Experience with UIDC insertion outside of menses in Kenya

Objective: To determine if women receiving intrauterine devices (IUCDs) outside of menses have an acceptable rate of insertion problems and subsequent IUCD-related complications.Design: Cross-sectional and prospective cohort study of insertions at times other than during menses.Setting: The study was carried out in two government family planning (FP) clinics in Nairobi,Kenya.Subjects: After appropriate pre-test and post-test HIV counselling, 1686 women requesting IUCDs at two FP clinics between 1994 and 1995 in Nairobi were enrolled at baseline into a study examining the effect of human complications. Six hundred and forty nine women (156 HIV-infected and 493 HIVuninfected) were selected for the four month follow up study. They were classified according to their menstrual cycle status at time of IUCD insertion.Main outcome measures: Problems at the time of insertion (pain, bleeding, immediate expulsion) and IUCD-related complications through four months.Results: Rates of immediate insertion problems were low in the women who had insertions during menses (7.0%), outside of menses (4.0%) or had oligomenorrhea/amenorrhea (2.6%). The adjusted odds ratios for IUCD insertion problems outside of menses and in oligomenorrhea/amenorrhea (versus women with insertion during menses) were 0.54 (95% CI 0.18 -1.59) and 0.39 (95% CI 0.12 -1.29) respectively. IUCD-related complications were higher in the iligomenorrhea/amenorrhea (11.5%) or insertion outside of menses (6.9%), than the within menses (4.3%) groups. However, the differences were not statistically significant. Adjusted odds ratios for IUCD outside of menses and oligomenorrhoea/amenorrhea groups were 1.65 (95% CI 0.21 - 12.91) and 2.72 (95% CI 0.34 - 21.71) respectively.Conclusion: The results confirm that the IUCD can be safely inserted outside of menses with minimal insertion difficulties and subsequent complications. Availability of IUCDs outside of menses may enhance IUCD acceptance in Kenya and create better opportunity for visualscreening of the cervix for sexually transmitted infections

Changes in iron-regulatory gene expression occur in human cell culture models of Parkinson's disease.

BACKGROUND: Neuronal iron accumulation is thought to be relevant to the pathogenesis of Parkinson's disease (PD), although the mechanism remains elusive. We hypothesized that neuronal iron uptake may be stimulated by functional mitochondrial iron deficiency. OBJECTIVE: To determine firstly whether the mitochondrial toxin, 1-methyl-4-phenylpyridinium iodide (MPP(+)), results in upregulation of iron-import proteins and transporters of iron into the mitochondria, and secondly whether similar changes in expression are induced by toxins with different mechanisms of action. METHODS: We used quantitative PCR and Western blotting to investigate expression of the iron importers, divalent metal transporter, transferrin receptor 1 and 2 (TfR1 and TfR2) and mitoferrin-2 and the iron exporter ferroportin in differentiated SH-SY5Y cells exposed to three different toxins relevant to PD, MPP(+), paraquat (a free radical generator) and lactacystin (an inhibitor of the ubiquitin-proteasome system (UPS)). RESULTS: MPP(+) resulted in increased mRNA and protein levels of genes involved in cellular iron import and transport into the mitochondria. Similar changes occurred following exposure to paraquat, another inducer of oxidative stress. Lactacystin also resulted in increased TfR1 mRNA levels, although the other changes were not found. CONCLUSION: Our results support the hypothesis of a functional mitochondrial iron deficit driving neuronal iron uptake but also suggest that differences exist in neuronal iron handling induced by different toxins

Testing KiDS cross-correlation redshifts with simulations

Measuring cosmic shear in wide-field imaging surveys requires accurate knowledge of the redshift distribution of all sources. The clustering-redshift technique exploits the angular cross-correlation of a target galaxy sample with unknown redshifts and a reference sample with known redshifts. It represents an attractive alternative to colour-based methods of redshift calibration. Here we test the performance of such clustering redshift measurements using mock catalogues that resemble the Kilo-Degree Survey (KiDS). These mocks are created from the MICE simulation and closely mimic the properties of the KiDS source sample and the overlapping spectroscopic reference samples. We quantify the performance of the clustering redshifts by comparing the cross-correlation results with the true redshift distributions in each of the five KiDS photometric redshift bins. Such a comparison to an informative model is necessary due to the incompleteness of the reference samples at high redshifts. Clustering mean redshifts are unbiased at |Δz|< 0.006 under these conditions. The redshift evolution of the galaxy bias of the reference and target samples represents one of the most important systematic errors when estimating clustering redshifts. It can be reliably mitigated at this level of precision using auto-correlation measurements and self-consistency relations, and will not become a dominant source of systematic error until the arrival of Stage-IV cosmic shear surveys. Using redshift distributions from a direct colour-based estimate instead of the true redshift distributions as a model for comparison with the clustering redshifts increases the biases in the mean to up to |Δz|∼0.04. This indicates that the interpretation of clustering redshifts in real-world applications will require more sophisticated (parameterised) models of the redshift distribution in the future. If such better models are available, the clustering-redshift technique promises to be a highly complementary alternative to other methods of redshift calibration

The merger that led to the formation of the Milky Way's inner stellar halo and thick disk

