bluuebunny/crossref_metadata_2025_split huggingface dataset:
Controlling the family-wise error rate in multi-arm, multi-stage trials
Authors: Crouch Luis A , Dodd Lori E , Proschan Michael A 
Published: March 2017

Background and aims: Multi-arm, multi-stage trials have recently gained attention as a means to improve the efficiency of the clinical trials process. Many designs have been proposed, but few explicitly consider the inherent issue of multiplicity and the associated type I error rate inflation. It is our aim to propose a straightforward design that controls family-wise error rate while still providing improved efficiency. Methods: In this article, we provide an analytical method for calculating the family-wise error rate for a multi-arm, multi-stage trial and highlight the potential for considerable error rate inflation in uncontrolled designs. We propose a simple method to control the error rate that also allows for computation of power and expected sample size. Results: Family-wise error rate can be controlled in a variety of multi-arm, mutli-stage trial designs using our method. Additionally, our design can substantially decrease the expected sample size of a study while maintaining adequate power. Conclusion: Multi-arm, multi-stage designs have the potential to reduce the time and other resources spent on clinical trials. Our relatively simple design allows this to be achieved while weakly controlling family-wise error rate and without sacrificing much power.
Evaluation of different recall periods for the US National Cancer Institute’s PRO-CTCAE
Authors: Mendoza Tito R , Dueck Amylou C , Bennett Antonia V , Mitchell Sandra A , Reeve Bryce B , Atkinson Thomas M , Li Yuelin , Castro Kathleen M , Denicoff Andrea , Rogak Lauren J , Piekarz Richard L , Cleeland Charles S , Sloan Jeff A. , Schrag Deborah , Basch Ethan 
Published: March 2017

Aims: The US National Cancer Institute recently developed the PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events). PRO-CTCAE is a library of questions for clinical trial participants to self-report symptomatic adverse events (e.g. nausea). The objective of this study is to inform evidence-based selection of a recall period when PRO-CTCAE is included in a trial. We evaluated differences between 1-, 2-, 3-, and 4-week recall periods, using daily reporting as the reference. Methods: English-speaking patients with cancer receiving chemotherapy and/or radiotherapy were enrolled at four US cancer centers and affiliated community clinics. Participants completed 27 PRO-CTCAE items electronically daily for 28 days, and then weekly over 4 weeks, using 1-, 2-, 3-, and 4-week recall periods. For each recall period, mean differences, effect sizes, and intraclass correlation coefficients were calculated to evaluate agreement between the maximum of daily ratings and the corresponding ratings obtained using longer recall periods (e.g. maximum of daily scores over 7 days vs 1-week recall). Analyses were repeated using the average of daily scores within each recall period rather than the maximum of daily scores. Results: A total of 127 subjects completed questionnaires (57% male; median age: 57). The median of the 27 mean differences in scores on the PRO-CTCAE 5-point response scale comparing the maximum daily versus the longer recall period (and corresponding effect size) was −0.20 (−0.20) for 1-week recall, −0.36 (−0.31) for 2-week recall, −0.45 (−0.39) for 3-week recall, and −0.47 (−0.40) for 4-week recall. The median intraclass correlation across 27 items between the maximum of daily ratings and the corresponding longer recall ratings for 1-week recall was 0.70 (range: 0.54–0.82), for 2-week recall was 0.74 (range: 0.58–0.83), for 3-week recall was 0.72 (range: 0.61–0.84), and for 4-week recall was 0.72 (range: 0.64–0.86). Similar results were observed for all analyses using the average of daily scores rather than the maximum of daily scores. Conclusion: A 1-week recall corresponds best to daily reporting. Although intraclass correlations remain stable over time, there are small but progressively larger differences between daily and longer recall periods at 2, 3, and 4 weeks, respectively. The preferred recall period for the PRO-CTCAE is the past 7 days, although investigators may opt for recall periods of 2, 3, or 4 weeks with an understanding that there may be some information loss.
The Broken “Ring of Fire”: A New Radiological Sign as Predictor of Syndesmosis Injury?
Authors: Calder James , Mitchell Adam , Lomax Adam , Ballal Moez S. , Grice John , van Dijk Niek , Lee Justin 
Published: March 2017

