bluuebunny/crossref_metadata_2025 huggingface dataset:
Infant outcomes after exposure to Tdap vaccine in pregnancy: an observational study
Authors: Walls Tony , Graham Patricia , Petousis-Harris Helen , Hill Linda , Austin Nicola
Published: January 2016

Objective

Pertussis vaccination during pregnancy has recently been recommended in both the USA and UK to prevent pertussis infection in infants. While there are no apparent safety concerns about the administration of Tdap vaccine during pregnancy, there is only limited safety data available. We aimed to closely monitor infants exposed to Tdap during pregnancy to look for any adverse outcomes that may be attributable to the vaccine.

Design

This was a prospective observational study, collecting information to evaluate the safety of Tdap vaccine for infants exposed during pregnancy. Infants were followed for between 6 and 12 months after birth, with 84% completing 12 months of follow-up. Information was obtained from objective sources including routine health visits and vaccination records wherever possible, as well as frequent parental reports.

Setting

The Canterbury region of New Zealand.

Patients

A cohort of 403 infants whose mothers had received Tdap vaccine.

Main outcome measures

Gestational age at birth, growth parameters, congenital anomalies, immunisation status and timeliness of immunisation, development of pertussis infection.

Results

There were no significant differences in birth weight, gestational age at birth, congenital anomalies or infant growth as compared with baseline population data. Infants of mothers who had received the vaccine were more likely to receive their vaccinations on time during infancy. No cases of pertussis occurred in this cohort despite high rates of disease in the community. We have not found any adverse events attributable to vaccine exposure.

Conclusions

These data add to the growing pool of evidence that the administration of Tdap vaccine during pregnancy is an appropriate strategy for reducing the burden of pertussis in infants.

Clinical trial registration

Australia New Zealand Clinical Trials Registry ACTRN12613001045707.
Non-response in a cross-sectional study of respiratory health in Norway
Authors: Abrahamsen Regine , Svendsen Martin Veel , Henneberger Paul K , Gundersen Gølin Finckenhagen , Torén Kjell , Kongerud Johny , Fell Anne Kristin Møller
Published: January 2016

Objectives

Declining participation in epidemiological studies has been reported in recent decades and may lead to biased prevalence estimates and selection bias. The aim of the study was to identify possible causes and effects of non-response in a population-based study of respiratory health in Norway.

Design

The Telemark study is a longitudinal study that began with a cross-sectional survey in 2013.

Setting

In 2013, a random sample of 50 000 inhabitants aged 16–50 years, living in Telemark county, received a validated postal questionnaire. The response rate was 33%. In this study, a random sample of 700 non-responders was contacted first by telephone and then by mail.

Outcome measures

Response rates, prevalence and OR of asthma and respiratory symptoms based on exposure to vapours, gas, dust or fumes (VGDF) and smoking. Causes of non-response.

Results

A total of 260 non-responders (37%) participated. Non-response was associated with younger age, male sex, living in a rural area and past smoking. The prevalence was similar for responders and non-responders for physician-diagnosed asthma and several respiratory symptoms. The prevalence of chronic cough and use of asthma medication was overestimated in the Telemark study, and adjusted prevalence estimates were 17.4% and 5%, respectively. Current smoking was identified as a risk factor for respiratory symptoms among responders and non-responders, while occupational VGDF exposure was a risk factor only among responders. The Breslow-Day test detected heterogeneity between productive cough and occupational VGDF exposure among responders.

Conclusions

The Telemark study provided valid estimates for physician-diagnosed asthma and several respiratory symptoms, while it was necessary to adjust prevalence estimates for chronic cough and use of asthma medication. Reminder letters had little effect on risk factor associations. Selection bias should be considered in future investigations of the relationship between respiratory outcomes and exposures.
Sex differences in body anthropometry and composition in individuals with and without diabetes in the UK Biobank
Authors: Peters Sanne A E , Huxley Rachel R , Woodward Mark
Published: January 2016

Objective

Type I and II diabetes are associated with a greater relative risk of cardiovascular diseases (CVD) in women than in men. Sex differences in adiposity storage may explain these findings.

Methods

A cross-sectional study of 480 813 participants from the UK Biobank without history of CVD was conducted to assess whether the difference in body size in people with and without diabetes was greater in women than in men. Age-adjusted linear regression analyses were used to obtain the mean difference in women minus men in the difference in body size measures, separately for type I and II diabetes.

Results

Body size was higher in individuals with diabetes than in individuals without diabetes, particularly in type II diabetes. Differences in body size between individuals with and without type II diabetes were more extreme in women than in men; compared to those without type II diabetes, body mass index and waist circumference were 1.94 (95% CI 1.82 to 2.07) and 4.84 (4.53 to 5.16) higher in women than in men, respectively. In type I diabetes, body size differed to a similar extent between those with and without diabetes in women as in men. This pattern was observed across all prespecified subgroups.

