bluuebunny/crossref_metadata_2025 huggingface dataset:
Pigment‐independent cAMP‐mediated epidermal thickening protects against cutaneous UV injury by keratinocyte proliferation
Authors: Scott Timothy L. , Christian Perry A. , Kesler Melissa V. , Donohue Kevin M. , Shelton Brent , Wakamatsu Kazumasa , Ito Shosuke , D'Orazio John
Published: August 2012

The epidermis increases pigmentation and epidermal thickness in response to ultraviolet exposure to protect against UV‐associated carcinogenesis; however, the contribution of epidermal thickness has been debated. In a humanized skin mouse model that maintains interfollicular epidermal melanocytes, we found that forskolin, a small molecule that directly activates adenylyl cyclase and promotes cAMP generation, up‐regulated epidermal eumelanin accumulation in fair‐skinned melanocortin‐1‐receptor (Mc1r)‐defective animals. Forskolin‐induced pigmentation was associated with a reproducible expansion of epidermal thickness irrespective of melanization or the presence of epidermal melanocytes. Rather, forskolin‐enhanced epidermal thickening was mediated through increased keratinocyte proliferation, indirectly through secreted factor(s) from cutaneous fibroblasts. We identified keratinocyte growth factor (Kgf) as a forskolin‐induced fibroblast‐derived cytokine that promoted keratinocyte proliferation, as forskolin induced Kgf expression both in the skin and in primary fibroblasts. Lastly, we found that even in the absence of pigmentation, forskolin‐induced epidermal thickening significantly diminished the amount of UV‐A and UV‐B that passed through whole skin and reduced the amount of UV‐B‐associated epidermal sunburn cells. These findings suggest the possibility of pharmacologic‐induced epidermal thickening as a novel UV‐protective therapeutic intervention, particularly for individuals with defects in pigmentation and adaptive melanization.
FOXP3, CBLBandITCHgene expression and cytotoxic T lymphocyte antigen 4 expression on CD4+CD25high T cells in multiple sclerosis
Authors: Sellebjerg F , Krakauer M , Khademi M , Olsson T , Sørensen P S
Published: August 2012

Expression of the forkhead box protein 3 (FoxP3) transcription factor is regulated by the E3 ubiquitin ligases Itch and Cbl-b and induces regulatory activity CD4+CD25high T cells. Treatment with interferon (IFN)-β enhances regulatory T cell activity in multiple sclerosis (MS). We studied the phenotype of CD4+CD25high T cells in MS by flow cytometry and its relationship with expression of the FOXP3, ITCH and CBLB genes. We found that untreated MS patients had lower cell surface expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) on CD4+CD25high T cells and higher intracellular CTLA-4 expression than healthy controls. Cell surface expression of CTLA-4 on CD4+CD25high T cells correlated with expression of FOXP3 mRNA in untreated patients and increased significantly with time from most recent injection in patients treated with IFN-β. FOXP3 mRNA expression correlated with CBLB and ITCH and T helper type 2 cytokine mRNA expression in MS patients. These data link expression of FOXP3, CBLB and ITCH mRNA and CTLA-4 expression on the surface of CD4+CD25high T cell in MS. We hypothesize that this may reflect alterations in the inhibitory effect of CTLA-4 or in regulatory T cell function.
Effects of temperature and food quality on age and size at maturity in ectotherms: an experimental test withAtlantic salmon
Authors: Jonsson Bror , Jonsson Nina , Finstad Anders G.
Published: August 2012

The reaction norm between growth rate, age and size at maturity in ectotherms is widely debated in ecological literature. It has been proposed that the effect depends on whether growth is affected by food quality or temperature (called theBerrigan–Charnov puzzle). The present experiment tested this forAtlantic salmon (Salmo salar).

We enhanced growth rates by increasing temperature and ratio of lipids to proteins in the food for groups ofAtlantic salmon. Both treatments gave higher percentages of early mature and therefore smaller adults in contrast to the proposedBerrigan–Charnov puzzle. There was a difference between sexes in that males could attain maturity 1 year younger than females when reared under similar environmental conditions.

Males that matured during the first year in sea water were smaller than similar aged immature males. The probability of thatAtlantic salmon attained maturity for the first time during their second year in sea increased with growth rate during the preceding winter and if fed a high‐lipid diet. Increased summer temperature exhibited no additional effect.

Similar aged fish reared at elevated temperature and fed high‐lipid diet attained maturity at a larger body mass and exhibited higher mass‐length‐ratios than those reared at natural temperature and fed a low‐lipid diet, indicating that structural growth has priority over lipid deposits.

Increased growth rate before the onset of maturation, whether this is owing to enhanced lipid content in food or increased water temperature, decreased age and therefore size at maturity. Enhanced lipid relative to protein content in food, but not temperature, had an additive positive effect on early maturation probability, likely due to increased amounts of reserve energy. These results may be general for ectotherm organisms.
Testing for heritable thrombophilia in children at Starship Children's Hospital: An audit of requests between 2004 and 2009
Authors: Bradbeer Peter , Teague Lochie , Cole Nyree
Published: August 2012

Aims:  The aim of this study was to review patterns of requests for heritable thrombophilia and to audit these findings against an international standard.

