bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is There a Right to the Death of the Foetus?
Authors: Mathison Eric , Davis Jeremy 
Published: February 2017

AbstractAt some point in the future – perhaps within the next few decades – it will be possible for foetuses to develop completely outside the womb. Ectogenesis, as this technology is called, raises substantial issues for the abortion debate. One such issue is that it will become possible for a woman to have an abortion, in the sense of having the foetus removed from her body, but for the foetus to be kept alive. We argue that while there is a right to an abortion, there are reasons to doubt that there is a right to the death of the foetus. Our strategy in this essay is to consider and reject three arguments in favour of this latter right. The first claims that women have a right not to be biological mothers, the second that women have a right to genetic privacy, and the third that a foetus is one's property. Furthermore, we argue that it follows from rejecting the third claim that genetic parents also lack a right to the destruction of cryopreserved embryos used for in vitro fertilization. The conclusion that a woman possesses no right to the death of the foetus builds upon the claims that other pro‐choice advocates, such as Judith Jarvis Thomson, have made.
Ways Out of the Patenting Prohibition? Human Parthenogenetic and Induced Pluripotent Stem Cells
Authors: Schickl Hannah , Braun Matthias , Dabrock Peter 
Published: February 2017

AbstractAccording to the judgement of the European Court of Justice in 2014, human parthenogenetic stem cells are excluded from the patenting prohibition of procedures based on hESC by the European Biopatent Directive, because human parthenotes are not human embryos. This article is based on the thesis that in light of the technological advances in the field of stem cell research, the attribution of the term ‘human embryo’ to certain entities on a descriptive level as well as the attribution of a normative protection status to certain entities based on the criterion of totipotency, are becoming increasingly unclear. The example of human parthenotes in particular demonstrates that totipotency is not at all a necessary condition for the attribution of the term ‘human embryo’. Furthermore, the example of hiPSC and somatic cells particularly shows that totipotency is also not a sufficient condition for the attribution of a normative protection status to certain entities. Therefore, it is not a suitable criterion for distinguishing between human embryos worthy of protection and human non‐embryos not worthy of protection. Consequently, this conclusion has repercussions for the patenting question. The strict delineation between an ethically problematic commercial use of human embryos and the concomitant patenting prohibition of hESC‐based procedures and an ethically unproblematic commercial use of human non‐embryos and the therefore either unrestrictedly permitted (cf. human parthenotes) or even unregulated (cf. hiPSC) patenting of procedures based on these alleged alternatives becomes increasingly blurred.
Human Dignity and Human Enhancement: A Multidimensional Approach
Authors: Kirchhoffer David G. 
Published: February 2017

AbstractIn the debates concerning the ethics of human enhancement through biological or technological modifications, there have been several appeals to the concept of human dignity, both by those favouring such enhancement and by those opposing it. The result is the phenomenon of ‘dignity talk', where opposing sides both appeal to the concept of human dignity to ground their arguments resulting in a moral impasse. This article examines the use of the concept of human dignity in the enhancement debates and reveals that the problem of dignity talk arises because proponents of various positions tend to ground human dignity in different features of the human individual. These features include species‐membership, possession of a particular capacity, a sense of self‐worth, and moral behaviour. The article proposes a solution to this problem by appealing to another feature of human beings, namely their being‐in‐relationship‐over‐time. Doing so enables us to understand dignity as a concept that affirms the worth of human individuals as complex, multidimensional wholes, rather than as isolated features. Consequently, the concept of human dignity can serve both a descriptive and a normative function in the enhancement debates. At a descriptive level, asking what advocates of a position mean when they refer to human dignity will reveal what aspects of being human they deem to be most valuable. The debate can then focus on these values. The normative function, although it cannot proscribe or prescribe all enhancement, approves only those enhancements that contribute to the flourishing of human individuals as multidimensional wholes.
Maximin Optimal Designs for Cluster Randomized Trials
Authors: Wu Sheng , Wong Weng Kee , Crespi Catherine M. 
Published: February 2017

