bluuebunny/crossref_metadata_2025 huggingface dataset:
Do baseline Cereblon gene expression and IL‐6 receptor expression determine the response to thalidomide–dexamethasone treatment in Multiple myeloma patients?
Authors: Bedewy Ahmed M. L. , EL‐Maghraby Shereen M.
Published: October 2013

Immunomodulatory drugs (IMiDs) are key components of treatment for hematologic malignancies, especially multiple myeloma (MM). Cereblon (CRBN) expression was described to be essential for the activity of thalidomide. Furthermore, IMiD binding to CRBN is cytotoxic to multiple myeloma cells and absence of CRBN confers IMiDs resistance. Interleukin‐6 (IL‐6) is a potent pleiotropic cytokine that regulates plasma cell (PC) growth via the IL‐6 receptor (IL‐6R). IL‐6/IL‐6R autocrine activity is implicated in the development and progression of cancers including cervical cancer, prostate cancer, and multiple myeloma. The aim of the study was to evaluate CRBN and IL‐6R expressions and their impact on clinical efficacy of dexamethasone–thalidomide therapy in multiple myeloma (MM) patients, in addition to their association with other clinical and prognostic parameters. Forty‐six newly diagnosed MM patients were enrolled in the study. We measured CRBN expression prior to therapy initiation by real‐time polymerase chain reaction in 46 bone marrow (BM) aspiration samples of patients and controls. In addition, IL‐6R expression was evaluated on BM biopsies of patients and controls by immunohistochemistry (IHC). Twenty‐eight males (60.9%) and 18 females (39.1%) were enrolled. The mean age was 65.11 ± 7.3 yr (range 39–77 yr). Median CRBN expression in 46 BM samples of MM patients was significantly higher than in controls (P < 0.001). Among established prognostic parameters, international staging system (ISS), serum beta‐2‐microglobulin (B2M), and serum albumin correlated reversely with CRBN expression. IL‐6R expression was significantly higher in patients than in controls. IL‐6R expression was significantly associated with response to treatment (P < 0.001), B2M (P = 0.032), and ISS (P = 0.028). Strong intensity expression was associated with low CRBN expression (P = 0.001).In conclusion, CRBN expression may provide a biomarker to predict response to IMiD in patients with MM and its high expression can serve as a marker of good prognosis. Strong IL‐6R expression is associated with poor response to therapy in multiple myeloma patients and may be used as a prognostic marker.
Association between statin use and intracerebral hemorrhage: a systematic review and meta‐analysis
Authors: Lei C. , Wu B. , Liu M. , Chen Y.
Published: October 2013

Background and purpose

Accumulating evidence suggests that statins exert neuroprotective effects, but whether their use affects the outcomes of intracerebral hemorrhage (ICH) remains controversial. Therefore, we performed a systematic review and meta‐analysis to investigate whether statin use before spontaneous ICH affects unfavorable functional outcome or mortality.

Methods

We searched the Cochrane Library, MEDLINE, EMBASE and China National Knowledge Infrastructure databases for studies examining the effects of pre‐ICH statin use on unfavorable functional outcome, mortality or neuroimaging outcomes in consecutively recruited patients with spontaneous ICH, regardless of the duration or dose of statin treatment.

Results

A total of 12 studies were included that examined the effects of pre‐ICH statin use on post‐ICH outcomes in 1652 subjects in the favors pre‐statin group and 5309 in the favors no pre‐ICH statin group. Meta‐analysis of 11 studies suggested that pre‐ICH statin use did not significantly affect mortality across all three time points tested [in‐hospital, 30 days, 90 days; odds ratio (OR) 0.85, 95% confidence interval (CI) 0.70–1.03]. However, meta‐analysis of seven studies showed that pre‐ICH statin use did significantly decrease 90‐day mortality (OR 0.72, 95% CI 0.59–0.88). Meta‐analysis of six studies showed that pre‐ICH statin use was not associated with significant changes in unfavorable functional outcome. Moreover, pre‐ICH statin use did not significantly affect admission hematoma volume (standardized mean difference 7.75, 95% CI −5.59 to 21.09).

Conclusion

Available evidence suggests that statin use before spontaneous ICH does not increase short‐term mortality, unfavorable functional outcome or post‐ICH hematoma volume at admission.
Trajectories of health‐related quality of life in children with epilepsy: A cohort study
Authors: Ferro Mark A. , Camfield Carol S. , Levin Simon D. , Smith Mary Lou , Wiebe Samuel , Zou GuangYong , Speechley Kathy N.
Published: October 2013

Purpose

Little is known about subgroups of children with epilepsy who may experience less favorable outcomes over time. The objectives of this study were to document trajectories of health‐related quality of life (HRQL) and to identify predictors of the trajectory group in children with new‐onset epilepsy.

Methods

Data were obtained from the Health Related Quality of Life in Children with Epilepsy Study, a prospective multisite study of children 4–12 years old with new‐onset epilepsy followed for 24 months. Health‐related quality of life was measured using the Quality of Life in Childhood Epilepsy questionnaire. Trajectories of HRQL were investigated using latent class trajectory modeling. Multinomial logistic regression was used to identify child, parent, and family predictors of HRQL trajectories.

