bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apremilast Alters Behavioral Responses to Ethanol in Mice: I. Reduced Consumption and Preference
Authors: Blednov Yuri A. , Da Costa Adriana J. , Tarbox Tamara , Ponomareva Olga , Messing Robert O. , Harris R. Adron 
Published: February 2018

BackgroundPhosphodiesterase type 4 (PDE4) inhibitors produce widespread anti‐inflammatory effects and reduce ethanol (EtOH) consumption in several rodent models. These drugs are potential treatments for several diseases, including central nervous system disorders, but clinical use is limited by their emetic activity. Apremilast is a selective PDE4 inhibitor with fewer gastrointestinal side effects that is FDA‐approved for the treatment of psoriasis.MethodsWe measured the acute and chronic effects of apremilast on EtOH consumption in male and female C57BL/6J mice using the continuous and intermittent 24‐hour 2‐bottle choice drinking models. We also studied the effects of apremilast on preference for sucrose or saccharin, spontaneous locomotor activity, and blood EtOH clearance. Finally, apremilast levels in plasma, liver, and brain were measured 1 or 2 hours after injection.ResultsIn the continuous and intermittent drinking tests, apremilast (15 to 50 mg/kg, p.o.) dose dependently reduced EtOH intake and preference in male and female mice. Higher doses of apremilast (30 to 50 mg/kg) also reduced total fluid intake in these mice. Chronic administration of apremilast (20 mg/kg) produced a stable reduction in EtOH consumption in both drinking tests with no effect on total fluid intake. The drinking effects were reversible after drug treatment was replaced with vehicle administration (saline) for 2 to 4 days. Six daily apremilast injections did not alter preference for saccharin or sucrose in male or female mice. Apremilast (20 mg/kg) transiently decreased spontaneous locomotor activity and did not alter blood EtOH clearance. The highest levels of apremilast were found in liver followed by plasma and brain.ConclusionsApremilast produced stable reductions in voluntary EtOH consumption and was rapidly distributed to plasma and tissues (including the brain), suggesting that it may be an improved PDE4 inhibitor for medication development and repurposing efforts to treat alcohol abuse.
Prostaglandin gel versus oxytocin – prelabour rupture of membranes at term – A randomised controlled trial
Authors: Mahomed Kassam , Wild Kellie , Weekes Christopher R. 
Published: February 2018

BackgroundPre‐labour rupture of membranes (PROM) at term is a common event with early induction of labour reducing infectious morbidity without increasing the caesarean rate. Syntocinon is commonly used for induction but prostaglandins are also routinely used. Large studies have shown no difference in the maternal and neonatal outcomes with either method.AimTo assess the safety and efficacy of vaginal prostaglandin (PG) compared to syntocinon for induction of labour in term‐PROM.MethodThis was a single‐centre randomised controlled trial at Ipswich Hospital of women presenting at ≥37 weeks gestation with PROM. Women were randomised and managed in labour as per local guidelines. Analysis was by intention to treat.ResultsOne hundred and eighty‐four women were recruited, 90 in the PG group and 94 in the oxytocin group. Women in both arms were of similar demographics and 53% of women in the PG group did not require any oxytocin. There was a statistically significant lower incidence of fetal heart rate abnormality in the PG group, 4.4% versus 12.8%. There was no difference in epidural use, caesarean section, maternal infection, admission to special care nursery or neonatal sepsis. Time to onset of labour was significantly longer in the PG group, 25.7 h versus 19.7 h but with no difference in the length of first stage. Maternal satisfaction was high in both groups with no significant difference in breastfeeding rates.ConclusionInduction of labour with oxytocin or vaginal prostaglandins are safe and efficacious options for women in the context of PROM at term.
Quality management of nuchal translucency ultrasound measurement in Australia
Authors: Nisbet Debbie , Robertson Ann , Mannil Blessy , Pincham Vanessa , Mclennan Andrew 
Published: February 2018