Background: Subcircumferential periosteal edema above the ankle joint is frequently present on magnetic resonance imaging (MRI) with syndesmosis injuries but has not been previously reported. Fluid height within the interosseous membrane also has not previously been shown to be associated with syndesmosis injury severity. Purpose: To investigate whether a new sign on MRI and measurement of the length of fluid within the interosseous membrane above the ankle may be used to enable identification of a syndesmosis injury and allow differentiation from lateral ligament injury. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: Three groups of patients (those with an isolated syndesmosis injury [SI group], isolated lateral ligament injury [LLI group], and no injury [NI group]) who had an ankle MRI for another reason were identified from a patient notes database and the MRI scans retrieved. The scans were anonymized and independently assessed by 8 clinicians (surgeons and radiologists) who were blinded to the diagnosis. The maximum length of fluid above the ankle within the intraosseous membrane was measured for each patient. The presence or absence of distal anterior, lateral, and posterior tibial periosteal edema was recorded (broken “ring of fire”). Results: Measurement of the length of fluid above the ankle had excellent intraobserver reliability (intraclass correlation coefficient, 0.97; 95% CI, 0.93-0.99) but poor interobserver reliability. Fluid extended higher in both the LLI group ( P = .0043) and SI group ( P = .0058) than the NI group, but there was no significant difference between the LLI and SI groups ( P = .3735), indicating that this measurement cannot differentiate between the injuries. The presence of the broken “ring of fire” around the distal tibia was significantly more frequent in the SI group when compared with both LLI and NI groups ( P < .00001). The sensitivity of this sign is 49%, but when present, this sign has a 98% specificity for syndesmosis injury. Conclusion: The presence of tibial subcircumferential periosteal edema 4 to 6 cm above the ankle joint (the “ring of fire”) is highly suggestive of a syndesmosis injury. This new radiological sign can assist with early identification of such injuries. The measurement of height of fluid above the ankle within the interosseous membrane is variable and cannot differentiate severe ankle sprains from high ankle sprains involving the syndesmosis.
Understanding Preferences for Treatment After Hypothetical First-Time Anterior Shoulder Dislocation: Surveying an Online Panel Utilizing a Novel Shared Decision-Making Tool
Authors: Streufert Ben , Reed Shelby D. , Orlando Lori A. , Taylor Dean C. , Huber Joel C. , Mather Richard C. 
Published: March 2017

Background: Although surgical management of a first-time anterior shoulder dislocation (FTASD) can reduce the risk of recurrent dislocation, other treatment characteristics, costs, and outcomes are important to patients considering treatment options. While patient preferences, such as those elicited by conjoint analysis, have been shown to be important in medical decision-making, the magnitudes or effects of patient preferences in treating an FTASD are unknown. Purpose: To test a novel shared decision-making tool after sustained FTASD. Specifically measured were the following: (1) importance of aspects of operative versus nonoperative treatment, (2) respondents’ agreement with results generated by the tool, (3) willingness to share these results with physicians, and (4) association of results with choice of treatment after FTASD. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A tool was designed and tested using members of Amazon Mechanical Turk, an online panel. The tool included an adaptive conjoint analysis exercise, a method to understand individuals’ perceived importance of the following attributes of treatment: (1) chance of recurrent dislocation, (2) cost, (3) short-term limits on shoulder motion, (4) limits on participation in high-risk activities, and (5) duration of physical therapy. Respondents then chose between operative and nonoperative treatment for hypothetical shoulder dislocation. Results: Overall, 374 of 501 (75%) respondents met the inclusion criteria, of which most were young, active males; one-third reported prior dislocation. From the conjoint analysis, the importance of recurrent dislocation and cost of treatment were the most important attributes. A substantial majority agreed with the tool’s ability to generate representative preferences and indicated that they would share these preferences with their physician. Importance of recurrence proved significantly predictive of respondents’ treatment choices, independent of sex or age; however, activity level was important to previous dislocators. A total of 125 (55%) males and 33 (23%) females chose surgery after FTASD, as did 37% of previous dislocators compared with 45% of nondislocators. Conclusion: When given thorough information about the risks and benefits, respondents had strong preferences for operative treatment after an FTASD. Respondents agreed with the survey results and wanted to share the information with providers. Recurrence was the most important attribute and played a role in decisions about treatment.
Myeloid p53 regulates macrophage polarization and venous thrombus resolution by inflammatory vascular remodeling in mice
Authors: Mukhopadhyay Subhradip , Antalis Toni M. , Nguyen Khanh P. , Hoofnagle Mark H. , Sarkar Rajabrata 
Published: March 2017