Key Findings

A total of 374 families responded at baseline and 283 (76%) completed the study. Five HRQL trajectories were observed: low‐increasing (4%), moderate‐decreasing (12%), moderate‐increasing (22%), high‐increasing (32%), and high‐stable (30%). Many children in the low‐increasing, moderate‐increasing, high‐increasing, and high‐stable had clinically meaningful improvements in HRQL: 82%, 47%, 63%, and 44%, respectively. In contrast, the majority of children in the moderate‐decreasing group (56%) experienced clinically meaningful declines in their HRQL. Factors predicting trajectories were number of antiepileptic drugs prescribed, presence of comorbid behavior or cognitive problems, parent depression, and family functioning and demands.

Significance

Results suggested that children with epilepsy are not homogenous but rather consist of groups with different trajectories and unique predictors of HRQL. Problems associated with child behavior and cognition were the strongest predictors identified. Given that several risk factors are modifiable, it is important to examine these as potential targets within a family‐centered framework to improve HRQL of children with new‐onset epilepsy.
Tonic seizures ofLennox‐Gastaut syndrome: Periictal single‐photon emission computed tomography suggests a corticopontine network
Authors: Intusoma Utcharee , Abbott David F. , Masterton Richard A. J. , Stagnitti Monique R. , Newton Mark R. , Jackson Graeme D. , Freeman Jeremy L. , Harvey A. Simon , Archer John S.
Published: October 2013

Purpose

Lennox‐Gastaut syndrome (LGS) is a severe epileptic disorder with characteristic electroclinical features but diverse etiologies. The shared electroclinical characteristics suggest that common cerebral networks are involved in generating seizures. We sought to reveal these networks by comparing ictal and interictal single‐photon emission computed tomography (SPECT).

Methods

We identified 10 ictal–interictalSPECTpairs from seven patients withLGS(median age 11 years; range 1–38) who were studied during video electroencephalography (EEG)–confirmed tonic seizures. We performed a voxel‐wise comparison of ictal and interictalSPECTstudies across the group. The evolution of blood flow changes was explored by examining early and late injection groups.

Key Findings

Median duration of tonic seizures was 10 s (range 6–29 s), and injection latency from seizure offset was −8 to 48 s. In the early injection group (<10 s; three studies), there was hyperperfusion over pons and cerebellar hemispheres (p < 0.05 cluster corrected family wise error), and hypoperfusion bilaterally over the pericentral region, with a trend toward hyperperfusion over bilateral superior and middle frontal gyri, and lateral parietal cortex. In the late injection group, there was hyperperfusion over midline and lateral cerebellar regions, with hypoperfusion widely over bilateral frontal regions.

Significance

This study suggests that the tonic seizures ofLGSresult from activity in a network, containing bilateral frontal and parietal association areas and the pons. We postulate that tonic seizures recruit the corticoreticular system, which connects frontal attentional areas to the pontine reticular formation, and is normally responsible for postural tone and orienting behavior.
Internal versus External Ownership Transition in Family Firms: An Embeddedness Perspective
Authors: Wiklund Johan , Nordqvist Mattias , Hellerstedt Karin , Bird Miriam
Published: October 2013

We investigate factors that influence family business owners’ choice between passing ownership within the family or to new external owners. Taking an embeddedness perspective focusing on owner–family structure and involvement, we hypothesize that ownership dispersion, number of potential heirs, multigenerational involvement, and whether the chief executive officer is a family member influence the choice of an internal or external transition of ownership. We build a longitudinal data set from a sample of 3,829 family firms and their ownership transitions. Our theorizing and findings regarding ownership transitions complements the abundant research on management succession and therefore constitutes an important contribution to the literature.
The Accidental Internationalists: A Theory of Born Globals
Authors: Hennart Jean–François
Published: October 2013

The distinguishing characteristic of international new ventures/born globals (INVs/BGs) is that they have foreign sales from the outset, or very quickly afterward. I argue that this is due to their business model. INVs/BGs sell to spatially dispersed customers distinctive niche products that incur low communication, transportation, and adaptation costs. In contrast to the firms described by the Uppsala model, selling to foreign customers does not require additional time or effort for INVs/BGs. Thus INVs/BGs can be seen as accidental internationalists.
Protective effect of a direct renin inhibitor in acute murine model of cardiotoxicity and nephrotoxicity
Authors: Rashikh Azhar , Pillai Krishna Kolappa , Najmi Abul Kalam
Published: October 2013

This study aimed to investigate the possible protective effects of aliskiren against doxorubicin (DXR)‐induced cardiorenal injury and to identify the mechanisms involved. Intraperitoneal administration of DXR (15 mg/kg, body weight, as a single dose) caused significant induction in the levels of angiotensin I, caspase‐3, lactate dehydrogenase (LDH), lipid peroxidation malondialdehyde (MDA), urea, and creatinine. Concomitant decline in the levels of albumin and total protein in plasma, reduction in reduced glutathione (GSH), and antiperoxidative enzyme superoxide dismutase (SOD) levels followed by ultrastructural alterations in the myocardial and renal tissues were also observed. Oral administration of aliskiren (100 mg/kg, for a period of 14 days) significantly prevented all these DXR‐induced adverse effects and maintained the rats near to normal status. However, telmisartan (10 mg/kg) pretreatment has shown slight protection in DXR‐induced renal injury as evidenced by broadening of podocyte foot process and narrowing of slit pore diameter. The results of aliskiren were compared with telmisartan which was used as reference in this study. These results suggested that aliskiren has protective effects against acute model of DXR‐induced cardiotoxicity and nephrotoxicity, implying that plasma renin activity plays a role in DXR‐induced cardio‐renal injury.
Spider toxins comprising disulfide‐rich and linear amphipathic domains: a new class of molecules identified in the lynx spider Oxyopes takobius
Authors: Vassilevski Alexander A. , Sachkova Maria Y. , Ignatova Anastasija A. , Kozlov Sergey A. , Feofanov Alexei V. , Grishin Eugene V.
Published: October 2013

