bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-perceived employability in Spain
Authors: Vargas Reyes , Sánchez-Queija María Inmaculada , Rothwell Andrew , Parra Águeda
Published: February 2018

Purpose

The purpose of this paper is to validate the self-perceived employability (SPE) scale (Rothwell et al., 2008) and explore its relationship with sociodemographic variables in Spain. The SPE is an employability scale designed to examine undergraduates’ expectations and self-perceptions of employability. The SPE includes internal and external dimensions of employability and has been satisfactorily tested in a variety of contexts.

Design/methodology/approach

The sample comprised 1,502 Spanish undergraduate students from a broad range of subject areas. Confirmatory factor analyses and exploratory factor analyses were conducted. Finally, the Spanish-self-perceived employability (S-SPE) was studied in relation to a set of demographic variables.

Findings

The results revealed similar findings to those reported by Rothwell et al. (2008), namely, four factors labeled: the external labor market’s demand for people in my subject field, my confidence in my skills and abilities, the status and credibility of my field of study and my engagement with my studies and academic performance. The external and internal employability dimensions were obtained by forcing a two-factor solution. Men scored higher than women in the S-SPE; science students scored higher than arts and humanities undergraduates and students with higher perceived income levels scored higher than those with lower perceived income levels.

Originality/value

The S-SPE can be used with Spanish speaking university students (Spanish being the second most widely spoken language in the world) and allows cross-cultural comparisons of undergraduates’ SPE. The S-SPE may help guide the development of social policies and programs designed to enhance employability. It can be used with undergraduates as a diagnostic instrument in career counseling, and as a self-assessment instrument which will enable undergraduates to acquire a greater degree of self-knowledge in relation to their employability.
Macedonia’s exports toward Southeast Europe through the gravity model
Authors: Apostolov Mico , Josheski Dushko
Published: February 2018

Purpose

The purpose of this paper is to examine the export performance of the Republic of Macedonia to its main trading partners from Southeast Europe; hence, the authors focus on the major importing countries which are most present in the Macedonian trade balance.

Design/methodology/approach

The data used in this paper are analyzed with gravity model, which has good characteristics and very stable performance. Further, the data sample is formed on major importers form the Southeastern Europe region.

Findings

The results show that the domestic country GDP is positively correlated with the exports from the source country to target countries and that Balkan countries have positive propensities to import from Macedonia, however, it was found that populations of source country and target country are negatively correlated with exports from the source country to target countries. Additionally, the business cycles had no positive effect on Macedonian export to the target countries.

Originality/value

Based on pertinent theoretical concepts and existing empirical findings, and by applying up-to-date methodological approach, case studies might bring vital contribution to the literature, which eventually leads to solid policy and practice.
Gene expression and ultrastructure of meso‐ and thermophilic methanotrophic consortia
Authors: Krukenberg Viola , Riedel Dietmar , Gruber‐Vodicka Harald R. , Buttigieg Pier Luigi , Tegetmeyer Halina E. , Boetius Antje , Wegener Gunter
Published: February 2018

The sulfate‐dependent, anaerobic oxidation of methane (AOM) is an important sink for methane in marine environments. It is carried out between anaerobic methanotrophic archaea (ANME) and sulfate‐reducing bacteria (SRB) living in syntrophic partnership. In this study, we compared the genomes, gene expression patterns and ultrastructures of three phylogenetically different microbial consortia found in hydrocarbon‐rich environments under different temperature regimes: ANME‐1a/HotSeep‐1 (60°C), ANME‐1a/Seep‐SRB2 (37°C) and ANME‐2c/Seep‐SRB2 (20°C). All three ANME encode a reverse methanogenesis pathway: ANME‐2c encodes all enzymes, while ANME‐1a lacks the gene for N5,N10‐methylene tetrahydromethanopterin reductase (mer) and encodes a methylenetetrahydrofolate reductase (Met). The bacterial partners contain the genes encoding the canonical dissimilatory sulfate reduction pathway. During AOM, all three consortia types highly expressed genes encoding for the formation of flagella or type IV pili and/or c‐type cytochromes, some predicted to be extracellular. ANME‐2c expressed potentially extracellular cytochromes with up to 32 hemes, whereas ANME‐1a and SRB expressed less complex cytochromes (≤ 8 and ≤ 12 heme respectively). The intercellular space of all consortia showed nanowire‐like structures and heme‐rich areas. These features are proposed to enable interspecies electron exchange, hence suggesting that direct electron transfer is a common mechanism to sulfate‐dependent AOM, and that both partners synthesize molecules to enable it.
The iron‐stress activated RNA 1 (IsaR1) coordinates osmotic acclimation and iron starvation responses in the cyanobacterium Synechocystis sp. PCC 6803
Authors: Rübsam Henriette , Kirsch Friedrich , Reimann Viktoria , Erban Alexander , Kopka Joachim , Hagemann Martin , Hess Wolfgang R. , Klähn Stephan
Published: February 2018

