bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance effects of top management team gender diversity during the merger and acquisition process
Authors: Parola Heather R. , Ellis Kimberly M. , Golden Peggy
Published: February 2015

Purpose

– The purpose of this paper is to uncover the performance effects of top management team (TMT) gender diversity in the merger and acquisition (M&A) process. To do so, an integration of the upper echelons perspective and the M&A process literature is offered to consider the “double-edge sword” of gender diversity on both pre- and post-integration performance. Additionally, the boundary effects of acquirer experience on the TMT gender diversity-performance relationship is examined.

Design/methodology/approach

– The hypotheses are tested in a sample of 310 acquisitions by Fortune 1,000 companies. Multiple regression analysis is utilized to test the effects on the two different performance variables.

Findings

– The findings reveal that TMT gender diversity is beneficial to pre-integration performance, but hinders post-integration performance. Additionally, the findings provide evidence that acquirer experience can overcome the negative effects of gender diversity in post-integration performance.

Originality/value

– This study contributes to a better understanding of the double-edge sword of TMT gender diversity by providing evidence that performance implications depend on the performance variable of interest. Specifically in the M&A context, gender diversity has differing effects on pre- and post-integration performance.
Effects of intellectual capital on innovative performance
Authors: Han Yuqian , Li Dayuan
Published: February 2015

Purpose

– The purpose of this paper is to demonstrate the relationship between intellectual capital and innovative performance, and to specify the boundary conditions and mechanisms of the relationship from a knowledge-based dynamic capability perspective.

Design/methodology/approach

– This study empirically analyzes the impact of intellectual capital on innovative performance and the role knowledge-based dynamic capability plays with a sample of 217 firms in China. To test the research hypotheses, regression analysis is applied.

Findings

– The results show that intellectual capital positively affects innovative performance, and knowledge-based dynamic capability is a mediator rather than a moderator which partly mediates the relationship between intellectual capital and innovative performance.

Practical implications

– The findings suggest that realizing superior innovative performance is dependent on a firm’s intellectual capital and its ability to sense opportunities and threats, to make timely and correct decisions, and to facilitate necessary changes efficiently.

Originality/value

– This study is the first to clarify whether knowledge-based dynamic capability plays a moderating role or a mediating role between intellectual capital and innovative performance. The present study thus helps move forward the understanding on the conditions and mechanisms of the effects of intellectual capital.
Impact of host country institutional context on subsidiary performance
Authors: Pattnaik Chinmay , Choe SoonKyoo , Singh Deeksha
Published: February 2015

Purpose

– The purpose of this paper is to examine the impact of quality of market supporting institutions (institutional quality) in host country and the similarities and differences of institutional quality between the home and host country (institutional distance) on subsidiary performance.

Design/methodology/approach

– Based on the conceptualization of new institutional economics, the authors divide quality of host country institutions into factor markets; product, capital, labor market and sociopolitical dimensions. The authors examine the impact of the quality these institutional dimensions in host countries and their difference between home and host country on the performance of 318 subsidiaries of 146 Korean listed manufacturing firms operating in 28 host countries from 2001 to 2006.

Findings

– The empirical results based on 1,129 observations show that institutional distance explains a significant variance in the subsidiary performance. In particular, the difference in quality of institutions in product, capital and labor market has negative impact on subsidiary performance. However, except for quality of regulation in labor market, host country institutional qualities do not significantly explain the variation in subsidiary performance.

Originality/value

– The evidence suggests that host country institutions matter substantially when considered with their relative similarity and difference with home country institutions. The impact of individual dimensions of institutions varies on subsidiary performance.
Upper limb spasticity management for patients who have received Botulinum Toxin A injection: Australian therapy practice
Authors: Cusick Anne , Lannin Natasha , Kinnear Bianca Zoe
Published: February 2015

Background/aim

To describe Australian physiotherapy and occupational therapy practice for patients who receive upper‐limb Botulinum Toxin‐A (BoNT‐A).

Method

Anonymous online survey asking about practice experience. Convenience sample of 128 BoNT‐A experienced occupational therapists and physiotherapists.

Results

The primary work setting was multidisciplinary inpatient or outpatient rehabilitation services where therapists had automatic referral to BoNT‐A patients. Patients expected BoNT‐A to improve functional movement, reduce hypertonicity, increase passive range, reduce pain, improve appearance and hand hygiene. Most patients were injected in multidisciplinary public hospital clinics and had median 2 pre‐injection (range 0–30) and 8 post‐injection (range 0–50) therapy sessions. Biceps, flexor digitorum profundus/superficialis and brachoradialis were most frequently injected. Injectors used therapist assessment information to select sites 68% of the time; only 44% of services had assessment protocols. Standardised therapy assessments examined motor performance, pain and function in that order of frequency. The greater the awareness and perceived relevance of an assessment the more often therapists used it. All therapists set goals, most collaboratively, and these mirrored patient expectations. The most common treatments were stretch, task‐specific functional training, strength training and home programmes.

