bluuebunny/crossref_metadata_2025 huggingface dataset:
Lamotrigine increases intracellular Ca2+ levels and Ca2+/calmodulin‐dependent kinase II activation in mouse dorsal root ganglion neurones
Authors: Lee E. S. , Ryu J. H. , Kim E.‐J. , Kim G.‐T. , Cho Y.‐W. , Park H.‐J. , Tak H.‐M. , Han J. , Kang D.
Published: December 2012

Aim

Lamotrigine is a neuroprotective agent that is used clinically for the treatment of seizures and neuropathic pain. A significant volume of literature has reported that lamotrigine exerts analgesic effect by blocking Ca2+ channels. However, little is known regarding the effect of lamotrigine on the intracellular Ca2+ concentration ([Ca2+]i). The aim of this study was to determine whether lamotrigine modulates [Ca2+]i in sensory neurones.

Methods

Lamotrigine‐induced changes in [Ca2+]i were measured in mouse dorsal root ganglion (DRG) neurones using the Ca2+‐sensitive fluorescent indicator Fluo 3‐AM and a confocal laser scanning microscope. Ca2+/calmodulin‐dependent kinase II (CaMKII) activation was assessed by the fluorescence intensity using immunocytochemical procedures.

Results

Treatment with 1, 10, 30 or 100 μm lamotrigine transiently increased [Ca2+]i in DRG neurones in a dose‐dependent manner. Treatment with 100 μm lamotrigine induced a significant (threefold) increase in the Ca2+ peak in the presence or absence of extracellular Ca2+. The lamotrigine‐induced Ca2+ increase was abolished or decreased by the treatment with a specific PLC inhibitor (U73122), IP3R antagonist (xestospongin C) or RyR antagonist (dantrolene). In some cells, treatment with 100 μm lamotrigine caused a transient Ca2+ increase, and the Ca2+ levels quickly fell to below the basal Ca2+ level observed prior to lamotrigine application. The decrease in basal Ca2+ levels was blocked by the treatment with a CaMKII inhibitor (KN93). Immunocytochemical analysis indicated that lamotrigine treatment increased the expression of phosphorylated CaMKII in DRG neurones.

Conclusion

Treatment with lamotrigine increased [Ca2+]i apparently as a result of Ca2+ release from intracellular stores and CaMKII activity.
Autophagy and Bcl‐2/BNIP3 death regulatory pathway in non‐small cell lung carcinomas
Authors: Karpathiou Georgia , Sivridis Efthimios , Koukourakis Michael , Mikroulis Dimitrios , Bouros Demosthenes , Froudarakis Marios , Bougioukas George , Maltezos Efstratios , Giatromanolaki Alexandra
Published: December 2012

We recently showed that non‐small cell lung carcinomas (NSCLCs) are of dismal prognosis when encompassing accelerated autophagic activity. The regulation of this abnormally functioning degradation system and its association with hypoxia and apoptosis in lung carcinoma patients is unexplored. In this study we used 115 NSCLC tissues to examine the immunohistochemical expression of four distinct molecules – the major regulator of autophagy Beclin 1, the anti‐apoptotic and anti‐autophagic protein Bcl‐2, the pro‐apoptotic and pro‐autophagic protein BNIP3, and a marker of hypoxia and glucolysis, the glucose transporter Glut 1. Most cases showed reduced reactivity for Beclin 1 (62%) and Bcl‐2 (82%) proteins, almost half of our sample revealed strong BNIP3 expression (57%), whereas most of the carcinomas strongly expressed Glut 1 antigen (71%). Beclin 1 expression showed no association with survival. Bcl‐2 positivity was a marker of good prognosis (p = 0.04), whereas BNIP3 (p = 0.0004) and Glut 1 (p = 0.03) expression correlated with poor outcome in Stage I disease. Autophagic status was negatively associated with Bcl‐2 (p = 0.0006), but positively with Glut 1 expression (p = 0.001). In conclusion, the accelerated autophagic status in NSCLC is unrelated to Beclin 1 and BNIP3 expression, but does show significant association with Bcl‐2 reactivity. Furthermore, we showed important correlations between glucolysis and autophagy, guiding new pathways in future lung carcinoma research.
Mutational and expressional analyses of SPOP, a candidate tumor suppressor gene, in prostate, gastric and colorectal cancers
Authors: Kim Min S. , Je Eun M. , Oh Ji E. , Yoo Nam J. , Lee Sug H.
Published: December 2012

Mounting evidence exists that alterations of ubiquitination processes are involved in cancer pathogenesis. Speckle‐type POZ protein (SPOP) is a key adaptor for Cul3‐based ubiquitination process. Recent studies reported that SPOP may be a tumor suppressor gene (TSG) and somatic mutation of SPOP was detected in prostate cancer (PCA). The aim of this study was to see whether alterations of SPOP protein expression and somatic mutation of SPOP gene are features of cancers. In this study, we analyzed SPOP somatic mutation in 45 gastric (GC), 45 colorectal cancer (CRC) and 45 PCA by single‐strand conformation polymorphism (SSCP). Also, we analyzed SPOP protein expression in 60 GC, 60 CRC and 60 PCA by immunohistochemistry. Overall, we detected three somatic missense mutations of SPOP gene in the coding sequences (p.Ser14Leu, p.Tyr87Cys and p.Phe133Leu). The mutations were observed in two PCA and one CRC. Of note, the p.Phe133Leu was a recurrent mutation reported in an earlier study. In the immunohistochemistry, SPOP protein was expressed in normal gastric, colonic and prostate epithelial cells, whereas it was lost in 30% of GC, 20% of CRC and 37% of PCA. Our data indicate that loss of SPOP expression was common in GC, CRC and PCA, but somatic mutation of SPOP in this study was rare in these tumors. Also, the data provide a possibility that loss of expression of SPOP gene might play a role in cancer pathogenesis by altering TSG functions of SPOP.
Endothelin antagonists for diabetic and non‐diabetic chronic kidney disease
Authors: Kohan Donald E. , Pollock David M.
Published: December 2012

