bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards a new kind of vaccine
Authors: Gorczynski Reginald M. , Hoffmann Geoffrey W. 
Published: January 2017

AbstractWe present new data showing that normal IgG immune responses comprise the production of two kinds of antibodies, namely anti-foreign and anti-anti-self antibodies. For example, immunization of C3H mice by two rounds of BL/6 skin grafting results in the production of anti-BL/6 antibodies plus antiidiotypic antibodies (C3H anti-anti-C3H) with the latter being detected using antibodies produced in a BL/6 anti-C3H immune response. Similarly, the IgG immune response of C3H mice to tetanus toxoid includes the production of C3H anti-anti-C3H antibodies. Antigen-specific antibodies produced in one alloimmunization plus antiidiotypic antibodies produced in the converse immunization can be used to synergistically induce specific tolerance. We show that infusions of anti-BL/6 antibodies together with BL/6 anti-anti-BL/6 antibodies specifically suppress an immune response to BL/6 lymphocytes in C3H mice. Specific tolerance was measured as suppression of the induction of BL/6-specific cytotoxic T cells. The two kinds of antibodies with complementary specificity are believed to stimulate two populations of T lymphocytes, and co-selection (mutual selection) of these two populations leads to a new stable steady state of the system that has specifically diminished reactivity to BL/6 tissue. Stimulation with a combination of anti-C3H and C3H anti-anti-C3H IgG antibodies furthermore down-regulates inflammation in a mouse model of inflammatory bowel disease. An analogous combination of C3H anti-BL/6 and BL/6 anti-anti-BL/6 antibodies significantly down-regulates tumour growth and metastases in BALB/c mice in the EMT6 transplantable breast cancer model. We conclude that a combination of certain antigen-specific and antiidiotypic antibodies has potential as a new class of vaccines based on the symmetrical immune network theory. This new kind of vaccine does not involve the production of antibodies. The prevention of two important degenerative diseases makes this a potential anti-aging technology.
Structural and functional dissection of the interplay between lipid and Notch binding by human Notch ligands
Authors: Suckling Richard J. , Korona Boguslawa , Whiteman Patricia , Chillakuri Chandramouli , Holt Laurie , Handford Penny A. , Lea Susan M. 
Published: January 2017

Abstract:Recent data have expanded our understanding of Notch signaling by identifying a C2 domain at the N-terminus of Notch ligands which has both lipid- and receptor-binding properties. We present novel structures of human ligands Jagged2 and DLL4 and human Notch-2, together with functional assays, which suggest that ligand-mediated coupling of membrane recognition and Notch binding is likely to be critical in establishing the optimal context for Notch signaling. Comparisons between the Jagged and Delta family show a huge diversity in the structures of the loops at the apex of the C2 domain implicated in membrane recognition and Jagged1 missense mutations which affect these loops and are associated with extrahepatic biliary atresia lead to a loss of membrane recognition, but do not alter Notch binding. Taken together, these data suggest that C2 domain binding to membranes is an important element in tuning ligand-dependent Notch signaling in different physiological contexts.
Hedge funds vs SEO firms: a comparative analysis
Authors: Hull Robert Martin , Kwak Sungkyu , Walker Rosemary 
Published: January 2017

Purpose
The purpose of this paper is to determine if hedge funds perform poorly as claimed by more recent research. The authors find hedge funds perform well from 2001 to 2013 when compared to sample of firms known to experience superior performance, namely, a sample of seasoned equity offerings (SEOs).

Design/methodology/approach
This paper uses a portfolio approach in comparing the performance of hedge funds and SEO firms. Other comparisons involve a number of common methodologies used to compute and analyze short-run and long-run returns.

Findings
Contrary to a growing and prevalent belief, the paper offers evidence hedge funds as a whole have performed well for a recent 13-year period. This finding includes periods up to six years around SEO announcement months.

Research limitations/implications
This paper is limited to examining monthly returns for a portfolio of hedge funds. This limitation led to incorporating a portfolio approach.

