bluuebunny/crossref_metadata_2025 huggingface dataset:
Restrictions imposed upon the transient and frequency response of networks
Authors: Chirlian Paul M.
Published: December 2016

Readily evaluated upper and lower bounds on the impulse, step, and frequency response of certain classes of networks are obtained. These bounds are the best possible and can be applied to integrated RC structures as well as lumped networks. These procedures can be extended to general networks.
Pandemics: A Very Short Introduction
Authors: McMillen Christian W.
Published: December 2016

The 2014 Ebola epidemic demonstrated the power of pandemics and their ability not only to destroy lives locally but also to capture imaginations worldwide. Pandemics: A Very Short Introduction provides a concise yet comprehensive account of pandemics throughout human history, illustrating the ways in which pandemic disease—including plague, tuberculosis, malaria, smallpox, cholera, influenza, and HIV/AIDS—has shaped history and how human history has shaped pandemic disease. By considering the explosion of medical research and the varying state responses, such as quarantine and travel restrictions, this Very Short Introduction shows why pandemics are both interesting from a medical standpoint and provide insight into the culture and politics of their time.
Zionism: A Very Short Introduction
Authors: Stanislawski Michael
Published: December 2016

Zionism: A Very Short Introduction explores the history of Zionism from the origins of modern Jewish nationalism in the 1870s to the present. While situating the history of Zionism within the wider context of Middle Eastern politics, British colonialism, and the policies of the State of Israel since its founding in 1948, this VSI focuses on its internal intellectual history and ideological developments and divides. It illuminates the development of the Zionist ideology from the appearance of Herzl to the Weizmann Era, from the creation of the state of Israel and the Six Day War of 1967 to the rise of the Peace Now movement.
A mass graph-based approach for the identification of modified proteoforms using top-down tandem mass spectra
Authors: Kou Qiang , Wu Si , Tolić Nikola , Paša-Tolić Ljiljana , Liu Yunlong , Liu Xiaowen
Published: December 2016

Motivation

Although proteomics has rapidly developed in the past decade, researchers are still in the early stage of exploring the world of complex proteoforms, which are protein products with various primary structure alterations resulting from gene mutations, alternative splicing, post-translational modifications, and other biological processes. Proteoform identification is essential to mapping proteoforms to their biological functions as well as discovering novel proteoforms and new protein functions. Top-down mass spectrometry is the method of choice for identifying complex proteoforms because it provides a ‘bird's eye view’ of intact proteoforms. The combinatorial explosion of various alterations on a protein may result in billions of possible proteoforms, making proteoform identification a challenging computational problem.

Results

We propose a new data structure, called the mass graph, for efficient representation of proteoforms and design mass graph alignment algorithms. We developed TopMG, a mass graph-based software tool for proteoform identification by top-down mass spectrometry. Experiments on top-down mass spectrometry datasets showed that TopMG outperformed existing methods in identifying complex proteoforms.

Availability and implementation

http://proteomics.informatics.iupui.edu/software/topmg/

Supplementary information

Supplementary data are available at Bioinformatics online.
Defining the clonality of peripheral T cell lymphomas using RNA-seq
Authors: Brown Scott D , Hapgood Greg , Steidl Christian , Weng Andrew P , Savage Kerry J , Holt Robert A
Published: December 2016

Motivation

In T-cell lymphoma, malignant T cells arising from a founding clone share an identical T cell receptor (TCR) and can be identified by the over-representation of this TCR relative to TCRs from the patient’s repertoire of normal T cells. Here, we demonstrate that TCR information extracted from RNA-seq data can provide a higher resolution view of peripheral T cell lymphomas (PTCLs) than that provided by conventional methods.

Results

For 60 subjects with PTCL, flow cytometry/FACS was used to identify and sort aberrant T cell populations from diagnostic lymph node cell suspensions. For samples that did not appear to contain aberrant T cell populations, T helper (TH), T follicular helper (TFH) and cytotoxic T lymphocyte (CTL) subsets were sorted. RNA-seq was performed on sorted T cell populations, and TCR alpha and beta chain sequences were extracted and quantified directly from the RNA-seq data. 96% of the immunophenotypically aberrant samples had a dominant T cell clone readily identifiable by RNA-seq. Of the samples where no aberrant population was found by flow cytometry, 80% had a dominant clone by RNA-seq. This demonstrates the increased sensitivity and diagnostic ability of RNA-seq over flow cytometry and shows that the presence of a normal immunophenotype does not exclude clonality.

Availability and Implementation

R scripts used in the processing of the data are available online at https://www.github.com/scottdbrown/RNAseq-TcellClonality

Supplementary information

Supplementary data are available at Bioinformatics online.
Family Functioning and Mood and Anxiety Symptoms in Adolescents Born Extremely Preterm
Authors: Burnett Alice C. , Lee Katherine J. , Cheong Jeanie L. Y. , De Luca Cinzia R. , Roberts Gehan , Wood Stephen J. , Doyle Lex W. , Anderson Peter J. ,   on behalf of the Victorian Infant Collaborative Study Group
Published: December 2016

Objective:

To (1) compare adolescent- and parent-perceived family functioning between extremely preterm/extremely low birth weight (<28 wk/<1000 g, EP/ELBW) and normal birth weight (>2499 g, NBW) adolescents and (2) determine whether adolescents' or parents' ratings of family functioning were related to concurrent depression and anxiety symptoms in the adolescent and whether these relationships varied by birth group.