Conclusions

Differences in body size associated with diabetes were significantly greater in women than in men in type II diabetes but not in type I diabetes. Prospective studies can determine whether sex differences in body size associated with diabetes underpin some of the excess risk for CVD in women with type II diabetes.
Microbiota-induced obesity requires farnesoid X receptor
Authors: Parséus Ava , Sommer Nina , Sommer Felix , Caesar Robert , Molinaro Antonio , Ståhlman Marcus , Greiner Thomas U , Perkins Rosie , Bäckhed Fredrik
Published: January 2016

Objective

The gut microbiota has been implicated as an environmental factor that modulates obesity, and recent evidence suggests that microbiota-mediated changes in bile acid profiles and signalling through the bile acid nuclear receptor farnesoid X receptor (FXR) contribute to impaired host metabolism. Here we investigated if the gut microbiota modulates obesity and associated phenotypes through FXR.

Design

We fed germ-free (GF) and conventionally raised (CONV-R) wild-type andFxr−/−mice a high-fat diet (HFD) for 10 weeks. We monitored weight gain and glucose metabolism and analysed the gut microbiota and bile acid composition, beta-cell mass, accumulation of macrophages in adipose tissue, liver steatosis, and expression of target genes in adipose tissue and liver. We also transferred the microbiota of wild-type andFxr-deficient mice to GF wild-type mice.

Results

The gut microbiota promoted weight gain and hepatic steatosis in an FXR-dependent manner, and the bile acid profiles and composition of faecal microbiota differed betweenFxr−/−and wild-type mice. The obese phenotype in colonised wild-type mice was associated with increased beta-cell mass, increased adipose inflammation, increased steatosis and expression of genes involved in lipid uptake. By transferring the caecal microbiota from HFD-fedFxr−/−and wild-type mice into GF mice, we showed that the obesity phenotype was transferable.

Conclusions

Our results indicate that the gut microbiota promotes diet-induced obesity and associated phenotypes through FXR, and that FXR may contribute to increased adiposity by altering the microbiota composition.
Clitolyophyllum akcaabatense gen. nov., sp. nov. (Agaricales, Tricholomatineae); a new fan-shaped clitocyboid agaric from Turkey
Authors: Sesli Ertugrul , Vizzini Alfredo , Ercole Enrico , Contu Marco
Published: January 2016

Clitolyophyllum akcaabatense gen. nov., sp. nov., is described based on both morphological and molecular data from Akcaabat, Trabzon, Turkey. Its characterizing features are a fan-shaped pileus, an eccentric and fibrillose stipe, 2–4 spored basidia, smooth, ellipsoid, and inamyloid white basidiospores, and growth on the bark of Picea orientalis (L.) Link. Phylogeny based on multigene molecular analysis (nrITS, nrLSU, rpb2 datasets) of the Tricholomatoid clade is provided. Photographs of fresh basidiomata and of the main micromorphological features are included.
Structural Similitude for Prestressed Vibration and Buckling of Eccentrically Stiffened Circular Cylindrical Panels and Shells by Energy Approach
Authors: Yu Wei , Li Zheng Liang
Published: January 2016

The objective of this study is to develop and validate similitude requirements and scaling laws for studying the real characteristics of structures easily and economically, especially for large structures. The generalized similitude requirements and the scaling law of orthogonally stiffened cylindrical panels and shells for buckling and free vibration are derived by applying the similitude transformation to the total energy of the structural system directly. In practice, due to either the difficulty of satisfying all of the similitude requirements simultaneously or to save experimental cost and time, distorted models with partial similarity are necessarily employed and approximate scaling laws are proposed. The partial similitude is mainly investigated first by using specific formulas of stiffness parameters and corresponding scaling laws are given. Also discussed herein are particular models with relaxations in the material properties of stiffeners, the materials of both the skin and the stiffeners and the material properties and geometry. The obtained results indicate that the distorted models are able to accurately predict the behavior of the prototype.
F-center mechanism of long-term relaxation in lead zirconate-titanate-based piezoelectric ceramics. 1. After-heating relaxation
Authors: Ishchuk V. M. , Kuzenko D. V.
Published: January 2016

Results of experimental investigation of relaxation aging processes in Pb(Zr,Ti)O3-based solid solutions after termination of external actions are presented. Heating, DC electric field, uniaxial pressure and some of their combinations were taken as external actions. In the main part of the present paper, we use heating as external action. The said processes are long-time one and are described by the logarithmic function of time.

Reversible and nonreversible relaxation processes take place depending on the action intensity. The relaxation rate depends on the action intensity also, and the said dependence has nonlinear and nonmonotonic form if external action leads to domain disordering.

The oxygen vacancies-based model for description of the long-time relaxation processes is suggested. The model takes into account oxygen vacancies on the sample’s surface ends, their conversion into [Formula: see text]- and [Formula: see text]-centers under external effects (due to the liberation of the pyroelectric charge) and subsequent relaxation of these centers into the simple oxygen vacancies after the actions termination. The initial sample’s state is electroneutrality one. F-center formation leads to the violation of the original sample’s electroneutrality, and generates DC electric field into the sample. Relaxation of F-centers is accompanied by decreasing of electric field, induced by them, and dielectric constant relaxation as consequent effect.
The deep-water trilobite association of the Silurian Coldwell Siltstone Formation of northern England and its wider significance
Authors: Storey Andrew J. , Thomas Alan T. , Owens Robert M.
Published: January 2016

