bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissociation between unconscious motor response facilitation and conflict in medial frontal areas
Authors: D’Ostilio Kevin , Garraux Gaëtan
Published: January 2012

Masked prime tasks have shown that sensory information that has not been consciously perceived can nevertheless modulate behavior. The neuronal correlates of behavioral manifestations of visuomotor priming remain debated, particularly with respect to the distribution and direction (i.e. increase or decrease) of activity changes in medial frontal areas. Here, we predicted that these discrepant results could be accounted for by two automatic and unconscious processes embedded in this task: response conflict and facilitation. We used event‐related functional magnetic resonance imaging (fMRI), as 24 healthy participants had to respond, as fast as possible, to a target arrow presented immediately after a subliminal masked prime arrow. There were three experimental conditions defined by the prime–target relationship: compatible, incompatible, and neutral. The classical visuomotor priming effect was reproduced, with relatively longer reaction times (RTs) in incompatible trials. Longer RTs in incompatible than in neutral trials were specifically associated with stronger blood oxygen level‐dependent (BOLD) activity in a conflict‐related network comprising the anterior cingulate cortex and right frontal associative areas. Motor response facilitation as shown by shorter RTs in compatible than in neutral trials was associated with reduced activation in a motor preparation network including the medial and lateral premotor cortices, as a result of the repetition suppression of the fMRI BOLD signal. The present results provide new insights into automatic and unconscious visuomotor priming processes, suggesting an involvement of either a cognitive or motor network, depending on the prime–target relationship.
Activity‐dependent actin dynamics are required for the maintenance of long‐term plasticity and for synaptic capture
Authors: Fonseca Rosalina
Published: January 2012

The maintenance of long‐lasting forms of plasticity, such as long‐term potentiation (LTP) is dependent on the capture of plasticity‐related proteins (PRPs) in an input‐specific manner – synaptic capture. Here, it is shown that LTP, induced at Schaffer collaterals–CA1 synapses in acute rat hippocampal slice preparation, is not sensitive to protein synthesis inhibition if N‐methyl‐d‐aspartate (NMDA) receptors are blocked, suggesting that synaptic activation is involved in the modulation of LTP maintenance. Similarly, it was found that synaptic activation also determines the sensitivity of LTP to manipulations of the actin cytoskeleton dynamics. Suspending synaptic activation or concomitant NMDA receptor inhibition is sufficient to rescue the impairment on LTP maintenance induced by actin polymerization blockade. Additionally, concomitant inhibition of protein degradation can partially prevent the LTP decay observed under actin polymerization blockade, suggesting that protein degradation is involved in the destabilization of LTP maintenance induced by actin polymerization blockade. Taken together, these observations suggest that LTP maintenance is determined by a balance of synthesis and degradation of PRPs modulated by synaptic activation and actin dynamics. Finally, it was uncovered that inhibition of actin depolymerization blocks synaptic capture, whereas inhibition of actin polymerization can extend the temporal window for synaptic capture. Additionally, inhibition of actin polymerization can rescue the impairment in synaptic capture induced by CaMKII inhibition, suggesting a link between CaMKII activation and modulation of actin dynamics during synaptic capture. These results show that an activity‐dependent regulation of actin dynamics plays a critical role in LTP maintenance and synaptic capture.
Regulator of calmodulin signaling knockout mice display anxiety‐like behavior and motivational deficits
Authors: Davis Maya M. , Olausson Peter , Greengard Paul , Taylor Jane R. , Nairn Angus C.
Published: January 2012

Regulator of calmodulin (CaM) signaling (RCS), when phosphorylated by protein kinase A (PKA) on Ser55, binds to CaM and inhibits CaM‐dependent signaling. RCS expression is high in the dorsal striatum, nucleus accumbens and amygdala, suggesting that the protein is involved in limbic‐striatal function. To test this hypothesis, we examined RCS knockout (KO) mice in behavioral models dependent on these brain areas. Mice were tested for food‐reinforced instrumental conditioning and responding under a progressive ratio (PR) schedule of reinforcement and in models of anxiety (elevated plus maze and open field). While RCS KO mice showed normal acquisition of a food‐motivated instrumental response, they exhibited a lower breakpoint value when tested on responding under a PR schedule of reinforcement. RCS KO mice also displayed decreased exploration in both the open arms of an elevated plus maze and in the center region of an open field, suggesting an enhanced anxiety response. Biochemical studies revealed a reduction in the levels of dopamine and cAMP‐regulated phosphoprotein (DARPP‐32) in the striatum of RCS KO mice. DARPP‐32 is important in reward‐mediated behavior, suggestive of a possible role for DARPP‐32 in mediating some of the effects of RCS. Together these results implicate a novel PKA‐regulated phosphoprotein, RCS, in the etiology of motivational deficits and anxiety.
Cellular anatomy, physiology and epileptiform activity in the CA3 region of Dcx knockout mice: a neuronal lamination defect and its consequences
Authors: Bazelot Michael , Simonnet Jean , Dinocourt Céline , Bruel‐Jungerman Elodie , Miles Richard , Fricker Desdemona , Francis Fiona
Published: January 2012

