bluuebunny/crossref_metadata_2025 huggingface dataset:
Group I metabotropic glutamate receptor‐mediated activation of PKC gamma in the nucleus accumbens core promotes the reinstatement of cocaine seeking
Authors: Schmidt Heath D. , Kimmey Blake A. , Arreola Adrian C. , Pierce R. Christopher
Published: February 2014

Emerging evidence indicates that type I metabotropic glutamate receptors (mGluRs) in the nucleus accumbens play a critical role in cocaine seeking. The present study sought to determine the role of accumbens core mGluR1, mGluR5 and protein kinase C (PKC) in cocaine priming‐induced reinstatement of drug seeking. Here, we show that intra‐accumbens core administration of the mGluR1/5 agonist DHPG (250 μM) promoted cocaine seeking in rats. Consistent with these results, administration of an mGluR1 (50.0 μM YM 298198) or mGluR5 (9.0 μM MPEP) antagonist directly into the accumbens core prior to a priming injection of cocaine (10 mg/kg) attenuated the reinstatement of drug seeking. mGluR1/5 stimulation activates a signaling cascade including PKC. Intracore microinjection of PKC inhibitors (10 μM Ro 31–8220 or 30.0 μM chelerythrine) also blunted cocaine seeking. In addition, cocaine priming‐induced reinstatement of drug seeking was associated with increased phosphorylation of PKCγ, but not PKCα or PKCβII, in the core. There were no effects of pharmacological inhibition of mGluR1, mGluR5 or PKC in the accumbens core on sucrose seeking. Together, these findings indicate that mGluR1 and mGluR5 activation in the accumbens core promotes cocaine seeking and that these effects are reinforcer specific. Furthermore, stimulation of mGluR1 and mGluR5 in the accumbens core may regulate cocaine seeking, in part, through activation of PKCγ.
Genome‐wide association analysis identifies quantitative trait loci for growth in a Landrace purebred population
Authors: Jung E. J. , Park H. B. , Lee J. B. , Yoo C. K. , Kim B. M. , Kim H. I. , Kim B. W. , Lim H. T.
Published: February 2014

Growth‐related traits are complex and economically important in the livestock industry. The aim of this study was to identify quantitative trait loci (QTL) and the associated positional candidate genes affecting growth in pigs. A genome‐wide association study (GWAS) was performed using the porcine single‐nucleotide polymorphism (SNP) 60K bead chip. A mixed‐effects model and linear regression approach were used for the GWAS. The data used in the study included 490 purebred Landrace pigs. All experimental animals were genotyped with 39 438 SNPs located throughout the pig autosomes. We identified a strong association between a SNP marker on chromosome 16 and body weight at 71 days of age (ALGA0092396, P = 5.35 × 10−9, Bonferroni adjusted P < 0.05). The SNP marker was located near the genomic region containing IRX4, which encodes iroquois homeobox 4. This SNP marker could be useful in the selective breeding program after validating its effect on other populations.
Systematic review with network meta‐analysis: the efficacy of anti‐tumour necrosis factor‐alpha agents for the treatment of ulcerative colitis
Authors: Stidham R. W. , Lee T. C. H. , Higgins P. D. R. , Deshpande A. R. , Sussman D. A. , Singal A. G. , Elmunzer B. J. , Saini S. D. , Vijan S. , Waljee A. K.
Published: February 2014

Background

Antibodies against tumour necrosis factor‐alpha (anti‐TNF) are effective therapies in the treatment of ulcerative colitis (UC), but their comparative efficacy is unknown.

Aim

To perform a network meta‐analysis comparing the efficacy of anti‐TNF agents in UC.

Methods

After screening 506 studies, reviewers extracted information on seven studies. Traditional meta‐analysis (TMA) was used to compare each anti‐TNF agent to placebo. Bayesian network meta‐analysis (NMA) was performed to compare the effects of anti‐TNF agents to placebo. In addition, sample sizes for comparative efficacy trials were calculated.

Results

Compared to placebo, TMA revealed that anti‐TNF agents result in a higher likelihood of induction of remission and response (RR: 2.45, 95% CI: 1.72–3.47 and RR: 1.65, 95% CI: 1.37–1.99 respectively) as well as maintenance of remission and response (RR: 2.00, 95% CI: 1.52–2.62 and RR: 1.76, 95% CI: 1.46–2.14 respectively). Individually, infliximab, adalimumab and goliumumab resulted in a higher likelihood of induction and maintenance for both remission and response. NMA found nonsignificant trends in comparisons of the individual agents. The required sample sizes for direct head‐to‐head trials between infliximab and adalimumab for induction and maintenance are 174 and 204 subjects respectively.

Conclusions

This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis. However, network meta‐analysis demonstrates that no single agent is clinically superior to the others and therefore, other factors such as cost, safety, route of administration and patient preference should dictate our choice of anti‐TNF agents. A randomised comparative efficacy trial between infliximab and adalimumab in UC is of practical size and should be performed.
Systematic review with meta‐analysis: the declining risk of colorectal cancer in ulcerative colitis
Authors: Castaño‐Milla C. , Chaparro M. , Gisbert J. P.
Published: February 2014

Background

Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC); however, the magnitude of this effect is open to debate.

Aim

To assess the risk of CRC in UC patients by systematic review and meta‐analysis.

