The knowledge of how magnetization looks inside a ferromagnet is often hindered by the limitations of the available experimental methods which are sensitive only to the surface regions or limited in ...spatial resolution. Here we report a vector tomographic reconstruction based on soft X-ray transmission microscopy and magnetic dichroism data, which has allowed visualizing the three-dimensional magnetization in a ferromagnetic thin film heterostructure. Different non-trivial topological textures have been resolved and the determination of their topological charge has allowed us to identify a Bloch point and a meron-like texture. Our method relies only on experimental data and might be of wide application and interest in 3D nanomagnetism.
Universal coverage of IVF pays off Vélez, M.P; Connolly, M.P; Kadoch, I.-J ...
Human reproduction (Oxford),
06/2014, Volume:
29, Issue:
6
Journal Article
Peer reviewed
Open access
STUDY QUESTION
What was the clinical and economic impact of universal coverage of IVF in Quebec, Canada, during the first calendar year of implementation of the public IVF programme?
SUMMARY ANSWER
...Universal coverage of IVF increased access to IVF treatment, decreased the multiple pregnancy rate and decreased the cost per live birth, despite increased costs per cycle.
WHAT IS KNOWN ALREADY
Public funding of IVF assures equality of access to IVF and decreases multiple pregnancies resulting from this treatment. Public IVF programmes usually mandate a predominant SET policy, the most effective approach for reducing the incidence of multiple pregnancies.
STUDY DESIGN, SIZE, DURATION
This prospective comparative cohort study involved 7364 IVF cycles performed in Quebec during 2009 and 2011 and included an economic analysis.
PARTICIPANTS/MATERIALS, SETTING, METHODS
IVF cycles performed in the five centres offering IVF treatment in Quebec during 2009, before implementation of the public IVF programme, were compared with cycles performed at the same centres during 2011, the first full calendar year following implementation of the programme. Data were obtained from the Canadian Assisted Reproductive Technologies Register (CARTR). Comparisons were made between the two periods in terms of utilization, pregnancy rates, multiple pregnancy rates and costs.
MAIN RESULTS AND THE ROLE OF CHANCE
The number of IVF cycles performed in Quebec increased by 192% after the new policy was implemented. Elective single-embryo transfer was performed in 1.6% of the cycles during Period I (2009), and increased to 31.6% during Period II (2011) (P < 0.001). Although the clinical pregnancy rate per embryo transfer was lower in 2011 than in 2009 (24.9 versus 39.9%, P < 0.001), the multiple pregnancy rate was greatly reduced (6.4 versus 29.4%, P < 0.001). The public IVF programme increased government costs per IVF treatment cycle from CAD$3730 to CAD$4759. Despite increased costs per cycle, the efficiency defined by the cost per live birth, which factored in downstream health costs up to 1 year post delivery, decreased from CAD$49 517 to CAD$43 362 per baby conceived by either fresh and frozen cycles.
LIMITATIONS, REASONS FOR CAUTION
The costs described in the economic model are likely an underestimate as they do not factor in many of the long-term costs that can occur after 1 year of age. The information collected in the Canadian ART register precludes the calculation of cumulative pregnancy rates.
WIDER IMPLICATIONS OF THE FINDINGS
Our study confirms that the implementation of a public IVF programme favouring eSET not only sharply decreases the incidence of multiple pregnancy, but also reduces the cost per live birth.
STUDY FUNDING/COMPETING INTEREST(S)
M.P.V. holds a fellowship award from the Canadian Institutes of Health Research (CIHR). The economic analysis performed by M.P.C. was supported by an unrestricted grant from Ferring Pharmaceutical.
The use of magnetic vector tomography/laminography has opened a 3D experimental window to access the magnetization at the nanoscale. These methods exploit the dependence of the magnetic contrast in ...transmission to recover its 3D configuration. However, hundreds of different angular projections are required leading to large measurement times. Here we present a fast method to dramatically reduce the experiment time specific for quasi two-dimensional magnetic systems. The algorithm uses the Beer-Lambert equation in the framework of X-ray transmission microscopy to obtain the 3D magnetic configuration of the sample. It has been demonstrated in permalloy microstructures, reconstructing the magnetization vector field with a reduced number of angular projections obtaining quantitative results. The throughput of the methodology is × 10-× 100 times faster than conventional magnetic vector tomography, making this characterization method of general interest for the community.
Hydrological distributed models demand large amounts of data, information and parameters in order to accurately represent the spatial variability of the main hydrological processes and inputs. The ...parameter estimation is always a complex and expensive task which is often unaffordable and therefore hydrologists are frequently forced to disregard distributed modelling in favour of lumped or semidistributed models. To solve this situation, we propose in this paper to split the effective parameter at each cell in two components: the hydrological characteristic (at point scale and maintaining its physical meaning) and a correction factor (common for all cells and taking into account all modelling errors including the temporal and spatial scale effects). The new split-parameter structure adopted in our distributed model (called TETIS) is coupled with the SCE-UA automatic optimization method in order to obtain the set of optimal correction factors of the model, without loosing the spatial variability described by the a priori estimated hydrological characteristics. Automatic procedures can be easily adapted to the split-parameter structure because the number of variables to be calibrated is dramatically reduced from thousands of cell parameters to a small number of common correction factors (one for each parameter map). Also, the optimum initial values of the state variables can be obtained automatically. In order to show the advantages of the new structure a real application is performed in a case study in which the calibration and the spatial and spatial–temporal validation processes have been carried out. The results can be considered as being excellent and it is concluded that automatic calibration with the SCE-UA algorithm has been shown to be reliable and fast.