Methods:

One hundred ninety-three EP/ELBW and 151 NBW adolescents (aged 15–20 yr) and their parents rated aspects of family functioning on the Family Environment Scale. Adolescents rated current depression and anxiety symptoms on the Center for Epidemiologic Studies Depression Scale-Revised and Beck Anxiety Inventory. Family functioning was compared across the groups using linear regression, and logistic regression was used to assess relationships between family functioning domains and elevated depression and anxiety scores.

Results:

Compared with NBW controls, EP/ELBW adolescents reported similar levels of family Cohesiveness and Expressiveness, but less Conflict, and more Organization and Control. Parent ratings of family functioning were similar between groups except for higher Control scores in EP/ELBW group parents. Poorer family functioning as rated by adolescents, but not parents, was associated with increased depression/anxiety symptoms. These findings were generally consistent across both the EP/ELBW and control groups.

Conclusion:

EP/ELBW adolescents report generally positive family functioning. While adolescents' perceptions of family functioning are associated with concurrent adolescent mental health, parental perceptions of family functioning may not be indicative of adolescents' mental health. Importantly, EP/ELBW adolescents do not appear to be more vulnerable to anxiety/depression in the context of poorly perceived family functioning than their NBW peers.
Donor Screening Experience for Fecal Microbiota Transplantation in Patients With Recurrent C. difficile Infection
Authors: Tariq Raseen , Weatherly Renee , Kammer Patricia , Pardi Darrell S. , Khanna Sahil
Published: December 2016

Goals:

To evaluate our experience with stool donor recruitment, screening, retention, and donor perception for fecal microbiota transplantation (FMT).

Background:

Multiply recurrentClostridium difficileinfection is being increasingly managed with FMT from donor stools. However, donor selection and recruitment is challenging due to lack of standard evidence-based guidelines, donor exclusion criteria, frequency of screening and donor commitment.

Methods:

Data on donors screened using institutional guidelines with history, blood and stool testing and their perspectives on donation were analyzed.

Results:

Overall 42 potential donors (21 known and 21 standard) were prescreened. Of known donors (median age 34 y, 66.6% female), none failed prescreening, blood or stool tests. Twelve standard donors (57%) failed prescreening based on history (depression, diarrhea, autoimmune disease, recent antibiotic exposure, colon polyps, pregnancy). Nine (median age 35 y, 44.4% female) passed blood and stool testing. On repeat screening, 3 were excluded (2-positive stool shiga toxin (asymptomatic), 1-pregnancy). One donor opted out and 5 became long-term donors; 3 have donated >50 times and 2 have donated >25 times. On the basis of donor perception questionnaire, most standard donors were aware of FMT forC. difficileinfection as a treatment option and would not consider 3-monthly blood and stool testing inconvenient.

Conclusions:

A significant proportion of healthy individuals who volunteered to become a standard donor failed prescreening and were not subjected to blood and stool testing. Repeat testing for asymptomatic donors may be a barrier to donor retention. Universal guidelines are needed to develop strategies to facilitate donor screening.
Cognition in Patients With a Clinical Diagnosis of Parkinson Disease and Scans Without Evidence of Dopaminergic Deficit (SWEDD): 2-Year Follow-Up
Authors: Wyman-Chick Kathryn A. , Martin Phillip K. , Minár Michal , Schroeder Ryan W.
Published: December 2016

Objective and Background:

More than 10% of patients clinically diagnosed with Parkinson disease demonstrate normal dopamine uptake on dopamine transporter single-photon emission computed tomography (DaTscan), but little is known about how cognitive function differs between patients with dopamine deficiency on DaTscan and patients with scans without evidence of dopaminergic deficit (SWEDD). We compared the cognitive function of these two groups of patients over 2 years.

Methods:

We retrospectively analyzed data obtained from the Parkinson’s Progression Markers Initiative on 309 participants clinically diagnosed with idiopathic Parkinson disease who had scored in the normal range on the Montreal Cognitive Assessment at baseline and had completed 1- and 2-year follow-up visits. We compared the Montreal Cognitive Assessment scores at 1 and 2 years between the 42 participants with SWEDD and the 267 with dopamine deficiency.

Results:

Mean cognitive scores did not differ significantly between groups at 1 year, but at 2 years the participants with SWEDD performed more poorly. At 2 years, 31% of the participants with SWEDD versus 15% of those with dopamine deficiency had statistically reliable cognitive impairment.