Conclusion

While trends in Australian assessment, goals and treatment practice were observed, greater consistency could be achieved if therapy practice guidelines existed. The gap is exacerbated by the absence of Australian BoNT‐A organisation and process of care spasticity management guidelines. This creates an environment where practice variability is inevitable. Recommendations to improve local service quality are made.
Management of non‐progressive dysarthria: practice patterns of speech and language therapists in the Republic of Ireland
Authors: Conway Aifric , Walshe Margaret
Published: February 2015

Background

Dysarthria is a commonly acquired speech disorder. Rising numbers of people surviving stroke and traumatic brain injury (TBI) mean the numbers of people with non‐progressive dysarthria are likely to increase, with increased challenges for speech and language therapists (SLTs), service providers and key stakeholders. The evidence base for assessment and intervention approaches with this population remains limited with clinical guidelines relying largely on clinical experience, expert opinion and limited research. Furthermore, there is currently little evidence on the practice behaviours of SLTs available.

Aims

To investigate whether SLTs in the Republic of Ireland (ROI) vary in how they assess and manage adults with non‐progressive dysarthria; to explore SLTs’ use of the theoretical principles that influence therapeutic approaches; to identify challenges perceived by SLTs when working with adults with non‐progressive dysarthria; and to determine SLTs’ perceptions of further training needs.

Methods & Procedures

A 33‐item survey questionnaire was devised and disseminated electronically via SurveyMonkey to SLTs working with non‐progressive dysarthria in the ROI. SLTs were identified through e‐mail lists for special‐interest groups, SLT manager groups and general SLT mailing lists. A reminder e‐mail was sent to all SLTs 3 weeks later following the initial e‐mail containing the survey link. The survey remained open for 6 weeks. Questionnaire responses were analysed using descriptive statistics. Qualitative comments to open‐ended questions were analysed through thematic analysis.

Outcomes & Results

Eighty SLTs responded to the survey. Sixty‐seven of these completed the survey in full. SLTs provided both quantitative and qualitative data regarding their assessment and management practices in this area. Practice varied depending on the context of the SLT service, experience of SLTs and the resources available to them. Not all SLTs used principles such as motor programming or neural plasticity to direct clinical work and some requested further direction in this area. SLTs perceived that the key challenges associated with working in this area were the compliance, insight and motivation of adults with dysarthria.

Conclusions & Implications

The use of specific treatment programmes varies amongst SLTs. A lack of resources is reported to restrict practice in both assessment and management. Ongoing research into the effectiveness of SLT interventions with adults with non‐progressive dysarthria is required to guide clinical decision‐making. SLTs identified further training needs which may provide direction for the development of professional training courses in the future.
Methane oxidation coupled to nitrate reduction under hypoxia by the Gammaproteobacterium Methylomonas denitrificans, sp. nov. type strain FJG1
Authors: Kits K. Dimitri , Klotz Martin G. , Stein Lisa Y.
Published: February 2015

Obligate methanotrophs belonging to the Phyla Proteobacteria and Verrucomicrobia require oxygen for respiration and methane oxidation; nevertheless, aerobic methanotrophs are abundant and active in low oxygen environments. While genomes of some aerobic methanotrophs encode putative nitrogen oxide reductases, it is not understood whether these metabolic modules are used for NOx detoxification, denitrification or other purposes. Here we demonstrate using microsensor measurements that a gammaproteobacterial methanotroph Methylomonas denitrificans sp. nov. strain FJG1T couples methane oxidation to nitrate reduction under oxygen limitation, releasing nitrous oxide as a terminal product. Illumina RNA‐Seq data revealed differential expression of genes encoding a denitrification pathway previously unknown to methanotrophs as well as the pxmABC operon in M. denitrificans sp. nov. strain FJG1T in response to hypoxia. Physiological and transcriptome data indicate that genetic inventory encoding the denitrification pathway is upregulated only upon availability of nitrate under oxygen limitation. In addition, quantitation of ATP levels demonstrates that the denitrification pathway employs inventory such as nitrate reductase NarGH serving M. denitrificans sp. nov. strain FJG1T to conserve energy during oxygen limitation. This study unravelled an unexpected metabolic flexibility of aerobic methanotrophs, thereby assigning these bacteria a new role at the metabolic intersection of the carbon and nitrogen cycles.
Closing the Rhetoric‐Reality Gap? Employees' Perspective of Performance Management in the Australian Public Service
Authors: Taylor Jeannette
Published: February 2015

Performance management has been hailed by its proponents as an essential tool to enhance public service performance. Yet, its actual capacity to improve public service performance continues to be questioned by many academics. This research on a small group of Australian Public Service employees examines their perceptions on the efficacy of the performance management system in their agencies. The study respondents did not believe that their work behaviours had significantly changed in response to performance management. Obstacles to high performance include perceptions of a poorly designed performance measurement system, an inadequate level and mix of rewards offered, and inconsistencies in the implementation process.
Fat Transfer and Fatal Macroembolization
Authors: Astarita Denis C. , Scheinin Lisa A. , Sathyavagiswaran Lakshmanan
Published: February 2015

Fat embolism is usually associated with long bone fractures or other trauma. The diagnosis is usually clinical, and in most cases, emboli are not fatal and not usually seen on gross examination. At the Los Angeles County Coroner's Office, we autopsied the victim of fatal macroscopic fat embolization to the lungs. The patient died during buttock enhancement surgery when fat from liposuction was injected into her buttocks. Fat embolism from liposuction and fat injection is reportedly rare, and macroscopic embolization is rarer still. Varicose veins can occur in the area of the sciatic notch and are known to cause painful sciatica symptoms. We suggest them as a potential conduit for macroscopic fat to reach the lungs. Simple pre‐operative questioning for sciatica symptoms and possible radiologic study to rule out sciatic varices seem prudent before undertaking buttock‐enhancing surgery. Careful fat injection with pre‐aspiration is always advised.
Sickle Cell Trait as a Contributory Cause of Death in Natural Disease
Authors: Podduturi Varsha , Guileyardo Joseph M.
Published: February 2015