In nature, microorganisms are exposed to multiple stress factors in parallel. Here, we investigated the response of the model cyanobacterium Synechocystis sp. PCC 6803 to simultaneous iron limitation and osmotic stresses. Iron is a major limiting factor for bacterial and phytoplankton growth in most environments. Thus, bacterial iron homeostasis is tightly regulated. In Synechocystis, it is mediated mainly by the transcriptional regulator FurA and the iron‐stress activated RNA 1 (IsaR1). IsaR1 is an important riboregulator that affects the acclimation of the photosynthetic apparatus to iron starvation in multiple ways. Upon increases in salinity, Synechocystis responds by accumulating the compatible solute glucosylglycerol (GG). We show that IsaR1 overexpression causes a reduction in the de novo GG synthesis rate upon salt shock. We verified the direct interaction between IsaR1 and the 5′UTR of the ggpS mRNA, which in turn drastically reduced the de novo synthesis of the key enzyme for GG synthesis, glucosylglycerol phosphate synthase (GgpS). Thus, IsaR1 specifically interferes with the salt acclimation process in Synechocystis, in addition to its primary regulatory function. Moreover, the salt‐stimulated GgpS production became reduced under parallel iron limitation in WT – an effect which is, however, attenuated in an isaR1 deletion strain. Hence, IsaR1 is involved in the integration of the responses to different environmental perturbations and slows the osmotic adaptation process in cells suffering from parallel iron starvation.
Transport Infrastructure and Logistics in the Making of Dubai Inc.
Authors: Ziadah Rafeef
Published: February 2018

This article interrogates the political economy of Dubai's Jebel Ali Port, ranked among the top ten container ports internationally by traffic, and its operating conglomerate, Dubai Ports World (DP World). The article aims to situate trade infrastructure in the production of Dubai's economic geography as a sea–air multimodal trading hub. Three interrelated arguments are put forward: that port infrastructure plays an essential role in linking diverse moments of capital accumulation in Dubai; that Dubai's state‐owned conglomerates have overseen a substantial internationalization of Dubai's capital through maritime port public–private partnership arrangements; and that the particularities of Dubai's repressive labour regime underpin its role in the logistics industry internationally.
The Real Effects of FAS 166/167 on Banks’ Mortgage Approval and Sale Decisions
Authors: DOU YIWEI , RYAN STEPHEN G. , XIE BIQIN
Published: February 2018

We examine the real effects of FAS 166 and FAS 167 on banks’ loan‐level mortgage approval and sale decisions. Effective in 2010, these standards tightened the accounting for securitizations and consolidation of securitization entities, respectively, causing banks to recognize an estimated $811 billion of securitized assets on balance sheet. We find that banks that recognize more securitized assets exhibit larger decreases in mortgage approval rates and larger increases in mortgage sale rates. These effects significantly exceed those of banks’ off–balance sheet securitized assets, consistent with our results being driven by the consolidation of securitization entities rather than by securitization per se. We conduct tests that help rule out the financial crisis as an alternative explanation for our results. Further analyses suggest that mechanisms underlying the results include consolidating banks’ reduced regulatory capital adequacy, increased market discipline, and consequent desire not to recognize high‐risk mortgages on balance sheet.
Microbial Quality and Shelf Life of Blueberry Purée Developed Using Cavitation Technology
Authors: Fan Lihua , Martynenko Alex , Doucette Craig , Hughes Timothy , Fillmore Sherry
Published: February 2018

Blueberry purée was developed using hydrodynamic cavitation technology. The product was made from entire blueberries without adding any food additives. In this study, microbial reduction following each processing stage (at the industry setting) and after product pasteurization at 86, 88, 90, 92, 94, and 96 °C was investigated. Microbial quality including total plate counts, yeast and molds, and heat‐resistant molds counts was determined. Shelf life of pasteurized products stored for up to 24 weeks at room temperature were assessed for microbial quality, soluble solids (°Brix), titratable acidity (citric acid %), pH, viscosity (cP) and flow rate (cm/30 s). Our results indicated that heat‐resistant molds, initially present in frozen blueberries with counts at 2.03 log CFU/200g, were totally inactivated at 94 to 96 °C with 1 to 2 min holding time. Shelf life study showed that no product spoilage was caused by bacteria, yeasts and heat‐resistant molds along with non‐significant changes of textural characteristics. This study provided useful information for the food industry to develop variety of fruit purée products with no wastes of fruit materials.

