bluuebunny/crossref_metadata_2025 huggingface dataset:
Transnationalising “Anti‐Popery”: Militant Protestant Preachers in the Nineteenth‐Century Anglo‐World
Authors: MacRaild Donald M.
Published: December 2014

Nineteenth‐century popular anti‐Catholicism may not have reached the intensity of the Gordon Riots of 1780, but it was nevertheless sustained and hostile. Whilst a deep‐rooted anti‐Catholicism shaped the British psyche, a specific anti‐Irish dimension also reared its head in response to epic migrations from the neighbouring island. This, in turn, saw traditions of intolerance spread around the globe as British and Irish migrants re‐peopled vast territories. For a time, specifically in the few decades after the 1840s, anti‐Catholic traditions were supported by a new brand of public theatre that became popular and financially rewarding. In one way, the emergence of a public style of no‐popery entertainment was an effect of mass migration, shared, ingrained Protestant identities, and urban modernity. By examining press reportage, contemporary writings, and the works of specific preachers, this article examines the global patterns of posturing and violence that marked the careers of itinerants like Charles Chiniquy, Baron de Camin, Fr Gavazzi, and John Sayers Orr, paying particular attention to the way these preachers and their supporters affected global Irish Catholic communities throughout the Anglo‐world.
Estimating the Elasticity of Taxable Income in New Zealand
Authors: Carey Simon , Creedy John , Gemmell Norman , Teng Josh
Published: December 2014

This paper produces regression estimates of the elasticity of taxable income in New Zealand using two new instruments applied to a substantial tax reform ‘experiment’. Instrumental variable methods are required to deal with endogeneity of the tax rate and taxable income in a non‐linear tax structure. However, in the New Zealand context, the ‘standard’ regression instrument is found to be unable to accommodate the substantial observed exogenous (non‐tax‐induced) changes in taxable income. Two new tax rate instruments are proposed, which use information on taxable income dynamics, for a panel of taxpayers over a period that involves no tax changes, to derive taxpayers’ counterfactual post‐reform incomes and tax rates expected in the absence of reform. The two instruments respectively measure, for each taxpayer, the tax rate associated with expected mean income, and the expected tax rate associated with the individual's expected conditional distribution of income. Applying these instruments to the 2001 New Zealand tax changes yields plausible estimates of the elasticity of taxable income around 0.5–0.7. Elasticities are found to be substantially higher for taxpayers with non‐wage‐and‐salary income compared with wage and salary only taxpayers. Results also confirm that non‐wage‐and‐salary income was especially responsive to the tax changes.
Recent Trends in Income Redistribution in Australia: Can Changes in the Tax‐Benefit System Account for the Decline in Redistribution?
Authors: Herault Nicolas , Azpitarte Francisco
Published: December 2014

We examine trends in the redistributive impact of the tax‐benefit system in Australia between 1994 and 2009 using a framework that allows us to separate the contributions of taxes, benefits, and taxes and benefits combined. Furthermore, we identify the effect of tax‐benefit policy reforms on income redistribution over the period. We find that after reaching a peak value in the late 1990s, the redistributive effect of taxes and benefits declined sharply. Although reforms to the tax‐benefit system contributed to the decline in redistribution, their contribution was limited compared to the role played by the changes in market income distribution.
Assessment of clinical manifestations, disease activity and organ damage in 996 Korean patients with systemic lupus erythematosus: comparison with other Asian populations
Authors: Joo Young Bin , Bae Sang Cheol
Published: December 2014

Aim

To describe the clinical manifestations, disease activity and organ damage in Korean patients with systemic lupus erythematosus (SLE).

Method

American College of Rheumatology (ACR) criteria, SLE Disease Activity Index (SLEDAI), and Systemic Lupus International Collaborating Clinics/ACR damage index (SDI) were assessed in patients with SLE from 1998 to 2012.

Results

A total of 996 SLE patients were analyzed. The common accrual of ACR criteria included: immunologic (93%), hematologic (93%), arthritic (66%) and nephritic (50%). In the inception cohort over 10 years of follow‐up (n = 120), the number of ACR criteria increased significantly (5.0 ± 1.2 to 5.7 ± 1.3), and nephritis, serositis and neuropsychiatric symptoms tended to increase continuously over time. SLEDAI‐2K decreased significantly (5.6 ± 3.4 to 4.1 ± 1.2), but the percentage of patients with SLEDAI scores ≥ 12 did not decrease over time. The common organ damages were musculoskeletal (14.9%) and renal (11.1%). The mean SDI score increased significantly (0.4 ± 0.8 to 1.1 ± 1.6) and renal damage had two peaks in 1 and 6–10 years, musculoskeletal and neuropsychiatric damage were predominant from 1 to 5 years, and ophthalmic damage increased sharply over 10 years.

Conclusion

Compared to other Asian cohorts, disease activity was lower and organ damage was less in our Korean cohort. Nephritis, serositis and neuropsychiatric symptoms increased continuously over time. Overall disease activity decreased significantly, but a small portion of severe disease activity continued during the disease course. The most common organ damage was musculoskeletal. The time in organ damage development varied, which reflects the possible causality, such as disease itself and/or treatment.
Review article: breath analysis in inflammatory bowel diseases
Authors: Kurada S. , Alkhouri N. , Fiocchi C. , Dweik R. , Rieder F.
Published: December 2014

Background

There is an urgent need for cheap, reproducible, easy to perform and specific biomarkers for diagnosis, differentiation and stratification of inflammatory bowel disease (IBD) patients. Technical advances allow for the determination of volatile organic compounds in the human breath to differentiate between health and disease.