We report data on the neuronal form, synaptic connectivity, neuronal excitability and epileptiform population activities generated by the hippocampus of animals with an inactivated doublecortin gene. The protein product of this gene affects neuronal migration during development. Human doublecortin (DCX) mutations are associated with lissencephaly, subcortical band heterotopia, and syndromes of intellectual disability and epilepsy. In Dcx−/Y mice, CA3 hippocampal pyramidal cells are abnormally laminated. The lamination defect was quantified by measuring the extent of the double, dispersed or single pyramidal cell layer in the CA3 region of Dcx−/Y mice. We investigated how this abnormal lamination affected two groups of synapses that normally innervate defined regions of the CA3 pyramidal cell membrane. Numbers of parvalbumin (PV)‐containing interneurons, which contact peri‐somatic sites, were not reduced in Dcx−/Y animals. Pyramidal cells in double, dispersed or single layers received PV‐containing terminals. Excitatory mossy fibres which normally target proximal CA3 pyramidal cell apical dendrites apparently contact CA3 cells of both layers in Dcx−/Y animals but sometimes on basilar rather than apical dendrites. The dendritic form of pyramidal cells in Dcx−/Y animals was altered and pyramidal cells of both layers were more excitable than their counterparts in wild‐type animals. Unitary inhibitory field events occurred at higher frequency in Dcx−/Y animals. These differences may contribute to a susceptibility to epileptiform activity: a modest increase in excitability induced both interictal and ictal‐like discharges more effectively in tissue from Dcx−/Y mice than from wild‐type animals.
Long‐term quality of life in patients with permanent sigmoid colostomy
Authors: Sjödahl R. , Schulz C. , Myrelid P. , Andersson P.
Published: January 2012

Aim  The study aimed to assess quality of life (QoL) in patients with a sigmoid colostomy using a simple general and disease‐specific instrument. A subgroup not doing well was identified and examined further.

Method  The Short Health Scale (SHS) is a four‐item instrument exploring severity of symptoms, function in daily life, worry, and general well‐being, using visual analogue scales ranging from 0 to 100 where 100 is the worst possible situation. The SHS was delivered to 206 patients with a sigmoid colostomy. It was returned by 181 (87.9%) patients [88 men; median age 73 (33–91) years]. Follow‐up was 61 (10–484) months for 178 (86.4%) patients returning usable questionnaires. A subgroup of 16 patients scoring more than 50 in all four items of the SHS was further examined with StomaQOL where 100 is best possible.

Results  The median score for severity of symptoms was 18 (2–95), function in daily life 21 (0–95), worry 17 (3–98) and general well‐being 22 (0–99). A score of < 50 in the SHS was recorded in 84.9%, 82.1%, 79.9% and 70.5% respectively. In the group scoring more than 50 in all four items patients diagnosed with irritable bowel syndrome constituted 43.8% to compare with 5.6% in the entire study group (P < 0.001). Median score for StomaQOL was 37 (22–62) in this group.

Conclusion  Most patients with a permanent sigmoid colostomy have a good QoL consistent with previous findings. However, this is reduced in a subgroup of patients diagnosed with irritable bowel syndrome.
Barium proctography vs magnetic resonance proctography for pelvic floor disorders: a comparative study
Authors: Pilkington S. A. , Nugent K. P. , Brenner J. , Harris S. , Clarke A. , Lamparelli M. , Thomas C. , Tarver D.
Published: January 2012

Aim  Accurate and reliable imaging of pelvic floor dynamics is important for tailoring treatment in pelvic floor disorders; however, two imaging modalities are available. Barium proctography (BaP) is widely used, but involves a significant radiation dose. Magnetic resonance (MR) proctography allows visualization of all pelvic midline structures but patients are supine. This project investigates whether there are measurable differences between BaP and MR proctography. Patient preference for the tests was also investigated.

Methods  Consecutive patients referred for BaP were invited to participate (National Research Ethics Service approved). Participants underwent BaP in Poole and MR proctography in Dorchester. Proctograms were reported by a consultant radiologist with pelvic floor subspecialization.

Results  A total of 71 patients were recruited. Both tests were carried out on 42 patients. Complete rectal emptying was observed in 29% (12/42) on BaP and in 2% (1/42) on MR proctography. Anismus was reported in 29% (12/42) on BaP and 43% (18/42) on MR proctography. MR proctography missed 31% (11/35) of rectal intussusception detected on BaP. In 10 of these cases no rectal evacuation was achieved during MR proctography. The measure of agreement between grade of rectal intussusception was fair (κ = 0.260) although MR proctography tended to underestimate the grade. Rectoceles were extremely common but clinically relevant differences in size were evident. Patients reported that they found MR proctography less embarrassing but harder to empty their bowel.

Conclusions  The results demonstrate that MR proctography under‐reports pelvic floor abnormalities especially where there has been poor rectal evacuation.
Indicators of self‐rated health in the Canadian population with diabetes
Authors: Badawi G. , Gariépy G. , Pagé V. , Schmitz N.
Published: January 2012

Diabet. Med. 29, 1021–1028 (2012)

Aims  Self‐rated health is a widely used measure of general health assessing risk factors and poor health outcomes in health surveys and clinical settings. The characteristics of self‐rated health may be different in populations with specific chronic conditions, such as populations with diabetes. This study investigates the characteristics of self‐rated health in a Canadian community sample of people with diabetes.

Methods  Self‐rated health was obtained from 1837 adults with Type 2 diabetes participating in the Montreal Diabetes Health and Well‐Being Study. Global disability and depression were assessed using the World Health Organization Disability Assessment Schedule II and the Patient Health Questionnaire, respectively. Logistic regressions studied the association between self‐rated health and depression, disability, diabetes‐related characteristics, socio‐demographic factors, social support and lifestyle‐related behaviours in both men and women.