Methods:  Review of requests for antithrombin, protein C, protein S, activated protein C resistance, Factor V Leiden and prothrombin G20210A mutation analysis in children <16 years between 1/1/2004 and 31/12/2009. Data for patient characteristics, test results, origin of request, requesting department and indication were obtained. The 2010 British Committee for Standards in Haematology (BCSH) clinical guidelines for testing for heritable thrombophilia was used as the standard for the audit.

Results:  On 269 patients, 379 requests were made. Thirty‐four per cent of tests were abnormal but only 36% of abnormal tests were repeated. Seven per cent of patients were confirmed with a heritable thrombophilia. Thirty‐four tests were performed on patients on anticoagulation. The median age was 6.903 years. Fifty‐three per cent of requests came from a ward, 28% from outpatients, 14% from an intensive care department and 5% from the emergency department. Departments most frequently requesting tests were neurology (20%), paediatric intensive care (15%) and cardiology (12%). Indications for testing were arterial thrombosis (5%), cerebral vein thrombosis (4%), deep vein thrombosis (12%), stroke (23%), asymptomatic relative (6%), intra‐abdominal vein thrombosis (8%), start oestrogen containing medication (2%), purpura fulminans (0.2%), heparin resistance (8%) and other (35%).

Discussion:  The large majority of requests did not satisfy the BCSH criteria. Requesting behaviours are haphazard. Better appreciation of the difficulties of interpreting results in children of different ages and in different clinical settings amongst paediatricians is required.
Appendicectomy at a children's hospital: what has changed over a decade?
Authors: Wilson Brooke E. , Cheney Lukas , Patel Bhavesh , Holland Andrew J. A.
Published: August 2012

Background

Appendicectomy remains the most common abdominal emergency procedure performed by surgeons. We reviewed appendicectomies for the calendar years 1999 and 2009 to assess any changes in the referral, presentation and management at a tertiary paediatric institution.

Methods

We performed a retrospective chart review on all appendicectomies at our institution in 1999 and 2009. Patients were identified using the International Classification of Diseases 9 and 10 Australian Modification codes. A P‐value of <0.05 was considered significant.

Results

The number of emergency appendicectomies more than doubled from 126 to 296 between 1999 and 2009. The rate of laparoscopic appendicectomy increased from <1% in 1999 to 70.3% in 2009. Overall, the mean patient age increased from 8.6 years in 1999 to 9.68 in 2009 (P = 0.005). There was an increase in the proportion (19.8% versus 39.5%, P < 0.001) and age (5.3 versus 8.8, P < 0.0001) of patients referred via inter‐hospital transfers between the two time periods. In 2009, laparoscopic surgery required on average 13.6 min longer than open surgery. This increase in surgical duration was offset by a decrease in the length of stay (5.0 ± 0.7 versus 3.5 ± 0.3, P < 0.0001).

Conclusions

Our institution has experienced an extraordinary rise in the number of appendicectomies performed, which cannot be explained by an increase in the local paediatric population alone. There appears to have been dramatic shift in the surgical care of children to our tertiary paediatric centre. The majority of appendicectomies in 2009 were laparoscopic, with a reduced length of stay despite longer operative times.
A Civil Rather Than Criminal Offence? Forced Marriage, Harm and the Politics of Multiculturalism in the UK
Authors: Quek Kaye
Published: August 2012

Research Highlights and Abstract

The British preference for civil remedies, rather than criminal measures, regarding forced marriage is examined and an explanation for this approach, put forward. The reluctance in the UK to criminalise forced marriage is traced, in part, to the influence that multicultural ideals have had on current British approaches to the practice. The state's tendency to conceptualise the harms of forced marriage principally in terms of a violation of choice (rather than as a matter of long-term violence against women), is also identified as significant to the British preference for civil remedies, over criminal legislation. A critical feminist analysis of UK government papers, policy documents, and Hansard debates, relating to the 2005 public enquiry on the criminalisation of forced marriage and to the Forced Marriage (Civil Protection) Act 2007, is undertaken. British discussions on the proposal to criminalise forced marriage are noted as lacking consideration of arguments that identify criminal legislation as a critical means of combating violence against women. The question is raised as to whether, by adopting such an approach, the state may be giving rise to a two-tier system of rights, in which minority group women are afforded a lesser protection of their human rights, as a result of their racial or cultural background.

This article examines the preference for civil, rather than criminal, measures that has emerged as the favoured policy approach for dealing with forced marriage in Britain. In particular, the article considers why, following much public and parliamentary debate, the option to criminalise forced marriage was rejected by UK lawmakers. It suggests that one explanation for this approach is the influence that multiculturalism, as a set of political ideals, has had on British policy on forced marriage in recent years. The article also identifies as significant the limited conception of the harms of forced marriage apparent in much UK government discourse, which fails to identify the practice principally as a form of violence against women, and therefore as a custom that should be subject to criminal legislation. It draws on a critical feminist analysis of UK government papers and policy initiatives dealing with forced marriage during the period of 1999–2007, in order to make this case. It concludes by raising the question of whether, in adopting a civil remedy approach, the state may be affording some women less protection of their human rights than others.
Naïve Theories of Social Groups
Authors: Rhodes Marjorie
Published: August 2012