Aim

Review and discuss medical literature on volatile organic compounds in exhaled human breath in GI disorders, focusing on diagnosis and differentiation of IBD.

Methods

A systematic search in PubMed, Ovid Medline and Scopus was completed using appropriate keywords. In addition, a bibliography search of each article was performed.

Results

Mean breath pentane, ethane, propane, 1‐octene, 3‐methylhexane, 1‐decene and NO levels were elevated (P < 0.05 to P < 10−7) and mean breath 1‐nonene, (E)‐2‐nonene, hydrogen sulphide and methane were decreased in IBD compared to healthy controls (P = 0.003 to P < 0.001). A combined panel of 3 volatile organic compounds (octene, (E)‐2‐nonene and decene) showed the best discrimination between paediatric IBD and controls (AUC 0.96). Breath condensate cytokines were higher in IBD compared to healthy individuals (P < 0.008). Breath pentane, ethane, propane, isoprene and NO levels correlated with disease activity in IBD patients. Breath condensate interleukin‐1β showed an inverse relation with clinical disease activity.

Conclusions

Breath analysis in IBD is a promising approach that is not yet ready for routine clinical use, but data from other gastrointestinal diseases suggest the feasibility for use of this technology in clinical practice. Well‐designed future trials, incorporating the latest breath detection techniques, need to determine the exact breath metabolome pattern linked to diagnosis and phenotype of IBD.
Frequent proviral integration of the human betaretrovirus in biliary epithelium of patients with autoimmune and idiopathic liver disease
Authors: Wang W. , Indik S. , Wasilenko S. T. , Faschinger A. , Carpenter E. J. , Tian Z. , Zhang Y. , Wong G. K.‐S. , Mason A. L.
Published: December 2014

Background

A human betaretrovirus (HBRV) has been linked with primary biliary cirrhosis (PBC) following the detection of viral particles in biliary epithelium by electron microscopy and cloning of the betaretrovirus genome from biliary epithelium and peri‐hepatic lymph nodes. Evidence for viral infection was found in the majority of PBC patients' peri‐hepatic lymph node samples. However, less than a third of the liver samples had detectable HBRV, whereas others were unable to detect betaretrovirus infection or noted the presence of virus in the liver of patients with other diagnoses.

Aims

To address the hypothesis that the betaretrovirus may be below the limits of detection in the liver, biliary epithelial cells (BEC) were investigated for the evidence of infection.

Methods

Ligation‐mediated PCR and next generation sequencing were used to detect proviral integrations in liver, lymph nodes and BEC isolated from liver transplant recipients. Hybridisation‐based assays were used to detect betaretroviral RNA in BEC.

Results

Unique HBRV integrations and betaretrovirus RNA were detected in the majority of biliary epithelia derived from patients with PBC, autoimmune hepatitis and cryptogenic liver disease but rarely in other liver transplant recipients with primary sclerosing cholangitis and other hepatic disorders. HBRV integrations were commonly found in PBC patients' lymph nodes but rarely in whole liver samples.

Conclusions

Human betaretrovirus infection is frequently observed at the site of disease in patients with primary biliary cirrhosis and also in biliary epithelium of patients with autoimmune hepatitis and cryptogenic liver disease.
Audit Market Structure and Competition in Australia
Authors: Carson Elizabeth , Redmayne Nives Botica , Liao Lin
Published: December 2014

The purpose of this review is to synthesise the existing research literature regarding the underlying structure and competitiveness of the Australian audit market. We consider the findings of Australian academic research, which has examined audit fees, non‐audit fees, market concentration, auditor choice, auditor switching and audit firm mergers. We identify the key metrics used to evaluate market structure in the academic literature and then document changes in these metrics in the Australian audit market for listed company audits during the period 2000–2011. Our analysis shows that the audit market is both highly segmented and supplier‐concentrated. We find that audit fees in Australia have increased over this period, which can be attributed to increased regulation and resulting increased audit effort needed to complete audit engagements in times of regulatory change and more recently, the global financial crisis. We provide regulators, standard setters and the profession with an evidenced‐based perspective on the market for the listed company audits, which is an important input into any future proposals to regulate the Australian audit market.
Prenatal Screening: An Ethical Agenda for the Near Future
Authors: de Jong Antina , de Wert Guido M.W.R.
Published: December 2014

Prenatal screening for foetal abnormalities such as Down's syndrome differs from other forms of population screening in that the usual aim of achieving health gains through treatment or prevention does not seem to apply. This type of screening leads to no other options but the choice between continuing or terminating the pregnancy and can only be morally justified if its aim is to provide meaningful options for reproductive choice to pregnant women and their partners. However, this aim should not be understood as maximizing reproductive choice per se. Only if understood as allowing prospective parents to avoid suffering related to living with (a child with) serious disorders and handicaps can prenatal screening be a publicly or collectively funded programme. The alternative of moving prenatal testing outside the healthcare system into the private sector is problematic, as it makes these tests accessible only to those who can afford to pay for it. New developments in prenatal screening will have to be assessed in terms of whether and to what extent they either contribute to or undermine the stated aim of providing meaningful options for reproductive choice. In the light of this criterion, this article discusses the introduction of the new non‐invasive prenatal test (NIPT), the tendency to widen the scope of follow‐up testing, as well as the possible future scenarios of genome‐wide screening and ‘prenatal personalised medicine’. The article ends with recommendations for further debate, research and analysis.
For Your Interest? The Ethical Acceptability of Using Non‐Invasive Prenatal Testing to Test ‘Purely for Information’
Authors: Deans Zuzana , Clarke Angus J. , Newson Ainsley J.
Published: December 2014