Results  Participants’ answers were dichotomized into excellent/very good/ good (78%) and fair/poor (22%) self‐rated health. Both depression (men: odds ratio 1.9, 95% CI 1.4–2.6; women: odds ratio 1.5, 95% CI 1.2–1.9) and disability (men: odds ratio 1.7, 95% CI 1.4–1.9; women: odds ratio 1.7, 95% CI 1.5–1.9) were associated with fair/poor self‐rated health. The associations remained unchanged even after controlling for diabetes characteristics. After controlling for confounding variables, chronic conditions were associated with fair/poor self‐rated health in both men and women. Obesity was associated with fair/poor self‐rated health in women only, while lifestyle behaviours such as being physically active and alcohol consumption were associated with good/very good/excellent self‐rated health in men.

Conclusions  In men and women, depression and disability are important factors that are associated with self‐rated health in a large sample of individuals with Type 2 diabetes.
Vitamin D and diabetes in Koreans: analyses based on the Fourth Korea National Health and Nutrition Examination Survey (KNHANES), 2008–2009
Authors: Rhee S. Y. , Hwang Y.‐C. , Chung H. Y. , Woo J.‐T.
Published: January 2012

Diabet. Med. 29, 1003–1010 (2012)

Aims  A causal relationship between vitamin D deficiency and the incidence of diabetes mellitus has been suggested, but little research has been conducted on the Korean population.

Methods  We analysed the glucose tolerance status and serum 25‐hydroxyvitamin D concentrations in 12 263 subjects > 19 years old who were registered for the Korea National Health and Nutrition Examination Survey, 2008–2009.

Results  Various demographic variables such as gender, age, season, resident area, physical activity, smoking, alcohol, marital status, education and occupation were associated with serum 25‐hydroxyvitamin D concentrations. After adjusting for these variables as confounders, 25‐hydroxyvitamin D concentrations in subjects with diabetes were significantly lower than those in subjects with normal glucose tolerance and those with impaired fasting glucose (P = 0.005). Compared with the ≥ 75 nmol/l subgroup of serum 25‐hydroxyvitamin D concentration, the odds ratios and 95% confidence intervals fordiabetes mellitus were 1.206 (95% CI 0.948–1.534) in the 50‐ to 74‐nmol/l subgroup, 1.339 (1.051–1.707) in the 25‐to49‐nmol/l subgroup and 1.759 (1.267–2.443) in the < 25‐nmol/l subgroup. Compared with the serum ≥ 75‐nmol/l 25‐hydroxyvitamin D subgroup, serum insulin and homeostasis model assessment 2%B, a marker of insulin secretory capacity, were significantly higher, and homeostasis model assessment 2%S, a marker of insulin sensitivity, was significantly lower in the < 25‐ and 25‐ to 49‐nmol/l serum 25‐hydroxyvitamin D subgroups than those in the other subgroups (P < 0.001).

Conclusions  The findings suggest that vitamin D deficiency, possibly involving altered insulin sensitivity, is associated with an increased risk for diabetes mellitus in the Korean population.
Andropausal symptoms in men with Type 2 diabetes
Authors: Fukui M. , Tanaka M. , Toda H. , Okada H. , Ohnishi M. , Mogami S. , Kitagawa Y. , Hasegawa G. , Yoshikawa T. , Nakamura N.
Published: January 2012

Diabet. Med. 29, 1036–1042 (2012)

Aims  Serum androgen concentration is reported to be low in patients with Type 2 diabetes. There have been no studies comparing andropausal symptoms such as sleep disturbance, depression, erectile dysfunction and lower urinary tract symptoms simultaneously between men with Type 2 diabetes and subjects without diabetes.

Methods  We compared andropausal symptom scores such as the Pittsburgh Sleep Quality Index, the Self‐Rating Depression Scale, the International Index of Erectile Function and the International Prostate Symptom Score in 296 men with Type 2 diabetes and in 267 subjects without diabetes. Furthermore, we evaluated relationships of andropausal symptom scores to various anthropometric factors and compared andropausal symptom scores according to diabetic complications in men with Type 2 diabetes.

Results  Andropausal symptom scores such as the Pittsburgh Sleep Quality Index, the Self‐Rating Depression Scale, the International Index of Erectile Function and the International Prostate Symptom Score were 4.2 ± 2.6 vs. 5.0 ± 3.3, P < 0.01 by unpaired Student’s t‐test, 34.8 ± 8.2 vs. 38.4 ± 9.3, P < 0.0001, 11.5 ± 6.4 vs. 9.9 ± 6.9, P < 0.01 and 7.3 ± 6.7 vs. 9.0 ± 7.1, P < 0.01 in subjects without diabetes and in patients with diabetes, respectively. The Pittsburgh Sleep Quality Index was higher in patients with neuropathy than without. The Self‐Rating Depression Scale was higher in patients with advanced retinopathy. The International Index of Erectile Function was lower in patients with advanced retinopathy and nephropathy. The International Index of Erectile Function was lower and the International Prostate Symptom Score was higher in patients with cardiovascular disease than without.

Conclusions  Our data demonstrated that men with Type 2 diabetes have higher prevalence of andropausal symptoms, especially those with diabetic complications.
Alcohol‐associated risks for young adults with Type 1 diabetes: a narrative review
Authors: Barnard K. , Sinclair J. M. A. , Lawton J. , Young A. J. , Holt R. I. G.
Published: January 2012

Diabet. Med. 29, 434–440 (2012)

Aim  To undertake a narrative review of the impact and pattern of alcohol consumption in young adults with Type 1 diabetes.