In addition to the conventional neurotoxins and cytotoxins, venom of the lynx spider Oxyopes takobius was found to contain two‐domain modular toxins named spiderines: OtTx1a, 1b, 2a and 2b. These toxins show both insecticidal activity (a median lethal dose against flesh fly larvae of 75 μg·g−1) and potent antimicrobial effects (minimal inhibitory concentrations in the range 0.1–10 μm). Full sequences of the purified spiderines were established by a combination of Edman degradation, mass spectrometry and cDNA cloning. They are relatively large molecules (~ 110 residues, 12.0–12.5 kDa) and consist of two distinct modules separated by a short linker. The N–terminal part (~ 40 residues) contains no cysteine residues, is highly cationic, forms amphipathic α–helical structures in a membrane‐mimicking environment, and shows potent cytolytic effects on cells of various origins. The C–terminal part (~ 60 residues) is disulfide‐rich (five S–S bonds), and contains the inhibitor cystine knot (ICK/knottin) signature. The N–terminal part of spiderines is very similar to linear cytotoxic peptides found in various organisms, whereas the C–terminal part corresponds to the usual spider neurotoxins. We synthesized the modules of OtTx1a and compared their activity to that of full‐length mature toxin produced recombinantly, highlighting the importance of the N–terminal part, which retained full‐length toxin activity in both insecticidal and antimicrobial assays. The unique structure of spiderines completes the range of two‐domain spider toxins.

Database

The protein sequences of the spiderines (OtTx) reported in this paper have been submitted to the UniProt Knowledgebase (UniProtKB) under accession numbers P86716–P86719, and the nucleotide sequences encoding OtTx have been submitted to the GenBank under accession numbers JX134894–JX134897.
Dynamic proteins: changes in structures, activities and networks
Authors: Miller Jenkins Lisa M. , Figeys Daniel
Published: October 2013

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Determinants and Effects of Corporate Lobbying
Authors: Hill Matthew D. , Kelly G. Wayne , Lockhart G. Brandon , Van Ness Robert A.
Published: October 2013

We examine the determinants and value effects of corporate lobbying, controlling for corporate political action committee (PAC) campaign contributions. We find evidence that firms with greater potential payoffs from favorable policy and regulations lobby most actively, and that managers often utilize both lobbying and campaign contribution channels to influence the political climate affecting the firm. We also find that shareholders value the lobbying activities pursued by management on their behalf, particularly if the firm does not have a PAC that contributed to an election campaign. The results are robust to a number of tests designed to mitigate potential omitted‐variable and self‐selection bias.
Long‐term dynamics of mycorrhizal root tips in a loblolly pine forest grown with free‐air CO2 enrichment and soil N fertilization for 6 years
Authors: Pritchard Seth G. , Taylor Benton N. , Cooper Emily R. , Beidler Katilyn V. , Strand Allan E. , McCormack M. Luke , Zhang Siyao
Published: October 2013

Large‐scale, long‐term FACE (Free‐Air CO2 enrichment) experiments indicate that increases in atmospheric CO2 concentrations will influence forest C cycling in unpredictable ways. It has been recently suggested that responses of mycorrhizal fungi could determine whether forest net primary productivity (NPP) is increased by elevated CO2 over long time periods and if forests soils will function as sources or sinks of C in the future. We studied the dynamic responses of ectomycorrhizae to N fertilization and atmospheric CO2 enrichment at the Duke FACE experiment using minirhizotrons over a 6 year period (2005–2010). Stimulation of mycorrhizal production by elevated CO2 was observed during only 1 (2007) of 6 years. This increased the standing crop of mycorrhizal tips during 2007 and 2008; during 2008, significantly higher mortality returned standing crop to ambient levels for the remainder of the experiment. It is therefore unlikely that increased production of mycorrhizal tips can explain the lack of progressive nitrogen limitations and associated increases in N uptake observed in CO2‐enriched plots at this site. Fertilization generally decreased tree reliance on mycorrhizae as tip production declined with the addition of nitrogen as has been shown in many other studies. Annual NPP of mycorrhizal tips was greatest during years with warm January temperatures and during years with cool spring temperatures. A 2 °C increase in average late spring temperatures (May and June) decreased annual production of mycorrhizal root tip length by 50%. This has important implications for ecosystem function in a warmer world in addition to potential for forest soils to sequester atmospheric C.
Dietary guild composition and disaggregation of avian assemblages under climate change
Authors: Ko Chia‐Ying , Schmitz Oswald J. , Barbet‐Massin Morgane , Jetz Walter
Published: October 2013