Conclusions:

This study provides evidence that some individuals clinically diagnosed with idiopathic Parkinson disease but with SWEDD demonstrate early cognitive decline. The results also suggest that recently diagnosed patients with SWEDD may be at even greater risk for cognitive decline than patients with DaTscan-confirmed early-stage Parkinson disease. While patients with SWEDD likely represent a heterogeneous group of etiologies, our results highlight the need to monitor these patients’ cognitive function over time.
Foraging in an unsteady world: bumblebee flight performance in field-realistic turbulence
Authors: Crall J. D. , Chang J. J. , Oppenheimer R. L. , Combes S. A.
Published: December 2016

Natural environments are characterized by variable wind that can pose significant challenges for flying animals and robots. However, our understanding of the flow conditions that animals experience outdoors and how these impact flight performance remains limited. Here, we combine laboratory and field experiments to characterize wind conditions encountered by foraging bumblebees in outdoor environments and test the effects of these conditions on flight. We used radio-frequency tags to track foraging activity of uniquely identified bumblebee (Bombus impatiens) workers, while simultaneously recording local wind flows. Despite being subjected to a wide range of speeds and turbulence intensities, we find that bees do not avoid foraging in windy conditions. We then examined the impacts of turbulence on bumblebee flight in a wind tunnel. Rolling instabilities increased in turbulence, but only at higher wind speeds. Bees displayed higher mean wingbeat frequency and stroke amplitude in these conditions, as well as increased asymmetry in stroke amplitude—suggesting that bees employ an array of active responses to enable flight in turbulence, which may increase the energetic cost of flight. Our results provide the first direct evidence that moderate, environmentally relevant turbulence affects insect flight performance, and suggest that flying insects use diverse mechanisms to cope with these instabilities.
Development of 2-phenylethanol plus acetic acid lures to monitor obliquebanded leafroller (Lepidoptera: Tortricidae) under mating disruption
Authors: Knight A. L. , Judd G. J. R. , Basoalto E. , El-Sayed A. M.
Published: December 2016

We evaluated the effectiveness of 2-phenylethanol (PET) in combination with acetic acid (AA) as a binary lure for monitoring male and female obliquebanded leafroller,Choristoneura rosaceana(Harris). Studies were conducted in apple,Malus domesticaBorkhausen, orchards treated with or without sex pheromone dispensers for mating disruption (MD). Open polypropylene vials, closed membrane cups, and rubber septa loaded with AA and/or PET in varying amounts were first evaluated in a series of trapping experiments. Membrane cups loaded with 800 mg of PET were as effective as 10-mg septa, but longer lasting, and were comparable to the open vials. A membrane cup AA lure was effective in tests, but further work is needed to increase its release rate and extend its activity. Catches of codling moth,Cydia pomonella(L.), andC. rosaceanawere unaffected by combining PET with (E,E)-8,10-dodecadien-1-ol, the sex pheromone of codling moth, pear ester, (E,Z)-2,4-ethyl-decadienoate, and AA lures. Adding (E)-4,8-dimethyl-1,3,7-nonatriene to this blend to enhance codling moth catch, significantly reduced catches ofC. rosaceana.PET+AA was a more attractive binary lure than AA plus phenylacetonitrile (PAN) forC. rosaceana.The addition of PET or PAN to traps already baited with the sex pheromone ofC. rosaceanasignificantly reduced male catches. Traps baited with PET+AA placed in blocks not treated with MD caught significantly fewerC. rosaceanathan traps baited with sex pheromone. In comparison, sex pheromone-baited traps in MD blocks caught ≤ 1 male moth per season which was significantly lower than total moth (> 10) or female moth (≥ 3) catch in these blocks with PET+AA. A high proportion (> 70%) of trapped females were mated in both untreated and MD-treated orchards. Further refinement of this binary, bisexual lure using membrane cup technology may allow the establishment of action thresholds and improve management timings forC. rosaceana.
A simulation-based evaluation of STRUCTURE software for exploring the introduction routes of invasive species
Authors: Lombaert Eric , Guillemaud Thomas , Deleury Emeline
Published: December 2016

Population genetic methods are widely used to retrace the introduction routes of invasive species. The unsupervised Bayesian clustering algorithm implemented in STRUCTURE is amongst the most frequently use of these methods, but its ability to provide reliable information about introduction routes has never been assessed. We used computer simulations of microsatellite datasets to evaluate the extent to which the clustering results provided by STRUCTURE were misleading for the inference of introduction routes. We focused on the simple case of an invasion scenario involving one native population and two independently introduced populations, because it is the sole scenario with two introduced populations that can be rejected when obtaining a particular clustering with a STRUCTURE analysis atK= 2 (two clusters). Results were classified as “misleading” or “non-misleading”. We then investigated the influence of two demographic parameters (effective size and bottleneck severity) and different numbers of loci on the type and frequency of misleading results. We showed that misleading STRUCTURE results were obtained for 10% of our simulated datasets and at a frequency of up to 37% for some combinations of parameters. Our results highlighted two different categories of misleading output. The first occurs in situations in which the native population has a low level of diversity. In this case, the two introduced populations may be very similar, despite their independent introduction histories. The second category results from convergence issues in STRUCTURE forK= 2, with strong bottleneck severity and/or large numbers of loci resulting in high levels of differentiation between the three populations.
Impact of gray matter signal regression in resting state and language task functional networks
Authors: Herrera Luis C. T. , Castellano Gabriela , Coan Ana C. , Ludwing M. , César C. L.
Published: December 2016

