bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitrification of Bovine Blastocysts Produced In Vitro Inflicts Selective Damage to the Inner Cell Mass
Authors: Gómez E , Muñoz M , Rodríguez A , Caamaño JN , Facal N , Díez C
Published: October 2008

Contents

In contrast to the embryos derived from live animals, the embryos produced in vitro undergo increased damage and reduced survival after cryopreservation, particularly when produced with serum. In medium containing serum, retinoic acid increases cell numbers in the inner cell mass and the trophectoderm without altering their relative proportions in the bovine blastocyst. In this work, in medium without serum, we analyzed the contribution of retinoic acid to the development of blastocyst and survival to vitrification, and found a strong cell reduction in the inner mass when compared to the trophectoderm. Day‐6 in vitro‐produced morulae were treated for 24 h with retinoic acid (0.7 and 1.4 μm) and subsequently cultured without additives for a further 24 h period. Day‐8 blastocyst production and cell counts in hatched blastocysts were unaffected by retinoic acid. However, Day‐7 expanded, vitrified embryos produced with retinoic acid 1.4 μm survived at lower rates than controls when cultured after warming. Vitrification greatly reduced cell numbers in the inner mass (p < 0.0001), while cells in the trophectoderm remained unaltered. Differential cell counts analysis in blastocysts should be taken up to replace unspecific determination of total cells to appreciate substantial modifications in their exact terms. The strong reduction we found in the inner cell mass could explain why in vitro survival to cryopreservation is sometimes scarcely informative on the viability of the embryo after transfer to recipients.
Primary Unilateral Fibroleiomyoma of the Ovary in a Pregnant Mare: A Case Report
Authors: Carstanjen B , Schönert S , Heblinski N , Gruber AD
Published: October 2008

Contents

Fibroleiomyomas of the ovary are rare. This smooth muscle tumour may develop and increase in size during pregnancy. Diagnosis is based on histological and immunohistochemical analyses. Histologically, the ovarian fibroleiomyoma consists of non‐invasive bundles of smooth muscle cells that synthesize collagen‐like extracellular matrix. This case report describes an ovarian fibroleiomyoma in a pregnant multiparous broodmare with a history of intermittent signs of colic.
Cervical Hypoplasia in Jennets: A Description of Two Cases
Authors: Payan‐Carreira R , Quaresma M
Published: October 2008

Contents

The authors describe two cases of cervical hypoplasia in jennets, detected during the gynaecological evaluation of two purebred females of the Portuguese donkey breed Asinina de Miranda. These jennets aged 10 and 15 years were referred for consultation by the local breeders association because of infertility detected during an artificial breeding programme. In both jennets the cervix was small, shorter than the usual and closed. In one of the females, outflow of semen during artificial insemination was reported. Clinical and ultrasonographic evaluation of the genital tract demonstrated that both ovaries were normally sized in both animals and presenting structures suggestive of regular ovarian activity. In one of the jennets, a small amount of air in the uterus was evidenced. In the other, signs indicative of atresia of the cervical canal were found. Vaginal examination showed that the cervix was reduced in size and shallowed in both animals. A diagnosis of congenital cervical hypoplasia was made in both cases and the animals were excluded from reproduction.
The burden of lung disease in Hong Kong: A report from the Hong Kong Thoracic Society
Authors: CHAN‐YEUNG Moira , LAI Christopher K.W. , CHAN Kin‐Sang , CHEUNG Amy H.K. , YAO Tzy‐Jyun , HO Alice S.S. , KO Fanny W. , YAM Loretta Y. , WONG Poon‐Chuen , TSANG Kenneth W. , LAM Wah‐Kit , HO James C. , CHU Chung‐Ming , YU Wai‐Cho , CHAN Hok‐Sum , IP Mary S.M. , HUI David S. , TAM Cheuk‐Yin
Published: October 2008

Background and objective:  The burden of lung disease in Hong Kong is not known. This study determined the mortality and hospitalization rates of respiratory diseases in Hong Kong in 2005, their trend in the past decade and their incidence/prevalence.

Methods:  Mortality data were obtained from the Department of Health and hospitalization data from the Hospital Authority, Hong Kong. Incidence/prevalence data were obtained from local registries or local studies. Trends of mortality and hospitalization rates of various respiratory diseases from 1997 and 2005 were calculated after age standardization and were tested for significance using negative binomial regression analysis. Age standardized mortality rates in Hong Kong were compared with those of the UK and globally.

Results:  Respiratory disease was the most common cause of mortality and hospitalization in Hong Kong in 2005. Globally and in the UK, cardiovascular disease ranked first in mortality. Respiratory infections ranked first in respiratory mortality, followed by respiratory tract cancer and chronic obstructive lung disease. Respiratory infections also ranked first followed by chronic obstructive lung disease in the utilization of respiratory inpatient bed‐days. While mortality rates from all respiratory diseases decreased in the past decade, hospitalization rates remained unchanged. Unlike other respiratory diseases, mortality from respiratory infections have increased since 2001. Smoking is the most important risk factor in non‐communicable respiratory diseases.