Numerous pre‐clinical studies have implicated endothelin‐1 in the pathogenesis of diabetic and non‐diabetic chronic kidney disease (CKD). Renal endothelin‐1 production is almost universally increased in kidney disease. The pathologic effects of endothelin‐1, including vasoconstriction, proteinuria, inflammation, cellular injury and fibrosis, are likely mediated by the endothelin A (ETA) receptor. ETA antagonism alone, and/or combined ETA/B blockade, reduces CKD progression. Based on the strong pre‐clinical data, several clinical trials using ETA antagonists were conducted. Small trials involving acute intravenous endothelin receptor blockade suggest that ETA, but not ETB, blockade exerts protective renal and vascular effects in CKD patients. A large phase 3 trial (ASCEND) examined the effects of avosentan, an endothelin receptor antagonist, on renal disease progression in diabetic nephropathy. Proteinuria was reduced after 3–6 months of treatment. However the study was terminated due to increased morbidity and mortality associated with avosentan‐induced fluid retention. Several phase 2 trials using avosentan at lower doses than in ASCEND, atrasentan or sitaxsentan (the latter two being highly ETA‐selective) showed reductions in proteinuria on top of renin‐angiotensin system blockade. Infrequent and clinically insignificant fluid retention was observed at the most effective doses. Additional trials using ETA blockers are ongoing or being planned in patients with diabetic nephropathy or focal segmental glomerulosclerosis. Moving forward, such studies must be conducted with careful patient selection and attention to dosing in order to minimize adverse side effects. Nonetheless, there is cause for optimism that this class of agents will ultimately prove to be effective for the treatment of CKD.
The prevalence, correlates and impact of anaemia among older people in Cuba, Dominican Republic, Mexico, Puerto Rico and Venezuela
Authors: Bryce Renata M. , Salas Aquiles , Acosta Daisy , Jimenez‐Velazquez Ivonne Z. , Llibre‐Rodriguez Juan J. , Sosa Ana Luisa , Teruel Beatriz Marcheco , Valhuerdi Adolfo , Ferri Cleusa P. , McKeigue Paul , Prince Martin J.
Published: December 2012

Anaemia among older people is increasingly recognized as a matter of public health concern. Data from low‐ and middle‐income countries are sparse. We surveyed 10915 people aged 65 years and over (8423 with blood tests) in catchment areas in Cuba, Dominican Republic, Puerto Rico, Venezuela and Mexico, to assess prevalence and correlates of anaemia and impact on disability. Prevalence varied widely between sites, from 6·4% in rural Mexico to 9·2% in urban Mexico, 9·8% in Venezuela, 19·2% in Cuba, 32·1% in Puerto Rico and 37·3% in Dominican Republic. Prevalence was higher in men and increased with age, but sociodemographic composition did not account for prevalence differences between sites. Standardized morbidity ratios indicated a much higher prevalence in Cuba (173), Puerto Rico (280) and Dominican Republic (332) compared with USA National Health and National Examination Surveys. Anaemia was associated with undernutrition, physical impairments, and serum creatinine. There was an association with greater African admixture in Dominican Republic but not in Cuba. African admixture is therefore unlikely to fully explain the high prevalence in the Caribbean islands, which may also arise from environmental, possibly dietary factors. Given an important independent contribution of anaemia to disability, more research is needed to identify preventable and treatable causes.
Role of pituitary dysfunction on cardiovascular risk in primary empty sella patients
Authors: Colao Annamaria , Cotta Oana R. , Ferone Diego , Torre Maria L. , Ferraù Francesco , Di Somma Carolina , Boschetti Mara , Teti Claudia , Savanelli Maria C. , Alibrandi Angela , Trimarchi Francesco , Cannavò Salvatore
Published: December 2012

Objective

Primary empty sella (PES) is a frequent anatomical condition rarely causing pituitary dysfunction. We assessed cardiovascular risk in a cohort of PES patients referred to Endocrine Units.

Design

The study was performed in three Italian tertiary referral centres. We evaluated pituitary function and cardiovascular risk, on the basis of lipid and glucose metabolism parameters and of Framingham score (FS), in 94 consecutive patients with PES diagnosis and in 94 gender, age and BMI matched controls.

Patients

Pituitary function was normal in 30 patients (group A), whereas a single or multiple pituitary hormone deficiency was demonstrated in 64 (group B). Growth hormone deficiency (GHD) was diagnosed in 56, central hypothyroidism in 35, hypogonadotropic hypogonadism in 32 and central hypoadrenalism in 24 cases.

Results

Framingham score was higher and glucose and lipid profile were worse in PES patients than in controls. Cardiovascular risk parameters were not different between group A and B. In group B, increased cardiovascular risk was associated with hypothyroidism and hypogonadism, but not with GHD. In group A, cardiovascular risk was higher and FT3 and FT4 levels were lower than in controls. Moreover, PES patients stratified for BMI showed a worse glucose and lipid profile and (in the overweight subgroup) higher FS than matched controls.