A network analysis of the resting state (RS) and language task (LT) of fRMI data sets is presented. Specifically, the analysis compares the impact of the global signal regression of gray matter signal on the graph parameters and community structure derived of functional data. It was found that, without gray matter signal regression (GSR), the group comparison showed no significant changes of the global metrics between the two conditions studied. With gray matter signal regression, significant differences between the global (local) metrics for the conditions were obtained. The mean degree, the clustering coefficient of the network and the mean value of the local efficiency were metrics with significant changes. The community structure of group connectivity matrices was explored for both conditions (RS and LT) and for different preprocessing steps. When gray matter signal regression was performed, small changes of the community structure were observed. Approximately, the same regions were classified in the same communities before and after GSR. This means, that the community structure of the data is weakly affected by this preprocessing step. The modularity index presented significant changes between conditions (RS and LT) and between different preprocessing pipeline.
Crystal structure of the ATPase-C domain of the chromatin remodeller Fun30 fromSaccharomyces cerevisiae
Authors: Liu Lan , Jiang Tao
Published: December 2016

Fun30 (Function unknown now 30) is a chromatin remodeller belonging to the Snf2 family. It has previously been reported to be a regulator of several cellular activities, including DNA repair, gene silencing and maintenance of chromatin structure. Here, the crystal structure of the Fun30 ATPase-C domain (the C-lobe of the ATPase domain) is reported at 1.95 Å resolution. Although the structure displays overall similarities to those of other Snf2 family members, a new structural module was found to be specific to the Fun30 subfamily. Fun30 ATPase-C was shown be monomeric in solution and showed no detectable affinity for dsDNA.
Crystal structure of (E)-9-({[4-(diethylamino)phenyl]imino}methyl)-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-8-ol
Authors: Faizi Md. Serajul Haque , Ahmad Musheer , Kapshuk Anatoly A. , Golenya Irina A.
Published: December 2016

The title compound, C23H29N3O, was synthesized from the condensation reaction of 8-hydroxyjulolidine-9-carbaldehyde andN,N-diethyl-p-phenylenediamine. The hydroxy group forms a intramolecular hydrogen bond to the imine N atom and generates anS(6) ring motif. The conformation about the C=N bond isE, and the aromatic ring of the julolidine moiety is inclined to the benzene ring by 3.74 (14)°. One of the fused non-aromatic rings of the julolidine moiety adopts an envelope conformation and the other has a screw-boat conformation. In the crystal, molecules are linked by C—H...π interactions involving the aromatic julolidine ring, forming slabs parallel to thebcplane. The tricyclic fragment of the julolidine ring and the azomethine C=N bond are disordered over two sets of sites with a refined occupancy ratio of 0.773 (3):0.227 (3).
An empirical model for assessing the effect of ports’ and hinterlands’ characteristics on homeports’ potential
Authors: Niavis Spyros , Vaggelas Georgios
Published: December 2016

Purpose

The significant benefits associated with cruise tourism have mobilized port industry, as progressively, a large number of ports are developing cruise operations. Although increasing cruise traffic is a major goal for cruise ports, homeporting constitutes a strategic target of the majority of ports due to its greater economic benefits for both the port itself and its hinterland. The establishment of homeport traffic in a cruise port is subjected to a variety of port internal and external factors. Taking these into account, the paper aims at defining elements that affect the potential of a cruise port to become a homeport.

Design/methodology/approach

A sample of 47 Mediterranean ports is selected to form the basis for the implementation of an ordinal regression model which links the likelihood of ports to attract homeport traffic with seven explanatory variables which emerged from relevant literature and are split in the main categories of ports’ and hinterlands’ characteristics. To fit the model into the paper’s data, ports are divided into three categories based on their homeport cruise traffic.

Findings

The results of the empirical model signify that both internal and external factors affect the potential of a port to become a cruise homeport. Concerning the internal factors, adequate infrastructure allowing the facilitation of the last generation of cruise ships and the presence of a private enterprise in ports’ operation seems to foster homeport traffic. Additionally, efficiency in operations seems to be a crucial element. On the other hand, the connectivity of port’s; hinterlands, tourist infrastructure and the level of economic growth are proved to be the hinterlands’ elements which increase the likelihood of a port to attract additional homeport traffic.

Practical implications

The model forms a comprehensive evaluation basis for whether a cruise port should intensify its pursuit of homeport traffic, as the estimated coefficients could support port and local authorities to understand their competitive position against other ports and spot their strengths and weaknesses.

Originality/value

The paper contributes in the research dealing with the identification of crucial elements of homeporting from the port’s point of view. Although, it should be mentioned that previous efforts targeting on revealing the characteristics affecting the homeporting potential of ports mostly have been based on questionnaires and expert judgements or empirical models in which the total – and not the homeport traffic – was used as the dependent variable. With the proposed empirical model, home-porting choice analysis is transferred, on the one hand, from the stated preferences level to the revealed preferences level and, on the other hand, from an indirect to a direct approximation of the issue.
Covariate Balancing through Naturally Occurring Strata
Authors: Alemi Farrokh , ElRafey Amr , Avramovic Ivan
Published: December 2016

Objective

To provide an alternative to propensity scoring (PS) for the common situation where there are interacting covariates.

Setting

We used 1.3 million assessments of residents of the United States Veterans Affairs nursing homes, collected from January 1, 2000, through October 9, 2012.

