bluuebunny/crossref_metadata_2025 huggingface dataset:
The Roots of the Early Vocabulary in Infants' Learning From Speech
Authors: Swingley Daniel
Published: October 2008

Psychologists have known for over 20 years that infants begin learning the speech-sound categories of their language during the first 12 months of life. This fact has dominated researchers' thinking about how language acquisition begins, although the relevance of this learning to the child's progress in language acquisition has never been clear. Recently, views of the role of infancy in language acquisition have begun to change, with a new focus on the development of the vocabulary. Infants' learning of speech-sound categories and infants' abilities to extract regularities in the speech stream allow learning of the auditory forms of many words. These word forms then become the foundation of the early vocabulary, support children's learning of the language's phonological system, and contribute to the discovery of grammar.
Terrorism, Violence, and Hope for Peace
Authors: Pyszczynski Tom , Rothschild Zachary , Abdollahi Abdolhossein
Published: October 2008

Terror management theory (TMT) is used to explore psychological forces that act to promote or discourage support for terrorism and violent counterterrorist policies. According to TMT, domination, humiliation, and perceived injustice threaten the self-esteem and cultural worldviews that protect people from death-related anxiety; the result may be hostility and violence directed against the threatening out-group as a way of defusing this threat. We review research documenting the role of terror management processes in promoting and discouraging support for terrorism and violent counterterrorist policies and discuss the implications of this research. The studies we review suggest that the same psychological forces that promote support for terrorist violence also promote support for aggressive counterterrorist policies and that these forces can be redirected to encourage support for more peaceful solutions on both sides of the current conflict between Islamic radical groups and Western nations.
From Genes to Brain to Antisocial Behavior
Authors: Raine Adrian
Published: October 2008

This review summarizes recent brain-imaging and molecular-genetic findings on antisocial, violent, and psychopathic behavior. A “genes to brain to antisocial behavior” model hypothesizes that specific genes result in structural and functional brain alterations that, in turn, predispose to antisocial behavior. For instance, a common polymorphism in the monoamine oxidase A ( MAOA) gene has been associated with both antisocial behavior and also reductions in the volume of the amygdala and orbitofrontal (ventral prefrontal) cortex—brain structures that are found to be compromised in antisocial individuals. Here I highlight key brain regions implicated in antisocial behavior, with an emphasis on the prefrontal cortex, along with ways these areas give expression to risk factors for antisocial behavior. Environmental influences may alter gene expression to trigger the cascade of events that translate genes into antisocial behavior. Neuroethical considerations include how responsibility and punishment should be determined given the hypothesis that neural circuits underlying morality are compromised in antisocial individuals.
Musical Disorders
Authors: Peretz Isabelle
Published: October 2008

Research over the last decade has provided compelling evidence that the ability to engage with music is a fundamental human trait, yet the biological basis of music remains largely unknown. Recent findings indicate that a small number of individuals have severe musical problems that have neurogenetic underpinnings. Such deficiencies are termed congenital amusia, an umbrella term for lifelong musical disabilities that cannot be attributed to mental retardation, deafness, lack of exposure to music, or brain damage after birth. Congenital amusia constitutes a natural experiment, giving us a rare chance to examine the biological basis of music by tracing causal links among genes, environment, brain, and behavior.
Sex, drugs, and politics: the HPV vaccine for cervical cancer
Authors: Casper Monica J. , Carpenter Laura M.
Published: October 2008

HPV is the most common sexually transmitted infection in the world. While most strains are relatively harmless, some increase a woman's risk of developing cervical cancer. This article explores the intimate, contested relationships among etiologies of cervical cancer, development and use of the new HPV vaccine, and contested notions of sexuality. We particularly focus on shifts in US health care and sexual politics, where the vaccine has animated longstanding concerns about vaccination (e.g. parental rights, cost, specialisation) and young women's bodies and behaviour. We conclude that vaccines are a distinctive kind of pharmaceutical, invoking notions of contagion and containment, and that politics shape every aspect of the pharmaceutical lifecourse.
Pharma in the bedroom . . . and the kitchen. . . . The pharmaceuticalisation of daily life
Authors: Fox Nick J. , Ward Katie J.
Published: October 2008

This paper examines the consequences of a new emphasis on lifestyle in the production, marketing and consumption of pharmaceuticals. Over the past decade, a range of medicines have become available that address aspects of lifestyle, while others have been the subject of lifestyle marketing. We argue, with recourse to a broad literature from the social sciences, economics and health services research and from our study of pharmaceutical consumption, that two processes can be discerned. First, there is a domestication of pharmaceutical consumption, with drugs available via home computers, and marketing of pharmaceuticals that focuses upon private or personal conditions and addresses domestic activities such as sex and cooking. Secondly, there is a pharmaceuticalisation of everyday life as the pharmaceutical industry introduces profitable medicines for a range of daily activities and pharmaceuticals come to be seen by consumers as a ‘magic bullet’ to resolve problems of daily life. We suggest that the pharmaceuticalisation of daily life links the economics and politics of pharmaceutical production to the private lives of citizens.
The great ambivalence: factors likely to affect service user and public acceptability of the pharmacogenomics of antidepressant medication
Authors: Barr Michael , Rose Diana
Published: October 2008

