bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Probiotics for Management of Acute Gastroenteritis
Authors: Szajewska Hania , Guarino Alfredo , Hojsak Iva , Indrio Flavia , Kolacek Sanja , Shamir Raanan , Vandenplas Yvan , Weizman Zvi 
Published: January 2014

ABSTRACTThe use of probiotics has been suggested in the treatment of acute gastroenteritis (AGE) in addition to early rehydration and avoidance of dietary restrictions. This document provides recommendations for the use of probiotics for the treatment of AGE in previously healthy infants and children based on a systematic review of previously completed systematic reviews and of randomized controlled trials (RCTs) published subsequently to these reviews. The recommendations were formulated only if at least 2 RCTs that used a given probiotic (with strain specification) were available. The GRADE system developed by the Grading of Recommendations, Assessment, Development, and Evaluations Working Group, was used to grade the strength of evidence and grades of recommendations used in these guidelines. It offers 4 categories of the quality of the evidence (high, moderate, low, and very low) and 2 categories of the strength of recommendation (strong or weak). The use of the following probiotics (in alphabetical order) may be considered in the management of children with AGE in addition to rehydration therapy: Lactobacillus rhamnosus GG (low quality of evidence, strong recommendation) and Saccharomyces boulardii (low quality of evidence, strong recommendation). Less compelling evidence is available for Lactobacillus reuteri DSM 17938 (very low quality of evidence, weak recommendation) and heat‐inactivated Lactobacillus acidophilus LB (very low quality of evidence, weak recommendation). The latter, although traditionally discussed with other probiotics, does not fit with the definition of probiotics. Other strains or combinations of strains have been tested, but evidence of their efficacy is weak or preliminary.
Kinase inhibitors: The next generation of therapies in the treatment of rheumatoid arthritis
Authors: MacFarlane Lindsey A. , Todd Derrick J. 
Published: January 2014

AbstractRheumatoid arthritis (RA) can be the source of significant pain and functional limitation. The past 20 years have seen a transition in treatment goals away from mere pain management toward disease modification through the suppression of autoimmunity. Disease‐modifying anti‐rheumatic drugs, such as methotrexate and biologic agents, impair disease progression and joint destruction. However, despite these achievements, a substantial subset of RA patients does not respond to or cannot tolerate current treatments for RA. Scientific insight into the cellular pathways of inflammation has revealed new therapeutic targets for the treatment of autoimmune diseases like RA. Attention has focused on pathways mediated by Janus kinase (JAK), mitogen‐activated protein kinase (MAPK), and spleen tyrosine kinase (Syk). This review article summarizes the evidence supporting the use of various kinase inhibitors, including the newly approved JAK inhibitor tofacitinib, in the treatment of RA.
Incidence and complications of peptic ulcer disease requiring hospitalisation have markedly decreased in Finland
Authors: Malmi H. , Kautiainen H. , Virta L. J. , Färkkilä N. , Koskenpato J. , Färkkilä M. A. 
Published: January 2014

SummaryBackgroundThe characteristics of peptic ulcer disease (PUD) are changing.AimTo evaluate time trends in the incidence of PUD and its complications in hospitalised patients at the beginning of the 21st century, drug therapies in out‐patient care as a risk factor for recurrent PUD, and medication used by PUD patients compared with the background population.MethodsIn this retrospective epidemiologic cohort study, data from the years 2000–2008 came from The Hospital District of Helsinki and Uusimaa, and the Finnish Care Register. All hospitalised adult patients with PUD in the capital region of Finland were included. The data were linked with nationwide Prescription Register of the Finnish Social Insurance Institution allowing detailed individual medicine purchase data.ResultsA total of 9951 peptic ulcers were detected among 8146 individual patients during the study period. The mean annual incidence of all peptic ulcers decreased from 121/100 000 (95% CI: 117–125) in 2000–2002, to 79 (95% CI: 76–82) in 2006–2008 [Incidence rate ratio = 0.62 (95% CI: 0.58–0.64), P < 0.001 after age and sex adjustment]. Decrease in incidence was seen in all age groups and in both sexes. The overall rate of severe complications of PUD was reduced. One‐year cumulative incidence of recurrent ulcers was 13%. Use of several drugs was associated with increased risk for recurrence. The purchases of various drugs were more common among PUD patients compared with background population.ConclusionsBoth the incidence and complication rates have markedly decreased during the study period. Recurrent peptic ulcer disease was associated with polypharmacy.
Induction of Neurotrophic and Differentiation Factors in Neural Stem Cells by Valproic Acid
Authors: Almutawaa Walaa , Kang Na Hyea , Pan Yi , Niles Lennard P. 
Published: January 2014