Methods

A systematic literature search was performed up to November 2013. We selected studies describing the incidence and prevalence of CRC in patients with UC. Articles were assessed for quality using the Newcastle‐Ottawa Scale. Cumulative incidence and incidence rates of CRC were combined and analysed using the generic inverse variance method. Sub‐analyses were performed to identify factors associated with an increased risk of developing CRC.

Results

A total of 81 studies (181 923 patients) met the inclusion criteria. The incidence rate of CRC in patients with UC was 1.58 per 1000 patient‐years (py) [95% confidence interval (CI), 1.39–1.76]. Results were heterogeneous (I2 = 81–89%). The incidence rate was 4.02/1000 py (95%CI = 2.74–5.31) in studies that only included patients with extensive colitis, and 1.24/1000 py (95%CI = 1.01–1.47) in population‐based studies. The incidence rate was 0.91/1000 py (95%CI = 0.61–1.2) in the first decade of disease, 4.07/1000 py (95%CI = 2.58–5.56) in the second, and 4.55/1000 py (95%CI = 2.64–6.46) in the third. The incidence rate decreased from 4.29/1000 py in the studies published in the 1950s to 1.21/1000 py in studies published in the last decade.

Conclusions

The risk of patients with ulcerative colitis developing colorectal cancer has decreased steadily over the last six decades, but the extent and duration of the disease increase this risk.
The eye of the caecilian Rhinatrema bivittatum (Amphibia: Gymnophiona: Rhinatrematidae)
Authors: Mohun Samantha M. , Wilkinson Mark
Published: February 2014

The reduction in the visual system of the Gymnophiona has been noted by many authors. Adult caecilian amphibians eyes are small, covered by skin and sometimes bone, with retinal cells that contain only rod opsins and co‐option of structures usually associated with the visual system used for novel sensory structures and functions. Here, we provide a description of the eye of Rhinatrema bivittatum, the first of any rhinatrematid caecilian, and consider its significance for our understanding of the nature of the eye in the last common ancestor of living caecilians. Characters discovered include zonule fibres, an aqueous humour and the remnants of an attachment that could be a protractor lentis muscle.
‘I saw what the future direction would be…’: Experiences of diabetes risk and physical activity after diabetes screening
Authors: Vähäsarja Kati , Kasila Kirsti , Kettunen Tarja , Rintala Pauli , Salmela Sanna , Poskiparta Marita
Published: February 2014

Objectives

To improve understanding of how individuals at high risk of type 2 diabetes experience the risk of diabetes and how these experiences relate to the adoption of physical activity as a protective behaviour.

Design

A qualitative study using semi‐structured interview with individuals identified by screening as at high risk of type 2 diabetes.

Methods

Fourteen individuals, aged 40–64, were interviewed twice, with a 2‐year interval between. Participants' experiences of their risk of diabetes and physical activity were assessed. The transcribed interview data were analysed using inductive qualitative content analysis.

Results

Two themes emerged from the data: a threatening risk perception and a rejected risk perception. The threatening risk perception occurred when the risk was unexpected by the participant, but became internalized through the screening procedure. The threatening perception also involved a commitment to increase physical activity to prevent diabetes. However, short‐term anxiety and subsequently emerging hopelessness were also part of this perception. The rejected risk perception involved indifference and scepticism regarding the risk. Here, physical activity behaviour and cognitions appeared to remain unchanged. Rejection also involved difficulties in accepting one's high‐risk identity. The rejecting group lacked motivation for increased physical activity, while the other group showed determination regarding increased physical activity, often leading to success.

Conclusion

Perceptions of the risk of diabetes emerged as threatening or as rejected. Participants' perceptions reflected varying and intertwining emotional, cognitive, and behavioural mechanisms for coping with the risk, all of which should be recognized in promoting physical activity among high‐risk individuals.

Statement of contribution

What is already known on this subject? Diabetes screening has few adverse psychological effects on screened individuals. Diabetes can be prevented by increased physical activity and modest weight loss among high‐risk individuals. The evidence on the effects of screening on protective behaviour is limited and inconsistent.

What does this study add?

High‐risk individuals' threatening perception of risk appears encouraging increased physical activity.

Individuals having problems in adjusting to high‐risk identification may not be motivated to engage in physical activity for prevention.

Failure to achieve the outcomes expected from lifestyle changes may lead people with threatening risk perception to a sense of hopelessness.
Panel‐based testing for inherited colorectal cancer: a descriptive study of clinical testing performed by a US laboratory
Authors: Cragun D. , Radford C. , Dolinsky J.S. , Caldwell M. , Chao E. , Pal T.
Published: February 2014

Next‐generation sequencing enables testing for multiple genes simultaneously (‘panel‐based testing’) as opposed to sequential testing for one inherited condition at a time (‘syndrome‐based testing’). This study presents results from patients who underwent hereditary colorectal cancer (CRC) panel‐based testing (‘ColoNext™’). De‐identified data from a clinical testing laboratory were used to calculate (1) frequencies for patient demographic, clinical, and family history variables and (2) rates of pathogenic mutations and variants of uncertain significance (VUS). The proportion of individuals with a pathogenic mutation who met national syndrome‐based testing criteria was also determined. Of 586 patients, a pathogenic mutation was identified in 10.4%, while 20.1% had at least one VUS. After removing eight patients with CHEK2 mutations and 11 MUTYH heterozygotes, the percentage of patients with ‘actionable’ mutations that would clearly alter cancer screening recommendations per national guidelines decreased to 7.2%. Of 42 patients with an ‘actionable’ result, 30 (71%) clearly met established syndrome‐based testing guidelines. This descriptive study is among the first to report on a large clinical series of patients undergoing panel‐based testing for inherited CRC. Results are discussed in the context of benefits and concerns that have been raised about panel‐based testing implementation.
Single‐incision laparoscopic ileorectal anastomosis
Authors: Naqi Syed Ali , Smyth James , Mortensen Neil , Hompes Roel , Cahill Ronan
Published: February 2014