Design

In stratified covariate balancing (SCB), data are divided into naturally occurring strata, where each stratum is an observed combination of the covariates. Within each stratum, cases with, and controls without, the target event are counted; controls are weighted to be as frequent as cases. This weighting procedure guarantees that covariates, or combination of covariates, are balanced, meaning they occur at the same rate among cases and controls. Finally, impact of the target event is calculated in the weighted data. We compare the performance ofSCB, logistic regression (LR), and propensity scoring (PS) in simulated and real data. We examined the calibration ofSCBandPSin predicting 6‐month mortality from inability to eat, controlling for age, gender, and nine other disabilities for 296,051 residents in Veterans Affairs nursing homes. We also performed a simulation study, where outcomes were randomly generated from treatment, 10 covariates, and increasing number of covariate interactions. The accuracy ofSCB,PS, andLRin recovering the simulated treatment effect was reported.

Findings

In simulated environment, as the number of interactions among the covariates increased,SCBand properly specifiedLRremained accurate but pairwiseLRand pairwisePS, the most common applications of these tools, performed poorly. In real data, application ofSCBwas practical.SCBwas better calibrated than linearPS, the most common method ofPS.

Conclusions

In environments where covariates interact,SCBis practical and more accurate than common methods of applyingLRandPS.
REIT Leverage and Return Performance: Keep Your Eye on the Target
Authors: Giacomini Emanuela , Ling David C. , Naranjo Andy
Published: December 2016

This article examines U.S. REIT leverage decisions and their effects on risk and return. We find that the speed at which REITs close the gap between current debt levels and target leverage levels is 17% annually. REITs that are highly levered relative to the average REIT tend to underperform REITs with less debt in their capital structure. However, REITs that are highly levered relative to their target leverage tend to perform better on a risk‐adjusted basis than under‐levered REITs. Taken together, our results show that REIT leverage has significant return performance effects conditional on deviations from target leverage.
Prospective and Explicit Clinical Validation of the Ottawa Heart Failure Risk Scale, With and Without Use of Quantitative NT‐proBNP
Authors: Stiell Ian G. , Perry Jeffrey J. , Clement Catherine M. , Brison Robert J. , Rowe Brian H. , Aaron Shawn D. , McRae Andrew D. , Borgundvaag Bjug , Calder Lisa A. , Forster Alan J. , Wells George A.
Published: December 2016

Objectives

We previously developed the Ottawa Heart Failure Risk Scale (OHFRS) to assist with disposition decisions for acute heart failure patients in the emergency department (ED). We sought to prospectively evaluate the accuracy, acceptability, and potential impact of OHFRS.

Methods

This prospective observational cohort study was conducted at six tertiary hospital EDs. Patients with acute heart failure were evaluated by ED physicians for the 10 OHFRS criteria and then followed for 30 days. Quantitative NT‐proBNP was measured where feasible. Serious adverse event (SAE) was defined as death within 30 days, admission to monitored unit, intubation, noninvasive ventilation, myocardial infarction, or relapse resulting in hospital admission within 14 days.

Results

We enrolled 1,100 patients with mean (±SD) age 77.7 (±10.7) years. SAEs occurred in 170 (15.5%) cases (19.4% if admitted and 10.2% if discharged). Compared to actual practice, using an admission threshold of OHFRS score > 1 would have increased sensitivity (71.8% vs. 91.8%) but increased admissions (57.2% vs. 77.6%). For 684 cases with NT‐proBNP values, using a threshold score > 1 would have significantly increased sensitivity (69.8% vs. 95.8%) while increasing admissions (60.8% vs. 88.0%). In only 11.9% of cases did physicians indicate discomfort with use of OHFRS.

Conclusion

Prospective clinical validation found the OHFRS tool to be highly sensitive for SAEs in acute heart failure patients, albeit with an increase in admission rates. When available, NT‐proBNP values further improve sensitivity. With adequate physician training, OHFRS should help improve and standardize admission practices, diminishing both unnecessary admissions for low‐risk patients and unsafe discharge decisions for high‐risk patients.
Ethics of Mitochondrial Replacement Techniques: A Habermasian Perspective
Authors: Palacios‐González César
Published: December 2016

Jürgen Habermas is regarded as a central bioconservative commentator in the debate on the ethics of human prenatal genetic manipulations. While his main work on this topic, The Future of Human Nature, has been widely examined in regard to his position on prenatal genetic enhancement, his arguments regarding prenatal genetic therapeutic interventions have for the most part been overlooked. In this work I do two things. First, I present the three necessary conditions that Habermas establishes for a prenatal genetic manipulation to be regarded as morally permissible. Second, I examine if mitochondrial replacement techniques meet these necessary conditions. I investigate, specifically, the moral permissibility of employing pronuclear transfer and maternal spindle transfer. I conclude that, according to a Habermasian perspective on prenatal genetic manipulation, maternal spindle transfer (without using a preselected sperm and egg) and pronuclear transfer are morally impermissible. Maternal spindle transfer is, in principle, morally permissible, but only when we have beforehand preselected a sperm and an egg for our reproductive purpose. These findings are relevant for bioconservatives, both for those who hold a Habermasian stance and for those who hold something akin to a Habermasian stance, because they answer the question: what should bioconservatives do regarding mitochondrial replacement techniques? In fact, the answer to this question does not only normatively prescribe what bioconservatives should do in terms of their personal morality, but it also points towards what kind of legislation regulating mitochondrial replacement techniques they should aim at.
Do Mitochondrial Replacement Techniques Affect Qualitative or Numerical Identity?
Authors: Liao S. Matthew
Published: December 2016