Summary
We consider design issues for cluster randomized trials (CRTs) with a binary outcome where both unit costs and intraclass correlation coefficients (ICCs) in the two arms may be unequal. We first propose a design that maximizes cost efficiency (CE), defined as the ratio of the precision of the efficacy measure to the study cost. Because such designs can be highly sensitive to the unknown ICCs and the anticipated success rates in the two arms, a local strategy based on a single set of best guesses for the ICCs and success rates can be risky. To mitigate this issue, we propose a maximin optimal design that permits ranges of values to be specified for the success rate and the ICC in each arm. We derive maximin optimal designs for three common measures of the efficacy of the intervention, risk difference, relative risk and odds ratio, and study their properties. Using a real cancer control and prevention trial example, we ascertain the efficiency of the widely used balanced design relative to the maximin optimal design and show that the former can be quite inefficient and less robust to mis-specifications of the ICCs and the success rates in the two arms.
Controlling the False Discoveries in LASSO
Authors: Huang Hanwen 
Published: February 2017

Summary
The LASSO method estimates coefficients by minimizing the residual sum of squares plus a penalty term. The regularization parameter in LASSO controls the trade-off between data fitting and sparsity. We derive relationship between and the false discovery proportion (FDP) of LASSO estimator and show how to select so as to achieve a desired FDP. Our estimation is based on the asymptotic distribution of LASSO estimator in the limit of both sample size and dimension going to infinity with fixed ratio. We use a factor analysis model to describe the dependence structure of the design matrix. An efficient majorization–minimization based algorithm is developed to estimate the FDP at fixed value of . The analytic results are compared with those of numerical simulations on finite-size systems and are confirmed to be correct. An application to the high-throughput genomic riboavin data set also demonstrates the usefulness of our method.
Resection of synchronous liver metastases between radiotherapy and definitive surgery for locally advanced rectal cancer: short‐term surgical outcomes, overall survival and recurrence‐free survival
Authors: Labori K. J. , Guren M. G. , Brudvik K. W. , Røsok B. I. , Waage A. , Nesbakken A. , Larsen S. , Dueland S. , Edwin B. , Bjørnbeth B. A. 
Published: February 2017

AbstractAimThere is debate as to the correct treatment algorithm sequence for patients with locally advanced rectal cancer with liver metastases. The aim of the study was to assess safety, resectability and survival after a modified ‘liver‐first’ approach.MethodThis was a retrospective study of patients undergoing preoperative radiotherapy for the primary rectal tumour, followed by liver resection and, finally, resection of the primary tumour. Short‐term surgical outcome, overall survival and recurrence‐free survival are reported.ResultsBetween 2009 and 2013, 45 patients underwent liver resection after preoperative radiotherapy. Thirty‐four patients (76%) received neoadjuvant chemotherapy, 24 (53%) concomitant chemotherapy during radiotherapy and 17 (43%) adjuvant chemotherapy. The median time interval from the last fraction of radiotherapy to liver resection and rectal surgery was 21 (range 7–116) and 60 (range 31–156) days, respectively. Rectal resection was performed in 42 patients but was not performed in one patient with complete response and two with progressive metastatic disease. After rectal surgery three patients did not proceed to a planned second stage liver (n = 2) or lung (n = 1) resection due to progressive disease. Clavien–Dindo ≥Grade III complications developed in 6.7% after liver resection and 19% after rectal resection. The median overall survival and recurrence‐free survival in the patients who completed the treatment sequence (n = 40) were 49.7 and 13.0 months, respectively. Twenty of the 30 patients who developed recurrence underwent further treatment with curative intent.ConclusionThe modified liver‐first approach is safe and efficient in patients with locally advanced rectal cancer and allows initial control of both the primary tumour and the liver metastases.
Prediction model for cardiac allograft vasculopathy: Comparison of three multivariable methods
Authors: Kransdorf Evan P. , Loghmanpour Natasha A. , Kanwar Manreet K. , Temkit M'hamed H. , Stehlik Josef 
Published: February 2017