The assembly process of our Galaxy can be retrieved using the motions and chemistry of individual stars. Chemo-dynamical studies of the nearby halo have long hinted at the presence of multiple components such as streams, clumps, duality and correlations between the stars' chemical abundances and orbital parameters. More recently, the analysis of two large stellar surveys have revealed the presence of a well-populated chemical elemental abundance sequence, of two distinct sequences in the colour-magnitude diagram, and of a prominent slightly retrograde kinematic structure all in the nearby halo, which may trace an important accretion event experienced by the Galaxy. Here report an analysis of the kinematics, chemistry, age and spatial distribution of stars in a relatively large volume around the Sun that are mainly linked to two major Galactic components, the thick disk and the stellar halo. We demonstrate that the inner halo is dominated by debris from an object which at infall was slightly more massive than the Small Magellanic Cloud, and which we refer to as Gaia-Enceladus. The stars originating in Gaia-Enceladus cover nearly the full sky, their motions reveal the presence of streams and slightly retrograde and elongated trajectories. Hundreds of RR Lyrae stars and thirteen globular clusters following a consistent age-metallicity relation can be associated to Gaia-Enceladus on the basis of their orbits. With an estimated 4:1 mass-ratio, the merger with Gaia-Enceladus must have led to the dynamical heating of the precursor of the Galactic thick disk and therefore contributed to the formation of this component approximately 10 Gyr ago. These findings are in line with simulations of galaxy formation, which predict that the inner stellar halo should be dominated by debris from just a few massive progenitors.Comment: 19 pages, 8 figures. Published in Nature in the issue of Nov. 1st, 2018. This is the authors' version before final edit

Who Watches the Watchmen? An Appraisal of Benchmarks for Multiple Sequence Alignment

Multiple sequence alignment (MSA) is a fundamental and ubiquitous technique in bioinformatics used to infer related residues among biological sequences. Thus alignment accuracy is crucial to a vast range of analyses, often in ways difficult to assess in those analyses. To compare the performance of different aligners and help detect systematic errors in alignments, a number of benchmarking strategies have been pursued. Here we present an overview of the main strategies--based on simulation, consistency, protein structure, and phylogeny--and discuss their different advantages and associated risks. We outline a set of desirable characteristics for effective benchmarking, and evaluate each strategy in light of them. We conclude that there is currently no universally applicable means of benchmarking MSA, and that developers and users of alignment tools should base their choice of benchmark depending on the context of application--with a keen awareness of the assumptions underlying each benchmarking strategy.Comment: Revie

Mannose Binding Lectin Is Required for Alphavirus-Induced Arthritis/Myositis

Mosquito-borne alphaviruses such as chikungunya virus and Ross River virus (RRV) are emerging pathogens capable of causing large-scale epidemics of virus-induced arthritis and myositis. The pathology of RRV-induced disease in both humans and mice is associated with induction of the host inflammatory response within the muscle and joints, and prior studies have demonstrated that the host complement system contributes to development of disease. In this study, we have used a mouse model of RRV-induced disease to identify and characterize which complement activation pathways mediate disease progression after infection, and we have identified the mannose binding lectin (MBL) pathway, but not the classical or alternative complement activation pathways, as essential for development of RRV-induced disease. MBL deposition was enhanced in RRV infected muscle tissue from wild type mice and RRV infected MBL deficient mice exhibited reduced disease, tissue damage, and complement deposition compared to wild-type mice. In contrast, mice deficient for key components of the classical or alternative complement activation pathways still developed severe RRV-induced disease. Further characterization of MBL deficient mice demonstrated that similar to C3−/− mice, viral replication and inflammatory cell recruitment were equivalent to wild type animals, suggesting that RRV-mediated induction of complement dependent immune pathology is largely MBL dependent. Consistent with these findings, human patients diagnosed with RRV disease had elevated serum MBL levels compared to healthy controls, and MBL levels in the serum and synovial fluid correlated with severity of disease. These findings demonstrate a role for MBL in promoting RRV-induced disease in both mice and humans and suggest that the MBL pathway of complement activation may be an effective target for therapeutic intervention for humans suffering from RRV-induced arthritis and myositis

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Evaluation of probabilistic photometric redshift estimation approaches for The Rubin Observatory Legacy Survey of Space and Time (LSST)

Many scientific investigations of photometric galaxy surveys require redshift estimates, whose uncertainty properties are best encapsulated by photometric redshift (photo-z) posterior probability density functions (PDFs). A plethora of photo-z PDF estimation methodologies abound, producing discrepant results with no consensus on a preferred approach. We present the results of a comprehensive experiment comparing 12 photo-z algorithms applied to mock data produced for The Rubin Observatory Legacy Survey of Space and Time Dark Energy Science Collaboration. By supplying perfect prior information, in the form of the complete template library and a representative training set as inputs to each code, we demonstrate the impact of the assumptions underlying each technique on the output photo-z PDFs. In the absence of a notion of true, unbiased photo-z PDFs, we evaluate and interpret multiple metrics of the ensemble properties of the derived photo-z PDFs as well as traditional reductions to photo-z point estimates. We report systematic biases and overall over/underbreadth of the photo-z PDFs of many popular codes, which may indicate avenues for improvement in the algorithms or implementations. Furthermore, we raise attention to the limitations of established metrics for assessing photo-z PDF accuracy; though we identify the conditional density estimate loss as a promising metric of photo-z PDF performance in the case where true redshifts are available but true photo-z PDFs are not, we emphasize the need for science-specific performance metrics