London measure of Unplanned Pregnancy: guidance for its use as an outcome measure

Background: The London Measure of Unplanned Pregnancy (LMUP) is a psychometrically validated measure of the degree of intention of a current or recent pregnancy. The LMUP is increasingly being used worldwide, and can be used to evaluate family planning or ­preconception care programs. However, beyond recommending the use of the full LMUP scale, there is no published guidance on how to use the LMUP as an outcome measure. Ordinal logistic regression has been recommended informally, but studies published to date have all used binary logistic regression and dichotomized the scale at different cut points. There is thus a need for evidence-based guidance to provide a standardized methodology for multivariate analysis and to enable comparison of results. This paper makes recommendations for the regression method for analysis of the LMUP as an outcome measure. Materials and methods: Data collected from 4,244 pregnant women in Malawi were used to compare five regression methods: linear, logistic with two cut points, and ordinal logistic with either the full or grouped LMUP score. The recommendations were then tested on the original UK LMUP data. Results: There were small but no important differences in the findings across the regression models. Logistic regression resulted in the largest loss of information, and assumptions were violated for the linear and ordinal logistic regression. Consequently, robust standard errors were used for linear regression and a partial proportional odds ordinal logistic regression model attempted. The latter could only be fitted for grouped LMUP score. Conclusion: We recommend the linear regression model with robust standard errors to make full use of the LMUP score when analyzed as an outcome measure. Ordinal logistic regression could be considered, but a partial proportional odds model with grouped LMUP score may be required. Logistic regression is the least-favored option, due to the loss of information. For logistic regression, the cut point for un/planned pregnancy should be between nine and ten. These recommendations will standardize the analysis of LMUP data and enhance comparability of results across studies

Pregnancy Intention and Pregnancy Outcome: Systematic Review and Meta-Analysis

Introduction Previous systematic reviews concluded that rigorous research on the relationships between pregnancy intentions and pregnancy outcomes is limited. They further noted that most studies were conducted in high-income countries and had methodological limitations. We aim to assess the current evidence base for the relationship between pregnancy intention and miscarriage, stillbirth, low birthweight (LBW) and neonatal mortality. In March 2015 Embase, PubMed, Scopus and PsychInfo were searched for studies investigating the relationship between pregnancy intention and the outcomes of interest. Methods Studies published since 1975 and in English, French or Spanish were included. Two reviewers screened titles and abstracts, read the full text of identified articles and extracted data. Meta-analyses were conducted where possible. Results Thirty-seven studies assessing the relationships between pregnancy intention and LBW were identified. A meta-analysis of 17 of these studies found that unintended pregnancies are associated with 1.41 times greater odds of having a LBW baby (95%CI 1.31, 1.51). Eight studies looking at miscarriage, stillbirth or neonatal death were found. The limited data concerning pregnancy loss and neonatal mortality precluded meta-analysis but suggest these outcomes may be more common in unintended pregnancies. Discussion While there seems to be an increased risk of adverse pregnancy outcome in unintended pregnancies, there has been little improvement in either the quantity of evidence from low-income countries or in the quality of evidence generally. Longitudinal studies of pregnancy intention and pregnancy outcome, where pregnancy intention is assessed prospectively with a validated measure and where analyses include confounding or mediating factors, are required in both high- and low-income countries

Flavor Phenomenology in General 5D Warped Spaces

We have considered a general 5D warped model with SM fields propagating in the bulk and computed explicit expressions for oblique and non-oblique electroweak observables as well as for flavor and CP violating effective four-fermion operators. We have compared the resulting lower bounds on the Kaluza-Klein (KK) scale in the RS model and a recently proposed model with a metric modified towards the IR brane, which is consistent with oblique parameters without the need for a custodial symmetry. We have randomly generated 40,000 sets of O(1) 5D Yukawa couplings and made a fit of the quark masses and CKM matrix elements in both models. This method allows to identify the percentage of points consistent with a given KK mass, which in turn provides us with a measure for the required fine-tuning. Comparison with current experimental data on Rb, FCNC and CP violating operators exhibits an improved behavior of our model with respect to the RS model. In particular, allowing 10% fine-tuning the combined results point towards upper bounds on the KK gauge boson masses around 3.3 TeV in our model as compared with 13 TeV in the RS model. One reason for this improvement is that fermions in our model are shifted, with respect to fermions in the RS model, towards the UV brane thus decreasing the strength of the modifications of electroweak observables.Comment: 28 pages, 7 figures, 4 table

Natural parasitism of the Citrus Leafminer (Lepidoptera: Gracillariidae) over eight years in seven citrus regions of São Paulo, Brazil