Sickle cell trait (SCT) affects 300 million people globally, and awareness is growing that SCT is not an entirely benign condition; however, most reported cases have been non‐natural deaths. Autopsy records from the Baylor University Medical Center (BUMC) in Dallas, Texas, contained seven natural deaths from January 2007 to October 2013 in which micro‐occlusive sickling was identified at autopsy and SCT confirmed by postmortem hemoglobin fractionation. Sickle crisis was never diagnosed clinically. These cases illustrate the importance of red cell morphology in autopsy material. When sickling is suspected, hemoglobin fractionation should be performed. If confirmed, SCT should be listed as an autopsy finding and the severity and distribution of sickling documented. Extensive micro‐occlusive sickling should be considered contributory to death; however, its relative importance depends on all facts of the case. Accurate reporting should facilitate further research and the development of evidence‐based preventative and supportive strategies for these patients.
Non‐medical prescription drug use (NMPDU) and poor quality of life in the Swedish general population
Authors: Abrahamsson Tove , Berglund Mats , Håkansson Anders
Published: February 2015

Background and Objectives

Quality of life has become an increasingly important measurement in the substance use field. The main aim of the present study was to examine the relationships between non‐medical use of prescription analgesics and sedatives and poor quality of life in the general population.

Methods

Data were drawn from a Swedish national household survey conducted in 2008–2009. A stratified sample of 58,000 individuals aged 15–64 was randomly selected, with a response rate of 38.3% (n = 22,095). We examined the relationships between non‐medical prescription drug use and quality of life in a logistic regression analysis, controlling for other substance use and sociodemographic variables.

Results

In the final logistic regression model, both non‐medical use of prescription analgesics and sedatives were independently associated with poor quality of life. Non‐medical use of prescription sedatives was the strongest correlate of poor quality of life among the substance use variables.

Discussion and Conclusions

The associations between non‐medical prescription drug use and poor quality of life might imply a need to better identify and provide treatment for this group, especially individuals with non‐medical prescription sedative use, which seems to be a particularly strong correlate of poor quality of life.

Scientific Significance

Using a large, general population sample, the present paper is one of few to examine the relationships between non‐medical prescription drug use and quality of life. (Am J Addict 2015;24:271–277)
Gastric fluid cytokines are associated with chorioamnionitis and white blood cell counts in preterm infants
Authors: Bry K J K , Jacobsson B , Nilsson S , Bry K
Published: February 2015

Aim

The aim of this study was to determine whether the concentration of cytokines in the gastric fluid at birth was associated with chorioamnionitis or funisitis and with the white blood cell counts of very premature newborns.

Methods

We retrieved gastric fluid from 27 preterm infants with a gestational age of <29 weeks within 1 h of birth and used enzyme‐linked immunosorbent assay to measure the concentrations of interleukin (IL)‐1beta, epithelial cell‐derived neutrophil‐activating peptide (ENA)‐78, IL‐8 and growth‐related oncogene (Gro)‐alpha. The presence of histologic chorioamnionitis or funisitis in the placentas and the highest white blood cell count of the infants during the first week of life were compared to the cytokine concentrations.

Results

Gastric fluid concentrations of IL‐1beta, ENA‐78, IL‐8 and Gro‐alpha were strongly associated with chorioamnionitis and funisitis. In addition, chorioamnionitis and funisitis and gastric aspirate cytokine levels were associated with the highest white blood cell counts of the infants during the first week of life.

Conclusion

This study suggests that levels of inflammatory cytokines in the gastric fluid of premature infants at birth can be used to assess the exposure of the infants to antenatal inflammation.
From lip to lab: salty tasting skin is the main clue that raises clinical suspicion of cystic fibrosis in young infants
Authors: Camargos Paulo , Gomes Daniela Lima , Alvim Cristina Gonçalves , Gomes Fabrício Silva , Cajazeiro Júnia Maria Drumond
Published: February 2015

Aim

This study developed a clinical decision rule (CDR) to rule in or rule out cystic fibrosis (CF) in the first weeks of life.

Methods

We combined a two‐step nonconcurrent birth cohort and a cross‐sectional controlled study in which observers and mothers were blinded to confirmatory sweat test results. Neonates from uncomplicated pregnancies and deliveries, with two subsequent tests for immunoreactive trypsinogen (IRT) higher than 70 ng/mL, were eligible to take part.

Results

We included 49 CF‐affected and 177 CF‐unaffected infants with an average age of 34 days. CF‐affected infants demonstrated statistically significant differences in weight gain, stool frequency and salty tasting skin from birth. Multivariate analysis showed that the main predictors of CF were salty tasting skin (odds ratio 17.2) and weight gain of <10.5 g per day (odds ratio 4.6). Depending on the CDR score, we obtained the following results: sensitivity (42.9–61.2%), specificity (89.6–96.5%), positive (62.5–77.8%) and negative (85.6–89.1%) predictive value and positive (5.8–12.3) and negative (0.4–0.6) likelihood ratio.