Aim

Minimally invasive approaches for stoma closure offer considerable benefits for patients. Single port access via an end ileostomy site after stoma take‐down in patients with prior total colectomy and a rectal stump remnant could allow restoration of ileorectal continuity by anastomosis but has not been detailed previously.

Methods

After mobilisation of the end ileostomy, the anvil of a circular stapler is secured into the open end of the distal ileum and the intestine returned into the abdominal cavity. A single port access device (in this description, a ‘surgical glove port’) is placed then into the stoma site and full laparoscopy performed. Once the rectal stump is identified and prepared, an intracorporeal anastomosis can be constructed in a tension‐free manner using a Knight‐Griffin technique. Leak‐testing can also be performed and the operation concluded with closure of the solitary incision.

Results

In selected cases, adhesiolysis and anastomosis can be safely performed in toto. If the peritoneal environment is challenging, access can be escalated to multiport laparoscopy or even laparotomy.

Conclusion

Initiation of ileorectal anastomosis construction by single port laparoscopy at least allows peritoneal assessment but can provide for the operation's completion. This can confer maximum patient benefit for the most minimally invasive option.
Dynamic cystocolpoproctography is superior to functional pelvic MRI in the diagnosis of posterior pelvic floor disorders: results of a prospective study
Authors: Faucheron J.‐L. , Barot S. , Collomb D. , Hohn N. , Anglade D. , Dubreuil A.
Published: February 2014

Aim

The accuracy of dynamic cystocolpoproctography (DCP) and dynamic MRI were compared in diagnosing posterior pelvic floor disorders.

Method

Fifty consecutive female patients (mean age 51 years) complaining of posterior compartment pelvic floor disorder and referred to a tertiary centre entered the prospective study. The Institutional Review Board stated that informed consent from the patients was not necessary for this study. Patients underwent a DCP and a supine functional MRI by two different radiologists. Assessment of radiological examinations was prospective and blind. All patients underwent surgery that led to the final diagnosis. Agreement between the operative diagnosis and the diagnoses following DCP and MRI was assessed using the weighted kappa statistic. A matched‐pairs McNemar's test was applied to demonstrate whether or not one radiological method was superior to the other.

Results

Full‐thickness rectal prolapse was best diagnosed by clinical examination. Internal rectal prolapse and peritoneocele were best diagnosed by DCP. A better agreement with the operative diagnosis, which is not true superiority, was observed for DCP compared with functional pelvic MRI for full‐thickness rectal prolapse, internal rectal prolapse and peritoneocele. There was no significant difference between DCP and functional pelvic MRI in the diagnosis of internal rectal prolapse (P = 0.125) or peritoneocele (P = 0.10).

Conclusion

As full‐thickness rectal prolapse, internal rectal prolapse and peritoneocele might be missed by functional pelvic MRI, there should still be a place for DCP in particular cases where the clinical diagnosis is not clear in women with symptomatic posterior pelvic floor disorders.
National Governance Bundles and Corporate Agency Costs: A Cross‐Country Analysis
Authors: Aslan Hadiye , Kumar Praveen
Published: February 2014

Manuscript Type

Conceptual and empirical

Research Question/Issue

Comparative corporate governance performance across countries cannot be captured adequately by ranking of single or a few national governance factors (NGFs). But it is also intractable to undertake separate comparative analyses of the large number of NGFs that potentially impact corporate governance mechanisms. How can NGFs be combined into national governance bundles (NGBs) that are informative of the level of agency costs at the firm level and are also convenient to use in comparative analyses?

Research Findings/Insights

We theoretically motivate and empirically identify the components of two NGBs that, at the firm level, have especially significant impact on controlling shareholder agency costs and the agency costs of debt financing, respectively. These NGBs (1) allow consolidation of the effects of various individual NGFs that have been considered separately in the literature, (2) reveal the complementarity and substitutability effects among NGFs and between NGFs and firm governance mechanisms, and (3) are convenient to apply through aggregate bundle scores.

Theoretical/Academic Implications

Forming NGBs by combining NGFs that have especially significant impact on specific agency costs is useful both theoretically and empirically. The theoretical analysis guides the identification of NGFs that may be especially influential on specific agency costs and these predictions can be verified empirically. Examining the effects of NGFs on the relation of firm‐level governance mechanisms and agency costs is useful in understanding the links between national‐ and firm‐level governance variables.

