bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generalized Estimating Equations
Authors: Hardin James W. , Hilbe Joseph M. 
Published: January 2014

AbstractCorrelated datasets develop when multiple observations are collected from a sampling unit (e.g., repeated measures of a bank over time, or hormone levels in a breast cancer patient over time), or from clustered data where observations are grouped based on a shared characteristic (e.g., observations on different banks grouped by zip code, or on cancer patients from a specific clinic). The generalized linear model framework for independent data is extended to model correlated data via the introduction of second‐order variance components directly into the independent data model's estimating equation. This generalization of the estimating equation from the independence model is thus referred to as a Generalized Estimating Equation (GEE). This article discusses the foundation of GEEs as well as how user‐specified correlation structures are accommodated in the model‐building process. This article also discusses the relationship and similarity to the underlying generalized linear model framework and we point out alternative approaches to GEEs for modeling correlated data such as fixed‐effects models and random‐effects models.
Group‐Randomized Trials
Authors: Murray David M. 
Published: January 2014

AbstractThe purpose of this article is to put group‐randomized trials (GRTs) in context in terms of other kinds of designs and in terms of the terminology used in other fields, to summarize their development in public health, to characterize the range of public health research areas that now employ GRTs, to characterize the state of practice with regard to the design and analysis of GRTs, to consider their future in public health research, and to review the steps required to plan a new GRT.
Proportional Odds Model
Authors: Liu Ivy , Mukherjee Bhramar 
Published: January 2014

AbstractOutcomes recorded on an ordinal scale, such as severity of migraine, stages of progression of disease, or degree of relief caused by treatment, occur commonly in clinical trials. Questionnaire data, which are often collected at each visit to gauge patient condition, routinely contain responses on an ordinal scale. Naïve dichotomization of the full ordinal scale leads to loss of information and efficiency while analyzing such outcomes. The proportional odds model is a popular choice for analyzing such ordinal outcomes. The current article provides a concise introduction to the proportional odds model and proceeds to review some more recent work related to this model. Specifically, we discuss the problem of analyzing stratified ordinal data in which observations from the same strata are correlated. Such correlated ordinal data may develop in multicenter clinical trials or with ordinal responses measured repeatedly on the same subject in longitudinal studies. Certain computing tools for fitting such models are discussed.
Nonparametric Methods
Authors: Wolfe Douglas A. 
Published: January 2014

AbstractThe motivation behind distribution‐free hypothesis tests and confidence intervals based on signs and ranks is discussed and standard text references are provided. Distribution‐free test and confidence interval procedures for the one‐sample, two‐sample, one‐way analysis of variance, two‐way analysis of variance, and independence settings are presented. Point estimation techniques, including Hodges–Lehmann estimators and contrast estimation, and multiple comparisons procedures are described. Basic references for censored data approaches and bootstrapping are provided.
ASCOTTrial
Authors: Mehlsen Jesper 
Published: January 2014

AbstractThe Anglo Scandinavian Cardiac Outcomes Trial (ASCOT) had two main objectives. The first objective was to determine and compare the effects of an amlodipine‐based therapy with an atenolol‐based therapy in hypertensive patients with mild‐to‐moderate risk of developing cardiovascular events (ASCOT‐BPLA). The second objective was in those patients with a serum cholesterol level at or below average to evaluate the possible beneficial effects on cardiovascular events of a statin compared with placebo (ASCOT‐LLA). ASCOT‐LLA was terminated prematurely after a mean observational period of 3.3 years because of a highly significant reduction in the primary endpoint of CHD events compared with placebo. ASCOT‐BPLA was also terminated prematurely after a mean observational period of 5.5 years because of significantly higher all cause mortality in the atenolol‐based treatment arm compared with the amlodipine‐based arm.
AIDSClinical Trials Group (ACTG)
Authors: Andersen Janet W. 
Published: January 2014

AbstractThe AIDS Clinical Trials Group (ACTG) is the largest Network conducting therapeutic clinical trials in AIDS and HIV, with active clinical sites in the United States, South America, Haiti, Africa, India, and Thailand. The ultimate goal of the ACTG is to identify drugs and other treatment modalities that will result in the successful control of HIV in infected persons.
DNA
Bank
Authors: Sivakumaran Theru A , Iyengar Sudha K 
Published: January 2014