Four studies examined children’s (ages 3–10, TotalN = 235) naïve theories of social groups, in particular, their expectations about how group memberships constrain social interactions. After introduction to novel groups of people, preschoolers (ages 3–5) reliably expected agents from one group to harm members of the other group (rather than members of their own) but expected agents to help members of both groups equally often. Preschoolers expected between‐group harm across multiple ways of defining social groups. Older children (ages 6–10) reliably expected agents to harm members of the other group and to help members of their own. Implications for the development of social cognition are discussed.
Geographic Variations in Cost of Living: Associations With Family and Child Well‐Being
Authors: Chien Nina C. , Mistry Rashmita S.
Published: August 2012

The effects of geographic variations in cost of living and family income on children’s academic achievement and social competence in first grade (mean age = 86.9 months) were examined, mediated through material hardship, parental investments, family stress, and school resources. Using data from the Early Childhood Longitudinal Study–Kindergarten Cohort (N = 17,565), higher cost of living was associated with lower academic achievement. For poor children only, higher cost of living was also detrimental to parental investments and school resources. Parental investments and school resources were more strongly associated with achievement for lower income than higher income children. Results suggest that cost of living intersects with income in meaningful ways for family and child well‐being and should be accounted for in the poverty measure.
Explaining Policy Ties in Presidential Congresses: A Network Analysis of Bill Initiation Data
Authors: Alemán Eduardo , Calvo Ernesto
Published: August 2012

Policy networks formed by co-authoring and co-sponsoring bills reflect one of the most important types of connection legislators develop while in office. We expect that in presidential countries, the probability of a tie between two legislators should be influenced by partisan membership, territorial linkages and the policy areas in which they develop expertise. Given the complex nature of relational data and the particular characteristics of bill initiation networks, we propose a new approach – bootstrapping an exponential graph model using augmented data reflective of the frequency of ties – to address the challenges of thinning dense networks.
Offshore Outsourcing and Non‐production Workers: Firm‐level Relationships Disaggregated by Skills and Suppliers
Authors: Tomiura Eiichi , Ito Banri , Wakasugi Ryuhei
Published: August 2012

In analysing the impact of offshoring on the skill composition, previous empirical studies have established that offshoring firms employ more non‐production workers. However, not all non‐production workers are highly skilled. This paper disaggregates non‐production workers into the following three categories: (i) skilled non‐production workers, (ii) unskilled non‐production workers and (iii) non‐production workers with special skills for offshoring and other overseas business management. By linking our offshoring survey data with firm‐level data for Japanese manufacturing firms, this paper finds that the share of skilled non‐production workers tends to be significantly high in offshoring firms but that of unskilled non‐production workers is not. As offshoring has expanded from production to non‐production tasks, this result implies that the distinction between skilled versus unskilled workers becomes critical among non‐production workers. Using our unique data on supplier types in offshoring, this paper finds that the share of non‐production workers for the management of overseas activities tends to be high in foreign direct investment firms and in firms outsourcing to foreign independent suppliers, but not in Japanese firms outsourcing to offshore suppliers located abroad but owned by other Japanese firms. This difference indicates that coordination burdens are likely to be at least partly mitigated by common languages or shared business practices. These findings suggest that offshoring has different impacts on employment depending on suppliers and the worker’s skill. The principal results are confirmed robust even after various firm characteristics are controlled for in panel regressions, though we should not give any causal interpretations.
Phenotypic variability in three families with valosin‐containing protein mutation
Authors: Spina S. , Van Laar A. D. , Murrell J. R. , Hamilton R. L. , Kofler J. K. , Epperson F. , Farlow M. R. , Lopez O. L. , Quinlan J. , DeKosky S. T. , Ghetti B.
Published: August 2012

Background and purpose

The phenotype of IBMPFD [inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia (FTD)] associated with valosin‐containing protein (VCP) mutation is described in three families.

Methods

Probands were identified based on a pathological diagnosis of frontotemporal lobar degeneration with TDP‐43‐positive inclusions type IV. VCP sequencing was carried out. Clinical data on affected family members were reviewed.

Results

Ohio family: four subjects presented muscle weakness and wasting. (One subject had both neuropathic and myopathic findings and another subject showed only evidence of myopathy. The etiology of weakness could not be ascertained in the remaining two subjects.) Two individuals also showed Parkinsonism (with associated FTD in one of the two). The proband's brain displayed FTLD‐TDP type IV and Braak stage five Parkinson's disease (PD). A VCP R191Q mutation was found. Pennsylvania family: 11 subjects developed IBMPFD. Parkinsonism was noted in two mutation carriers, whilst another subject presented with primary progressive aphasia (PPA). A novel VCP T262A mutation was found. Indiana family: three subjects developed IBMPFD. FTD was diagnosed in two individuals and suspected in the third one who also displayed muscle weakness. A VCP R159C mutation was found.

Conclusions

We identified three families with IBMPFD associated with VCP mutations. Clinical and pathological PD was documented for the first time in members of two families. A novel T262A mutation was found. One individual had PPA: an uncommon presentation of IBMPFD.
Early infarct FLAIR hyperintensity is associated with increased hemorrhagic transformation after thrombolysis
Authors: Kufner A. , Galinovic I. , Brunecker P. , Cheng B. , Thomalla G. , Gerloff C. , Campbell B. C. V. , Nolte C. H. , Endres M. , Fiebach J. B. , Ebinger M.
Published: August 2012

Background and purpose

Absence of FLAIR hyperintensity within an acute infarct is associated with stroke onset <4.5 h. However, some patients rapidly develop FLAIR hyperintensity within this timeframe. We hypothesized that development of early infarct FLAIR hyperintensity would predict hemorrhagic transformation (HT) in patients treated with tissue plasminogen activator (tPA) < 4.5 h after onset.