Key Points
Endogenous p53 within myeloid cells regulates venous thrombus resolution, intrathrombus macrophage polarization, and fibrosis. The p53 agonist quinacrine accelerates resolution of established venous thrombus, a potential translational benefit in patients with DVT.
A novel melittin nano-liposome exerted excellent anti-hepatocellular carcinoma efficacy with better biological safety
Authors: Mao Jie , Liu Shujun , Ai Min , Wang Zhuo , Wang Duowei , Li Xianjing , Hu Kaiyong , Gao Xinghua , Yang Yong 
Published: March 2017

AbstractMelittin is the main effective component of bee venom and has extensive biological functions; however, serious side effects have restricted its clinical application. Preclinical and clinical studies showed that the main adverse events were allergic reaction and pain at the administration site. To decrease the toxicity, we prepared melittin nano-liposomes by encapsulating melittin with poloxamer 188 and explored the inhibitory activities on liver cancer together with biological safety. Here, we showed that melittin nano-liposomes significantly inhibited the survival of hepatocellular carcinoma (HCC) cells in vitro and prominently suppressed the growth of subcutaneous and orthotopic HCC transplantation tumors in vivo. It was important that it induced less inflammation and allergy in mice compared with melittin. Overall, melittin nano-liposomes would have a better application in HCC therapy due to its significant anti-tumor activity and better biological safety.
Antiarrhythmic drugs for out-of-hospital cardiac arrest with refractory ventricular fibrillation
Authors: Tagami Takashi , Yasunaga Hideo , Yokota Hiroyuki 
Published: March 2017

AbstractThis article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2017. Other selected articles can be found online at http://ccforum.com/series/annualupdate2017. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
Mechanical ventilation in obese ICU patients: from intubation to extubation
Authors: De Jong Audrey , Chanques Gerald , Jaber Samir 
Published: March 2017

AbstractThis article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2017. Other selected articles can be found online at http://ccforum.com/series/annualupdate2017. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
Novel insights in ICU-acquired respiratory muscle dysfunction: implications for clinical care
Authors: Jonkman Annemijn H. , Jansen Diana , Heunks Leo M. A. 
Published: March 2017

AbstractThis article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2017. Other selected articles can be found online at http://ccforum.com/series/annualupdate2017. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
Antioxidant properties of the carotenoid extracts of three Deinococcus–Thermus phylum bacteria, Meiothermus sp. strains RP and TP and Thermus sp. strain YY from Paniphala hot spring, India
Authors: Mukherjee Trinetra , Bose Sucharita , Mukhopadhyay Subhra Kanti 
Published: March 2017

Abstract
Background
The purpose of the study was to extract carotenoids from thermophilic bacteria which show efficient antioxidant and protein oxidation inhibition properties, characterize and identify those isolates, extract the carotenoids in different solvents, quantify the carotenoids and perform concentration-dependent and solvent-dependent quantitative assays validated and analysed by appropriate statistical tests.

Methods
Three pigment-forming thermophilic strains were isolated from water sample of Paniphala hot spring, India, and tentatively identified by 16S ribosomal DNA (rDNA) homology. Different concentrations of the carotenoid extracts (100, 80, 40 and 20 μg) in three solvents, methanol, DMSO and water, were used to determine the antioxidant activity through five methods: the DPPH (1,1-diphenyl-2-picrylhydrazyl) assay, the ABTS (2,2-azino-bis (3-ethylbenz-thiazoline-6-sulfonic acid)) assay, the hydrogen peroxide assay, TOC (total antioxidant capacity) assay and inhibition of protein oxidation assay. Statistical analysis of mean, standard deviation, ANOVA and Pearson correlation coefficient was performed in Microsoft Excel statistical package.