AbstractBackgroundCardiac allograft vasculopathy (CAV) remains an important cause of graft failure after heart transplantation (HT). Although many risk factors for CAV have been identified, there are no clinical prediction models that enable clinicians to determine each recipient's risk of CAV.MethodsWe studied a cohort of 14 328 heart transplant recipients whose data were reported to the International Society for Heart and Lung Transplantation Registry between 2000 and 2010. The cohort was divided into training (75%) and test (25%) sets. Multivariable modeling was performed in the test set using variables available at the time of heart transplant using three methods: (i) stepwise Cox proportional hazard, (ii) regularized Cox proportional hazard, and (iii) Bayesian network.ResultsCardiac allograft vasculopathy developed in 4259 recipients (29.7%) at a median time of 3.0 years after HT. The regularized Cox proportional hazard model yielded the optimal performance and was also the most parsimonious. We deployed this model as an Internet‐based risk calculator application.ConclusionsWe have developed a clinical prediction model for assessing a recipient's risk of CAV using variables available at the time of HT. Application of this model may allow clinicians to determine which recipients will benefit from interventions to reduce the risk of development and progression of CAV.
Evaluation of the safety of endoscopic radiofrequency ablation for malignant biliary stricture using a digital peroral cholangioscope (with videos)
Authors: Ogura Takeshi , Onda Saori , Sano Tatsushi , Takagi Wataru , Okuda Atsushi , Miyano Akira , Nishioka Nobu , Imanishi Miyuki , Amano Mio , Masuda Daisuke , Higuchi Kazuhide 
Published: February 2017

Background and AimThe clinical impact of catheter‐based radiofrequency ablation (RFA) under endoscopic retrograde cholangiopancreatography (ERCP) guidance has recently been reported; however, severe adverse events have also been noted. If tumor is not present in the biliary tract, severe adverse events such as perforation or bleeding as a result of vessel injury around the biliary tract may occur. In addition, the effectiveness of RFA may not be sufficient based solely on radiographic guidance. The aim of the present study was to evaluate the actual feasibility of intraductal RFA by peroral cholangioscope (POCS) evaluation before/after RFA.MethodsIn this retrospective study carried out between July and September 2016, consecutive patients who underwent RFA for malignant biliary stricture and POCS evaluation before/after RFA were enrolled. Primary endpoint of this study was technical feasibility of RFA, which was evaluated by POCS. Secondary endpoints were rates and types of adverse event.ResultsA total of 12 consecutive patients were retrospectively enrolled in this study. Stent placement using uncovered metal stents had been previously done in six patients before RFA. Tumor was seen in the biliary tract in all patients. RFA was technically successful in all patients, and clinical success was confirmed in all patients by POCS imaging. Adverse events were seen in only one patient. Median stent patency was 154 days.ConclusionsRFA for malignant biliary stricture may be safe. To confirm the feasibility and efficacy of RFA, additional cases, prospective studies, and a comparison study between with and without endobiliary RFA are needed.
Efficacy of midazolam‐ versus propofol‐based sedations by non‐anesthesiologists during therapeutic endoscopic retrograde cholangiopancreatography in patients aged over 80 years
Authors: Han Su Jung , Lee Tae Hoon , Park Sang‐Heum , Cho Young Sin , Lee Yun Nah , Jung Yunho , Choi Hyun Jong , Chung Il‐Kwun , Cha Sang‐Woo , Moon Jong Ho , Cho Young Deok , Kim Sun‐Joo 
Published: February 2017

Background and AimAs society ages, the need for endoscopic retrograde cholangiopancreatography (ERCP) is increasing. This prospective comparative study evaluated the safety and efficacy of midazolam‐ versus propofol‐based sedations by non‐anesthesiologists during therapeutic ERCP in patients over 80 years of age.MethodsA total of 100 patients over 80 years of age who required therapeutic ERCP were enrolled and randomly received midazolam + fentanyl (MF group) or propofol + fentanyl (PF group) sedation. Endoscopic sedation was titrated to a moderate level and carried out by trained registered nurses. Main outcome measurements were sedation safety in terms of cardiopulmonary components and efficacy measured on a 10‐point visual analogue scale (VAS).ResultsRegarding safety, hypoxia occurred in seven (14%) in the MF group and in eight patients (16%) in the PF group (P = 0.779). Increased O2 supply was more frequent in the PF group (32% vs 42%), albeit not significantly so. There were no differences in the frequency of hypotension, bradycardia or tachycardia between the two groups. Mean VAS score for overall satisfaction with sedation by patients, endoscopists, and nurses and the scores for pain during the procedures were not different between the two groups. There was no significant difference in the procedure outcomes or rate of ERCP‐related complications.ConclusionsThere were no significant differences of safety and efficacy between midazolam‐ and propofol‐based sedation in patients over 80 years of age. Increased O2 supply was more frequent in the propofol group, but the prevalence of hypoxia did not differ significantly.
Chronic liraglutide therapy induces an enhanced endogenous glucagon‐like peptide‐1 secretory response in early type 2 diabetes
Authors: Kramer Caroline K. , Zinman Bernard , Choi Haysook , Connelly Philip W. , Retnakaran Ravi 
Published: February 2017

