bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fallacies of last observation carried forward analyses
Authors: Lachin John M 
Published: September 2015

Background: Last observation carried forward is a common statistical approach to the analysis of longitudinal repeated measures data where some follow-up observations may be missing. In a last observation carried forward analysis, a missing follow-up visit value is replaced by (imputed as) that subject’s previously observed value, that is, the last observation is carried forward. The combination of the observed and imputed data is then analyzed as though there were no missing data. Purpose: There have been numerous statistical demonstrations of faults of this approach. In 2012, the National Research Council’s Panel on Handling Missing Data in Clinical Trials issued a report that raised concerns with the use of last observation carried forward and described alternative methods that offer greater statistical validity. Nevertheless, the method persists, and its use is rampant. A search of the key word “last observation carried forward” using Google Scholar yielded “about 2480” published citations during 2014 alone, the overwhelming majority presenting the results of scientific studies. However, there has not been a simple explanation of the statistical deficiencies of last observation carried forward. Such a description is presented herein. Results: A simple repeated measures model is described for quantitative observations at two times (e.g. 1 and 2 years), with complete values at 1 year that are used to impute by last observation carried forward the missing values at 2 years under the missing completely at random assumption. This results in a mixture distribution of observed and imputed values at 2 years with mean and variance that are a function of the mixture of the 1- and 2-year distributions. The expressions show that last observation carried forward is only unbiased when the distribution of the observed values at 1 year is exactly equal to the distribution of the missing values at 2 years, the latter, of course, being unknown. Limitations: When the values at 2 years are not randomly missing, no simple expressions for the mean and variance of the mixture distribution are possible without additional unverifiable assumptions. Conclusion: All analyses using last observation carried forward are of questionable veracity, if not being outright specious (definition: appearing to be true but actually false). It is hoped that future studies will make a more vigorous attempt to minimize the amount of missing data and that more valid statistical analyses will be employed in cases where missing data occur. Last observation carried forward should not be employed in any analyses.
Ethical complexities in standard of care randomized trials: A case study of morning versus nighttime dosing of blood pressure drugs
Authors: Kim Scott YH , Miller Franklin G 
Published: September 2015

Background: Pragmatic trials comparing “standard of care” treatments provide comparative effectiveness data to make practice of medicine more evidence-based. With electronic health records, recruiting and conducting such trials can be relatively inexpensive. But some worry that the traditional research ethics framework poses unnecessary obstacles and is not appropriate for evaluating such clinical trials. This concern is based on the view (which we call the “Standard of Care Principle”) that such research is similar to usual clinical practice and therefore does not raise significant ethical issues since everyone in the research study will receive an accepted standard of care treatment. Methods: A case study of a pragmatic randomized clinical trial (Blood Pressure Medication Timing study) comparing morning versus nighttime dosing of antihypertensive medications. The Blood Pressure Medication Timing study has been proposed as a paradigm example of why the Standard of Care Principle obviates the need for traditional levels of ethical scrutiny and how the current regulatory framework poses unnecessary obstacles to research. We provide an ethical analysis of the Blood Pressure Medication Timing study, drawing on the empirical literature as well as on normative analysis. Results: The Standard of Care Principle is the main ethical rationale given by commentators for asserting that the Blood Pressure Medication Timing study does not require “significant ethical debate” and by investigators for the assertion that the Blood Pressure Medication Timing study is minimal risk and thus eligible for lessened regulatory requirements. However, the Blood Pressure Medication Timing study raises important ethical issues, including whether it is even necessary, given the considerable randomized clinical trial evidence in support of nighttime dosing, a much larger (N ≈ 17,000) confirmatory randomized clinical trial already in progress, evidence for safety of nighttime dosing, and the cost-free availability of the intervention. Furthermore, the Standard of Care Principle provides a misleading basis for analyzing the informed consent requirements, especially regarding the requirement to disclose alternative courses of treatment that “might be advantageous to the subject.” Conclusion: The Standard of Care Principle is ethically inadequate and misleading even when it is applied to the pragmatic randomized clinical trial proposed as a paradigm case for its application.
Optimising enteral nutrition in critically ill patients by reducing fasting times
Authors: Segaran Ella , Barker Ian , Hartle Andrew 
Published: September 2015