Mitochondrial replacement techniques (MRTs), known in the popular media as 'three‐parent' or 'three‐person' IVFs, have the potential to enable women with mitochondrial diseases to have children who are genetically related to them but without such diseases. In the debate regarding whether MRTs should be made available, an issue that has garnered considerable attention is whether MRTs affect the characteristics of an existing individual or whether they result in the creation of a new individual, given that MRTs involve the genetic manipulation of the germline. In other words, do MRTs affect the qualitative identity or the numerical identity of the resulting child? For instance, a group of panelists on behalf of the UK Human Fertilisation and Embryology Authority (HFEA) has claimed that MRTs affect only the qualitative identity of the resulting child, while the Working Group of the Nuffield Council on Bioethics (NCOB) has argued that MRTs would create a numerically distinct individual. In this article, I shall argue that MRTs do create a new and numerically distinct individual. Since my explanation is different from the NCOB's explanation, I shall also offer reasons why my explanation is preferable to the NCOB's explanation.
Is Mitochondrial Donation Germ‐Line Gene Therapy? Classifications and Ethical Implications
Authors: Newson Ainsley J. , Wrigley Anthony
Published: December 2016

The classification of techniques used in mitochondrial donation, including their role as purported germ‐line gene therapies, is far from clear. These techniques exhibit characteristics typical of a variety of classifications that have been used in both scientific and bioethics scholarship. This raises two connected questions, which we address in this paper: (i) how should we classify mitochondrial donation techniques?; and (ii) what ethical implications surround such a classification? First, we outline how methods of genetic intervention, such as germ‐line gene therapy, are typically defined or classified. We then consider whether techniques of mitochondrial donation fit into these, whether they might do so with some refinement of these categories, or whether they require some other approach to classification. To answer the second question, we discuss the relationship between classification and several key ethical issues arising from mitochondrial donation. We conclude that the properties characteristic of mitochondrial inheritance mean that most mitochondrial donation techniques belong to a new sub‐class of genetic modification, which we call ‘conditionally inheritable genomic modification’ (CIGM).
Social support available for substance‐dependent mothers from families with parental substance abuse
Authors: Wiig Eli Marie , Halsa Astrid , Haugland Bente Storm Mowatt
Published: December 2016

Substance‐dependent mothers, who have grown up with parental substance abuse, struggle during and after treatment to abstain from substances while trying to process traumatic experiences and integrate their family into society. The aim of this study was to explore the social support available for these mothers to help them stay abstinent and create safe family environments for themselves and their children. Using purposeful sampling, we approached nine mothers admitted for 1 year to a family ward at a substance abuse clinic and their significant others. Through in‐depth, qualitative interviews, first with the mothers, later with their significant others, we investigated characteristics of the available social support. The findings indicated that the significant others had limited resources and were themselves exposed to adverse and cumulative psychosocial and socioeconomic risk factors. Their relationships with the mothers were, nevertheless, close, consistent and reliable. Supporting the existing social network should be an integrated part of the work of family welfare services aiming to help substance‐dependent mothers from families with parental substance abuse to rehabilitate and to integrate successfully into local communities.
Association between corpus callosum development on magnetic resonance imaging and diffusion tensor imaging, and neurodevelopmental outcome in neonates born very preterm
Authors: Malavolti Anna M , Chau Vann , Brown‐Lum Meisan , Poskitt Kenneth J , Brant Rollin , Synnes Anne , Grunau Ruth E , Miller Steven P
Published: December 2016

Aim

To characterize corpus callosum development in neonates born very preterm from early in life to term‐equivalent age and its relationship with neurodevelopmental outcome at 18 months corrected age.

Method

In a prospective cohort of 193 neonates born preterm, 24 to 32 weeks' gestation, we used magnetic resonance imaging and diffusion tensor imaging acquired early in life (n=193) and at term‐equivalent age (n=159) to measure corpus callosum development: mid‐sagittal area (including corpus callosum subdivisions) and length, and fractional anisotropy from the genu and splenium. We examined the association of (1) intraventricular haemorrhage (IVH) and white matter injury (WMI) severity, and (2) neurodevelopmental outcome at 18 months corrected age with corpus callosum development.

Results

Severe WMI and severe IVH were strongly associated with reduced corpus callosum area (both p<0.001) and WMI with lower fractional anisotropy (p=0.002). Mild WMI predicted smaller corpus callosum area only posteriorly; mild IVH predicted smaller area throughout. Adverse motor outcome was associated with smaller corpus callosum size in the posterior subdivision (p=0.003). Abnormal cognitive outcomes were associated with lower corpus callosum fractional anisotropy (p=0.008).