The citrus leafminer (CLM) Phyllocnists citrella Stainton (Lepidoptera: Gracillariidae) was frst recorded in Brazil in 1996. In 1998, the parasitoid Ageniaspis citricola Logvinovskaya (Hymenoptera: Encyrtdae) was introduced and established in many regions of the country. In this study, 130 onehour-samplings of sweet orange leaves (Citrus sinensis [L.] Osbeck) hostng CLM pupal chambers were carried out to estmate the CLM parasitsm rate (%) by its parasitoids in 7 regions of São Paulo State between 2000 and 2008. The sample sizes varied from 10 to 275 leaves (mean = 65). The most abundant parasitoid was the encyrtd A. citricola (found in 91.8% of the samplings). The highest level of CLM parasitsm by A. citricola was recorded in the southern region (Botucatu), 70.2 ± 6.6 (mean ± SEM), and the lowest level was recorded in the northern region (Barretos), 12.8 ± 5.7%. CLM parasitsm by A. citricola and by natve parasitoids (Galeopsomyia fausta LaSalle, Cirrospilus spp. and Elasmus sp.) did not differ between seasons. The 6-fold increase in the use of insectcides in citrus groves, afer 2004 when the Huanglongbing (HLB) disease was found in São Paulo State, did not reduce the level of CLM parasitsm. The level of parasitsm was 50.8 ± 4.2% before the advent of HLB (2000–2004) and 56.0 ± 4.4% thereafer (2005–2008), indicatng adaptaton of A. citricola in a disturbed agroecosystem.A minadora das folhas dos citros (MFC), Phyllocnistis citrella Stainton (Lepidoptera: Gracillariidae), foi encontrada pela primeira vez no Brasil em 1996. Em 1998, o parasitoide Ageniaspis citricola Logvinovskaya (Hymenoptera: Encyrtidae) foi introduzido e se estabeleceu em várias regiões do país. Nesse estudo, foram feitas130 amostragens, de uma hora, de folhas de laranjeiras doces [Citrus sinensis (L.) Osbeck] com câmaras pupais da MFC, para se estimar o parasitismo da MFC em 7 regiões do estado de São Paulo, entre 2000 e 2008. O tamanho das amostras variou de 10 a 275 folhas (média = 65). O parasitoide mais abundante foi o encirtídeo A. citricola (encontrado em 91.8% das amostragens). O maior parasitismo da MFC por A. citricola foi observado na região sul do estado (Botucatu), 70,2 ± 6,6 (média ± EPM), e o menor parasitismo na região norte (Barretos), 12,8 ± 5,7%. O parasitismo da MFC por A. citricola e seus parasitoides nativos (Galeopsomyia fausta LaSalle, Cirrospilus spp. and Elasmus sp.) não diferiram entre as estações do ano. O aumento de seis vezes no uso de inseticidas nos pomares de citros, após 2004, quando o Huanglongbing (HLB) foi encontrado no estado de São Paulo, não reduziu o nível de parasitismo da MFC. O nível médio de parasitismo foi de 50,8 ± 4,2%, antes do HLB (2000-2004), e 56,0 ± 4,4%, após o HLB (2005-2008), indicando a adaptação de A. citricola a um agroecossistema perturbado.info:eu-repo/semantics/publishedVersio

Prevalence and Determinants of Unintended Pregnancy in Mchinji District, Malawi; Using a Conceptual Hierarchy to Inform Analysis

Background: In 2012 there were around 85 million unintended pregnancies globally. Unintended pregnancies unnecessarily expose women to the risks associated with pregnancy, unsafe abortion and childbirth, thereby contributing to maternal mortality and morbidity. Studies have identified a range of potential determinants of unplanned pregnancy but have used varying methodologies, measures of pregnancy intention and analysis techniques. Consequently there are many contradictions in their findings. Identifying women at risk of unplanned pregnancy is important as this information can be used to help with designing and targeting interventions and developing preventative policies. Methods: 4,244 pregnant women from Mchinji District, Malawi were interviewed at home between March and December 2013. They were asked about their pregnancy intention using the validated Chichewa version of the London Measure of Unplanned Pregnancy, as well as their socio-demographics and obstetric and psychiatric history. A conceptual hierarchical model of the determinants of pregnancy intention was developed and used to inform the analysis. Multiple random effects linear regression was used to explore the ways in which factors determine pregnancy intention leading to the identification of women at risk of unplanned pregnancies. Results: 44.4% of pregnancies were planned. On univariate analyses pregnancy intention was associated with mother and father’s age and education, marital status, number of live children, birth interval, socio-economic status, intimate partner violence and previous depression all at p<0.001. Multiple linear regression analysis found that increasing socio-economic status is associated with increasing pregnancy intention but its effect is mediated through other factors in the model. Socio-demographic factors of importance were marital status, which was the factor in the model that had the largest effect on pregnancy intention, partner’s age and mother’s education level. The effect of mother’s education level was mediated by maternal reproductive characteristics. Previous depression, abuse in the last year or sexual abuse, younger age, increasing number of children and short birth intervals were all associated with lower pregnancy intention having controlled for all other factors in the model. This suggests that women in Mchinji District who are either young, unmarried women having their first pregnancy, or older, married women who have completed their desired family size or recently given birth, or women who have experienced depression, abuse in the last year or sexual abuse are at higher risk of unintended pregnancies. Conclusion: A simple measure of pregnancy intention with well-established psychometric properties was used to show the distribution of pregnancy planning among women from a poor rural population and to identify those women at higher risk of unintended pregnancy. An analysis informed by a conceptual hierarchical model shed light on the pathways that lead from socio-demographic determinants to pregnancy intention. This information can be used to target family planning services to those most at risk of unplanned pregnancies, particularly women with a history of depression or who are experiencing intimate partner violence