BackgroundNuchal translucency measurement has an established role in first trimester screening. Accurate measurement requires that technical guidelines are followed. Performance can be monitored by auditing the distribution of measurements obtained in a series of cases.AimsThe primary aim is to develop an accessible, theory‐based educational program for individuals whose distribution of measurements at audit falls outside an acceptable range, and assess operator performance following this intervention.Materials and MethodsOperators whose nuchal translucency measurement distributions fall outside a normal range (38–65% above the median) were expected to undergo a teleconference tutorial. Accessible from anywhere in Australia, the one hour tutorials were run by a senior sonographer (to explain technical ultrasound aspects) and the audit program manager (to explain the audit process).ResultsIn 2011, 83 operators attended the teleconference tutorials. Compared to a random comparison group of operators meeting standard in 2011, teleconference tutorial attendees were significantly more likely to: (i) operate in rural or regional, rather than metropolitan, centres (P = 0.001); (ii) be less experienced (P < 0.0005); and (iii) have lower annual scan numbers (P = 0.0012). Improvement in nuchal translucency measurement quality was seen after one audit cycle and was maintained over subsequent years. The mean percentage of the study cohort reaching standard over the five‐year audit was 77.8% which was not statistically different from the average for the comparison cohort of all other audited operators (79.3%; P = 0.61).ConclusionsTeleconference tutorials are a convenient, accessible and effective way to obtain immediate and sustained improvement in operator performance.
Called to “Ankle Alley”: Tactical Infrastructure, Migrant Injuries, and Emergency Medical Services on the US–Mexico Border
Authors: Jusionyte Ieva 
Published: February 2018

ABSTRACTIn southern Arizona, emergency responders rescue and transport unauthorized migrants who get hurt crossing the border, either when scaling the steel fence in urban areas or taking remote and dangerous routes through the desert. Using data collected during ethnographic research between 2015 and 2017 with firefighters trained as EMTs or paramedics, the article shows how Border Patrol's tactical infrastructure produces specific patterns of traumatic injury that are not only routine but also deliberate, allowing us to trace government's responsibility for what it presents as the unintentional consequence of security buildup on the US–Mexico border. [migration, emergency, infrastructure, border, accident]
Folic Acid Supplementation throughout pregnancy: psychological developmental benefits for children
Authors: Henry Lesley‐Anne , Cassidy Tony , McLaughlin Marian , Pentieva Kristina , McNulty Helene , Walsh Colum P. , Lees‐Murdock Diane 
Published: February 2018

AbstractAimTo test the effect of folic acid supplements taken throughout pregnancy on children's psychosocial development.MethodA randomised controlled trial of folic acid supplementation in pregnancy, with parental rating using the Resiliency Attitudes and Skills Profile (RASP), the Strengths and Difficulties Questionnaire (SDQ) and the Trait Emotional Intelligence Questionnaire Child Short Form (TEIQue‐CSF). Children aged 6–7 whose mothers received folic acid throughout pregnancy (n = 22) were compared to those whose mothers only received it during the first trimester (n = 17).ResultsChildren whose mothers received the full‐term supplement scored significantly higher on emotional intelligence and resilience. Hierarchical multiple regression analysis identified folate level at 36th gestational week as an important predictor of emotional intelligence (EI) and resilience.ConclusionAlthough conclusions must be drawn with caution, this research presents a number of potential implications, the main one being a proposed policy recommendation for women to take folic acid for the duration of pregnancy rather than stopping at the end of the first trimester. The second is the potential for future research to explore the possible psychological and social development benefits and in line with this to try and identify the explanatory mechanism involved.
Systematic review: non A‐E, seronegative or indeterminate hepatitis; what is this deadly disease?
Authors: Brennan P. N. , Donnelly M. C. , Simpson K. J. 
Published: February 2018

SummaryBackgroundA significant proportion of cases of acute liver failure (ALF) do not have an identifiable cause; so called “non A‐E,” “non A, non B, non C,” “seronegative” or “indeterminate” hepatitis. However, this entity is clinically not well described.AimTo collate the known incidence and outcomes in indeterminate hepatitis. This systematic review sought to identify potential aetiologies that ought to be considered, and identify likely future objectives in classification and treatment strategies for indeterminate hepatitis.MethodsLiterature review to determine aetiological factors, prevalence and outcomes relating to indeterminate hepatitis.ResultsThere is significant heterogeneity within the reported cases of indeterminate hepatitis in the literature. Some of the potential infective aetiologies which are reviewed here include: parvovirus B19 (PVB19), herpes simplex virus (HSV), Toga‐Like Virus and the Annelloviridae (including SEN‐V). Interestingly, this condition predominately affects middle aged women, with subacute progression of the liver failure. In addition, the prognosis of indeterminate hepatitis is poor, with reduced spontaneous survival compared with other causes of acute liver failure and increased need for emergency liver transplantation.ConclusionsWhilst various pathological processes have been implicated in the development of indeterminate hepatitis, the specific cause remains elusive. There is an urgent need for general consensus on a specific definition and exclusion of confounding aetiologies with coordinated multicentre investigation of this rare condition to identify aetiology and develop therapies to reduce the significant mortality and need for emergency liver transplantation associated with this condition.
Low risk of hepatotoxicity from rifampicin when used for cholestatic pruritus: a cross‐disease cohort study
Authors: Webb G. J. , Rahman S. R. , Levy C. , Hirschfield G. M. 
Published: February 2018