Methods  Data sources: MEDLINE, EMBASE, PsycINFO, The Cochrane Library, Web of Science, meeting abstracts of the European Association for the Study of Diabetes, the American Diabetes Association and Diabetes UK, Current Controlled Trials, ClinicalTrials.gov, UK Clinical Research Network, scrutiny of bibliographies of retrieved papers and contact with experts in the field. Inclusion criteria: relevant studies of any design of alcohol consumption and young adults with Type 1 diabetes (age 14–25 years) were included. The key outcomes were the quantity, pattern and impact of alcohol consumption, the effect on diabetes control and the effect of interventions to minimize the risks of alcohol for this population.

Results  Six articles and two conference abstracts met the inclusion criteria. There were six cross‐sectional studies, one qualitative study and one within‐subjects design study. Quality of studies was variable. Alcohol use amongst young adults with Type 1 diabetes was reported to be common and potentially harmful. There was a paucity of evidence on interventions to minimize the risks of alcohol in this target group.

Conclusions  Research is required to understand the social context of alcohol consumption in this population with a view to developing appropriate interventions to minimize the risks associated with its use.
The long‐term cost‐effectiveness of obesity prevention interventions: systematic literature review
Authors: Lehnert T. , Sonntag D. , Konnopka A. , Riedel‐Heller S. , König H.‐H.
Published: January 2012

Obesity prevention provides a major opportunity to improve population health. As health improvements usually require additional and scarce resources, novel health technologies (interventions) should be economically evaluated. In the prevention of obesity, health benefits may slowly accumulate over time and it can take many years before an intervention has reached full effectiveness. Decision‐analytic simulation models (DAMs), which combine evidence from diverse sources, can be utilized to evaluate the long‐term cost‐effectiveness of such interventions. This literature review summarizes long‐term economic findings (defined as ≥40 years) for 41 obesity prevention interventions, which had been evaluated in 18 cost‐utility analyses, using nine different DAMs. Interventions were grouped according to their method of delivery, setting and risk factors targeted into behavioural (n = 21), community (n = 12) and environmental interventions (n = 8). The majority of interventions offered good value for money, while seven were cost‐saving. Ten interventions were not cost‐effective (defined as >50,000 US dollar), however. Interventions that modified a target population's environment, i.e. fiscal and regulatory measures, reported the most favourable cost‐effectiveness. Economic findings were accompanied by a large uncertainty though, which complicates judgments about the comparative cost‐effectiveness of interventions.
Inside New Labour
Authors: Gamble Andrew
Published: January 2012

Since Labour lost office in 2010 the spate of memoirs about the New Labour era has been uneven in quality, but at their best they provide rival insider accounts by the actors themselves of the events in which they were involved. A variety of memoirs are considered, in particular those focusing on the three chief architects of New Labour—Blair, Brown and Mandelson—and the complicated political and personal relationships between them. The memoirs throw new light upon Gordon Brown's campaign to oust Tony Blair as prime minister, and the reasons why Blair did not seek to move Brown as chancellor. They provide reflections on the nature of political leadership and the different styles and policy priorities of Blair and Brown, why the New Labour years ended in such a major defeat, and why the New Labour project lasted as long as it did.
Embedding Quality in the Agro‐food System: The Dynamics and Implications of Place‐Making Strategies in the Olive Oil Sector of Alto Palancia, Spain
Authors: Moragues‐Faus Ana M. , Sonnino Roberta
Published: January 2012

Although agro‐food researchers have been calling for studies that uncover the tensions inherent in the process of construction of alternative food networks, the literature has mostly focused on individual initiatives, which make it difficult to address the implications of these processes in the wider territorial context where they operate. To overcome this fragmentation and begin to draw theoretical generalizations, we compare the different strategies used by three cooperatives of olive oil producers in the Alto Palancia County (Spain). Based on a set of in‐depth interviews with key food chain actors, the analysis uses the concept of embeddedness to examine the interplay between the social (trust and collective action) and the spatial (relationship with place) dimensions that characterise the olive oil networks. As we argue, this interplay plays a crucial role in shaping governance arrangements that are in turn responsible for constructing the quality attributes of the product. In addition to generating new insights into the nature of the relationship between food quality, power and place, the paper highlights the potential of both embeddedness and dis‐embeddedness processes in delivering rural development benefits, as well as the importance of supporting collective place‐making strategies that contribute to the creation of regional economic spaces.
Magnetic resonance imaging abnormalities in children with epilepsy
Authors: Durá‐Travé T. , Yoldi‐Petri M. E. , Esparza‐Estaún J. , Gallinas‐Victoriano F. , Aguilera‐Albesa S. , Sagastibelza‐Zabaleta A.
Published: January 2012

Background and purpose:  The aim of this study is to analyze the proportional distribution of epilepsy and epileptic syndromes in children and to describe the magnetic resonance imaging (MRI) abnormalities found in these patients.

Methods:  Data from 457 children aged 1 month to 15 years at the time of diagnosis of epilepsy were recorded. A routine MRI has been requested in all patients with epilepsy at diagnosis according to a standardized pediatric seizure protocol. Abnormalities on MRI were classified as either significant or non‐significant (standardized scoring system). International League Against Epilepsy criteria were used for diagnoses.