Background Enteral nutrition is currently the route of choice for feeding critically ill patients with a functioning gut but delivery is commonly associated with disruptions. Common reasons for interruptions to enteral nutrition are fasting for diagnostic procedures, surgery and airway management. These interruptions result in significant calorie deficits that are associated with increased complications. We aimed to describe the specific interruptions in our patient group and the impact they have on nutrition delivery before and after implementation of a fasting guideline. Methods A service improvement project was undertaken over two different time points, 1 year apart, to evaluate the effectiveness of a fasting guideline in a general/trauma ICU in a London teaching hospital. Results There were 62 interruptions to enteral nutrition delivery with the first data collection and 64 in the second. Prolonged fasting before and after surgery and airway procedures were initially identified as the two most important causes of delays. Implementation of the fasting guideline resulted in statistical and clinical improvements in reducing fasting for airways procedures. The calorie deficit also statistically and clinically decreased as a result of the guideline. Conclusions We conclude that the introduction of a simple guideline stipulating reduced fasting times before ICU procedures can result in less time lost in feed interruptions and improved enteral nutrition delivery.
Divergence with gene flow across a speciation continuum of Heliconius butterflies
Authors: Supple Megan A. , Papa Riccardo , Hines Heather M. , McMillan W. Owen , Counterman Brian A. 
Published: September 2015

AbstractBackgroundA key to understanding the origins of species is determining the evolutionary processes that drive the patterns of genomic divergence during speciation. New genomic technologies enable the study of high-resolution genomic patterns of divergence across natural speciation continua, where taxa pairs with different levels of reproductive isolation can be used as proxies for different stages of speciation. Empirical studies of these speciation continua can provide valuable insights into how genomes diverge during speciation.MethodsWe examine variation across a handful of genomic regions in parapatric and allopatric populations ofHeliconiusbutterflies with varying levels of reproductive isolation. Genome sequences were mapped to 2.2-Mb of theH. eratogenome, including 1-Mb across the red color pattern locus and multiple regions unlinked to color pattern variation.ResultsPhylogenetic analyses reveal a speciation continuum of pairs of hybridizing races and incipient species in theHeliconius eratoclade. Comparisons of hybridizing pairs of divergently colored races and incipient species reveal that genomic divergence increases with ecological and reproductive isolation, not only across the locus responsible for adaptive variation in red wing coloration, but also at genomic regions unlinked to color pattern.DiscussionWe observe high levels of divergence between the incipient speciesH. eratoandH. himera, suggesting that divergence may accumulate early in the speciation process. Comparisons of genomic divergence between the incipient species and allopatric races suggest that limited gene flow cannot account for the observed high levels of divergence between the incipient species.ConclusionsOur results provide a reconstruction of the speciation continuum across theH. eratoclade and provide insights into the processes that drive genomic divergence during speciation, establishing the H. erato clade as a powerful framework for the study of speciation.
Polyphenols from marine brown algae target radiotherapy-coordinated EMT and stemness-maintenance in residual pancreatic cancer
Authors: Aravindan Sheeja , Ramraj Satish Kumar , Somasundaram Somasundaram T. , Herman Terence S. , Aravindan Natarajan 
Published: September 2015

Abstract
Introduction
Therapy-associated onset of stemness-maintenance in surviving tumor-cells dictates tumor relapse/recurrence. Recently, we recognized the anti-pancreatic cancer (PC) potential of seaweed polyphenol manifolds and narrowed down three superior drug-deliverables that could serve as adjuvants and benefit PC cure. Utilizing the PC- cancer stem cells (PC-CSCs) grown ex vivo and mouse model of residual-PC, we investigated the benefits of seaweed polyphenols in regulating stemness-maintenance.