Conclusions:  Respiratory disease is responsible for the highest health‐care burden locally. Increased efforts in improving management and prevention of these diseases, including tobacco control, improving air quality and vaccination against influenza and pneumococci, are necessary.
Hypocretin /orexin preferentially activates caudomedial ventral tegmental area dopamine neurons
Authors: Vittoz Nicole M. , Schmeichel Brooke , Berridge Craig W.
Published: October 2008

The hypocretin/orexin (HCRT) neuropeptide system modulates behavioral state and state‐dependent processes via actions on multiple neuromodulatory transmitter systems. Recent studies indicate that HCRT selectively increases dopamine (DA) neurotransmission within the prefrontal cortex (PFC) and the shell subregion of the nucleus accumbens (NAs), but not the core subregion of the nucleus accumbens (NAc). The circuitry underlying the differential actions of HCRT across distinct DA systems is unclear. The current study examined whether HCRT preferentially activates PFC‐ and NAs‐projecting relative to NAc‐projecting DA neurons within the VTA. One week after infusion of the retrograde tracer fluorogold (FG) into the medial PFC, NAc or NAs, animals received a ventricular infusion of HCRT‐1. Subsequent analyses conducted across the rostral‐caudal extent of the VTA determined the degree to which: (i) Fos‐immunoreactivity (ir) was observed within tyrosine hydroxylase (TH)‐ir neurons; (ii) TH‐ir was observed within FG‐ir neurons; and (iii) Fos‐ir was observed within FG‐ir neurons. HCRT significantly increased Fos‐ir in VTA DA (TH‐ir) neurons, primarily in a restricted population of small‐to‐medium‐sized DA neurons located within the caudomedial VTA. Furthermore, within this region of the VTA, PFC‐ and NAs‐projecting TH‐ir neurons were more likely to contain Fos‐ir than were NAc‐projecting TH‐ir neurons. These results provide novel evidence that HCRT selectively activates PFC‐ and NAs‐projecting DA neurons within the VTA, and suggest a potential role for HCRT in PFC‐ and NAs‐dependent cognitive and/or affective processes. Moreover, these and other observations suggest that the dysregulation of HCRT–DA interactions could contribute to cognitive/affective dysfunction associated with a variety of behavioral disorders.
The past, present and future of cystoscopy: the fusion of cystoscopy and novel imaging technology
Authors: Lee Christopher S.D. , Yoon Cheol Yong , Witjes J. Alfred
Published: October 2008

Non‐muscle‐invasive bladder cancer is a frequent disease with many recurrences, making it a labour‐intensive and costly disease. In part, these frequent recurrences are due to inadequate diagnosis. Diagnostic reference standards to date are urinary cytology and cysto‐urethroscopy, but both standards have significant limitations. Urinary cytology is specific, but the sensitivity, especially for low‐grade tumours, is very low. Moreover, the reproducibility of cytology is low. However, cysto‐urethroscopy misses many tumours, especially flat carcinoma in situ, causing flaws in the initial diagnosis and treatment, i.e. transurethral resection. Therefore, new techniques are necessary to improve the detection of bladder cancer. Here we review the advantage and disadvantage of conventional white‐light and fluorescence‐based cystoscopy, and discuss novel endoscopic imaging techniques that are in the clinical and preclinical stage of development.
Continent cutaneous diversion
Authors: Fisch Margit , Thüroff Joachim W.
Published: October 2008

Continent urinary diversion requires the creation of a reservoir, ureteric implantation and establishment of a continence mechanism in the efferent segment. This review is a short overview on the history of different techniques in current use. Reservoirs with high volume and low pressure can be fashioned by antimesenteric opening and spherical reconfiguration of the bowel. Previously, techniques for ureteric implantation were simply transferred to continent urinary diversion. Currently the need for antirefluxive ureteric implantation techniques is questioned and there is a trend towards refluxive implantation. To create a continence mechanism, simple and reproducible procedures. e.g. the incorporation of the efferent segment into the pouch wall (e.g. appendix stoma, flap valve T mechanism, serosal‐lined extramural tunnel) have been developed. Long‐term data for different surgical techniques show excellent continence and acceptable complication rates.
Treatment of metastatic urothelial cancer: opportunities for drug discovery and development
Authors: Sonpavde Guru , Sternberg Cora N.
Published: October 2008

Conventional first‐line platinum‐based combination chemotherapy with gemcitabine/cisplatin and standard or dose‐dense methotrexate, vinblastine, doxorubicin and cisplatin yields high response rates but suboptimal long‐term outcomes for advanced urothelial cancer. Salvage therapy is an unmet need, with disappointing outcomes. The emergence of novel biological agents offers the promise of improved outcomes. Neoadjuvant therapy preceding cystectomy for muscle‐invasive bladder cancer provides an important paradigm and an interesting approach in developing novel agents. Patients who are not candidates for cisplatin require special attention. A multidisciplinary approach and collaboration among laboratory scientists, oncologists, urologists and radiation oncologists is necessary to make therapeutic advances. Recent and ongoing trials of novel chemotherapeutic and biological agents are reviewed.
The economic impact of overactive bladder syndrome in six Western countries
Authors: Irwin Debra E. , Mungapen Laura , Milsom Ian , Kopp Zoe , Reeves Penny , Kelleher Con
Published: October 2008

OBJECTIVE

To calculate up‐to‐date estimates of the economic impact of overactive bladder syndrome (OAB) with and without urgency urinary incontinence (UUI) on the health sector of six countries (Canada, Germany, Italy, Spain, Sweden and the UK), as OAB is a significant health concern for adults aged >18 years living in Western countries.