Results:  The prevalence of significant MRI abnormalities was 21.9% (in infants 42.3%, in childhood 18.2%, and in adolescents 15.9%). The most common abnormalities included white‐matter lesions (27.6%), volume loss (19.6%), gray‐matter lesions (19.6%), and ventricular enlargement (12%).

Conclusions:  The use of MRI and a reliable standardized scoring system at diagnosis of epilepsy in children identified a high rate of significant abnormalities findings. This may have important implications for practice guidelines in this population.
Stress among Mothers of Children with Intellectual Disabilities in Urban India: Role of Gender and Maternal Coping
Authors: John Aesha
Published: January 2012

Background  The study assessed stress among mothers of young children with intellectual disabilities in urban India and examined the extent to which child functioning and maternal coping predict maternal stress. Through qualitative analyses, the study identified negative and positive dimensions of Indian mothers’ caregiving experiences.

Materials and Methods  Mothers completed Parenting Stress Index‐Short Form, and children’s teachers completed Vineland‐II teacher rating form. Maternal responses to a semi‐structured interview were rated to assess maternal coping and content analysed to derive qualitative themes.

Results  Three‐fourths of the sample obtained a clinically significant stress score, and maternal coping emerged as a robust predictor of stress for mothers of boys with intellectual disabilities. Qualitative analyses indicated positive and negative maternal experiences related to self, child, family and community.

Conclusions  The high level of stress has important clinical implications. Similarly, the significant role of maternal coping, moderating role of child gender and the multidimensional caregiving experiences have implications for future research and family interventions in India.
Non‐Audit Services and Knowledge Spillovers: Evidence from New Zealand
Authors: Knechel W. Robert , Sharma Divesh S. , Sharma Vineeta D.
Published: January 2012

Abstract:  New Zealand provides a natural laboratory to test whether knowledge spillovers arise from auditor‐provided non‐audit services. Unlike prior research, we do not assume constant audit quality but first test whether audit quality varies with auditor‐provided non‐audit services and audit efficiency. Results show that higher non‐audit fees paid to the auditor in conjunction with shorter audit lag does not reduce the quality of the audit. Results reveal a negative association between non‐audit fees and audit lag, thus suggesting the presence of knowledge spillovers. However, the knowledge spillover effect is limited to the city office providing both the audit and non‐audit services.
Why Do Firms Go Public? The Role of the Product Market
Authors: Jong Abe de , Huijgen Carel A. , Marra Teye A. , Roosenboom Peter
Published: January 2012

Abstract:  This paper investigates the effect of product market characteristics on the decision to go public. When firms decide to go public or remain private, they trade off product market related costs and benefits. Costs arise from the loss of confidential information to competitors, e.g., in the IPO prospectus and subsequent mandated public disclosures, while benefits emerge from raising capital allowing the firm to strengthen its position in the product market. Our results show that UK firms are more likely to go public when they operate in a more profitable industry and in an industry with lower barriers to entry. These firms are more likely to go public in order to improve their position in the product market and to deter new entrants into the industry. However, firms from more competitive industries and firms with smaller market share are less likely to go public. For these firms the loss of confidential information to rivals outweighs the benefits of going public.
Hybrid approaches for the two‐scenario max–min knapsack problem
Authors: Hanafi Saïd , Mansi Raïd , Wilbaut Christophe , Fréville Arnaud
Published: January 2012

In this paper, we deal with the two‐scenario max–min knapsack (MNK) problem. First, we consider several formulations of MNK as a mixed integer programming problem. Then, we propose a hybrid method as an alternative to solve the MNK exactly. The approach combines relaxation technique and the temporary setting of variables to improve iteratively two sequences of upper and lower bounds. More precisely, pseudo‐cuts are added to the problem to strengthen the bounds and reduce the gap between the best lower bound and the best upper bound. The algorithm stops when the proof of the optimality of the best solution is found. We also use a reduction technique to set some variables definitively at their optimal values. Numerical experiments demonstrate the robustness of the approach. In particular, our algorithm is efficient to solve large and correlated instances of MNK.
Critical distance: doing development education through international volunteering
Authors: Diprose Kristina
Published: January 2012

Development education is an under‐theorised aspect of international volunteering, yet it is implicit in the mission statements of many sending organisations when they promise a transformative experience. What does international volunteering offer, and can it make returned volunteers ‘think global’? This paper suggests a tentative definition of development education, outlining key pedagogical concepts that can be applied to analysis of international volunteering projects. Case study research about Platform2, a pilot ‘Global Learning’ scheme funded by the UK government, explores components and challenges of delivery. Discussion highlights the importance of formal structuring of educational opportunities, how international volunteering can both perpetuate and disrupt stereotypes of the global South, the role of proximity in expanding volunteers' capacity to think critically about development, as well as the drawbacks of jumping scale to learn about citizenship.
The Effectiveness of Implementing an Electronic Health Record on Diabetes Care and Outcomes
Authors: Herrin Jeph , da Graca Briget , Nicewander David , Fullerton Cliff , Aponte Phil , Stanek Greg , Cowling Terianne , Collinsworth Ashley , Fleming Neil S. , Ballard David J.
Published: January 2012

Objective

To assess the impact of electronic health record (EHR) implementation on primary care diabetes care.

Data Sources

Charts were abstracted semi‐annually for 14,051 diabetes patients seen in 34 primary care practices in a large, fee‐for‐service network from January 1, 2005 to December 31, 2010. The study sample was limited to patients aged 40 years or older.

Study Design

A naturalistic experiment in which GE Centricity Physician Office–EMR 2005 was rolled out over a staggered 3‐year schedule.