Abstract

Most diseases are multifactorial and are caused by a combination of genetic and environmental factors. Similarly, the way a person responds to a drug is also a complex trait that is influenced by many different genes. Paradigms to identify causative genetic variants responsible for disease or response to drugs are well described in the literature, and the following essential elements are required for successful completion of such studies: (
1
) rapid detection of genetic variation; (
2
) large number of samples of high quality with well‐characterized clinical data from participants, which includes longitudinal follow‐up for effect of treatment; (
3
) advanced informatics for storage and retrieval of samples and data; and (
4
) establishment of correlation between clinical and genetic data through modern statistical techniques. Although the basic conventions for sample collection in gene mapping were already established, it was only after completion of Human Genome Project and the initiation of the International HapMap Project that the need for large databases of well‐phenotyped study participants collected under unified protocols with DNA available was expressed. These endeavors resulted in the establishment of national and international DNA banks aimed initially at mapping specific disease entities, but later encompassing more global undertakings. Establishment of these DNA biobanks has not been without ethical, legal, and personal controversies, although their value to the biomedical research community is indisputable. The overall outcome of these initiatives is that the promise of personalized medicine is nearby, particularly for identification of the genetic variations responsible for drug response. We anticipate that clinical trials could perform genetic prescreening to exclude people who are unresponsive to treatment, which reduces side effects and increases the effectiveness of the drug for particular subgroups. This model is already being implemented for the P450 class of drugs, with the hope of more to come.
Benefit/Risk Assessment in Prevention Trials
Authors: Costantino Joseph P. 
Published: January 2014

AbstractBenefit/risk assessment (B/RA) is a mathematical procedure to estimate the probability of detrimental outcomes, beneficial outcomes and the net‐effect anticipated from exposure to a given agent or procedure. B/RAs of health‐related outcomes are used for public health planning, decision‐making regarding health care financing, and therapeutic decision‐making in clinical practice. Information obtained from B/RAs based on findings from controlled clinical trials, particularly those with double‐masking of treatment, are most informative for health care planning and decision making because such information is less likely to be bias than is information obtained from observational studies. Thus, B/RAs in prevention trials are an excellent source of information to use as the basis for health care planning and decision‐making. Applications of R/BA in prevention trials are performed as supplements for planning, monitoring and analyzing the trial. These applications can be categorized into three types of assessments. This article provides a description of the three types of assessment performed in prevention trials, defines the statistical algorithms used for each type of assessment and discusses several key methodological and practical issues involve with the application of B/RA to health‐related outcomes.
The counterintuitive effect of summer‐to‐fall mixed layer deepening on eukaryotic new production in the Sargasso Sea
Authors: Fawcett Sarah E. , Lomas Michael W. , Ward Bess B. , Sigman Daniel M. 
Published: January 2014

AbstractThe Sargasso Sea is characterized by strong summertime stratification that is thought to drive oligotrophy, but export production is surprisingly similar to that of high‐latitude regions with ample major nutrient supply. Here we use the summer‐to‐fall progression in the northwestern Sargasso Sea to investigate the relationship between upper ocean stratification and phytoplankton nitrogen (N) uptake. Euphotic zone particles collected in July, October, and December were sorted by flow cytometry, and the 15N/14N of separated prokaryotic and eukaryotic phytoplankton was analyzed. The 15N/14N of Prochlorococcus and Synechococcus was always low, indicating uniform reliance on recycled N. In July and in two fall profiles, the 15N/14N of eukaryotic phytoplankton was high, reflecting consumption of subsurface nitrate. In three other fall profiles, eukaryotic 15N/14N was similar to prokaryote 15N/14N, suggesting a shift toward more complete reliance on recycled N. The progressive deepening of the mixed layer from summer to fall, although reducing the surface‐to‐deep density contrast, increases the density difference of the euphotic zone as a whole from underlying nutrient‐rich waters, which may play a role in the observed decline in euphotic zone nitrate supply into the fall. The apparent summertime nitrate supply to the euphotic zone, when the mixed layer is shallowest, may help to explain the surprisingly high export production of the subtropical and tropical ocean.
Optical measurements of small deeply penetrating bubble populations generated by breaking waves in the Southern Ocean
Authors: Randolph Kaylan , Dierssen Heidi M. , Twardowski Michael , Cifuentes‐Lorenzen Alejandro , Zappa Christopher J. 
Published: January 2014