Results
The isolates were tentatively identified as Meiothermus sp. strain RP, Meiothermus sp. strain TP and Thermus strain YY. Meiothermus sp. formed red coloured pigment, whereas Thermus sp. formed yellow coloured pigment. All of the extracts showed positive results in DPPH assay, ABTS assay and hydrogen peroxide radical scavenging assay with best results obtained when the extracts were dissolved in water. Total antioxidant capacity assay was also high in all the extracts. Protein oxidation inhibition activity was only seen in extracts of strain YY. One-way ANOVA (analysis of variance) clearly showed that choice of solvent influenced the antioxidant capacity of all of the extracts.

Conclusions
Newer and efficient antioxidative compounds are constantly being searched for, and the carotenoid extracts of RP, TP and YY have been shown to catalyze various types of antioxidative reactions, including protein oxidation inhibition by YY. Thus, all these extracts have huge potential to be industrially and pharmaceutically useful.
Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials
Authors: Taylor Carolyn , Correa Candace , Duane Frances K. , Aznar Marianne C. , Anderson Stewart J. , Bergh Jonas , Dodwell David , Ewertz Marianne , Gray Richard , Jagsi Reshma , Pierce Lori , Pritchard Kathleen I. , Swain Sandra , Wang Zhe , Wang Yaochen , Whelan Tim , Peto Richard , McGale Paul ,   for the Early Breast Cancer Trialists’ Collaborative Group
Published: March 2017

Purpose Radiotherapy reduces the absolute risk of breast cancer mortality by a few percentage points in suitable women but can cause a second cancer or heart disease decades later. We estimated the absolute long-term risks of modern breast cancer radiotherapy. Methods First, a systematic literature review was performed of lung and heart doses in breast cancer regimens published during 2010 to 2015. Second, individual patient data meta-analyses of 40,781 women randomly assigned to breast cancer radiotherapy versus no radiotherapy in 75 trials yielded rate ratios (RRs) for second primary cancers and cause-specific mortality and excess RRs (ERRs) per Gy for incident lung cancer and cardiac mortality. Smoking status was unavailable. Third, the lung or heart ERRs per Gy in the trials and the 2010 to 2015 doses were combined and applied to current smoker and nonsmoker lung cancer and cardiac mortality rates in population-based data. Results Average doses from 647 regimens published during 2010 to 2015 were 5.7 Gy for whole lung and 4.4 Gy for whole heart. The median year of irradiation was 2010 (interquartile range [IQR], 2008 to 2011). Meta-analyses yielded lung cancer incidence ≥ 10 years after radiotherapy RR of 2.10 (95% CI, 1.48 to 2.98; P < .001) on the basis of 134 cancers, indicating 0.11 (95% CI, 0.05 to 0.20) ERR per Gy whole-lung dose. For cardiac mortality, RR was 1.30 (95% CI, 1.15 to 1.46; P < .001) on the basis of 1,253 cardiac deaths. Detailed analyses indicated 0.04 (95% CI, 0.02 to 0.06) ERR per Gy whole-heart dose. Estimated absolute risks from modern radiotherapy were as follows: lung cancer, approximately 4% for long-term continuing smokers and 0.3% for nonsmokers; and cardiac mortality, approximately 1% for smokers and 0.3% for nonsmokers. Conclusion For long-term smokers, the absolute risks of modern radiotherapy may outweigh the benefits, yet for most nonsmokers (and ex-smokers), the benefits of radiotherapy far outweigh the risks. Hence, smoking can determine the net effect of radiotherapy on mortality, but smoking cessation substantially reduces radiotherapy risk.
Modeling and simulation of bus assem-bling process using DES/ABS approach
Authors: Pawlewski Pawel , Kluska Kamila 
Published: March 2017

