Intrauterine exposure to mild analgesics during pregnancy and the occurrence of cryptorchidism and hypospadia in the offspring: The Generation R Study

This article is available open access through the publisher’s website. Copyright @ 2012 The Authors.BACKGROUND - Recently, over-the-counter mild analgesic use during pregnancy has been suggested to influence the risk of reproductive disorders in the offspring. We examined the influence of maternal exposure to mild analgesics during pregnancy on the occurrence of cryptorchidism and hypospadia in their offspring. METHODS - Associations between maternal exposure to mild analgesics during pregnancy and cryptorchidism or hypospadia in the offspring were studied in 3184 women participating in a large population-based prospective birth cohort study from early pregnancy onwards in the Netherlands (2002–2006), the Generation R Study. Cryptorchidism and hypospadia were identified during routine screening assessments performed in child health care centres by trained physicians. The use of mild analgesics was assessed in three prenatal questionnaires in pregnancy, resulting in four periods of use, namely, periconception period, first 14 weeks of gestation, 14–22 weeks of gestation and 20–32 weeks of gestation. Logistic regression analyses were used to study the associations between maternal exposure to mild analgesics and cryptorchidism and hypospadia. RESULTS - The cumulative prevalence over 30 months of follow up was 2.1% for cryptorchidism and 0.7% for hypospadia. Use of mild analgesics in the second period of pregnancy (14–22 weeks) increased the risk of congenital cryptorchidism [adjusted odds ratio (OR) 2.12; 95% confidence interval (CI) 1.17–3.83], primarily due to the use of acetaminophen (paracetamol) (adjusted OR 1.89; 95% CI 1.01–3.51). Among mothers of cryptorchid sons, 33.8% reported (23 of 68) the use of mild analgesics during pregnancy, compared with 31.8% (7 of 22) of mothers with a boy with hypospadia and 29.9% (926 of 3094) of mothers with healthy boys. CONCLUSIONS - Our results suggest that intrauterine exposure to mild analgesics, primarily paracetamol, during the period in pregnancy when male sexual differentiation takes place, increases the risk of cryptorchidism.Erasmus University Rotterdam, School of Law and Faculty of Social Sciences, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR), Rotterdam

The algebra of lexical semantics

Abstract. The current generative theory of the lexicon relies primar-ily on tools from formal language theory and mathematical logic. Here we describe how a different formal apparatus, taken from algebra and automata theory, resolves many of the known problems with the gener-ative lexicon. We develop a finite state theory of word meaning based on machines in the sense of Eilenberg [11], a formalism capable of de-scribing discrepancies between syntactic type (lexical category) and se-mantic type (number of arguments). This mechanism is compared both to the standard linguistic approaches and to the formalisms developed in AI/KR. 1 Problem Statement In developing a formal theory of lexicography our starting point will be the informal practice of lexicography, rather than the more immediately related for-mal theories of Artificial Intelligence (AI) and Knowledge Representation (KR). Lexicography is a relatively mature field, with centuries of work experience an

A prospective observational study of bacteraemia in adults admitted to an urban Mozambican hospital

Background. Bacteraemia is a common cause of fever among patients presenting to hospitals in  sub-Saharan Africa. The worldwide rise of antibiotic resistance makes empirical therapy increasingly  difficult, especially in resource-limited settings.Objectives. To describe the incidence of bacteraemia in febrile adults presenting to Maputo Central Hospital (MCH), an urban referral hospital in the capital of Mozambique, and characterise the causative  organisms and antibiotic susceptibilities. We aimed to describe the antibiotic prescribing habits of local doctors, to identify areas for quality improvement.Methods. Inclusion criteria were: (i) .18 years of age; (ii) axillary temperature .38‹C or .35‹C; (iii) admission to MCH medical wards in the past 24 hours; and (iv) no receipt of antibiotics as an inpatient. Blood cultures were drawn from enrolled patients and incubated using the BacT/Alert automated system (bioMerieux, France). Antibiotic susceptibilities were tested using the Kirby-Bauer disc diffusion method.Results. Of the 841 patients enrolled, 63 (7.5%) had a bloodstream infection. The most common isolates were Staphylococcus aureus, Escherichia coli, and non-typhoidal Salmonella. Antibiotic resistance was common, with 20/59 (33.9%) of all bacterial isolates showing resistance to ceftriaxone, the broadest-spectrum antibiotic commonly available at MCH. Receipt of insufficiently broad empirical antibiotics was associated with poor in-hospital outcomes (odds ratio 8.05; 95% confidence interval 1.62 - 39.91;  p=0.04).Conclusion. This study highlights several opportunities for quality improvement, including educating doctors to have a higher index of suspicion for bacteraemia, improving local antibiotic guidelines,  improving communication between laboratory and doctors, and increasing the supply of some key antibiotics