Methods

Consecutive acute stroke patients treated with intravenous tPA <4.5 h after onset who had MRI before and 1 day after thrombolysis were included. Two raters (blind to HT) independently identified FLAIR hyperintensity with reference to the diffusion‐weighted image (DWI) lesion. HT was assessed using T2* MRI at 24 h. Hemorrhagic infarction (HI) was defined as petechial HT without mass effect, and parenchymal hematoma (PH) as HT with mass effect. Multivariable logistic regression analysis for HT included FLAIR status, baseline National Institutes of Health Stroke Scale and DWI lesion volume, leukoaraiosis (Wahlund score), serum glucose and reperfusion.

Results

Of 109 patients, 33 (30%) had acute FLAIR hyperintensity. HT occurred in 17 patients (15.6%; 15 HI, 2 PH). HT was more common in FLAIR‐positive patients than FLAIR‐negative patients (33.3% vs. 9.2%, P = 0.009). Median time‐to‐scan and median time‐to‐thrombolysis did not differ significantly between patients with HT and without [97 IQR(68, 155) vs. 90 IQR(73, 119), P = 0.5; 120 IQR(99, 185) vs. 125 IQR(95, 150), P = 0.6, respectively]. In multivariable analysis, only FLAIR hyperintensity was independently associated with HT after thrombolysis (OR 18; 95% CI 2–175, P = 0.013).

Conclusions

Early development of FLAIR hyperintensity within the area of diffusion restriction is associated with increased risk of HT after thrombolysis in acute stroke patients.
The flexibility of partial information transmission in the auditory channel: The role of perceptual discriminability
Authors: Gong Diankun , Ma Weiyi , Hu Jiehui , Hu Qingqing , Lai Yongxiu , Yao Dezhong
Published: August 2012

A stimulus contains multiple attributes. Under certain circumstances, some information can be transmitted to the next cognitive stage before the processing of other information. An examination of partial information transmission is essential in improving our understanding of the mechanism of information processing. By manipulating two attributes, namely, pitch and intensity, this study examined whether the transmission speed of an attribute could be influenced by its perceptual discriminability. Using a choice go/no‐go paradigm, this study presented adults with two pieces of pure tones and measured their LRPs. Results showed that pitch and intensity were transmitted earlier as partial information in the high pitch‐ and intensity‐discriminability conditions, respectively. Thus, this study demonstrated that the transmission speed of a certain attribute could be modulated by its perceptual discriminability.
Pregnancy‐associated acquired haemophilia A: results from the European Acquired Haemophilia (EACH2) registry
Authors: Tengborn L , Baudo F , Huth‐Kühne A , Knoebl P , Lévesque H , Marco P , Pellegrini F , Nemes L , Collins P ,   on behalf of the EACH2 registry contributors
Published: August 2012

Please cite this paper as: Tengborn L, Baudo F, Huth‐Kühne A, Knoebl P, Lévesque H, Marco P, Pellegrini F, Nemes L, Collins P on behalf of the EACH2 registry contributors. Pregnancy‐associated acquired haemophilia A: results from the European Acquired Haemophilia (EACH2) registry. BJOG 2012;119:1529–1537.

Objective  The European Acquired Haemophilia registry (EACH2) collected data on the demographics, diagnosis, underlying disorders, bleeding characteristics, treatment, and outcome of women with acquired haemophilia A (AHA), a rare and often severe bleeding disorder caused by autoantibodies directed against coagulation factor VIII.

Design  Prospective, multi‐centre, large‐scale, pan‐European registry.

Setting  A total of 117 haemophilia centres in 13 European countries.

Population  Pregnancy‐associated AHA.

Methods  Data were reported using a web‐based electronic case report form. Diagnosis was based on the presence of a prolonged activated partial thromboplastin time, reduced coagulation Factor VIII level and positive inhibitor assay.

Main outcome measures  Presenting characteristics, time to diagnosis, haemostatic treatment and outcome, immunosuppressive treatment and outcome.

Results  The EACH2 registry (n = 501) documented 42 (8.4%) cases of AHA associated with the peripartum period, a median Factor VIII level at diagnosis of 2.5 (range 0–25) IU/dl and inhibitor titre of 7.8 (range 0.7–348) BU/ml. Antepartum inhibitors were evident in eight women. Time to diagnosis of AHA after delivery was 89 (range 21–120) days. First‐line haemostatic treatment was successful in 20/23 (87%) women treated. Bleeding episodes resolved in 17/18 (94%) women treated with a bypassing agent and 29/39 (74%) women achieved complete remission with first‐line immunosuppressive treatment. Two babies experienced postnatal bleeding, suggesting transplacental transfer of the antibody. All women were alive at last follow‐up.

Conclusions  Although rare, pregnancy‐associated AHA may cause severe bleeding‐related morbidity. Once diagnosed, women respond well to haemostatic treatment with bypassing agents and immunosuppression. Awareness of peripartum AHA requires improvement to facilitate rapid and appropriate management.
The risk of vesicovaginal and urethrovaginal fistula after hysterectomy performed in the English National Health Service—a retrospective cohort study examining patterns of care between 2000 and 2008
Authors: Hilton P , Cromwell DA
Published: August 2012

Please cite this paper as: Hilton P, Cromwell D. The risk of vesicovaginal and urethrovaginal fistula after hysterectomy performed in the English National Health Service—a retrospective cohort study examining patterns of care between 2000 and 2008. BJOG 2012;119:1447–1454.