MATERIALS AND METHODS

The prevalence data derived from the EPIC study were combined with healthcare resource‐use data to derive current direct and indirect 1‐year or annual cost of illness estimates for OAB including UUI in Canada, Germany, Italy, Spain, Sweden and the UK. This model estimates the direct healthcare costs attributed to OAB, as well as the impact of work absenteeism.

RESULTS

The estimated average annual direct cost of OAB per patient ranged between €262 in Spain and €619 in Sweden. The estimated total direct cost burden for OAB per country ranges between €333 million in Sweden and €1.2 billion in Germany and the total annual direct cost burden of OAB in these six countries is estimated at €3.9 billion. In addition, nursing home costs were estimated at €4.7 billion per year and it was estimated that work absenteeism related to OAB costs €1.1 billion per year.

CONCLUSIONS

The cost of illness for OAB is a substantial economic and human burden. This study may under‐estimate the true economic burden, as not all costs for sequelae associated with OAB have been included. Cost‐effective treatments and management strategies that can reduce the burden of OAB and in particular UUI have the potential to significantly reduce this economic burden.
Sex differences in past tense overregularization
Authors: Kidd Evan , Lum Jarrad A.G.
Published: October 2008

Hartshorne and Ullman (2006

) presented naturalistic language data from 25 children (15 boys, 10 girls) and showed that girls produced more past tense overregularization errors than did boys. In particular, girls were more likely to overregularize irregular verbs whose stems share phonological similarities with regular verbs. It was argued that the result supported the Declarative/Procedural model of language, a neuropsychological analogue of the dual‐route approach to language. In the current study we present experimental data that are inconsistent with these naturalistic data. Eighty children (40 males, 40 females) aged 5;0–6;9 completed a past tense elicitation task, a test of declarative memory, and a test of non‐verbal intelligence. The results revealed no sex differences on any of the measures. Instead, the best predictors of overregularization rates were item‐level features of the test verbs. We discuss the results within the context of dual versus single route debate on past tense acquisition.
Biological and environmental initial conditions shape the trajectories of cognitive and social‐emotional development across the first years of life
Authors: Feldman Ruth , Eidelman Arthur I.
Published: October 2008

Human development is thought to evolve from the dynamic interchange of biological dispositions and environmental provisions; yet the effects of specific biological and environmental birth conditions on the trajectories of cognitive and social‐emotional growth have rarely been studied. We observed 126 children at six time‐points from birth to 5 years. Intelligence, maternal sensitivity, and child social engagement were repeatedly tested. Effects of neonatal vagal tone (VT) and maternal postpartum depressive symptoms on growth‐rates were assessed. Cognitive development showed a substantial growth‐spurt between 2 and 5 years and social engagement increased rapidly across the first year and more gradually thereafter. VT improved cognitive and social‐emotional growth‐rates across the first year, whereas maternal depressive symptoms interfered with growth from 2 to 5 years. Differences between infants with none, one, or two non‐optimal birth conditions increased with age. Findings shed light on the dynamics of early development as it is shaped by biological and environmental initial conditions.
Governance Regimes and Nationality Diversity in Corporate Boards: A Comparative Study of Germany, the Netherlands and the United Kingdom
Authors: Van Veen Kees , Elbertsen Janine
Published: October 2008

Manuscript Type:Empirical

Research Question:In this study, the level of nationality diversity of a corporate board is seen as directly dependent on the governance regime of the country of origin of the company. Therefore, to what extent can differences in nationality diversity in corporate boards be explained by structural differences in governance regimes in different countries?

Research Findings:A number of hypotheses about the level of nationality diversity in company boards in Germany, the Netherlands, and the UK have been derived. These have been tested and confirmed to a large extent. Governance regime effects are strong, even when controlled for the most relevant company effects.

Theoretical Implications:For the first time, the explanation of nationality diversity has been directly connected to the characteristics of a country's governance regime. Additionally, the relative strength of competing country and company forces was discussed and tested.

Policy Implications:This study shows how the increase in the diversity of nationalities on corporate boards, as result of global economic forces, are translated through national institutions. On a company level, this implies that the governance regime of a company's country of origin might be either an asset or a liability. It also shows the importance of national‐level institutions when it comes to the ways global economic forces exercise a differentiating effect on the board composition of large multinational enterprises.
The Influence of Qualified Foreign Institutional Investors on the Association between Default Risk and Audit Opinions: Evidence from the Chinese Stock Market
Authors: Ting Wei , Yen Sin‐Hui , Chiu Chien‐Liang
Published: October 2008

Manuscript Type: Empirical

Research Question/Issue: Numerous studies demonstrate that audit opinions provide strong signals to investors/debt holders warning of firms’ default probability. When foreign investors were allowed to enter the Chinese stock market, the role of audit opinions grew in importance. In this study, we examine the relationships between audit opinions and default probability within the Chinese stock market, and explore whether there was any significant shift in this relationship following the entry of Qualified Foreign Institutional Investors (QFIIs).