Methods
ALDH+CD44+CD24+ PC-CSCs from Panc-1, Panc-3.27, MiaPaCa-2, or BxPC-3 cells-derived xenografts grown ex vivo were either mock-irradiated, exposed to fractionated irradiation (FIR, 2Gy/D for 5 days), treated with polyphenols (100 μg/ml) of Hormophysa triquerta (HT-EA), Spatoglossum asperum (SA-EA) or Padina tetrastromatica (PT-EA) with/without FIR were examined for cell viability, transcription of 93 stem-cell-related molecules (QPCR profiling). Polyphenol-dependent regulation of FIR-transactivated Oct4, Zic3, EIF4C, Nanog, and LIF (QPCR) and functional translation of Nanog, SOX2, and OCT3/4 (immunoblotting) were examined in Panc-1/Panc-3.27/MiaPaCa-2/BxPC-3-xenografts derived PC-CSCs. Effect of seaweed-polyphenols in the regulation of EMT (N-Cadherin), pluripotency- (SOX2, OCT3/4, Nanog) and stemness-maintenance (PI3KR1, LIF, CD44) in therapy (FIR, 2Gy/D for 5D/wk for 3-weeks) resistant residual tumors were examined by tissue microarray construction and automated immunohistochemistry.

Results
Ex vivo exposure of PC-CSCs to SA-EA, PT-EA and HT-EA exhibit dose-dependent inhibition of cell viability. FIR amplified the transcription of 69, 80, 74 and 77 stem-cell related genes in MiaPaCa-2-, Panc-1-, Panc-3.27- and BXPC3-established xenograft-derived ALDH+CD44+CD24+PC-CSCs. Treatment with SA-EA, PT-EA, or HT-EA completely suppressed FIR-activated stem-cell transcriptional machinery in ALDH+CD44+CD24+PC-CSCs established from MiaPaCa-2, Panc-1, Panc-3.27 and BXPC3 xenografts. QPCR validated EIF4C, OCT3/4, Nanog, LIF, and ZIC3 transcriptional profile outcomes. Nanog, Sox2, and OCT3/4 immunoblotting affirmed the PC-CSC radiosensitizing benefit of seaweed polyphenols. Residual-PC tissues microarrayed and immunostained after in vivo treatments recognized complete regulation of FIR-induced SOX2, OCT3/4, Nanog, LIF, CD44, PIK3R1, N-Cadherin, and E-Cadherin with SA-EA, PT-EA, and HT-EA.

Conclusions
These data, for the first time, documented the EMT/stemness-maintenance in therapy-resistant PC-CSCs. Further, the data suggest that seaweed polyphenols may inhibit PC relapse/recurrence by targeting therapy-orchestrated stem-cell signaling in residual cells.
Using online vacancies and web surveys to analyse the labour market: a methodological inquiry
Authors: Kureková Lucia Mýtna , Beblavý Miroslav , Thum-Thysen Anna 
Published: September 2015

AbstractThis paper discusses methodological issues arising from the use of online job vacancy data and voluntary web-based surveys to analyse the labour market. We highlight the advantages and possible disadvantages of using online data and suggest strategies for overcoming selected methodological issues. We underline the difficulties in adjusting for representativeness of online job vacancies, but nevertheless argue that this rich source of data should be exploited.JEL codes:E4, J2
Long-Term Cardiac Safety Analysis of NCCTG N9831 (Alliance) Adjuvant Trastuzumab Trial
Authors: Advani Pooja P. , Ballman Karla V. , Dockter Travis J. , Colon-Otero Gerardo , Perez Edith A. 
Published: September 2015