Practitioner/Policy Implications

The parsimony and tractability afforded by the NGBs in understanding various aspects of corporate governance performance should prove useful to policymakers, international business managers, and investors. By providing readily available indicators of different agency costs at the firm level, these bundles can guide policymakers in setting the legal and regulatory framework for corporate governance at the national level.
Non‐interactive effects of plant invasion and landscape modification on native communities
Authors: Gooden Ben , French Kris
Published: February 2014

Aim

Biological invasions and anthropogenic habitat modification are considered to be the leading drivers of global environmental change, yet their synergistic impacts on native communities remain poorly understood. We tested the effects of an invasive grass,Stenotaphrum secundatum, on an endangered coastal swamp forest community across an anthropogenic land use gradient. We also investigated the relative importance of landscape versus local community attributes in mediating the effects ofS. secundatuminvasion on the community.

Location

Four hundred kilometres of the coastline of south‐eastern Australia.

Methods

We compared the diversity, composition and recruitment of resident vegetation in 32 invaded and 32 non‐invaded forest stands across an anthropogenic land use gradient. Local disturbance and environmental attributes of the forest (e.g. fire severity, litter abundance, canopy openness, vegetation structure) and adjacent landscape matrix (e.g. cover of forest, urban and agricultural land) were measured in detail at each site.

Results

Invasion was associated with substantial local extinctions of native plant species (i.e. 83% fewer species in invaded sites), altered community compositions and an 85% reduction in rates of woody plant recruitment. Local disturbances and environmental attributes of forest stands and adjacent landscape matrix were similar between invaded and native sites. Invasion caused a twofold increase in litter biomass, which we hypothesize is the primary mechanism by which the invader excludes native species. Landscape modification had no effect on the diversity of adjacent swamp forest. There was no interactive effect of landscape modification and invasion on the native community; species losses in response to invasion were high regardless of the condition of the adjacent matrix.

Main conclusions

We show that impacts of non‐native species are not dependent on landscape context and, unexpectedly, that invasion by an alien plant poses a greater threat to diversity of endangered swamp forests than modification of the adjacent matrix.
Neuroimaging and neurodevelopmental outcome of preterm infants with a periventricular haemorrhagic infarction located in the temporal or frontal lobe
Authors: Soltirovska Salamon Aneta , Groenendaal Floris , van Haastert Ingrid C , Rademaker Karin J , Benders Manon J N L , Koopman Corine , de Vries Linda S
Published: February 2014

Aim

The aim of the study was to compare clinical and neuroimaging characteristics and neurodevelopmental outcome in preterm infants with a periventricular haemorrhagic infarction (PVHI) located in the temporal or frontal periventricular white matter.

Method

The study was a retrospective hospital‐based study of preterm infants with a frontal PVHI (n=21; 11 males, 10 females; mean birthweight 1527g; mean gestational age 30.3wks) or temporal PVHI (n=13; five males, eight females; mean birthweight 1205g; mean gestational age 30.2wks) admitted to the neonatal intensive care unit between 1990 and 2012. The clinical course, results of neuroimaging studies, and neurodevelopmental outcomes of preterm infants with a gestational age less than 34 weeks with a confirmed PVHI on early cranial ultrasonography and/or magnetic resonance imaging were reviewed. For assessment of neurodevelopmental outcome we used the Griffiths Mental Development Scales, the Movement Assessment Battery for Children, the Gross Motor Function Classification System, the Wechsler Preschool and Primary Scale of Intelligence, the Child Behavior Checklist, and ophthalmological assessment. An unfavourable neurodevelopmental outcome was defined as moderately or severely atypical neurological examination during the last visit: presence of cerebral palsy, epilepsy, a hearing or visual impairment, and/or atypical cognitive development (Griffiths Mental Development Scales developmental quotient or Wechsler Preschool and Primary Scale of Intelligence <85).

Results

Unfavourable outcome was observed in 12 out of 13 children with a temporal PVHI compared with six out of 21 children with a frontal PVHI (p=0.002). Only one of the included infants with a PVHI in the temporal white matter developed cerebral palsy, which was due to a parietal PVHI in the contralateral hemisphere. Cognitive impairment was noted in seven infants with a frontal PVHI and five with a temporal PVHI. There were more infants with a temporal PVHI who developed visual impairment (n=5) or behavioural problems (n=7) compared with those with a frontal PVHI (visual impairment (n=2), behavioural problems (n=3).

Interpretation

PVHI located in the temporal or frontal lobe is almost invariably related to a typical motor outcome, but carries a risk of cognitive, behavioural, and visual problems, especially in infants with a PVHI located in the temporal lobe.
Duration and patterns of habitual physical activity in adolescents and young adults with cerebral palsy
Authors: Shkedy Rabani Anat , Harries Netta , Namoora Ibtisam , Al‐Jarrah Muhammed D , Karniel Amir , Bar‐Haim Simona
Published: February 2014

Aim

Adolescents and young adults with cerebral palsy (CP) show reduced motor function and gait efficiency, and lower levels of habitual physical activity (HPA), than adolescents with typical development and children with CP. This study examined activity duration and patterns in this population in the Middle East through long‐term monitoring of a large sample using accelerometers.

Method

Adolescents and young adults with bilateral CP at Gross Motor Function Classification System (GMFCS) levels II, III, and IV, were monitored in their habitual environment for four consecutive days with ActivPAL3 monitors. Time spent in sedentary, standing, and walking activities, and frequency of walking steps and transitions, were analysed for each GMFCS level.