Whilst antidepressant medications are widely used, they are ineffective for nearly 40 per cent of users and cause numerous adverse drug reactions. The pharmacogenomics of depression attempts to better understand the role of genetic variation in antidepressant metabolism in the hope of improving drug efficacy and tolerability. In this paper we present findings from a series of focus groups with the general public and with mental health service users in four European sites. Results indicate broad support for genome‐based therapies for depression. Findings, however, also show a wide spread of ambivalence regarding the nature and causes of depression, as well as the use of antidepressant medication. We argue that these uncertainties may negatively impact public and user acceptability of the pharmacogenomics of antidepressants.
LOVE AS SACRIFICE, LOVE AS MUTUALITY: RESPONSE TO JEFFREY TILLMAN
Authors: Browning Don
Published: October 2008

Jeffrey Tillman is perceptive in noticing that certain Protestant theologians have used evolutionary theory to become more sympathetic to Roman Catholic views of Christian love. But he is incorrect in saying that these formulations deemphasize a place for self‐sacrifice in Christian love. Christian love defined as a strenuous equal‐regard for both other and self also requires sacrificial efforts to restore love as equal‐regard when finitude and sin undermine genuine mutuality and community.
IN PRAISE OF FOLLY? THEOLOGY AND THE UNIVERSITY
Authors: Peterson Gregory R.
Published: October 2008

To suppose the possibility of dialogue between theology and science is to suppose that theology is an intellectually worthy partner to engage in dialogue with science. The status of theology as a discipline, however, remains contested, one sign of which is the absence of theology from the university. I argue that a healthy theology‐science dialogue would benefit from the presence of theology as an academic discipline in the university. Theology and theologians would benefit from the much closer contact with university disciplines, including the sciences. The university and the sciences would benefit from the presence of theology, providing a department of ultimate concern, where big questions may be asked and ideologies critiqued. A university theology would need to meet standards of academic integrity.
IS THEOLOGY RESPECTABLE AS METAPHYSICS?
Authors: Jones Nicholaos
Published: October 2008

Theology involves inquiry into God's nature, God's purposes, and whether certain experiences or pronouncements come From God. These inquiries are metaphysical, part of theology's concern with the veridicality of signs and realities that are independent from humans. Several research programs concerned with the relation between theology and science aim to secure theology's intellectual standing as a metaphysical discipline by showing that it satisfies criteria that make modern science reputable, on the grounds that modern science embodies contemporary canons of respectability for metaphysical disciplines. But, no matter the ways in which theology qua metaphysics is shown to resemble modern science, these research programs seem destined for failure. For, given the currently dominant approaches to understanding modern scientific epistemology, theological reasoning is crucially dissimilar to modern scientific reasoning in that it treats the existence of God as a certainty immune to refutation. Barring the development of an epistemology of modern science that is amenable to theology, theology as metaphysics is intellectually disreputable.
MAINTAINING RESPECTABILITY: RESPONSE TO NICHOLAOS JONES
Authors: Peterson Gregory R.
Published: October 2008

Nicholaos Jones argues that theology is not a respectable discipline because of its inability to meet the standards of contemporary science. Although Jones makes a bold claim, I suggest that he has not made his case by focusing on the question of defining science and metaphysics appropriately, the analysis of the literature he cites, and his central claim that theology presupposes the absolute certainty of God.
UNDERSTANDING AND RESPONDING TO HUMAN EVIL: A MULTICAUSAL APPROACH
Authors: Peters Karl E.
Published: October 2008

One task of religion is delivering human beings from evil within and between themselves. Defining good as well‐being or functioning well, evil as impaired functioning, and doing evil as impairing the functioning of others, this essay explores how religions in consort with other social institutions might understand and respond to evil in light of contemporary scientific knowledge. To understand evil I use a multicausal approach that includes both biological and sociocultural environmental causes. I illustrate the use of this approach by analyzing how we might understand and respond to human rage and violence.
DEVELOPMENT OF OBJECTIVE CRITERIA TO EVALUATE THE AUTHENTICITY OF REVELATION
Authors: Mustafa Tariq
Published: October 2008

Science has been dazzlingly successful in explaining nature. Scientific advances also have led to certain undesirable, though unintended, side effects, one of which is alienation from the spiritual. Revelation comes from the Divine. But what is the status of authenticity of a particular piece claimed to be revelation? What is its historical validity and current state of preservation? This essay proposes to develop a list of rational criteria, in consultation with all stakeholders, for addressing the subject. The aim is to bring objectivity into this discourse by placing it more on the turf of reason rather than basing it on considerations of faith and prior allegiance.
EFFICIENCY AND PRODUCTIVITY CHANGE IN THE ENGLISH HIGHER EDUCATION SECTOR FROM 1996/97 TO 2004/5*
Authors: JOHNES JILL
Published: October 2008