Practical implications
The findings suggest that a portfolio of hedge funds are an important investment consideration. This consideration has practical implications because investing in a portfolio of hedge funds has become more available for all investors in recent years.

Social implications
Society can be enhanced as this paper helps future investors make optimal investment decisions.

Originality/value
This paper adds to the hedge fund research by being the first paper to compare the performance of hedge funds with that for firms undergoing an important corporate event. The findings are new and can impact investment decision making.
Using beamforming to maximise the detection capability of small, sparse seismometer arrays deployed to monitor oil field activities
Authors: Verdon James P. , Kendall J.‐Michael , Hicks Stephen P. , Hill Philip 
Published: January 2017

ABSTRACTLike most other industrial activities that affect the subsurface, hydraulic fracturing carries the risk of reactivating pre‐existing faults and thereby causing induced seismicity. In some regions, regulators have responded to this risk by imposing traffic light scheme‐type regulations, where fracture stimulation programs must be amended or shut down if events larger than a given magnitude are induced. Some sites may be monitored with downhole arrays and/or dense near‐surface arrays, capable of detecting very small microseismic events. However, such monitoring arrangements will not be logistically or economically feasible at all sites. Instead, operators are using small, sparse arrays of surface seismometers to meet their monitoring obligations.The challenge we address in this paper is to maximise the detection thresholds of such small, sparse, surface arrays so that they are capable of robustly identifying small‐magnitude events whose signal‐to‐noise ratios may be close to 1. To do this, we develop a beamforming‐and‐stacking approach, computing running short‐term/long‐term average functions for each component of each recorded trace (P, SH, and SV), time‐shifting these functions by the expected travel times for a given location, and performing a stack.We assess the effectiveness of this approach with a case study using data from a small surface array that recorded a multi‐well, multi‐stage hydraulic fracture stimulation in Oklahoma over a period of 8 days. As a comparison, we initially used a conventional event‐detection algorithm to identify events, finding a total of 17 events. In contrast, the beamforming‐and‐stacking approach identified a total of 155 events during this period (including the 17 events detected by the conventional method). The events that were not detected by the conventional algorithm had low‐signal‐to‐noise ratios to the extent that, in some cases, they would be unlikely to be identified even by manual analysis of the seismograms. We conclude that this approach is capable of improving the detection thresholds of small, sparse arrays and thus can be used to maximise the information generated when deployed to monitor industrial sites.
Metabolic theory predicts animal self‐thinning
Authors: Jonsson Tomas 
Published: January 2017

Summary

The metabolic theory of ecology (MTE) predicts observed patterns in ecology based on metabolic rates of individuals. The theory is influential but also criticized for a lack of firm empirical evidence confirming MTE's quantitative predictions of processes, e.g. outcome of competition, at population or community level.
Self‐thinning is a well‐known population level phenomenon among plants, but a much less studied phenomenon in animal populations and no consensus exists on what a universal thinning slope for animal populations might be, or if it exists.
The goal of this study was to use animal self‐thinning as a tool to test population‐level predictions from MTE, by analysing (i) if self‐thinning can be induced in populations of house crickets (Acheta domesticus) and (ii) if the resulting thinning trajectories can be predicted from metabolic theory, using estimates of the species‐specific metabolic rate of A. domesticus.
I performed a laboratory study where the growth of A. domesticus was followed, from hatching until emergence as adults, in 71 cohorts of five different starting densities.
Ninety‐six per cent of all cohorts in the three highest starting densities showed evidence of self‐thinning, with estimated thinning slopes in general being remarkably close to that expected under metabolic constraints: A cross‐sectional analysis of all data showing evidence of self‐thinning produced an ordinary least square (OLS) slope of −1·11, exactly that predicted from specific metabolic allometry of A. domesticus. This result is furthermore supported by longitudinal analyses, allowing for independent responses within cohorts, producing a mean OLS slope across cohorts of −1·13 and a fixed effect linear mixed effects models slope of −1·09. Sensitivity analysis showed that these results are robust to how the criterion for on‐going self‐thinning was defined. Finally, also as predicted by metabolic theory, temperature had a negative effect on the thinning intercept, producing an estimate of the activation energy identical to that suggested by MTE.
This study demonstrates a direct link between the metabolic rate of individuals and a population‐level ecological process and as such provides strong support for research that aims to integrate body mass, via its effect on metabolism, consumption and competition, into models of populations and communities.
Local demographic and epidemiological patterns in theLinum marginale–Melampsora liniassociation: a multi‐year study
Authors: Susi Hanna , Thrall Peter H. , Barrett Luke G. , Burdon Jeremy J. 
Published: January 2017