Results

Measurements were made on 222 participants (132 males, 90 females; mean age 16y 9mo SD 2y, range 13y 4mo–22y). The Mann–Whitney U test demonstrated significant differences (p<0.05) between GMFCS levels, showing reduced walking and standing activity and increased sedentary duration at higher GMFCS levels (p<0.001), except for increased standing time between GMFCS levels II and III (p=0.07). Participants in educational facilities exhibited less sedentary behaviour than those who were homebound (p<0.05).

Interpretation

These descriptions of duration and frequency of active and sedentary behaviours may serve as a basis for recommendations to minimize inactivity in this population. Adolescents and young adults with CP in the Middle East demonstrate similar patterns of HPA to their peers in other regions.
Would you rather have your brain injury at five or twenty‐five?
Authors: Forsyth Rob
Published: February 2014

This commentary is on the original article by Anderson et al. on pages 329–336 of this issue.
High‐Intensity Focused Ultrasound Ablation of Myocardium In Vivo and Instantaneous Biological Response
Authors: Zheng Minjuan , Shentu Weihui , Chen Dingzhang , Sahn David J. , Zhou Xiaodong
Published: February 2014

Objective

This study aimed to evaluate the instantaneous biological response of canine myocardium in vivo to high‐intensity focused ultrasound (HIFU) ablation, and thereby determine the feasibility of this method.

Methods

Left ventricle myocardium HIFU ablation was performed on six dogs at four levels of HIFU energy (acoustic intensity was 3000 W/cm2; ablation durations were 1.2, 2.4, 3.6, and 4.8 sec, respectively). Gross lesion volumes were confirmed and assessed by tetrazolium chloride (TTC) staining, hematoxylin–eosin (HE) staining, and electron microscopy. Global cardiac function and focal wall motion were evaluated by echocardiography. Blood enzymes and cardiac troponin T (CTnT) were tested after ablation. HIFU ablation was repeated on another set of six fresh canine hearts in vitro at the same four energy levels. Focal maximum temperatures were detected both in vivo and in vitro.

Results

Different sizes of ablation via HIFU can be created in beating hearts using controlled energy emission. Focal maximum temperatures varied from 62 ± 4.8°C to 81 ± 12.9°C. The lesion sizes were significantly smaller in vivo than in vitro, as verified by TTC and HE staining. Focal wall motion immediately decreased after ablation (P < 0.05), although the ejection fraction (EF) and E/A ratio were unchanged (P > 0.05). Enzymes and CTnT immediately increased.

Conclusion

HIFU can be used for the controllable ablation of myocardial tissue, with instantly increased serum markers, decreased regional wall motion, and unaffected left ventricular global function.
How does Firm Size Moderate Firms' Ability to Benefit from Invention? Evidence from Patents and Scientific Publications
Authors: Belenzon Sharon , Patacconi Andrea
Published: February 2014

Using novel firm‐level panel data, this paper investigates how firms' ability to benefit from invention is moderated by firm size. We distinguish between output indicators of applied research using patents versus output indicators of basic research using scientific publications in “hard science” journals. Our results show that the relationship between performance and patents is stronger for small firms than for large firms. By contrast, the relationship between performance and scientific publications is stronger for large firms than for small firms. We also investigate several mechanisms that may be responsible for these firm size effects. Cost‐spreading, complementary assets and especially large firm's inertia all appear to exert a significant influence on the appropriability of patented research. Conversely, a key role of published research seems to be that of complementing large firms' marketing and sales efforts.
A Structural Approach to Handling Endogeneity in Strategic Management: The Case of RBV
Authors: Nandialath Anup Menon , Dotson Jeffrey P. , Durand Rodolphe
Published: February 2014

In this paper we posit that the lack of consensus about empirical tests of resource based view (RBV) could be the result of endogenous resource picking on the part of firms. If resources are endogenously selected, regression based methods that examine their connection to firm performance will be mis‐estimated. We show that traditional remedies for endogeneity do not resolve this problem when returns to resources are heterogeneous (as theorized under RBV) and when managers act with at least partial knowledge of the expected, idiosyncratic return (as theorized under the strategic factor market hypotheses). As such, we develop a Bayesian approach that solves this endogeneity problem by directly incorporating resource picking into the modeling framework. We illustrate the validity of our approach through the use of a comprehensive simulation study and show that our proposed approach outperforms traditional linear models (including traditional cures of endogeneity and unobserved heterogeneity) under a variety of conditions. Our findings suggest that: (1) research in strategy requires a more careful and deeper understanding of potential sources of endogeneity and (2) the use of Bayesian methods in management can help develop more theoretically motivated empirical approaches to hypothesis testing.
Partner Geographic and Organizational Proximity and the Innovative Performance of Knowledge‐Creating Alliances
Authors: Capaldo Antonio , Petruzzelli Antonio Messeni
Published: February 2014