In this study we use a distance function approach to derive Malmquist productivity indexes for 112 English higher education institutions (HEIs) over the period 1996/97 to 2004/5. The analysis shows that HEIs have experienced an annual average increase in productivity of 1 per cent. Further investigation reveals that HEIs have enjoyed an annual average increase in technology of 6 per cent combined with a decrease in technical efficiency of 5 per cent. Rapid changes in the higher education sector appear to have had a positive effect on the technology of production but this has been achieved at the cost of lower technical efficiency.
EXCESS‐ENTRY THEOREM: THE IMPLICATIONS OF LICENSING*
Authors: MUKHERJEE ARIJIT , MUKHERJEE SOMA
Published: October 2008

We show that, in the presence of technology licensing, entry in an industry with Cournot competition may lead to a socially insufficient, number of firms. Insufficient entry occurs if the own marginal cost of the entrant is sufficiently high. Hence, the justification for anticompetitive entry regulation due to the standard excess‐entry result may not be justified in the presence of licensing. However, if the own marginal cost of the entrant is very low, licensing may create excessive entry for those entry costs where entry does not occur without licensing; thus licensing reduces social welfare though it increases competition.
MONETARY POLICY EFFECTS ON FINANCIAL RISK PREMIA*
Authors: SÖDERLIND PAUL
Published: October 2008

The effect of monetary policy on financial risk premia is analysed in a simple general equilibrium model with sticky wages and an optimizing central bank. Analytical results show that equity risk premia and term premia are higher under inflation targeting than under output targeting, and that inflation risk premia are higher for policies that strike a balance between output and inflation stability (and achieve a social optimum) than for policies that target only one of them.
Alief in Action (and Reaction)
Authors: GENDLER TAMAR SZABÓ
Published: October 2008

Abstract: I introduce and argue for the importance of a cognitive state that I callalief. An alief is, to a reasonable approximation, an innate or habitual propensity to respond to an apparent stimulus in a particular way. Recognizing the role that alief plays in our cognitive repertoire provides a framework for understanding reactions that are governed by non‐conscious or automatic mechanisms, which in turn brings into proper relief the role played by reactions that are subject to conscious regulation and deliberate control.
The Evolution Of Pretence: From Intentional Availability To Intentional Non‐Existence
Authors: GÓMEZ JUAN‐CARLOS
Published: October 2008

Abstract: I address the issue of how pretence emerged in evolution by reviewing the (mostly negative) evidence about pretend behaviour in non‐human primates, and proposing a model of the type of information processing abilities that humans had to evolve in order to be able to pretend. Non‐human primates do not typically pretend: there are just a few examples of potential pretend actions mostly produced by apes. The best, but still rare, examples are produced by so‐called ‘enculturated’ apes (reared by humans) and among them specially those that have been systematically trained to use symbols (so‐called ‘linguistic’ apes). A hypothesis that would explain the lack of pretence in apes is that they lack the mentalistic ability of theory of mind. However, in the last years apes have been demonstrated to possess relatively sophisticated social cognitive skills, some of them ontogenetically appearing in humans alongside with or even after pretend play. As a solution to the paradox, I discuss a model according to which pretence is supported by a mechanism capable of computing intentional relations with non‐existing objects or properties (Intentional non‐existence), as opposed to mechanisms computing intentional relations with existing, although not necessarily currently perceived, objects (Intentional availability). Apes possess the latter, which allows them to solve a variety of theory of mind tasks, but not the former, which typically prevents them from developing pretence.
Which Factors Affect Bond Underwriting Fees? The Role of Banking Relationships
Authors: Iannotta Giuliano , Navone Marco
Published: October 2008

The question of which factors are relevant in determining bond underwriting fees is empirically investigated by analysing 2,202 bond issues completed by European firms during the 1993 – 2003 period. Four major results emerge from the analysis. First, the introduction of the single currency in 1999 has generated an increase in competition among banks, and, as a result, a reduction in underwriting fees. Second, a strong relationship with the issuer's main bank reduces the level of underwriting fees. Third, new issuers are charged with lower underwriter fees relative to firms that have completed issues without building any strong relationship with a bank. Fourth, higher reputation banks charge lower underwriting fees. The implications of these findings are also discussed.
Levels of Generality in the Legal Reasoning of the European Court of Justice
Authors: Conway Gerard
Published: October 2008

The level of generality or of abstraction used to describe a precedent, a right, or the legislative intent behind a statutory provision or constituent purpose behind a constitutional provision can have a decisive impact on the outcome of a case. Characterising it in narrow terms has the effect of reducing the scope of decision of a judgment; conversely, a broader characterisation provides more leeway for a judge in a case to encompass its facts within the precedent, right or purpose in issue. The issue raised by the level of generality problem is the extent to which courts have a discretion or freedom of manoeuvre as to the level of generality they decide upon, and thus whether generality and abstraction are manipulable in the hands of judges and are not really predetermined by the legal sources in question or an established judicial method of interpretation. Uncontrolled judicial discretion of this kind is problematic from the point of view of the rule of law and democracy, especially when adjudication concerns constitutional provisions, the equivalent in the EU being interpretation by the European Court of Justice (ECJ) of the EU Treaties; reversal of ECJ interpretation through Treaty amendment is particularly difficult to achieve because it requires unanimous coordination by the Member States. This article examines two alternative ways of determining the correct or appropriate level of generality issue in ECJ interpetation, coherence or the legal traditions of the Member States, and argues in favour of the latter as a less subjective method. Application of the two alternative approaches is tested in two areas of EU law, state liability and criminal law.
Enlargement at the European Court of Justice: Law, Language and Translation
Authors: McAuliffe Karen
Published: October 2008