Purpose Significant improvement in survival outcomes has been established with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2) –positive early breast cancer treatment. However, trastuzumab may increase the risk of cardiac toxicity, and long-term evaluation of its incidence and risk factors are warranted. Methods NCCTG (Alliance) N9831 trial compared adjuvant doxorubicin and cyclophosphamide (AC) followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or paclitaxel plus trastuzumab followed by trastuzumab alone (arm C) in patients with HER2-positive breast cancer. Cumulative incidence of cardiac events (CE) and left ventricular ejection fraction (LVEF) were evaluated in 1,944 women who proceeded to post-AC therapy. Risk factors for trastuzumab-induced cardiac toxicity were identified by Cox regression models. Results The 6-year cumulative incidence of CE was 0.6% in arm A, 2.8% in arm B, and 3.4% in arm C. At a median follow-up of 9.2 years, only two additional CHF diagnoses (of 1,046 patients) occurred beyond our previously reported follow-up time of 3.75 years. LVEF recovered in the majority of the patients who developed CHF. There were two cardiac deaths in arm A and one each in arms B and C. Age of 60 years or older, registration LVEF less than 65%, and use of antihypertensive medications were associated with an increased risk of CE in arms B and C. Conclusion The cumulative incidence of CE at 6 years was slightly higher with the addition of trastuzumab; however, the late development of CE is infrequent. Trastuzumab (in the context of anthracycline- and taxane-based therapy) continues to have a favorable benefit-risk ratio.
Concurrent Chemoradiation for Cancer of the Cervix: Results of a Multi-Institutional Study From the Setting of a Developing Country (India)
Authors: Nandakumar Ambakumar , Kishor Rath Goura , Chandra Kataki Amal , Poonamalle Bapsy P. , Gupta Prakash C. , Gangadharan Paleth , Mahajan Ramesh C. , Nath Bandyopadhyay Manas , Kumaraswamy  , Vallikad Elizabeth , Visweswara Rudrapatna N. , Selvaraj Roselind Francis , Sathishkumar Krishnan , Daniel Vijaykumar Dampilla , Jain Ankush , Lakshminarayana Sudarshan Kondalli 
Published: September 2015

PurposeThe primary output of hospital-based cancer registries is data on cancer stage and treatment-based survival that can be used to evaluate patient care, but because there are many challenges in obtaining follow-up details, a separate study on patterns of care and patterns of survival for patients at selected sites was initiated under the National Cancer Registry Programme of India. This article presents the results for cervical cancer.Patients and MethodsA standardized patient information form was used to record patient information, and data were entered into a central repository—the National Centre for Disease Informatics and Research. The study patients were from 12 institutions and were diagnosed between January 1, 2006, and December 31, 2008. Patterns of treatment were assessed for 7,336 patients, and patterns of survival were determined for 2,669 patients from six institutions, at least 70% of whom had data regarding follow-up as of December 31, 2012.ResultsOf 7,336 patients, 55.5% received optimal radiotherapy (RT). In all, 80.9% of patients had locally advanced cancers (stage IIB to IVA), 51.1% received RT alone, and 44.4% received concurrent chemoradiation (RTCT). In 1,753 patients with locally advanced cancers, significantly better survival was observed with RTCT than with RT alone (5-year cumulative survival, 70.2% v 47.3%; hazard ratio, 0.48; 95% CI, 0.41 to 0.56).ConclusionA conservative estimate indicates that, on an annual basis, 38,771 patients with cervical cancers in India alone do not get the benefit of RTCT and thus they have poorer survival. There is a need to reiterate the National Cancer Institute's alert that advised supplementing chemotherapy to radiation for locally advanced cancer of the cervix in the context of the developing world, where 84.3% of cancers of the cervix occur.
Adiponectin Levels Differentiate Metabolically Healthy vs Unhealthy Among Obese and Nonobese White Individuals
Authors: Ahl Scott , Guenther Mitchell , Zhao Shi , James Roland , Marks Jacqueline , Szabo Aniko , Kidambi Srividya 
Published: September 2015

Context:
Adiponectin levels (ADPN) are lower in individuals with central obesity and cardiometabolic diseases. Conversely, studies have shown paradoxical hyperadiponectinemia (HA) in metabolically healthy obese (MHO) individuals of non-European descent. Moreover, individuals with higher sc to visceral adipose tissue (ie, higher peripheral adiposity) distribution have higher ADPNs. However, it is not known whether metabolically healthy individuals have predominantly peripheral adiposity along with higher ADPNs.

Objective:
This study aimed to evaluate the association of ADPN and adiposity distribution with metabolic health in white individuals.

Design and Setting:
This was a cross-sectional study of members of “Take Off Pounds Sensibly” weight loss club and their relatives.

Participants:
We recruited 2486 (72% women, 61% obese) individuals. They were defined as metabolically healthy by absence of hypertension, diabetes, and dyslipidemia; and they were further classified into metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Waist-to-hip ratios (WHRs) were used as markers of adiposity distribution. Insulin resistance was measured using homeostasis model assessment.