We adopt a knowledge‐based perspective to investigate the individual and interaction effects of partner geographic and organizational proximity on the innovative performance of knowledge‐creating alliances. Our econometric analysis on a sample of 1,515 interfirm dyadic knowledge‐creating R&D alliances shows that both geographic distance between allied firms and their affiliation with the same business group negatively affect the alliance innovative performance. However, when jointly considered, the two examined partner characteristics positively moderate each other's effect on alliance innovative performance, so revealing a complementary effect on it. We argue that, while the existence of group ties between geographically distant organizations reduces the negative influence of geographic distance on the partners' ability to integrate their knowledge within the alliance, collaborating with remote partners weakens the negative influence of the existence of group ties between partners on knowledge diversity in alliances. We conclude that geographic distance and organizational proximity are contingent upon one another in their effect on the innovative performance of knowledge‐creating alliances and that distance (proximity) in one dimension can be bridged (overcome) by proximity (distance) in another dimension.
Uncovering clinical and radiological associations of triphasic waves in acute encephalopathy: a case–control study
Authors: Sutter R. , Kaplan P. W.
Published: February 2014

Background and purpose

Triphasic waves (TWs) are archetypal waveforms seen on electroencephalography (EEG) in some forms of encephalopathy. Their particular underlying pathological substrates are largely unexplored. This case–control study was designed to identify and quantify specific clinical and neuroradiological associations underlying TWs and to determine if TWs predicate outcome.

Methods

From 2004 to 2012, adult encephalopathic patients with TWs (cases) were matched 1:1 with encephalopathic patients without TWs (controls) by Glasgow Coma Scale (GCS) and the frequency range of EEG background activity. Clinical characteristics, neuroimaging and outcomes were assessed.

Results

The mean age of 190 patients (95 with and 95 without TWs) was 66.6 years (±15.6). In multivariable analyses, patients with TWs had significantly higher odds for liver insufficiency [odds ratio (OR) = 8.10, 95% confidence interval (CI) 1.98–33.08], alcohol abuse (OR = 3.65, 95% CI 1.25–10.63), subcortical brain atrophy (OR = 2.82, 95% CI 1.39–5.71) and respiratory tract infections (OR = 1.28, 95% CI 1.01–4.71). With each additional independent predictor, the odds increased for the occurrence of TWs (1 predictor, OR = 2.40, 95% CI 1.16–5.13; ≥2 predictors, OR = 9.20, 95% CI 3.27–25.62). Mortality was 15% and tended to be higher in patients with TWs (19% with vs. 11% without TWs).

Conclusions

Alcohol abuse, liver insufficiency, infections and subcortical brain atrophy were independently associated with TWs in patients matched for clinical and EEG features of encephalopathy. These associations strengthen the hypothesis that TWs evolve from an interplay of pathological neurostructural, metabolic and toxic conditions. When matched for EEG background activity and GCS, TWs were not associated with death.
Hearing loss may be a non‐motor feature of Parkinson's disease in older people in Taiwan
Authors: Lai S.‐W. , Liao K.‐F. , Lin C.‐L. , Lin C.‐C. , Sung F.‐C.
Published: February 2014

Background and purpose

The aim of this study was to explore whether hearing loss is associated with the risk of Parkinson's disease in the elderly in Taiwan.

Methods

Using claims data of the Taiwan National Health Insurance Program, 4976 patients (aged 65 years or older) with newly diagnosed hearing loss from 2000 to 2010 were identified and 19 904 subjects without hearing loss were randomly selected as comparisons, frequency matched by sex, age and index year of diagnosing hearing loss. The incidence of Parkinson's disease by the end of 2010 and the associated risk factors were investigated.

Results

The incidence of Parkinson's disease in the hearing loss group was 1.77‐fold higher than that in the non‐hearing‐loss group (3.11 vs. 1.76 per 1000 person‐years). After controlling for confounding factors, the adjusted hazard ratio (HR) of Parkinson's disease was 1.53 (95% CI 1.17, 1.99) for the hearing loss group compared with the non‐hearing‐loss group. Male sex (HR = 1.33, 95% CI 1.02, 1.74), age (for each year, HR = 1.06, 95% CI 1.04, 1.09), hypertension (HR = 1.70, 95% CI 1.26, 2.30) and cerebrovascular disease (HR = 1.78, 95% CI 1.37, 2.32) were also significantly associated with the risk of Parkinson's disease.

Conclusions

Hearing loss correlates with an increased risk of Parkinson's disease in the elderly. Further studies are needed to confirm whether hearing loss could be a non‐motor feature of Parkinson's disease.
Neuroinfectious diseases at a European neurological tertiary care center: one‐third of patients require treatment in the neurological intensive care unit
Authors: Buchholz G. , Ormanns S. , Pfister H.‐W. , Koedel U. , Klein M.
Published: February 2014

Background and purpose

Studies on the impact of infectious diseases affecting the nervous system are sparse.

Methods

All patients with neuroinfectious diseases (NIDs) who were treated at our Department of Neurology from 2005 until 2009 were retrospectively analyzed.

Results

Patients with NIDs required treatment at the intensive care unit in 34.8%. The mortality rate of patients with NIDs was significantly higher than that of other inpatients with neurological diseases (5.1% vs. 3.0%, respectively, P = 0.018).

Conclusion

In summary, this study shows that patients with NIDs are severely ill and mortality is high.
The influence of pre‐settlement and early post‐settlement processes on the adult distribution and relative dominance of two invasive mussel species
Authors: Jones Lisa A. , Ricciardi Anthony
Published: February 2014

The structure of a community is governed by a complex combination of processes whose relative importance varies over time and space. Larval dynamics, settlement and recruitment are thought to be important processes limiting adult abundance and distribution of benthic invertebrates with planktonic larvae.