Climate change is expected to cause geographic redistributions of species. To the extent that species within assemblages have different niche requirements, assemblages may no longer remain intact and dis‐ and reassemble at current or new geographic locations. We explored how climate change projected by 2100 may transform the world's avian assemblages (characterized at a 110 km spatial grain) by modeling environmental niche‐based changes to their dietary guild structure under 0, 500, and 2000 km‐dispersal distances. We examined guild structure changes at coarse (primary, high‐level, and mixed consumers) and fine (frugivores, nectarivores, insectivores, herbivores, granivores, scavengers, omnivores, and carnivores) ecological resolutions to determine whether or not geographic co‐occurrence patterns among guilds were associated with the magnitude to which guilds are functionally resolved. Dietary guilds vary considerably in their global geographic prevalence, and under broad‐scale niche‐based redistribution of species, these are projected to change very heterogeneously. A nondispersal assumption results in the smallest projected changes to guild assemblages, but with significant losses for some regions and guilds, such as South American insectivores. Longer dispersal distances are projected to cause greater degrees of disassembly, and lead to greater homogenization of guild composition, especially in northern Asia and Africa. This arises because projected range gains and losses result in geographically heterogeneous patterns of guild compensation. Projected decreases especially of primary and mixed consumers most often are compensated by increases in high‐level consumers, with increasing uncertainty about these outcomes as dispersal distance and degree of guild functional resolution increase. Further exploration into the consequences of these significant broad‐scale ecological functional changes at the community or ecosystem level should be increasingly on the agenda for conservation science.
Community composition has greater impact on the functioning of marine phytoplankton communities than ocean acidification
Authors: Eggers Sarah L. , Lewandowska Aleksandra M. , Barcelos e Ramos Joana , Blanco‐Ameijeiras Sonia , Gallo Francesca , Matthiessen Birte
Published: October 2013

Ecosystem functioning is simultaneously affected by changes in community composition and environmental change such as increasing atmospheric carbon dioxide (CO2) and subsequent ocean acidification. However, it largely remains uncertain how the effects of these factors compare to each other. Addressing this question, we experimentally tested the hypothesis that initial community composition and elevatedCO2are equally important to the regulation of phytoplankton biomass. We full‐factorially exposed three compositionally different marine phytoplankton communities to two differentCO2levels and examined the effects and relative importance (ω2) of the two factors and their interaction on phytoplankton biomass at bloom peak. The results showed that initial community composition had a significantly greater impact than elevatedCO2on phytoplankton biomass, which varied largely among communities. We suggest that the different initial ratios between cyanobacteria, diatoms, and dinoflagellates might be the key for the varying competitive and thus functional outcome among communities. Furthermore, the results showed that depending on initial community composition elevatedCO2selected for larger sized diatoms, which led to increased total phytoplankton biomass. This study highlights the relevance of initial community composition, which strongly drives the functional outcome, when assessing impacts of climate change on ecosystem functioning. In particular, the increase in phytoplankton biomass driven by the gain of larger sized diatoms in response to elevatedCO2potentially has strong implications for nutrient cycling and carbon export in future oceans.
Using CO2 to enhance carbon capture and biomass applications of freshwater macroalgae
Authors: Cole Andrew J. , Mata Leonardo , Paul Nicholas A. , de Nys Rocky
Published: October 2013

A major limiting factor in the development of algae as a feedstock for the bioenergy industry is the consistent production and supply of biomass. This study is the first to access the suitability of the freshwater macroalgal genus Oedogonium to supply biomass for bioenergy applications. Specifically, we quantified the effect of CO2 supplementation on the rate of biomass production, carbon capture, and feedstock quality of Oedogonium when cultured in large‐scale outdoor tanks. Oedogonium cultures maintained at a pH of 7.5 through the addition of CO2 resulted in biomass productivities of 8.33 (±0.51) g DW m−2 day−1, which was 2.5 times higher than controls which had an average productivity of 3.37 (±0.75) g DW m−2 day−1. Under these productivities, Oedogonium had a carbon content of 41–45% and a higher heating value of 18.5 MJ kg−1, making it an ideal biomass energy feedstock. The rate of carbon fixation was 1380 g C m−2 yr−1 and 1073.1 g C m−2 yr−1 for cultures maintained at a pH of 7.5 and 8.5, and 481 g C m−2 yr−1 for cultures not supplemented with CO2. This study highlights the potential of integrating the large‐scale culture of freshwater macroalgae with existing carbon waste streams, for example coal‐fired power stations, both as a tool for carbon sequestration and as an enhanced and sustainable source of bioenergy.
Mode of larval development as a key factor to explain contrasting effects of temperature on species richness across oceans
Authors: Pappalardo Paula , Fernández Miriam
Published: October 2013

Aim

It has been proposed that the mode of larval development (MLD) could explain the exceptions to the latitudinal gradient of species richness exhibited by several groups of marine organisms. We evaluate the generality of the latitudinal patterns of species richness for different MLDs, and analyse the effects of environmental variables on species richness – explicitly considering feeding type during the larval phase – to identify the relevance of the dichotomies between feeding and non‐feeding larvae and between pelagic and non‐pelagic development.

Location

South America, from 10° to 54° S in the south‐western Atlantic and from 18° to 54° S in the south‐eastern Pacific.

Methods

Using molluscs and crustaceans in two oceans, we deconstructed latitudinal patterns of species richness for three MLDs (planktotrophic, lecithotrophic and direct development). The effects of sea water temperature, chlorophyll a concentration and shelf area on the spatial variation in species richness were analysed for each MLD.