SummaryMany theoretical and empirical studies operate from an assumption that pathogens have a significant influence on the fecundity and life span of their host species. However, there are surprisingly little data investigating the long‐term fitness impacts and genetic consequences that arise from pathogen infection in natural populations. Here, we address this gap through the analysis of a dataset investigating the local population dynamics of a native host plant (Linum marginale) and an associated rust pathogen (Melampsora lini) across 12 years.To investigate patterns of disease prevalence and severity and track effects on host fecundity and demography, we conducted censuses on an annual basis at a single site. AnnualM. liniinfection prevalence ranged from 0% to 99%. Severe epidemics occurred in 3‐ to 4‐year cycles causing high overwintering mortality and subsequent changes in the relative abundance of different host phenotypes. Host population size oscillated in response to epidemics and declined towards the end of the observation period. Changes in host numbers were found to affect disease severity but not infection prevalence.Melampsora liniinfection increasedL. marginalefecundity; the infected plants produced threefold more seed capsules on average than uninfected plants (13·3 vs. 4·3 seed capsules per plant).To investigate how variation in environmental conditions affects epidemiology and host demography, we identified climatic factors affecting host growth, overwintering and disease severity. Winter (June) rainfall increased host overwintering success and summer (December) rainfall favoured host growth. The progress ofM. linidisease epidemics benefited from optimal temperatures in February and suffered from rainfall in January.We further examined links between the genetic structure of the pathogen population and disease dynamics. There was a positive correlation between mean pathogen infectivity (as measured across a host differential set) and the severity of disease epidemics.Synthesis. Our results provide new insights into local drivers and consequences of pathogen epidemiology in natural populations.Melampsora liniinfection can have profound consequences on the phenotype, demography and population structure ofLinum marginaleby increasing host fecundity, overwinter mortality and disease resistance.
A Lib Dem Perspective on Centre‐Left Politics Post‐2015
Authors: Cable Vince 
Published: January 2017

AbstractThis article analyses the political crisis faced by the centre‐left, not just in the UK but throughout the Western world, with few exceptions (Canada). The Liberal Democrat party has been a victim of that crisis, though there are encouraging signs of recovery and there is scope for a wider realignment on the centre‐left.
Reduction in colposcopy workload and associated clinical activity following human papillomavirus (HPV) catch‐up vaccination programme in Scotland: an ecological study
Authors: Cruickshank ME , Pan J , Cotton SC , Kavanagh K , Robertson C , Cuschieri K , Cubie H , Palmer T , Pollock KG 
Published: January 2017

