bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic profile of paclitaxel in the plasma, lung, and diaphragm following intravenous or intrapleural administration in rats
Authors: Li Jie , Tang Jian , Li Yingjie , Yu Jianqi , Zhang Baoshi , Yu Changhai
Published: May 2014

Background

The optimal chemotherapy route for non‐small cell lung cancers involving the phrenic nerve and diaphragm is unclear. The pharmacokinetic properties of paclitaxel following intravenous (IV) or intrapleural (IP) administration were analyzed in the plasma, lung, and diaphragm in a rat model. The purpose of this study was to determine whether IP injection increased paclitaxel concentration in the diaphragm.

Methods

Paclitaxel was administered by IV or IP to male Sprague‐Dawley rats. The concentration of drug in the plasma, lung, and diaphragm was determined using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). The pharmacokinetic parameters area under the curve (AUC), mean residence time (MRT), peak plasma concentration (Cmax), and half‐life (t1/2) were analyzed.

Results

Paclitaxel concentration in the plasma, lung, and diaphragm decreased quickly following IV administration. However, after IP injection, paclitaxel reached a high concentration in the plasma, lung, and diaphragm that declined gradually. Significant differences in all parameters, except Cmax in the lung, were observed between the two routes of administration (all P < 0.05). Plasma exposure to paclitaxel IP was 41.1% of that observed after IV in the first 24 hours (P < 0.05). IP also significantly increased exposure of paclitaxel in comparison with IV administration to 267.3% and 905.7% of IV administration in the lung and diaphragm, respectively (P < 0.05).

Conclusion

These results suggest that IP administration may reduce systemic distribution of paclitaxel and increase the concentration in the lung and diaphragm. This could increase therapeutic efficacy by increasing the available drug and reduce systemic toxicity.
What Drives Portfolio Pumping in the Korean Equity Fund Market?
Authors: Lee Jinho , Baek Kang , Park Young S.
Published: May 2014

This paper analyzes whether portfolio pumping by fund managers is widespread in the Korean equity fund market, and identifies the factors encouraging this behavior. The study results demonstrate that (i) fund managers are tempted to distort fund performance through portfolio pumping at year‐end (when their achievement is evaluated); (ii) this manipulation occurs more actively in small funds and those with good past performance; (iii) portfolio pumping is observed more in products of foreign or small‐sized asset management companies; and (iv) although statistically less significant, fund managers are tempted to undertake price manipulation when their holdings have low liquidity.
Postinfectious bronchiolitis obliterans in children: the South American contribution
Authors: Castro‐Rodriguez Jose A. , Giubergia Veronica , Fischer Gilberto B. , Castaños Claudio , Sarria Edgar E. , Gonzalez Ramiro , Mattiello Rita , Vega‐Briceño Luis E. , Murtagh Patricia
Published: May 2014

Postinfectious bronchiolitis obliterans (PIBO) is an infrequent chronic lung that causes irreversible obstruction and, or, obliteration of the smaller airways. This review particularly focuses on more than 30 studies from South America.

Conclusion

The initial PIBO event occurs in the early years of life and is strongly associated with adenovirus infection and the need for mechanical ventilator support. Treatment requires a multidisciplinary strategy. Multicentre studies are needed to determine progression, optimal management and long‐term follow‐up.
Holocene environmental change in theSkallingen area, easternNorthGreenland, based on a lacustrine record
Authors: Wagner Bernd , Bennike Ole
Published: May 2014

A lacustrine record from a small lake,LilleSnehaSø, in theSkallingen area indicates that the region was deglaciated in the earlyHolocene, prior to 8000 cal. aBP. Deglaciation was probably triggered by high temperatures, but it took more than 1000 years for the lake and the catchment to stabilize. Chironomids were amongst the first invertebrates to colonize the lake. The fossil chironomid assemblage is fairly rich and comparable to other records from further south inGreenland. The pioneer vegetation in the area consisted of mosses and herbaceous plants. The oldest remains of woody plants (Salix arctica) are dated toc. 7700 cal. aBP, and remains ofDryas integrifoliaappear at around 6700 cal. aBP; these are the only woody plants recorded. Maximum concentrations of chironomids, maximum occurrence of ephippia of the water fleaDaphnia pulex, highest organic matter contents and lowest minerogenic input fromc.7700 to 4400 cal. aBPprobably reflect theHolocene thermal maximum (HTM). The highest temperatures during theHTMare indicated around 7000 cal. aBP, whenSalix arctica, which is considered a warmth‐loving plant, had a maximum. Comparisons withHolocene records fromEast andNorthGreenland show similar immigration histories and similar trends, with theLittleIceAge as the coldest period during theHolocene, culminating about 150 years ago. Subsequent warming does not indicate environmental conditions comparable to theHTMyet at this stage. The occurrence of several warmth‐demanding species particularly in the earlyHolocene sediments indicates redeposition and implies that temperatures in the past, most likely during an interglacial period, were significantly higher than during theHTM.
Effects of short‐term detraining following blood flow restricted low‐intensity training on muscle size and strength
Authors: Yasuda Tomohiro , Loenneke Jeremy P. , Ogasawara Riki , Abe Takashi
Published: May 2014