Objective  To estimate rates of vesicovaginal and urethrovaginal fistula among women undergoing hysterectomy by indication and type of procedure, and to assess trends in risk over time.

Design  Retrospective cohort using data from Hospital Episode Statistics.

Setting  English National Health Service (NHS) hospitals.

Population  Women undergoing hysterectomy for selected common conditions in English NHS hospitals between January 2000 and December 2008.

Methods  Unadjusted rates of urogenital fistula were calculated by type of procedure and indication. Logistic regression was used to assess whether the risk of fistula was associated with age, or had changed over time.

Main outcome measure  Rate of urogenital fistula (vesicovaginal and urethrovaginal fistula) within 1 year of hysterectomy.

Results  Among 343 771 women undergoing hysterectomy, the overall rate of fistula was 1 in 788. The rate varied by indication and procedure, being highest following radical hysterectomy for cervical cancer (1 in 87; 95% CI 61–128) and lowest following vaginal hysterectomy for prolapse (1 in 3861; 95% CI 2550–6161). After total abdominal hysterectomy for endometriosis, menstrual problems or fibroids, the risk of fistula was lower in women aged 50 years or over than in women under 40 years (adjusted odds ratio 0.61; 95% CI 0.38–0.98). The overall rate of fistula increased by 46% during the study period.

Conclusions  The risk of urogenital fistula was associated with type of hysterectomy and indication; the risk increased during the study period, and was lower after hysterectomy for benign conditions in women aged 50 years or over.
Evaluation of adjunctive perampanel in patients with refractory partial‐onset seizures: Results of randomized global phase III study 305
Authors: French Jacqueline A. , Krauss Gregory L. , Steinhoff Bernhard J. , Squillacote David , Yang Haichen , Kumar Dinesh , Laurenza Antonio
Published: August 2012

Purpose:  To assess the efficacy and safety of once‐daily doses of perampanel 8 and 12 mg when added to 1–3 concomitantly administered, approved antiepileptic drugs (AEDs) in patients with uncontrolled partial‐onset seizures.

Methods:  Study 305 was a multicenter, double‐blind, placebo‐controlled trial in patients aged 12 years and older with ongoing seizures despite prior therapy with at least two AEDs, and currently receiving 1–3 AEDs. Equal randomization to once‐daily oral perampanel 8 or 12 mg, or placebo was performed. Patients entered a 19‐week double‐blind treatment phase comprising a 6‐week titration period, with weekly 2‐mg dose increments, followed by a 13‐week maintenance period. Primary efficacy end points were the responder rate (proportion of patients who had a ≥50% reduction in seizure frequency during treatment per 28 days relative to baseline), and the percent change in seizure frequency per 28 days relative to pre‐perampanel baseline. A secondary end point was percent change in the frequency of complex partial plus secondarily generalized seizures. Adverse events (AEs) were monitored throughout the study.

Key Findings:  Three hundred eighty‐six patients were randomized and treated with study medication. Of these, 321 patients completed the study. The 50% responder rates (intent‐to‐treat analysis) were 14.7%, 33.3%, and 33.9%, respectively, for placebo, perampanel 8 mg, and perampanel 12 mg, with significant improvements over placebo for both perampanel 8 mg (p = 0.002) and 12 mg (p < 0.001). The median percent change from baseline in seizure frequency per 28 days (intent‐to‐treat analysis) was −9.7%, −30.5%, and −17.6% for placebo, 8 mg, and 12 mg, respectively, with significant reductions compared with placebo for both 8 mg (p < 0.001) and 12 mg (p = 0.011). For complex partial seizures plus partial seizures that secondarily generalized, the median percent change in frequency was −32.7% (8 mg), −21.9 (12 mg), and −8.1% (placebo), with significant reductions for both 8 mg (p < 0.001) and 12 mg (p = 0.005). The most frequent (occurring in ≥10% of patients in any treatment group) treatment‐emergent AEs were dizziness, somnolence, fatigue, and headache, with an apparent dose effect suggested for all except headache.

Significance:  This phase III trial demonstrated that adjunctive treatment with once‐daily perampanel at 8 mg and 12 mg was effective in improving seizure control in patients 12 years and older with refractory partial‐onset seizures. These study results also demonstrated that once‐daily doses of 8 mg and 12 mg were safe and acceptably tolerated in this study. Perampanel demonstrated a favorable risk/benefit ratio in this population.
Duration of untreated bipolar disorder: missed opportunities on the long road to optimal treatment
Authors: Drancourt N. , Etain B. , Lajnef M. , Henry C. , Raust A. , Cochet B. , Mathieu F. , Gard S. , MBailara K. , Zanouy L. , Kahn J. P. , Cohen R. F. , Wajsbrot‐Elgrabli O. , Leboyer M. , Scott J. , Bellivier F.
Published: August 2012

Objective:  Duration of untreated illness represents a potentially modifiable component of any diagnosis‐treatment pathway. In bipolar disorder (BD), this concept has rarely been systematically defined or not been applied to large clinically representative samples.