Calorimetric Investigation of Copper Binding in the N-Terminal Region of the Prion Protein at Low Copper Loading: Evidence for an Entropically Favorable First Binding Event

Although the Cu²⁺-binding sites of the prion protein have been well studied when the protein is fully saturated by Cu²⁺, the Cu²⁺-loading mechanism is just beginning to come into view. Because the Cu²⁺-binding modes at low and intermediate Cu²⁺ occupancy necessarily represent the highest-affinity binding modes, these are very likely populated under physiological conditions, and it is thus essential to characterize them in order to understand better the biological function of copper–prion interactions. Besides binding-affinity data, almost no other thermodynamic parameters (e.g., Δ<i>H</i> and Δ<i>S</i>) have been measured, thus leaving undetermined the enthalpic and entropic factors that govern the free energy of Cu²⁺ binding to the prion protein. In this study, isothermal titration calorimetry (ITC) was used to quantify the thermodynamic parameters (<i>K</i>, Δ<i>G</i>, Δ<i>H</i>, and <i>T</i>Δ<i>S</i>) of Cu²⁺ binding to a peptide, PrP­(23–28, 57–98), that encompasses the majority of the residues implicated in Cu²⁺ binding by full-length PrP. Use of the buffer <i>N</i>-(2-acetomido)-aminoethanesulfonic acid (ACES), which is also a well-characterized Cu²⁺ chelator, allowed for the isolation of the two highest affinity binding events. Circular dichroism spectroscopy was used to characterize the different binding modes as a function of added Cu²⁺. The <i>K</i>_d values determined by ITC, 7 and 380 nM, are well in line with those reported by others. The first binding event benefits significantly from a positive entropy, whereas the second binding event is enthalpically driven. The thermodynamic values associated with Cu²⁺ binding by the Aβ peptide, which is implicated in Alzheimer’s disease, bear striking parallels to those found here for the prion protein

State of the field: What can political ethnography tell us about anti-politics and democratic disaffection?

This article adopts and reinvents the ethnographic approach to uncover what governing elites do, and how they respond to public disaffection. Although there is significant work on the citizens’ attitudes to the governing elite (the demand side) there is little work on how elites interpret and respond to public disaffection (the supply side). We argue that ethnography is the best available research method for collecting data on the supply side. In doing so, we tackle long-standing stereotypes in political science about the ethnographic method and what it is good for. We highlight how the innovative and varied practices of contemporary ethnography are ideally suited to shedding light into the ‘black box’ of elite politics. We demonstrate the potential pay-off with reference to important examples of elite ethnography from the margins of political science scholarship. The implications from these rich studies, we argue, suggest a reorientation of how we understand the drivers of public disaffection and the role that political elites play in exacerbating cynicism and disappointment. We conclude by pointing to the benefits to the discipline in embracing elite ethnography both to diversify the methodological toolkit in explaining the complex dynamics of disaffection,and to better enable engagement in renewed public debate about the political establishment

The retreat from locative overgeneralisation errors : a novel verb grammaticality judgment study

Whilst some locative verbs alternate between the ground- and figure-locative constructions (e.g. Lisa sprayed the flowers with water/Lisa sprayed water onto the flowers), others are restricted to one construction or the other (e.g. *Lisa filled water into the cup/*Lisa poured the cup with water). The present study investigated two proposals for how learners (aged 5–6, 9–10 and adults) acquire this restriction, using a novel-verb-learning grammaticality-judgment paradigm. In support of the semantic verb class hypothesis, participants in all age groups used the semantic properties of novel verbs to determine the locative constructions (ground/figure/both) in which they could and could not appear. In support of the frequency hypothesis, participants’ tolerance of overgeneralisation errors decreased with each increasing level of verb frequency (novel/low/high). These results underline the need to develop an integrated account of the roles of semantics and frequency in the retreat from argument structure overgeneralisation