ObjectiveTo measure patterns of clinical activity at colposcopy before and after vaccinated women entered the Scottish Cervical Screening Programme (SCSP).DesignPopulation‐based observational study using nationally collected data.SettingScottish colposcopy clinics.SampleAll women with a date of birth on or after 1 January 1985 who attended colposcopy in Scotland between 2008 and 2014.MethodsRoutinely collected data from the Scottish National Colposcopy Clinical Information Audit System (NCCIAS) were extracted, including: referral criteria, referral cervical cytology, colposcopic findings, clinical procedures, and histology results. Analysis was restricted to those referred to colposcopy at age 20 or 21 years.Main outcome measuresReferral criteria, positive predictive value of colposcopy, default rates, and rates of cervical biopsies and treatments.ResultsA total of 7372 women referred for colposcopy at age 20 or 21 years were identified. There was a downward trend in the proportion of those referred with abnormal cytology (2008/9, 91.0%; 2013/14, 90.3%; linear trend P = 0.03). Women were less likely to have diagnostic or therapeutic interventions. The proportion with no biopsy (2008/9, 19.5%; 2013/14, 26.9%; linear trend P < 0.0001) and no treatment (2008/9, 74.9%; 2013/14, 91.8%; linear trend P < 0.0001) increased over the period of observation.ConclusionsA reduction in clinical activity related to abnormal screening referrals is likely to be associated with the human papillomavirus (HPV) catch‐up immunisation programme. Referral criteria and the service provision of colposcopy needs to be planned carefully, taking account of the increasing number of women who have been immunised against HPV that will be entering cervical screening programmes worldwide.Tweetable abstractColposcopy referral criteria and service planning need attention following HPV immunisation programme.
Stakeholder perspectives on barriers and facilitators of inclusive education in the Solomon Islands
Authors: Sharma Umesh , Loreman Tim , Simi Janine 
Published: January 2017

This paper reports perceived barriers and facilitators of disability‐inclusive education, and outcomes of an effective system of inclusive education in the Solomon Islands. Data were gathered from a variety of stakeholder group participants (n = 10) and individual key informants (n = 2), ranging from parents of children with disabilities to government representatives. The results revealed a unique perspective on disability‐inclusive education in this context, and provided insight into possible directions towards a more inclusive system.
‘Going beyond the Troika’: Power and discourse in Portuguese austerity politics
Authors: MOURY CATHERINE , STANDRING ADAM 
Published: January 2017

AbstractThis article analyses the margin of manoeuvre of Portuguese executives after the onset of the sovereign debt crisis in 2010–2015. To obtain a full understanding of what happened behind the closed doors of international meetings, different types of data are triangulated: face‐to‐face interviews; investigations by journalists; and International Monetary Fund and European Union official documents. The findings are compared to the public discourse of Prime Ministers José Sócrates and Pedro Passos‐Coelho. It is shown that while the sovereign debt crisis and the bail‐out limited the executive's autonomy, they also made them stronger in relation to other domestic actors. The perceived need for ‘credibility’ in order to avoid a ‘negative’ reaction from the markets – later associated with the conditions of the bail‐out – concurrently gave the executives a legitimate justification to concentrate power in their hands and a strong argument to counter the opponents of their proposed reforms. Consequently, when Portuguese ministers favoured policies that were in congruence with those supported by international actors, they were able to use the crisis to advance their own agenda. Disagreement with Troika representatives implied the start of a negotiation process between the ministers and international lenders, the final outcome of which depended on the actors’ bargaining powers. These strategies, it is argued, constitute a tactic of depoliticisation in which both the material constraints and the discourse used to frame them are employed to construct imperatives around a narrow selection of policy alternatives.
State of the Field
Authors: ROBERTS KENNETH M. 
Published: January 2017

AbstractAlthough scholars of West European politics have long debated whether the region's highly institutionalised party systems were becoming de‐aligned and electorally unstable, the political fallout from the post‐2008 financial crisis has lent a new sense of urgency to the debate. The threats posed to party systems by economic crises are hardly unique to Europe, however. The Latin American experience with the debt crisis of the 1980s and 1990s suggests that party system upheaval was not simply a function of retrospective economic voting during the period of crisis. It was also attributable to programmatically de‐aligning policy responses to crises – namely the ‘bait‐and‐switch’ imposition of austerity and adjustment measures by labour‐based, left‐leaning parties that were traditional champions of statist and redistributive policies. Such patterns of reform made it difficult for party systems to channel societal resistance to market orthodoxy in the post‐adjustment era, setting the stage for convulsive ‘reactive sequences’ when such resistance arose outside and against mainstream parties through varied forms of social and electoral protest, typically on the left flank. This article explores the political fallout from the European and Latin American economic crises from a comparative perspective, arguing that it is essential to think beyond the short‐term political dynamics of crisis management to consider the longer‐term institutional legacies and fragilities of the different political alignments forged around crisis‐induced policy reforms.
Prescription Drug Monitoring Programs Produce a Limited Impact on Painkiller Prescribing in Medicare Part D
Authors: Yarbrough Courtney R. 
Published: January 2017