AbstractBubble size distributions ranging from 0.5 to 125 μm radius were measured optically during high winds of 13 m s−1 and large‐scale wave breaking as part of the Southern Ocean Gas Exchange Experiment. Very small bubbles with radii less than 60 µm were measured at 6–9 m depth using optical measurements of the near‐forward volume scattering function and critical scattering angle for bubbles (∼80°). The bubble size distributions generally followed a power law distribution with mean slope values ranging from 3.6 to 4.6. The steeper slopes measured here were consistent with what would be expected near the base of the bubble plume. Bubbles, likely stabilized with organic coatings, were present for time periods on the order of 10–100 s at depths of 6–9 m. Here, relatively young seas, with an inverse wave age of approximately 0.88 and shorter characteristic wave scales, produced lower bubble concentrations, shallower bubble penetration depths, and steep bubble size distribution slopes. Conversely, older seas, with an inverse wave age of 0.70 and longer characteristic wave scales, produced relatively higher bubble concentrations penetrating to 15 m depth, larger bubble sizes, and shallower bubble size distribution slopes. When extrapolated to 4 m depth using a previously published bubble size distribution, our estimates suggest that the deeply penetrating small bubbles measured in the Southern Ocean supplied ∼36% of the total void fraction and likely contributed to the transfer and supersaturation of low‐solubility gases.
Deep water circulation in the Luzon Strait
Authors: Zhao Wei , Zhou Chun , Tian Jiwei , Yang Qingxuan , Wang Bin , Xie Lingling , Qu Tangdong 
Published: January 2014

AbstractDeep water circulation in the Luzon Strait, which connects the Pacific deep circulation with the South China Sea throughflow, is investigated using a set of oceanographic observations combined with results from three numerical experiments. Both the in situ observations and the model show a deep water overflow in the Luzon Strait. Their results suggest that the deep Pacific water first flows into the Luzon Strait through the Bashi Channel (1.2 Sv, 1 Sv = 1 × 106 m3 s−1) and the Taltung Canyon (0.4 Sv), then turns southward along the Luzon Trough, and finally enters the South China Sea primarily through two gaps in the Heng‐Chun Ridge. Overall, the mean transport of the Luzon Strait overflow is about 1.5 Sv. Results from numerical experiments suggest that strong diapycnal mixing in the South China Sea and Luzon Strait, which sustains the baroclinic pressure gradient across the Luzon Strait, is the primary driving mechanism of the deep circulation in the Luzon Strait.
Multihop relaying for broadband wireless access systems at 800 and 3500 MHz in rural areas
Authors: Chee Kin Lien , Feng Wei , Kürner Thomas 
Published: January 2014

AbstractThis paper addresses the coverage enhancement for broadband wireless access (BWA) at 800 and 3500 MHz in a rural scenario in north Germany using multi‐hop relay concepts. The investigation is divided into two phases: In phase I, the coverage of a single BWA system in a rural area is predicted and verified with measurement data. In phase II, the coverage from the BWA system is analyzed and enhanced through the deployment of relay stations. The number of relay stations required for each carrier frequency is determined, and the positions of the relay stations are identified via three different relay placement algorithms, namely path‐loss‐based, distance‐based, and hybrid algorithms. At 800 MHz, the path‐loss‐based algorithm requires seven relay stations to achieve an overall coverage of 95%. The hybrid and distance‐based algorithms require 11 and 14 relay stations, respectively, to achieve the same coverage. At 3500 MHz, path‐loss based and hybrid algorithms require 19 and 16 relay stations, respectively, to achieve the same coverage. The distance‐based requires 20 relay stations to achieve an overall coverage of 82%. Further increase of relay stations has led to higher interference. Lastly, the transmit power of the relay station is optimized via an intelligent power allocation scheme. The results show that 20% of the total transmit powers from 14 relay stations can be saved at 800 MHz whereas 18% of the total transmit powers from the 20 relay stations can be saved at 3500 MHz.
Angioedema of the upper aerodigestive tract: risk factors associated with airway intervention and management algorithm
Authors: Brook Christopher D. , Devaiah Anand K. , Davis Elizabeth M. 
Published: January 2014