Two invasive molluscs with similar morphology and resource needs, the Eurasian zebra mussel Dreissena polymorpha and the quagga mussel Dreissena rostriformis bugensis, co‐occur in several North American lakes and rivers but often differ in their adult distribution over depth. Following establishment, the quagga mussel typically replaces the zebra mussel in abundance, particularly in deeper waters. A field sampling programme conducted over 3 years in a lotic system (the Soulanges Canal connected to the St. Lawrence River) examined the extent to which adult distribution and the differential dominance of these two species are determined by larval supply (i.e. larval abundance near settlement sites), settlement and recruitment.

Total dreissenid larval abundance in the water column at two depths was determined weekly, and larval competence (size) and species‐specific larval composition was estimated, during the main settlement period over three consecutive years. The pattern of total dreissenid settlement over the depth gradient was determined by deployment of settlement plates at both depths. Total abundance and proportional abundance of zebra mussel and quagga mussel juveniles and adults in each depth zone were determined monthly from July to September each year.

Mean dreissenid larval size did not differ between depths and the supply of late‐stage larvae was generally low, but total larval abundance was consistently greater in deeper water. This differential larval abundance established settlement and recruitment patterns in the canal but contrasted predictions based on total adult dreissenid abundance – which was higher in the shallow zone. Therefore, the significant factor dictating the abundance of adult mussels in these two depth zones must be post‐recruitment mortality, rather than larval supply, settlement or recruitment.

Despite a strong species‐specific adult depth zonation, larvae and juveniles showed no consistent differences in species proportions over the depth gradient. In fact, zebra mussels dominated larval abundance at both depths for c. 50% of the sampling dates and dominated juvenile abundance at both depths throughout most of the sampling period. In contrast, the proportional abundance of zebra mussels in the adult dreissenid community was consistently 4–5 times higher in the shallow zone.

These results indicate that larval supply, settlement and recruitment processes are not responsible for determining total adult dreissenid distribution or species dominance. Rather, these patterns appear to be governed by post‐recruitment factors that manifest themselves in later stages of mussel development and growth.
Generalist versus specialist strategies of plasticity: snail responses to predators with different foraging modes
Authors: Hoverman Jason T. , Cothran Rickey D. , Relyea Rick A.
Published: February 2014

Phenotypic plasticity is a common adaptation to environmental heterogeneity, and theory predicts that the evolution of constitutive versus plastic strategies should depend on the frequency of alternative environments, the magnitude of constraints and the costs of plasticity per se. However, it is unclear how species should evolve when they experience more than two environments that favour divergent phenotypes, particularly when they have absolute constraints on their morphology.

We examined the plasticity of three freshwater snail species (Helisoma anceps, H. campanulata and H. trivolvis) in response to three environments: (i) no predator; (ii) shell‐invading water bugs (Belostoma flumineum) and (iii) shell‐crushing crayfish (Orconectes rusticus). We found distinct responses by each snail species to the predator treatments. Helisoma anceps starts with a relatively low, narrow and thick shell that becomes lower and thicker in response to crayfish but is unresponsive to water bugs. In contrast, H. campanulata starts with a relatively high, wide and thin shell that becomes lower and wider in response to water bugs but is unresponsive to crayfish. Helisoma trivolvis starts with a shell of intermediate height and width while the predators induce defences in different directions.

These results suggest that H. trivolvis has a generalist plastic strategy while H. anceps and H. campanulata have specialised plastic strategies orientated against a single type of predator at the potential cost of being unable to respond to others.

We then performed predation trials to determine predator preferences using a mixture of the three species. After 2 weeks of exposure to crayfish cues, H. anceps had higher survival than both H. trivolvis and H. campanulata with uncaged crayfish. After 2 weeks of exposure to water bug cues, both H. trivolvis and H. campanulata had higher survival than H. anceps with uncaged water bugs. When predation trials were conducted after 5 weeks of exposure to predator cues, H. trivolvis and H. campanulata reached a size refuge from both predators and this shifted predation pressure to H. anceps.

Collectively, these results suggest that closely related prey species with different absolute constraints in their morphology had different defences that are either specialised or generalised to alternative environments.
Food resources and vegetation structure mediate climatic effects on species richness of birds
Authors: Ferger Stefan W. , Schleuning Matthias , Hemp Andreas , Howell Kim M. , Böhning‐Gaese Katrin
Published: February 2014

Aim

Climate is widely recognized as a major predictor of species richness patterns along large‐scale environmental gradients. Nevertheless, the mechanisms by which climate influences species richness are still a matter of debate. We disentangle whether climate influences species richness of birds directly via physiological limitations or indirectly via vegetation structure or the availability of food resources.

Location

Mount Kilimanjaro, Tanzania.

Methods

We recorded bird species richness along an elevational gradient from 870 to 4550 m a.s.l. We quantified local climatic conditions, vegetation structure and the availability of food resources, and applied path analysis to disentangle their direct and indirect effects on species richness of all birds, frugivores and insectivores.

Results

Overall, we recorded 2945 individuals from 114 bird species. Species richness of all birds was closely correlated with temperature, vegetation structure and invertebrate biomass and both direct and indirect (via vegetation structure and availability of food resources) climatic effects were important for the diversity of the whole, trophically heterogeneous bird community. The species richness of insectivorous birds was linked to vegetation structure and invertebrate biomass, while the richness of frugivores was strongly associated with fruit abundance. Climatic factors influenced bird species richness of both avian feeding guilds exclusively indirectly via vegetation structure and availability of food resources.