ObjectiveTo measure the impact of prescription drug monitoring programs (PDMPs) on prescribing of opioid and nonopioid painkillers.Data Source2010–2013 physician‐level Medicare Part D prescribing data released by the Centers for Medicare and Medicaid Services and Propublica.Study DesignUsing difference‐in‐differences models with physician‐level fixed effects, the study compares prescribing in states with and without PDMPs for opioid and nonopioid analgesics, oxycodone, hydrocodone, and opioids by controlled substances Schedules II–IV.Principal FindingsPrescription drug monitoring programs were associated with a 5.2 percent decrease in days supply prescribed per physician for oxycodone in addition to smaller reductions for hydrocodone and opioids overall (2.8 percent and 2 percent, respectively) and a small increase in prescribing for Schedule IV opioids. PDMPs were not associated with changes for nonopioid analgesics or other opioids in Schedules II and III. The effects of PDMPs were negated in states where statutes explicitly did not require use of the PDMP.ConclusionsPrescription drug monitoring programs have a modest effect targeted at the high‐profile drug oxycodone among the Medicare Part D population and an even smaller effect for hydrocodone and opioids in general. The findings suggest some substitution toward lower schedule opioids. Substantially addressing the widespread opioid abuse problem will require enhancing existing PDMPs or implementing new policies.
Intervention quality is not routinely assessed in Cochrane systematic reviews of radiation therapy interventions
Authors: Abdul Rahim Mohamad R , James Melissa L , Hickey Brigid E 
Published: January 2017

AbstractIntroductionThe aim of this study was to maximise the benefits from clinical trials involving technological interventions such as radiation therapy. High compliance to the quality assurance protocols is crucial. We assessed whether the quality of radiation therapy intervention was evaluated in Cochrane systematic reviews.MethodsWe searched 416 published Cochrane systematic reviews and identified 67 Cochrane systematic reviews that investigated radiation therapy or radiotherapy as an intervention. For each systematic review, either quality assurance or quality control for the intervention was identified by a description of such processes in the published systematic reviews.ResultsOf the 67 Cochrane systematic reviews studied, only two mentioned quality assurance or quality control.ConclusionsOur findings revealed that 65 of 67 (97%) Cochrane systematic reviews of radiation therapy interventions failed to consider the quality of the intervention. We suggest that advice about the evaluation of intervention quality be added to author support materials.
The effect of data availability in measuring fund managers’ after‐tax alphas
Authors: Chen Zhe , Gallagher David R. , Warren Geoffrey J. 
Published: January 2017

AbstractWe examine potential sources of measurement error when evaluating the after‐tax performance of fund managers based on periodic snapshots of their holdings alone, compared with when daily transactions data are also available. To do this, we compare portfolio return estimates based on imputed trades from monthly, quarterly and semi‐annual snapshots with estimates that also incorporate daily trades for a sample of active institutional equity portfolios. This method allows us to directly measure the contribution of interim trading before tax, while more accurately estimating the tax effects associated with turnover through observing actual trade prices. Further, availability of both trade and holdings data permits the identification of how contributions and tax effects arise from income and capital gains sources, as well as how they vary across investment styles and market conditions.
Interdisciplinary management of an adult patient with significant restorative treatment needs and a complex malocclusion
Authors: Shah N , Ong DC‐V , Freer E 
Published: January 2017

AbstractTransverse maxillary deficiency may be associated with dental crowding, compromised aesthetics and impaired function. Non‐surgical correction of maxillary transverse deficiency through rapid maxillary expansion is routinely performed for young patients; however, surgical intervention is generally required for adults. An interdisciplinary treatment approach is necessary to achieve the desired treatment objectives for challenging cases. This case report demonstrates a pleasing treatment outcome for a patient with a severe maxillary transverse deficiency, significant crowding and extensive active caries.