Research Findings/Insights: We find that audit opinions began providing signals of potential default risk only after QFIIs entered the market; suggesting that in the post‐December 2002 period, auditors’ decisions in China became more conservative, and that institutional investors began to play a monitoring role.

Theoretical/Academic Implications: This study provides support for institutional theory through the provision of empirical evidence showing that audit opinions, as signals of potential default risk, may actually be less efficient in immature markets than in more mature markets. Furthermore, the role of audit opinions in providing such signals to outside investors can clearly be affected by the introduction of new monitoring mechanisms. The results imply that market maturity could prompt firms to provide more accurate information.

Practitioner/Policy Implications: The strengthening of security laws could increase confidence among investors in China, thereby providing evidence to market participants showing that the more accurate information and greater efficiency of audit opinions, arising as a direct result of the entry of QFIIs, could lead to expansion of the Chinese investment environment.
Corporate Governance and Corporate Social Responsibility Synergies and Interrelationships
Authors: Jamali Dima , Safieddine Asem M. , Rabbath Myriam
Published: October 2008

Manuscript Type: Empirical

Research Questions/Issue: This paper seeks to explore the interrelationships between corporate governance (CG) and corporate social responsibility (CSR): first, theoretically, by reviewing the literature and surveying various postulations on offer; second, empirically, by investigating the conception and interpretation of this relationship in the context of a sample of firms operating in Lebanon. Accordingly, the paper seeks to highlight the increasing cross‐connects or interfaces between CG and CSR, capitalizing on fresh insights from a developing country perspective.

Research Findings/Results: A qualitative interpretive research methodology was adopted, drawing on in‐depth interviews with the top managers of eight corporations operating in Lebanon, with the findings suggesting that the majority of managers conceive of CG as a necessary pillar for sustainable CSR. These findings are significant and interesting, implying that recent preoccupation with CG in developing countries is starting to be counterbalanced by some interest/attention to CSR, with growing appreciation of their interdependencies and the need to move beyond CG conformance toward voluntary CSR performance.

Theoretical Implications: This study makes two important contributions. First, it suggests that there is a salient two‐way relationship and increasing overlap between CG and CSR. While much previous literature has researched CG and CSR independently, this paper makes the case for considering them jointly and systematically. Second, the paper outlines a number of theoretical propositions that can serve as the basis for future research on the topic, particularly in developing countries, given that the data and theoretical propositions are both derived from and tailored to developing country contexts.

Practical Implications: This study can potentially alert managers to the increasing overlap between the CG and CSR agendas and the need to exert diligent systematic efforts on both fronts. CG and CSR share more in common than previously assumed, and this needs to be accounted for by practitioners. The research can also alert policy makers in developing countries to the need to increase the vigilance and capacity of the regulatory and judicial systems in the context of CG reform and to increase institutional pressures, particularly of the coercive and normative variety to enhance CSR adoption.
Beyond Dichotomy: The Curvilinear Impact of Employee Ownership on Firm Performance
Authors: Guedri Zied , Hollandts Xavier
Published: October 2008

Manuscript type: Empirical

Research Question/Issue: This study examines the impact of employee stock ownership and board employee representation on firm performance.

Research Findings/Results: Results drawn from a longitudinal analysis of a sample of 230 French firms over the period 2000–2005 provide support for an inverted U‐shaped relationship between employee ownership and accounting‐based performance measures. However, this relationship is not supported when a market‐based performance measure is used. We also found that the inflection point of the inverted U‐shaped relationship between employee ownership and firm performance does not depend upon the level of employee representation on the board.

Theoretical Implications: This study addresses the inconsistency of results found so far in the literature examining the performance implications of employee ownership by proposing a theoretical framework and providing empirical support for the hypothesis suggesting that the relationship between employee ownership and firm performance is not linear, but indeed, has an inverted U‐shape.

Practical Implications: In a governance context characterized by a spectacular increase in employee ownership fostered by a pervasive support from both managers and government, our results suggest that performance implications of employee ownership are positive up to a certain point, after which the marginal effect of employee ownership on firm performance becomes negative. As a result, our findings suggest that managers and shareholders should be careful when launching and increasing the level of employee ownership to not go beyond specific inflection points.
Math Performance in Stressful Situations
Authors: Beilock Sian L.
Published: October 2008

Whether because individuals are made aware of negative stereotypes about how they should perform or are in a high-stakes testing situation, a stressful environment can adversely affect the success people have in solving math problems. I review work examining how unwanted failure in math occurs and individual differences in those most likely to fail. This work suggests that a high-stress situation creates worries about the situation and its consequences that compete for the working memory (WM) normally available for performance. Consequently, the performance of individuals who rely most heavily on WM for successful execution (i.e., higher-WM individuals) is most likely to decline when the pressure is on.
‘On MSN with buff boys’: Self‐ and other‐identity claims in the context of small stories1
Authors: Georgakopoulou Alexandra
Published: October 2008

