bluuebunny/crossref_metadata_2025_split huggingface dataset:
Withdrawal of valproic acid treatment during pregnancy and seizure outcome: Observations from EURAP
Authors: Tomson Torbjörn , Battino Dina , Bonizzoni Erminio , Craig John , Lindhout Dick , Perucca Emilio , Sabers Anne , Thomas Sanjeev V , Vajda Frank ,   the EURAP Study Group
Published: June 2016

SummaryBased on data from the EURAP observational International registry of antiepileptic drugs (AEDs) and pregnancy, we assessed changes in seizure control and subsequent AED changes in women who underwent attempts to withdraw valproic acid (VPA) during the first trimester of pregnancy. Applying Bayesian statistics, we compared seizure control in pregnancies where VPA was withdrawn (withdrawal group, n = 93), switched to another AED (switch group, n = 38), or maintained (maintained‐therapy group, n = 1,588) during the first trimester. The probability of primarily or secondarily generalized tonic–clonic seizures (GTCS) was lower in the maintained‐therapy group compared with the other two groups, both in the first trimester and for the entire duration of pregnancy. GTCS were twice as common during pregnancy in the withdrawal (33%) and switch groups (29%) compared with the maintained‐treatment group (16%). Limitations in the data and study design do not allow to establish a cause–effect relationship between treatment changes and seizure outcome, but these observations provide a signal that withdrawal of, or switch from, VPA during the first trimester could lead to loss of seizure control, and highlight the need for a specifically designed prospective observational study.
Risk Control: Who Cares?
Authors: Taylor Nick 
Published: June 2016

AbstractThe performance of recently introduced risk‐control indices is evaluated and tested with respect to a set of competing indices. Applying a method of moments methodology to these data reveals that the performance of strategies that track risk‐control indices have economic and statistical significance to investors with realistic risk aversion parameter values. However, this performance varies over time and appears to be determined by macroeconomic and liquidity conditions.
The added values of multiplex reverse transcriptase‐PCR followed by mutation screening in the initial evaluation of acute leukemia
Authors: Kim B. , Cho Y.‐U. , Bae M.‐H. , Jang S. , Seo E.‐J. , Chi H.‐S. , Park C.‐J. 
Published: June 2016

SummaryIntroductionThis study investigates the benefits of using multiplex reverse transcriptase‐PCR (RT‐PCR) in addition to standard karyotyping during the initial evaluation of acute leukemia.MethodsA total of 1114 consecutive specimens from patients with acute leukemia were tested using a commercial multiplex RT‐PCR kit (HemaVision, DNA Diagnostic). NPM1 and CEBPA mutations were selectively tested in acute myeloid leukemia (AML) patients with multiplex RT‐PCR negativity.ResultsIn specimens with optimal cytogenetics, the frequency of recurrent translocations was 31.3%, and cryptic translocations were detected in 2.1% of samples. The concordance rate between karyotyping and multiplex RT‐PCR was 97.5%. In addition to the established functions, we demonstrated the additional benefits of multiplex RT‐PCR, including successful molecular characterization, even in cytogenetically suboptimal specimens (5.7%); detection of submicroscopic aberrations (1.0%); detection of rare but potentially significant translocations or variants (2.5%); selection of AML candidates for mutation analysis (68.3%); and finally exclusion of recurrent translocations in patients with acute lymphoblastic leukemia or mixed phenotype acute leukemia (22.5%).ConclusionWe reconfirmed the accuracy and reliability of multiplex RT‐PCR for diagnosing acute leukemia and demonstrated additional advantages of this system for the initial evaluation of acute leukemia. Thus, multiplex RT‐PCR is worth considering in diagnostic testing of acute leukemias.
The value of eosinophil VCS parameters in predicting hepatotoxicity of antituberculosis drugs
Authors: Shen T. , Gu D. , Zhu Y. , Shi J. , Xu D. , Cao X. 
Published: June 2016