We investigated the effects of 3 weeks of detraining on muscle cross‐sectional area (CSA) and one‐repetition maximum strength (1‐RM) in young men who had previously participated in 6 weeks (3 days week−1) of bench press training [blood flow restricted low‐intensity (LI‐BFR; n = 10, 20% 1‐RM) or high‐intensity (HI; n = 7, 75% 1‐RM)]. Bench press 1‐RM and muscle CSA of triceps brachii (TB) and pectoralis major (PM) were evaluated before (pre) and after training period (post) as well as after detraining period (detraining). Bench press 1‐RM was higher at both post and detraining than at pre for LI‐BFR (P<0·01) and the HI (P<0·01). TB and PM muscle CSA were higher at both post and detraining than at pre for the HI group (P<0·01), while the LI‐BFR group only increased (P<0·01) at post. Relative dynamic strength (1‐RM divided by TB muscle CSA) was higher at both post and detraining than at pre for the HI group (P<0·01), while the LI‐BFR group only increased (P<0·01) at detraining. In conclusion, increased muscle strength following 6 weeks of training with LI‐BFR as well as HI was well preserved at 3 weeks of detraining. HI‐induced muscle strength appears to be dependent upon both neural adaptations and muscle hypertrophy with training and detraining. On the other hand, LI‐BFR‐induced muscle strength appears to be related primarily to muscle hypertrophy with training and to neural adaptations with detraining.
ALADYN – a spatially explicit, allelic model for simulating adaptive dynamics
Authors: Schiffers Katja H. , Travis Justin M. J.
Published: May 2014

ALADYN is a freely available cross‐platform C++ modeling framework for stochastic simulation of joint allelic and demographic dynamics of spatially‐structured populations. Juvenile survival is linked to the degree of match between an individual's phenotype and the local phenotypic optimum. There is considerable flexibility provided for the demography of the considered species and the genetic architecture of the traits under selection. ALADYN facilitates the investigation of adaptive processes to spatially and/or temporally changing conditions and the resulting niche and range dynamics. To our knowledge ALADYN is so far the only model that allows a continuous resolution of individuals’ locations in a spatially explicit landscape together with the associated patterns of selection.
Influence of 1100 years of burning on the central African rainforest
Authors: Tovar Carolina , Breman Elinor , Brncic Terry , Harris David J. , Bailey Richard , Willis Katherine J.
Published: May 2014

Four major forest types are currently present in the central African rainforest; mixed forest, Marantaceae forest, monodominant Gilbertiodendron forest and swamp forest. These forest types span vast areas and demonstrate highly significant differences in diversity and productivity; yet factors responsible for their formation are poorly understood. One hypothesis is that they are as a consequence of different intensities of past human activity, in particular burning. Here we present results from fossil charcoal contained in 12 sediment cores spanning the last 2500 yr and covering a spatial area of more than 900 km2. These records demonstrate that burning started in the last 1100 yr with areas currently covered by Marantaceae forest undergoing more frequent burning events than the other forest types. In comparison monodominant Gilbertiodendron forest appear to have undergone large burning events only in the past 200 yr. These records also demonstrate a lack of spatial relationship between fire events at the different sites (discontinuous and asynchronous) suggesting that these fires resulted from localised burning events probably caused by human ignitions. Whilst the large spatial scale of past human activities in the South American rainforest is now widely acknowledged, these results indicate, for the first time, the significant impact that early human populations had on the community composition of central African rainforest.
Cortical muscle control of spontaneous movements in human neonates
Authors: Kanazawa Hoshinori , Kawai Masahiko , Kinai Takahiro , Iwanaga Kougorou , Mima Tatsuya , Heike Toshio
Published: May 2014

Anatomical studies show the existence of corticomotor neuronal projections to the spinal cord before birth, but whether the primary motor cortex drives muscle activity in neonatal ‘spontaneous’ movements is unclear. To investigate this issue, we calculated corticomuscular coherence (CMC) and Granger causality in human neonates. CMC is widely used as an index of functional connectivity between the primary motor cortex and limb muscles, and Granger causality is used across many fields of science to detect the direction of coherence. To calculate CMC and Granger causality, we used electroencephalography (EEG) to measure activity over the cortical region that governs leg muscles, and surface electromyography (EMG) over the right and left tibialis anterior muscles, in 15 healthy term and preterm neonates, during spontaneous movements without any external stimulation. We found that 17 leg muscles (10 right, seven left) in 12 neonates showed significant CMC, whose magnitude significantly correlated with postnatal age only in the beta frequency band. Further analysis revealed Granger causal drive from EEG to EMG in 14 leg muscles. Our findings suggest that the primary motor cortex drives muscle activity when neonates move their limbs. Moreover, the positive correlation between CMC magnitude and postnatal age suggests that corticomuscular communication begins to develop during the neonatal stage. This process may facilitate sensory‐motor integration and activity‐dependent development.
Spike detection from noisy neural data in linear‐probe recordings
Authors: Takekawa Takashi , Ota Keisuke , Murayama Masanori , Fukai Tomoki
Published: May 2014

Simultaneous recordings of multiple neuron activities with multi‐channel extracellular electrodes are widely used for studying information processing by the brain's neural circuits. In this method, the recorded signals containing the spike events of a number of adjacent or distant neurons must be correctly sorted into spike trains of individual neurons, and a variety of methods have been proposed for this spike sorting. However, spike sorting is computationally difficult because the recorded signals are often contaminated by biological noise. Here, we propose a novel method for spike detection, which is the first stage of spike sorting and hence crucially determines overall sorting performance. Our method utilizes a model of extracellular recording data that takes into account variations in spike waveforms, such as the widths and amplitudes of spikes, by detecting the peaks of band‐pass‐filtered data. We show that the new method significantly improves the cost–performance of multi‐channel electrode recordings by increasing the number of cleanly sorted neurons.
The Prevalence of Helicobacter pylori Gastritis in Newly Diagnosed Children with Inflammatory Bowel Disease
Authors: Roka Kleoniki , Roubani Aikaterini , Stefanaki Kalliopi , Panayotou Ioanna , Roma Eleftheria , Chouliaras Giorgos
Published: May 2014