This is a study of self‐ and other‐identity claims such as ascriptions, assessments and categorizations in the classroom interactional data of female adolescent students of a London comprehensive school. The study follows an identities‐in‐interaction approach and attends to the occurrence of identity claims in stories of recent mediated interactions (e.g. on MSN, by text) between tellers and male suitors, which I collectively call small stories. In a narrative‐interactional analysis of such claims in two small stories, I postulate a distinction between taleworld and telling identity claims that allows me to show how the sequential context of the claims has implications for their interactional uptake. I specifically focus on the relational organization of the identity claims in contrastive pairs of positive and negative attributes and on their contribution to the stories' tellership rights and tellability. My main aim is to show how identity claims can be intimately linked with and discursively invoke solidified roles (cf. known, habitual) that hold above and beyond the local context. I argue that the three interactional features of iterativity, narrativity and stylization hold the key to uncovering the links between identity claims with solidified roles.
Prosodic cues of identity construction: Intensity in Greek young women's conversational narratives1
Authors: Archakis Argiris , Papazachariou Dimitris
Published: October 2008

The present paper examines the discourse functions of intensity in the context of narrative direct speech quotations. We argue that differentiation in intensity functions as a contextualization cue signalling involvement as well as power negotiation. Intensity, therefore, seems to be an ambivalent signal acquiring its meaning in interaction with other contextual parameters. More specifically, we argue that a louder voice is preferred in in‐group talk representations as a contextualization cue of a high involvement style in conversations between intimate young peers. Lower intensity, on the other hand, is used by young female narrators in the representation of talk with authority‐out‐group figures, as a means of reducing the authority of the adult voices represented in their narratives. The qualitative analysis of our data is further supported by quantitative analysis. We conclude that intensity differentiation in the direct speech quotations of young female narrators functions as a contextualization cue signalling, on the one hand, their independence from adult authority and, on the other, their in‐group bonds.
‘Taking advantage’ or fleeing persecution? Opposing accounts of asylum seeking
Authors: Every Danielle , Augoustinos Martha
Published: October 2008

This paper discursively analyses advocates' explanations of asylum seeking in the 2001 Australian parliamentary debates. Previous research has mapped the negative discourses used to present asylum seekers as economic migrants ‘taking advantage’ of soft laws. This paper analyses how advocates oppose this rhetoric, re‐categorising asylum seekers as potential refugees, and establishing Australia as legally and morally responsible for providing protection. This paper examines three influences shaping advocates' arguments: opposing anti‐asylum seeker rhetoric; theories of the formation of anti‐asylum seeker public opinion; and the parliamentary and wider liberal democratic intellectual political framework. It then analyses four extracts taken from political speeches in the parliament, focussing on the rhetorical strategies used to counter a pervasive ‘culture of disbelief’ against asylum seekers.
MONETARY AND FISCAL INTERACTIONS: SHORT‐RUN AND LONG‐RUN IMPLICATIONS
Authors: Isaac Alan G.
Published: October 2008

We model policy interactions in a growing economy. Unemployment can persist and matters for the real wage; conflicting claims underpin inflation outcomes; and aggregate demand determines capacity utilization and unemployment. Monetary policy is characterized by a Taylor rule. Fiscal policy is characterized by a marginal tendency to run deficits or surpluses. We address three questions: can monetary policy ensure macroeconomic stability in the absence of coordinated fiscal policy, can fiscal policy ensure macroeconomic stability when the monetary authority pegs the interest rate, and can policy authorities trade‐off some sustained inflation for a long‐run improvement in unemployment rates?
The Performance of Characteristics‐based Indices1
Authors: Amenc Noël , Goltz Felix , Le Sourd Véronique
Published: October 2008

This paper analyses a set of characteristics‐based indices that, it has been argued, outperform market cap‐weighted indices. We analyse the performance of an exhaustive list of these indices and show that i) the outperformance over value‐weighted indices may be negative over long time periods, and ii) there is no significant outperformance over equal‐weighted indices. An analysis of the style and sector exposures of characteristics‐based indices reveals a significant value tilt. When this tilt is properly adjusted for, the abnormal returns of these indices decrease considerably. Moreover, it is straightforward to construct portfolios with higher Sharpe ratios than characteristics‐based indices through factor or sector tilts.
Do Inflation‐Linked Bonds Still Diversify?
Authors: Brière Marie , Signori Ombretta
Published: October 2008

The diversifying power of inflation‐linked (IL) bonds relative to traditional asset classes has changed significantly. In this paper, we study the dynamics of conditional volatilities and correlations for three asset classes, IL bonds, nominal bonds and equities, in the USA and Europe. Using a DCC‐MVGARCH for the period 1997–2007, we highlight the change that took place in 2003. Although IL bonds once had definite diversification power, they are now highly correlated with nominal bonds and have reached similar volatility levels. As a result, the two asset classes are practically substitutable. This seems to be due to more stable inflation expectations and to a more liquid IL bond market. Although diversification was a valuable reason for introducing IL bonds in a global portfolio before 2003, this is no longer the case. Dynamic portfolio optimisation using our estimates of conditional correlations and volatilities clearly demonstrates that the optimal weight of IL bonds in a portfolio decreased sharply in 2003 in favour of nominal bonds and equities.
Body Mass Index, Migraine, Migraine Frequency and Migraine Features in Women
Authors: Winter AC , Berger K , Buring JE , Kurth T
Published: October 2008