Conclusions

Primary empty sella patients show increased cardiovascular risk, regardless of BMI. A worse lipid and glucose profile and higher FS were associated with secondary hypothyroidism, even subclinical, as well as hypogonadism.
Family group conferences: context, process and ways forward
Authors: Frost Nick , Abram Fiona , Burgess Hannah
Published: December 2012

This is the first part of a two‐part review of the literature, policy and practice relating to family group conferences (FGCs). This first paper explores the background, the global policy context, the theoretical foundations and the process of undertaking FGCs. The literature is extensive in relation to these elements of FGCs, unlike the limited literature relating to outcomes, which is examined in the second part of this review. In the subsequent review, we examine the issue of outcomes, research findings and explore future challenges in implementing FGCs.
Aspirin‐/TMZ‐coloaded Microspheres Exert Synergistic Antiglioma Efficacy via Inhibition of β‐catenin Transactivation
Authors: Shi Zhen‐Dong , Qian Xiao‐Min , Liu Chao‐Yong , Han Lei , Zhang Kai‐Liang , Chen Lu‐Yue , Zhang Jun‐Xia , Pu Pei‐Yu , Yuan Xu‐Bo , Kang Chun‐Sheng ,   Chinese Glioma Cooperative Group (CGCG)
Published: December 2012

Background and Aims

Currently temozolomide (TMZ) as a potent agent is widely used to treat the glioblastoma multiforme (GBM), whereas recurrence due to intrinsic or acquired therapeutic resistance often occurs. Combination chemotherapy with TMZ may be a promising therapeutic strategy to improve treatment efficacy.

Methods

Aspirin, TMZ, and aspirin‐/TMZ‐coloaded poly (L‐lactide‐co‐glycolide) (PLGA) microspheres were prepared by spray drying, and cytotoxicities of glioblastoma cells were measured.

Results

Aspirin microsphere treatment induced slight apoptosis and modestly inhibited proliferation of LN229 and U87 cells in vitro and in vivo through inhibition of β‐catenin transactivation. However, aspirin‐/TMZ‐coloaded microspheres presented synergistic antitumor efficacy compared with single TMZ‐loaded microspheres. Aspirin/TMZ microspheres induced more apoptosis and repressed proliferation of LN229 and U87 cells. Corresponding to inhibition of β‐catenin signaling, β‐catenin/TCF4 transcriptional activity and STAT3 luciferase activity were strongly suppressed, and downstream targets expression was decreased. Furthermore, aspirin/TMZ microsphere intratumoral injection downregulated the expression of β‐catenin, TCF4, pAKT, pSTAT3, and PCNA and delayed tumor growth in nude mice harboring subcutaneous LN229 xenografts.

Conclusions

Aspirin sensitized TMZ chemotherapy efficacy through inhibition of β‐catenin transactivation; furthermore, the coloaded microspheres achieved a sustained release action to reduce the TMZ dosage, offering the potential for improved treatment of glioblastomas.
A process for assessing the offsetability of biodiversity impacts
Authors: Pilgrim John D. , Brownlie Susie , Ekstrom Jonathan M. M. , Gardner Toby A. , von Hase Amrei , Kate Kerry ten , Savy Conrad E. , Stephens R. T. Theo , Temple Helen J. , Treweek Jo , Ussher Graham T. , Ward Gerri
Published: December 2012

Biodiversity offsetting is increasingly being used to reconcile the objectives of conservation and development. It is generally acknowledged that there are limits to the kinds of impacts on biodiversity that can or should be offset, yet there is a paucity of policy guidance as to what defines these limits and the relative difficulty of achieving a successful offset as such limits are approached. In order to improve the consistency and defensibility of development decisions involving offsets, and to improve offset design, we outline a general process for evaluating the relative offsetability of different impacts on biodiversity. This process culminates in a framework that establishes the burden of proof necessary to confirm the appropriateness and achievability of offsets, given varying levels of: conservation concern for affected biodiversity; residual impact magnitude; opportunity for suitable offsets; and feasibility of offset implementation in practice. Rankings for biodiversity conservation concern are drawn from existing conservation planning tools and approaches, including the IUCN Red List, Key Biodiversity Areas, and international bank environmental safeguard policies. We hope that the proposed process will stimulate much‐needed scientific and policy debate to improve the integrity and accountability of both regulated and voluntary biodiversity offsetting.
Sequestering carbon and restoring renosterveld through fallowing: a practical conservation approach for the Overberg, Cape Floristic Region, South Africa
Authors: Mills Anthony J. , Birch Sarah‐Jane C. , Stanway Rosanne , Huyser Onno , Chisholm Ryan A. , Sirami Clelia , Spear Dian
Published: December 2012

Carbon credits are a potential source of funding for restoration initiatives that contribute to achieving conservation targets in important biodiversity areas. Here we investigated whether fallowing sequesters carbon; a first step in assessing the viability of using carbon financing to promote restoration of threatened vegetation in agricultural landscapes. We used renosterveld, a critically endangered shrubland vegetation of the Cape Floristic Region, as a case study. Carbon stocks of soil and biomass in active fields, fallow fields and intact renosterveld were compared. The total carbon stocks measured in fallow fields (82 Mg C ha−1) show that fallowing can sequester carbon lost in the conversion from intact renosterveld (84 Mg C ha−1) to active fields (69 Mg C ha−1) and that revenues of US$ 10 – 48 ha−1 yr−1 from carbon credits could accrue. Our findings suggest that carbon financing could be used to incentivise ecological restoration in marginal agricultural landscapes.
Responders to insulin therapy at 18 months in adults with newly diagnosed diabetes: which insulin regimen?
Authors: Idris I. , Pillai A. , Fernando D. J. , Thomson G. , Tate H.
Published: December 2012

Objectives

To describe baseline characteristics of responders to insulin therapy (HbA1c targets < 58 mmol/mol, 7.5%) at 18 months among adults with newly diagnosed diabetes.