Method:  In a well‐characterized sample of 501 patients with BD, we estimated the duration of untreated bipolar disorder (DUB: the interval between the first major mood episode and first treatment with a mood stabilizer). Associations between DUB and clinical onset and the temporal sequence of key clinical milestones were examined.

Results:  The mean DUB was 9.6 years (SD 9.7; median 6). The median DUB for those with a hypomanic onset (14.5 years) exceeded that for depressive (13 years) and manic onset (8 years). Early onset BD cases have the longest DUB (P < 0.0001). An extended DUB was associated with more mood episodes (P < 0.0001), more suicidal behaviour (P = 0.0003) and a trend towards greater lifetime mood instability (e.g. rapid cycling, possible antidepressant‐induced mania).

Conclusion:  Duration of untreated bipolar disorder (DUB) will only be significantly reduced by more aggressive case finding strategies. Reliable diagnosis (especially for BD‐II) and/or instigation of recommended treatments is currently delayed by insufficient awareness of the early, polymorphous presentations of BD, lack of systematic screening and/or failure to follow established guidelines.
Deconstructing the familiality of variability in momentary negative and positive affect
Authors: Jacobs N. , Menne‐Lothmann C. , Derom C. , Thiery E. , van Os J. , Wichers M.
Published: August 2012

Objective:  The daily life, affective phenotypes of momentary negative affect (NA), positive affect (PA) variability and NA variability are associated with future depressive symptomatology. This study investigates the extent to which genetic and environmental factors contribute to the inter‐individual differences in these daily life, affective phenotypes.

Method:  Two hundred and seventy‐nine female twins from the Flemish (Belgium) general population participated in an experience sampling study measuring affect in daily life. Structural equation modelling was used to fit univariate and bivariate models.

Results:  Genetic factors explained, respectively, 18%, 18% and 35% of the inter‐individual differences in momentary NA, PA variability and NA variability. Non‐shared environmental factors were found to explain the remaining inter‐individual variation. In addition, 41% of the association between positive and NA variability was attributed to shared genetic factors.

Conclusion:  Results of this study show that daily life patterns of affective expression are subject to substantial environmental influence. Prospective assessments of the effect of interventions on these expressions may therefore represent a powerful tool to prevent transition from subclinical depressive symptomatology to a clinical outcome or to reduce symptomatology in those with clinical depression.
Determination of GHG and ammonia emissions from stored dairy cattle slurry by using a floating dynamic chamber
Authors: MINATO Keiko , KOUDA Yasuyuki , YAMAKAWA Masaaki , HARA Satoshi , TAMURA Tadashi , OSADA Takashi
Published: August 2012

We developed a system for measuring emissions from stored slurry by using a floating dynamic chamber. CH4, CO2, N2O and NH3 emitted from the storage tank of a dairy cattle farm in eastern Hokkaido were measured during summer 2008 (7/16–8/6), fall 2008 (10/2–10/26), spring 2009 (6/2–6/21) and winter 2009 (3/11). Average daily gas emission rates in summer, fall and spring were, respectively, 54.8, 54.2 and 34.3 g/m2 for CH4; 602, 274 and 254 g/m2 for CO2; 55.4, 68.2 and trace mg/m2 for N2O; and 0.55, 0.73 and 0.46 g/m2 for NH3. CH4, CO2 and NH3 emission rates during the brief measurement period in winter were reduced to 1/4, 1/23 and 1/2, respectively, of summer emission rate levels. All gas emissions showed diurnal fluctuation and were greatest during the daytime, when the ambient temperature rose. CH4, NH3 and CO2 emissions increased significantly during the daytime, and the daily emission (in grams) of each gas was positively correlated with maximum daily temperature. According to the combined spring, summer and fall measurements, the CH4, N2O and NH3 annual emission factors were 1.42% (g CH4/g volatile solids), 0.02% (g N2O‐N/g total N) and 0.43% (g NH3‐N/g total N), respectively.
Anandamide Transforms Noncopulating Rats into Sexually Active Animals
Authors: Canseco-Alba Ana , Rodríguez-Manzo Gabriela
Published: August 2012

Introduction

Noncopulating (NC) male rats are apparently normal and healthy animals that will not mate despite repeated exposure to sexually receptive females. Several lines of evidence suggest the involvement of endogenous opioids in this sexual inhibitory state. Endogenous opioids and endocannabinoids are neuromodulators of neurotransmitter release, although through different mechanisms.

Aim

To establish if the endocannabinoid anandamide was able to induce sexual behavior expression in male rats classified as noncopulators.

Methods

NC male rats were intraperitoneally (i.p.) injected with anandamide or vehicle and tested for copulatory behavior with a receptive female during 120 minutes. Fourteen days after anandamide or vehicle injection, the animals were subjected to a second sexual behavior test during 60 minutes.

Main Outcome Measures

The percentage of rats showing male sexual behavior responses: mount, intromission, ejaculation, and copulation resumption after ejaculation and the specific sexual behavior parameters were quantified.

Results

Anandamide injection induced sexual behavior expression in 50% of previously NC rats, while the NC animals injected with vehicle did not show sexual behavior. The responding animals executed several successive ejaculatory series and were still capable of showing sexual behavior 14 days after anandamide injection. Copulation in these rats (the first copulatory series) was characterized by a large number of mounts and intromissions preceding ejaculation, as well as by statistically significant increases in the latencies to mount, intromit, and ejaculate when compared with the sexual performance of sexually naïve animals copulating for the first time.