The upper Wenlock Coldwell Siltstone Formation of Cumbria and North Yorkshire, which accumulated in the Lake District Basin, contains a deep-water, trilobite-dominated fauna that is documented in detail here. The trilobites of the formation are revised on the basis of new material and existing museum collections.
Delops nobilis marri
Rickards and
Struveria howgillensis
Rickards are considered conspecific with
Dalmanites mobergi
Hede and
Dalmanites simricus
Hede respectively from the Swedish Colonus Shale. Based on the type species,
Delops
Rickards is recognized as a senior synonym of
Lygdozoon
Holloway. A new genus,
Rickardsia
, is erected to accommodate
Dalmanites mobergi
Hede,
Delops nobilis
(Thomas), and
Delops dermolac
Šnajdr, which share characters that differentiate them from the type and other species of
Delops
. The fauna referred to previously as the
Delops–Miraspis
Assemblage is renamed the
Rickardsia-Miraspis
Association, and redefined to take account of new data. The trilobites
Decoroproetus
sp. nov.? and a cheirurid, and the brachiopods
Leangella segmentum
(Lindström) and
Protozyga
? sp., are recognized in the fauna for the first time. Comparable trilobite and brachiopod assemblages occur at the same stratigraphical level in the Welsh Basin, southern Sweden, Poland and the Czech Republic, and together with that of the Coldwell Siltstone Formation, are considered to have invaded these areas during a eustatic lowstand during the late Wenlock Epoch. Comparison with other assemblages suggests that all occupied depths that were not less than the shallowest limits of benthic assemblage (BA) 5.
Parallel Expanded Event Simulation of Tightly Coupled Systems
Authors: Kunz Georg , Stoffers Mirko , Landsiedel Olaf , Wehrle Klaus , Gross James
Published: January 2016

The technical evolution of wireless communication technology and the need for accurately modeling these increasingly complex systems causes a steady growth in the complexity of simulation models. At the same time, multi-core systems have become the de facto standard hardware platform. Unfortunately, wireless systems pose a particular challenge for parallel execution due to a
tight coupling
of network entities in space and time. Moreover, model developers are often domain experts with no in-depth understanding of parallel and distributed simulation. In combination, both aspects severely limit the performance and the efficiency of existing parallelization techniques. We address these challenges by presenting
parallel expanded event simulation
, a novel modeling paradigm that extends discrete events with durations that span a period in simulated time. The resulting
expanded events
form the basis for a conservative synchronization scheme that considers overlapping expanded events eligible for parallel processing. We then put these concepts into practice by implementing H
orizon
, a parallel expanded event simulation framework specifically tailored to the characteristics of multi-core systems. Our evaluation shows that H
orizon
achieves considerable speedups in synthetic as well as real-world simulation models and considerably outperforms the current state-of-the-art in distributed simulation.
RFVP
Authors: Yazdanbakhsh Amir , Pekhimenko Gennady , Thwaites Bradley , Esmaeilzadeh Hadi , Mutlu Onur , Mowry Todd C.
Published: January 2016

This article aims to tackle two fundamental memory bottlenecks: limited off-chip bandwidth (bandwidth wall) and long access latency (memory wall). To achieve this goal, our approach exploits the inherent error resilience of a wide range of applications. We introduce an approximation technique, called Rollback-Free Value Prediction (RFVP). When certain safe-to-approximate load operations miss in the cache, RFVP predicts the requested values. However, RFVP does not check for or recover from load-value mispredictions, hence, avoiding the high cost of pipeline flushes and re-executions. RFVP mitigates the memory wall by enabling the execution to continue without stalling for long-latency memory accesses. To mitigate the bandwidth wall, RFVP drops a fraction of load requests that miss in the cache after predicting their values. Dropping requests reduces memory bandwidth contention by removing them from the system. The drop rate is a knob to control the trade-off between performance/energy efficiency and output quality. Our extensive evaluations show that RFVP, when used in GPUs, yields significant performance improvement and energy reduction for a wide range of quality-loss levels. We also evaluate RFVP’s latency benefits for a single core CPU. The results show performance improvement and energy reduction for a wide variety of applications with less than 1% loss in quality.
Juries
Authors: Vallejos Elvira Perez , Koene Ansgar , Carter Chris James , Statache Ramona , Rodden Tom , McAuley Derek , Cano Monica , Adolphs Svenja , O'Malley Claire , Pothong Kruakae , Coleman Stephen
Published: January 2016

A quick journey through prevention science (e.g., substance misuse prevention) and a comparison between online and offline risks, harm, and vulnerability in children suggests that new approaches and interventions are needed to promote Internet safety and minimise the new sources of risk associated with accessing the Internet. In this paper we present a new methodological approach to promote digital literacy and positively influence the way in which young people interact with the Internet:
iRights Youth Juries.
These juries offer a solution for the challenge of how to engage children and young people in activities that, rather than simply promoting Internet safety, aim to provide the knowledge and the confidence required for developing healthy digital citizens. This approach thus begins to move beyond the notion of the Internet as a simple cause of social change, approaching it instead as an opportunity to engage knowledgeably with the digital world and maximise citizenship.
Privacy concerns arising from internet service personalization filters
Authors: Koene Ansgar , Perez Elvira , Carter Christopher J. , Statache Ramona , Adolphs Svenja , O'Malley Claire , Rodden Tom , McAuley Derek
Published: January 2016