Non‐invasive prenatal testing (NIPT) is an emerging form of prenatal genetic testing that provides information about the genetic constitution of a foetus without the risk of pregnancy loss as a direct result of the test procedure. As with other prenatal tests, information from NIPT can help to make a decision about termination of pregnancy, plan contingencies for birth or prepare parents to raise a child with a genetic condition. NIPT can also be used by women and couples to test purely ‘for information’. Here, no particular action is envisaged following the test; it is motivated entirely by an interest in the result. The fact that NIPT can be performed without posing a risk to the pregnancy could give rise to an increase in such requests. In this paper, we examine the ethical aspects of using NIPT ‘purely for information’, including the competing interests of the prospective parents and the future child, and the acceptability of testing for ‘frivolous’ reasons. Drawing on several clinical scenarios, we claim that arguments about testing children for genetic conditions are relevant to this debate. In addition, we raise ethical concerns over the potential for objectification of the child. We conclude that, in most cases, using NIPT to test for adult‐onset conditions, carrier status or non‐serious traits presenting in childhood would be unacceptable.
Overall survival and competing risks of death in patients with Waldenström macroglobulinaemia: an analysis of theSurveillance,Epidemiology andEndResults database
Authors: Castillo Jorge J. , Olszewski Adam J. , Kanan Sandra , Meid Kirsten , Hunter Zachary R. , Treon Steven P.
Published: December 2014

Waldenström macroglobulinaemia (WM) is a rare and incurable lymphoma. Given that the survival ofWMpatients can be prolonged, our objective was to describe trends in overall survival (OS) and analyse competing risks of death in patients withWM. The analysis included 5784 patients diagnosed withWMbetween 1991 and 2010 from theSurveillance,Epidemiology andEndResults (SEER) database. Multivariate hazard models forOSand cumulative incidence of death were fitted according to epoch of diagnosis (1991–2000 vs. 2001–10) while adjusting for age, sex, race, histology, site of involvement and registry. MedianOSfor the 1991–2000 and the 2001–10 cohorts was 6 and 8 years, respectively (P < 0·001). In the multivariate analysis, betterOS[hazard ratio (HR) 0·73, 95% confidence interval (CI) 0·67–0·79;P < 0·001] was seen in the 2001–10 cohort. Survival benefits were identified, for the 2001–10 cohort, in almost every stratum analysed, with the exception of patients aged <50 years and blacks. In the multivariate competing‐risk analysis, the 2001–10 cohort experienced lower rates ofWM‐related (HR0·57, 95%CI0·49–0·66;P < 0·001) and non‐WM‐related deaths (HR0·72, 95%CI0·66–0·79;P < 0·001). In conclusion, there have been significant improvements inOS,WM‐related and non‐WM‐related mortality in patients withWMdiagnosed in the last decade.
Use of eltrombopag after romiplostim in primary immune thrombocytopenia
Authors: González‐Porras José Ramón , Mingot‐Castellano María Eva , Andrade Marcio M. , Alonso Rafael , Caparrós Isabel , Arratibel María Carmen , Fernández‐Fuertes Fernando , Cortti Maria José , Pascual Cristina , Sánchez‐González Blanca , Bernat Silvia , Fuertes‐Palacio Miguel Angel , Vázquez‐Paganini Juan Andrés , Olivera Pavel E. , Alvarez‐Román María Teresa , Jarque Isidro , Cortés Montserrat , Martínez‐Robles Violeta , Díaz‐Gálvez Francisco Javier , Calbacho María , Fernández‐Miñano Carmen , Garcia‐Frade Javier , González‐López Tomás José
Published: December 2014

The thrombopoietin receptor agonists (THPO‐RAs), romiplostim and eltrombopag, are effective and safe in immune thrombocytopenia (ITP). However, the value of their sequential use when no response is achieved or when adverse events occur with one THPO‐RA has not been clearly established. Here we retrospectively evaluated 51 primary ITP adult patients treated with romiplostim followed by eltrombopag. The median age of our cohort was 49 (range, 18–83) years. There were 32 women and 19 men. The median duration of romiplostim use before switching to eltrombopag was 12 (interquartile range 5–21) months. The reasons for switching were: lack of efficacy (n = 25), patient preference (n = 16), platelet‐count fluctuation (n = 6) and side‐effects (n = 4). The response rate to eltrombopag was 80% (41/51), including 67% (n = 35) complete responses. After a median follow‐up of 14 months, 31 patients maintained their response. Efficacy was maintained after switching in all patients in the patient preference, platelet‐count fluctuation and side‐effect groups. 33% of patients experienced one or more adverse events during treatment with eltrombopag. We consider the use of eltrombopag after romiplostim for treating ITP to be effective and safe. Response to eltrombopag was related to the cause of romiplostim discontinuation.
Long‐term follow‐up of dose‐adjusted EPOCH plus rituximab (DA‐EPOCH‐R) in untreated patients with poor prognosis large B‐cell lymphoma. A phase II study conducted by the Spanish PETHEMA Group
Authors: Purroy Noelia , Bergua Juan , Gallur Laura , Prieto Julio , Lopez Luis A. , Sancho Juan M. , García‐Marco Jose A. , Castellví Josep , Montes‐Moreno Santiago , Batlle Ana , de Villambrosia Sonia Gonzalez , Carnicero Fernando , Ferrando‐Lamana Lucía , Piris Miguel A , Lopez Andrés
Published: December 2014