BackgroundAngioedema of the upper aerodigestive tract can lead to significant airway obstruction. To date no articles have delineated risk factors for progression after initial evaluation.MethodsThis article presents the results of a retrospective study of patients with angioedema at a single institution. Patients included were consecutive otolaryngology consultations for angioedema in the emergency department (ED) from 1999 to 2003. All patients were evaluated by an otolaryngologist and underwent fiber‐optic laryngoscopy, which was repeated serially depending on findings. Data was collected on demographics, comorbidities, intubation, disposition, and progression of angioedema.ResultsA total of 177 patients were included in the study: 32 (18%) patients required intubation; 25 (14%) on initial presentation and 7 (4%) who progressed from an initially stable airway to requiring intervention after reevaluation. Analysis of variance (ANOVA) demonstrated a statistically significant variance between location of edema and rate of intubation, with higher rates in the pharynx and larynx vs the lip and face. Patients who required intubation after progression between serial evaluations were statistically more likely to have edema that involved deeper portions of the aerodigestive tract. Patients who required intubation were statistically more likely to be older (average age 61.8 vs 55.1 years, p = 0.03).ConclusionIn this large series of patients managed for aerodigestive angioedema we demonstrate risk factors associated with airway intervention, and risk factors associated with clinical progression on serial examination to airway intervention. In addition, we demonstrate a successful management algorithm for patients with aerodigestive angioedema.
Impact of vitamin D deficiency upon clinical presentation in nasal polyposis
Authors: Schlosser Rodney J. , Soler Zachary M. , Schmedes Gregg W. , Storck Kristina , Mulligan Jennifer K. 
Published: January 2014

BackgroundThe objective of this work was to determine if specific chronic rhinosinusitis with nasal polyps (CRSwNP) populations are at risk for vitamin D3 (VD3) deficiency and if VD3 levels correlate with radiographic measures of disease severity or eosinophilia.MethodsThis study was a retrospective review of an academic rhinology practice. CRSwNP patients who had VD3 levels and CT scan within 6 months of each other were included. CT scans were graded using Lund‐Mackay scoring (LMS) and peripheral eosinophil counts were measured. Demographic data including race, gender, age, body mass index, atopic status, and presence of asthma were collected. CRSwNP was subdivided into allergic fungal rhinosinusitis (AFRS), aspirin‐exacerbated respiratory disease (AERD), and other CRSwNP. Multivariate analysis was performed to examine correlations and control for confounding factors.ResultsInsufficient VD3 levels were found in 55% of all CRSwNP patients. VD3 correlated with African American race because nearly 80% of all African Americans had insufficient VD3 levels. Lower VD3 levels also correlated with more severe mucosal disease on CT scans as measured by LMS. There was no correlation between VD3 levels and age, gender, body mass index, atopy, asthma, or CRSwNP subtype.ConclusionVD3 insufficiency/deficiency is common in CRSwNP patients, especially those of African American race. Lower levels of VD3 are associated with worse LMS on CT. The role of VD3 in CRSwNP warrants further investigation.
Comprehensive sequencing of PALB2 in patients with breast cancer suggests PALB2 mutations explain a subset of hereditary breast cancer
Authors: Fernandes Priscilla H. , Saam Jennifer , Peterson Jenny , Hughes Elisha , Kaldate Rajesh , Cummings Shelly , Theisen Aaron , Chen Sonia , Trost Jeffrey , Roa Benjamin B. 
Published: January 2014