The enlargement of the EU to 25 Member States in May 2005, followed by the accession of two more states in January 2007, raised a number of questions concerning the organisational structure of that Union—the sheer scale of the largest EU expansion to date highlighted the need to restructure EU institutions. For the European Court of Justice (ECJ), enlargement meant a huge influx of people to staff new divisions in the administrative hierarchy of the Court. This article describes the process and effects of enlargement at the ECJ, particularly in relation to translation and the language regime of that Court. Prior to the May 2004 and January 2007 enlargements there was a general perception among those working at the Court that enlargement would result in significant dislocation of life at that institution. In particular, it was felt that the translation directorate would not be able to cope with the addition of 11 ‘new’ languages to the list of official EU languages. The reality, however, was far from the disaster that many had predicted. That said, even a mere year following the May 2004 enlargement, a number of changes in the functioning and dynamics of that Court were already noticeable.
How Transparent are EU ‘Comitology’ Committees in Practice?
Authors: Brandsma Gijs Jan , Curtin Deirdre , Meijer Albert
Published: October 2008

Much of the debate on transparency is normative in nature: more transparency is ‘good’ from the perspective of democratic accountability. After all, without information on what decisions are being taken and by whom, it will not be possible for various accountability forums to hold actors to account. This article goes beyond the rhetoric on the need for more transparency in the political system of the EU and examines, in practice as a matter of empirical research, how much transparency there really is. It also goes beyond a purely legal approach to access to information that depends upon the active participation of citizens and others in challenging refusals by specific institutions to grant access to specific documents. We are interested rather in the question as to what extent the institutions are systematically and pro‐actively providing access to their documents via the internet. We focus on the Register of Comitology of the European Commission as a relatively limited case study and, within this context, limit ourselves further to a study of all the documents published in the latest year for which a benchmark was available—2005. Are all comitology documents that exist in fact made available through this public register?
Loss Sharing Rules for Bank Holding Companies: An Assessment of the Federal Reserve's Source‐of‐Strength Policy and the FDIC's Cross Guarantee Authority
Authors: Bradley Christine M. , Jones Kenneth D.
Published: October 2008

In this article, we critically examine two policies designed to protect the deposit insurance funds—the Federal Reserve Board's source‐of‐strength policy and the FDIC's cross‐guarantee authority. We discuss why each of the policies was adopted and how effective each has been in practice since its implementation. We then evaluate the future application and usefulness of the two policies in light of the structural changes that have resulted from industry consolidation and the financial modernization of the 1990s.
Operational Risk Measurement in Banking Institutions and Investment Firms: New European Evidences
Authors: Bonsón Enrique , Escobar Tomás , Flores Francisco
Published: October 2008

The banking/investment sector must deal with a new variable, Operational Risk, for explaining various recent crises and bankruptcies. Operational Risk, which can be defined briefly as the risk generated by possible failures of a entity's Information Systems (IS), must be measured, covered, mitigated and managed by applying a series of methodologies, each of which assumes that the IS of the bank operates at a certain Stage of Sophistication. The present study proposes a scheme of evolution that details the stages of enhancement in the sophistication of their IS that banking entities may implement, so as to be capable of capturing, mitigating and managing Operational Risk. Using econometric methods, we create a proxy variable to capture the IS Sophistication of each entity. Then, the factor of entity size has been analyzed, and the country effect is explored. Additionally, the importance of intangible assets is weighted, among others entity aspects. The entity size has been revealed as the variable with most influence on the plans formulated in this respect by European entities, against other variables also considered in the present study, such as the country effect or the importance of intangible assets. The work shows how IS decisions referring to Operational Risk management are very influenced by size. It could introduce competition differences in the European banking system.
Quality of child–parent attachment moderates the impact of antenatal stress on child fearfulness
Authors: Bergman K. , Sarkar P. , Glover V. , O’Connor T.G.
Published: October 2008

Background:  Animal studies have shown that prenatal stress has persisting effects on several aspects of offspring development; more recent studies show that this effect may be eliminated by positive postnatal rearing. Human studies of prenatal anxiety/stress are now also beginning to document links between antenatal stress/anxiety and behavioural and cognitive development of the child; however, there is no human evidence as to whether the early caregiving environment moderates the effect of antenatal anxiety/stress on child outcomes.

Methods:  Antenatal and postnatal measures of stress were collected on 123 women who were recruited from an antenatal clinic. Laboratory‐based assessment of the children’s cognitive development and fearfulness were assessed when the children were aged 17 months. In addition, child–parent attachment quality was assessed using the Strange Situation.

Results:  Attachment classification moderated the link between antenatal stress and observed fearfulness. The effect of antenatal stress on fearfulness was most accentuated in children with an Insecure/Resistant attachment classification; the significant antenatal stress × attachment classification interaction held after controlling for postnatal stress and obstetric, social and demographic factors. Attachment did not moderate the effects of antenatal anxiety on cognitive development.