Personal service customization, or personalization, is one of the core tools that are being used by on-line providers of information services such as search engines, social media, news sites and product recommender systems to optimize the individual user experience in hopes of attracting and keeping users. In this paper we will examine the user profile models that are used to achieve this information personalization. From a citizen centric perspective, our concerns focus on the degree of privacy intrusion that is implicitly required to determine the parameter settings of the information filter profile and the ethical implications of the personal behavior predicting properties of the user model itself.
Understanding academic attitudes towards the ethical challenges posed by social media research
Authors: Carter Chris James , Koene Ansgar , Perez Elvira , Statache Ramona , Adolphs Svenja , O'Malley Claire , Rodden Tom , McAuley Derek
Published: January 2016

In this paper, we outline an online survey-based study seeking to understand academic attitudes towards social media research ethics (SMRE). As the exploratory phase of a wider research project, findings are discussed in relation to the responses of 30 participants, spanning multiple faculties and locations at one international university. The paper presents an empirical measure of attitudes towards social media research ethics, reflecting core issues outlined throughout the nascent Internet-mediated research (IMR) literature, in addition to survey questions relating to familiarity with SMRE guidance, and experience of reviewing SMRE proposals from students and/or as part of the university's research ethics committees (RECs). Findings indicate notable variance in academic attitudes towards the ethical challenges of social media research, reflecting the complexity of decision-making within this context and further emphasising the need to understand influencing factors. Future directions are discussed in relation to the tentative findings presented by the current study.
The asymmetrical 'relationship'
Authors: Richardson Kathleen
Published: January 2016

In this paper I examine the model of asymmetrical 'relationship' that is imported from prostitution-client sex work to human-robot sex. Specifically, I address the arguments proposed by David Levy who identifies prostitution/sex work as a model that can be imported into human-robot sex relations. I draw on literature in anthropology that deals with the anthropomorphism of nonhuman things and the way that
things
reflect back to us gendered notions of sexuality. In the final part of the paper I propose that prostitution is no ordinary activity and relies on the ability to use a person as a thing and this is why parallels between sex robots and prostitution are so frequently found by their advocates.
Who is to change?
Authors: Winkel Thomas Dyrmann , Jensen Thessa , Poulsen Søren Bolvig
Published: January 2016

This paper discusses nudging and provocative communication as possible approaches to designing behavioural change concerning minimisation of waste within the framework of Løgstrup's ontological ethics. Waste management companies are confronted with ethical concerns as their course of action consequently affects their relationship with the citizens whose waste they manage. Waste management companies might be experts within their field, but they are challenged when entering new contexts and must therefore redefine or reframe their role in society. This became evident during an action research project as an ethical challenge was identified through a strategic workshop facilitated for AVV in relation to the Nulskrald project. The main focus of Nulskrald is citizen empowerment as well as organisational learning and responsibility. Through Løgstrup's ontological ethics the ethical demand, as it is posed by 'the other person' towards the 'I', will show concerns and possibilities for engaging citizens, while at the same time resulting in organisational development. Therefore, the research question is: what ethical issues and organisational implications exist concerning the use of nudging and provocative communication, respectively?
Structure-Driven Developments of 26S Proteasome Inhibitors
Authors: Śledź Paweł , Baumeister Wolfgang
Published: January 2016

The 26S proteasome is a 2.5-MDa complex, and it operates at the executive end of the ubiquitin-proteasome pathway. It is a proven target for therapeutic agents for the treatment of some cancers and autoimmune diseases, and moreover, it has potential as a target of antibacterial agents. Most inhibitors, including all molecules approved for clinical use, target the 20S proteolytic core complex; its structure was determined two decades ago. Hitherto, efforts to develop inhibitors targeting the 19S regulatory particle subunits have been less successful. This is, in part, because the molecular architecture of this subcomplex has been, until recently, poorly understood, and high-resolution structures have been available only for a few subunits. In this review, we describe, from a structural perspective, the development of inhibitory molecules that target both the 20S and 19S subunits of the proteasome. We highlight the recent progress achieved in structure-based drug-discovery approaches, and we discuss the prospects for further improvement.
Therapeutic Potential of T Cell Chimeric Antigen Receptors (CARs) in Cancer Treatment: Counteracting Off-Tumor Toxicities for Safe CAR T Cell Therapy
Authors: Gross Gideon , Eshhar Zelig
Published: January 2016

A chimeric antigen receptor (CAR) is a recombinant fusion protein combining an antibody-derived targeting fragment with signaling domains capable of activating T cells. Recent early-phase clinical trials have demonstrated the remarkable ability of CAR-modified T cells to eliminate B cell malignancies. This review describes the choice of target antigens and CAR manipulations to maximize antitumor specificity. Benefits and current limitations of CAR-modified T cells are discussed, with a special focus on the distribution of tumor antigens on normal tissues and the risk of on-target, off-tumor toxicities in the clinical setting. We present current methodologies for pre-evaluating these risks and review the strategies for counteracting potential off-tumor effects. Successful implementation of these approaches will improve the safety and efficacy of CAR T cell therapy and extend the range of cancer patients who may be treated.
Endothelial mitochondria regulate the intracellular Ca2+ response to fluid shear stress
Authors: Scheitlin Christopher G. , Julian Justin A. , Shanmughapriya Santhanam , Madesh Muniswamy , Tsoukias Nikolaos M. , Alevriadou B. Rita
Published: January 2016