SummaryIntroductionDrug‐induced liver injury (DILI) is the most frequent cause of discontinuation of antituberculosis medication and difficult to predict. In recent years, liver eosinophilia has been associated with incidence of DILI. We hypothesize that morphologic changes in reactive eosinophils associated with DILI may be determined by LH750 (Beckman Coulter, Fullerton, CA) with VCS technology.MethodsThe absolute eosinophil (AEC), percentage of eosinophil (EOSI%), VCS parameters, and standard deviation (SD) of 500 health controls, 376 patients without DILI, and 50 DILI patients were compared in terms of diagnostic sensitivity and specificity for DILI.ResultsIn DILI patients, the increased mean eosinophil volume (MEV) and size variability (MEV‐SD) were observed prior to alanine aminotransferase (ALT) elevations. The MEV was correlated well with ALT after therapy. The ROC curve analyses revealed that the MEV and MEV‐SD had larger areas under curves (0.894, 0.815, in the week prior to DILI) compared to other parameters. Using a cutoff of 163.15 fL for the MEV and a cutoff of 17.11 for MEV‐SD, the sensitivities of 81% and 72% and specificities of 82% and 80% were achieved, respectively, which are higher than other parameters prior to DILI occurred.ConclusionsThe MEV with size variability (MEV‐SD) is a quantitative, objective, and more sensitive parameter and has a potential to be an additional indicator for DILI.
Intracellular recycling and cross‐presentation by MHC class I molecules
Authors: van Endert Peter 
Published: June 2016

SummaryCross‐presentation of internalized antigens by dendritic cells requires efficient delivery of Major Histocompatibility Complex (MHC) class I molecules to peptide‐loading compartments. Strong evidence suggests that such loading can occur outside of the endoplasmic reticulum; however, the trafficking pathways and sources of class I molecules involved are poorly understood. Examination of non‐professional, non‐phagocytic cells has revealed a clathrin‐independent, Arf6‐dependent recycling pathway likely traveled by internalized optimally loaded (closed) class I molecules. Some closed and all open MHC class I molecules travel to late endosomes to be degraded but might also partly be re‐loaded with peptides and recycled. Studies of viral interference revealed pathways in which class I molecules are directed to degradation in lysosomes upon ubiquitination at the surface, or upon AP‐1 and HIV‐nef‐dependent misrouting from the Golgi network to lysosomes. While many observations made in non‐professional cells remain to be re‐examined in dendritic cells, available evidence suggests that both recycling and neo‐synthesized class I molecules can be loaded with cross‐presented peptides. Recycling molecules can be recruited to phagosomes triggered by innate signals such as TLR4 ligands, and may therefore specialize in loading with phagocytosed antigens. In contrast, AP‐1‐dependent accumulation at, or trafficking through, a Golgi compartment of newly synthesized molecules appears to be important for cross‐presentation of soluble proteins and possibly of long peptides that are processed in the so‐called vacuolar pathway. However, significant cell biological work will be required to confirm this or any other model and to integrate knowledge on MHC class I biochemistry and trafficking in models of CD8+ T‐cell priming by dendritic cells.
Regulation of protein synthesis and autophagy in activated dendritic cells: implications for antigen processing and presentation
Authors: Argüello Rafael J. , Reverendo Marisa , Gatti Evelina , Pierre Philippe 
Published: June 2016

SummaryAntigenic peptides presented in the context of major histocompatibility complex (MHC) molecules originate from the degradation of both self and non‐self proteins. T cells can therefore recognize at the surface of surveyed cells, the self‐peptidome produced by the cell itself (mostly inducing tolerance) or immunogenic peptides derived from exogenous origins. The initiation of adaptive immune responses by dendritic cells (DCs), through the antigenic priming of naïve T cells, is associated to microbial pattern recognition receptors engagement. Activation of DCs by microbial product or inflammatory cytokines initiates multiple processes that maximize DC capacity to present exogenous antigens and stimulate T cells by affecting major metabolic and membrane traffic pathways. These include the modulation of protein synthesis, the regulation of MHC and co‐stimulatory molecules transport, as well as the regulation of autophagy, that, all together promote exogenous antigen presentation while limiting the display of self‐antigens by MHC molecules.
Dynamics of the membrane–cytoskeleton interface in MHC class II‐restricted antigen presentation
Authors: Bretou Marine , Kumari Anita , Malbec Odile , Moreau Hélène D. , Obino Dorian , Pierobon Paolo , Randrian Violaine , Sáez Pablo J. , Lennon‐Duménil Ana‐Maria 
Published: June 2016

