central venous pressure were recorded during nonhypotensive lower body negative pressure (LBNP; -10 mm Hg) and nonhypertensive positive pressure (LBPP; +10 mm Hg) in 11 treated HFrEF (left ventricular ejection fraction 25±6% [mean±standard deviation]) patients and 14 similarly aged controls. Single-unit muscle sympathetic nerve activity discharge was termed either anticipated, if firing frequency exhibited classic negative-feedback responses, or paradoxical. LBNP and LBPP had no heart rate, stroke volume, or blood pressure effects (
P
>0.05). Estimated central venous pressure decreased with LBNP (
P
<0.05), increased with LBPP (
P
<0.05), and was consistently higher in HFrEF (
P
<0.05). During LBNP, the ratio of single units with anticipated and paradoxical discharge was similar in HFrEF (18:7) and controls (27:5), whereas LBPP elicited paradoxical reflex excitation in a greater proportion of HFrEF single units (7:18 versus 24:6;
P
=0.0001). Consequently, LBPP increased mean single-unit firing frequency (
P
<0.05) and did not inhibit multiunit muscle sympathetic nerve activity of HFrEF subjects (
P
<0.05 versus controls). Firing of 12/18 HFrEF (but no control) single units increased during both LBPP and LBNP.

Conclusion—
These findings provide the first evidence in human HFrEF for an augmented excitatory cardiopulmonary–muscle sympathetic nerve activity reflex response to increased preload, incorporating 2 distinct single-unit populations with differing firing properties.
Amplitude Spectrum Area to Guide Defibrillation
Authors: Ristagno Giuseppe , Mauri Tommaso , Cesana Giancarlo , Li Yongqin , Finzi Andrea , Fumagalli Francesca , Rossi Gianpiera , Grieco Niccolò , Migliori Maurizio , Andreassi Aida , Latini Roberto , Fornari Carla , Pesenti Antonio 
Published: December 2014

Background—
This study sought to validate the ability of amplitude spectrum area (AMSA) to predict defibrillation success and long-term survival in a large population of out-of-hospital cardiac arrests.

Methods and Results—
ECGs recorded by automated external defibrillators from different manufacturers were obtained from patients with cardiac arrests occurring in 8 city areas. A database, including 2447 defibrillations from 1050 patients, was used as the derivation group, and an additional database, including 1381 defibrillations from 567 patients, served as validation. A 2-second ECG window before defibrillation was analyzed, and AMSA was calculated. Univariable and multivariable regression analyses and area under the receiver operating characteristic curve were used for associations between AMSA and study end points: defibrillation success, sustained return of spontaneous circulation, and long-term survival. Among the 2447 defibrillations of the derivation database, 26.2% were successful. AMSA was significantly higher before a successful defibrillation than a failing one (13±5 versus 6.8±3.5 mV-Hz) and was an independent predictor of defibrillation success (odds ratio, 1.33; 95% confidence interval, 1.20–1.37) and sustained return of spontaneous circulation (odds ratio, 1.22; 95% confidence interval, 1.17–1.26). Area under the receiver operating characteristic curve for defibrillation success prediction was 0.86 (95% confidence interval, 0.85–0.88). AMSA was also significantly associated with long-term survival. The following AMSA thresholds were identified: 15.5 mV-Hz for defibrillation success and 6.5 mV-Hz for defibrillation failure. In the validation database, AMSA ≥15.5 mV-Hz had a positive predictive value of 84%, whereas AMSA ≤6.5 mV-Hz had a negative predictive value of 98%.

Conclusions—
In this large derivation-validation study, AMSA was validated as an accurate predictor of defibrillation success. AMSA also appeared as a predictor of long-term survival.