Data Collection

Chart audits were conducted using the AMA/Physician Consortium Adult Diabetes Measure set. The primary outcome was the HealthPartners’ “optimal care” measure: HbA1c ≤ 8 percent; LDL cholesterol < 100 mg/dl; blood pressure < 130/80 mmHg; not smoking; and documented aspirin use in patients ≥40 years of age.

Principal Findings

After adjusting for patient age, sex, and insulin use, patients exposed to the EHR were significantly more likely to receive “optimal care” when compared with unexposed patients (p < .001), with an estimated difference of 9.20 percent (95% CI: 6.08, 12.33) in the final year between exposed patients and patients never exposed. Components of the optimal care bundle showing positive improvement after adjustment were systolic blood pressure <80 mmHg, diastolic blood pressure <130 mmHg, aspirin prescription, and smoking cessation. Among patients exposed to EHR, all process and outcome measures except HbA1c and lipid control showed significant improvement.

Conclusion

Implementation of a commercially available EHR in primary care practice may improve diabetes care and clinical outcomes.
Connecting here and there: A model of long‐distance relationship maintenance
Authors: MEROLLA ANDY J.
Published: January 2012

This study examines a model of long‐distance relationship maintenance. The model captures the relational cognition and communication partners enact before, during, and after periods of separation to sustain relational quality. Phase 1 of this study, through inductive analysis, identified 178 forms of maintenance. Phases 2 and 3 employed factor analysis and produced support for a 10‐factor model. Subsequent tests assessed how these factors predicted intimacy, satisfaction, and stress for long‐distance dating partners. Although several of the factors were significant predictors, the effects were not uniform. The strength and directionality of effects depended on the interactional style of partners' maintenance (i.e., intrapersonal, dyadic, or network) and the time of its enactment (i.e., before, during, or after periods of separation).
The natural polyamines spermidine and spermine prevent bone loss through preferential disruption of osteoclastic activation in ovariectomized mice
Authors: Yamamoto Tomomi , Hinoi Eiichi , Fujita Hiroyuki , Iezaki Takashi , Takahata Yoshifumi , Takamori Misa , Yoneda Yukio
Published: January 2012

BACKGROUND AND PURPOSE

Although naturally occurring polyamines are indispensable for a variety of cellular events in eukaryotic cells, little attention has been paid to their physiological and pathological significance in bone remodelling to date. In this study, we evaluated the pharmacological properties of several natural polyamines on the functionality and integrity of bone in both in vitro and in vivo experiments.

EXPERIMENTAL APPROACH

Mice were subjected to ovariectomy (OVX) and subsequent oral supplementation with either spermidine or spermine for determination of the bone volume together with different parameters regarding bone formation and resorption by histomorphometric analyses in vivo. Pre‐osteoclasts were cultured with receptor activator of NF‐κB ligand (RANKL), with or without spermidine and spermine to determine cellular maturation by tartrate‐resistant acid phosphatase (TRAP) staining and cellular viability by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide reduction in vitro.

KEY RESULTS

Spermidine or spermine, given in drinking water for 28 days, significantly prevented the increased osteoclast surface/bone surface ratio and the reduced bone volume following OVX in mice. Either spermidine or spermine significantly inhibited the increased number of multinucleated TRAP‐positive cells in osteoclasts cultured with RANKL in a concentration‐dependent manner without affecting cell survival.

CONCLUSIONS AND IMPLICATIONS

The natural polyamines spermidine and spermine prevented OVX‐induced bone loss through the disruption of differentiation and maturation of osteoclasts, rather than affecting osteoblasts. The supplementation with these natural polyamines could be beneficial for the prophylaxis as well as therapy of metabolic bone diseases such as post‐menopausal osteoporosis.
Revisiting cardiovascular regeneration with bone marrow‐derived angiogenic and vasculogenic cells
Authors: Lee Sangho , Yoon Young‐sup
Published: January 2012

Cell‐based therapy has emerged as a promising therapy for cardiovascular disease. Particularly, bone marrow (BM)‐derived cells have been most extensively investigated and have shown encouraging results in preclinical studies. Clinical trials, however, have demonstrated split results in post‐myocardial infarction cardiac repair. Mechanistically, transdifferentiation of BM‐derived cells into cardiovascular tissue demonstrated by earlier studies is now known to play a minor role in functional recovery, and humoral and paracrine effects turned out to be main mechanisms responsible for tissue regeneration and functional recovery. With this advancement in the mechanistic insight of BM‐derived cells, new efforts have been made to identify cell population, which can be readily isolated and obtained in sufficient quantity without mobilization and have higher therapeutic potential. Recently, haematopoietic CD31+ cells, which are more prevalent in bone marrow and peripheral blood, have been revealed to have angiogenic and vasculogenic activities and strong potential for therapeutic neovascularization in ischaemic tissues. This article will cover the recent advances in BM‐derived cell‐based therapy and implication of CD31+ cells.

LINKED ARTICLES This article is part of a themed section on Regenerative Medicine and Pharmacology: A Look to the Future. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue‐2
Resveratrol dimers are novel sphingosine kinase 1 inhibitors and affect sphingosine kinase 1 expression and cancer cell growth and survival
Authors: Lim Keng Gat , Gray Alexander I , Pyne Susan , Pyne Nigel J
Published: January 2012

BACKGROUND AND PURPOSE

Sphingosine kinase 1 catalyses formation of the bioactive lipid, sphingosine 1‐phosphate, which protects cancer cells from apoptosis. Therefore, sphingosine kinase 1 is a novel target for intervention with anti‐cancer agents. We have assessed the effect of the anti‐cancer agent, resveratrol and its dimers (ampelopsin A and balanocarpol) on sphingosine kinase 1 activity and on survival of MCF‐7 breast cancer cells.