Results

We found remarkably similar trends in species richness deconstructed by MLD. Planktotrophic species richness decreased polewards, and the converse pattern was observed in direct developers. In the majority of groups with lecithotrophic development, species richness increased from middle to higher latitudes. The main component explaining the variation in species richness was the spatial structure of sea water temperature. Temperature showed positive effects on planktotrophic species and negative effects in almost all lecithotrophic or direct‐developing groups in both oceans and both taxa.

Main conclusions

The similar relationship of temperature with lecithotrophic and direct developers, which contrasts with planktotrophic species, suggests that food availability during planktonic larval development is a critical factor determining species distribution of marine invertebrates. We ruled out the cost of brooding as a single causal factor explaining the poleward increase in diversity of direct developers. Simple linear models can describe changes in the proportion of species with temperature within each MLD.
Disparities in arteriovenous fistula placement in older hemodialysis patients
Authors: Patibandla Bhanu K. , Narra Akshita , DeSilva Ranil , Chawla Varun , Vin Yael , Brown Robert S. , Goldfarb‐Rumyantzev Alexander S.
Published: October 2013

The benefits of an arteriovenous fistula (AVF) as the preferred vascular access for hemodialysis have been clearly demonstrated. However, only about 20% of patients in the United States initiate hemodialysis with an AVF. In this study, we assessed whether disparities exist in the type of first hemodialysis access placed prior to dialysis start (rather than that used at dialysis initiation), to detect whether certain disadvantaged groups might have lower likelihood of AVF placement. Study cohort of 118,767 incident hemodialysis patients ≥67 years of age (1/2005–12/2008) derived from the United States Renal Data System was linked with Medicare claims data to identify the type of initial access placed predialysis. We used logistic regression model with outcome being the initial predialysis placement of an AVF as opposed to an arteriovenous graft or a central venous catheter. Increasing age, female sex, black race, lower body mass index, urban location, certain comorbidities, and shorter pre–end‐stage renal disease nephrology care are all associated with a significantly lower likelihood of AVF placement as initial access predialysis. Our study suggests the presence of significant disparities in the placement of an AVF as initial hemodialysis vascular access. We suggest that additional attention should be paid to these patient groups to improve disparities by patient education, earlier referral, and close follow‐up.
Relationship between adhesion molecules and virological response to pegylated interferon‐alpha‐2a treatment in patients with chronic hepatitis B: A pilot study
Authors: Gong Xueyan , Qin Bo , Ma Qian
Published: October 2013

Aim

We performed a clinical study to investigate potential association between serum levels of soluble adhesion molecules and virological response to pegylated interferon‐alpha‐2a (PEG IFN‐α‐2a) treatment in patients with chronic hepatitis B (CHB).

Methods

Thirty‐two patients with chronic hepatitis B virus genotype B were recruited in this study, who were treated with PEG IFN‐α‐2a 180 μg every week and then followed up for 24 weeks. Thirty healthy control subjects were recruited from volunteer blood donors. Serum concentrations of soluble intercellular adhesion molecule‐1 (sICAM‐1), soluble vascular cell adhesion molecule‐1 (sVCAM‐1), soluble E‐selectin (sE‐selectin), soluble L‐selectin (sL‐selectin) in patients were investigated by enzyme‐linked immunoassay before and after treatment.

Results

Serum concentrations of sICAM‐1, sVCAM‐1, sE‐selectin and sL‐selectin in CHB patients were significantly higher compared to the control group before treatment (P < 0.00001, respectively). In CHB patients responding to the PEG IFN‐α‐2a treatment, serum levels of sICAM‐1, sVCAM‐1, sE‐selectin and sL‐selectin were higher than those in non‐responders before treatment (PI = 0.001, PV = 0.002, PE = 0.02, PL = 0.004). The levels of sICAM‐1, sVCAM‐1, sE‐selectin and sL‐selectin decreased in virological responders of treatment at 12 and 24 weeks (PI = 0.0001, PV = 0.00004, PE = 0.002, PL = 0.0004; PI = 0.00007, PV = 0.00001, PE = 0.0003, PL = 0.00003), while no obvious changes were observed in non‐responders (P > 0.05, respectively).

Conclusion

Results obtained indicated increased levels of sICAM‐1, sVCAM‐1, sE‐selectin and sL‐selectin could be related to virological response to PEG IFN‐α‐2a treatment in CHB patients, and have a prognostic effect on virological response.
Immunohistochemistry of soft tissue tumours – review with emphasis on 10 markers
Authors: Miettinen Markku
Published: October 2013

Immunohistochemistry is an integral component in the proper analysis of soft tissue tumours, and a simple panel of six markers is useful in practical triage: CD34, desmin, epithelial membrane antigen (EMA), keratin cocktail AE1/AE3, S100 protein and alpha smooth muscle actin (SMA). These markers frequently assist in the differential diagnosis of fibroblastic, myoid, nerve sheath and perineurial cell tumours, synovial and epithelioid sarcoma and others. However, they all are multispecific, so that one has to be cognizant of their distribution in normal and neoplastic tissues. Four additional useful markers for specific tumour types are discussed here: CD31 and ERG for vascular endothelial tumours, and KIT and DOG1/Ano‐1 for gastrointestinal stromal tumours (GISTs). However, hardly any marker is totally monospecific for any one type of tumour. Furthermore, variably lineage‐specific markers do not usually distinguish between benign and malignant proliferations, so that this distinction has to be made on histological grounds. Immunohistochemical evaluation is most useful, efficient and cost‐effective when used in the context of careful histological evaluation by an experienced pathologist, aware of all diagnostic entities and their histological spectra. Additional diagnostic steps that must be considered in difficult cases include clinicoradiological correlation and additional sampling of remaining wet tissue, if possible.
Neuroendocrine differentiation correlates with hormone receptor expression and decreased survival in patients with invasive breast carcinoma
Authors: Kwon Sun Young , Bae Young Kyung , Gu Mi Jin , Choi Jung Eun , Kang Su Hwan , Lee Soo Jung , Kim Aeri , Jung Hye Ra , Kang Sun Hee , Oh Hoon Kyu , Park Ji Young
Published: October 2013