Main conclusions

We reveal the importance of trophic interactions for generating species richness patterns along large‐scale environmental gradients. Our results challenge the general assumption that temperature and water availability influence species richness mostly directly, and underscore the importance of vegetation structure and the availability of food resources as principal mediators of climatic effects on species richness patterns on macroecological scales.
Identifying factors associated with changes in physical functioning in an older population
Authors: Chen Chun‐Min , Chang Wen‐Chiung , Lan Tzuo‐Yun
Published: February 2014

Aim

The present study evaluated the association between changes in physical functioning and a variety of factors in an older population in Taiwan.

Methods

The data of 907 participants were derived from a three‐wave cohort study of aging, the Functioning and Aging Study in Taipei, with a study period from 2005 to 2009. Functional status was assessed using activities of daily living, instrumental activities of daily living and mobility tasks, and classified as being normal, with mild disability, moderate disability, and severe disability. All potential factors were allocated into five groups including demography, chronic diseases, geriatric conditions, lifestyle and physical assessments. Generalized estimating equations and generalized linear mixed‐effects models were used to identify factors responsible for changes in physical functioning across different waves of data.

Results

The proportion of elderly participants with normal function decreased with time throughout the study period. The results of Generalized estimating equations and mixed effects models showed nearly identical sets of factors. These included age, living arrangements, social support, self‐rated health, stroke, diabetes, Parkinson's disease, osteoporosis, depression, cognition, vision, history of fracture and falls, incontinence of urine and feces, physical activity, body mass index, and short physical performance battery.

Conclusions

Older persons with stroke, Parkinson's disease, diabetes, osteoporosis, geriatric conditions and poor short physical performance battery score should be considered as the target of prevention against functional decline. Those not living with spouses, with poor self‐rated health, with low social support, being underweight or obese and with a sedentary lifestyle might also require major attention. Geriatr Gerontol Int 2015; 15: 156–164.
The RNA‐binding protein Spo5 promotes meiosis II by regulating cyclin Cdc13 in fission yeast
Authors: Arata Mayumi , Sato Masamitsu , Yamashita Akira , Yamamoto Masayuki
Published: February 2014

Meiosis comprises two consecutive nuclear divisions, meiosis I and II. Despite this unique progression through the cell cycle, little is known about the mechanisms controlling the sequential divisions. In this study, we carried out a genetic screen to identify factors that regulate the initiation of meiosis II in the fission yeast Schizosaccharomyces pombe. We identified mutants deficient in meiosis II progression and repeatedly isolated mutants defective in spo5, which encodes an RNA‐binding protein. Using fluorescence microscopy to visualize YFP‐tagged protein, we found that spo5 mutant cells precociously lost Cdc13, the major B‐type cyclin in fission yeast, before meiosis II. Importantly, the defect in meiosis II was rescued by increasing CDK activity. In wild‐type cells, cdc13 transcripts increased during meiosis II, but this increase in cdc13 expression was weaker in spo5 mutants. Thus, Spo5 is a novel regulator of meiosis II that controls the level of cdc13 expression and promotes de novo synthesis of Cdc13. We previously reported that inhibition of Cdc13 degradation is necessary to initiate meiosis II; together with the previous information, the current findings indicate that the dual control of Cdc13 by de novo synthesis and suppression of proteolysis ensures the progression of meiosis II.
FTY720 stimulated ROS generation and the Sty1/Atf1 signaling pathway in the fission yeast Schizosaccharomyces pombe
Authors: Hagihara Kanako , Mizukura Aya , Kitai Yuki , Yao Mariko , Ishida Kouki , Kita Ayako , Kunoh Tatsuki , Masuko Takashi , Matzno Sumio , Chiba Kenji , Sugiura Reiko
Published: February 2014

Fingolimod hydrochloride (FTY720) is the first‐in‐class immune modulator known as sphingosine 1‐phosphate (S1P) receptor agonists. FTY720 has also been reported to exert a variety of physiological functions such as antitumor effect, angiogenesis inhibition, and Ca2+ mobilization. Here, we show that FTY720 treatment induced reactive oxygen species (ROS) accumulation, and investigated the effect of FTY720 on the stress‐activated MAP kinase Spc1/Sty1, a functional homologue of p38 MAPK, using a Renilla luciferase reporter construct fused to the CRE, which gives an accurate measure of the transcriptional activity of Atf1 and thus serves as a faithful readout of the Spc1/Sty1 MAPK signaling in response to oxidative stresses. FTY720 stimulated the CRE responses in a concentration‐dependent manner, which was markedly reduced by deletion of the components of the Spc1/Sty1 MAPK pathway. The blockade of ROS production by NAC (N‐acetyl‐l‐cysteine) significantly reversed the FTY720‐induced ROS accumulation, subsequent activation of the Spc1/Sty1 MAPK pathway, and inhibition of cell proliferation. Cells lacking the components of the Spc1/Sty1 MAPK exhibited higher sensitivity to FTY720 and higher ROS levels upon FTY720 treatment than in wild‐type cells. Thus, our results demonstrate the usefulness of fission yeast for elucidating the FTY720‐mediated signaling pathways involving ROS.