Discussion:  These findings provide the first human evidence that postnatal parenting may moderate the adverse effects of antenatal stress. These results raise developmental questions about the timing and effect of interventions to reduce the adverse effects of antenatal stress exposure.
Cocoa butter lotion for prevention of striae gravidarum: a double‐blind, randomised and placebo‐controlled trial*
Authors: Osman H , Usta IM , Rubeiz N , Abu‐Rustum R , Charara I , Nassar AH
Published: October 2008

Objective  To assess whether application of cocoa butter lotion reduces the development of striae gravidarum (SG).

Design  Multicentre, double‐blind, randomised and placebo‐controlled trial.

Setting  Beirut and Tripoli, Lebanon.

Population  Nulliparous women presenting for prenatal care.

Methods  Nulliparous women presenting in the first trimester were randomly assigned to receive a lotion containing cocoa butter or a placebo lotion. Women were instructed to apply the assigned lotion daily until delivery.

Main outcome measure The development of striae over the abdomen, breasts and thighs postpartum.

Results Of 210 women enrolled, 175 (83%) completed the study. Ninety‐one women received the study lotion and 84 received the placebo. There was no difference in the development of SG (45.1% versus 48.8%; P = 0.730) or the severity of SG between cases and controls. The results did not change when presence of stretch marks at enrolment or compliance with the regimen were taken into account.

Conclusion  Topical application of a lotion containing cocoa butter does not appear to reduce the likelihood of developing striae gravidarum.
A randomised controlled trial of early versus delayed oxytocin augmentation to treat primary dysfunctional labour in nulliparous women
Authors: Hinshaw K , Simpson S , Cummings S , Hildreth A , Thornton J
Published: October 2008

Background  Oxytocin is widely used to speed up slow labour, especially in nulliparous women, but randomised trials, apart from one reported only in abstract, have been too small to exclude important effects.

Objective  To test the hypothesis that early use of oxytocin reduces the need for caesarean delivery.

Design  A randomised controlled trial.

Setting  Twelve obstetric units within the Northern and Yorkshire regions in the North East of England.

Participants  A total of 412 low‐risk nulliparous women in spontaneous labour at term, who had been diagnosed with primary dysfunctional labour were recruited from January 1999 to December 2001.

Intervention  Immediate oxytocin administration (active group) or oxytocin withheld for up to 8 hours (conservative group).

Main outcome measures  Caesarean section and operative vaginal delivery rates. The length of labour measured from the time of randomisation to delivery. The rate of maternal Edinburgh Postnatal Depression Scale (EPDS) greater than 12 (major depression) within 48 hours of delivery.

Results  The caesarean section rates were 13.5% active versus 13.7% controls (OR 0.98, 95% CI 0.6–1.7). Operative delivery, 24.5% versus 30.9% (OR 0.73, 95% CI 0.5–1.1). The median (interquartile range) randomisation to delivery interval in the active group was 5 hours 52 minutes (3:57–8:28) and in the conservative group 9 hours 8 minutes (5:06–13:16) (P < 0.001). The rate of EPDS >12 was 20% in the active arm versus 15% among controls (OR 1.26, 95% CI 0.7–2.2). There was one perinatal death in each group and no major differences in perinatal outcomes.

Conclusions  Among nulliparous women with primary dysfunctional labour, early use of oxytocin does not reduce caesarean section or short‐term postnatal depression. However, it shortens labour considerably and may reduce operative vaginal deliveries.
Serious toxicity associated with continuous nevirapine‐based HAART in pregnancy
Authors: Van Schalkwyk JE , Alimenti A , Khoo D , Maan E , Forbes JC , Burdge DR , Gilgoff S , Money DM
Published: October 2008

Objective  This study was designed to determine the safety of nevirapine (NVP)‐based highly active antiretroviral therapy (HAART) in a cohort of HIV‐positive pregnant women.

Design  This was a prospective cohort study of HIV‐positive pregnant women.

Population and setting  All HIV‐positive women treated with HAART during pregnancy from January 1997 to February 2004 at the British Columbia (BC) Women’s Hospital in Vancouver, BC, Canada.

Methods  Demographic and clinical data were collected to compare antiretroviral drug toxicities in women treated antenatally with NVP‐based or non‐NVP‐based HAART. Multivariate analyses were then used to investigate determinants of toxicity.

Results  From 1997 to 2004, 103 HIV‐positive pregnant women received HAART. Equivalent numbers of women were initially treated with NVP‐based (54%) and non‐NVP‐based (46%) HAART. The groups did not differ by clinical or demographic parameters and duration of HAART exposure was similar between groups. Toxicities necessitating treatment discontinuation were observed in 6 of 56 NVP‐exposed women (2 cases each of grade 2, 3, and 4 toxicity) compared with 1 of 47 in the non‐NVP‐exposed women. First time use of NVP approached significance as a predictor for toxicity, with a toxicity rate of 12.5% (6/48) observed among those taking NVP for the first time (adjusted OR 2.68, 95% CI 0.49–14.6).