This prospective multi‐institutional phase II study was designed to assess the efficacy and safety of dose‐adjustedEPOCH(etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) plus rituximab (DA‐EPOCH‐R) in untreated patients with poor prognosis large B‐cell lymphomas. Eighty‐one patients diagnosed with diffuse large B‐cell lymphoma (DLBCL,n = 68), primary mediastinalDLBCL(n = 6) and follicular lymphoma Grade 3b (n = 7), with an age‐adjusted International Prognostic Index >1, were eligible for analysis. Median age was 60 years (range: 21–77). Sixty‐five patients (80·2%) achieved complete response. After a median follow‐up time of 64 months, 10‐year event‐free survival and overall survival (OS) were 47·8% and 63·6%, respectively. None of the studied clinical and biological characteristics were associated with poorer outcome. Interestingly, patients withBCL6rearrangement achieved a 10‐yearOSof 100%, while patients withBCL2rearrangement exhibited a poorer outcome compared to activated B‐cell tumours and germinal centre B‐cell withoutBCL2rearranged tumours. Results achieved withDA‐EPOCH‐Rshowed a good long‐term outcome and a tolerable toxicity profile in high‐risk large B cell lymphoma patients. Outcome was not affected by tumour cell proliferation or by cell of origin, highlighting the requirement of new biological markers for patient subclassification of high‐riskDLBCLpatients.
3,3′‐Diindolylmethane attenuates LPS‐mediated acute liver failure by regulating miRNAs to target IRAK4 and suppress Toll‐like receptor signalling
Authors: Tomar S , Nagarkatti M , Nagarkatti P S
Published: December 2014

Background and Purpose

Acute liver failure (ALF) is a severe and potentially lethal clinical syndrome. 3,3′‐Diindolylmethane (DIM) is a natural plant‐derived compound with anti‐cancer activities. Recently, DIM has also been shown to have anti‐inflammatory properties. Here, we tested the hypothesis that DIM would suppress endotoxin‐induced ALF.

Experimental Approach

We investigated the therapeutic potential of DIM in a mouse model of D‐galactosamine/Lipopolysaccharide (GalN/LPS)‐induced ALF. The efficacy of DIM treatment was assessed by survival, liver histopathology, serum levels of alanine transaminase, pro‐inflammatory cytokines and number of activated liver macrophages. Effects of DIM on the expression of two miRNAs, 106a and 20b, and their predicted target gene were measured by qRT‐PCR and Western blotting. Effects of DIM on the release of TNF‐α from RAW264.7 macrophages transfected with mimics of these miRNAs and activated by LPS was assessed by elisa.

Key Results

DIM treatment protected mice from ALF symptoms and reduced the number of activated liver macrophages. DIM increased expression of miR‐106a and miR‐20b in liver mononuclear cells and decreased expression of their predicted target gene IL‐1 receptor‐associated kinase 4 (IRAK4), involved in signalling from Toll‐like receptor 4 (TLR4). In vitro transfection of RAW264.7 cells using miRNA mimics of miR‐106a and 20b decreased expression of IRAK4 and of TNF‐α secretion, following LPS stimulation.

Conclusions and Implications

DIM attenuated GalN/LPS‐induced ALF by regulating the expression of unique miRNAs that target key molecules in the TLR4 inflammatory pathway. DIM may represent a potential novel hepatoprotective agent.
High‐affinity σ1 protein agonist reduces clinical and pathological signs of experimental autoimmune encephalomyelitis
Authors: Oxombre B , Lee‐Chang C , Duhamel A , Toussaint M , Giroux M , Donnier‐Maréchal M , Carato P , Lefranc D , Zéphir H , Prin L , Melnyk P , Vermersch P
Published: December 2014

Background and Purpose

Selective agonists of the sigma‐1 receptor (σ1 protein) are generally reported to protect against neuronal damage and modulate oligodendrocyte differentiation. Human and rodent lymphocytes possess saturable, high‐affinity binding sites for compounds binding to the σ1 protein and potential immunomodulatory properties have been described for σ1 protein ligands. Experimental autoimmune encephalomyelitis (EAE) is recognized as a valuable model of the inflammatory aspects of multiple sclerosis (MS). Here, we have assessed the role of a σ1 protein agonist, containing the tetrahydroisoquinoline‐hydantoin structure, in EAE.

Experimental Approach

EAE was induced in SJL/J female mice by active immunization with myelin proteolipid protein (PLP)139–151 peptide. The σ1 protein agonist was injected i.p. at the time of immunization (day 0). Disease severity was assessed clinically and by histopathological evaluation of the CNS. Phenotyping of B‐cell subsets and regulatory T‐cells were performed by flow cytometry in spleen and cervical lymph nodes.

Key Results

Prophylactic treatment of EAE mice with the σ1 protein agonist prevented mononuclear cell accumulation and demyelination in brain and spinal cord and increased T2 B‐cells and regulatory T‐cells, resulting in an overall reduction in the clinical progression of EAE.