Aims

Invasive breast carcinoma (IBC) with neuroendocrine (NE) differentiation has been controversial in terms of its definition and clinical outcome. We investigated the incidence and clinical significance of NE differentiation in patients with IBC.

Methods and results

We performed immunohistochemistry for NE markers, chromogranin‐A and synaptophysin on 1428 IBC samples using tissue microarrays and classified cases with NE differentiation into two groups, focal (1–49% tumour cells positive for any NE marker) and diffuse (≥50% tumour cells positive) groups. Fifty‐nine cases (4.1%) showed NE differentiation immunohistochemically, and the majority did not show typical NE morphology. The presence of NE differentiation showed a significant association with positive oestrogen receptor (P = 0.001) and progesterone receptor (P = 0.008) status. Patients with NE differentiation showed worse overall survival (OS) and disease‐free survival (DFS) than those without NE differentiation in both univariate (P < 0.001 for both) and multivariate (OS, P = 0.004; DFS, P < 0.001) analyses.

Conclusions

IBC with NE differentiation is a distinct subtype of mammary carcinoma with an aggressive clinical outcome.
Occult hepatitis B virus coinfection in HIV‐positive African migrants to the UK: a point prevalence study
Authors: Chadwick D , Doyle T , Ellis S , Price D , Abbas I , Valappil M , Geretti AM
Published: October 2013

Objectives

Occult (surface antigen‐negative/DNA‐positive) hepatitis B virus (HBV) infection is common in areas of the world where HBV is endemic. The main objectives of this study were to determine the prevalence of occult HBV infection in HIV‐infected African migrants to the UK and to determine factors associated with occult coinfection.

Methods

This anonymized point‐prevalence study identified Africans attending three HIV clinics, focussing on patients naïve to antiretroviral therapy (ART). Stored blood samples were tested for HBV DNA. Prevalence was calculated in the entire cohort, as well as in subpopulations. Risk factors for occult HBV coinfection were identified using logistic regression analysis.

Results

Among 335 HIV‐positive African migrants, the prevalence of occult HBV coinfection was 4.5% [95% confidence interval (CI) 2.8–7.4%] overall, and 6.5% (95% CI 3.9–10.6%) and 0.8% (95% CI 0.2–4.6%) in ART‐naïve and ART‐experienced patients, respectively. Among ART‐naïve anti‐HBV core (anti‐HBc)‐positive patients, the prevalence was 16.4% (95% CI 8.3–25.6%). The strongest predictor of occult coinfection was anti‐HBc positivity [odds ratio (OR) 7.4; 95% CI 2.0–27.6]. Median HBV DNA and ALT levels were 54 IU/mL [interquartile range (IQR) 33–513 IU/mL] and 22 U/L (IQR 13–27 U/L), respectively.

Conclusions

Occult HBV coinfection remains under‐diagnosed in African HIV‐infected patients in the UK. Given the range of HBV DNA levels observed, further studies are warranted to determine its clinical significance and to guide screening strategies and ART selection in these patients.
The diet of Common GuillemotUria aalgechicks provides evidence of changing prey communities in the North Sea
Authors: Anderson Helen B. , Evans Peter G. H. , Potts Jacqueline M. , Harris Michael P. , Wanless Sarah
Published: October 2013

Local differences in feeding conditions have been suggested as a cause of regional variation in seabird demography but multi‐colony comparisons of diet are rare. InUKwaters the main fish eaten by seabirds during the breeding season belong to three families: Ammodytidae, Clupeidae and Gadidae. Climate change and fishing are affecting these fish stocks and so probably impact on predators such as seabirds. We used standardized observations of prey brought in for chicks to make the first integrated assessment of the diet of Common GuillemotUria aalgechicks at aUKscale. Chick diet varied markedly among the 23 colonies sampled between 2006 and 2011. Sandeels (Ammodytidae), probably Lesser SandeelsAmmodytes marinus, were the commonest prey. Their contribution to the diet varied both latitudinally and among marine regions, with the proportion significantly higher for a given latitude on the west coast compared to the east. The non‐sandeel component of the diet showed latitudinal changes, with small clupeids, probably SpratsSprattus sprattus, predominant at southern colonies whereas juvenile gadids were the main alternative to sandeels in the north. Comparison of our Guillemot chick diet with data collected 15–30 years earlier suggests that the proportion of sandeels in the diet has decreased at colonies bordering the North Sea. No significant change was apparent in Atlantic colonies but historical data were limited. The early years of our study coincided with a population explosion of Snake PipefishEntelurus aequoreusin the Northeast Atlantic and North Sea. Pipefish were recorded in Guillemot chick diet at several northern and northwestern colonies in 2006 and 2007 but have been absent since 2009. Spatial and temporal variation in chick diet accorded broadly with patterns expected as a result of rising sea temperatures and impacts of fishing. Guillemot chick diet could potentially be a useful indicator of changes in the distribution and abundance of forage fish.
Measurement equivalence of touch‐screen computerized and paper‐based diabetes‐specific quality‐of‐life questionnaires
Authors: Lee Eun‐Hyun , Lee Young Whee , Lee Kwan‐Woo , Kim Dae Jung , Kim Yong‐Seong , Nam Moon‐Suk
Published: October 2013

