Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Funding: The authors thank the Wellcome Trust (102705) and the Universities of Aberdeen and Cape Town for funding. This research was also supported, in part, by National Institutes of Health GM53522 and GM083016 to DLW. KF and BNL are funded by the Fonds Wetenschappelijk Onderzoek, BNL is the recipient of an European Research Commission consolidator grant and participates in the European Union FP7 programs EUBIOPRED and MedALL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Unintended pregnancy: magnitude and correlates in six urban sites in Senegal

BACKGROUND: In Senegal, unintended pregnancy has become a growing concern in public health circles. It has often been described through the press as a sensational subject with emphasis on the multiple infanticide cases as a main consequence, especially among young unmarried girls. Less scientific evidence is known on this topic, as fertility issues are rarely discussed within couples. In a context where urbanization is strong, economic insecurity is persistent and the population is globalizing, it is important to assess the magnitude of unintended pregnancy among urban women and to identify its main determinants. METHODS: Data were collected in 2011 from a representative sample of 9614 women aged 15–49 years in six urban sites in Senegal. For this analysis, we include 5769 women who have ever been pregnant or were pregnant at the time of the survey. These women were asked if their last pregnancy in the last two years was ‘wanted ’then’, ‘wanted later’ or ‘not wanted’. Pregnancy was considered as unintended if the woman responded ‘wanted later’ or ‘not wanted’. Descriptive analyses were performed to measure the magnitude of unintended pregnancies, while multinomial logistic regression models were used to identify factors associated with the occurrence of unintended pregnancy. The analyses were performed using Stata version 12. All results were weighted. RESULTS: The results show that 14.3% of ever pregnant women reported having a recent unintended pregnancy. The study demonstrates important distinctions between women whose last pregnancy was intended and those whose last pregnancy was unintended. Indeed, this last group is more likely to be poor, from a young age (< 25 years) and multiparous. In addition, it appears that low participation of married women in decision-making within the couple (management of financial resources) and the lack of discussion on family planning issues are associated with greater experience of unintended pregnancy. CONCLUSION: This study suggests a need to implement more targeted programs that guarantee access to family planning for all women in need. In urban areas that are characterized by economic insecurity, as in Senegal, it is important to consider strategies for promoting communication within couples on fertility issues

Quantitative imaging of concentrated suspensions under flow

We review recent advances in imaging the flow of concentrated suspensions, focussing on the use of confocal microscopy to obtain time-resolved information on the single-particle level in these systems. After motivating the need for quantitative (confocal) imaging in suspension rheology, we briefly describe the particles, sample environments, microscopy tools and analysis algorithms needed to perform this kind of experiments. The second part of the review focusses on microscopic aspects of the flow of concentrated model hard-sphere-like suspensions, and the relation to non-linear rheological phenomena such as yielding, shear localization, wall slip and shear-induced ordering. Both Brownian and non-Brownian systems will be described. We show how quantitative imaging can improve our understanding of the connection between microscopic dynamics and bulk flow.Comment: Review on imaging hard-sphere suspensions, incl summary of methodology. Submitted for special volume 'High Solid Dispersions' ed. M. Cloitre, Vol. xx of 'Advances and Polymer Science' (Springer, Berlin, 2009); 22 pages, 16 fig

Pressure is not a state function for generic active fluids

Pressure is the mechanical force per unit area that a confined system exerts on its container. In thermal equilibrium, it depends only on bulk properties (density, temperature, etc.) through an equation of state. Here we show that in a wide class of active systems the pressure depends on the precise interactions between the active particles and the confining walls. In general, therefore, active fluids have no equation of state, their mechanical pressures exhibit anomalous properties that defy the familiar thermodynamic reasoning that holds in equilibrium. The pressure remains a function of state, however, in some specific and well-studied active models that tacitly restrict the character of the particle-wall and/or particle-particle interactions.Comment: 8 pages + 9 SI pages, Nature Physics (2015

Self-Supervised Discovery of Anatomical Shape Landmarks

Statistical shape analysis is a very useful tool in a wide range of medical and biological applications. However, it typically relies on the ability to produce a relatively small number of features that can capture the relevant variability in a population. State-of-the-art methods for obtaining such anatomical features rely on either extensive preprocessing or segmentation and/or significant tuning and post-processing. These shortcomings limit the widespread use of shape statistics. We propose that effective shape representations should provide sufficient information to align/register images. Using this assumption we propose a self-supervised, neural network approach for automatically positioning and detecting landmarks in images that can be used for subsequent analysis. The network discovers the landmarks corresponding to anatomical shape features that promote good image registration in the context of a particular class of transformations. In addition, we also propose a regularization for the proposed network which allows for a uniform distribution of these discovered landmarks. In this paper, we present a complete framework, which only takes a set of input images and produces landmarks that are immediately usable for statistical shape analysis. We evaluate the performance on a phantom dataset as well as 2D and 3D images.Comment: Early accept at MICCAI 202

Avoiding Treatment Interruptions: What Role Do Australian Community Pharmacists Play?