Background

Recent studies have shown that patients with inflammatory bowel disease (IBD) are less likely to be infected with Helicobacter pylori compared with non‐IBD patients. We aimed to study the prevalence of H. pylori‐positive and H. pylori‐negative gastritis in newly diagnosed children with IBD in comparison to those with non‐IBD in Greece.

Materials and Methods

All children who underwent first esophagogastroduodenal endoscopy between 2002 and 2011 were retrospectively included. Four groups were studied: patients with Crohn's disease (CD), ulcerative colitis (UC), IBD unclassified (IBDU), and non‐IBD individuals (non‐IBD). Helicobacter pylori infection was defined by positive culture or by positive histology and CLO test. Those children with negative or not available culture and only one positive test (histology or CLO) were further evaluated by urea breath test, and the positives were also included in the infected group.

Results

We studied 159 patients with IBD (66 CD, 34 UC, and 59 IBDU) and 1209 patients in non‐IBD individuals. Helicobacter pylori gastritis was less frequent in the IBD group (3.8% vs 13.2% in the control group, p < .001), whereas IBD patients were significantly older than non‐IBD children (p < .001). Children with H. pylori‐negative gastritis were 3.3 times more likely to belong in the IBD group compared with H. pylori‐positive patients (p = .006).

Conclusions

Occurrence of H. pylori gastritis is less frequent in children with IBD compared with controls. Our study confirms an inverse association between H. pylori and IBD. Future studies are needed to distinguish between a true protective role of H. pylori and a confounding effect due to previous antibiotic use in children with IBD.
High‐fat and high‐cholesterol diet rapidly induces non‐alcoholic steatohepatitis with advanced fibrosis in Sprague–Dawley rats
Authors: Ichimura Mayuko , Kawase Miku , Masuzumi Miki , Sakaki Mika , Nagata Yasuo , Tanaka Kazunari , Suruga Kazuhito , Tamaru Shizuka , Kato Shigeko , Tsuneyama Koichi , Omagari Katsuhisa
Published: May 2014

Aim

The development of fibrosis is considered an important phase in the progress of non‐alcoholic steatohepatitis (NASH) towards the end stage of liver disease, including cirrhosis. However, few small animal models can display NASH‐associated fibrosis. We aimed to establish a dietary model of NASH with rapid progression to fibrosis using genetically normal rats.

Methods

Nine‐week‐old male Sprague–Dawley rats were fed with normal, high‐fat (HF), or two types of high‐fat and high‐cholesterol (HFC) diets for 9 weeks (n = 5 each). All HFC diets contained 1.25% or 2.5% cholesterol.

Results

The rats fed with the HF diet developed mild steatosis and inflammation without fibrosis at 18 weeks of age, whereas all rats given the HFC diet developed obvious steatosis and inflammation with hepatocyte ballooning and fibrosis. Two of five (40%) rats given the HFC diet containing 2.5% cholesterol progressed to liver cirrhosis. Hepatic total cholesterol levels were significantly higher in rats given the HFC, than the normal or HF diets. The HFC diet significantly and dose‐dependently decreased microsomal triglyceride transfer protein expression. Cholesterol tended to suppress carnitine palmitoyltransferase activity and adenosine triphosphate‐binding cassette transporter G5 expression. Adding cholesterol to the HF diet modified hepatic lipid metabolism at the molecular level.

Conclusion

The HFC diet induced hepatic features of NASH and eventually progressed cirrhosis in Sprague–Dawley rats within 9 weeks.
Physicochemical properties, antioxidant activity and inhibition ofα‐glucosidase of a novel fermented pepper (Capsiccum annuum L.) leaves‐based vinegar
Authors: Song Young‐Ran , Shin Nam‐Sik , Baik Sang‐Ho
Published: May 2014

The aim of this study was to utilise by‐product pepper leaves for vinegar production due to its nutritional value. Changes in physicochemical and functional properties in four main process from raw material (leaves) to lactic acid (juice), alcohol (wine) and acetic acid (vinegar) fermentations were evaluated and compared. Their nutritional compositions were significantly different and particularly the wine and vinegar had higher total phenol content and their expanded diversity than the juice and then leaves (P < 0.05). Difference in values for phenolic compound was highly correlated with their α‐glucosidase inhibitory (AGI) and antioxidant capacities in DPPH and superoxide radical scavenging and reducing power assays (r = 0.919–0.981); vinegar ≥ wine > juice > leaves. Especially, AGI activity was greatly enhanced depending on fermentation steps beyond expectation. Thus, these data confirm that pepper leaves is a good functional source and the vinegar fermentation improved the functionality in stages.
Prescription Frequency and Predictors for the Use of Novel Direct Oral Anticoagulants for Secondary Stroke Prevention in the First Year after Their Marketing in Europe – A Multicentric Evaluation
Authors: Luger Sebastian , Hohmann Carina , Kraft Peter , Halmer Ramona , Gunreben Ignaz , Neumann-Haefelin Tobias , Kleinschnitz Christoph , Walter Silke , Haripyan Veronika , Steinmetz Helmuth , Foerch Christian , Pfeilschifter Waltraud
Published: May 2014

Background

Direct oral anticoagulants (DOAC) are alternatives to the use of vitamin K antagonists (VKA) as oral anticoagulant therapies to prevent stroke in patients with atrial fibrillation.