AbstractValproic acid (VPA), a short‐chain fatty acid, is used clinically as an anticonvulsant and mood stabilizer. Valproic acid also inhibits histone deacetylase activity, which is associated with histone hyperacetylation and changes in gene expression. In this study, we examined the effects of VPA on the expression of selected neurotrophic and differentiation factors in C17.2 neural stem cells. Reverse transcription‐polymerase chain reaction analysis revealed a significant increase in conserved dopamine neurotrophic factor (CDNF) and glial cell line‐derived neurotrophic factor mRNA expression, after treatment with clinically relevant concentrations of VPA (0.5 or 1.0 mM) for 24 hr. Increases in the protein expression of CDNF and mesencephalic astrocyte‐derived neurotrophic factor were also observed, after similar treatment with VPA. In addition, significant increases in the mRNA levels of the early dopaminergic neuron marker, nuclear receptor‐related protein 1(Nurr1), and the transcriptional regulator, early growth response protein 1 (Egr1), were observed after treatment with VPA for 24 hr. C17.2 neural stem cells exhibited high basal mRNA expression of brain‐derived neurotrophic factor and SRY (sex determining region Y)‐box 2 (Sox2), which was not altered by VPA treatment. Western analysis revealed hyperacetylation of histone H3 proteins in C17.2 cells after VPA treatment for 24 hr or 48 hr, suggesting involvement of an epigenetic mechanism in the observed gene induction by this drug. These findings support a role for VPA in modulating neurotrophic and differentiation factor expression, in keeping with its reported neuroprotective and neurodevelopmental effects.
Inference for reaction networks using the linear noise approximation
Authors: Fearnhead Paul , Giagos Vasilieos , Sherlock Chris 
Published: January 2014

SummaryWe consider inference for the reaction rates in discretely observed networks such as those found in models for systems biology, population ecology, and epidemics. Most such networks are neither slow enough nor small enough for inference via the true state‐dependent Markov jump process to be feasible. Typically, inference is conducted by approximating the dynamics through an ordinary differential equation (ODE) or a stochastic differential equation (SDE). The former ignores the stochasticity in the true model and can lead to inaccurate inferences. The latter is more accurate but is harder to implement as the transition density of the SDE model is generally unknown. The linear noise approximation (LNA) arises from a first‐order Taylor expansion of the approximating SDE about a deterministic solution and can be viewed as a compromise between the ODE and SDE models. It is a stochastic model, but discrete time transition probabilities for the LNA are available through the solution of a series of ordinary differential equations. We describe how a restarting LNA can be efficiently used to perform inference for a general class of reaction networks; evaluate the accuracy of such an approach; and show how and when this approach is either statistically or computationally more efficient than ODE or SDE methods. We apply the LNA to analyze Google Flu Trends data from the North and South Islands of New Zealand, and are able to obtain more accurate short‐term forecasts of new flu cases than another recently proposed method, although at a greater computational cost.
Researchers and teachers learning together and from each other using video‐based multimodal analysis
Authors: Davidsen Jacob , Vanderlinde Ruben 
Published: January 2014

AbstractThis paper discusses a year‐long technology integration project during which teachers and researchers joined forces to explore children's collaborative activities through the use of touch screens. In the research project discussed in this paper, 16 touch screens were integrated into teaching and learning activities in two separate classrooms; the learning and collaborative processes were captured by using a video, collecting over 150 hours of footage. By using digital research technologies and a longitudinal design, the authors of the research project studied how teachers and children gradually integrated touch screens into their teaching and learning. This paper examines the methodological usefulness of video‐based multimodal analysis. Through reflection on the research project, we discuss how, by using video‐based multimodal analysis, researchers and teachers can study children's touch‐screen supported collaboration and how researchers and teachers can learn together.
A multicentre study of primary breast diffuse large B‐cell lymphoma in the rituximab era
Authors: Hosein Peter J. , Maragulia Jocelyn C. , Salzberg Matthew P. , Press Oliver W. , Habermann Thomas M. , Vose Julie M. , Bast Martin , Advani Ranjana H. , Tibshirani Robert , Evens Andrew M. , Islam Nahida , Leonard John P. , Martin Peter , Zelenetz Andrew D. , Lossos Izidore S. 
Published: January 2014