Results:
Among the four groups, MHNO had the lowest WHRs (higher peripheral adiposity) and highest ADPN, and MUO had highest WHRs (higher central adiposity) and lowest ADPN (P &lt; .001). Among both nonobese and obese, metabolically healthy individuals had higher ADPN than metabolically unhealthy individuals (P &lt; .05) after adjustment for age, sex, and body mass index. MHNO also had lower WHRs compared with MUNO (P &lt; .01). Although WHRs were lower among MHO compared with MUO, the difference was not significant. In addition, nonobese and obese individuals with HA (defined using sex-specific cutoffs) had lower homeostasis model assessment and dyslipidemia compared with individuals without HA.

Conclusions:
Higher ADPN and lower WHRs (higher peripheral adiposity) are associated with better metabolic health in both nonobese and obese white individuals. These results suggest that ADPN and peripheral adiposity play a key role in determining the metabolic health independent of body mass index.
Material Agency In User-Centred Design Practices
Authors: Sauer Sabrina 
Published: September 2015

Abstract
This paper investigates (digital) materiality through an analysis of the “sociomaterial configuration” (Orlikowski 2009) of the participatory design project SensorLab (2010). In SensorLab, users were enrolled as designers: a group of high school students developed and tested smart pollution-sensing prototypes in a public park in Amsterdam. Concepts from science and technology studies, specifically the notion of the “dance of agency” (Pickering 1995), are used to trace how ‘smartness’ materialises in the form of the SensorLab’s prototypes. The exploratory case study draws conclusions about (1) how materiality performs its agency and invites improvisations during prototype design and (2) how the student-designers use their tacit knowledge as situated expertise to improvise with construction materials and technology. The deconstruction of the assemblage of human/material agency suggests that while the student- designers are readily accommodated to develop prototypes, the material agency of the sensor technology resists improvisation as compared with the other available materials. The extent to which the black-boxed sensor technology allows the student-designers to become ‘smart’ is therefore debatable.
The Objective Identification Of Hazards – The Essential Condition To A Real Evaluation Of Occupational Injuries And Illnesses’ Risks
Authors: Bernevig-Sava Mihai-Adrian , Lohan Nicoleta Monica , Baciu Constantin , Bejinariu Costică 
Published: September 2015

Abstract
The paper discuss about the process of hazards identification in order to evaluate occupational injuries and illnesses’ risks, a problem that has been debated in many publications by different specialists, but which has not been concretized as a framed step in a defined context, without permiting the evaluator or the evaluation team to introduce the subjectivism as an influence factor.
Integrating Risk Analysis With Safety Dyagnostic In Complex Industrial Systems: Modeling Hazard
Authors: Cioca Lucian Ionel , Moraru Roland Iosif , Băbuţ Gabriel Bujor , Ungureanu Nicolae Stelian 
Published: September 2015

Abstract
Admitting as known the instruments that lends itself to highlighting the causes - consequences relationships in an industrial plant, the purpose of this research is, on the one hand, to integrate these relationships in the safety diagnostic procedures and, on the other hand, to use these “consequences” to forecast future failures likely to occur within the technical system. In this context, the paper aims to study systemic hazard models to develop structural, functional and behavioural models, describing a complex industrial system
Physical Training Methods For Mine Rescuers In 2015
Authors: Costa Cristian , Lupu Lucian , Edelhauser Eduard 
Published: September 2015

Abstract
We have studied physical mine rescue training programs and health-related and rescue-related fitness tasks during a mine rescue competition, made in China and Australia and on these basis we have design our own pre physical training method. We have stored the heart rate measured in bites per minute (bpm) during the 2012 year periodical training for 21 mine rescuers. We have designed a physical training procedure based on six training models: Body Building, Method of isometric efforts, Method of Interval Training, Volume variation method, Structured method for basic grip and release and Specific work method. Then we measured again during the 2014 year periodical training, the heart rate for the same mine rescuer having the physical training procedure performed before. We have notice that the trained person have now lower bpm, during the tests that could represent better performances during the rescue actions. Our research were made in the Laboratory for Risk-Rescue Operations of the INCD INSEMEX Petroşani, Romania.