BACKGROUNDThis study sought to determine the prevalence of PALB2 mutations in a cohort referred for diagnostic testing for hereditary breast cancer.METHODSSanger sequencing was used to analyze the entire coding region and flanking introns of PALB2 in anonymized DNA samples from 1479 patients. Samples were stratified into a “high‐risk” group, 955 samples from individuals predicted to have a high probability of carrying a mutation in BRCA1 or BRCA2 based on their personal and family history, and a “lower‐risk” group consisting of 524 samples from patients with breast cancer, but fewer risk factors for being a BRCA1 or BRCA2 mutation carrier. All patients were known to be negative for deleterious sequence mutations and large rearrangements in BRCA1 and BRCA2.RESULTSWe identified 12 disease‐associated PALB2 mutations among the 1479 patients (0.8%). The PALB2 mutations included 8 nonsense, 3 frameshift mutations and a splice‐site mutation. The mutation prevalence for the high‐risk population was 1.05% (95% CI = 0.5‐1.92), whereas that for the lower‐risk population was 0.38% (95% CI = 0.05‐1.37). We identified 59 PALB2 variants of uncertain significance (VUS) among 57 of the 1479 patients (3.9%).CONCLUSIONSThese results suggest that PALB2 mutations occur at a frequency of ∼1% in patients with hereditary breast cancer. Cancer 2014;120:963–967. © 2013 American Cancer Society.
EWS‐FLI‐1 regulates the neuronal repressor gene REST, which controls Ewing sarcoma growth and vascular morphology
Authors: Zhou Zhichao , Yu Ling , Kleinerman Eugenie S. 
Published: January 2014

BACKGROUNDRE1‐silencing transcription factor (REST), a neuronal repressor gene, regulates neuronal stem cell differentiation. Ewing sarcoma may originate from neural crest cells. In the current study, the authors investigated whether REST plays a role in the growth of this tumor.METHODSREST expression was determined by Western blot analysis and reverse transcription‐polymerase chain reaction in 3 human Ewing sarcoma cell lines and 7 patient tumor samples. The role of REST in tumor growth and tumor vascular morphology was determined using a Ewing sarcoma xenograft model. Immunofluorescence staining, Hypoxyprobe, and terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling (TUNEL) assays were performed to investigate the impact of REST on pericyte marker expression, hypoxia, and apoptosis in vivo.RESULTSHigh levels of REST were expressed in all 3 human Ewing sarcoma cell lines and in 6 of the 7 patient tumor samples. Overexpression of EWS‐FLI‐1 in human mesenchymal stem cells and human neural progenitor cells was found to increase REST expression. Inhibition of EWS‐FLI‐1 using small interfering RNA decreased REST expression in human Ewing sarcoma cells. Inhibition of REST did not affect EWS‐FLI‐1, but significantly suppressed tumor growth in vivo, reduced the tumor vessel pericyte markers α‐ smooth muscle actin (SMA) and desmin, increased hypoxia and apoptosis in tumor tissues, and decreased the expression of delta‐like ligand 4 (DLL4) and Hes1.CONCLUSIONSInhibition of REST suppressed tumor growth, inhibited pericyte marker expression, and increased tumor hypoxia and apoptosis. Because tumor vessel function has been linked to tumor growth and metastases, REST may be a new therapeutic target in patients with Ewing sarcoma. Cancer 2014;120:579–588. © 2014 American Cancer Society.
Origin of 5‐Hydroxymethylfurfural Stability in Water/Dimethyl Sulfoxide Mixtures
Authors: Tsilomelekis George , Josephson Tyler R. , Nikolakis Vladimiros , Caratzoulas Stavros 
Published: January 2014

AbstractIn the present work, we combined vibrational spectroscopy with electronic structure calculations to understand the solvation of HMF in DMSO, water, and DMSO/water mixtures and to provide insights into the observed hindrance of HMF rehydration and aldol condensation reactions if it is dissolved in DMSO/water mixtures. To achieve this goal, the attenuated total reflection FTIR spectra of a wide composition range of binary and ternary mixtures were measured, analyzed, and compared to the findings of ab initio DFT calculations. The effect of solvent on the HMF CO and OH vibrational modes reveals significant differences that are ascribed to different intermolecular interactions between HMF and DMSO or water. We also found that DMSO binds to HMF more strongly than water, and interactions with the HMF hydroxyl group are stronger than those with the HMF carbonyl group. We also showed the preferential solvation of HMF CO groups by DMSO if HMF is dissolved in DMSO/water mixed solvent. Frontier molecular orbital theory was used to examine the influence of the solvent on side reactions. The results show that HMF solvation by DMSO increases its LUMO energy, which reduces its susceptibility to nucleophilic attack and minimizes undesirable hydration and humin‐formation reactions. This result, together with the preferential solvation of HMF by DMSO, provide an explanation for the enhanced HMF stability in DMSO/water mixtures observed experimentally.