SummaryPrimary breast diffuse large B‐cell lymphoma (DLBCL) is a rare subtype of non‐Hodgkin lymphoma (NHL) with limited data on pathology and outcome. A multicentre retrospective study was undertaken to determine prognostic factors and the incidence of central nervous system (CNS) relapses. Data was retrospectively collected on patients from 8 US academic centres. Only patients with stage I/II disease (involvement of breast and localized lymph nodes) were included. Histologies apart from primary DLBCL were excluded. Between 1992 and 2012, 76 patients met the eligibility criteria. Most patients (86%) received chemotherapy, and 69% received immunochemotherapy with rituximab; 65% received radiation therapy and 9% received prophylactic CNS chemotherapy. After a median follow‐up of 4·5 years (range 0·6–20·6 years), the Kaplan–Meier estimated median progression‐free survival was 10·4 years (95% confidence interval [CI] 5·8–14·9 years), and the median overall survival was 14·6 years (95% CI 10·2–19 years). Twelve patients (16%) had CNS relapse. A low stage‐modified International Prognostic Index (IPI) was associated with longer overall survival. Rituximab use was not associated with a survival advantage. Primary breast DLBCL has a high rate of CNS relapse. The stage‐modified IPI score is associated with survival.
Metabolic syndrome and cardiovascular risk among long‐term survivors of acute lymphoblastic leukaemia ‐ From the St. Jude Lifetime Cohort
Authors: Nottage Kerri A. , Ness Kirsten K. , Li Chenghong , Srivastava Deokumar , Robison Leslie L. , Hudson Melissa M. 
Published: January 2014

SummaryAdult survivors of childhood acute lymphoblastic leukaemia (ALL) have a four‐fold excess risk of mortality from cardiovascular disease. This cardiovascular risk has not been fully characterized. ALL survivors [n = 784, median age 31·7 years (18·9–59·1)] in the St. Jude Lifetime Cohort Study underwent evaluation for cardiovascular risk and metabolic syndrome (MetS) according to National Cholesterol Education Program – Adult Treatment Panel III criteria. Comparisons were made to 777 age‐, sex‐, and race‐matched controls from the National Health and Nutrition Examination Survey (NHANES). MetS was identified in 259 survivors (33·6%) and associated with older age in 5‐year increments (relative risk [RR] 1·13, 95% confidence interval [CI] 1·06–1·19) and prior cranial radiotherapy (CRT) (with craniospinal radiation: RR 1·88, 95%CI 1·32–2·67; without: RR 1·67, 95%CI 1·26–2·23). Measures of obesity were highly prevalent among female survivors and CRT recipients. Compared to NHANES controls, ALL survivors had a higher risk of MetS (RR 1·43, 95%CI 1·22–1·69), hypertension (RR 2·43, 95%CI 2·06–2·86), low high‐density lipoprotein (RR 1·40, 95%CI 1·23–1·59), obesity (RR 1·47, 95%CI 1·29–1·68) and insulin resistance (1·64, 95%CI 1·44–1·86). This large study of clinically evaluated ALL survivors identified a high prevalence of MetS, obesity and cardiovascular risk, particularly in CRT recipients, underscoring the need for screening and aggressive reduction of modifiable risks.
Evolution of the Southampton Enhanced Recovery Programme for radical cystectomy and the aggregation of marginal gains
Authors: Smith Julian , Meng Zhao Wu , Lockyer Richard , Dudderidge Tim , McGrath John , Hayes Matthew , Birch Brian 
Published: January 2014