EXPERIMENTAL APPROACH

Ampelopsin A and balanocarpol were purified from Hopea dryobalanoides and their effect on sphingosine kinase 1 activity and expression, [3H] thymidine incorporation, ERK‐1/2 phosphorylation and PARP activity assessed in MCF‐7 cells.

KEY RESULTS

Resveratrol, ampelopsin A and balanocarpol were novel inhibitors of sphingosine kinase 1 activity. Balanocarpol was a mixed inhibitor (with sphingosine) of sphingosine kinase 1 with a Kic= 90 ± 10 µM and a Kiu of ∼500 µM. Balanocarpol and ampelopsin A also induced down‐regulation of sphingosine kinase 1 expression and reduced DNA synthesis, while balanocarpol stimulated PARP cleavage in MCF‐7 breast cancer cells. Resveratrol was a competitive inhibitor (with sphingosine) of sphingosine kinase 1 with a Kic= 160 ± 40 µM, reduced sphingosine kinase 1 expression and induced PARP cleavage in MCF‐7 cells.

CONCLUSIONS AND IMPLICATIONS

Each molecule of balanocarpol may bind at least two sphingosine kinase 1 catalytic molecules to reduce the activity of each simultaneously. These findings suggest that resveratrol, ampelopsin A and balanocarpol could perturb sphingosine kinase 1‐mediated signalling and this might explain their activity against MCF‐7 breast cancer cells.

LINKED ARTICLE

This article is commented on by Hergst and Yun, pp. 1603–1604 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2012.01898.x
FTY720 (fingolimod) increases vascular tone and blood pressure in spontaneously hypertensive rats via inhibition of sphingosine kinase
Authors: Spijkers Léon JA , Alewijnse Astrid E , Peters Stephan LM
Published: January 2012

BACKGROUND AND PURPOSE FTY720 (Fingolimod) is a recently approved orally administered drug for the treatment of multiple sclerosis. Phase II and III clinical trials have demonstrated that this drug modestly increases BP. We previously showed that inhibition of sphingosine kinase increases vascular tone and BP in hypertensive, but not normotensive rats. Since FTY720 is reported to have inhibitory effects on sphingosine kinase, we investigated whether FTY720 increases vascular tone and BP only in hypertensive rats via this mechanism.

EXPERIMENTAL APPROACH The contractile and BP modulating effects of FTY720 were studied in vivo and ex vivo (wire myography) in age‐matched normotensive Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs).

KEY RESULTS Oral administration of FTY720 induced an increase in mean arterial pressure in SHR, whereas a decrease in BP was observed in WKY rats, as measured 24 h after administration. Similar to the sphingosine kinase inhibitor dimethylsphingosine (DMS), FTY720 induced large contractions in isolated carotid arteries from SHR, but not in those from WKY. In contrast, the phosphorylated form of FTY720 did not induce contractions in isolated carotid arteries from SHR. FTY720‐induced contractions were inhibited by endothelium denudation, COX and thromboxane synthase inhibitors, and by thromboxane receptor antagonism, indicating that (like DMS‐induced contractions) they were endothelium‐dependent and mediated by thromboxane A2.

CONCLUSIONS AND IMPLICATIONS These data demonstrate that FTY720 increases vascular tone and BP only in hypertensive rats, most likely as a result of its inhibitory effect on sphingosine kinase.
Key role of PI3Kγ in monocyte chemotactic protein‐1‐mediated amplification of PDGF‐induced aortic smooth muscle cell migration
Authors: Fougerat A , Smirnova NF , Gayral S , Malet N , Hirsch E , Wymann MP , Perret B , Martinez LO , Douillon M , Laffargue M
Published: January 2012

BACKGROUND AND PURPOSE

Vascular smooth muscle cell (SMC) migration within the arterial wall is a crucial event in atherogenesis and restenosis. Monocyte chemotactic protein‐1/CC‐chemokine receptor 2 (MCP‐1/CCR2) signalling is involved in SMC migration processes but the molecular mechanisms have not been well characterized. We investigated the role of PI3Kγ in SMC migration induced by MCP‐1.

EXPERIMENTAL APPROACHES

A pharmacological PI3Kγ inhibitor, adenovirus encoding inactive forms of PI3Kγ and genetic deletion of PI3Kγ were used to investigate PI3Kγ functions in the MCP‐1 and platelet‐derived growth factor (PDGF) signalling pathway and migration process in primary aortic SMC.

KEY RESULTS

The γ isoform of PI3K was shown to be the major signalling molecule mediating PKB phosphorylation in MCP‐1‐stimulated SMC. Using a PI3Kγ inhibitor and an adenovirus encoding a dominant negative form of PI3Kγ, we demonstrated that PI3Kγ is essential for SMC migration triggered by MCP‐1. PDGF receptor stimulation induced MCP‐1 mRNA and protein accumulation in SMCs. Blockade of the MCP‐1/CCR2 pathway or pharmacological inhibition of PI3Kγ reduced PDGF‐stimulated aortic SMC migration by 50%. Thus PDGF promotes an autocrine loop involving MCP‐1/CCR2 signalling which is required for PDGF‐mediated SMC migration. Furthermore, SMCs isolated from PI3Kγ‐deficient mice (PI3Kγ−/−), or mice expressing an inactive PI3Kγ (PI3KγKD/KD), migrated less than control cells in response to MCP‐1 and PDGF.