Methods

A retrospective UK study derived from 479 general practices electronic dataset. We included all adults (age > 18 years) with newly diagnosed diabetes who required insulin therapy within 6 months of diagnosis. The data comprised insulin regimen (long‐acting only; premixed insulin only; basal bolus insulin regimen), gender, Townsend quintile, baseline and an 18‐month measurement of clinical and biochemical variables. Multiple imputations were undertaken and logistic regression used to assess the effect of covariates.

Results

A total of 1492 patients (aged 19–93 years) were analysed. Means (SD) baseline HbA1c and BMI were 10.3% (2.6%) and 29.6 (7.0%), respectively. Following multiple imputation for missing data, logistic regression analysis indicated important covariates to achieve HbA1c targets were baseline HbA1c, lipid lowering therapy, gender and age. Including all covariates, those treated with premixed insulin were 47% more likely to achieve target HbA1c at 18 months than those treated with a basal‐bolus regimes (adjusted OR 1.47; 95% CI 1.12–1.92, P = 0.006)) and 32% more likely than those treated with long‐acting insulin was (adjusted OR 1.32; 95% CI 1.01–1.74, P = 0.044). Those with a higher baseline HbA1c level, on lipid‐lowering therapy, women and younger patients had a lower response rate. Mean weight gain (SD) was 2.4 kg (8.5 kg) and was not influenced by treatment regimen.

Conclusion

The use of premixed insulin regimen among newly diagnosed patients with diabetes appears to be most effective in reaching HbA1c target values, independent of other confounders. The appropriate choice of insulin regimen at initiation should therefore take into account various metabolic and psychosocial factors.
The effects of multidisciplinary rehabilitation in patients with early‐to‐middle‐stage Huntington's disease: a pilot study
Authors: Thompson J. A. , Cruickshank T. M. , Penailillo L. E. , Lee J. W. , Newton R. U. , Barker R. A. , Ziman M. R.
Published: December 2012

Background and purpose

Despite advances in the understanding of Huntington's disease (HD), treatment remains symptomatic. Multidisciplinary rehabilitation, however, appears to impact disease progression. Here we show the feasibility, safety and efficacy of a 9‐month multidisciplinary rehabilitation programme in a small cohort of patients with early‐to‐middle‐stage HD.

Methods

Twenty patients with HD were assigned to two groups, equally matched for cognitive and motor scores. One group received the intervention, whilst the other served as control. The Unified‐Huntington's‐Disease‐Rating‐Scale‐Total‐Motor‐Score was the primary outcome measure. Neurocognitive/psychological tests, body composition, postural stability, strength and quality of life assessments were secondary outcome measures.

Results

The intervention reduced motor and postural stability deterioration, with minor improvements in depression, cognition and quality of life. Significant gains were observed for fat‐free mass and strength.

Conclusion

This pilot study suggests that a prolonged multidisciplinary rehabilitation programme in early‐to‐middle‐stage HD is feasible, well‐tolerated and associated with therapeutic benefit. Further explorative, larger studies are warranted.
Do evolutionary life‐history trade‐offs influence prostate cancer risk? a review of population variation in testosterone levels and prostate cancer disparities
Authors: Alvarado Louis Calistro
Published: December 2012

An accumulation of evidence suggests that increased exposure to androgens is associated with prostate cancer risk. The unrestricted energy budget that is typical of Western diets represents a novel departure from the conditions in which men's steroid physiology evolved and is capable of supporting distinctly elevated testosterone levels. Although nutritional constraints likely underlie divergent patterns of testosterone secretion between Westernized and non‐Western men, considerable variability exists in men's testosterone levels and prostate cancer rates within Westernized populations. Here, I use evolutionary life history theory as a framework to examine prostate cancer risk. Life history theory posits trade‐offs between investment in early reproduction and long‐term survival. One corollary of life history theory is the ‘challenge hypothesis’, which predicts that males augment testosterone levels in response to intrasexual competition occurring within reproductive contexts. Understanding men's evolved steroid physiology may contribute toward understanding susceptibility to prostate cancer. Among well‐nourished populations of Westerners, men's testosterone levels already represent an outlier of cross‐cultural variation. I hypothesize that Westernized men in aggressive social environments, characterized by intense male–male competition, will further augment testosterone production aggravating prostate cancer risk.
The impact of insecticide resistance on Culex pipiens immunity
Authors: Vézilier Julien , Nicot Antoine , De Lorgeril Julien , Gandon Sylvain , Rivero Ana
Published: December 2012