Shear stress is known to stimulate an intracellular free calcium concentration ([Ca2+]i) response in vascular endothelial cells (ECs). [Ca2+]i is a key second messenger for signaling that leads to vasodilation and EC survival. Although it is accepted that the shear-induced [Ca2+]i response is, in part, due to Ca2+ release from the endoplasmic reticulum (ER), the role of mitochondria (second largest Ca2+ store) is unknown. We hypothesized that the mitochondria play a role in regulating [Ca2+]i in sheared ECs. Cultured ECs, loaded with a Ca2+-sensitive fluorophore, were exposed to physiological levels of shear stress. Shear stress elicited [Ca2+]i transients in a percentage of cells with a fraction of them displaying oscillations. Peak magnitudes, percentage of oscillating ECs, and oscillation frequencies depended on the shear level. [Ca2+]i transients/oscillations were present when experiments were conducted in Ca2+-free solution (plus lanthanum) but absent when ECs were treated with a phospholipase C inhibitor, suggesting that the ER inositol 1,4,5-trisphosphate receptor is responsible for the [Ca2+]i response. Either a mitochondrial uncoupler or an electron transport chain inhibitor, but not a mitochondrial ATP synthase inhibitor, prevented the occurrence of transients and especially inhibited the oscillations. Knockdown of the mitochondrial Ca2+ uniporter also inhibited the shear-induced [Ca2+]i transients/oscillations compared with controls. Hence, EC mitochondria, through Ca2+ uptake/release, regulate the temporal profile of shear-induced ER Ca2+ release. [Ca2+]i oscillation frequencies detected were within the range for activation of mechanoresponsive kinases and transcription factors, suggesting that dysfunctional EC mitochondria may contribute to cardiovascular disease by deregulating the shear-induced [Ca2+]i response.
Orai1 and STIM1 in ER/PM junctions: roles in pancreatic cell function and dysfunction
Authors: Son Aran , Park Seonghee , Shin Dong Min , Muallem Shmuel
Published: January 2016

Membrane contact sites (MCS) are critical junctions that form between the endoplasmic reticulum (ER) and membranes of various organelles, including the plasma membrane (PM). Signaling complexes, including mediators of Ca2+ signaling, are assembled within MCS, such as the ER/PM junction. This is most evident in polarized epithelial cells, such as pancreatic cells. Core Ca2+ signaling proteins cluster at the apical pole, the site of inositol 1,4,5-trisphosphate-mediated Ca2+ release and Orai1/transient receptor potential canonical-mediated store-dependent Ca2+ entry. Recent advances have characterized the proteins that tether the membranes at MCS and the role of these proteins in modulating physiological and pathological intracellular signaling. This review discusses recent advances in the characterization of Ca2+ signaling at ER/PM junctions and the relation of these junctions to physiological and pathological Ca2+ signaling in pancreatic acini.
Calorie restriction leads to greater Akt2 activity and glucose uptake by insulin-stimulated skeletal muscle from old rats
Authors: Wang Haiyan , Arias Edward B. , Cartee Gregory D.
Published: January 2016

Skeletal muscle insulin resistance is associated with many common age-related diseases, but moderate calorie restriction (CR) can substantially elevate glucose uptake by insulin-stimulated skeletal muscle from both young and old rats. The current study evaluated the isolated epitrochlearis muscle from ∼24.5-mo-old rats that were either fed ad libitum (AL) or subjected to CR (consuming ∼65% of ad libitum, AL, intake beginning at ∼22.5 mo old). Some muscles were also incubated with MK-2206, a potent and selective Akt inhibitor. The most important results were that in isolated muscles, CR vs. AL resulted in 1) greater insulin-stimulated glucose uptake 2) that was accompanied by significantly increased insulin-mediated activation of Akt2, as indicated by greater phosphorylation on both Thr309and Ser474along with greater Akt2 activity, 3) concomitant with enhanced phosphorylation of several Akt substrates, including an Akt substrate of 160 kDa on Thr642and Ser588, filamin C on Ser2213and proline-rich Akt substrate of 40 kDa on Thr246, but not TBC1D1 on Thr596; and 4) each of the CR effects was eliminated by MK-2206. These data provide compelling new evidence linking greater Akt2 activation to the CR-induced elevation of insulin-stimulated glucose uptake by muscle from old animals.
Maintaining K+balance on the low-Na+, high-K+diet
Authors: Cornelius Ryan J. , Wang Bangchen , Wang-France Jun , Sansom Steven C.
Published: January 2016