Conclusion

The CDR could provide a reliable index of clinical suspicion and timely referral for sweat testing in settings without newborn screening programmes and may also be applied to false‐negative individuals where such programmes already exist.
Autoimmune gastritis in autoimmune thyroid disease
Authors: Venerito M. , Radünz M. , Reschke K. , Reinhold D. , Frauenschläger K. , Jechorek D. , Di Mario F. , Malfertheiner P.
Published: February 2015

Background

Autoimmune gastritis leads to oxyntic gastric atrophy, a condition at increased risk for gastric cancer. Autoimmune gastritis in conjunction with autoimmune thyroid disease has been reported previously.

Aim

In a case–control study in patients with autoimmune thyroid disease to evaluate the usefulness of serum pepsinogens for the identification of oxyntic gastric atrophy, and to determine the relationship of Helicobacter pylori with oxyntic gastric atrophy.

Methods

Patients with autoimmune thyroid disease (cases) and goitre (controls) were prospectively enrolled in the study. Pepsinogen (PG) I levels ≤25 μg/mL and PG I/II ratio ≤3 were indicative for oxyntic gastric atrophy. Antibodies against H. pylori, CagA and parietal cells were also determined. Esophagogastroduodenoscopy with biopsies was offered to patients with serological oxyntic gastric atrophy.

Results

In total, 34 autoimmune thyroid disease patients and 30 controls were enrolled. Serological oxyntic gastric atrophy was present only in autoimmune thyroid disease patients (8/34, 23.5%, OR 8.3, 95% CI = 1.9–36.2). In all eight patients oxyntic gastric atrophy was confirmed by histology. OLGA stage I, II, III and IV was described in 0%, 33%, 50% and 17% of the cases, respectively. About, 89% and 11% of oxyntic gastric atrophy patients were seropositive for antibodies against parietal cells or H. pylori infection, respectively. Gastric atrophy involved the angulus/antrum in 50% of patients with autoimmune gastritis.

Conclusions

The seroprevalence of oxyntic gastric atrophy is high in patients with autoimmune thyroid disease, and testing of serum pepsinogens should be included in the clinical assessment of these patients. H. pylori infection is unlikely to be a principal factor in the pathogenesis of oxyntic gastric atrophy in patients with autoimmune thyroid disease. In autoimmune gastritis, gastric atrophy can spread from the oxyntic towards the antral mucosa.
Religious adaptation of a parenting programme: process evaluation of the Family Links Islamic Values course for Muslim fathers
Authors: Scourfield J. , Nasiruddin Q.
Published: February 2015

Background

Amid concern about the reach and inclusivity of parenting interventions, attempts have been made to culturally adapt programmes for specific ethnic or linguistic groups. This paper describes a novel approach of the religious adaptation of a parenting programme, namely the Family Links Islamic Values course.

Methods

A small‐scale qualitative process evaluation was conducted on one Family Links Islamic Values course for Muslim fathers in the South of England in order to describe the intervention as implemented and its theory of change, as well as the acceptability of the programme to the participants. The data consisted of 13 semi‐structured interviews (10 with parents and three with staff), 25 h of observation and reading of programme manuals.

Results

A logic model is presented to describe the theoretical basis of the intervention. The programme was highly acceptable to fathers who valued the integration of religious teachings and were generally very positive about their experience of attending the course. Post‐course interviews with both fathers and mothers mentioned some positive changes in fathers as a result of their attendance.

Conclusions

It is important to be responsive to the needs of some British Muslims for religiously credible interventions. This small‐scale process evaluation needs to be followed by a robust evaluation of programme outcomes for parents and children.
NFATc1 deletion in T lymphocytes inhibits the allergic trait in a murine model of asthma
Authors: Koch S. , Reppert S. , Finotto S.
Published: February 2015

Background

NFATc1 isoforms are highly regulated in peripheral T cells where they contribute to the effector function and cell homeostasis.

Objective

Here, we investigated the role of NFATc1 in asthma and in T cells.

Methods

In a murine model of allergic asthma, we analysed differences in T‐cell development in this allergic disease model, between wild‐type and NFATc1 conditional knockout mice. Thus, we performed quantitative real‐time PCR to investigate the mRNA expression of Th2‐associated genes as well as genes that are involved in IgE immunoglobulin class‐switch. Additionally, we used ELISA, Western blot and flow cytometry (FACS) to analyse protein concentrations of Th1‐, Th2‐ and Th17‐specific transcription factors and cytokines and the Th2 chemokine, thymus and activation‐regulated chemokine/chemokine ligand 17 (TARC/CCL17) by ELISA.

Results

Mice lacking NFATc1 in CD4+ T cells display a significant reduction in lung Th2 and Th17 as well as an increase of Th1 cells in an experimental asthma model. Additionally, Batf gene, a recently described transcription factor of the Th2 and Th17 cell differentiation as well as a key T and B transcription factor involved in the IgE immunoglobulin class‐switch, was found decreased in the lungs of these mice. As a consequence, serum OVA‐specific IgE and IgG1 levels were found significantly decreased after allergen exposure and in the absence of NFATc1 in T cells in experimental allergic asthma.