Does Intragastric Balloon Treatment for Obesity in Chronic Kidney Disease Heighten Acute Kidney Injury Risk?

Background: The outcomes of intragastric balloon (IGB) placement to achieve weight loss in obese patients with chronic kidney disease (CKD) have not been reported to date. This study aimed to assess the safety and efficacy of the IGB as a weight-loss treatment among this patient population. Methods: A prospective, single-arm, ‘first in CKD' interventional study was conducted in patients with a body mass index >35 kg/m2 and CKD stages 3-4, referred for weight loss. After clinical assessment, the IGB was endoscopically inserted into the stomach and kept in place for 6 months. Complications, adverse events, acceptability, weight loss and metabolic responses were monitored over 6 months. Results: Eleven participants were recruited over 18 months. Two patients withdrew (1 prior to IGB insertion and 1 early removal after 3 days due to persistent vomiting) from the study; 9 patients completed the study. There were 5 episodes of acute kidney injury (AKI), occurring in 3 patients. After 6 months, the mean body mass decreased by 9.6% (SD ±6.8). Median waist circumference and total cholesterol decreased significantly (-7.7 cm; interquartile range (IQR) -15.3 to -3.9; and -0.2 mmol/l; IQR -0.6 to -0.05, respectively), with no changes in estimated glomerular filtration rate, blood pressure, triglycerides, adipokines, inflammation, or arterial stiffness measured by carotid-femoral pulse wave velocity. At IGB removal, there was 1 new case each of gastritis and esophagitis. Conclusions: Treatment with IGB has only moderate efficacy on weight loss; yet it results in a high rate of complications in obese patients with established CKD. The risk of AKI may be raised due to increased risk of dehydration secondary to gastrointestinal symptoms associated with IGB placement and reduced baseline kidney function

In vitro efficacy of tavaborole topical solution, 5% after penetration through nail polish on ex vivo human fingernails

This document is the Accepted Manuscript of the following article: Aditya K. Gupta, et al, 'In vitro efficacy of tavaborole topical solution, 5% after penetration through nail polish on ex vivo human fingernails', Journal of Dermatological Treatment, Jan 2018. Under embargo until 10 January 2019. The final, published version is available online at doi: https://doi.org/10.1080/09546634.2017.1422078.Background: Topical antifungal treatments for onychomycosis are applied to clean, unpolished nails for 48 weeks or longer. Patients often wish to mask their infection with nail polish yet there is no evidence to suggest antifungal efficacy in the presence of nail polish. Objective: To determine if tavaborole retains the ability to penetrate the nail plate and inhibit fungal growth in the presence of nail polish. Method: Tavaborole was applied to human fingernails painted with 2 or 4 coats of nail polish, and unpainted nails in an ex vivo model. Nails were mounted on TurChub ® chambers seeded with Trichophyton rubrum and allowed to incubate for 7 days. Antifungal activity was assessed by measuring zones of inhibition. Results and conclusion: Tavaborole exhibited antifungal activity in all experimental groups. The zones of inhibition of T. rubrum for all experimental groups (2 or 4 coats of polish, unpolished) were greater than infected controls (polished and unpolished), p s <.001. Tavaborole penetrates polished nails and kills T. rubrum in this ex vivo model.Peer reviewe

Identification of the endophilins (SH3p4/p8/p13) as novel binding partners for the beta1-adrenergic receptor.