Because of their role as vectors of diseases, the evolution of insecticide resistance in mosquitoes has been intensively investigated. Insecticide resistance is associated to a wide range of pleiotropic effects on several key life‐history traits of mosquitoes such as longevity and behavior. However, despite its potential implications in pathogen transmission, the effects of insecticide resistance on mosquito immunity have received little, if any, attention. Here, we investigate the impact of insecticide resistance in Culex pipiens, an epidemiologically important vector of a wide array of pathogens. Using both isogenic laboratory strains and field‐caught mosquitoes, we investigate the impact of two main insecticide resistance mechanisms (metabolic detoxification and target site modification) on the relative transcription of several genes involved in the immune response to pathogens, at both their constitutive and inducible levels. Our results show a discrepancy between the isogenic laboratory lines and field‐collected mosquitoes: While in the isogenic strains, insecticide‐resistant mosquitoes show a drastic increase in immune gene expression, no such effect appears in the field. We speculate on the different mechanisms that may underlie this discrepancy and discuss the risks of making inferences on the pleiotropic effects of insecticide‐resistant genes by using laboratory‐selected insecticide‐resistant lines.
Functional characterization of the galactan utilization system of Geobacillus stearothermophilus
Authors: Tabachnikov Orly , Shoham Yuval
Published: December 2012

Type I galactan is a pectic polysaccharide composed of β‐1,4 linked units of d‐galactose and is part of the main plant cell wall polysaccharides, which are the most abundant sources of renewable carbon in the biosphere. The thermophilic bacterium Geobacillus stearothermophilus T‐6 possesses an extensive system for the utilization of plant cell wall polysaccharides, including a 9.4‐kb gene cluster, ganREFGBA, which encodes galactan‐utilization elements. Based on enzyme activity assays, the ganEFGBA genes, which probably constitute an operon, are induced by short galactosaccharides but not by galactose. GanA is a glycoside hydrolase family 53 β‐1,4‐galactanase, active on high molecular weight galactan, producing galactotetraose as the main product. Homology modelling of the active site residues suggests that the enzyme can accommodate at least eight galactose molecules (at subsites −4 to +4) in the active site. GanB is a glycoside hydrolase family 42 β‐galactosidase capable of hydrolyzing short β‐1,4 galactosaccharides into galactose. Applying both GanA and GanB on galactan resulted in the full degradation of the polymer into galactose. The ganEFG genes encode an ATP‐binding cassette sugar transport system whose sugar‐binding lipoprotein, GanE, was shown to bind galacto‐oligosaccharides. The utilization of galactan by G. stearothermophilus involves the extracellular galactanase GanA cleaving galactan into galacto‐oligosaccharides that enter the cell via a specific transport system GanEFG. The galacto‐oligosaccharides are further degraded by the intracellular β‐galactosidase GanB into galactose, which is then metabolized into UDP‐glucose via the Leloir pathway by the galKET gene products.

Database

Nucleotide sequence data have been deposited in the GenBank database under the accession number JF327803.
Does COMT genotype influence the effects of d‐amphetamine on executive functioning?
Authors: Wardle M. C. , Hart A. B. , Palmer A. A. , de Wit H.
Published: December 2012

In a widely cited study, Mattay et al. reported that amphetamine (0.25 mg/kg oral, or 17 mg for a 68 kg individual) impaired behavioral and brain indices of executive functioning, measured using the Wisconsin Card Sorting Task (WCST) and N‐Back working memory task, in 6 individuals homozygous for the met allele of the val158met polymorphism in the catechol‐O‐methyltransferase (COMT) gene, whereas it improved executive functioning in 10 individuals homozygous for the more active val allele. We attempted to replicate their behavioral findings in a larger sample, using similar executive functioning tasks and a broader range of amphetamine doses. Over four sessions, n = 200 healthy normal adults received oral placebo, d‐amphetamine 5, 10, and 20 mg (average of 0.07, 0.15 and 0.29 mg/kg), under counterbalanced double‐blind conditions and completed WCST and N‐back tests of executive functioning. Amphetamine had typical effects on blood pressure and processing speed but did not affect executive functioning. COMT genotype (val158met) was not related to executive functioning under placebo or amphetamine conditions, even when we compared only the homozygous val/val and met/met genotypes at the highest dose of amphetamine (20 mg). Thus, we were not able to replicate the behavioral interaction between COMT and amphetamine seen in Mattay et al. We discuss possible differences between the studies and the implications of our findings for the use of COMT genotyping to predict clinical responses to dopaminergic drugs, and the use of intermediate phenotypes in genetic research.
Methane indicator values for peatlands: a comparison of species and functional groups
Authors: Gray Alan , Levy Peter E. , Cooper Mark D. A. , Jones Timothy , Gaiawyn Jenny , Leeson Sarah R. , Ward Susan E. , Dinsmore Kerry J. , Drewer Julia , Sheppard Lucy J. , Ostle Nick J. , Evans Chris D. , Burden Annette , Zieliński Piotr
Published: December 2012

Previous studies have shown a correspondence between the abundance of particular plant species and methane flux. Here, we apply multivariate analyses, and weighted averaging, to assess the suitability of vegetation composition as a predictor of methane flux. We developed a functional classification of the vegetation, in terms of a number of plant traits expected to influence methane production and transport, and compared this with a purely taxonomic classification at species level and higher. We applied weighted averaging and indirect and direct ordination approaches to six sites in the United Kingdom, and found good relationships between methane flux and vegetation composition (classified both taxonomically and functionally). Plant species and functional groups also showed meaningful responses to management and experimental treatments. In addition to the United Kingdom, we applied the functional group classification across different geographical regions (Canada and the Netherlands) to assess the generality of the method. Again, the relationship appeared good at the site level, suggesting some general applicability of the functional classification. The method seems to have the potential for incorporation into large‐scale (national) greenhouse gas accounting programmes (in relation to peatland condition/management) using vegetation mapping schemes. The results presented here strongly suggest that robust predictive models can be derived using plant species data (for use in national‐scale studies). For trans‐national‐scale studies, where the taxonomic assemblage of vegetation differs widely between study sites, a functional classification of plant species data provides an appropriate basis for predictive models of methane flux.
Developing competencies for medical librarians in Pakistan
Authors: Ullah Midrar , Anwar Mumtaz A.
Published: December 2012

Objective

To identify competencies for medical librarians and get these validated from head librarians and employers.