Practical Application

This study provides useful information for the food industry to develop safe liquid food products using cavitation technology without wasting any raw materials.
Membrane fluidification by ethanol stress activates unfolded protein response in yeasts
Authors: Navarro‐Tapia Elisabet , Querol Amparo , Pérez‐Torrado Roberto
Published: February 2018

The toxic effect of ethanol is one of the most important handicaps for many biotechnological applications of yeasts, such as bioethanol production. Elucidation of ethanol stress response will help to improve yeast performance in biotechnological processes. In the yeast Saccharomyces cerevisiae, ethanol stress has been recently described as an activator of the unfolded protein response (UPR), a conserved intracellular signalling pathway that regulates the transcription of ER homoeostasis‐related genes. However, the signal and activation mechanism has not yet been unravelled. Here, we studied UPR's activation after ethanol stress and observed the upregulation of the key target genes, like INO1, involved in lipid metabolism. We found that inositol content influenced UPR activation after ethanol stress and we observed significant changes in lipid composition, which correlate with a major membrane fluidity alteration by this amphipathic molecule. Then, we explored the hypothesis that membrane fluidity changes cause UPR activation upon ethanol stress by studying UPR response against fluidification or rigidification agents and by studying a mutant, erg2, with altered membrane fluidity. The results suggest that the membrane fluidification effects of ethanol and other agents are the signal for UPR activation, a mechanism that has been proposed in higher eukaryotes.
Dissecting the 2017 National Security Strategy: Implications for Senior Administrators (the Devil in the Details)
Authors: Weaver John M.
Published: February 2018

On 18 December 2017 President Trump released his National Security Strategy (NSS). It is the quintessential document that will serve as the azimuth for key government leaders to guide them through the execution of core functions at federal departments and agencies in the months and years to come. At 55 pages, it outlines key issues that he and by extension, his National Security Council, see as of paramount concern for the United States. Broadly, Trump looks to: (1) protect the homeland; (2) promote US prosperity; (3) leveraging strength to preserve peace; and (4) advance US influence in the world (NSS, 2017, p. 4).
Reflectance and biochemical responses of maize plants to drought and re‐watering cycles
Authors: Sun C.X. , Li C.C. , Zhang C.Y. , Hao L.Y. , Song M. , Liu W. , Zhang Y.L.
Published: February 2018

The ability to recover from drought stress after re‐watering is an important feature that will enable plants to cope with the predicted increase in episodic drought. The effects of pre‐drought and re‐watering conditions on leaf spectral properties and their relationships with the biochemical processes that underlie the recovery from pre‐drought conditions should be better understood. The reflectance spectra, 10 spectral reflectance indices (SRIs) and biochemical characteristics of maize (Zea mays) leaves were monitored 7, 14, 21 and 28 days after the initiation of soil drought stress during two successive cycles of drought and re‐watering periods. The leaf reflectance of the two inbred maize lines increased under the drought stress, especially in the visible spectral range. In addition, an obvious recovery of the leaf reflectance was only observed in the first re‐watering period, and its value remained higher than that of the control plants during the second recovery period. A recovery lag in the pigment contents was also observed during the second cycle. The recovery variations in the pattern and magnitude of the SRIs and the total contents of C, N and P that were measured in response to the re‐watering during both cycles were diverse and complex; both full and partial recoveries were observed. The SRIs representing different physiological attributes of plant growth, including the water index, red edge position, photochemical reflectance index and near‐infrared reflectance at 800 nm, showed strong linear relationships (P < 0.01 or 0.05) with the growth and biochemical traits across the successive drought and re‐watering cycles. The results suggest that maize plants can adjust their leaf reflectance properties and employ growth and biochemical strategies to adapt to cyclic drought stress and recover from drought stress after re‐watering.
Apremilast Alters Behavioral Responses to Ethanol in Mice: II. Increased Sedation, Intoxication, and Reduced Acute Functional Tolerance
Authors: Blednov Yuri A. , Da Costa Adriana J. , Harris R. Adron , Messing Robert O.
Published: February 2018

Background

In our companion paper, we reported that the phosphodiesterase type 4 inhibitor apremilast reduced ethanol (EtOH) intake and preference in different drinking models in male and female C57BL/6J mice. In this study, we measured the effects of apremilast on other behaviors that are correlated with EtOH consumption.