ObjectiveTo describe and assess the evolution of an enhanced recovery programme (ERP) for open radical cystectomy.Patients and MethodsWe introduced a mentored ERP for radical cystectomy in January 2011. The programme underwent service evaluation and multiple changes in August 2012 that we define as marginal gains. We present a retrospective review of 133 consecutive patients undergoing open radical cystectomy, grouped according to the three stages of the ERP from October 2008 to April 2013: (1) non‐ERP group (October 2008 to December 2010): n = 69; (2) ERP‐1 group (January 2011 to July 2012): n = 37; and (3) ERP‐2 group (August 2012 to April 2013): n = 27. Primary outcomes were length of hospital stay (LOS), readmission, morbidity at 90 days using the Clavien classification system and mortality. Secondary outcomes were time to flatus, ileus rates, re‐operation rates and oncological outcomes.ResultsThere were no differences in patient demographics among any of the groups for: age, gender, BMI, American Society of Anesthesiologists score and the use of neoadjuvant chemotherapy. There were no differences in readmission, morbidity and mortality rates. The overall 90‐day mortality was six patients (4.5%). There were significant differences in ileus rates between the non‐ERP, the ERP‐1 and the ERP‐2 groups: 44.9% (31 patients), 29.7% (11 patients) and 14.8% (four patients), respectively (P = 0.017). There was a significant difference in the presence of pathological lymphadenopathy in the ERP‐2 group: non‐ERP group, 10.1%; ERP‐1 group, 16.2%; and ERP‐2 group, 44.4%; P = 0.002. There was also a difference in the mean (sd) lymph node yield in ERP‐2: non‐ERP group, 8.4 (5.4) nodes; ERP‐1, 8.2 (6.4) nodes; and ERP‐2, 16.7 (5.4) nodes (P < 0.001). The median (range) LOS was 14 (7–91) days, 10 (6–55) days and 7 (3–99) days in the non‐ERP, ERP‐1 and ERP‐2 groups, respectively (P < 0.001).ConclusionsAuditing an already successful ERP and implementing a number of marginal gains has led to a significant decrease in the median LOS for radical cystectomy. The LOS for open radical cystectomy at University Hospital Southampton has halved. In the second phase of our ERP, our median LOS is 7 days.
Positive allosteric modulators of the μ‐opioid receptor: a novel approach for future pain medications
Authors: Burford N T , Traynor J R , Alt A 
Published: January 2014

Morphine and other agonists of the μ‐opioid receptor are used clinically for acute and chronic pain relief and are considered to be the gold standard for pain medication. However, these opioids also have significant side effects, which are also mediated via activation of the μ‐opioid receptor. Since the latter half of the twentieth century, researchers have sought to tease apart the mechanisms underlying analgesia, tolerance and dependence, with the hope of designing drugs with fewer side effects. These efforts have revolved around the design of orthosteric agonists with differing pharmacokinetic properties and/or selectivity profiles for the different opioid receptor types. Recently, μ‐opioid receptor‐positive allosteric modulators (μ‐PAMs) were identified, which bind to a (allosteric) site on the μ‐opioid receptor separate from the orthosteric site that binds an endogenous agonist. These allosteric modulators have little or no detectable functional activity when bound to the receptor in the absence of orthosteric agonist, but can potentiate the activity of bound orthosteric agonist, seen as an increase in apparent potency and/or efficacy of the orthosteric agonist. In this review, we describe the potential advantages that a μ‐PAM approach might bring to the design of novel therapeutics for pain that may lack the side effects currently associated with opioid therapy.Linked ArticlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
Tariff Structure, Trade Expansion, and Canadian Protectionism, 1870–1910
Authors: Beaulieu Eugene , Cherniwchan Jevan 
Published: January 2014

AbstractCanada's trade policy at the end of the 19th century is commonly viewed as protectionist and extremely costly. In this paper, we employ the Anderson‐Neary Trade Restrictiveness Index to re‐examine this view. Based on product‐level customs data, we show that Canadian trade policy between 1870 and 1910 was more restrictive than previously understood, but created smaller welfare losses than previously believed. These results are primarily driven by high tariffs on inelastic, non‐competing import goods. Although Canada's tariff structure becomes more restrictive over the period, our findings indicate it was not as protectionist or as costly as once thought.
How Would One Extra Year of High School Affect Academic Performance in University? Evidence from an Educational Policy Change
Authors: Krashinsky Harry 
Published: January 2014