Several G-protein coupled receptors, such as the beta1-adrenergic receptor (beta1-AR), contain polyproline motifs within their intracellular domains. Such motifs in other proteins are known to mediate protein-protein interactions such as with Src homology (SH)3 domains. Accordingly, we used the proline-rich third intracellular loop of the beta1-AR either as a glutathione S-transferase fusion protein in biochemical "pull-down" assays or as bait in the yeast two-hybrid system to search for interacting proteins. Both approaches identified SH3p4/p8/p13 (also referred to as endophilin 1/2/3), a SH3 domain-containing protein family, as binding partners for the beta1-AR. In vitro and in human embryonic kidney (HEK) 293 cells, SH3p4 specifically binds to the third intracellular loop of the beta1-AR but not to that of the beta2-AR. Moreover, this interaction is mediated by the C-terminal SH3 domain of SH3p4. Functionally, overexpression of SH3p4 promotes agonist-induced internalization and modestly decreases the Gs coupling efficacy of beta1-ARs in HEK293 cells while having no effect on beta2-ARs. Thus, our studies demonstrate a role of the SH3p4/p8/p13 protein family in beta1-AR signaling and suggest that interaction between proline-rich motifs and SH3-containing proteins may represent a previously underappreciated aspect of G-protein coupled receptor signaling

Fit for the future? The place of global health in the UK's postgraduate medical training: a review.

OBJECTIVES: That health is now global is increasingly accepted. However, a 'mismatch between present professional competencies and the requirements of an increasingly interdependent world' has been identified. Postgraduate training should take account of the increasingly global nature of health; this paper examines the extent to which they currently do. DESIGN: Trainees across 11 medical specialties reviewed the content of their postgraduate curriculum. SETTING: Not relevant. PARTCIPANTS: None. MAIN OUTCOME MEASURES: Competencies were coded as 'UK' (statement only relevant to UK work), 'global' (statement with an explicit reference to aspects of health outside the UK) or generic (relevant both to the UK and international settings). RESULTS: Six of the 11 curricula reviewed contained global health competencies. These covered the global burden or determinants of disease and appropriate policy responses. Only one College required trainees to 'be aware of the World Health Organization', or 'know the local, national and international structures for health care'. These cross-cutting competencies have applicability to all specialties. All 11 curricula contained generic competencies where a global health perspective and/or experience could be advantageous, e.g. caring for migrant or culturally different patients. CONCLUSION: Trainees in all specialties should achieve a minimum requirement of global health awareness. This can be achieved through a small number of common competencies that are consistent across core curricula. These should lead on from equivalent undergraduate competencies. Addressing the current gap in the global health content of postgraduate medical curricula will ensure that the UK has health professionals that are trained to meet the health challenges of the future

The Plasmodium falciparum, Nima-related kinase Pfnek-4: a marker for asexual parasites committed to sexual differentiation

&lt;b&gt;Background&lt;/b&gt; Malaria parasites undergo, in the vertebrate host, a developmental switch from asexual replication to sexual differentiation leading to the formation of gametocytes, the only form able to survive in the mosquito vector. Regulation of the onset of the sexual phase remains largely unknown and represents an important gap in the understanding of the parasite's complex biology. &lt;b&gt;Methods:&lt;/b&gt; The expression and function of the Nima-related kinase Pfnek-4 during the early sexual development of the human malaria parasite Plasmodium falciparum were investigated, using three types of transgenic Plasmodium falciparum 3D7 lines: (i) episomally expressing a Pfnek-4-GFP fusion protein under the control of its cognate pfnek-4 promoter; (ii) episomally expressing negative or positive selectable markers, yeast cytosine deaminase-uridyl phosphoribosyl transferase, or human dihydrofolate reductase, under the control of the pfnek-4 promoter; and (iii) lacking a functional pfnek-4 gene. Parasite transfectants were analysed by fluorescence microscopy and flow cytometry. In vitro growth rate and gametocyte formation were determined by Giemsa-stained blood smears. &lt;b&gt;Results:&lt;/b&gt; The Pfnek-4-GFP protein was found to be expressed in stage II to V gametocytes and, unexpectedly, in a subset of asexual-stage parasites undergoing schizogony. Culture conditions stimulating gametocyte formation resulted in significant increase of this schizont subpopulation. Moreover, sorted asexual parasites expressing the Pfnek-4-GFP protein displayed elevated gametocyte formation when returned to in vitro culture in presence of fresh red blood cells, when compared to GFP- parasites from the same initial population. Negative selection of asexual parasites expressing pfnek-4 showed a marginal reduction in growth rate, whereas positive selection caused a marked reduction in parasitaemia, but was not sufficient to completely abolish proliferation. Pfnek-4- clones are not affected in their asexual growth and produced normal numbers of stage V gametocytes. &lt;b&gt;Conclusions:&lt;/b&gt; The results indicate that Pfnek-4 is not strictly gametocyte-specific, and is expressed in a small subset of asexual parasites displaying high rate conversion to sexual development. Pfnek-4 is not required for erythrocytic schizogony and gametocytogenesis. This is the first study to report the use of a molecular marker for the sorting of sexually-committed schizont stage P. falciparum parasites, which opens the way to molecular characterization of this pre-differentiated subpopulation