Methods

The effects of apremilast (20 mg/kg) on the following behaviors were studied in male and female C57BL/6J mice: locomotor response to a novel situation; EtOH‐ and lithium chloride (LiCl)‐induced conditioned taste aversion (CTA) to saccharin; conditioned place preference (CPP) and conditioned place avoidance (CPA) to EtOH; severity of handling‐induced convulsions after EtOH administration; EtOH‐induced anxiolytic‐like behavior in the elevated plus maze; duration of EtOH‐induced loss of righting reflex (LORR); recovery from EtOH‐induced motor impairment on the rotarod; and acute functional tolerance (AFT) to EtOH's ataxic effects.

Results

Apremilast did not change the acquisition of EtOH‐induced CPP, severity of acute withdrawal from EtOH, or EtOH's anxiolytic‐like effect. Apremilast did not alter the extinction of EtOH‐ or LiCl‐induced CTA, but may interfere with acquisition of CTA to EtOH. Apremilast increased the acquisition of CPA to EtOH, reduced locomotor responses to a novel situation, and prolonged the duration of LORR and the recovery from acute motor incoordination induced by EtOH. The longer recovery from the ataxic effect may be attributed to reduced development of AFT to EtOH.

Conclusions

Our results suggest that apremilast increases the duration of EtOH intoxication by reducing AFT. Apremilast also reduces some aspects of general reward and increases EtOH's aversive properties, which might also contribute to its ability to reduce EtOH drinking.
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

Background

Phosphodiesterase 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.

Methods

We 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.

Results

In 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.

Conclusions

Apremilast 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.
Euthanasia and addiction: a comment from the Netherlands
Authors: Boer Theo
Published: February 2018

Commentary to: The need to exercise caution in accepting addiction as a reason for performing euthanasia
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

Background

Pre‐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.

Aim

To assess the safety and efficacy of vaginal prostaglandin (PG) compared to syntocinon for induction of labour in term‐PROM.

Method

This 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.

Results

One 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.

Conclusion

Induction 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

Background

Nuchal 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.

Aims

The 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 Methods

Operators 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).

Results

In 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).

Conclusions

Teleconference 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

In 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

Aim

To test the effect of folic acid supplements taken throughout pregnancy on children's psychosocial development.

Method

A 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).

Results

Children 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.

Conclusion

Although 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

Background

A 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.

Aim

To 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.

Methods

Literature review to determine aetiological factors, prevalence and outcomes relating to indeterminate hepatitis.

Results

There 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.

Conclusions

Whilst 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

Background

The use of rifampicin for cholestatic pruritus is accompanied by concerns over safety, but the availability of real‐world prescribing data is relatively limited.

Aim

We 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.

Methods

Retrospective 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.

Results

After 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.

Conclusions

Given 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

Based 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

In 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

A 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

Immune 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

Brentuximab 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.
A truth that does not always speak its name: How Hollander and Turowetz's findings confirm and extend the engaged followership analysis of harm‐doing in the Milgram paradigm
Authors: Haslam S. Alexander , Reicher Stephen D.
Published: February 2018

Hollander and Turowetz (2017, Br. J. Soc. Psychol., 56, 655–674) present important data from post‐experimental interviews with participants in Milgram's ‘obedience’ research. In these, participants responded to various questions about their perceptions of the study and their behaviour by indicating that they trusted the Experimenter not to let them inflict serious harm. Relatively few participants indicated that they acted as they did because they were committed to the Experimenter or to science. We argue, however, that there are two key reasons why this evidence is not inconsistent with claims that harm‐doing is a product of engaged followership. The first is that (in contrast to the data obtained from later post‐experimental surveys) the conversational logic of the interviews does not topicalize a discussion or valorization of science, but instead requires participants to defend themselves against an accusation of improper behaviour. The second is that participants’ accounts of their behaviour nevertheless revolved around expressions of trust in the Experimenter which can themselves be seen as manifestations of shared identity and engaged followership. Nevertheless, we argue that H&T's analysis points to significant ways in which the engaged followership account and its broader implications for understanding perpetrator behaviour can be embellished.
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.