SummaryBackgroundThe use of rifampicin for cholestatic pruritus is accompanied by concerns over safety, but the availability of real‐world prescribing data is relatively limited.AimWe sought to describe the rate and characteristics of rifampicin‐induced hepatitis in a mixed aetiology cohort of patients with established liver disease and cholestatic pruritus.MethodsRetrospective review of records for out‐patients commenced on rifampicin for pruritus 2012‐2016 inclusive. Rifampicin‐induced hepatitis was recorded where alanine aminotransferase activity (ALT) increased to both ≥5 × baseline and ≥5 × upper limit of normal (ULN), or to both ≥3 × baseline and ≥3 × ULN with concurrent elevation in serum bilirubin to ≥2 × baseline and ≥2 × ULN, in addition to a Roussel‐Uclaf Causality Assessment Method score of “probable” or “highly probable” for rifampicin causality.ResultsAfter exclusions, we reviewed 105 patients who took rifampicin for a median of 131 days. Most had primary biliary cholangitis or primary sclerosing cholangitis; 40 (38.1%) were men and median age was 44 years (IQR: 32‐57). 44 (41.9%) patients had baseline serum bilirubin ≥2 × ULN and 28 (26.7%) ALT ≥3 × ULN. 5 (4.8%) developed rifampicin‐induced hepatitis at a median of 70(range 27‐130) days after drug initiation. No individual or laboratory baseline characteristics were significantly associated with subsequent development of hepatitis. All cases of hepatitis recovered after drug cessation, although one patient was hospitalised and received corticosteroids.ConclusionsGiven the efficacy of rifampicin for an important sub‐group of those with cholestatic pruritus, adult patients, including those with jaundice, can be counselled that 95% of prescriptions are safe, and where hepatitis occurs, including at long latency, drug cessation appears effective.
New insights in Type I and II CD20 antibody mechanisms‐of‐action with a panel of novel CD20 antibodies
Authors: Meyer Saskia , Evers Mitchell , Jansen Johannes H. M. , Buijs Jos , Broek Blanca , Reitsma Stephanie E. , Moerer Petra , Amini Mojtaba , Kretschmer Anna , ten Broeke Toine , den Hartog Marcel T. , Rijke Mark , Klein Christian , Valerius Thomas , Boross Peter , Leusen Jeanette H. W. 
Published: February 2018

SummaryBased on their mechanisms‐of‐action, CD20 monoclonal antibodies (mAbs) are grouped into Type I [complement‐dependent cytotoxicity (CDC) and antibody‐dependent cell‐mediated cytotoxicity (ADCC)] and Type II [programmed cell death (PCD) and ADCC] mAbs. We generated 17 new hybridomas producing CD20 mAbs of different isotypes and determined unique heavy and light chain sequence pairs for 13 of them. We studied their epitope binding, binding kinetics and structural properties and investigated their predictive value for effector functions, i.e. PCD, CDC and ADCC. Peptide mapping and CD20 mutant screens revealed that 10 out of these 11 new mAbs have an overlapping epitope with the prototypic Type I mAb rituximab, albeit that distinct amino acids of the CD20 molecule contributed differently. Binding kinetics did not correlate with the striking differences in CDC activity among the mIgG2c mAbs. Interestingly, chimerization of mAb m1 resulted in a mAb displaying both Type I and II characteristics. PCD induction was lost upon introduction of a mutation in the framework of the heavy chain affecting the elbow angle, supporting that structural changes within this region can affect functional activities of CD20 mAbs. Together, these new CD20 mAbs provide further insights in the properties dictating the functional efficacy of CD20 mAbs.
Hepatitis E virus – key points for the clinical haematologist
Authors: O'Gorman Joanne , Burke Áine , O'Flaherty Niamh 
Published: February 2018