A low-Na+, high-K+diet (LNaHK) is considered a healthier alternative to the “Western” high-Na+diet. Because the mechanism for K+secretion involves Na+reabsorptive exchange for secreted K+in the distal nephron, it is not understood how K+is eliminated with such low Na+intake. Animals on a LNaHK diet produce an alkaline load, high urinary flows, and markedly elevated plasma ANG II and aldosterone levels to maintain their K+balance. Recent studies have revealed a potential mechanism involving the actions of alkalosis, urinary flow, elevated ANG II, and aldosterone on two types of K+channels, renal outer medullary K+and large-conductance K+channels, located in principal and intercalated cells. Here, we review these recent advances.
31P magnetization transfer measurements of Pi→ATP flux in exercising human muscle
Authors: Sleigh Alison , Savage David B. , Williams Guy B. , Porter David , Carpenter T. Adrian , Brindle Kevin M. , Kemp Graham J.
Published: January 2016

Fundamental criticisms have been made over the use of 31P magnetic resonance spectroscopy (MRS) magnetization transfer estimates of inorganic phosphate (Pi)→ATP flux (VPi-ATP) in human resting skeletal muscle for assessing mitochondrial function. Although the discrepancy in the magnitude of VPi-ATP is now acknowledged, little is known about its metabolic determinants. Here we use a novel protocol to measure VPi-ATP in human exercising muscle for the first time. Steady-state VPi-ATP was measured at rest and over a range of exercise intensities and compared with suprabasal oxidative ATP synthesis rates estimated from the initial rates of postexercise phosphocreatine resynthesis (VATP). We define a surplus Pi→ATP flux as the difference between VPi-ATP and VATP. The coupled reactions catalyzed by the glycolytic enzymes GAPDH and phosphoglycerate kinase (PGK) have been shown to catalyze measurable exchange between ATP and Pi in some systems and have been suggested to be responsible for this surplus flux. Surplus VPi-ATP did not change between rest and exercise, even though the concentrations of Pi and ADP, which are substrates for GAPDH and PGK, respectively, increased as expected. However, involvement of these enzymes is suggested by correlations between absolute and surplus Pi→ATP flux, both at rest and during exercise, and the intensity of the phosphomonoester peak in the 31P NMR spectrum. This peak includes contributions from sugar phosphates in the glycolytic pathway, and changes in its intensity may indicate changes in downstream glycolytic intermediates, including 3-phosphoglycerate, which has been shown to influence the exchange between ATP and Pi catalyzed by GAPDH and PGK.
Inflammatory Cytokines and Antipsychotic-Induced Weight Gain: Review and Clinical Implications
Authors: Fonseka Trehani M. , Müller Daniel J. , Kennedy Sidney H.
Published: January 2016

Antipsychotic medications (APs), particularly second-generation APs, are associated with significant weight gain in schizophrenia patients. Recent evidence suggests that the immune system may contribute to antipsychotic-induced weight gain (AIWG) via AP-mediated alterations of cytokine levels. Antipsychotics with a high propensity for weight gain, such as clozapine and olanzapine, influence the expression of immune genes, and induce changes in serum cytokine levels to ultimately down-regulate neuroinflammation. Since inflammatory cytokines are normally involved in anorexigenic responses, reduced inflammation has been independently shown to mediate changes in feeding behaviours and other metabolic parameters, resulting in obesity. Genetic variation in pro-inflammatory cytokines is also associated with both general obesity and weight change during AP treatment, and thus, may be implicated in the pharmacogenetics of AIWG. At this time, preliminary data support a cytokine-mediated model of AIWG which may have clinical utility in developing more effective metabolic monitoring guidelines and prevention measures. However, further research is still needed to clearly elucidate the validity of this immune model. This article reviews the evidence implicating inflammatory cytokines in AIWG and its potential clinical relevance.
Diagnostic Delay of Endometriosis in the Netherlands
Authors: Staal A.H.J. , van der Zanden M. , Nap A.W.
Published: January 2016

Background/Aims: Endometriosis has a long diagnostic delay that is influenced by varying socio-economic and healthcare factors. In the Dutch situation, these factors are not yet identified. The aim of this study is to determine the length of the diagnostic delay of endometriosis in the Netherlands and to identify which variables affect this delay. Methods: A retrospective study among 139 patients diagnosed with endometriosis in a secondary care hospital with a specialized multidisciplinary endometriosis team. The diagnostic process was evaluated using a questionnaire-guided telephonic interview. Results: The median time interval from the onset of symptoms to diagnosis was 89 months or 7.4 years, divided in 7 months patient delay, 35 months general practitioner (GP) delay and 5 months gynecologist delay. Determinants for a longer diagnostic delay were young age at onset of symptoms, use of oral contraceptives or analgesics prescribed by GP, alternative diagnoses considered by the GP, and cyclic symptoms. Subfertility as presenting symptom resulted in faster diagnosis. Conclusion: This study shows that the time interval to the diagnosis of endometriosis is long and mainly consists of the period of time the woman consults her first line medical professional.
Nutrition in Pancreatic Cancer: A Review
Authors: Gärtner Simone , Krüger Janine , Aghdassi Ali A. , Steveling Antje , Simon Peter , Lerch Markus M. , Mayerle Julia
Published: January 2016