We evaluated the association of body mass index (BMI) with migraine and migraine specifics in a cross-sectional study of 63 467 women aged ≥ 45 years, of whom 12 613 (19.9%) reported any history of migraine and 9195 had active migraine. Compared with women without migraine and a BMI < 23 kg/m2, women with a BMI ≥ 35 kg/m2 had adjusted odds ratios (ORs) (95% confidence intervals) of 1.03 (0.95, 1.12) for any history of migraine. Findings were similar for active migraineurs. Women with a BMI of ≥ 35 kg/m2 had increased risk for low and high migraine frequency, with the highest estimate for women who reported daily migraine. Compared with women with the lowest associated risk (migraine frequency < 6 times/year; BMI between 27.0 and 29.9 kg/m2), women with a BMI ≥ 35 kg/m2 had an OR of daily migraine of 3.11 (1.12, 8.67). Among the women with active migraine, a BMI ≥ 35 kg/m2 was associated with increased risk of phonophobia and photophobia and decreased risk of a unilateral pain characteristic and migraine aura. Our data confirm previous findings that the association between BMI with migraine is limited to migraine frequency and specific migraine features.
First Mutation in the Voltage-Gated Nav1.1 Subunit Gene SCN1A with Co-Occurring Familial Hemiplegic Migraine and Epilepsy
Authors: Castro M-J , Stam AH , Lemos C , de Vries B , Vanmolkot KRJ , Barros J , Terwindt GM , Frants RR , Sequeiros J , Ferrari MD , Pereira-Monteiro JM , van den Maagdenberg AMJM
Published: October 2008

Almost all mutations in the SCN1A gene, encoding the α1 subunit of neuronal voltage-gated Nav1.1 sodium channels, are associated with severe childhood epilepsy. Recently, two mutations were identified in patients with pure familial hemiplegic migraine (FHM). Here, we identified a novel SCN1A L263V mutation in a Portuguese family with partly co-segregating hemiplegic migraine and epilepsy. The L263V mutation segregated in five FHM patients, three of whom also had epileptic attacks, occurring independently from their hemiplegic migraine attacks. L263V is the first SCN1A mutation associated with FHM and co-occurring epilepsy in multiple mutation carriers, and is the clearest molecular link between migraine and epilepsy thus far. The results extend the clinical spectrum associated with SCN1A mutations and further strengthen the molecular evidence that FHM and epilepsy share, at least in part, similar molecular pathways.
Analysis of RYR1 Haplotype Profile in Patients with Malignant Hyperthermia
Authors: Carpenter D. , Morris A. , Robinson R. L. , Booms P. , Iles D. , Halsall P. J. , Steele D. , Hopkins P. M. , Shaw M.‐A.
Published: October 2008

This study represents a new approach to characterising patients at risk of malignant hyperthermia (MH) through the use of a recently published method for identifying high‐risk haplotypes in candidate genes. We present analysis based upon the largest standardised and genotyped database of MH patients worldwide. We used unphased RYR1 SNP data directly to (1) assess RYR1 haplotype frequency differences between susceptible cases and control groups and (2) analyse population‐based association via clustering of RYR1 haplotypes based on disease risk. Our results show a significant difference in RYR1 haplotype frequency between susceptible cases and UK Caucasian population controls. Furthermore we identify a high‐risk cluster of haplotypes that is associated with the commonest UK MH mutation p.G2434R/c.7300G>A. These results demonstrate the applicability of this new and practical method for population based association analysis.
A Genetic Study of the Ghrelin and Growth Hormone Secretagogue Receptor (GHSR) Genes and Stature
Authors: Gueorguiev M. , Lecoeur C. , Benzinou M. , Mein C. A. , Meyre D. , Vatin V. , Weill J. , Heude B. , Grossman A. B. , Froguel P. , Korbonits M.
Published: October 2008

Growth and nutrition are interrelated and influenced by multiple genetic and environmental factors. We studied whether common variants in ghrelin and ghrelin receptor (GHSR) genes could play a role in stature variation in the general population and in families ascertained for obesity.

Selected tagging SNPs in the ghrelin and GHSR genes were genotyped in 263 Caucasian families recruited for childhood obesity (1,275 subjects), and in 287 families from a general population (1,072 subjects). We performed familial testing for associations in the entire population and in a sub‐set of the samples selected for a case‐control study. In the case‐control study for height (cases were selected from the obese cohort with mean ZH = 3.17 ± 0.15 confidence interval (CI) versus controls with mean ZH 0.14 ± 0.09), we found an association with a 2 base‐pair intronic deletion in the GHSR gene (rs10618418) (p = 0.006, odds ratio (OR) 1.86, 95% CI [1.26;2.74] under additive model), although when adjusting for BMI, the association disappeared (p = 0.06). Individuals carrying no deletion or who were heterozygous were significantly more frequent among the tall obese population (52% vs. 36% in controls, p = 0.007, OR 1.97, 95%CI [1.22;3.18]). However, the association was not maintained after correcting for multiple testing. Familial association testing of the ghrelin and GHSR genes and their interaction testing failed to show that any combination of SNPs had any significant effect. Thus, our results suggest that common variants of the ghrelin and GHSR genes are not major contributors to height variation in a French population.
Impact and Quantification of the Sources of Error in DNA Pooling Designs
Authors: Jawaid A. , Sham P.
Published: October 2008