Conclusions and Implications

This σ1 protein agonist, containing the tetrahydroisoquinoline‐hydantoin structure, decreased the magnitude of inflammation in EAE. This effect was associated with increased proportions of B‐cell subsets and regulatory T‐cells with potential immunoregulatory functions. Targeting of the σ1 protein might thus provide new therapeutic opportunities in MS.
The catalytic topoisomerase II inhibitor dexrazoxane induces DNA breaks, ATF3 and the DNA damage response in cancer cells
Authors: Deng Shiwei , Yan Tiandong , Nikolova Teodora , Fuhrmann Dominik , Nemecek Andrea , Gödtel‐Armbrust Ute , Kaina Bernd , Wojnowski Leszek
Published: December 2014

Background and Purpose

The catalytic topoisomerase II inhibitor dexrazoxane has been associated not only with improved cancer patient survival but also with secondary malignancies and reduced tumour response.

Experimental Approach

We investigated the DNA damage response and the role of the activating transcription factor 3 (ATF3) accumulation in tumour cells exposed to dexrazoxane.

Key Results

Dexrazoxane exposure induced topoisomerase IIα (TOP2A)‐dependent cell death, γ‐H2AX accumulation and increased tail moment in neutral comet assays. Dexrazoxane induced DNA damage responses, shown by enhanced levels of γ‐H2AX/53BP1 foci, ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3‐related), Chk1 and Chk2 phosphorylation, and by p53 accumulation. Dexrazoxane‐induced γ‐H2AX accumulation was dependent on ATM. ATF3 protein was induced by dexrazoxane in a concentration‐ and time‐dependent manner, which was abolished in TOP2A‐depleted cells and in cells pre‐incubated with ATM inhibitor. Knockdown of ATF3 gene expression by siRNA triggered apoptosis in control cells and diminished the p53 protein level in both control and dexrazoxane ‐treated cells. This was accompanied by increased γ‐H2AX accumulation. ATF3 knockdown also delayed the repair of dexrazoxane ‐induced DNA double‐strand breaks.

Conclusions and Implications

As with other TOP2A poisons, dexrazoxane induced DNA double‐strand breaks followed by activation of the DNA damage response. The DNA damage‐triggered ATF3 controlled p53 accumulation and generation of double‐strand breaks and is proposed to serve as a switch between DNA damage and cell death following dexrazoxane treatment. These findings suggest a mechanistic explanation for the diverse clinical observations associated with dexrazoxane.
The Ca2+ channel inhibitor 2‐APB reverses β‐amyloid‐induced LTP deficit in hippocampus by blocking BAX and caspase‐3 hyperactivation
Authors: Hu Wei‐Yan , He Zhi‐Yong , Yang Lu‐Jun , Zhang Ming , Xing Da , Xiao Zhi‐Cheng
Published: December 2014

Background and Purpose

At the early stage of Alzheimer's disease (AD), the accumulation of β‐amyloid (Aβ) oligomers disturbs intracellular Ca2+ homeostasis and disrupts synaptic plasticity of brain neurons. Prevention of Aβ‐induced synaptic failure remains an unsolved problem for the treatment of AD. Here, the effects of 2‐aminoethoxydiphenyl borate (2‐APB), a non‐specific, but moderately potent Ca2+ channel inhibitor, on Aβ‐induced deficit of synaptic long‐term potentiation (LTP) and the underlying molecular mechanisms were explored.

Experimental Approach

We used hippocampal slices and primary cultures of hippocampal neurons from C57BL/6 mice. Methods applied in our study included electrophysiological recording, membrane protein extraction, Western blot assay and Ca2+ imaging.

Key Results

2‐APB at 10 μM effectively reversed suppression by oligomeric Aβ1–42 (500 nM) of LTP in hippocampal slices. 2‐APB also restored phosphorylation and trafficking of the glutamate receptor subunit GluA1 in Aβ‐treated hippocampal slices, supporting its protective action on synaptic function. Aβ‐mediated abnormal neuronal [Ca2+]i elevation and hyperactivation of the mitochondrial apoptotic proteins BAX, caspase‐3, and glycogen synthase kinase‐3β, were blocked by 2‐APB pretreatment. Moreover, the defict in long term potentiation deficit in hippocampal slices from APPswe/PS1ΔE9 gene mutant mice was rescued by 2‐APB at 10 μM.

Conclusions and Implication

These data demonstrate that 2‐APB is a potentially useful chemical to protect synaptic plasticity against neurotoxic effects of Aβ in AD.
Beyond Surrogacy—A Multi‐taxon Approach to Conservation Biogeography
Authors: Smith‐Patten Brenda D. , Patten Michael A.
Published: December 2014

Biogeographic analysis of species turnover (β diversity) of plants and animals among regions often yields conflicting results, with regions of high β diversity identified for some taxonomic groups but not others. Such discordance calls into question the use of surrogate taxa to forge conservation plans. This discordance begs for a means of comparing multiple taxa across phyla in a manner that is cost‐effective, considers limitations in computer resources in certain global regions, and is understood by policy makers and land managers. As a test case for a method taking into account these considerations, we used species lists for ten organismal groups (spanning plants, vertebrates, and invertebrates) to identify regions of high β diversity using Monmonier's algorithm, a spatially explicit technique that is readily implemented and interpreted. Data were for montane (>1000 m elevation) species across the Eastern Arc of Tanzania and Kenya and surrounding areas. Our results indicate that surrogacy does not make for the most effective expenditure of conservation efforts. We also show that to use a multi‐taxon approach one need not rely on intensive surveys of areas in order to make conservation decisions, including reserve selection. Our approach also eliminates the need for complex modeling and comparisons common to many GIS‐based complementarity techniques. Additionally, a wide variety of socioeconomic, political, demographic, geological, climatological, and evolutionary factors can be incorporated into the technique to help shape conservation biogeography from a local and regional perspective. This technique can bridge the gap between conservation biogeography theory and application in tropical regions and beyond.
How Barriers to Collaboration Prevent Progress in Demand for Knowledge: A Dyadic Study of Small and Medium‐Sized Firms, Research and Technology Organizations and Universities
Authors: Goduscheit René Chester , Knudsen Mette Præst
Published: December 2014