Sustained exogenous stimulation of a hormone‐specific receptor can affect endogenous hormonal regulation. In this context, little is known about the impact of chronic treatment with glucagon‐like peptide‐1 (GLP‐1) agonists on the endogenous GLP‐1 response. We therefore evaluated the impact of chronic liraglutide therapy on endogenous GLP‐1 and glucose‐dependent insulinotropic polypeptide (GIP) response to an oral glucose challenge. A total of 51 people with type 2 diabetes of 2.6 ± 1.9 years’ duration were randomized to daily subcutaneous liraglutide or placebo injection and followed for 48 weeks, with an oral glucose tolerance test (OGTT) every 12 weeks. GLP‐1 and GIP responses were assessed according to their respective area under the curve (AUC) from measurements taken at 0, 30, 60, 90 and 120 minutes during each OGTT. There were no differences in AUCGIP
between the groups. By contrast, although fasting GLP‐1 was unaffected, the liraglutide arm had ~2‐fold higher AUCGLP

‐1 at 12 weeks (
P
< .001), 24 weeks (
P
< .001), 36 weeks (
P
= .03) and 48 weeks (
P
= .03), as compared with placebo. Thus, chronic liraglutide therapy induces a previously unrecognized, robust and durable enhancement of the endogenous GLP‐1 response, highlighting the need for further study of the long‐term effects of incretin mimetics on L‐cell physiology.
Benign mitochondrial myopathy with exercise intolerance in a large multigeneration family due to a homoplasmic m.3250T>C mutation in MTTL1
Authors: Darin N. , Hedberg‐Oldfors C. , Kroksmark A.‐K. , Moslemi A.‐R. , Kollberg G. , Oldfors A. 
Published: February 2017

Background and purposeMost mitochondrial disorders with onset in early childhood are progressive and involve multiple organs. The m.3250T>C mutation in MTTL1 has previously been described in a few individuals with a possibly riboflavin‐responsive myopathy and an association with sudden infant death syndrome was suspected. We describe a large family with this mutation and evaluate the effect of riboflavin treatment.MethodsMedical data were collected with the help of a standardized data collection form. Sanger sequencing was used to screen for variants in mitochondrial DNA and the proportion of the mutation was analyzed in different tissues. Biochemical and muscle morphological investigations of muscle tissue were performed in two individuals. The effect of riboflavin treatment was evaluated in two individuals.ResultsThirteen family members experienced exercise intolerance with fatigue and weakness. Inheritance was maternal with 100% penetrance. The course was either static or showed improvement over time. There was no evidence of other organ involvement except for a possible mild transient cardiac enlargement in one child. Muscle investigations showed isolated complex I deficiency and mitochondrial proliferation. The level of m.3250T>C was apparently 100%, i.e. homoplasmic, in all examined tissues. Riboflavin treatment showed no effect in any treated family member and there have been no cases of sudden infant death in this family.ConclusionsThis study illustrates the importance of considering mitochondrial disorders in the work‐up of individuals with exercise intolerance and provides a better understanding of the phenotype associated with the m.3250T>C mutation in MTTL1.
People with epilepsy obtain added value from education in groups: results of a qualitative study
Authors: Ridsdale L. , Philpott S. J. , Krooupa A.‐M. , Morgan M. 
Published: February 2017