CONCLUSIONS AND IMPLICATIONS

PI3Kγ is essential for MCP‐1‐stimulated aortic SMC migration and amplifies cell migration induced by PDGF by an autocrine/paracrine loop involving MCP‐1 secretion and CCR2 activation. PI3Kγ is a promising target for the treatment of aortic fibroproliferative pathologies.
The Power of Voice: Managerial Affective States and Future Firm Performance
Authors: MAYEW WILLIAM J. , VENKATACHALAM MOHAN
Published: January 2012

We measure managerial affective states during earnings conference calls by analyzing conference call audio files using vocal emotion analysis software. We hypothesize and find that, when managers are scrutinized by analysts during conference calls, positive and negative affects displayed by managers are informative about the firm's financial future. Analysts do not incorporate this information when forecasting near‐term earnings. When making stock recommendation changes, however, analysts incorporate positive but not negative affect. This study presents new evidence that managerial vocal cues contain useful information about a firm's fundamentals, incremental to both quantitative earnings information and qualitative “soft” information conveyed by linguistic content.
The Credit Ratings Game
Authors: BOLTON PATRICK , FREIXAS XAVIER , SHAPIRO JOEL
Published: January 2012

The collapse of AAA‐rated structured finance products in 2007 to 2008 has brought renewed attention to conflicts of interest in credit rating agencies (CRAs). We model competition among CRAs with three sources of conflicts: (1) CRAs conflict of understating risk to attract business, (2) issuers' ability to purchase only the most favorable ratings, and (3) the trusting nature of some investor clienteles. These conflicts create two distortions. First, competition can reduce efficiency, as it facilitates ratings shopping. Second, ratings are more likely to be inflated during booms and when investors are more trusting. We also discuss efficiency‐enhancing regulatory interventions.
Why Does the Law Matter? Investor Protection and Its Effects on Investment, Finance, and Growth
Authors: MCLEAN R. DAVID , ZHANG TIANYU , ZHAO MENGXIN
Published: January 2012

Investor protection is associated with greater investment sensitivity to q and lower investment sensitivity to cash flow. Finance plays a role in causing these effects; in countries with strong investor protection, external finance increases more strongly with q, and declines more strongly with cash flow. We further find that q and cash flow sensitivities are associated with ex post investment efficiency; investment predicts growth and profits more strongly in countries with greater q sensitivities and lower cash flow sensitivities. The paper's findings are broadly consistent with investor protection promoting accurate share prices, reducing financial constraints, and encouraging efficient investment.
Synthesis and Characterization of Iron Oxide Embedded Hydroxyapatite Bioceramics
Authors: Ansar Ereath Beeran , Ajeesh Manmadhan , Yokogawa Yoshiyuki , Wunderlich Wilfried , Varma Harikrishna
Published: January 2012

A homogeneous dispersion of nano iron oxide (IO) crystallites inside the hydroxyapatite (HA) particles was achieved by a co‐precipitation method. This highly stable colloidal dispersion of magnetic nano composite (HAIO) was made without the use of any surfactants. The in situ generated dispersion of the composite powders showed submicron HA particles with ~5 nm iron oxide inside. The phase analysis results showed the presence of hydroxyapatite (HA) and iron oxide with no tertiary phase. The enhancement of relative peak intensities with increased percentage of iron oxide phase in X‐ray diffraction analysis suggests the formation of iron oxide together with HA without affecting the phase purity of the latter, which is important when the biological behavior of HA is concerned. This also confirms the quantitative nature of the precipitated nanocomposites. The High Resolution Transmission Electron Microscope (HRTEM) of the composite shows elongated crystal flakes or platelike surfaces of HA crystallites having particle sizes in the range 70–100 nm. HRTEM with XRD analysis matches HAIO only with iron oxide particles of Magnetite (Fe3O4) and HA phases. The FTIR data confirm that the introduction of iron oxide did not produce any considerable change in the chemical structure of HA.
A Study of the Microstructure and Vickers Indentation Fracture Toughness of Silicon Carbide Coatings on TRISO Fuel Particles
Authors: Zhang Huixing , López‐Honorato Eddie , Javed Athar , Shapiro Ian , Xiao Ping
Published: January 2012

In this study, the microstructure and Vickers indentation fracture toughness (VIF fracture toughness) of three different types of silicon carbide (SiC) coatings (stoichiometric SiC, SiC with excess silicon and SiC with excess carbon) were investigated. SiC coatings were produced on tri‐isotropic fuel particles by fluidized bed chemical vapor deposition (FBCVD). The microstructure was investigated using a scanning electron microscope (SEM) and X‐ray diffraction, while a transmission electron microscope was used for the analysis of defects and micro‐cracks. The VIF fracture toughness was measured using Vickers indentation. The fracture beneath the indenter consists of Palmqvist cracks as observed using SEM. Based on this crack mode, VIF fracture toughness values of 3.51, 4.03, and 4.93 MPa·m1/2 for stoichiometric, extra‐C and extra‐Si SiC coatings were obtained, respectively. It was found that stress‐induced micro‐cracks seem to be a mechanism for the fracture behavior, which gave SiC coatings with high VIF fracture toughness. The difference in the VIF fracture toughness of FBCVD SiC coatings is discussed in terms of defects and grain morphology.