Conclusion  Continuous NVP use in pregnancy resulted in a relatively higher rate of toxicity, and all cases of NVP toxicity occurred in women exposed to NVP for the first time during pregnancy.
Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life
Authors: Painter RC , Osmond C , Gluckman P , Hanson M , Phillips DIW , Roseboom TJ
Published: October 2008

Objective  Maternal undernutrition during gestation is associated with increased metabolic and cardiovascular disease in the offspring. We investigated whether these effects may persist in subsequent generations.

Design  Historical cohort study.

Setting  Interview during a clinic or home visit or by telephone.

Population  Men and women born in the Wilhelmina Gasthuis in Amsterdam between November 1943 and February 1947.

Methods  We interviewed cohort members (F1) born around the time of the 1944–45 Dutch famine, who were exposed or unexposed to famine in utero, about their offspring (F2).

Main outcome measures  Birthweight, birth length, ponderal index and health in later life (as reported by F1) of the offspring (F2) of 855 participating cohort members, according to F1 famine exposure in utero.

Results  F1 famine exposure in utero did not affect F2 (n = 1496) birthweight, but, among the offspring of famine‐exposed F1 women, F2 birth length was decreased (−0.6 cm, P adjusted for F2 gender and birth order = 0.01) and F2 ponderal index was increased (+1.2 kg/m3, P adjusted for F2 gender and birth order = 0.001). The association remained unaltered after adjusting for possible confounders. The offspring of F1 women who were exposed to famine in utero also had poor health 1.8 (95% CI 1.1–2.7) times more frequently in later life (due to miscellaneous causes) than that of F1 unexposed women.

Conclusions  We did not find transgenerational effects of prenatal exposure to famine on birthweight nor on cardiovascular and metabolic disease rates. F1 famine exposure in utero was, however, associated with increased F2 neonatal adiposity and poor health in later life. Our findings may imply that the increase in chronic disease after famine exposure in utero is not limited to the F1 generation but persists in the F2 generation.
Induction of labour in nulliparous and multiparous women: a UK, multicentre, open‐label study of intravaginal misoprostol in comparison with dinoprostone
Authors: Calder AA , Loughney AD , Weir CJ , Barber JW
Published: October 2008

Objective  To compare the efficacy and safety of a 25‐microgram vaginal tablet of misoprostol (APL202) with dinoprostone (3‐mg vaginal tablet) in cervical ripening and labour induction.

Design  A randomised, open‐label, noninferiority, comparative study in two maternal populations.

Setting  Eighteen NHS study centres across the UK.

Population  Nulliparous or multiparous women with a singleton pregnancy eligible for induction of labour.

Methods  Women were randomised to receive either misoprostol, initially 25 micrograms (50 micrograms in nulliparous women with Bishop score ≤4) followed by 25 micrograms after 4 and 8 hours, or dinoprostone, initially 3 mg followed by 3 mg after 6 hours. Clinical noninferiority of misoprostol was defined as an absolute difference between treatments of no more than 10% for the primary outcome.

Main outcome measures  The number of vaginal deliveries achieved within 24 hours of labour induction. Maternal and fetal safety outcomes.

Results  A total of 626 women were randomised to misoprostol (n = 318) or dinoprostone (n = 308) treatment. The rate of vaginal deliveries achieved within 24 hours of induction did not significantly differ between the misoprostol and dinoprostone (43 versus 47%; 3.74% difference, 95% CI −3.58 to 11.05, respectively) treatment groups. The treatments were generally comparable for other secondary efficacy measures. Maternal and fetal adverse events were similarly distributed across the misoprostol and dinoprostone groups.

Conclusions  Low‐dose misoprostol is efficacious in cervical ripening and labour induction and demonstrates a similar fetal and maternal safety profile to dinoprostone.
Mannose‐binding lectin gene polymorphism and resistance to therapy in women with recurrent vulvovaginal candidiasis
Authors: Donders GGG , Babula O , Bellen G , Linhares IM , Witkin SS
Published: October 2008

Precis  Women with recurrent vulvovaginal candidiasis (RVC) due to a polymorphism in codon 54 of the MBL2 gene respond better to fluconazole maintenance therapy than do women with other underlying causes.

Objective  To explain differences in response rates to maintenance therapy with fluconazole in women suffering from RVC by evaluating associations with a polymorphism in the gene coding for mannose‐binding lectin (MBL).

Design  Follow‐up study, neted case‐control group.

Setting  Women attending vulvoginitis clinic for RVC.

Population  Women participating in a multicentric study in Belgium with a degressive dose of fluconazole for RVC (the ReCiDiF trial) were divided into good responders, intermediate responders and nonresponders according to the number of relapses they experienced during therapy. From 109 of these women with adequate follow‐up data, vaginal lavage with 2 ml of saline were performed at the moment of a proven acute attack at inclusion in the study, before maintenance treatment was started. A buccal swab was obtained from 55 age‐matched women without a history of Candida infections, serving as a control group.

Methods  Extracted DNA from buccal or vaginal cells was tested for codon 54 MBL2 gene polymorphism by polymerase chain reaction and endonuclease digestion.