Conclusions and Clinical Relevance

Targeting NFATc1 in T lymphocytes ameliorated the allergic trait in the airways of NFATc1fl/flxCD4Cre mice. NFATc1 emerges as a novel target for anti‐allergy intervention.
Lower anti‐echovirus antibody responses in children presenting to hospital with asthma exacerbations
Authors: Iwasaki J. , Chai L. Y. , Khoo S.‐K. , Bizzintino J. , Laing I. A. , Le Souëf P. N. , Thomas W. R. , Hales B. J.
Published: February 2015

Background

Rhinoviruses from the Enterovirus genus cause frequent infections and induce remarkably high titres of anticapsid antigen antibodies in asthmatics, while the prevalence of neutralising antibodies to the gut‐trophic echoviruses from the same genus is diminished.

Objective

To assess the absolute and specific antibody titres to VP1 antigens of the gut‐trophic enteroviruses, echovirus 30 and Sabin 1 poliovirus, in asthmatic and non‐asthmatic children.

Methods

Recombinant polypeptides representing the VP1 capsid antigens of echovirus 30 and Sabin poliovirus 1 were produced. Their ability to bind IgG1 antibodies from the plasma of asthmatic (n = 45) and non‐asthmatic (n = 29) children were quantitated by immunoassays that incorporated immunoabsorptions to remove cross‐reactivity.

Results

The IgG1 antibody titres and prevalence of antibody binding to echovirus 30 were significantly lower for asthmatic children compared to controls (P < 0.05) and inversely correlated with total IgE levels for the whole study population (r = ‐0.262; P < 0.05). There was no difference in the prevalence and titre between groups to the VP1 antigen of Sabin poliovirus. Anti‐tetanus toxoid titres measured for comparison did not correlate with anti‐echovirus or poliovirus, but correlated with anti‐rhinovirus titres in controls but not asthmatics, where the titres were higher for the asthmatic group.

Conclusions and Clinical Relevance

The associations of lower antibody titres of asthmatic children to echovirus reported here and those of our previous findings of a heightened response to rhinovirus suggest a dichotomy where respiratory enterovirus infection/immunity increases the probability of developing asthma and enteric infections lower the risk. This provides further support for the concept of intestinal infection playing a key role in the development of allergic respiratory disease.
Maternal plasma and breastmilk viral loads are associated with HIV-1-specific cellular immune responses among HIV-1-exposed, uninfected infants in Kenya
Authors: Liu A Y , Lohman-Payne B , Chung M H , Kiarie J , Kinuthia J , Slyker J , Richardson B , Lehman D , Farquhar C , John-Stewart G
Published: February 2015

Infants exposed to maternal HIV-1 provide an opportunity to assess correlates of HIV-1-specific interferon (IFN)-γ responses and may be informative in the development of HIV-1 vaccines. HIV-1-infected women with CD4 counts 200–500 cells/mm3 were randomized to short-course zidovudine/nevirapine (ZDV/NVP) or highly active anti-retroviral therapy (HAART) between 2003 and 2005. Maternal plasma and breastmilk HIV-1 RNA and DNA were quantified during the first 6–12 months postpartum. HIV-1 gag peptide-stimulated enzyme-linked immunospot (ELISPOT) assays were conducted in HIV-1-exposed, uninfected infants (EU), and correlates were determined using regression and generalized estimating equations. Among 47 EU infants, 21 (45%) had ≥1 positive ELISPOT result during follow-up. Infants had a median response magnitude of 177 HIV-1-specific spot-forming units (SFU)/106 peripheral blood mononuclear cells (PBMC) [interquartile range (IQR) = 117–287] directed against 2 (IQR = 1–3) gag peptide pools. The prevalence and magnitude of responses did not differ by maternal anti-retroviral (ARV) randomization arm. Maternal plasma HIV-1 RNA levels during pregnancy (P = 0·009) and breastmilk HIV-1 DNA levels at 1 month (P = 0·02) were associated with a higher magnitude of infant HIV-1-specific ELISPOT responses at 1 month postpartum. During follow-up, concurrent breastmilk HIV-1 RNA and DNA (cell-free virus and cell-associated virus, respectively) each were associated positively with magnitude of infant HIV-1-specific responses (P = 0·01). Our data demonstrate the importance of antigenic exposure on the induction of infant HIV-1-specific cellular immune responses in the absence of infection.
Predicting microscale shifts in the distribution of the butterflyPlebejus argusat the northern edge of its range
Authors: Hodgson Jenny A. , Bennie Jonathan J. , Dale Gemma , Longley Natalie , Wilson Robert J. , Thomas Chris D.
Published: February 2015