Methods

The survey method was used. A structured questionnaire, listing 84 competency statements, covering eight areas, prepared after extensive literature review, expert scrutiny and pilot testing, using a 5‐point Likert scale was distributed among the head librarians and chairpersons of library committees (CLC) in 115 medical libraries.

Results

Sixty seven (58%) useable responses were received from head librarians and 63 (55%) from CLC. Of the 84 competency statements 83 were validated by the head librarians, 44 receiving four or higher mean score while the other 39 statements getting mean scores in the range of 3.97 and 3.06. The CLC validated 80 statements. Only 27 statements received four or higher mean score from CLC while the other 53 got mean scores in the range of 3.97 and 3.22.

Conclusions

Medical librarians are required to be well versed with all those competencies which are needed for general librarianship. In addition, they are expected to have adequate knowledge of health sciences environment including medical terminologies and concepts. Sound knowledge of some competencies specific for medical libraries is an additional requirement for library personnel.
How reliable are Malaise traps for biomonitoring? – A bivariate species abundance model evaluation using alpine Chironomidae (Diptera)
Authors: Diserud Ola H. , Stur Elisabeth , Aagaard Kaare
Published: December 2012

In this study, the potential of Malaise traps to collect representative portions of an insect community was investigated. To do so, the complete catch (nearly 22 000 specimens) of male Chironomidae (Diptera) from five parallel Malaise traps along an alpine stream was identified and assigned to 108 different species. The traps were run for 4 weeks in June and July, 2008.

The similarity in community composition between parallel samples, that is, from different traps the same week, was evaluated by fitting a bivariate Poisson‐lognormal species abundance model. The estimated correlation in this bivariate distribution was used as a measure of similarity since this approach is utilising all the available species abundance information and accounts for the sampling process.

Estimated similarities showed non‐significant differences in chironomid community structure between parallel samples. The five Malaise traps sampled equally representative portions of the Chironomidae community present at the site, so the traps were found to be very reliable in the monitoring of Chironomidae community structure.

Application of the bivariate correlation as a similarity measure offers advantages over traditional measures because it takes account of the complete species abundance distributions. This approach provides an approximately unbiased estimate of similarity despite varying sample sizes and detection/non‐detection of species that are present, but rare.
Interleukin‐7 supports survival of T‐cell receptor‐β‐expressing CD4− CD8− double‐negative thymocytes
Authors: Xiong Juan , Parker Brooks L. , Dalheimer Stacy L. , Yankee Thomas M.
Published: December 2012

Among the milestones that occur during T‐cell development in the thymus is the expression of T‐cell receptor‐β (TCR‐β) and the formation of the pre‐TCR complex. Signals emanating from the pre‐TCR trigger survival, proliferation and differentiation of T‐cell precursors. Although the pre‐TCR is essential for these cell outcomes, other receptors, such as Notch and CXCR4, also contribute. Whether interleukin‐7 (IL‐7) participates in promoting the survival or proliferation of pre‐TCR‐expressing cells is controversial. We used in vitro and in vivo models of T‐cell development to examine the function of IL‐7 in TCR‐β‐expressing thymocytes. Culturing TCR‐β‐expressing CD4− CD8− double‐negative thymocytes in an in vitro model of T‐cell development revealed that IL‐7 reduced the frequency of CD4+ CD8+ double‐positive thymocytes at the time of harvest. The mechanism for this change in the percentage of double‐positive cells was that IL‐7 promoted the survival of thymocytes that had not yet differentiated. By preserving the double‐negative population, IL‐7 reduced the frequency of double‐positive thymocytes. Interleukin‐7 was not required for proliferation in the in vitro system. To follow this observation, we examined mice lacking CD127 (IL‐7Rα). In addition to the known effect of CD127 deficiency on T‐cell development before TCR‐β expression, CD127 deficiency also impaired the development of TCR‐β‐expressing double‐negative thymocytes. Specifically, we found that Bcl‐2 expression and cell cycle progression were reduced in TCR‐β‐expressing double‐negative thymocytes in mice lacking CD127. We conclude that IL‐7 continues to function after TCR‐β is expressed by promoting the survival of TCR‐β‐expressing double‐negative thymocytes.
Can liquefied debris flows deposit clean sand over large areas of sea floor? Field evidence from the Marnoso‐arenacea Formation, Italian Apennines
Authors: TALLING PETER J. , MALGESINI GIUSEPPE , FELLETTI FABRIZIO
Published: December 2012