Conclusion

The endocannabinoid anandamide transforms previously NC rats into sexually active animals, capable of showing sexual behavior in a long-lasting manner. Only half of the NC population responds to anandamide injection, suggesting that different mechanisms underlie the sexual inhibition of NC rats. The endocannabinoid system seems to play a role in the regulation of male rat sexual behavior expression.
Laparoscopic spleen‐preserving distal pancreatectomy: A consecutive series at an experienced centre
Authors: Schloericke Erik , Zimmermann Markus , Roblick Uwe Johannes , Hildebrand Phillip , Hoffmann Martin , Jungbluth Thomas , Bader Franz Georg , Bruch Hans‐Peter , Buerk Conny Georg
Published: August 2012

Aim

The increasing experience within the area of laparoscopic procedures has paved the way for technically‐complex procedures, such as distal pancreatectomy. In order to avoid complications associated with concomitant splenectomy, these procedures are increasingly performed with spleen preservation. A drawback is the low number of cases, which does not allow for an evidence‐based comparison between laparoscopic and open procedures, and spleen‐preserving and concomitant splenectomy procedures.

Patients and Methods

Between 2006 and 2010, all data for patients who underwent a laparoscopic distal pancreatectomy (LDP) at the Department of Surgery, University of Schleswig‐Holstein, Luebeck, Germany, were collected are stored in a prospectively‐maintained database. Patients with tumours in the pancreatic tail and body that did not exceed the level of the portal vein were included in this database.

Results

A total of 22 patients who underwent LDP could be included in the evaluation. Ten of those patients underwent a laparoscopic spleen‐preserving distal pancreatectomy (LSPDP), while the remaining 12 received an LDP with splenectomy (LDPwS). The median operation time was 155 min (range: 98–253) for the LSPDP group, and 201 min (range: 60–310) for the LDPwS group (P = 0.06). The median hospital stay was 8.5 days (range: 5–23) in the LSPDP group compared to 11 days (range: 4–41) in the LDPwS group (P = 0.06). Pancreatic fistula occurred in two patients from each group. It caused an intraabdominal haemorrhage in one patient of the LSPDP group, which required re‐laparoscopy. Two patients experienced subphrenic abscesses in the LDPwS group and were treated interventionally. Histological examination revealed six cystadenomas and five pseudocysts (maximum diameter: 7 cm) in the LDPwS group, and six neuroendocrine tumours (maximum diameter: 2 cm) in the LSPDP group.

Conclusion

LDP can be performed safely. The optic magnification provided by laparoscopy facilitates LSPDP, as dissection of the splenic vessels can be avoided. Although not significant, there was a trend towards reduced hospital stay and operating time for LSPDP. Oncologic outcomes and morbidity seem to not be inferior to open procedures. The size of the tumours and the peripancreatic, as well as paraneoplastic, tissue alterations determine the indication for splenectomy.
Evaluating a sustainability index for nutrients in a short rotation energy cropping system
Authors: Sochacki Stanley J. , Harper Richard J. , Smettem Keith R. J. , Dell Bernard , Wu Hongwei
Published: August 2012

In dryland environments 3–5 year rotations of tree crops and agriculture represent a major potential bioenergy feedstock and a means to restore landscape hydrologic balances and phytoremediate sites, while maintaining food production. In soils with low natural fertility, the long‐term viability of these systems will be critically affected by site nutrient status and subsequent cycling of nutrients. A nutrient assimilation index (NAI) was developed to allow comparison of species and tree component nutrient assimilation and to optimize nutrient management, by quantifying different strategies to manage site nutrients. Biomass, nutrient export and nutrient use efficiency were assessed for three short rotation tree crop species. Nutrient exports following harvest at 3 years of high density (4000 trees ha−1) were consistently higher in Pinus radiata, with values of 85 kg ha−1 of N, 11kg ha−1 of P, and 62 kg ha−1 of K, than Eucalyptus globulus and Eucalyptus occidentalis. Component NAI was generally in the order of leaf<twig<bark<root<stem‐wood for N, P, K, S, Ca, and Mg. The NAI ranged from 0.06 Mg kg−1 for N in leaves of P. radiata to 4.7 Mg kg−1 for P in stem‐wood of E. occidentalis, indicating higher sustainability of wood biomass compared with leaf biomass. The leaves for each species contained between 40 and 60% of the total nutrient contents while comprising around 25–30% of the total biomass. These nutrient exports via biomass removal are similar to those that follow 3 years of wheat production in the same region, indicating there is no additional drawdown of nutrient reserves during the tree cropping phase of the rotation.
Shape Memory Alloy Expandable Pedicle Screw to Enhance Fixation in Osteoporotic Bone: Primary Design and Finite Element Simulation
Authors: Tabesh Majid , Goel Vijay , Elahinia Mohammad H.
Published: August 2012