SummaryAntigen presentation refers to the ability of cells to show MHC‐associated determinants to T lymphocytes, leading to their activation. MHC class II molecules mainly present peptide‐derived antigens that are internalized by endocytosis in antigen‐presenting cells (APCs). Here, we describe how the interface between cellular membranes and the cytoskeleton regulates the various steps that lead to the presentation of exogenous antigens on MHC class II molecules in the two main types of APCs: dendritic cells (DCs) and B lymphocytes. This includes antigen uptake, processing, APC migration, and APC–T cell interactions. We further discuss how the interaction between APC‐specific molecules and cytoskeleton elements allows the coordination of antigen presentation and cell migration in time and space.
The role of islet antigen presenting cells and the presentation of insulin in the initiation of autoimmune diabetes in the NOD mouse
Authors: Unanue Emil R. , Ferris Stephen T. , Carrero Javier A. 
Published: June 2016

SummaryWe have been examining antigen presentation and the antigen presenting cells (APCs) in the islets of Langerhans of the non‐obese diabetic (NOD) mouse. The purpose is to identify the earliest events that initiate autoimmunity in this confined tissue. Islets normally have a population of macrophages that is distinct from those that inhabit the exocrine pancreas. Also found in NOD islets is a minor population of dendritic cells (DCs) that bear the CD103 integrin. We find close interactions between beta cells and the two APCs that result in the initiation of the autoimmunity. Even under non‐inflammatory conditions, beta cells transfer insulin‐containing vesicles to the APCs of the islet. This reaction requires live cells and intimate contact. The autoimmune process starts in islets with the entrance of CD4+ T cells and an increase in the CD103+ DCs. Mice deficient in the Batf3 transcription factor never develop diabetes due to the absence of the CD103/CD8α lineage of DCs. We hypothesize that the 12–20 peptide of the beta chain of insulin is responsible for activation of the initial CD4+ T‐cell response during diabetogenesis.
The quest of pain education leaders in Canada and the United States: a qualitative study
Authors: Carr Eloise C.J. , Watt‐Watson Judy , McGillion Michael , Huizinga Anne 
Published: June 2016

AbstractAimsTo determine key factors that stimulate and drive the ongoing interests of leaders in the field of pain to continue to work for change and to explore how they use their own experiences in their teaching.BackgroundThe assessment and management of acute and chronic pain remains a challenge and the pain education of pre‐licensure/undergraduate health professionals (e.g. nurses, physicians, etc.) continues to be suboptimal. Understanding the motivations of pain leaders may provide insights to facilitate the future development of pain clinicians.DesignA Narrative enquiry.MethodsA purposeful sample of 17 Canadian and USA leaders in pain education participated. Data were collected between September 2012–January 2013 using recorded semi‐structured telephone interviews. Transcripts were coded to provide storied experiences (themes).FindingsSix themes were identified as a stimulus for pain leaders: An early pain experience, mentorship and circumstances, a personal shift in understanding, catalysts (institutional or political), recognition of barriers and a determination to improve. Their work towards change appeared to be motivated by their pain ‘quest’ where leaders embraced their personal experiences of pain, a need for social action and individual change.ConclusionsEducational approaches for health professionals usually focus on the importance of knowledge, skills and attitudes to be competent in pain care. To inspire and educate young health professionals about pain management we suggest the development of future pain leaders may require a different approach that recognizes personal stories of pain, includes a local pain champion and incorporates a model of mentorship.
Commentary: Supporting preterm children's parents matters – a reflection on Treyvaud et al. (2016)
Authors: Jaekel Julia 
Published: June 2016