Current advances in technology have enabled the development of a computer‐based questionnaire that provides advantages over the paper‐based mode of administration, such as automatic data entry, storage and calculations. However, before implementing a computer‐based questionnaire, its equivalence with the original paper‐based questionnaire must first be demonstrated. The purpose of this study was to evaluate the measurement equivalence of the computerized Diabetes‐Specific Quality‐of‐Life questionnaire (cD‐QOL) with its original paper‐based counterpart. A two‐period crossover design was used in this study. The measurement equivalence was evaluated using quadratic weighted kappa coefficients, intraclass correlations and Cronbach's alpha comparisons. The cD‐QOL was equivalent to its original paper‐based counterpart. Participants preferred the cD‐QOL over the paper‐based questionnaire and reported that it was easy to use.
Biosimilars: how similar?
Authors: Strand V. , Cronstein B.
Published: October 2013

As patents expire on biological agents for the treatment of rheumatic diseases, we have the opportunity to develop non‐proprietary biologic agents, biosimilars. The development and approval of these agents present novel challenges to both pharma and regulatory agencies although there is great promise of high quality, less expensive biologic agents for the treatment of rheumatic diseases. Here, we review the definitions of biosimilars, the regulatory challenges to approval of these agents and the record of approvals of biosimilars to date.
Significant involvement of nuclear factor‐κB‐inducing kinase in proper differentiation of αβ and γδ T cells
Authors: Eshima Koji , Okabe Motohito , Kajiura Satoshi , Noma Haruka , Shinohara Nobukata , Iwabuchi Kazuya
Published: October 2013

Nuclear factor‐κB‐inducing kinase (NIK) is known to play a critical role in maintaining proper immune function. This is exemplified in the spontaneous mutant mouse lacking functional NIK, alymphoplasia (aly), which is simultaneously immune‐compromised and autoimmune‐prone. To investigate the role of NIK in αβ T‐cell repertoire formation, we analysed T‐cell development in aly/aly mice bearing a transgenic T‐cell receptor (TCR). Although there were no apparent abnormalities in the mature αβ T cells of non‐transgenic aly/aly mice, the maturation efficiency of idiotypehigh+ T cells in the TCR‐transgenic mice was lower in aly/aly mice compared with those found in aly/+ mice, suggesting that the mature αβ T‐cell repertoire could be altered by the absence of functional NIK. In one strain of TCR‐transgenic aly/aly mice with a negatively selecting H‐2 background, the proportion of CD8low+ idiotypehigh+ cells, which are thought to potentially represent the γδ lineage of T cells, was markedly decreased. When the γδ T cells in non‐transgenic aly/aly mice were investigated, the proportion of γδ T cells in the peripheral organs of aly/aly mice was found to be one‐half to one‐fifth of those in aly/+ mice. Analyses of bone marrow chimera mice indicated that NIK in host cells, rather than in donor cells was important for generating a normal number of peripheral γδ T cells. Collectively, these results suggest that NIK could be involved in thymic positive selection of some αβ T cells and that NIK in non‐haematopoietic cells is important for the optimal development and/or maintenance of γδ T cells.
Bank and Non‐Bank Financial Deepening and Economic Growth: The Nigerian Experience (1981–2010)
Authors: Iyoboyi Martins
Published: October 2013

The paper aimed at empirically investigating the impact of financial deepening on the growth of an economy, with particular emphasis on Nigeria over the period 1981–2010. Financial deepening was segregated to capture both bank and non‐bank financial variables, because both are imperative to economic activities. The study therefore combined a proxy of banking sector development with stock market development to capture the influence of financial deepening on growth. The analysis is based on the bound testing approach to cointegration. The empirical results confirm cointegrated relationship between economic growth and financial deepening. The study also showed that, in the period of study, while there is bidirectional causality between bank financial deepening and economic growth, causality runs from economic growth to non‐bank financial deepening. The results of the investigation are in favour of the finance‐growth cum growth‐finance hypothesis. For the period under study, Nigeria's economic growth is sensitive to changes in financial deepening, past level of growth and the openness of the economy. It is therefore imperative that policies which seek to deliberately increase financial depth be vigorously pursued, in order to stimulate growth and consequently further deepen the financial sector of the economy.
Art Maps – Mapping the Multiple Meanings of Place
Authors: Sinker Rebecca , Giannachi Gabriella , Carletti Laura
Published: October 2013

Digital technology enables us to prospect, generate, assemble and share eclectic materials, creating virtual journeys, stories or exhibitions through the internet, viewed on computer but also on location via mobile devices. How does the ability to create and curate in this way enhance or transform our access to and understanding of art, as well as our experience of place? What kind of meanings are we making for ourselves and others? And how are the creative responses of audiences viewed and valued in relation to the museum's curated collection? This article explores these questions through the development of Art Maps, a web and mobile application that enables people to locatively and creatively explore the relationship between art and place. Through participant research we are examining possibilities for a more open approach to interpreting Tate's digitised collection of art, testing the notional democratic shift from the museum as keeper of knowledge to co‐creator with the audience.
Beauty and the Beast – Can Life Drawing Support Female Students in Challenging Gendered Media Imagery?
Authors: Stanhope Clare
Published: October 2013