The analysis of genome wide variation offers the possibility of unravelling the genes involved in the pathogenesis of disease. Genome wide association studies are also particularly useful for identifying and validating targets for therapeutic intervention as well as for detecting markers for drug efficacy and side effects. The cost of such large‐scale genetic association studies may be reduced substantially by the analysis of pooled DNA from multiple individuals. However, experimental errors inherent in pooling studies lead to a potential increase in the false positive rate and a loss in power compared to individual genotyping. Here we quantify various sources of experimental error using empirical data from typical pooling experiments and corresponding individual genotyping counts using two statistical methods. We provide analytical formulas for calculating these different errors in the absence of complete information, such as replicate pool formation, and for adjusting for the errors in the statistical analysis. We demonstrate that DNA pooling has the potential of estimating allele frequencies accurately, and adjusting the pooled allele frequency estimates for differential allelic amplification considerably improves accuracy. Estimates of the components of error show that differential allelic amplification is the most important contributor to the error variance in absolute allele frequency estimation, followed by allele frequency measurement and pool formation errors. Our results emphasise the importance of minimising experimental errors and obtaining correct error estimates in genetic association studies.
Efficacy and safety of using mesh or grafts in surgery for anterior and/or posterior vaginal wall prolapse: systematic review and meta‐analysis
Authors: Jia X , Glazener C , Mowatt G , MacLennan G , Bain C , Fraser C , Burr J
Published: October 2008

Background  The efficacy and safety of mesh/graft in surgery for anterior or posterior pelvic organ prolapse is uncertain.

Objectives  To systematically review the efficacy and safety of mesh/graft for anterior or posterior vaginal wall prolapse surgery.

Search strategy  Electronic databases and conference proceedings were searched, experts and manufacturers contacted, and reference lists of retrieved papers scanned.

Selection criteria  Randomised controlled trials (RCTs), nonrandomised comparative studies, registries, case series involving at least 50 women, and RCTs published as conference abstracts from 2005 onwards.

Data collection and analysis  One reviewer screened titles/abstracts, undertook data extraction, and assessed study quality. Data analysis was conducted for three subgroups: anterior, posterior, and anterior and/or posterior repair (not reported separately).

Results  Forty‐nine studies involving 4569 women treated with mesh/graft were included. Study quality was generally high. Median follow up was 13 months (range 1–51 months). In anterior repair, there was short‐term evidence that mesh/graft (any type) significantly reduced objective prolapse recurrence rates compared with no mesh/graft (relative risk 0.48, 95% CI 0.32–0.72). Nonabsorbable synthetic mesh had a significantly lower objective prolapse recurrence rate (8.8%, 48/548) than absorbable synthetic mesh (23.1%, 63/273) and biological graft (17.9%, 186/1041), but a higher erosion rate (10.2%, 68/666) than absorbable synthetic mesh (0.7%, 1/147) and biological graft (6.0%, 35/581). There was insufficient information to compare any of the other outcomes regardless of prolapse type.

Conclusions  Evidence for most outcomes was too sparse to provide meaningful conclusions. Rigorous long‐term RCTs are required to determine the comparative efficacy of using mesh/graft.
A randomised comparison of SurePath liquid‐based cytology and conventional smear cytology in a colposcopy clinic setting
Authors: Sykes PH , Harker DY , Miller A , Whitehead M , Neal H , Wells JE , Peddie D
Published: October 2008

Objective  The objective of this study was to compare the sensitivity of cervical cytology using conventional smears and SurePath liquid‐based cytology (LBC).

Design  Prospective randomised evaluation of diagnostic test.

Setting  A single institution colposcopy clinic.

Population  Women attending first visit colposcopy appointments were offered entry into the study.

Methods  Cervical cytology samples from 913 women of age 16–75 years were randomly processed as SurePath LBC or conventional smears. Conventional smears were taken for 453 women and a SurePath LBC taken for 451 women. Cytology results were correlated with colposcopic findings and histology from colposcopic biopsies, treatment and follow up.

Main outcome measures  To compare the sensitivity of SurePath LBC and conventional smears for histologically proven abnormality. Other outcome measures include a comparison of their sensitivity for high‐grade abnormalities and their satisfactory rate.

Results  Accounting for all randomised samples, there was a trend towards improved sensitivity for SurePath LBC (79.1 versus 73.7%, P = 0.1). However, excluding unsatisfactory cytology (and samples not taken) eliminated this trend; the sensitivity for both LBC and conventional smears for any epithelial abnormality was 81%. With a threshold of atypical squamous cells of uncertain significance (ASC‐US), both SurePath LBC and conventional smears had a sensitivity of 92% for high‐grade lesions. SurePath LBC was less likely to be reported as unsatisfactory (2.7 versus 9.1%, P < 0.0001).