AbstractThis paper uses a unique policy change in Ontario, Canada, to provide direct evidence on how reducing the length of high school would impact student performance in university. After a five‐year educational program was eliminated from Ontario high schools and replaced with a four‐year program, two graduating cohorts with different amounts of high school education simultaneously entered university. The results demonstrate that students who receive one less year of high school education perform significantly worse than their counterparts in all subjects, even after the age difference between the cohorts is accounted for.
Social Security and Family Support
Authors: Leroux M.‐L. , Pestieau P. 
Published: January 2014

AbstractThis paper shows how the role of the market, the state and the family in providing old‐age support has evolved over time with changes in factors such as the reliability and the effectiveness of family support, the interest rate, the cost of public funds, and earning inequality. Agents with different productivity vote over the size of a Beveridgian pension system. When children assistance is certain, agents may rely exclusively on family and prefer no pension. However, when the size and the probability of family generosity decrease, social security is more likely to emerge.
Viewpoint: Boosting Recessions
Authors: Ng Serena 
Published: January 2014

AbstractThis paper explores the effectiveness of boosting, often regarded as the state of the art classification tool, in giving warning signals of recessions 3, 6, and 12 months ahead. Boosting is used to screen as many as 1,500 potentially relevant predictors consisting of 132 real and financial time series and their lags. Estimation over the full sample 1961:1–2011:12 finds that there are fewer than 10 important predictors and the identity of these variables changes with the forecast horizon. There is a distinct difference in the size and composition of the relevant predictor set before and after mid‐1980. Rolling window estimation reveals that the importance of the term and default spreads are recession specific. The Aaa spread is the most robust predictor of recessions three and 6 months ahead, while the risky bond and 5‐year spreads are important for 12 months ahead predictions. Certain employment variables have predictive power for the two most recent recessions when the interest rate spreads were uninformative. Warning signals for the post‐1990 recessions have been sporadic and easy to miss. The results underscore the challenge that changing characteristics of business cycles pose for predicting recessions.
Managerial versus Production Wages: Offshoring, Country Size, and Endowments
Authors: Benz Sebastian , Kohler Wilhelm 
Published: January 2014

AbstractWe explore the role of trade in differentiated final goods as well as offshoring of tasks for inequality both within and between countries, emphasizing the distinction between managerial and production labour. We extend Grossman and Rossi‐Hansberg (2012), where task trade is driven by external economies of scale, by considering asymmetric endowments. Identifying possible equilibrium patterns of task trade, we find little scope for two‐way trade if endowments are asymmetric. Our numerical simulations identify non‐monotonicities between the level of offshoring and measures of within‐country as well as between‐country inequality.
Laparoscopic intersphincteric resection for low rectal cancer: comparison of stapled and manual coloanal anastomosis
Authors: Cong J. C. , Chen C. S. , Ma M. X. , Xia Z. X. , Liu D. S. , Zhang F. Y. 
Published: January 2014

AbstractAimThe study aim was to analyse the safety and feasibility of laparoscopic intersphincteric resection with stapled coloanal anastomosis for low rectal cancer.MethodBetween March 2009 and August 2010, 22 patients underwent laparoscopic intersphincteric resection with a stapled coloanal anastomosis without a diverting ileostomy. The results were compared retrospectively with hand‐sewn coloanal anastomoses performed between January 2001 and May 2009, which included 55 open and 38 laparoscopic intersphincteric resections. The morbidity comparison only included data relevant to the anastomosis. Function was compared using the Saito function questionnaire and the Wexner score and only involved data relevant to the laparoscopy.ResultsThe anastomotic complication rates were similar for fistula, bleeding and neorectal mucosal prolapse (P = 0.526, P = 0.653 and P = 0.411, respectively). Anastomotic leakage and stricture formation of the stapled coloanal anastomosis were significantly lower than those of the hand‐sewn coloanal anastomosis (P = 0.037 and P = 0.028, respectively). There were no significant differences in the Saito function questionnaire and the Wexner score between the stapled and hand‐sewn coloanal anastomotic groups (all P > 0.05).ConclusionLaparoscopic intersphincteric resection with a stapled coloanal anastomosis is technically feasible and is less likely to result in anastomotic leakage and stricture formation than a hand‐sewn anastomosis.