The Marnoso‐arenacea Formation in the Italian Apennines is the only ancient rock sequence where individual submarine sediment density flow deposits have been mapped out in detail for over 100 km. Bed correlations provide new insight into how submarine flows deposit sand, because bed architecture and sandstone shape provide an independent test of depositional process models. This test is important because it can be difficult or impossible to infer depositional process unambiguously from characteristics seen at just one outcrop, especially for massive clean‐sandstone intervals whose origin has been controversial. Beds have three different types of geometries (facies tracts) in downflow oriented transects. Facies tracts 1 and 2 contain clean graded and ungraded massive sandstone deposited incrementally by turbidity currents, and these intervals taper relatively gradually downflow. Mud‐rich sand deposited by cohesive debris flow occurs in the distal part of Facies tract 2. Facies tract 3 contains clean sandstone with a distinctive swirly fabric formed by patches of coarser and better‐sorted grains that most likely records pervasive liquefaction. This type of clean sandstone can extend for up to 30 km before pinching out relatively abruptly. This abrupt pinch out suggests that this clean sand was deposited by debris flow. In some beds there are downflow transitions from turbidite sandstone into clean debrite sandstone, suggesting that debris flows formed by transformation from high‐density turbidity currents. However, outsize clasts in one particular debrite are too large and dense to have been carried by an initial turbidity current, suggesting that this debris flow ran out for at least 15 km. Field data indicate that liquefied debris flows can sometimes deposit clean sand over large (10 to 30 km) expanses of sea floor, and that these clean debrite sand layers can terminate abruptly.
Intermediate/borderline disseminated cutaneous leishmaniasis
Authors: Paniz Mondolfi Alberto E. , Duffey Gabrielle Baker , Horton Lucy E. , Tirado Mariantonieta , Reyes Jaimes Oscar , Perez‐Alvarez Alexandra , Zerpa Olga
Published: December 2012

Leishmaniasis is a diverse group of vector‐borne diseases caused by a subset of predominantly intracellular protozoal species of the genus Leishmania. Cutaneous disease may be subdivided into localized, intermediate, and diffuse forms. Intermediate cutaneous leishmaniasis is distributed widely in Latin America and is characterized by cutaneous lesions, which may be accompanied by mucosal disease and demonstrate a tendency toward chronicity and relapse as well as resistance to standard treatment regimens. Leishmania parasites of the subgenus Viannia have been identified as the major etiologic agent of this subset of infections. The present review provides a brief perspective on leishmaniasis followed by a review of classification, transmission, clinical presentation, and evolution of disease, immunology, and current treatment approaches for the intermediate/borderline disseminated subset of cutaneous leishmaniasis.
The −2T/C polymorphism in the adrenocorticotropin receptor gene affects stress perception of patients with alopecia areata
Authors: Guo Hong‐Wei , Guo Hong , Li Ke‐Shen , Wu Jiang , Yang Shao‐Yan , Liu Bao‐Heng , Hao Fei , Bai Yun
Published: December 2012

Background

Altered hypothalamic–pituitary–adrenal (HPA) axis response involved in the pathogenesis of stress‐associated alopecia areata (AA) has been reported. A novel polymorphism −2T>C of the adrenocorticotropin receptor (ACTHR) can result in an insufficient HPA response to stress; therefore, the functional polymorphism may underlie a role in stress‐associated AA.

Objective

To investigate the relationship between psychosocial factors and the risk of developing AA and to detect the association between the −2T>C polymorphism of ACTHR and AA.

Methods

Stressful situations were evaluated using Holmes and Rahe's social readjustment rating scale. The ACTHR −2T>C polymorphism was examined in 263 patients with AA and 241 controls.

Results

Significant elevation of psychological stress experienced by some patients with AA compared with controls (Z = 6.628, P < 0.01). The frequency of the ACTHR C allele showed a significant difference between patients with AA and controls (P = 0.004). Allele C is the risk allele with a dominant model as the −2C allele occurred more often in patients with AA (P = 0.001). There were significant differences between patients with AA with a severe stress attack versus patients with AA with no obvious stress (P < 0.001), whereas the genotype frequencies were not correlated with the type, duration of disease, and age at onset. Notably, the C allele carrier was significantly associated with stress risk in both AA and controls (P = 0.002, OR = 1.576, 95% CI: 1.148–2.162; P = 0.042, OR = 1.529, 95% CI: 1.022–2.288).

Conclusions

These findings suggest AA in some patients may be associated with stress. The ACTHR gene −2T>C variant may be one important factor that influences stress perception of patients with AA.
The Italian Euromelanoma Day: evaluation of results and implications for future prevention campaigns
Authors: Suppa Mariano , Altomare Gianfranco , Cannavò Serafinella P. , Capizzi Rodolfo , Catricalà Caterina , Colombo Enrico , Fargnoli Maria C. , Fossati Barbara , Frascione Pasquale , Lisi Paolo , Santini Marcello , Scalvenzi Massimiliano , Peris Ketty
Published: December 2012

Background

Melanoma incidence/mortality is increasing worldwide. “Euromelanoma Day” is a pan‐European campaign for skin cancer prevention. Results of the 2010 Euromelanoma Day in Italy are reported herein.

Materials and methods

A questionnaire was used to collect data on participants' characteristics and suspected skin cancers.

Result

A total of 1085 participants was screened (64.1% females, median age 44 years). Suspicion rate, detection rate, and positive predictive values for melanoma were 1.3, 0.28 and 21.4%, respectively. Poorly educated, ≥35 years old, pale‐skinned males were at higher risk for skin cancer than highly educated, <35 years old, darker‐skinned females, although the latter groups reported sun‐seeking behaviors. Full skin examination and dermoscopy were performed in 85.5 and 79.2% of participants.