How does life drawing impact on a group of 14–16‐year‐old female art and design students and their perception of body image? In contemporary Western society, we are bombarded with advertising, social media and celebrity culture on a daily basis, often with a focus on body image. This article questions whether, due to this visual assault, young female students have a democratic choice in forming a relationship with the body. Alternatively, do they feel pressured into conforming to a media led image? This article analyses the reaction of a group of GCSE fine art students to life drawing and a naked female nude. It questions their perceptions of ‘normal’ and discusses if art‐based research projects can challenge contemporary issues and young female students' perception of body image.
We are Spanish, Born under Franco's Dictatorship, and we are Developing the Posbolonian Uniform Performance as a Form of Global Activism
Authors: Camarero Pilar Pérez , Cruzado Raúl Díaz‐Obregón
Published: October 2013

The Posbolonian Uniform is a creative, artistic and performative response, undertaken as a criticism and opposition to the losses of democratic freedoms that have occurred in Spain recently. It is a bid by two university instructors for the use of artistic tools, specifically performance art, as a means of social transformation in their academic environments. It is a creative rebellion and academic disobedience seeking a depoliticization of education – a change in social reconstruction through the consolidation of critical thinking tools, as art ideally should be.
Climate and vegetation hierarchically structure patterns of songbird distribution in the Canadian boreal region
Authors: Cumming S. G. , Stralberg D. , Lefevre K. L. , Sólymos P. , Bayne E. M. , Fang S. , Fontaine T. , Mazerolle D. , Schmiegelow F. K. A. , Song S. J.
Published: October 2013

Environmental factors controlling the distribution and abundance of boreal avifauna are not fully understood, limiting our ability to predict the consequences of a changing climate and industrial development activities underway. We used a compilation of avian point‐count data, collected over 1990–2008 from nearly 36 000 locations, to model the abundance of individual forest songbird species within the Canadian boreal forest. We evaluated 30 vegetation and 101 climatic variables, representing most of the widely‐used dimensions of climate space, along with less usual measures of inter‐annual variability. Regression tree models allowed us to calculate the relative importance of climate and vegetation variable classes according to avian migration strategy without the need for a priori variable selection or dimension reduction. We tested for hierarchical habitat selection by formulating hypotheses on the locations of variables within the model tree structures. Climate variables explained the majority (77%) of deviance explained over 98 species modelled. As may be expected at high latitudes, we found energy availability (temperature, 65%) to be more important than moisture availability (precipitation, 12%). The contributions of inter‐ and intra‐annual climate variability (28%) were about half that of mean conditions. The relatively large contribution of remotely‐sensed vegetation metrics (23%) highlighted the importance of local vegetation heterogeneity controlled by non‐climatic factors. The two most important vegetation variables were landcover type and April leaf area index. When selected, these generally occurred in a model's right subtree, consistent with predictions from hierarchical habitat selection theory. When occupying the root node, landcover effectively delineated the historical forest‐prairie ecotone, reflecting the current disequilibrium between climate and vegetation due to human land use. Our findings suggest a large potential for avian distributional shifts in response to climate change, but also demonstrate the importance of finer scale vegetation heterogeneity in the spatial distribution of boreal birds.
Predicting top predator habitats in the Southwest Indian Ocean
Authors: Mannocci Laura , Laran Sophie , Monestiez Pascal , Dorémus Ghislain , Van Canneyt Olivier , Watremez Pierre , Ridoux Vincent
Published: October 2013

Top predators need to develop optimal strategies of resources and habitats utilization in order to optimize their foraging success. At the individual scale, a predator has to maximize his intake of food while minimizing his cost of foraging to optimize his energetic gain. At the ecosystem scale, we hypothesized that foraging strategies of predators also respond to their general energetic constraints. Predators with energetically costly lifestyles may be constrained to select high quality habitats whereas more phlegmatic predators may occupy both low and high quality habitats. The objectives of this study were 1) to investigate predator responses to heterogeneity in habitat quality with reference to their energetic strategies and 2) to evaluate their responses to contemporaneous versus averaged habitat quality. We collected cetacean and seabird data from an aerial survey in the Southwest Indian Ocean, a region characterized by heterogeneous oceanographic conditions. We classified cetaceans and seabirds into energetic guilds and described their habitats using remotely sensed covariates at contemporaneous and time‐averaged resolutions and static covariates. We used generalized additive models to predict their habitats at the regional scale. Strategies of habitat utilization appeared in accordance with predators energetic constraints. Cetaceans responded to the heterogeneity in habitat quality, with higher densities predicted in more productive areas. However, the costly Delphininae appeared to be more dependent on habitat quality (showing a 1‐to‐13 ratio between the lowest and highest density sectors) than the more phlegmatic sperm and beaked whales (showing only a 1‐to‐3 ratio). For seabirds, predictions primarily reflected colony locations, although the colony effect was stronger for costly seabirds. Moreover, our results suggest that predators may respond better to persistent oceanographic features. To provide a third dimension to habitat quality, cetacean strategies of utilization of the vertical habitat could be related to the distribution of micronekton in the water column.