This paper presents the results of the project, which goal is to analyze the production process capability after reengineering the assembly process due to expansion of a bus production plant. The verification of the designed work organization for the new configuration of workstations on new production hall is necessary. To solve these problems authors propose a method based on mixing DES (Discrete Event Simulation) and ABS (Agent Based Simulation) approach. DES is using to model the main process – material flow (buses), ABS is using to model assembling operations of teams of workers.One of obtained goal is to build a simulation model, which presents the new assembly line in the factory, taking into ac-count the arrangement of workstations and work teams in the new production hall as well as the transport between workstations. Second goal is to present work organization of work teams and division of individual workers’ labor (who belongs to a particular work team and performs operations on buses in a particular workstation) in order to determine the best allocation of tasks and the optimum size of individual work teams. Proposed solution enables to determine the effect of assembly interferences on the work of particular work teams and the efficiency of the whole production system, to define the efficiency of the designed assembly lines and proposing changes aimed at the quality improvement of the created conception.
Between the Profiles Pay Per View and the Protection of Personal Data: the Product is You
Authors: Chávez Valdivia Ana Karin 
Published: March 2017

Perhaps in the past was difficult to imagine that the moment in which someone could register each purchase that has been made, each book that has been read or each thing that has been said would come. That there would be companies storing data about our physical activity, behaviors, preferences and choices all the time. Most of the personal data comes from acts as daily as installing an application, completing a form, purchasing a product or requesting a service. This information provided sometimes consciously, voluntarily and with relative knowledge of the destination that will have, contrasts with situations in which data are inferred, deduced, extracted and manipulated. In this sense, within a context in which the only access to the database has been left behind to give way to the creation of these by third parties, we wonder about the possible denaturation of the personal data and sensitive information that when get transformed in raw material through the analysis of existent connections and extraction of new data implicit in the multitude of information compiled in public or private databases, would convert people into an essential product for the market; while the development of citizen profiles pay per view would allow predicting behaviors, selections and multiple deployments in different aspects of our lives. It is probable that in the defenselessness condition where we are now for having passed from personal space to social one and from there to the market many times without our knowledge and consent makes necessary to reconsider the current forms of protection and mechanisms of legal protection around our personal data.
Mastoscopic sentinel lymph node biopsy in breast
cancer
Authors: Ding Boni , Zhang Hongyan , Li Xiaorong , Qian Liyuan , Chen Xuedong , Wu Wei , Wen Yanguang , Zhao Yujun 
Published: March 2017

Abstract
Background: Previous studies have demonstrated
that mastoscopic sentinel lymph node biopsy
(MSLNB) has good identification rate (IR) and low false
negative rate (FNR). However, few studies have directly
compared the surgical performance and peri- and post-operative
factors of MSLNB with conventional sentinel lymph
node biopsy (SLNB).

Methodology: Sixty patients diagnosed with breast cancer
were recruited and randomly assigned to one of the three
groups: MSLNB, SLNB and SLNB with lipolysis injection.
Peri- and post-operative parameters were compared using
general linear models. To examine the effect of age on
these parameters, we performed separate analysis stratified
by age (≤50 years old vs. >50 years old).

Results: Patients in the MSLNB group experienced longer
surgery and suffered higher surgical cost than patients
who underwent conventional SLNB or SLNB with lipolysis
injection (p<0.0001). Despite this, they had significantly
less blood loss than those who underwent conventional
SLNB (22.0±7.0 ml vs.73.5±39.6 ml; p<0.0001). Analysis by
age group indicates a similar pattern of difference among
the three groups. MSLNB and conventional SLNB have
similar IR and FNR.

Conclusion: As a minimally invasive technique, MSLNB
can significantly reduce blood loss while providing similar
IR and FNR, indicating that it can be a promising alternative
to conventional SLNB.

Conclusion: Variations in popliteal artery terminal
branching pattern occurred in 7.4% to 17.6% of patients.
Pre-surgical detection of these variations with MD CTA
may help to reduce the risk of iatrogenic arterial injury by
enabling a better surgical treatment plan.