Aims

We assembled a representative secondary prevention cohort from four tertiary care stroke centers to identify factors that independently influence therapeutic decision making 1) not to anticoagulate with either VKA or DOAC and 2) to use DOAC if the patient appears suitable for oral anticoagulant therapy.

Methods

We identified all patients discharged with the diagnoses ‘ischemic stroke’ (ICD-10 code 163) or ‘transient ischemic attack’ (G45) in combination with ‘atrial fibrillation’ (148) during 1 year. We performed binary logistic regression analyses to identify factors independently influencing the aforementioned decisions.

Results

Our cohort comprised 758 patients. At discharge from the stroke service, 374 patients (49·3%) received oral anticoagulant therapy. Older age, severe stroke, poor recovery in the acute phase, and higher serum creatinine were independent factors to withhold oral anticoagulant therapy, whereas prior oral anticoagulant therapy favored the decision to anticoagulate. Among patients who were anticoagulated, prescription was balanced for VKA (50·3%) and DOAC (49·7%). Renal function and prior oral anticoagulant therapies were the most important factors in this decision.

Conclusions

Shortly after their marketing, DOAC are used as frequently as VKA for secondary stroke prevention in patients with atrial fibrillation. The decision between VKA and DOAC is mainly determined by the patient's renal function and the absence or presence of prior oral anticoagulant therapy.
BiFeO3 Ceramics: Processing, Electrical, and Electromechanical Properties
Authors: Rojac Tadej , Bencan Andreja , Malic Barbara , Tutuncu Goknur , Jones Jacob L. , Daniels John E. , Damjanovic Dragan
Published: May 2014

Bismuth ferrite (BiFeO3), a perovskite material, rich in properties and with wide functionality, has had a marked impact on the field of multiferroics, as evidenced by the hundreds of articles published annually over the past 10 years. Studies from the very early stages and particularly those on polycrystalline BiFeO3 ceramics have been faced with difficulties in the preparation of the perovskite free of secondary phases. In this review, we begin by summarizing the major processing issues and clarifying the thermodynamic and kinetic origins of the formation and stabilization of the frequently observed secondary, nonperovskite phases, such as Bi25FeO39 and Bi2Fe4O9. The second part then focuses on the electrical and electromechanical properties of BiFeO3, including the electrical conductivity, dielectric permittivity, high‐field polarization, and strain response, as well as the weak‐field piezoelectric properties. We attempt to establish a link between these properties and address, in particular, the macroscopic response of the ceramics under an external field in terms of the dynamic interaction between the pinning centers (e.g., charged defects) and the ferroelectric/ferroelastic domain walls.
Knowledge Management in Supply Chains: The Role of Explicit and Tacit Knowledge
Authors: Schoenherr Tobias , Griffith David A. , Chandra Aruna
Published: May 2014

We theorize, building on the knowledge‐based view and the theoretical distinction between explicit and tacit knowledge, that knowledge management capability across the supply chain manifests itself in explicit and tacit knowledge, which in turn effectuates supply chain performance. The model is tested with survey data from 195 small‐ and medium‐sized enterprises reporting on their primary supply chain. The results indicate that the supply chain's knowledge management capability manifests itself in both explicit and tacit knowledge, with the latter being influenced more strongly. Moreover, it was found that while both explicit and tacit knowledge influence supply chain performance, the latter exerts a significantly greater impact than the former. Exploratory post hoc analyses add robustness to these findings and investigate mechanisms inherent to the transformation of tacit into explicit knowledge. Overall, this research contributes to academic theory development in logistics and supply chain management by the dichotomization of knowledge types and the demonstration of their differential magnitude of effects, and to managerial practice by providing important guidance for logistics managers structuring their knowledge management efforts across supply chains.
Checklists for external validity: a systematic review
Authors: Dyrvig Anne‐Kirstine , Kidholm Kristian , Gerke Oke , Vondeling Hindrik
Published: May 2014

Rationale, aims and objectives

The quality of the current literature on external validity varies considerably. An improved checklist with validated items on external validity would aid decision‐makers in judging similarities among circumstances when transferring evidence from a study setting to an implementation setting. In this paper, currently available checklists on external validity are identified, assessed and used as a basis for proposing a new improved instrument.

Method

A systematic literature review was carried out in Pubmed, Embase and Cinahl on English‐language papers without time restrictions. The retrieved checklist items were assessed for (i) the methodology used in primary literature, justifying inclusion of each item; and (ii) the number of times each item appeared in checklists.

Results

Fifteen papers were identified, presenting a total of 21 checklists for external validity, yielding a total of 38 checklist items. Empirical support was considered the most valid methodology for item inclusion. Assessment of methodological justification showed that none of the items were supported empirically. Other kinds of literature justified the inclusion of 22 of the items, and 17 items were included on the basis of consensus. On 36 occasions, the items were presented without methodological justification for inclusion. Assessment of frequency/occurrence showed that items were mentioned in one to at most 17 checklists.