Main outcome measures  Frequency of MBL2 condon 54 allele B in women with optimal or poor response to maintenance therapy in composition with controls.

Results  Women (n = 109) suffering from RVC were more likely to carry the variant MBL2 codon 54 allele B than control women (20 versus 6.6%, OR 3.4 [95% CI 1.3–8.2], P = 0.01). B alleles were present in 25% of the 36 women not suffering from any recurrence during the maintenance therapy with decreasing doses of fluconazole (OR 4.9 [95% CI 1.9–12.5], P = 0.0007 versus controls), in 20% of the 43 women with sporadic recurrences (OR 3.6 [95% CI 1.4–9.2], P = 0.007 versus controls) and in 15% of the 30 women who had to interrupt the treatment regimen due to frequent relapses (P = 0.097 versus controls).

Conclusions  The MBL2 codon 54 gene polymorphism is more frequent in Belgian women suffering from RVC than in controls. The presence of the B allele is associated with a superior response to fluconazole maintenance therapy as compared with RVC patients without this polymorphism. We conclude that RVC due to deficient MBL production is more easily helped with antifungal medication than is RVC due to some other mechanism.
A randomised controlled trial comparing GnRH antagonist Cetrorelix with GnRH agonist Leuprorelin for endometrial thinning prior to transcervical resection of endometrium
Authors: Bhatia K , Doonan Y , Giannakou A , Bentick B
Published: October 2008

Objectives  To compare the effectiveness of leuprorelin and cetrorelix, when used as preoperative endometrial thinning agents prior to transcervical resection of endometrium (TCRE).

Design  A prospective, double‐blind randomised controlled trial.

Setting  Gynaecological department of a UK district general hospital.

Participants  A total of 106 premenopausal women with dysfunctional uterine bleeding, undergoing TCRE.

Interventions  Women were equally randomised to 3.75 mg of leuprorelin acetate (3–4 weeks) or 3 mg cetrorelix (4–7 days) prior to TCRE. About 1 ml saline was given as placebo in both arms.

Main outcome measures  Amenorrhoea rate at 6 months, endometrial thickness using transvaginal ultrasound on the day of operation.

Results  A total of 100 women completed the trial with no loss to follow up. Amenorrhoea rate at 6 months after surgery was high in both groups (80% cetrorelix and 84% leuprorelin) with no statistical significance. All endometrial outcome measures including endometrial thickness on ultrasound, histology and operative appearance were more favourable in leuprorelin group as compared with cetrorelix (P values 0.013, <0.001 and 0.003 respectively). More women in leuprorelin group had hot flushes as compared with cetrorelix (15/50 versus 6/50; P = 0.047). No significant differences were seen in other outcome measures.

Conclusions  In dosages used, leuprorelin produced more consistent thinning of the endometrium as compared with cetrorelix, although this did not make any significant difference to operative or menstrual outcomes. The endometrial thinning effect with cetrorelix does appear to be more favourable than that seen at postmenstrual phase in other studies. The optimum (possibly higher) dosage of cetrorelix for this purpose has not yet been established.
Experiences and expectations of women with urogenital prolapse: a quantitative and qualitative exploration
Authors: Srikrishna S , Robinson D , Cardozo L , Cartwright R
Published: October 2008

Objective  To explore the expectations and goals of women undergoing surgery for urogenital prolapse using both a quantitative quality of life approach exploring symptom bother and a qualitative interview‐based approach exploring patient goals and expectations.

Design  Prospective observational study.

Setting  Tertiary referral centre for urogynaecology.

Population  Forty‐three women with symptomatic pelvic organ prolapse were recruited from the waiting list for pelvic floor reconstructive surgery.

Methods  All women were assessed with a structured clinical interview on an individual basis. The data obtained were transcribed verbatim and then analysed thematically based on the grounded theory. Individual codes and subcodes were identified to develop a coding framework. The prolapse quality‐of‐life (pQoL) questionnaire was used to determine the impact of pelvic organ prolapse on the woman’s daily life. We arbitrarily classified ‘bother’ as minimal, mild, moderate and marked if scores ranged from 0 to 25, 25–50, 50–75 and 75–100, respectively. The degree of prolapse was objectively quantified using the pelvic organ prolapse quantification (POP‐Q) system. Quantitative data were analysed using SPSS. Ethical approval was obtained from the Kings College Hospital Ethics Committee.

Main outcome measures  Quantitative data from POP‐Q, subjective data from pQoL, qualitative data based on the structured clinical interview.

Results  Forty‐three women were recruited over the first 1 year of the study. Their mean age was 56 years (range 36–78) and mean parity was 2 (range 0–6). The mean ordinal stage of the prolapse was 2 (range stages 1–4). Quantitative analysis of the pQoL data suggested that the main domains affected were prolapse impact on life (mean score 74.71) and personal relationships (mean score 46.66). Qualitative analysis based on the clinical interview suggested that these women were most affected by the actual physical symptoms of prolapse (bulge, pain and bowel problems) as well by the impact prolapse has on their sexual function.