Species are often observed to occur in restricted patches of particularly warm microclimate at their high latitude/altitude geographic range margin. In these areas, global warming is expected to cause small‐scale expansion of the occupied area, but most previous studies of range expansion have used very coarse scale data. Using high resolution microclimate models together with detailed field surveys, we tested whether the butterflyPlebejus argus, occurring on limestone grassland in north Wales, was responding as might be expected due to climate change in the last 30–40 yr. The abundance of adultPlebejus argusat 100 m resolution in 2011 was strongly affected by elevation and near‐ground temperatures in May. A statistical model including microclimate, fitted to 2011 data, was successful (67% correct) at hindcasting the occurrence ofPlebejus argusin 1983 when the average May air temperature was 1.4°C cooler. However, the model was less accurate at hindcasting occurrences in 1972 (50% correct). Given the distribution of micro‐sites in this landscape, we predict that further warming of approximately 1°C would make the majority of sites highly microclimatically suitable for this species. There are a growing number of long‐term studies of range change, and investigations into the mechanisms driving them, but still surprisingly few that explicitly make and test predictions with independent data. Our tests are a valuable example of how accurate predictions of distribution change can be, but also of the inevitable uncertainties. Improved understanding of how well models predict will be very important to plan robust climate change adaptation measures.
Searching for the neural basis of reserve against memory decline: intellectual enrichment linked to larger hippocampal volume in multiple sclerosis
Authors: Sumowski J. F. , Rocca M. A. , Leavitt V. M. , Riccitelli G. , Sandry J. , DeLuca J. , Comi G. , Filippi M.
Published: February 2015

Background and purpose

Active engagement in intellectually enriching activities (e.g. reading, hobbies) builds ‘reserve’ against memory decline in elders and persons with multiple sclerosis (MS), but the neural basis for this protective influence of enrichment is unknown. Herein the neuroanatomical basis of reserve against memory decline in MS patients is investigated.

Methods

Relapse‐onset MS patients (N = 187) underwent 3.0 T magnetic resonance imaging of the brain to quantify T2 lesion volume (T2LV) and normalized volumes of total brain, total white, total grey (using SIENAX) and thalamus, caudate, putamen, pallidum, amygdala and hippocampus (using FIRST). Patients completed a survey quantifying their engagement in early life intellectual enrichment (i.e. reading, hobbies). Verbal and visuospatial episodic memory was assessed with neuropsychological tasks in a representative subsample (N = 97).

Results

Controlling for demographics and T2LV, intellectual enrichment was specifically linked to larger normalized hippocampal volume (rp = 0.213, P = 0.004), with no link to other brain volumes/structures. Moreover, greater intellectual enrichment moderated/attenuated the negative relationship between normalized total brain volume (i.e. overall cerebral atrophy) and normalized hippocampal volume (i.e. hippocampal atrophy; P = 0.001) whereby patients who engaged in more early life intellectual enrichment better maintained hippocampal volume in the face of worse overall cerebral atrophy. Finally, the link between greater intellectual enrichment and better memory was partially mediated through larger hippocampal volume.

Conclusions

These findings support larger hippocampal volume as one key component of the neuroanatomical basis of reserve against memory decline in MS. These findings are consistent with previous literature on experience‐dependent neuroplasticity within the hippocampus.
Letter to the Editor
Authors: Freeman David E.
Published: February 2015

See article by Naylor et al.
Histamine suppresses regulatory T cells mediated by TGF‐β in murine chronic allergic contact dermatitis
Authors: Tamaka Kyoko , Seike Masahiro , Hagiwara Tamio , Sato Atsushi , Ohtsu Hiroshi
Published: February 2015

Regulatory T cells (Tregs) suppress effector T cells and ameliorate contact hypersensitivity (CH); however, the role of Tregs in chronic allergic contact dermatitis (CACD) has not been assessed. Repeated elicitation of CH has been used to produce CACD models in mice. We previously showed that the presence of histamine facilitates the creation of eczematous lesions in this model using histidine decarboxylase (HDC) (−/−) mice. Therefore, the effects of histamine on Tregs in the CACD model were investigated in this study. CACD was developed by repeated epicutaneous application of 2, 4, 6‐trinitro‐1‐chlorobenzene (TNCB) on HDC (+/+) and HDC (−/−) murine skin to assess the effects of histamine in CACD. Histamine aggravated CACD in the murine model and suppressed the number of Tregs in the skin. Histamine also suppressed the level of TGF‐β1 in this model. Recombinant TGF‐β1 or anti‐TGF‐β1 antibody was injected into the dorsal dermis of HDC (+/+) mice daily just before TNCB challenge to determine the effects of histamine‐regulated TGF‐β on the Treg population in CACD. Recombinant TGF‐β1 injection promoted the infiltration of Tregs in the skin and the production of IL‐10; however, anti‐TGF‐β1 antibody injection suppressed the number of Tregs in the skin and the production of IL‐10. Histamine suppresses the number of Tregs in CACD, and this effect is mediated by TGF‐β.
Readthrough of stop codons by use of aminoglycosides in cells from xeroderma pigmentosum group C patients
Authors: Kuschal Christiane , Khan Sikandar G. , Enk Benedikt , DiGiovanna John J. , Kraemer Kenneth H.
Published: February 2015

Readthrough of premature termination (stop) codons (PTC) is a new approach to treatment of genetic diseases. We recently reported that readthrough of PTC in cells from some xeroderma pigmentosum complementation group C (XP‐C) patients could be achieved with the aminoglycosides geneticin or gentamicin. We found that the response depended on several factors including the PTC sequence, its location within the gene and the aminoglycoside used. Here, we extended these studies to investigate the effects of other aminoglycosides that are already on the market. We reasoned that topical treatment could deliver much higher concentrations of drug to the skin, the therapeutic target, and thus increase the therapeutic effect while reducing renal or ototoxicity in comparison with systemic treatment. Our prior clinical studies indicated that only a few percent of normal XPC expression was associated with mild clinical disease. We found minimal cell toxicity in the XP‐C cells with several aminoglycosides. We found increased XPC mRNA expression in PTC‐containing XP‐C cells with G418, paromomycin, neomycin and kanamycin and increased XPC protein expression with G418. We conclude that in selected patients with XP, topical PTC therapy can be investigated as a method of personalized medicine to alleviate their cutaneous symptoms.
The NK1 receptor antagonist aprepitant attenuates NK1 agonist‐induced scratching behaviour in the gerbil after intra‐dermal, topical or oral administration
Authors: Costantini Vivian J. A. , Corsi Mauro , Dünstl Georg , Bettelini Letizia , Zonzini Laura , Gerrard Philip
Published: February 2015