Background: Pancreatic cancer is the fourth leading cause of cancer-related mortality in both genders. More than 80% of patients suffer from significant weight loss at diagnosis and over time develop severe cachexia. Early nutritional support is therefore essential. Summary: This review evaluates the different nutritional therapies, such as enteral nutrition, parenteral nutrition and special nutritional supplements, on nutritional status, quality of life and survival. Key Message: Due to the high prevalence of malnutrition and the rapid development of anorexia-cachexia-syndrome, early nutritional intervention is crucial and supported by clinical data. Practical Implications: Enteral nutrition should be preferred over parenteral nutrition. Omega-3 fatty acids and L-carnitine are promising substances for the prevention of severe cachexia, but further randomized controlled trials are needed to establish generally accepted guidelines on nutrition in pancreatic cancer.
Feeding Challenges in Patients with Esophageal and Gastroesophageal Cancers
Authors: Reim Daniel , Friess Helmut
Published: January 2016

Background: Patients undergoing treatment for esophagogastric or esophageal cancer are exposed to a considerably high risk of malnutrition due to early obstruction of the gastrointestinal passage. Presently most of the patients undergo modern multimodal therapies which require chemoradiation or chemotherapy ahead of surgery. Therefore reconstruction of the obstructed gastrointestinal passage is considerably delayed. Surgery as the only curative option after neoadjuvant treatment is the mainstay of therapy in this setting. However, many patients are at risk for the development of postoperative complications associated with the complexity of the surgical procedure. Therefore enteral feeding as a prerequisite to avoid malnutrition represents a special therapeutic challenge. Summary: This review describes the recent literature on the incidence and influence of perioperative malnutrition on oncologic outcome, measures to determine patients at risk, possible strategies to reduce or avoid malnutrition by supportive enteral/parenteral nutrition, implementation of the enhanced recovery after surgery programs and feeding routes, but also surgical and adjuvant procedures in the curative and palliative setting for patients undergoing treatment for gastroesophageal cancers. Key Messages: Appropriate identification of patients at risk is crucial to avoid malnutrition. Early nutritional interventions during multimodal/neoadjuvant treatment may be beneficial for weight loss reduction although the evidence is not conclusive. Pouch reconstructions during surgery should be applied in order to increase quality of life and eating capacity. Reduction of postoperative complications could provide potential benefits. In palliative patients, insertion of self-expanding metal stents can reduce dysphagia and improve quality of life, but does not prolong overall survival. Further evidence is required to determine the value of the procedures and measures described in this review. Practical Implications: Nutritional risk scoring should be performed for every gastroesophageal cancer patient. Sophisticated reconstruction methods and early recovery programs should be enforced to reduce perioperative starvation periods. Self-expanding metal stents should be used for palliative patients.
Intracranial Hypertension as an Acute Complication of Aseptic Meningoencephalitis with Leptomeningeal Contrast Enhancement on FLAIR MRI
Authors: Wolf Marc E. , Eisele Philipp , Schweizer Yvonne , Alonso Angelika , Gass Achim , Hennerici Michael G. , Szabo Kristina
Published: January 2016

We report a case of a 19-year-old woman who developed intracranial hypertension as an unusual clinical complication of severe aseptic meningoencephalitis probably due to a diminished cerebrospinal fluid reabsorption capacity or leptomeningeal transudation as a consequence of blood-brain barrier dysfunction. These severe inflammatory changes were accompanied by prominent leptomeningeal contrast enhancement best visualized on fluid-attenuated inversion recovery magnetic resonance imaging. In such a prolonged course, a continuous lumbar drainage might be a temporary option to provide rapid symptom relief to the patient.
Chondrosarcoma of the Rib Mimicking Malignant Pleural Mesothelioma
Authors: Furukawa Masashi , Tao Hiroyuki , Tanaka Toshiki , Onoda Hideko , Murakami Tomoyuki , Okabe Kazunori
Published: January 2016

A 62-year-old man with a history of long-term asbestos exposure was found to have a chest wall tumor invading the sixth rib on chest computed tomography. The computed tomography also revealed multiple plaques in the pleura. Malignant pleural mesothelioma was suspected, and thoracoscopic surgery was performed. Thoracoscopy revealed that the tumor location was extrapleural. Thus, excisional biopsy was performed. The tumor was histologically diagnosed as chondrosarcoma. Additional wide resection of the chest wall, including the fifth, sixth, and seventh ribs, was performed. Chest wall reconstruction was performed with a polypropylene mesh.
Anterior Segment Scleral Fluorescein Angiography in the Evaluation of Ciliary Body Neoplasm: Two Case Reports
Authors: Marvasti Amir H. , Berry Jesse , Sibug Saber Maria E. , Kim Jonathan W. , Huang Alex S.
Published: January 2016