Conclusion

This paper provides building blocks for the development of a new checklist for external validity. The next step is provision of empirical evidence for the checklist items to be selected, and finally, development and validation of a checklist on external validity.
Bayesian bivariate meta‐analysis of sensitivity and specificity: summary of quantitative findings in 50 meta‐analyses
Authors: Menke Jan
Published: May 2014

Rationale, aims and objectives

Meta‐analyses of diagnostic test accuracy are important elements in evidence‐based medicine. However, currently there is no overview of related quantitative findings that were obtained in a large number of real meta‐analyses. This study aimed at providing such empirical summary.

Methods

From the literature 50 meta‐analyses were randomly selected that had reported their 2 × 2 count data of sensitivity and specificity. Descriptive statistics, assessment of between‐study heterogeneity and bivariate random‐effects meta‐analysis of sensitivity and specificity were performed with a novel Bayesian program code. The bivariate model parameters were also converted to the parameters of the closely related hierarchical summary receiver operating characteristic (HSROC) model.

Results

Among the 50 meta‐analyses, the studies per meta‐analysis ranged from 5 to 45 and the disease prevalence from 2.3 to 71%. Significant between‐study heterogeneity was found in 43 of 50 meta‐analyses, favouring a random‐effects model over a fixed‐effects model. Empirical distributions of sensitivity and specificity, positive and negative likelihood ratios, and other model results are presented in the full text numerically and graphically.

Conclusions

Studies of diagnostic test accuracy can be well meta‐analysed within a Bayesian framework, and the presented quantitative findings provide an orientation when interpreting the results of the standard bivariate/HSROC model.
E‐Learning Module on Chronic Low Back Pain in Older Adults: Evidence of Effect on Medical Student Objective Structured Clinical Examination Performance
Authors: Weiner Debra K. , Morone Natalia E. , Spallek Heiko , Karp Jordan F. , Schneider Michael , Washburn Carol , Dziabiak Michael P. , Hennon John G. , Elnicki D. Michael ,   the University of Pittsburgh Center of Excellence in Pain Education
Published: May 2014

The Institute of Medicine has highlighted the urgent need to close undergraduate and graduate educational gaps in treating pain. Chronic low back pain (CLBP) is one of the most common pain conditions, and older adults are particularly vulnerable to potential morbidities associated with misinformed treatment. An e‐learning case‐based interactive module was developed at the University of Pittsburgh Center of Excellence in Pain Education, one of 12 National Institutes of Health–designated centers, to teach students important principles for evaluating and managing CLBP in older adults. A team of six experts in education, information technology, pain management, and geriatrics developed the module. Teaching focused on common errors, interactivity, and expert modeling and feedback. The module mimicked a patient encounter using a standardized patient (the older adult with CLBP) and a pain expert (the patient provider). Twenty‐eight medical students were not exposed to the module (Group 1) and 27 were exposed (Group 2). Their clinical skills in evaluating CLBP were assessed using an objective structured clinical examination (OSCE). Mean scores were 62.0 ± 8.6 for Group 1 and 79.5 ± 10.4 for Group 2 (P < .001). Using an OSCE pass–fail cutoff score of 60%, 17 of 28 Group 1 students (60.7%) and 26 of 27 Group 2 students (96.3%) passed. The CLBP OSCE was one of 10 OSCE stations in which students were tested at the end of a Combined Ambulatory Medicine and Pediatrics Clerkship. There were no between‐group differences in performance on eight of the other nine OSCE stations. This module significantly improved medical student clinical skills in evaluating CLBP. Additional research is needed to ascertain the effect of e‐learning modules on more‐advanced learners and on improving the care of older adults with CLBP.
Prevention of materno‐foetal transmission of hepatitis B in sub‐Saharan Africa: the evidence, current practice and future challenges
Authors: Howell J. , Lemoine M. , Thursz M.
Published: May 2014

Hepatitis B (HBV) infection is highly endemic in sub‐Saharan Africa (SSA), where more than 8% of the population remain chronic HBV carriers. SSA has one of the highest HBV‐related liver cancer rates in the world (CA Cancer J Clin, 55, 2005, 74) and HBV‐related liver cancer is the most common cause of premature death in West Africa (Lancet Oncol, 9, 2008, 683; Hepatology, 39, 2004, 211). As such, HBV represents a significant global threat to health in the African continent. Most SSA countries have elected to vaccinate all children against HBV through the WHO‐sponsored Expanded Program of Immunization and the current recommendation from WHO‐AFRO is for birth‐dose HBV vaccination to prevent maternal/child transmission (MFT) and early horizontal transmission of HBV. However, in Africa, HBV vaccine coverage remains low and HBV birth‐dose vaccination has not been implemented. HBV transmission from mother to child in the early perinatal period therefore remains a significant contributor to the burden of HBV‐related disease in SSA. This review explores the evidence for materno‐foetal transmission of HBV in SSA, outlining current practice for HBV MFT prevention and identifying the significant challenges to implementation of HBV prevention in SSA.
What's the Point of Blame? A Paradigm Based Explanation
Authors: Fricker Miranda
Published: May 2014