This article analyses the challenging collaboration between small and medium‐sized enterprises (SMEs) and knowledge institutions. The aim of the article is to shed light on the barriers, which hinder collaboration, and to investigate the particular role of research and technology organizations (RTOs) as potential mediators of collaboration between SMEs and universities. On the basis of a unique sample consisting of 151 SMEs, RTOs and universities from seven countries, the differences across dyads of potential collaborations are identified. In particular, the article finds that both firms and universities with collaboration experience with the other partner in general perceive higher barriers than inexperienced firms or universities. In terms of the mediating role of RTOs, the article illustrates that universities perceive lower barriers when collaborating with RTOs than with SMEs. A similar tendency to a mediating role of RTOs can be found among the SMEs' perception of university collaboration. Finally, the analysis shows that the knowledge institutions perceive the SMEs as very important collaboration partners, but the same sense of importance is not shared by the SMEs regarding collaboration with the knowledge institutions. Hence, there seems to be a quite unbalanced view on the potential of the collaborative ties, which is further discussed in the conclusion.
mtDNA mutations variously impact mtDNA maintenance throughout the human embryofetal development
Authors: Steffann J. , Monnot S. , Bonnefont J.‐P.
Published: December 2014

Mitochondria are the largest generator of ATP in the cell. It is therefore expected that energy‐requiring processes such as oocyte maturation, early embryonic or fetal development, would be adversely impacted in case of mitochondrial deficiency. Human mitochondrial DNA (mtDNA) mutations constitute a spontaneous model of mitochondrial failure and offer the opportunity to study the consequences of energetic defects over fertility and embryofetal development. This review provides an update on the mtDNA metabolism in the early preimplantation embryo, and compiles data showing the impact of mtDNA mutations over mtDNA segregation. Despite convincing evidences about the essential role of mitochondria in oogenesis and preimplantation development, no correlation between the presence of a mtDNA mutation and fertilization failure, impaired oocyte quality, or embryofetal development arrest was found. In some cases, mutant cells might upregulate their mitochondrial content to overcome the bioenergetic defects induced by mtDNA mutations, and might escape negative selection. Finally we discuss some of the clinical consequences of these observations.
Pathological response of locally advanced rectal cancer to preoperative chemotherapy without pelvic irradiation
Authors: Bensignor T. , Brouquet A. , Dariane C. , Thirot‐Bidault A. , Lazure T. , Julié C. , Nordlinger B. , Penna C. , Benoist S.
Published: December 2014

Aim

Pathological response to chemotherapy without pelvic irradiation is not well defined in rectal cancer. This study aimed to evaluate the objective pathological response to preoperative chemotherapy without pelvic irradiation in middle or low locally advanced rectal cancer (LARC).

Methods

Between 2008 and 2013, 22 patients with middle or low LARC (T3/4 and/or N+ and circumferential resection margin < 2 mm) and synchronous metastatic disease or a contraindication to pelvic irradiation underwent rectal resection after preoperative chemotherapy. The pathological response of rectal tumour was analysed according to the Rödel tumour regression grading (TRG) system. Predictive factors of objective pathological response (TRG 2–4) were analysed.

Results

All patients underwent rectal surgery after a median of six cycles of preoperative chemotherapy. Of these, 20 (91%) had sphincter saving surgery and an R0 resection. Twelve (55%) patients had an objective pathological response (TRG 2–4), including one complete response. Poor response (TRG 0–1) to chemotherapy was noted in 10 (45%) patients. In univariate analyses, none of the factors examined was found to be predictive of an objective pathological response to chemotherapy. At a median follow‐up of 37.2 months, none of the 22 patients experienced local recurrence. Of the 19 patients with Stage IV rectal cancer, 15 (79%) had liver surgery with curative intent.

Conclusion

Preoperative chemotherapy without pelvic irradiation is associated with objective pathological response and adequate local control in selected patients with LARC. Further prospective controlled studies will address the question of whether it can be used as a valuable alternative to radiochemotherapy in LARC.
Improving recognition and referral of patients with an increased familial risk of colorectal cancer: results from a randomized controlled trial
Authors: Dekker N. , Hermens R. P. , de Wilt J. H. , van Zelst‐Stams W. A. , Hoogerbrugge N. ,   the RISCO study group
Published: December 2014

Aim

Only 12–49% of colorectal cancer (CRC) patients and their first‐degree relatives with an increased familial CRC risk are referred for cancer prevention measures (surveillance colonoscopies or genetic counselling). The study was performed to evaluate the effectiveness and feasibility of a novel strategy to improve the uptake of genetic counselling for high risk individuals and surveillance colonoscopy for moderate risk groups.

Method

Eighteen hospitals participated in a clustered randomized controlled trial. Patients in nine hospitals received usual care (group A). Nine other hospitals received the novel strategy (group B) including access to a website for patients and clinicians, patient‐targeted brochures and clinician‐targeted education and pocket referral cards. Data before and after dissemination of the strategy were collected from questionnaires and medical records.