Conclusions  In this context, with a threshold of ASC‐US, both SurePath LBC and conventional smears offer high sensitivity for the detection of CIN2/3, but SurePath LBC is less likely to be reported as unsatisfactory.
Maternal mortality in sub‐Saharan Africa: the contribution of ineffective blood transfusion services
Authors: Bates I , Chapotera GK , McKew S , Van Den Broek N
Published: October 2008

In sub‐Saharan Africa, where blood supply is critically inadequate, severe haemorrhage is a leading cause of maternal deaths. The aim of this review was to estimate the impact of lack of blood on maternal deaths and identify reasons and potential solutions. Databases and websites from 1970 to 2007 were searched for information concerning maternal deaths and near misses due to haemorrhage in sub‐Saharan Africa. Original studies that provided qualitative or quantitative information about blood transfusion services in relation to obstetric deaths or near misses were included. Data about maternal haemorrhage deaths associated with lack of blood for transfusion and reasons for blood shortages were extracted from the full text of articles by two independent reviewers using predesigned, piloted forms. Twenty of 37 selected studies described a direct association between maternal deaths and lack of blood transfusions. Five of 37 provided quantitative information which showed that overall 26% (16–72%) of maternal haemorrhage deaths were due to lack of blood. Reasons included nonaffordability of blood, lack of blood donors, unwillingness of relatives to donate and inadequate supplies and transport. Lack of blood for emergency transfusions is a major, but poorly quantified and under‐researched cause of maternal deaths in sub‐Saharan Africa. Potential solutions include more blood donations, better financing mechanisms and more efficient management systems. Complementary approaches to prevent severe anaemia and treat hypovolaemia are important to reduce use of transfusions.
Customised birthweight percentiles: does adjusting for maternal characteristics matter?
Authors: Hutcheon JA , Zhang X , Cnattingius S , Kramer MS , Platt RW
Published: October 2008

Objective  The objective of this study was to determine whether the improved prediction of risk for perinatal mortality obtained with the use of a customised birthweight standard can also be obtained with the use of a non‐customised but intrauterine‐based standard.

Design  Population‐based cohort study.

Setting  Sweden.

Population  Births in the Swedish Medical Birth Register between 1992 and 2001 (n = 782 303) with complete data on birthweight, gestational age, sex, maternal age, pre‐pregnancy body mass index, height, parity, and ethnicity.

Methods  We calculated the relative risks (RRs) of stillbirth and early neonatal mortality among small‐for‐gestational‐age (SGA) births as established by (1) a customised standard, (2) a population standard based on birthweights, and (3) a population standard based on a best estimate of intrauterine weights.

Main outcome measures  Stillbirth and early neonatal mortality (<7 days).

Results  The RRs of stillbirth and early neonatal mortality among SGA births as classified by the intrauterine standard were similar to those among SGA births as classified by the customised standard and much higher than those among SGA births as classified by the birthweight standard.

Conclusions  A non‐customised but intrauterine‐based standard has a similar ability to predict risk for stillbirth and early neonatal mortality as a customised birthweight standard. The process of customising population weight‐for‐gestational‐age standards to account for maternal characteristics does little to improve prediction of perinatal mortality.
Non‐hospital delivery and permanent congenital and early‐onset hearing loss in a developing country
Authors: Olusanya BO , Wirz SL , Luxon LM
Published: October 2008

Objective  The objective of this study was to determine the role of non‐hospital delivery and other risk factors for permanent congenital and early‐onset hearing loss (PCEHL) in a developing country.

Design  Matched case–control study.

Setting  Four primary healthcare centres in inner‐city Lagos, Nigeria.

Population  Fifty‐six infants with PCEHL and 280 normal hearing controls matched for age and sex from a population of infants not older than 3 months attending Bacille de Calmette‐Guérin immunisation clinics.

Methods  Conditional logistic regression analyses of infant and maternal characteristics associated with PCEHL, and the evaluation of population exposure to each risk factor.

Main outcome measures  Adjusted matched odds ratios and population attributable risk percent (PAR%).

Results  Children with PCEHL were significantly more likely to be first born (OR 1.9, 95% CI 1.1–3.6) without skilled attendants at birth (OR 2.4, 95% CI 1.3–4.5) and have a history of neonatal jaundice requiring exchange blood transfusion (NNJ/EBT) (OR 9.6, 95% CI 2.4–38.2) but less likely to be small for gestational age (SGA) (OR 0.1, 95% CI 0.0–0.5). After controlling for other covariates, the absence of skilled attendants at birth (OR 4.2, 95% CI 2.0–8.6) and NNJ/EBT (OR 19.1, 95% CI 4.3–85.5) emerged as predictors of PCEHL, while SGA (OR 0.1, 95% CI 0.0–0.2) retained its inverse relationship with PCEHL. The PAR% was 35.9% for the lack of skilled attendants at birth and 10.6% for having NNJ/EBT. About 23% of children with PCEHL did not exhibit any risk factors.

Conclusions  NNJ/EBT and the absence of skilled attendant at birth rather than the place of delivery are significant predictors of PCEHL in this study population. Targeted hearing screening using these risk factors would facilitate the detection of about 77% of children with PCEHL.