Conclusions  While disease‐specific QoL questionnaires allow broad comparisons to be made assessing patient bother, they may lack the sensitivity to assess individual symptoms. A qualitative approach may individualise patient care and ultimately improve patient satisfaction and overall outcome when treating women complaining of urogenital prolapse.
Effect of margin status on cervical intraepithelial neoplasia recurrence following LLETZ in women over 50 years
Authors: Manchanda R , Baldwin P , Crawford R , Vowler SL , Moseley R , Latimer J , Welton K , Shafi M
Published: October 2008

Objective  To establish the effect of margin status on recurrence following large loop excision of the transformation zone (LLETZ) in women over 50 years.

Study design  Prospectively collected data of women over 50 years, who underwent LLETZ for suspected cervical intraepithelial neoplasia between 1998 and 2003, were analysed. Women were followed up for up to over 6 years.

Setting  District colposcopy service based at a gynae‐oncology cancer centre.

Main outcome measures  The main outcome measure included histologically detected recurrence. Any abnormal cytology on follow up was also documented.

Methods  Prospectively collected data were analysed from the colposcopy database. Recurrence was analysed using Kaplan–Meir plots and Cox regression. Fisher’s exact test was used to determine the association between margins and grade. The Kruskal–Wallis and Mann–Whitney U tests were used to compare age and duration of follow up between groups.

Results  A total of 118 women underwent LLETZ and 92 were included in the final analysis. Margins were designated as clear (n = 62), involved (n = 22) or uncertain (n = 8). Histological recurrence occurred in 12 while abnormal cytology was demonstrated in 17 women. One woman with involved margins developed cervical cancer. Individuals with clear margins were less likely to have recurrence than those with involved margins (Hazard Ratio (HR) 0.18, 95% CI: 0.06–0.59). Involved margins were more common with high‐grade than low‐grade lesions (P = 0.002).

Conclusion  The data show an association between disease recurrence and the finding of involved margins in this cohort.
Prevalence and risk factors of severe obstetric haemorrhage
Authors: Al‐Zirqi I , Vangen S , Forsen L , Stray‐Pedersen B
Published: October 2008

Objective  To determine the prevalence, causes, risk factors and acute maternal complications of severe obstetric haemorrhage.

Design  Population‐based registry study.

Population  All women giving birth (307 415) from 1 January 1999 to 30 April 2004 registered in the Medical Birth Registry of Norway. Information about socio‐economic risk factors was obtained from Statistics Norway.

Methods  Cross‐tabulation was used to study prevalence, causes and acute maternal complications of severe obstetric haemorrhage. Associations of severe obstetric haemorrhage with demographic, medical and obstetric risk factors were estimated using multiple logistic regression models.

Main outcome measure  Severe obstetric haemorrhage (blood loss of > 1500 ml or blood transfusion).

Results  Severe obstetric haemorrhage was identified in 3501 women (1.1%). Uterine atony, retained placenta and trauma were identified causes in 30, 18 and 13.9% of women, respectively. The demographic factors of a maternal age of ≥30 years and South‐East Asian ethnicity were significantly associated with an increased risk of haemorrhage. The risk was lower in women of Middle Eastern ethnicity, more than three and two times higher for emergency caesarean delivery and elective caesarean than for vaginal birth, respectively, and substantially higher for multiple pregnancies, von Willebrand’s disease and anaemia (haemoglobin <9 g/dl) during pregnancy. Admissions to an intensive care unit, postpartum sepsis, hysterectomy, acute renal failure and maternal deaths were significantly more common among women with severe haemorrhage.

Conclusion  The high prevalence of severe obstetric haemorrhage indicates the need to review labour management procedures. Demographic and medical risk factors can be managed with extra vigilance.
Use of nicotine replacement therapy during pregnancy and stillbirth: a cohort study
Authors: Strandberg‐Larsen K , Tinggaard M , Nybo Andersen A‐M , Olsen J , Grønbæk M
Published: October 2008

Objective  The objective of this study was to examine whether the use of nicotine replacement therapy (NRT) during pregnancy increases the risk of stillbirth.

Design  Cohort study with prospective data.

Setting  Denmark 1996–2002.

Population  A total of 87 032 singleton pregnancies enrolled in the Danish National Birth Cohort for which information on NRT use as well as smoking was available.

Methods  Outcome of pregnancy was identified by register linkage, with <1% loss to follow up. We conducted Cox regression analyses to estimate the hazard ratio (HR) and 95% CI of stillbirth according to the use of NRT, type of NRT use and a combination of NRT use and smoking.

Main outcome measures  Stillbirth, defined as delivery of a dead fetus after 20 completed weeks of gestation.

Results  A total of 495 pregnancies (5.7 in 1000 births) ended in stillbirth, 8 of which were among NRT users (4.2 in 1000 births). After adjustment for confounders, women who used NRT during pregnancy had a HR of 0.57 (95% CI 0.28–1.16) for stillbirth compared with those who did not use NRT. Smoking during pregnancy was associated with an increased risk of stillbirth (HR 1.46, 95% CI 1.17–1.82), while women who both smoked and used NRT had a HR of 0.83 (95% CI 0.34–2.00) compared with nonsmoking women who did not use NRT.

Conclusion  Our study does not indicate that use of NRT during pregnancy increases the risk of stillbirth.