OBJECTIVE: To explore the reported practice of Australian community pharmacists when dealing with medication supply requests in absence of a valid prescription. METHODS: Self-administered questionnaire was posted to 1490 randomly selected community pharmacies across all Australian states and territories. This sample was estimated to be a 20% of all Australian community pharmacies. RESULTS: Three hundred eighty five pharmacists participated in the study (response rate achieved was 27.9% (there were 111 undelivered questionnaires). Respondents indicated that they were more likely to provide medications to regular customers without a valid prescription compared to non-regular customers (p&lt;0.0001). However, supply was also influenced by the type of prescription and the medication requested. In the case of type of prescription (Standard, Authority or Private) this relates to the complexity/probability of obtaining a valid prescription from the prescriber at a later date (i.e. supply with an anticipated prescription). Decisions to supply and/or not supply related to medication type were more complex. For some cases, including medication with potential for abuse, the practice and/or the method of supply varied significantly according to age and gender of the pharmacist, and pharmacy location (p&lt;0.05). CONCLUSIONS: Although being a regular customer does not guarantee a supply, results of this study reinforce the importance for patients having a regular pharmacy, where pharmacists were more likely to continue medication supply in cases of patients presenting without a valid prescription. We would suggest, more flexible legislation should be implemented to allow pharmacists to continue supplying of medication when obtaining a prescription is not practical

Attitudes to and management of fertility among primary health care physicians in Turkey: An epidemiological study

BACKGROUND: The subject of infertility has taken its place in the health sector at the top level. Since primary health care services are insufficient, most people, especially women, keep on suffering from it all over the world, namely in underdeveloped or developing countries. The aim of this study was to determine primary care physicians' opinions about the approach to infertility cases and their place within primary health care services (PHCSs). METHODS: The study was conducted between October 2003 and April 2004. The study group comprised 748 physicians working in PHCSs. They were asked to fill in a questionnaire with questions pertaining to infertility support, laboratory and treatment algorithms, as well as the demographic characteristics. The data was evaluated using the chi square test, percentage rates and a logistic regression model. RESULTS: The multivariate analyses showed that having a previous interest in infertility and having worked for a postgraduate period of between 5–9 years and ≥10 years were the variables that most positively influenced them in their approach to cases of infertility (p < 0.05, each one). Just 28.7% of the physicians indicated that they believed cases of infertility could be evaluated at the primary care level. The most frequently proposed reason for indicating 'difficulty in practice' (n = 533) was inadequate provision of equipment in PHCSs (55.7%). The physicians reported that they were able to perform most of the supportive treatments and proposals (between 64.6%–87.7%). The most requested laboratory investigations were the instruction of patients in taking basal body temperatures and semen analysis (89.7% and 88.7%, respectively). The most preferential course of treatment was that of sexually transmitted diseases (95.5%). CONCLUSION: It is clear that not enough importance is attached to the provision of care to infertile couples within PHCSs. This leads us to conclude that an integration of infertility services in primary care would be appropriate after strengthening the PHCSs

Disturbance and diversity at two spatial scales

The spatial scale of disturbance is a factor potentially influencing the relationship between disturbance and diversity. There has been discussion on whether disturbances that affect local communities and create a mosaic of patches in different successional stages have the same effect on diversity as regional disturbances that affect the whole landscape. In a microcosm experiment with metacommunities of aquatic protists, we compared the effect of local and regional disturbances on the disturbance–diversity relationship. Local disturbances destroyed entire local communities of the metacommunity and required reimmigration from neighboring communities, while regional disturbances affected the whole metacommunity but left part of each local community intact. Both disturbance types led to a negative relationship between disturbance intensity and Shannon diversity. With strong local disturbance, this decrease in diversity was due to species loss, while strong regional disturbance had no effect on species richness but reduced the evenness of the community. Growth rate appeared to be the most important trait for survival after strong local disturbance and dominance after strong regional disturbance. The pattern of the disturbance–diversity relationship was similar for both local and regional diversity. Although local disturbances at least temporally increased beta diversity by creating a mosaic of differently disturbed patches, this high dissimilarity did not result in regional diversity being increased relative to local diversity. The disturbance–diversity relationship was negative for both scales of diversity. The flat competitive hierarchy and absence of a trade-off between competition and colonization ability are a likely explanation for this pattern

Allergen Uptake, Activation, and IL-23 Production by Pulmonary Myeloid DCs Drives Airway Hyperresponsiveness in Asthma-Susceptible Mice

Maladaptive, Th2-polarized inflammatory responses are integral to the pathogenesis of allergic asthma. As regulators of T cell activation, dendritic cells (DCs) are important mediators of allergic asthma, yet the precise signals which render endogenous DCs “pro-asthmatic”, and the extent to which these signals are regulated by the pulmonary environment and host genetics, remains unclear. Comparative phenotypic and functional analysis of pulmonary DC populations in mice susceptible (A/J), or resistant (C3H) to experimental asthma, revealed that susceptibility to airway hyperresponsiveness is associated with preferential myeloid DC (mDC) allergen uptake, and production of Th17-skewing cytokines (IL-6, IL-23), whereas resistance is associated with increased allergen uptake by plasmacytoid DCs. Surprisingly, adoptive transfer of syngeneic HDM-pulsed bone marrow derived mDCs (BMDCs) to the lungs of C3H mice markedly enhanced lung IL-17A production, and rendered them susceptible to allergen-driven airway hyperresponsiveness. Characterization of these BMDCs revealed levels of antigen uptake, and Th17 promoting cytokine production similar to that observed in pulmonary mDCs from susceptible A/J mice. Collectively these data demonstrate that the lung environment present in asthma-resistant mice promotes robust pDC allergen uptake, activation, and limits Th17-skewing cytokine production responsible for driving pathologic T cell responses central to the development of allergen-induced airway hyperresponsiveness