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This 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
Distinct and combined effects of disciplinary composition and methodological support on problem solving in groups
Authors: Schöfer Malte , Maranzana Nicolas , Aoussat Améziane , Bersano Giacomo , Buisine Stéphanie
Published: February 2018

Several reasons for the use of multidisciplinary teams composed of individuals with natural science and engineering background in problem‐solving processes exist. The most important are the integration of science‐based technologies into products and processes, and benefits for the problem‐solving process thanks to new knowledge and new perspectives on problems. In this study we analyse the implications of interdisciplinary (science – engineering) group problem solving from a managerial as well as from a cognitive perspective. We then report on an experiment investigating the impact of problem‐relevant disciplinary group composition and methodological support on the problem‐solving process and its outcome. The findings of the experiment have managerial, theoretical, and pedagogical implications related to early phases of New Product/Process Design processes in high‐technology and scientific knowledge‐related domains.
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.
Molecular and clinical studies in 8 patients with Temple syndrome
Authors: Gillessen‐Kaesbach G. , Albrecht B. , Eggermann T. , Elbracht M. , Mitter D. , Morlot S. , van Ravenswaaij‐Arts C.M.A. , Schulz S. , Strobl‐Wildemann G. , Buiting K. , Beygo J.
Published: February 2018

Temple syndrome (TS14, #616222) is a rare imprinting disorder characterised by phenotypic features including pre‐ and postnatal growth retardation, muscular hypotonia and feeding difficulties in infancy, early puberty and short stature with small hands and feet and often truncal obesity. It is caused by maternal uniparental disomies, paternal deletions and primary imprinting defects that affect the chromosomal region 14q32 and lead to a disturbed expression of imprinted genes in this region. Here, we present detailed clinical data of 8 patients with Temple syndrome, 4 with an imprinting defect, 2 with an imprinting defect in a mosaic state as well as 1 complete and 1 segmental maternal uniparental disomy of chromosome 14.
Novel short curved sphincterotome for wire‐guided cannulation and endoscopic sphincterotomy
Authors: Kawakami Hiroshi , Kubota Yoshimasa , Ban Tesshin
Published: February 2018

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Kant's subjective deduction: A reappraisal
Authors: Kemp Ryan S.
Published: February 2018

In 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.
Learning deep representation for trajectory clustering
Authors: Yao Di , Zhang Chao , Zhu Zhihua , Hu Qin , Wang Zheng , Huang Jianhui , Bi Jingping
Published: February 2018

Trajectory clustering, which aims at discovering groups of similar trajectories, has long been considered as a corner stone task for revealing movement patterns as well as facilitating higher level applications such as location prediction and activity recognition. Although a plethora of trajectory clustering techniques have been proposed, they often rely on spatio‐temporal similarity measures that are not space and time invariant. As a result, they cannot detect trajectory clusters where the within‐cluster similarity occurs in different regions and time periods. In this paper, we revisit the trajectory clustering problem by learning quality low‐dimensional representations of the trajectories. We first use a sliding window to extract a set of moving behaviour features that capture space‐ and time‐invariant characteristics of the trajectories. With the feature extraction module, we transform each trajectory into a feature sequence to describe object movements and further employ a sequence‐to‐sequence auto‐encoder to learn fixed‐length deep representations. The learnt representations robustly encode the movement characteristics of the objects and thus lead to space‐ and time‐invariant clusters. We evaluate the proposed method on both synthetic and real data and observe significant performance improvements over existing methods.
From quiescent bureaucracy to “undocumented wonder”: Explaining the Indian Election Commission's expanding mandate
Authors: Ahuja Amit , Ostermann Susan L.
Published: February 2018

Public institutions in the developing world are often characterized by institutional capture or decay. Yet, India's Election Commission (EC) has become one of its most powerful regulatory bodies. We use a process‐tracing approach to explain the EC's surprising expansion of mandate, arguing that in a federal democracy: (a) when institutional constraints are weakened, (b) when state‐based actors demand a competent and neutral arbiter, and (c) when entrepreneurial bureaucratic actors take advantage of moments of political opportunity, those aspects of the bureaucracy that can credibly meet these demands are able to successfully expand their powers. Changes in Model Code Implementation and Election Duration attest to the EC's broader role. The EC's experience suggests that a weak executive can facilitate the strengthening of state institutions and that, under federalism, state‐based electoral forces can produce strong national institutions.