When we hope to explain and perhaps vindicate a practice that is internally diverse, philosophy faces a methodological challenge. Such subject matters are likely to have explanatorily basic features that are not necessary conditions. This prompts a move away from analysis to some other kind of philosophical explanation. This paper proposes a paradigm based explanation of one such subject matter: blame. First, a paradigm form of blame is identified—‘Communicative Blame’—where this is understood as a candidate for an explanatorily basic form of blame. Second, its point and purpose in our lives is investigated and found to reside in its power to increase the alignment of the blamer and the wrongdoer's moral understandings. Third, the hypothesis that Communicative Blame is an explanatorily basic form of blame is tested out by seeing how far other kinds of blame can reasonably be understood as derivative, especially in respect of blame's point and purpose. Finally, a new and quasi‐political worry about blame is raised.
Dutch Books, Coherence, and Logical Consistency
Authors: Mahtani Anna
Published: May 2014

In this paper I present a new way of understanding Dutch Book Arguments: the idea is that an agent is shown to be incoherent iff (s)he would accept as fair a set of bets that would result in a loss under any interpretation of the claims involved. This draws on a standard definition of logical inconsistency. On this new understanding, the Dutch Book Arguments for the probability axioms go through, but the Dutch Book Argument for Reflection fails. The question of whether we have a Dutch Book Argument for Conditionalization is left open.
Not as Different as We Want to Be: Attitudinally Consistent Trait Desirability Leads to Exaggerated Associations Between Personality and Sociopolitical Attitudes
Authors: Ludeke Steven , Tagar Michal Reifen , DeYoung Colin G.
Published: May 2014

Research connecting sociopolitical attitudes to personality typically relies exclusively on self‐report measures of personality. A recently discovered mechanism of bias in self‐reports highlights a particular challenge for this approach. Specifically, individuals tend to report exaggerated levels of a trait to the extent that they view that trait as desirable. In a community sample of 443 participants, differences in sociopolitical attitudes were associated with differences in the extent to which individuals provided biased self‐reports for a given trait (relative to trait levels indicated by peer‐report or an objective measure) as well as differences in views of the desirability of that trait. Further, the tendency to misrepresent traits in a manner consistent with one's sociopolitical attitudes was mediated by differences in views of trait desirability. Thus, although meaningful personality differences exist among those with differing sociopolitical attitudes, those differences may not be as large as people with opposing sociopolitical attitudes might like them to be.
New Avenues for the Study of Agenda Setting
Authors: Eissler Rebecca , Russell Annelise , Jones Bryan D.
Published: May 2014

Existing literature on the agenda‐setting process is grounded and well cited in studies of U.S. national institutions, but emerging scholarship has taken the fundamental principles of agenda setting—attention, information, and learning—and has extended their applicability to understudied participants and institutions. This essay highlights three areas of study that have undergone particular growth during the last few years and best represent the trend of applying the well understood dynamics of agenda setting to a broader swath of participants in the policy process. We first examine how scholars have focused on agenda setting within U.S. state and local governments and the way these institutions balance their agenda‐setting needs internally, while still trying to be heard within a federal system. Second, we highlight policy scholars' contributions to create better definitions and measures of the relationship between the media and policy process. Finally, we explore the contributions to the broader agenda‐setting literature made by scholars examining non‐U.S. institutions. These three categories are but a part of the growing trend in the subfield to expand the scope of agenda‐setting research.
Theories of the Policy Process: Contemporary Scholarship and Future Directions
Authors: Petridou Evangelia
Published: May 2014

The object of policy research is the understanding of the interaction among the machinery of the state, political actors, and the public. To facilitate this understanding, a number of complementary theories have developed in the course of more than two decades. This article reviews recent scholarship on the established theories of the policy process, mostly published in 2011 and 2012. Additionally, scholarship extending these theories is identified and new theories of policy process are discussed. This review finds that the established theories have generated substantive scholarship during the period under review and have also been the springboard for much of the recent thinking in policy research.
Leader personality and 360‐degree assessments of leader behavior
Authors: Bergman David , Lornudd Caroline , Sjöberg Lennart , Von Thiele Schwarz Ulrica
Published: May 2014

To investigate the relationship between personality and multi‐source feedback, we assessed 190 health care managers by applying the Understanding Personal Potential personality test, which provides comprehensive measurement of the Big Five dimensions and eight narrower personality traits. Managers' leadership behaviors were assessed by colleagues, supervisors, a random sample of each manager's subordinates as well as the managers themselves using a 360‐degree change, production, employee (CPE) instrument. Hierarchical multivariate regression analysis showed that the Big Five variables were significantly related to the Managers' leadership behavior in all CPE dimensions. Also, addition of narrow personality variables to the Big Five increased explained variance in leadership behavior. This study is the first of its kind to include the full range of viewpoints in a 360‐degree instrument, along with a large number of subordinate assessments. We found that both the strength of the relationship between personality and behavior and the configuration of different predictors varied depending on who did the rating and what leadership orientation was investigated, and this observation merits further investigation.
Update of the HLA class I eplet database in the website based registry of antibody‐defined HLA epitopes
Authors: Duquesnoy R. J.
Published: May 2014

Eplets are small configurations of polymorphic amino acid residues on human leukocyte antigen (HLA) molecules and are considered as essential components of HLA epitopes recognized by antibodies. This report describes a new design of the eplet repertoire in HLA‐ABC alleles used in Luminex kits for antibody testing. There were three steps (1): identify all combinations of polymorphic residues with HLA molecular modeling within a 3‐Å radius, (2) determine polymorphic residue compositions of 3 Å patches from amino acid sequences of HLA alleles in Luminex panels and (3) annotate eplets from one or more patches present on one allele or shared by the same group of alleles. There are now 270 HLA‐ABC eplets in the Registry, of which 219 are in antibody‐accessible positions on the molecular surface and 51 are defined solely by residue polymorphisms located below the molecular surface. Each eplet has a list of Luminex and non‐Luminex alleles for which mismatch acceptability can be determined.
DKWSLLL, a Versatile DXXXLL‐Type Signal with Distinct Roles in the Cu+‐Regulated Trafficking of ATP7B
Authors: Lalioti Vasiliki , Hernandez‐Tiedra Sonia , Sandoval Ignacio V.
Published: May 2014