Experiments were conducted to develop a model to study the effect of oral and topical administration of the NK1 receptor antagonist aprepitant, on scratching behaviour in gerbils. The gerbil was selected due to its relevance for human NK1 receptor pharmacology. Intradermal injection of a specific NK1 receptor agonist GR73632 (100 nmol/100 µl) at the rostral back of gerbils produced scratching of the injection site. This could be attenuated by intradermal co‐administration of a selective NK1 receptor antagonist aprepitant (30–100–300 nmol), demonstrating the role of dermal NK1 receptor in elicitation of scratching behaviour. Likewise, scratching was attenuated by oral (0.3–3–30 mg/kg) or topical application (0.01–0.1–1% w/v) of aprepitant and pharmacokinetic analysis of aprepitant levels in brain, blood and skin supported that efficacy of topically applied aprepitant was due to dermal rather than central target engagement. In conclusion, we showed that NK1 agonist‐induced scratching in the gerbil can be reversed by systemic and topical administration of aprepitant. This test system may provide a useful model for the in vivo assessment of putative antipruritic agents.
Biodegradable behaviour and fatigue life of ZEK100 magnesium alloy in simulated physiological environment
Authors: Zhao J. , Gao L.‐L. , Gao H. , Yuan X. , Chen X.
Published: February 2015

The fatigue life of ZEK100 magnesium alloy in the phosphate buffered solution for various immersion intervals was investigated by experiments and theoretical predictions. The biodegradable behaviours of ZEK100 magnesium alloy were also studied. Microstructure observation showed that the corrosion behaviours were characterized by pitting corrosion. The corrosion rate decreased a lot in the initial 7 d and then almost stayed unchanged. After 28 d immersion, the elastic modulus almost kept stable, while the yield strength and the ultimate strength decreased a lot, which indicated that corrosion had important effects on the tensile mechanical properties. It showed that the fatigue life of the samples under the same stress conditions decreased with increasing immersion time under the asymmetric stress‐controlled cyclic loading. Considering the effect of corrosion on the material failure, a modified fatigue life model was proposed for magnesium alloy under corrosion.
Renal involvement in mushroom poisoning: The case of Orellanus syndrome
Authors: Esposito Pasquale , La Porta Edoardo , Calatroni Marta , Bianzina Stefania , Libetta Carmelo , Gregorini Marilena , Rampino Teresa , Dal Canton Antonio
Published: February 2015

Although mushroom poisoning is a rare cause of acute renal injury, in some cases it may lead to the development of a severe and irreversible renal failure. Orellanus syndrome is the most important example of organic renal damage related to mushroom consumption. It is caused by the ingestion of orellanine, the main toxin of different types of Cortinarius mushrooms (Cortinarius speciosissimus, C. orellanus, C. orellanoides, etc.), and it is characterized by progressive clinical phases with a predominant kidney involvement, finally requiring renal replacement therapy in about 10% of cases. Renal damage is often late and associated with a histological picture of interstitial nephritis. Diagnosis is essentially clinical and no specific therapy has been shown to be effective in preventing and treating renal damage. Here, we describe the case of a patient with mixed wild mushroom poisoning, presenting the typical clinical signs and course of the Orellanus syndrome. This case offers us the opportunity to review the main clinical features of this severe and little‐known intoxication.
Identification of Viable Helicobacter pylori in Drinking Water Supplies by Cultural and Molecular Techniques
Authors: Santiago Paula , Moreno Yolanda , Ferrús M. Antonía
Published: February 2015

Background

Helicobacter pylori is one of the most common causes of chronic bacterial infection in humans, directly related to peptic ulcer and gastric cancer. It has been suggested that H. pylori can be acquired through different transmission routes, including water. In this study, culture and qPCR were used to detect and identify the presence of H. pylori in drinking water. Furthermore, the combined techniques PMA‐qPCR and DVC‐FISH were applied for detection of viable cells of H. pylori.

Results

Among 24 drinking water samples, 16 samples were positive for the presence of H. pylori, but viable cells were only detected in six samples. Characteristic colonies, covered by a mass of bacterial unspecific growth, were observed on selective agar plates from an only sample, after enrichment. The mixed culture was submitted to DVC‐FISH and qPCR analysis, followed by sequencing of the amplicons. Molecular techniques confirmed the growth of H. pylori on the agar plate.