SummaryIn recent years there has been a paradigm shift in our understanding of the epidemiology and clinical features of hepatitis E virus (HEV) infection. Once classically described as an acute hepatitis associated with waterborne outbreaks in areas of poor sanitation, HEV is now recognised to be endemic in Europe and is probably zoonotic in origin. Evidence for transfusion‐transmitted HEV has prompted the introduction of blood donor screening in a number of countries, but the risk to the haematology patient from food sources remains. The aim of this review therefore, is to equip the clinical haematologist with the knowledge required to diagnose HEV infection and to aid decision‐making in patient management. The article also provides information on addressing patient concerns about their risk of acquiring hepatitis E and how this risk can be mitigated.
Time trend analysis of long term outcome of patients with haematological malignancies admitted at dutch intensive care units
Authors: de Vries Vera A. , Müller Marcella C. A. , Sesmu Arbous M. , Biemond Bart J. , Blijlevens Nicole M. A. , Kusadasi Nuray , Choi Goda C. W. , Vlaar Alexander P. J. , van Westerloo David J. , Kluin‐Nelemans Hanneke C. , van den Bergh Walter M. ,   the HEMA‐ICU Study Group
Published: February 2018

SummaryA few decades ago, the chances of survival for patients with a haematological malignancy needing Intensive Care Unit (ICU) support were minimal. As a consequence, ICU admission policy was cautious. We hypothesized that the long‐term outcome of patients with a haematological malignancy admitted to the ICU has improved in recent years. Furthermore, our objective was to evaluate the predictive value of the Acute Physiology and Chronic Health Evaluation (APACHE) II score. A total of 1095 patients from 5 Dutch university hospitals were included from 2003 until 2015. We studied the prevalence of patients' characteristics over time. By using annual odds ratios, we analysed which patients' characteristics could have had influenced possible trends in time. A approximated mortality rate was compared with the ICU mortality rate, to study the predictive value of the APACHE II score. Overall one‐year mortality was 62%. The annual decrease in one‐year mortality was 7%, whereas the APACHE II score increased over time. Decreased mortality rates were particularly observed in high‐risk patients (acute myeloid leukaemia, old age, low platelet count, bleeding as admission reason and need for mechanical ventilation within 24 h of ICU admission). Furthermore, the APACHE II score overestimates mortality in this patient category.
Humoral immune failure defined by immunoglobulin class and immunoglobulin G subclass deficiency is associated with shorter treatment‐free and overall survival in Chronic Lymphocytic Leukaemia
Authors: Crassini Kyle R. , Zhang Eva , Balendran Shalini , Freeman Jane A. , Best O. Giles , Forsyth Cecily J. , Mackinlay Naomi J. , Han Ping , Stevenson William S. , Mulligan Stephen P. 
Published: February 2018

SummaryImmune dysfunction attributed to hypogammaglobulinaemia is common in chronic lymphocytic leukaemia (CLL) and infection is a major contributor to morbidity and mortality. A higher incidence of multiple immunoglobulin and immunoglobulin G (IgG) subclass deficiency was associated with more advanced disease (P < 0·001 and P < 0·001, respectively) in a cohort of 147 CLL patients. Multiple immunoglobulin and IgG subclass deficiency were significantly associated with shorter treatment‐free survival (TFS) (P < 0·001 and P = 0·006, respectively). The association between disease stage and immune dysfunction demonstrated by these data suggest aspects of immune deficiency correlate with disease severity and may be associated with shorter TFS in CLL.
Brentuximab vedotin prior to allogeneic stem cell transplantation in Hodgkin lymphoma: a report from the EBMT Lymphoma Working Party
Authors: Bazarbachi Ali , Boumendil Ariane , Finel Hervé , Mohty Mohamad , Castagna Luca , Peggs Karl S. , Blaise Didier , Afanasyev Boris , Diez‐Martin José L. , Sierra Jorge , Bloor Adrian , Martinez Carmen , Robinson Stephen , Malladi Ram , El‐Cheikh Jean , Corradini Paolo , Montoto Silvia , Dreger Peter , Sureda Anna 
Published: February 2018