In the liver, the P‐type ATPase and membrane pump ATP7B plays a crucial role in Cu+ donation to cuproenzymes and in the elimination of excess Cu+. ATP7B is endowed with a COOH‐cytoplasmic (DE)XXXLL‐type traffic signal. We find that accessory (Lys −3, Trp −2, Ser −1 and Leu +2) and canonical (D −4, Leu 0 and Leu +1) residues confer the DKWSLLL signal with the versatility required for the Cu+‐regulated cycling of ATP7B between the trans‐Golgi network (TGN) and the plasma membrane (PM). The separate mutation of these residues caused a disruption of the signal, resulting in different ATP7B distribution phenotypes. These phenotypes indicate the key roles of specific residues at separate steps of ATP7B trafficking, including sorting at the TGN, transport from the TGN to the PM and its endocytosis, and recycling to the TGN and PM. The distinct roles of ATP7B in the TGN and PM and the variety of phenotypes caused by the mutation of the canonical and accessory residues of the DKWSLLL signal can explain the separate or joined presentation of Wilson's cuprotoxicosis and the dysfunction of the cuproenzymes that accept Cu+ at the TGN.
Prophylactic platelet transfusions in patients with blood malignancies: cost analysis of a randomized trial
Authors: Campbell Helen E. , Estcourt Lise J. , Stokes Elizabeth A. , Llewelyn Charlotte A. , Murphy Michael F. , Wood Erica M. , Stanworth Simon J. ,   TOPPS Study Investigators
Published: May 2014

Background

This cost analysis uses data from a randomized trial comparing a no prophylaxis versus prophylactic platelet (PLT) transfusion policy (counts <10 × 109/L) in adult patients with hematologic malignancies. Results are presented for all patients and separately for autologous hematopoietic stem cell transplantation (HSCT) (autoHSCT) and chemotherapy/allogeneic HSCT (chemo/alloHSCT) patients.

Study Design and Methods

Data were collected to 30 days on PLT and red blood cell (RBC) transfusions, major bleeds, serious adverse events, critical care, and hematology ward stay. Data were costed using 2011 to 2012 UK unit costs and converted into US$. Sensitivity analyses were performed on uncertain cost variables.

Results

Across the whole trial no prophylaxis saved costs compared to prophylaxis: −$1760 per patient (95% confidence interval [CI], −$3250 to −$249; p < 0.05). For autoHSCT patients there was no cost difference between arms: −$110 per patient (95% CI, −$1648 to $1565; p = 0.89). For chemo/alloHSCT patients no prophylaxis cost significantly less than prophylaxis: −$5686 per patient (95% CI, −$8580 to −$2853; p < 0.01). The cost impact of no prophylaxis differed significantly between subgroups. Sensitivity analyses varying daily treatment costs and ward stay for chemo/alloHSCT patients reduced cost differences to −$941 per patient (p = 0.21) across the whole trial and −$2927 per patient (p < 0.05) in chemo/alloHSCT subgroup.

Conclusions

It is unclear whether a no‐prophylaxis policy saves costs overall. In chemo/alloHSCT patients cost savings are apparent but their magnitude is sensitive to a number of variables and must be considered alongside clinical data showing increased bleeding rates. In autoHSCT patients savings generated through lower PLT use in no‐prophylaxis arm were offset by cost increases elsewhere, for example, additional RBC transfusions. Cost‐effectiveness analyses of alternative PLT transfusion policies simultaneously considering costs and patient‐reported outcomes are warranted.
Primary autoimmune neutropenia in adults: case report and review of the literature
Authors: Mariotti Jacopo , Caberlon Sabrina , Bertinato Elena , Podda Gianmarco , Pugliano Maria Teresa , Cattaneo Marco
Published: May 2014

Background

Primary autoimmune neutropenia (AIN) is a rare and often unrecognized disorder in adults.

Study Design and Methods

We report the case of a patient referred to our institution for weight loss and severe chronic neutropenia with a negative personal history for severe recurrent infections.

Results

The patient was diagnosed with a lung infiltrate, and a bronchoalveolar lavage was positive for Pseudomonas aeruginosa. Antibiotic therapy was performed with resolution of infection, but persistence of neutropenia. Several investigations excluded the most common causes of neutropenia and a marrow trephine showed a maturation arrest of the myeloid lineage. Treatment with granulocyte–colony‐stimulating factor (G‐CSF) caused a transient increase in neutrophil counts. Based on the mild clinical history and the short‐lived increase in neutrophil count after G‐CSF, primary AIN was suspected. Intravenous immunoglobulins induced a short‐lived increase in neutrophil count; primary AIN was confirmed about 5 months after discharge by direct and indirect granulocyte immunofluorescence tests. The patient was discharged and no further therapy was required for persistent severe neutropenia in the absence of recurrent infections.