Interpretation

In newborn infants born very preterm, brain injury is associated with changes in simple metrics of corpus callosum development. In this population, the development of the corpus callosum, as reflected by size and microstructure, is associated with neurodevelopmental outcomes at 18 months corrected age.
Basolateral amygdala supports the maintenance of value and effortful choice of a preferred option
Authors: Hart Evan E. , Izquierdo Alicia
Published: December 2016

The basolateral amygdala (BLA) is known to be involved in appetitive behavior, yet its role in cost‐benefit choice of qualitatively different rewards (more/less preferred), beyond magnitude differences (larger/smaller), is poorly understood. We assessed the effects of BLA inactivations on effortful choice behavior. Rats were implanted with cannulae in BLA and trained to stable lever pressing for sucrose pellets on a progressive ratio schedule. Rats were then introduced to a choice: chow was concurrently available while they could work for the preferred sucrose pellets. Rats were infused with either vehicle control (aCSF) or baclofen/muscimol prior to test. BLA inactivations produced a significant decrease in lever presses for sucrose pellets compared to vehicle, and chow consumption was unaffected. Inactivation had no effect on sucrose pellet preference when both options were freely available. Critically, when lab chow was not concurrently available, BLA inactivations had no effect on the number of lever presses for sucrose pellets, indicating that primary motivation in the absence of choice remains intact with BLA offline. After a test under specific satiety for sucrose pellets, BLA inactivation rendered animals less sensitive to devaluation relative to control. The effects of BLA inactivations in our task are not mediated by decreased appetite, an inability to perform the task, a change in food preference, or decrements in primary motivation. Taken together, BLA supports the specific value and effortful choice of a preferred option.
Irradiation withUV‐C inhibitsTNF‐α‐dependent activation of theNF‐κB pathway in a mechanism potentially mediated by reactive oxygen species
Authors: Szoltysek Katarzyna , Walaszczyk Anna , Janus Patryk , Kimmel Marek , Widlak Piotr
Published: December 2016

Pathways depending on theNF‐κB transcription factor are essential components of cellular response to stress. Plethora of stimuli modulatingNF‐κB includes inflammatory signals, ultraviolet radiation (UV) and reactive oxygen species (ROS), yet interference between different factors affectingNF‐κB remains relatively understudied. Here, we aim to characterize the influence ofUVradiation onTNF‐α‐induced activity of theNF‐κB pathway. We document inhibition ofTNF‐α‐induced activation ofNF‐κB and subsequent suppression ofNF‐κB‐regulated genes in cells exposed toUV‐C several hours beforeTNF‐α stimulation. Accumulation ofROSand subsequent activation ofNRF2, p53,AP‐1 andNF‐κB‐dependent pathways, with downstream activation of antioxidant mechanisms (e.g.,SOD2 andHMOX1 expression), is observed in theUV‐treated cells. Moreover,NF‐κB inhibition is not observed if generation ofUV‐inducedROSis suppressed by chemical antioxidants. It is noteworthy that stimulation withTNF‐α also generates a wave ofROS, which is suppressed in cells pre‐treated byUV. We postulate that irradiation withUV‐C activates antioxidant mechanisms, which in turn affectROS‐mediated activation ofNF‐κB byTNF‐α. Considering a potential cross talk between p53 andNF‐κB, we additionally compare observed effects in p53‐proficient and p53‐deficient cells and find theUV‐mediated suppression ofTNF‐α‐activatedNF‐κB in both types of cells.
Interventional therapies and in‐hospital outcomes in acute coronary syndromes complicated by von Willebrand disease
Authors: Fogarty P. F. , Blair A. , Vega R. , Matthai W. H. , Gimotty P. A.
Published: December 2016

Introduction

von Willebrand disease (VWD) is one of the most common inherited bleeding disorders.

Aim

Investigate the impact of the VWD bleeding tendency on in‐hospital management of acute coronary syndromes (ACS).

Methods

Using discharge data from the National Inpatient Sample (NIS), the features of presentation and in‐hospital treatment among ACS hospital discharges with and without a VWD diagnosis were investigated. A total of 264 case discharges and 705 860 control discharges were identified.

Results and Conclusions

There was a significantly higher percentage of women among the case discharges compared to the control discharges (59.5% and 39.4%, respectively; P < 0.001). The rate of medical therapy alone [i.e. avoidance of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] was significantly higher among unstable angina cases than controls (55.0% vs. 46.4%; P = 0.01), and among cases undergoing PCI, bare‐metal stents (BMS) were utilized in preference to drug‐eluting stents (DES) (adjusted OR = 3.5); P < 0.001). No difference in in‐hospital death was identified, but reported bleeding among discharges that underwent CABG was higher in cases compared to controls (12.9% vs. 5.2%; P = 0.047). Although medical and interventional management of ACS appears to be well tolerated in the majority of hospitalized patients with VWD, the gender ratio is reversed, interventions and DES are utilized less frequently and procedure‐related bleeding may be increased, calling for further study.
Cognitive therapy as an early treatment for post‐traumatic stress disorder in children and adolescents: a randomized controlled trial addressing preliminary efficacy and mechanisms of action
Authors: Meiser‐Stedman Richard , Smith Patrick , McKinnon Anna , Dixon Clare , Trickey David , Ehlers Anke , Clark David M. , Boyle Adrian , Watson Peter , Goodyer Ian , Dalgleish Tim
Published: December 2016

Background

Few efficacious early treatments for post‐traumatic stress disorder (PTSD) in children and adolescents exist. Previous trials have intervened within the first month post‐trauma and focused on secondary prevention of later post‐traumatic stress; however, considerable natural recovery may still occur up to 6‐months post‐trauma. No trials have addressed the early treatment of established PTSD (i.e. 2‐ to 6‐months post‐trauma).