Conclusions

The 2010 Italian Euromelanoma Day produced good results in terms of melanoma detection/suspicion rates, likely due to the extensive use of full clinical and dermoscopic examinations. The campaign failed to attract many high‐risk individuals. Targeted communication strategies are needed to this regard.
Cytomegalovirus disease in African‐American kidney transplant patients
Authors: McGee J. , Mave V. , Yau C.L. , Killackey M. , Paramesh A. , Buell J. , Slakey D.P. , Hamm L.L. , Zhang R.
Published: December 2012

Background

Cytomegalovirus (CMV) disease is a serious infection after kidney transplantation. The risk factors and the impact of CMV disease in African‐American (AA) kidney transplant patients have not been well characterized.

Methods

We performed a retrospective analysis on 448 AA patients transplanted between 1996 and 2005. A 3‐month universal chemoprophylaxis with ganciclovir or valganciclovir was administered to CMV donor‐positive/recipient‐negative (D+/R−) patients and to those treated with anti‐thymocyte globulin for rejection, but not routinely to those with other D/R serostatus.

Results

A total of 31 AA patients (7%) developed clinical CMV disease. Compared with other D/R serostatus groups, the D+/R− group had the highest 3‐year cumulative incidence of CMV disease (16.9% vs. 6.3% in D+/R+, 4.9% in D−/R+, and 2.4% in D−/R−). The D+/R− group also had the worst 3‐year death‐censored allograft survival (75% vs. 92% in D+/R+, 94% in D−/R+, and 96% in D−/R−, log‐rank P = 0.01). Multivariate analysis found that D+/R− serostatus (odds ratio [OR] 5.4, 95% confidence interval [CI] 0.6–48.2, P = 0.003) and donor age > 60 years (OR 9.1, 95% CI 1.3–65, P = 0.03) were independent risk factors for CMV disease.

Conclusion

The D+/R− group has the highest incidence of CMV disease and the worst 3‐year renal allograft survival despite 3‐month universal prophylaxis. Prolonged chemoprophylaxis may be needed to prevent the late development of CMV disease and to improve allograft survival in the high‐risk group of AA kidney transplant recipients.
Housing Supply, Demand and Price: Construction Cost, Rental Price and House Price Indices
Authors: Tsai I‐Chun
Published: December 2012

Housing prices are subject to the impacts of supply as well as demand. While supply is affected by construction costs, demand is determined by the renting/buying considerations of the public. As a result, the construction cost index (CCI) on the supply side and the rental price index (RPI) on the demand side should be closely related to the house price index (HPI). The present study adopts three price indices of the Taiwan housing market, the CCI, the RPI and the HPI, and examines long‐term and short‐term correlations among the three indices. Empirical results indicate that the relationships among three indices are nonlinear. More interestingly, this article finds that the HPI stimulates changes in the CCI and the RPI, although construction costs and rent are viewed as fundamentals in the existing literature. This phenomenon is rather obvious when deviations of the latter two indices from the HPI are greater. The corrective behavior of the HPI is more notable under these circumstances.
Firm Efficiency in Cambodia's Garment Industry on the Eve of the Multi‐Fiber Arrangement Termination
Authors: Vixathep Souksavanh , Matsunaga Nobuaki
Published: December 2012

Applying a frontier analysis to 2004 firm‐level data, the present paper investigates firm efficiency and its determinants for Cambodia's garment industry. The study finds that firm experience and remuneration are crucial for improving scale efficiency and overall technical efficiency, while effective use of capital and adequate labor‐skill development are important for enhancing a firm's technical capabilities. Foreign‐owned enterprises with a relatively larger share of foreign labor outperform local firms. However, the present study does not reveal evidence of any advantages of a cluster‐type concentration in Phnom Penh and export markets, nor of any positive impacts of product specialization. The findings imply a need to support skill development for workers and local managers at the middle management level, and to streamline foreign direct investment measures to attract greater numbers of efficient foreign enterprises, so as to promote the development of the garment industry as a whole.
A process for the development and application of simulation models in applied economics
Authors: Doole Graeme J. , Pannell David J.
Published: December 2012

Simulation models are widely used in applied economics to improve understanding of how a system could behave under different conditions. However, the potential degree to which such models can influence decision making depends on their ability to provide an adequate description of the important elements of a given problem. A systematic and robust procedure for the development and application of such models in agricultural, ecological, environmental and natural resource economics is presented. This process is based on the authors’ experience across a broad range of model types and applications and extensive literature review. The practical impact of simulation models is argued to be greater where stakeholders and technical experts are consulted extensively throughout the modelling process.
Rapid diagnostic method for discriminating two types of COI sequences in the gall‐forming aphid Tetraneura nigriabdominalis (Hemiptera: Aphididae) by multiplex polymerase chain reaction
Authors: Lee Wonhoon , Otsuki Akiko , Akimoto Shin‐ichi
Published: December 2012

Tetraneura nigriabdominalis (Sasaki, 1899) is a galling aphid that is distributed widely in Eurasia. In the present study, a diagnostic multiplex polymerase chain reaction (PCR) protocol was developed to discriminate two types of the cytochrome oxidase subunit I (COI) sequences in this species, and its usefulness was examined from 25 samples of T. nigriabdominalis. Multiplex PCR and electrophoresis revealed that 10 and 15 samples had one band of 133 bp (type A) and 426 bp (type B), respectively. This discrimination was identical to the division of the 25 samples based on the alignments of COI sequences (511 bp), indicating high accuracy of this protocol in distinguishing the two types. This protocol is useful for studying microgeographic distributions of the two types and genetic diversities in T. nigriabdominalis.