The properties of shape memory alloys, specifically the equiatomic intermetallic NiTi, are unique and significant in that they offer simple and effective solutions for some of the biomechanical issues encountered in orthopedics. Pedicle screws, used as an anchoring point for the implantation of spinal instrumentations in the spinal fracture and deformity treatments, entail the major drawback of loosening and backing out in osteoporotic bone. The strength of the screw contact with the surrounding bone diminishes as the bone degrades due to osteoporosis. The SMArtTM pedicle screw design is developed to address the existing issue in degraded bone. It is based on the interaction of bi-stable shape memory-superelastic elements. The bi-stable assembly acts antagonistically and consists of an external superelastic tube that expands the design protrusions when body temperature is attained; also an internal shape memory wire, inserted into the tube, retracts the assembly while locally heated to above the body temperature. This innovative bi-stable solution augments the pull-out resistance while still allowing for screw removal. The antagonistic wire-tube assembly was evaluated and parametrically analyzed as for the interaction of the superelastic tube and shape memory wire using a finite element model developed in COMSOL Multiphysics®. The outcomes of the simulation suggest that shape memory NiTi inserts on the SMArtTM pedicle screw can achieve the desired antagonistic functionality of expansion and retraction. Consequently, a parametric analysis was conducted over the effect of different sizes of wires and tubes. The dimensions for the first sample of this innovative pedicle screw were determined based on the results of this analysis.
Intermittent and recurrent episodes of subclinical hypothyroidism, central hypothyroidism and T3-toxicosis in an elderly woman
Authors: Megías Marta Cano , Iglesias Pedro , Villanueva Mercedes García , Díez Juan José
Published: August 2012

Exogenous thyrotoxicosis is usually caused by ingestion of excessive amounts of thyroid hormone, which could be intentional or surreptitious (known as factitious thyrotoxicosis). Non-pharmacological exogenous thyrotoxicosis is an exceptional event. One example is alimentary thyrotoxicosis, which is caused by the ingestion of meat or sausage containing thyroid tissue, inadvertently mixed with traces of muscles and other tissues of the animal's neck (hamburger thyrotoxicosis). We report for the first time a patient who had recurrent episodes of triiodothyronine (T3) toxicosis for several years due to inadvertent chronic consumption of contaminated traditional Spanish cold meat with porcine thyroid.
A widely displaced Galeazzi-equivalent lesion with median nerve compromise
Authors: Galanopoulos Ilias , Fogg Quentin , Ashwood Neil , Fu Katherine
Published: August 2012

We present the case of a 14-year-old boy with a right distal radial fracture accompanied by a severely displaced complete distal ulnar physeal separation and associated median nerve compromise. This injury is known as Galeazzi-equivalent lesion in children and is an extremely rare injury associated with growth arrest. Recognition of the lesion can be difficult but wide displacement may be associated with other significant injuries such as neurovascular compromise. Prompt intervention reversed the neurological symptoms. At 10-month postoperation there was neither growth arrest nor loss of motion. Complete separation of the ulna physis remains often because of soft tissue interposition or capsule problems and prompt reduction is recommended in the literature as a priority.
Right ventricular inflow tract obstruction secondary to metastatic cutaneous squamous cell carcinoma
Authors: Hunter Jonathan Michael , Reid Angeline Louise , Stride Peter John , Dettrick Andrew
Published: August 2012

We report the case of an immunocompetent 83-year-old man with metastatic neoplastic infiltration of the heart from primary squamous cell carcinoma (SCC) of the skin. Death was from cardiopulmonary collapse due to left ventricular failure with features of right ventricular inflow tract obstruction. Metastatic tumours involving the heart rarely originate from cutaneous SCC though have been reported in the literature in both immunocompetent and postrenal-transplant recipient patients. Most involve the pericardium and only rarely the endocardium or the myocardium. While the prognosis is generally poor, palliative radiotherapy may provide significant symptom relief. Cardiac metastases should be considered in patients with advanced cancer, especially when they show cardiac symptoms and signs.
Safe physiotherapy interventions in large cervical disc herniations: Figure 1
Authors: Keramat Keramat Ullah , Gaughran Aisling
Published: August 2012

A 34-year-old woman was seen in a physiotherapy department with signs and symptoms of cervical radiculopathy. Loss of cervical lordosis and a large paracentral to intraforaminal disc prolapse (8 mm) at C5–C6 level was reported on MRI. She was taking diclofenac sodium, tramadol HCl, diazepam and pregabalin for the preceding 2 months and no significant improvement, except temporary relief, was reported. She was referred to physiotherapy while awaiting a surgical opinion from a neurosurgeon. In physiotherapy she was treated with mobilisation of the upper thoracic spine from C7 to T6 level. A cervical extension exercise was performed with prior voluntary extension of the thoracic spine and elevated shoulders. She was advised to continue the same at home. General posture advice was given. Signs and symptoms resolved within the following four sessions of treatment over 3 weeks. Surgical intervention was subsequently deemed unnecessary.
AN IMPROVED MODEL FOR ASSESSING THE FDH-COST EFFICIENCY
Authors: PARYAB KHALIL , SHIRAZ RASHED KHANJANI , JALALZADEH LEILA
Published: August 2012

Recently Leleu [A linear programming framework for free disposal hull (FDH) technologies and cost functions: Primal and dual models] presented a linear model for assessing the FDH-cost function with various returns to scale assumptions. He stated that economic inefficiency can be computed as the ratio of the observed cost to the minimum cost and, as usual, the allocative inefficiency is computed as the ratio between the economic and the technical inefficiencies. In this paper, we propose a modified model with various returns to scale assumptions that has fewer constraints and variables than Leleu's model and obtains the FDH-cost efficiency directly. Reducing nm constraints and nm variables, where n is the number of DMUs and m is the number of inputs, leads to the computational advantage of our model over that of Leleu.