Methods

Twenty‐nine youth (8–17 years) with PTSD (according to age‐appropriate DSM‐IV or ICD‐10 diagnostic criteria) after a single‐event trauma in the previous 2–6 months were randomly allocated to Cognitive Therapy for PTSD (CT‐PTSD; n = 14) or waiting list (WL; n = 15) for 10 weeks.

Results

Significantly more participants were free of PTSD after CT‐PTSD (71%) than WL (27%) at posttreatment (intent‐to‐treat, 95% CI for difference .04–.71). CT‐PTSD yielded greater improvement on child‐report questionnaire measures of PTSD, depression and anxiety; clinician‐rated functioning; and parent‐reported outcomes. Recovery after CT‐PTSD was maintained at 6‐ and 12‐month posttreatment. Beneficial effects of CT‐PTSD were mediated through changes in appraisals and safety‐seeking behaviours, as predicted by cognitive models of PTSD. CT‐PTSD was considered acceptable on the basis of low dropout and high treatment credibility and therapist alliance ratings.

Conclusions

This trial provides preliminary support for the efficacy and acceptability of CT‐PTSD as an early treatment for PTSD in youth. Moreover, the trial did not support the extension of ‘watchful waiting’ into the 2‐ to 6‐month post‐trauma window, as significant improvements in the WL arm (particularly in terms of functioning and depression) were not observed. Replication in larger samples is needed, but attention to recruitment issues will be required.
Why patients self‐refer to the Emergency Department: A qualitative interview study
Authors: Kraaijvanger Nicole , Rijpsma Douwe , Willink Lisa , Lucassen Peter , van Leeuwen Henk , Edwards Michael
Published: December 2016

Rationale, aims, and objectives

There have been multiple studies investigating reasons for patients to self‐refer to the Emergency Department (ED). The majority made use of questionnaires and excluded patients with urgent conditions. The goal of this qualitative study is to explore what motives patients have to self‐refer to an ED, also including patients in urgent triage categories.

Methods

In a large teaching hospital in the Netherlands, a qualitative interview study focusing on reasons for self‐referring to the ED was performed. Self‐referred patients were included until no new reasons for attending the ED were found. Exclusion criteria were as follows: not mentally able to be interviewed or not speaking Dutch. Patients who were in need of urgent care were treated first, before being asked to participate. Interviews followed a predefined topic guide. Practicing cyclic analysis, the interview topic guide was modified during the inclusion period. Interviews were recorded on an audio recorder, transcribed verbatim, and anonymized. Two investigators independently coded the information and combined the codes into meaningful clusters. Subsequently, these were categorized into themes to build a framework of reasons for self‐referral to the ED. Characteristic quotes were used to illustrate the acquired theoretical framework.

Results

Thirty self‐referred patients were interviewed. Most of the participants were male (63%), with a mean age of 46 years. Two main themes emerged from the interviews that are pertinent to the patients' decisions to attend the ED: (1) health concerns and (2) practical issues.

Conclusions

This study found that there are 2 clearly distinctive reasons for self‐referral to the ED: health concerns or practical motives. Self‐referral because of practical motives is probably most suitable for strategies that aim to reduce inappropriate ED visits.
Effects of diet and insulin on dopamine transporter activity and expression in rat caudate‐putamen, nucleus accumbens, and midbrain
Authors: Jones Kymry T. , Woods Catherine , Zhen Juan , Antonio Tamara , Carr Kenneth D. , Reith Maarten E. A.
Published: December 2016

Food restriction (FR) and obesogenic (OB) diets are known to alter brain dopamine transmission and exert opposite modulatory effects on behavioral responsiveness to psychostimulant drugs of abuse. Mechanisms underlying these diet effects are not fully understood. In this study, we examined diet effects on expression and function of the dopamine transporter (DAT) in caudate‐putamen (CPu), nucleus accumbens (NAc), and midbrain regions. Dopamine (DA) uptake by CPu, NAc or midbrain synapto(neuro)somes was measured in vitro with rotating disk electrode voltammetry or with [3H]DA uptake and was found to correlate with DAT surface expression, assessed by maximal [3H](–)‐2‐β‐carbomethoxy‐3‐β‐(4‐fluorophenyl)tropane binding and surface biotinylation assays. FR and OB diets were both found to decrease DAT activity in CPu with a corresponding decrease in surface expression but had no effects in the NAc and midbrain. Diet treatments also affected sensitivity to insulin‐induced enhancement of DA uptake, with FR producing an increase in CPu and NAc, likely mediated by an observed increase in insulin receptor expression, and OB producing a decrease in NAc. The increased expression of insulin receptor in NAc of FR rats was accompanied by increased DA D2 receptor expression, and the decreased DAT expression and function in CPu of OB rats was accompanied by decreased DA D2 receptor expression. These results are discussed as partial mechanistic underpinnings of diet‐induced adaptations that contribute to altered behavioral sensitivity to psychostimulants that target the DAT.

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