Results

Data were complete for 358 (44%) of 820 CRC patients and 50 (36%) of 137 clinicians before dissemination of the strategy and 392/862 patients (45%) and 47/137 clinicians (34%) after. Referral for cancer prevention measures was assessed at a median of 8 (2–12) months after CRC diagnosis in groups A and B before the dissemination of the strategy and in group A after. In group B referral was assessed at a median of 9 (4–11) months after the dissemination of the strategy. Uptake of genetic counselling by high risk patients was equal in groups A and B, being 33% before and 15% after (P = 0.003). Uptake of surveillance colonoscopy by moderate risk relatives did not change significantly (group A, 36% before vs 41% after; group B, 33% before vs 19% after). In group B 94/140 patients (67%) and 25/72 clinicians (35%) visited the website and 34/140 (24%) patients read the brochure. Patients valued clinicians' information as most useful, followed by the patient brochure. Clinicians preferred pocket cards and education.

Conclusion

Our strategy did not improve referral for cancer prevention measures. Although the newly offered strategy elements were appreciated, patients preferred clinicians' advice regarding referral for cancer prevention measures. It may be useful to aim future interventions at healthcare professionals rather than patients to improve the prevention of familial cancer.
Anarchist Participatory Development: A Possible New Framework?
Authors: Wald Navé
Published: December 2014

This article examines the ongoing critiques and debates around the ‘participatory turn’ in development theory and practice and suggests anarchism as a practice‐oriented theoretical framework for engaging with what participatory development ought to achieve. Explicit links are constructed between key terms in these development debates and anarchist political philosophy, and a call is made for greater attention to anarchism as a theoretical framework for radical and transformative development practice. This article then analyses empirical experiences of ‘anarchistic partnerships’ between development experts and grassroots peasant‐indigenous organizations in north‐west Argentina, who, although not self‐identifying as anarchist, adhere to ideals such as horizontal prefigurative politics and radical democracy that are effectively anarchist in their orientation. These experiences challenge the NGO–social movement divide and offer a virtually unexplored form of radical development practice that is worthy of further academic attention. Thus, while this article is concerned with familiar debates in development studies, it offers some preliminary directions for advancing theoretical and practical knowledge regarding transformative participation.
OWN‐NATIONALITY BIAS: EVIDENCE FROM UEFA CHAMPIONS LEAGUE FOOTBALL REFEREES
Authors: Pope Bryson R. , Pope Nolan G.
Published: December 2014

We examine the existence and magnitude of own‐nationality bias. Using player‐match level data from 12 seasons of the UEFA Champions League (UCL) and referee assignment policies that pair players and referees from the same country, we determine the bias that referees exhibit toward players from their native country. Players officiated by a referee from the same country receive a 10% increase in beneficial foul calls. Referees' own‐nationality bias is more pronounced for national team players, players at home, and in later stages of the tournament. Elite referees exhibit as much, or more, own‐nationality bias as their less experienced counterparts. (JEL L83, J15)
Geographical distribution, climatic variability and thermo‐tolerance of Chagas disease vectors
Authors: de la Vega Gerardo J. , Medone Paula , Ceccarelli Soledad , Rabinovich Jorge , Schilman Pablo E.
Published: December 2014

Understanding the relationship between geographic range limits and physiological traits of vector species is under increasing demand to predict the potential effects of global warming, not only in terms of geographic distribution of vector species but also in terms of the risk of disease transmission. Like in many other insect species, the geographical distribution of Chagas’ disease vectors is affected by temperature. This study examines, for the first time, the relationship between the limits of geographic distribution and thermo‐tolerance of the most important vectors of Chagas disease, Triatoma infestans in southern South America and Rhodnius prolixus in northern South America and Central America, to test the climatic variability hypothesis (CVH). We applied species distribution modeling (SDM) using bioclimatic variables and identified the most important limiting factors of the habitat suitability. Then, we measured and compared: the critical thermal maximum (CTmax) and the upper lethal temperature (ULT) (measured by thermo‐limit respirometry), chilled coma recovery (i.e. the time to recovery from 4 h at 0°C) and the critical thermal minimum (CTmin). For both species the minimum temperature of the coldest month was the most important abiotic factor restricting their geographic distribution. By taking a correlative approach and testing predictions with thermal tolerance traits, it was possible to explain the southern limit distribution for both species in terms of physiological constraints. The greater temperature tolerance of T. infestans compared to R. prolixus supports the CVH.
Role of large‐ and fine‐scale variables in predicting catch rates of larval Pacific lamprey in the Willamette Basin, Oregon
Authors: Schultz Luke D. , Mayfield Mariah P. , Sheoships Gabe T. , Wyss Lance A. , Clemens Benjamin J. , Whitlock Steven L. , Schreck Carl B.
Published: December 2014

Pacific lamprey Entosphenus tridentatus is an anadromous fish native to the Pacific Northwest of the USA. That has declined substantially over the last 40 years. Effective conservation of this species will require an understanding of the habitat requirements for each life history stage. Because its life cycle contains extended freshwater rearing (3–8 years), the larval stage may be a critical factor limiting abundance of Pacific lamprey. The objective of our study was to estimate the influence of barriers and habitat characteristics on the catch‐per‐unit‐effort (CPUE) of larval Pacific lamprey in the Willamette River Basin, Oregon, USA. We sampled lampreys at multiple locations in wadeable streams throughout the basin in 2011–13 and used an information theoretic approach to examine the relative influence of fine‐ and large‐scale predictors of CPUE. Pacific lamprey was observed across the basin, but its relative abundance appeared to be limited by the presence of natural and artificial barriers in some sub‐basins. Lower velocity habitats such as off‐channel areas and pools contained higher densities of larval lamprey; mean Pacific lamprey CPUE in off‐channel habitats was 4 and 32 times greater than in pools and riffles respectively. Restoration and conservation strategies that improve fish passage, enhance natural hydrologic and depositional processes and increase habitat heterogeneity will likely benefit larval Pacific lamprey.
The diffusion and impact of the corporation in 1910
Authors: Foreman‐Peck James , Hannah Leslie
Published: December 2014