Conclusion

Primary AIN should be considered early in the diagnostic process of isolated neutropenia, to avoid expensive and time‐consuming unnecessary diagnostic procedures.
Transverse Demagnetization Dynamics of a Unitary Fermi Gas
Authors: Bardon A. B. , Beattie S. , Luciuk C. , Cairncross W. , Fine D. , Cheng N. S. , Edge G. J. A. , Taylor E. , Zhang S. , Trotzky S. , Thywissen J. H.
Published: May 2014

Untwisting the Spin Spiral

Ultracold Fermi gases in the so-called unitary regime—where the diverging interactions between atoms make their thermodynamics universal—are an excellent test bed for an array of strongly interacting matter systems. The transport characteristics in this regime are particularly intriguing, and a discrepancy between two- and three-dimensional transport coefficients has been observed.

Bardon
et al.

(p.
722
) studied the demagnetization dynamics of a three-dimensional Fermi gas. The gas was initially polarized along a single direction and was noninteracting. An applied magnetic field gradient then caused a spin spiral to form; as the gas relaxed from this state, the authors extracted the diffusion coefficient and observed the buildup of interactions between the atoms.
Neurosensory Perception of Environmental Cues Modulates Sperm Motility Critical for Fertilization
Authors: McKnight Katherine , Hoang Hieu D. , Prasain Jeevan K. , Brown Naoko , Vibbert Jack , Hollister Kyle A. , Moore Ray , Ragains Justin R. , Reese Jeff , Miller Michael A.
Published: May 2014

Scents and Sperm

Once sperm enter the female reproductive tract, they have an arduous task to find an egg at a distant, often concealed, location.

McKnight
et al.

(p.
754
) show that
Caenorhabditis elegans
make this task more or less difficult, depending on pheromones in the external environment. Pheromones perceived by female sensory neurons modulate the synthesis of ovarian prostaglandins, which provide sperm positional information. Thus, environmental cues can indirectly impact sperm function even when the sperm themselves are not directly exposed.
A Call for Deep-Ocean Stewardship
Authors: Mengerink Kathryn J. , Van Dover Cindy L. , Ardron Jeff , Baker Maria , Escobar-Briones Elva , Gjerde Kristina , Koslow J. Anthony , Ramirez-Llodra Eva , Lara-Lopez Ana , Squires Dale , Sutton Tracey , Sweetman Andrew K. , Levin Lisa A.
Published: May 2014

The precautionary approach and collaborative governance must balance deep-ocean use and protection.
Late Pleistocene Human Skeleton and mtDNA Link Paleoamericans and Modern Native Americans
Authors: Chatters James C. , Kennett Douglas J. , Asmerom Yemane , Kemp Brian M. , Polyak Victor , Blank Alberto Nava , Beddows Patricia A. , Reinhardt Eduard , Arroyo-Cabrales Joaquin , Bolnick Deborah A. , Malhi Ripan S. , Culleton Brendan J. , Erreguerena Pilar Luna , Rissolo Dominique , Morell-Hart Shanti , Stafford Thomas W.
Published: May 2014

American Beauty

Modern Native American ancestry traces back to an East Asian migration across Beringia. However, some Native American skeletons from the late Pleistocene show phenotypic characteristics more similar to other, more geographically distant, human populations.

Chatters
et al.

(p.
750
) describe a skeleton with a Paleoamerican phenotype from the eastern Yucatan, dating to approximately 12 to 13 thousand years ago, with a relatively common extant Native American mitochondrial DNA haplotype. The Paleoamerican phenotype may thus have evolved independently among Native American populations.
Cas9 Targeting and the CRISPR Revolution
Authors: Barrangou Rodolphe
Published: May 2014

Uncovering how an RNA-protein molecular scalpel targets DNA will advance our ability to engineer genomes.
The Art of Longevity

The Oldest Living Things in the World
by Rachel Sussman

University of Chicago Press, Chicago, 2014. 304 pp. $45, £31.50. ISBN 9780226057507.
Authors: Farmer Jared
Published: May 2014

Photographer Sussman presents portraits of really long-lived organisms from around the world.
How Great a Separation?
The Gap
The Science of What Separates Us from Other Animals

By Thomas Suddendorf

Basic Books, New York, 2013. 366 pp. $29.99, C$34.50. ISBN 9780465030149.
Authors: Sim Bryan
Published: May 2014

Tapping recent findings from cognitive science and ethology, Suddendorf searches for what sets humans apart from other animals.
Toward Recyclable Thermosets
Authors: Long Timothy E.
Published: May 2014

Advances in synthesis are leading to thermoset plastics that can be converted to the starting monomers.

[Also see Report by

García
et al.

]
Needed: More Females in Animal and Cell Studies
Authors: Couzin-Frankel Jennifer
Published: May 2014

To correct bias, the National Institutes of Health will ask researchers to use more female animals and cells in research.
Bones From a Watery 'Black Hole' Confirm First American Origins
Authors: Balter Michael
Published: May 2014

The bones of a teenage girl who lived as early as 13,000 years ago, found in a deep underwater cave in Mexico, confirm other recent evidence that today's Native Americans have deep roots in the Americas.
No Stopping the Collapse of West Antarctic Ice Sheet
Authors: Sumner Thomas
Published: May 2014

A computer model and radar data show that one melting glacier the size of Uruguay could wreak havoc at the bottom of the world—and far beyond.
The Hunt for Missing Genes
Authors: Kaiser Jocelyn
Published: May 2014

Identifying healthy human "knockouts"—people completely lacking a specific gene—may suggest new biomedical treatments.