Introduction: Anterior segment tumors can be difficult to detect until tumor growth is substantial enough to cause local signs or symptoms. Earlier detection may result in improved outcomes, particularly the ability to option for globe-conserving therapy. Multiple diagnostic modalities such as ultrasound or optical coherence tomography exist to aid for earlier detection of ciliary body tumors, but they also have limitations. Here we describe the potential for scleral angiography as an adjunctive modality to assist in evaluating anterior segment ciliary body tumors. Case Presentations: A 61-year-old Caucasian male and a 57-year-old Hispanic female presented for ciliary body tumor evaluation. The Caucasian male notably had abnormal scleral, episcleral, and conjunctival vessels in the affected eye. Scleral angiography was performed in both cases with the abnormal vasculature highlighted in the Caucasian male. The Hispanic female did not demonstrate abnormal scleral angiographic patterns. Notably, the Caucasian male also had regions of abnormal scleral angiography arising in locations of otherwise normal appearing sclera. Both patients had the affected eyes enucleated. Histology of the enucleated eyes demonstrated a ciliary body melanoma in the Caucasian male associated with abnormal vascular and tumor infiltration of the scleral bed. The Hispanic female had a pigmented ciliary body adenoma without involvement of the scleral bed. Conclusion: With limited sample size, scleral angiography has the potential to detect abnormal scleral vascular patterns in otherwise normal appearing sclera in cases of ciliary body tumor with scleral vascular invasion.
Emerging Concepts in Paracrine Mechanisms in Regenerative Cardiovascular Medicine and Biology
Authors: Hodgkinson Conrad P. , Bareja Akshay , Gomez José A. , Dzau Victor J.
Published: January 2016

In the past decade, substantial evidence supports the paradigm that stem cells exert their reparative and regenerative effects, in large part, through the release of biologically active molecules acting in a paracrine fashion on resident cells. The data suggest the existence of a tissue microenvironment where stem cell factors influence cell survival, inflammation, angiogenesis, repair, and regeneration in a temporal and spatial manner.
The Rapid Capture of Attention by Rewarded Objects
Authors: Donohue Sarah E. , Hopf Jens-Max , Bartsch Mandy V. , Schoenfeld Mircea A. , Heinze Hans-Jochen , Woldorff Marty G.
Published: January 2016

When a stimulus is associated with a reward, it becomes prioritized, and the allocation of attention to that stimulus increases. For low-level features, such as color, this reward-based allocation of attention can manifest early in time and as a faster and stronger shift of attention to targets with that color, as reflected by the N2pc (a parieto-occipital electrophysiological component peaking at ∼250 msec). It is unknown, however, if reward associations can similarly modulate attentional shifts to complex objects or object categories, or if reward-related modulation of attentional allocation to such stimuli would occur later in time or through a different mechanism. Here, we used magnetoencephalographic recordings in 24 participants to investigate how object categories with a reward association would modulate the shift of attention. On each trial, two colored squares were presented, one in a target color and the other in a distractor color, each with an embedded object. Participants searched for the target-colored square and performed a corner discrimination task. The embedded objects were from either a rewarded or non-rewarded category, and if a rewarded-category object were present within the target-colored square, participants could earn extra money for correct performance. We observed that when the target color contained an object from a rewarded versus a non-rewarded category, the neural shift of attention to the target was faster and of greater magnitude, although the rewarded objects were not relevant for correct task performance. These results suggest that reward associations of complex objects can rapidly modulate attentional allocation to a target.
Near-optimal Integration of Magnitude in the Human Parietal Cortex
Authors: Tickle Hannah , Speekenbrink Maarten , Tsetsos Konstantinos , Michael Elizabeth , Summerfield Christopher
Published: January 2016

Humans are often observed to make optimal sensorimotor decisions but to be poor judges of situations involving explicit estimation of magnitudes or numerical quantities. For example, when drawing conclusions from data, humans tend to neglect the size of the sample from which it was collected. Here, we asked whether this sample size neglect is a general property of human decisions and investigated its neural implementation. Participants viewed eight discrete visual arrays (samples) depicting variable numbers of blue and pink balls. They then judged whether the samples were being drawn from an urn in which blue or pink predominated. A participant who neglects the sample size will integrate the ratio of balls on each array, giving equal weight to each sample. However, we found that human behavior resembled that of an optimal observer, giving more credence to larger sample sizes. Recording scalp EEG signals while participants performed the task allowed us to assess the decision information that was computed during integration. We found that neural signals over the posterior cortex after each sample correlated first with the sample size and then with the difference in the number of balls in either category. Moreover, lateralized beta-band activity over motor cortex was predicted by the cumulative difference in number of balls in each category. Together, these findings suggest that humans achieve statistically near-optimal decisions by adding up the difference in evidence on each sample, and imply that sample size neglect may not be a general feature of human decision-making.
Empire Versus Empire
Authors: Kim Jimin
Published: January 2016

Many studies on u.s.-Korea relations describe the bilateral interactions to 1905 and the restored diplomatic relations after Korea’s liberation in 1945. This study focuses instead on the interwar years proceeding from the premise that American understandings of colonial Korea are important to grasp u.s. wartime planning for Korea’s future. It explores unofficial levels of interactions, representations, and perceptions of Japan and the United States regarding colonial Korea. On one hand, American writers and professionals portrayed Korea as a developing country needing critical help from Japanese colonizers that coincided with imperial imperatives. On the other hand, professional scholars and u.s. government officials began to look at Japan’s rule in Korea from a more critical perspective, observing problems with Japanese rule in Korea in economic, political, and social affairs. u.s. officials posted in Korea, in particular, saw how Koreans were suffering from Japan’s discrimination and harsh rule. This repressive colonial rule was creating appeal for communism among the Korean people. u.s. officials began to doubt the feasibility of Japan’s pan-Asian doctrine, questioning if it could be a successful ruler. These varied American views of colonial Korea became the basis of u.s. policy toward post-colonial Korea after 1945.