SummaryBrentuximab vedotin (BV) is an anti‐CD30 antibody‐drug conjugate. Preliminary data suggest that BV might improve outcomes after allogeneic stem cell transplantation (SCT) for Hodgkin lymphoma (HL) when used as pre‐transplant salvage therapy. Between 2010 and 2014, 428 adult patients underwent an allogeneic SCT for classical HL at participating centres of the European Society for Blood and Marrow Transplantation. We compared the outcomes of 210 patients who received BV prior to allogeneic SCT with that of 218 patients who did not receive BV. The median follow‐up for survivors was 41 months. Patients in the BV group were more heavily pre‐treated (median pre‐allograft treatment lines: 4 vs. 3). The two groups were comparable in terms of disease status, performance status, comorbidities, prior autologous SCT, type of donor, conditioning and in vivo T cell depletion. In multivariate analysis, pre‐allograft BV had no impact on acute graft‐versus‐host disease (GVHD), non‐relapse mortality, cumulative incidence of relapse, progression‐free survival or overall survival (OS), but significantly reduced the risk of chronic GVHD (hazard ratio = 0·64; 95% confidence interval = 0·45–0·92; P < 0·02). Older age, poor performance status, use of pre‐transplant radiotherapy and active disease at SCT adversely affected OS. Patients allografted for HL after prior exposure to BV do not have a superior outcome after allogeneic SCT except for a lower risk of chronic GVHD. However, BV may improve the outlook of allogeneic SCT by helping otherwise refractory patients to achieve a more favourable disease status, facilitating allotransplant success.
Eicosanoids, prostacyclin and cyclooxygenase in the cardiovascular system
Authors: Mitchell Jane A , Kirkby Nicholas S 
Published: February 2018

Eicosanoids represent a diverse family of lipid mediators with fundamental roles in physiology and disease. Within the eicosanoid superfamily are prostanoids, which are specifically derived from arachidonic acid by the enzyme cyclooxygenase (COX). COX has two isoforms; COX‐1 and COX‐2. COX‐2 is the therapeutic target for the nonsteroidal anti‐inflammatory drug (NSAID) class of pain medications. Of the prostanoids, prostacyclin, first discovered by Sir John Vane in 1976, remains amongst the best studied and retains an impressive pedigree as one of the fundamental cardiovascular protective pathways. Since this time, we have learnt much about how eicosanoids, COX enzymes and prostacyclin function in the cardiovascular system, knowledge that has allowed us, for example, to harness the power of prostacyclin as therapy to treat pulmonary arterial hypertension and peripheral vascular disease. However, there remain many unanswered questions in our basic understanding of the pathways, and how they can be used to improve human health. Perhaps, the most important and controversial outstanding question in the field remains; ‘how do NSAIDs produce their much publicized cardiovascular side‐effects?’ This review summarizes the history, biology and cardiovascular function of key eicosanoids with particular focus on prostacyclin and other COX products and discusses how our knowledge of these pathways can applied in future drug discovery and be used to explain the cardiovascular side‐effects of NSAIDs.Linked ArticlesThis article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc
Housing Interventions and the Chronic and Acute Risks of Family Homelessness: Experimental Evidence for Education
Authors: Cutuli J. J. , Herbers Janette E. 
Published: February 2018

This study considers risk associated with family homelessness for school functioning and experimental evidence on the effects of different housing interventions over time. Students in homeless families (N = 172; Mage = 7.31; SD = 4.15) were randomized to housing interventions that focus on acute risks (community‐based rapid rehousing), chronic risks (permanent subsidy), or usual care (UC). A matched group of low‐income, housed students served as an additional reference for effects on attendance, school mobility, and reading and math achievement across 4 years. Findings partially support the chronic‐risk hypothesis that family homelessness interferes with achievement through its relation to deep poverty. Children randomly assigned to UC perform as well or better than children assigned to housing interventions in this municipality.
Kant's subjective deduction: A reappraisal
Authors: Kemp Ryan S. 
Published: February 2018

AbstractIn the A‐preface of theCritique of Pure Reason, Kant kindly warns his readers to pay special attention to the chapter on the “Deduction of the Pure Concepts of the Understanding.” Looking to mitigate the reader's effort, Kant goes on to explain the chapter's methodology, suggesting that the inquiry will have “two sides.” One side deals with the “objective validity” of the pure categories of the understanding; he calls this the “objective deduction.” The other deals with the powers of cognition on which the understanding rests; he calls this the “subjective deduction.” Having gone to such great lengths to outline his method ahead of time, it comes as no small surprise that the actual chapter offers no clear indication of where the two deductions are located. In this essay, I attempt to solve this puzzle. On the way, I engage with both traditional and recent interpretations of the subjective deduction, arguing that they fail—in one way or another—to satisfy the criteria that Kant develops in the preface.