Conclusions

Our results demonstrate for the first time that H. pylori can survive and be potentially infective in drinking water, showing that water distribution systems could be a potential route for H. pylori transmission.
Intestinal metaplasia of the bladder with dysplasia: a risk factor for carcinoma?
Authors: Gordetsky Jennifer , Epstein Jonathan I
Published: February 2015

Aims

Intestinal metaplasia (IM) of the bladder is a benign glandular proliferation, where the urothelium becomes lined by intestinal‐type epithelium. There is no association between IM and an increased risk for the development of adenocarcinoma. However, in rare cases IM shows dysplasia, similar to that of the gastrointestinal tract. We evaluated the significance of urothelial IM with dysplasia.

Methods and results

Consultation cases were searched for IM of the bladder with dysplasia. We identified 20 cases, including 17 males and females, aged 31–85 years (mean 60 years). Twelve (60%) patients had low‐grade dysplasia and eight (40%) patients had high‐grade dysplasia. Focal dysplasia was found in eight (40%) patients and non‐focal dysplasia in 12 (60%) patients. IM with dysplasia was found with concurrent adenocarcinoma in eight (40%) cases. Five of these patients (63%) had disease recurrence and three (38%) patients died from their disease. IM with dysplasia was found with concurrent urothelial carcinoma in one case. Eleven patients had IM with dysplasia without evidence of malignancy. Of these, one went on to develop non‐invasive, high‐grade papillary urothelial carcinoma.

Conclusions

Clinical follow‐up is recommended in cases of IM with dysplasia, as a significant number of these cases are associated with concurrent carcinoma.
Comparison of immunoreactive score, HER2/neu score and H score for the immunohistochemical evaluation of somatostatin receptors in bronchopulmonary neuroendocrine neoplasms
Authors: Specht Elisa , Kaemmerer Daniel , Sänger Jörg , Wirtz Ralph M , Schulz Stefan , Lupp Amelie
Published: February 2015

Aims

Due to the growing number of somatostatin receptor (SSTR) targeting analogues and radiopeptides used for the diagnosis and therapy of neuroendocrine neoplasms (NEN), the assessment of SSTR subtype status has increasingly gained predictive value. In pathology, the SSTR protein levels are detected routinely by immunohistochemistry (IHC); however, a lack of a standardized evaluation system persists. Thus, in the present investigation, three well‐established semi‐quantitative scoring systems [immunoreactive score (IRS), human epidermal growth factor receptor 2 (HER2)/neu score, H score] used commonly for SSTR‐IHC evaluation in NEN were compared.

Methods and results

A total of 240 formalin‐fixed, paraffin‐embedded tumour samples from 90 patients with bronchopulmonary NEN were examined by IHC and quantitative reverse transcription–polymerase chain reaction (qRT–PCR) for SSTR1, 2A, 3, 4 and 5 expression. Using both methods, SSTR1, 2A and 5 were the most frequently expressed subtypes. For all SSTR subtypes, all three scores correlated well with each other and with qRT–PCR data. However, the IRS was the most meaningful score with the best correlation to mRNA levels.

Conclusions

Because a unified IHC scoring system for SSTR analysis is needed urgently to optimize the theranostics of NEN, among the scores tested, the IRS seems to be the most suitable according to our results. It provides sufficient accuracy combined with high practicability.
Tumour border configuration in colorectal cancer: proposal for an alternative scoring system based on the percentage of infiltrating margin
Authors: Karamitopoulou Eva , Zlobec Inti , Koelzer Viktor Hendrik , Langer Rupert , Dawson Heather , Lugli Alessandro
Published: February 2015

Aims

Information on tumour border configuration (TBC) in colorectal cancer (CRC) is currently not included in most pathology reports, owing to lack of reproducibility and/or established evaluation systems. The aim of this study was to investigate whether an alternative scoring system based on the percentage of the infiltrating component may represent a reliable method for assessing TBC.

Methods and results

Two hundred and fifteen CRCs with complete clinicopathological data were evaluated by two independent observers, both ‘traditionally’ by assigning the tumours into pushing/infiltrating/mixed categories, and alternatively by scoring the percentage of infiltrating margin. With the pushing/infiltrating/mixed pattern method, interobserver agreement (IOA) was moderate (κ = 0.58), whereas with the percentage of infiltrating margins method, IOA was excellent (intraclass correlation coefficient of 0.86). A higher percentage of infiltrating margin correlated with adverse features such as higher grade (P = 0.0025), higher pT (P = 0.0007), pN (P = 0.0001) and pM classification (P = 0.0063), high‐grade tumour budding (P < 0.0001), lymphatic invasion (P < 0.0001), vascular invasion (P = 0.0032), and shorter survival (P = 0.0008), and was significantly associated with an increased probability of lymph node metastasis (P < 0.001).

Conclusions

Information on TBC gives additional prognostic value to pathology reports on CRC. The novel proposed scoring system, by using the percentage of infiltrating margin, outperforms the ‘traditional’ way of reporting TBC. Additionally, it is reproducible and simple to apply, and can therefore be easily integrated into daily diagnostic practice.
HISTORY AS PHILOSOPHY
Authors: CRACRAFT JAMES
Published: February 2015

Historians have taken a beating in recent times from an array of critics troubled by our persistent unwillingness to properly theorize our work. This essay contends that their criticisms have generally failed to make headway among mainstream historians owing to a little noticed cognitive byproduct of our work that I call history as philosophy. In so doing I offer a novel defense of professional history as it has been understood and practiced in the Anglophone world over the last half‐century or so while suggesting, in conclusion, that historians could not do other than they do without serious psychic and societal loss.