Background and purposeHaving epilepsy requires individuals to learn about self‐management. So far, trials of self‐management courses have not included in‐depth qualitative evaluations of how the learning method influences participants’ perceptions and behaviour. We aimed to interview participants who had attended a course, as part of a randomized controlled trial, to examine: (i) their perceptions of what they valued and negative aspects of the intervention, and (ii) whether and in what ways they continued to make use of the training.MethodsTwenty participants were selected within 6 months of undertaking a course from the larger randomized controlled trial conducted in England. Semi‐structured interviews were based on a topic guide.ResultsParticipants’ characteristics were representative of the clinical and demographic characteristics of the trial group. Their mean age was 44 years, half were male, and three‐quarters had had epilepsy for over 10 years and had experienced one or more seizures in the previous month. Participants valued the opportunity to meet ‘people like them’. Structured learning methods encouraged them to share and compare feelings and experience. Specific benefits included: overcoming the sense of ‘being alone’ and improving self‐acceptance through meeting people with similar experience. Over half reported that this, and comparison of attitudes and experience, helped them to improve their confidence to talk openly, and make changes in health behaviours.ConclusionsPeople feel socially isolated in long‐term poorly controlled epilepsy. They gain confidence and self‐acceptance from interactive groups. Expert‐facilitated courses that encourage experiential learning can help people learn from each other, and this may enhance self‐efficacy and behaviour change.
Evaluation of observer‐ and industry‐based catch data in a recreational charter fishery
Authors: Gray C. A. , Kennelly S. J. 
Published: February 2017

AbstractThere is international recognition for greater inclusion of recreational fisheries catch data in species, fisheries and ecosystem assessments. Recreational charter fisheries provide important social services and contribute to total species catches. This study compares and validates industry logbook catch and effort data (1,357 trips) against observer data (154 trips) across six ports in a recreational charter fishery in eastern Australia. The mean numbers of clients and fishing effort (hours) per trip varied inconsistently between data sources and among ports. Logbooks did not adequately report released catches, and the mean number of species retained per trip was consistently underestimated in logbooks compared to observer data. For both data sources, catch rates of total individuals and key species displayed similar trends across different units of effort; catch per hour, client, client/hour and trip. The mean catch rates of total individuals and most key species, except those retained for bait, were similar across data sources, as were estimates of total fleet harvests. The length compositions of retained catches of some key species displayed truncation of larger organisms in the observer data whereas other species did not. Despite the shortcomings of the logbook data, future fishery and species monitoring strategies could include industry and observer data sources.
Cost‐effectiveness analysis of late prophylaxis vs. on‐demand treatment for severe haemophilia A in Italy
Authors: Coppola A. , D'Ausilio A. , Aiello A. , Amoresano S. , Toumi M. , Mathew P. , Tagliaferri A. ,   the Potter Study Group
Published: February 2017

IntroductionLong‐term regular administrations of factor VIII (FVIII) concentrate (prophylaxis) initiated at an early age prevents bleeding in patients with severe haemophilia A (HA). The 5‐year prospective Italian POTTER study provided evidence of benefits in adolescents and adults of late prophylaxis (LP) vs. on‐demand therapy (OD) in reducing bleeding episodes and joint morbidity and improving quality of life; however, costs were increased.AimThe aim of this study was to determine the cost‐effectiveness of LP vs. OD with sucrose‐formulated recombinant FVIII in adolescents and adults with severe HA in Italy.MethodsA Markov model evaluated lifetime cost‐effectiveness of LP vs. OD in patients with severe HA in Italy, from both the healthcare and societal perspectives. Clinical input parameters were taken from the POTTER study and published literature. Health utility values were assigned to each health state as measured by the joint disease severity Pettersson score. Costs were expressed in Euro (€) 2014, including drug and other medical costs. Sensitivity analyses were performed considering societal perspective (including productivity lost) and varying relative risk of bleeding episodes between regimens. Clinical outcomes and costs were discounted at 6% according to previous studies.ResultsLifetime incremental discounted quality‐adjusted life‐years (QALYs) were +4.26, whereas incremental discounted costs were +€229,694 from a healthcare perspective, with estimated incremental cost‐effectiveness ratios (ICERs) equal to €53,978/QALY. Sensitivity analyses confirmed the base‐case results showing lower ICERs with the societal perspective.ConclusionLate prophylaxis vs. on‐demand therapy results in a cost‐effective approach with ICERs falling below the threshold considered acceptable in Italy.