Children born preterm or with low birth weight (LBW) grow up with an increased risk for a range of neurodevelopmental, cognitive, socioemotional, and academic problems. While long‐term effects of preterm and LBW birth have traditionally been studied from a deficit perspective, Treyvaud et al. correctly state that the increased risk for impairments in this population urgently requires identification of protective factors. Their new findings add to empirical evidence from observational studies showing that sensitive parenting can protect preterm children from negative developmental outcomes. In order to identify strategies that support preterm children's life chances, well‐designed longitudinal studies, such as the one by Treyvaud et al., are indispensable. Next, we will need large randomized trials to test the causality between intervention‐induced parenting changes and preterm children's long‐term outcomes. We need interdisciplinary and international collaboration to study preterm parent–child dyads within multimethod frameworks and uncover the highly complex mechanisms that shape individual developmental trajectories.
The pay‐offs of maternal care increase as offspring develop, favouring extended provisioning in an egg‐feeding frog
Authors: Dugas M. B. , Moore M. P. , Martin R. A. , Richards‐Zawacki C. L. , Sprehn C. G. 
Published: June 2016

AbstractOffspring quantity and quality are components of parental fitness that cannot be maximized simultaneously. When the benefits of investing in offspring quality decline, parents are expected to shift investment towards offspring quantity (other reproductive opportunities). Even when mothers retain complete control of resource allocation, offspring control whether to allocate investment to growth or development towards independence, and this shared control may generate parent–offspring conflict over the duration of care. We examined these predictions by, in a captive colony, experimentally removing tadpoles of the strawberry poison frog (Oophaga pumilio) from the mothers that provision them with trophic eggs throughout development. Tadpoles removed from their mothers were no less likely to survive to nutritional independence (i.e. through metamorphosis) than were those that remained with their mothers, but these offspring were smaller at metamorphosis and were less likely to survive to reach adult size, even though they were fedad libitum. Tadpoles that remained with their mothers developed more slowly than those not receiving care, a pattern that might suggest that offspring extracted more care than was in mothers’ best interests. However, the fitness returns of providing care increased with offspring development, suggesting that mothers would be best off continuing care until tadpoles initiated metamorphosis. Although the benefits of parental investment in offspring quality are often thought to asymptote at high levels, driving parent–offspring conflict over weaning, this assumption may not hold over natural ranges of investment, with selection on both parents and offspring favouring extended durations of parental care.
Sibship effects on dispersal behaviour in a pre‐industrial human population
Authors: Nitsch A. , Lummaa V. , Faurie C. 
Published: June 2016

AbstractUnderstanding dispersal behaviour and its determinants is critical for studies on life‐history maximizing strategies. Although many studies have investigated the causes of dispersal, few have focused on the importance of sibship, despite that sibling interactions are predicted to lead to intrafamilial differences in dispersal patterns. Using a large demographic data set from pre‐industrial Finland (n = 9000), we tested whether the sex‐specific probability of dispersal depended on the presence of same‐sex or opposite‐sex elder siblings who can both compete and cooperate in the family. Overall, following our predictions, the presence of same‐sex elder siblings increased the probability of dispersal from natal population for both sexes, whereas the number of opposite‐sex siblings had less influence. Among males, dispersal was strongly linked to access to land resources. Female dispersal was mainly associated with competition over availability of mates but likely mediated by competition over access to wealthy mates rather mate availabilityper se. Besides ecological constraints, sibling interactions are strongly linked with dispersal decisions and need to be better considered in the studies on the evolution of family dynamics and fitness maximizing strategies in humans and other species.
Cognitive and Neural Effects of Vision‐Based Speed‐of‐Processing Training in Older Adults with Amnestic Mild Cognitive Impairment: A Pilot Study
Authors: Lin Feng , Heffner Kathi L. , Ren Ping , Tivarus Madalina E. , Brasch Judith , Chen Ding‐Geng , Mapstone Mark , Porsteinsson Anton P. , Tadin Duje 
Published: June 2016