With new and comprehensive data on the international spread of listed and unlisted corporations before the First World War, this article shows the prominence of common law and Scandinavian civil law in the process. This association is interpreted as demonstrating the strong contribution of liberal (laissez‐faire) industrial stances. The findings confirm an extended version of Rajan and Zingales's hypothesis that trade and capital openness are necessary for companies to flourish. Despite the possibilities that companies were created for fraud and exploitation, countries using the corporate form more extensively before 1914 had higher GDP per capita. Through this process, the benefit of imperialism extended to British dominions, but not much, if at all, to British dependent colonies.
Fatigue strength of severely notched specimens made of Ti–6Al–4V under multiaxial loading
Authors: Berto F. , Campagnolo A. , Lazzarin P.
Published: December 2014

The present paper deals with multiaxial fatigue behaviour of severely notched components made of titanium grade 5 alloy (Ti–6Al–4V). The experimental tests have been carried out under combined Mode I and Mode III loadings, both in phase and out of phase. Cylindrical specimens weakened by circumferential notches have been employed. Different nominal load ratios have been applied in the tests (R = −1, 0 and 0.5). The specimens had a notch‐tip radius smaller than 0.1 mm, a notch depth equal to 6 mm and an opening angle of 90°. The results obtained by multiaxial fatigue testing are depicted in comparison with data from pure modes of loading on smooth and notched samples, characterized by a load ratio in the range −3 ≤ R ≤ 0.5. A large bulk of new fatigue data (more than 160) is summarized in the manuscript. The data are first plotted in terms of the nominal stress amplitudes, and then they are reanalysed by means of the local energy measured in the control volumes surrounding the notch tip. The dependence of the size of the control radius as a function of the loading mode is analysed. A very different behaviour is found for tension and torsion, corresponding to a different notch sensitivity.
Effectiveness of a large reserve network in protecting freshwater biodiversity: a test for the Iberian Peninsula
Authors: Hermoso Virgilio , Filipe Ana Filipa , Segurado Pedro , Beja Pedro
Published: December 2014

Although coverage by protected areas is increasing worldwide, their capacity to protect freshwater biodiversity is uncertain. This may be the case of the European Natura 2000, the world's largest reserve network, given its primary focus on terrestrial biodiversity. We tested this hypothesis by assessing the effectiveness of Natura 2000 in protecting freshwater biodiversity and associated key ecological processes in the Iberian Peninsula, where more than 25% of land is under some kind of protection.

We compiled distributional data on 91 species of freshwater fish, amphibians and aquatic reptiles, at the subcatchment scale (c. 20 km2 resolution), for the whole Iberian Peninsula, and assessed the proportion of their ranges covered by Natura 2000. We also explored the coverage of the main environmental gradients, and the capacity of Natura 2000 to offer protection against human impacts. To do so, we evaluated land‐use intensity and the human footprint within and upstream of protected areas, both of which might compromise the protection of biodiversity. Finally, we also analysed the incidence of reservoirs within and downstream of protected areas.

Natura 2000 broadly covers the main environmental gradients in the Iberian Peninsula, but fails to provide sufficient coverage of freshwater biodiversity, with <20% of the range of species covered on average. This would be insufficient to achieve a modest conservation target of 25% of the range for more than 80% of species, including most of species specifically listed in the legislation. Moreover, although the network tends to comprise areas with the least human impact, it seems to be vulnerable to the propagation of upstream effects (intensive land use downstream) and the loss of downstream connectivity (reservoirs).

Large reserve networks, primarily designed to protect terrestrial biodiversity, may not offer adequate protection for freshwater biodiversity. We recommend revisiting the design of Natura 2000 to improve the representation of freshwater biodiversity and enhance its capacity to address threats and particular ecological needs, such as for migration. Given the high pressure on land and the poor condition of the remaining unprotected habitat, conservation efforts must minimise the conflict of interest and management costs.
Theorising the Thaw: Geopolitics in a Changing Arctic
Authors: Bruun Johanne M. , Medby Ingrid A.
Published: December 2014

As the effects of climate change are becoming more and more pronounced, the Arctic region is attracting renewed attention from politicians, transnational corporations, and environmentalists alike, many of whom are based geographically far from the region itself. Interests span from the prospects of vast oil and mineral riches and shorter international shipping routes, to preserving what is often framed as a fragile, pristine environment. As a resource frontier and a wilderness, but also a homeland and a space of culture to its inhabitants, the Arctic is characterised by potentially conflicting geographical imaginaries and visions of both the present as well as the future of the region. Hence, the political geographies of the Arctic are both messy and complex. This paper examines some of the principal themes and issues of Arctic geopolitics and offers a discussion of how scholars of Political Geography have engaged the topic at a time when an increasing number of academics are directing their analytical gaze towards the North. Focusing on publications from the past decade, it aims to contextualise scholarly debates on Arctic geopolitics and illustrate the complexity and richness of the topic.