ObjectivesTo examine the cognitive and neural effects of vision‐based speed‐of‐processing (VSOP) training in older adults with amnestic mild cognitive impairment (aMCI) and contrast those effects with an active control (mental leisure activities (MLA)).DesignRandomized single‐blind controlled pilot trial.SettingAcademic medical center.ParticipantsIndividuals with aMCI (N = 21).InterventionSix‐week computerized VSOP training.MeasurementsMultiple cognitive processing measures, instrumental activities of daily living (IADLs), and two resting state neural networks regulating cognitive processing: central executive network (CEN) and default mode network (DMN).ResultsVSOP training led to significantly greater improvements in trained (processing speed and attention: F1,19 = 6.61, partial η2 = 0.26, P = .02) and untrained (working memory: F1,19 = 7.33, partial η2 = 0.28, P = .01; IADLs: F1,19 = 5.16, partial η2 = 0.21, P = .03) cognitive domains than MLA and protective maintenance in DMN (F1, 9 = 14.63, partial η2 = 0.62, P = .004). VSOP training, but not MLA, resulted in a significant improvement in CEN connectivity (Z = −2.37, P = .02).ConclusionTarget and transfer effects of VSOP training were identified, and links between VSOP training and two neural networks associated with aMCI were found. These findings highlight the potential of VSOP training to slow cognitive decline in individuals with aMCI. Further delineation of mechanisms underlying VSOP‐induced plasticity is necessary to understand in which populations and under what conditions such training may be most effective.
Interventions to Address Potentially Inappropriate Prescribing in Community‐Dwelling Older Adults: A Systematic Review of Randomized Controlled Trials
Authors: Clyne Barbara , Fitzgerald Ciaran , Quinlan Aisling , Hardy Colin , Galvin Rose , Fahey Tom , Smith Susan M. 
Published: June 2016

ObjectivesTo perform a systematic review to determine the effectiveness of interventions designed to reduce potentially inappropriate prescribing (PIP) in community‐dwelling older adults.DesignSystematic review and narrative synthesis.SettingPrimary and community care.ParticipantsCommunity‐dwelling older adults.MeasurementsThe primary outcome was change in PIP measured using implicit or explicit tools. Studies were grouped into organizational, professional, financial, regulatory, and multifaceted interventions.ResultsTwelve randomized controlled trials were identified with baseline PIP prevalence of 18% to 100%. Four of six organizational interventions reported a reduction in PIP, particularly through pharmacists conducting medication reviews. Evidence of the effectiveness of multidisciplinary teams was weak. Both of the two professional (targeting prescriber's directly) interventions were computerized clinical decision support interventions and were effective in decreasing new PIP but not existing PIP. Three of four multifaceted approaches were effective in reducing PIP. The risk of bias was often high, particularly in reporting selection bias.ConclusionInterventions including organizational (pharmacist interventions), professional (computerized clinical decision support systems), and multifaceted approaches appear beneficial in terms of reducing PIP, but the range of effect sizes reported was modest, and it is unclear whether such interventions can result in clinically significant improvements in patient outcomes. Ongoing assessment of interventions to reduce PIP is needed in community‐dwelling older adults, particularly in relation to preventing initiation of PIP.
Relationship Between Perceived Risk of Falling and Adoption of Precautions to Reduce Fall Risk
Authors: Blalock Susan J. , Gildner Paula L. , Jones Jennifer L. , Bowling James M. , Casteel Carri H. 
Published: June 2016

ObjectivesTo better understand the relationship between perceived risk of falling and awareness and adoption of four specific precautions that older adults have taken to reduce this risk.DesignCross‐sectional.SettingData were collected in in‐person interviews conducted in the homes of study participants. Interviews conducted between March 2011 and September 2013 and lasted an average of 60–90 minutes.ParticipantsA stratified sampling strategy designed to enroll an equal number of homebound and nonhomebound participants was used. All participants (N = 164) were recruited from central North Carolina.MeasurementsParticipants were asked about 1‐year fall history, perceived risk of falling, restriction of activities because of fear of falling, awareness of four recommended fall prevention behaviors (exercise, annual medication review, bathroom grab bars, safe footwear), and current practice of these behaviors.ResultsIn bivariate analyses, individuals who were aware of two behaviors recommended to reduce the risk of falling (exercise, use of safe footwear) and had adopted these behaviors perceived their risk of falling as lower than individuals who were aware of the recommended behaviors but had not adopted them. Moreover, in multivariate analyses, individuals who did not know that exercise is recommended to reduce the risk of falling perceived their risk of falling as lower than those who were aware of this recommendation and had adopted it. Individuals were least likely to be aware that medication reviews and exercise are recommended to reduce fall risk.ConclusionAwareness of behaviors recommended to reduce fall risk appears necessary for adoption of these behaviors to reduce perceived risk. Fall‐prevention campaigns should emphasize behaviors where awareness is low.