In previous studies of a genetic isolate, we identified significant linkage of attention deficit hyperactivity disorder (ADHD) to 4q, 5q, 8q, 11q and 17p. The existence of unique large size families ...linked to multiple regions, and the fact that these families came from an isolated population, we hypothesized that two-locus interaction contributions to ADHD were plausible. Several analytical models converged to show significant interaction between 4q and 11q (P<1 × 10(-8)) and 11q and 17p (P<1 × 10(-6)). As we have identified that common variants of the LPHN3 gene were responsible for the 4q linkage signal, we focused on 4q-11q interaction to determine that single-nucleotide polymorphisms (SNPs) harbored in the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 genes, to double the risk of developing ADHD. This interaction not only explains genetic effects much better than taking each of these loci effects by separated but also differences in brain metabolism as depicted by proton magnetic resonance spectroscopy data and pharmacogenetic response to stimulant medication. These findings not only add information about how high order genetic interactions might be implicated in conferring susceptibility to develop ADHD but also show that future studies of the effects of genetic interactions on ADHD clinical information will help to shape predictive models of individual outcome.
Major depressive disorder (MDD) affects around 350 million people worldwide; however, the underlying genetic basis remains largely unknown. In this study, we took into account that MDD is a ...gene-environment disorder, in which stress is a critical component, and used whole-genome screening of functional variants to investigate the 'missing heritability' in MDD. Genome-wide association studies (GWAS) using single- and multi-locus linear mixed-effect models were performed in a Los Angeles Mexican-American cohort (196 controls, 203 MDD) and in a replication European-ancestry cohort (499 controls, 473 MDD). Our analyses took into consideration the stress levels in the control populations. The Mexican-American controls, comprised primarily of recent immigrants, had high levels of stress due to acculturation issues and the European-ancestry controls with high stress levels were given higher weights in our analysis. We identified 44 common and rare functional variants associated with mild to moderate MDD in the Mexican-American cohort (genome-wide false discovery rate, FDR, <0.05), and their pathway analysis revealed that the three top overrepresented Gene Ontology (GO) processes were innate immune response, glutamate receptor signaling and detection of chemical stimulus in smell sensory perception. Rare variant analysis replicated the association of the PHF21B gene in the ethnically unrelated European-ancestry cohort. The TRPM2 gene, previously implicated in mood disorders, may also be considered replicated by our analyses. Whole-genome sequencing analyses of a subset of the cohorts revealed that European-ancestry individuals have a significantly reduced (50%) number of single nucleotide variants compared with Mexican-American individuals, and for this reason the role of rare variants may vary across populations. PHF21b variants contribute significantly to differences in the levels of expression of this gene in several brain areas, including the hippocampus. Furthermore, using an animal model of stress, we found that Phf21b hippocampal gene expression is significantly decreased in animals resilient to chronic restraint stress when compared with non-chronically stressed animals. Together, our results reveal that including stress level data enables the identification of novel rare functional variants associated with MDD.
Abstract
Background
In low transmission settings early diagnosis is the main strategy to reduce adverse outcomes of malaria in pregnancy; however, microscopy and rapid diagnostic tests (RDTs) are ...inadequate for detecting low-density infections. We studied the performance of the highly sensitive-RDT (hsRDT) and the loop mediated isothermal DNA amplification (LAMP) for the detection of
P. falciparum
in pregnant women.
Methods
A cross-sectional study was conducted in two malaria-endemic municipalities in Colombia. We screened pregnant women in the context of an antenatal care program in health facilities and evaluated five tests (microscopy, conventional RDT, hsRDT, LAMP and nested polymerase chain reaction-PCR) for the detection of
P. falciparum
in peripheral blood, using a quantitative reverse transcription PCR (qRT-PCR) as the reference standard. Diagnostic performance of hsRDT and LAMP were compared with routine testing.
Results
The prevalence of
P. falciparum
was 4.5% by qRT-PCR, half of those infections were subpatent. The sensitivity of the hsRDT (64.1%) was slightly better compared to microscopy and cRDT (59 and 53.8% respectively). LAMP had the highest sensitivity (89.7%) for detecting
P. falciparum
and the ability to detect very low-density infections (minimum parasite density detected 0.08 p/μL).
Conclusions
There is an underestimation of
Plasmodium
spp. infections by tests routinely used in pregnant women attending antenatal care visits. LAMP methodology can be successfully implemented at local hospitals in malaria-endemic areas. The relevance of detecting and treating this sub-patent
P. falciparum
infections in pregnant women should be evaluated.
Trial registration
ClinicalTrials.gov, Identifier:
NCT03172221
, Date of registration: May 29, 2017.
Domain configuration has been studied by magnetic force microscopy and micromagnetic simulations in NdCo honeycomb lattices in comparison with similar patterned structures made of polycrystalline Co. ...The change in material anisotropy from in-plane to weak perpendicular magnetic anisotropy (wPMA) modifies the basic domain structure and relevant topological defects in the magnetization in each case: from in-plane domains, vortices, antivortices and half vortices in Co lattices to parallel stripe patterns with dislocations in NdCo samples with large enough thickness. A characteristic feature of wPMA materials is the possibility to drive the system from in-plane to stripe pattern configuration playing with sample thickness (during growth) or with magnetic anisotropy (as a function of temperature). It has allowed us to observe complex magnetic textures within the stripe pattern of NdCo samples imprinted from previous magnetic vortex and antivortex states that nucleate within the honeycomb lattice during the early stages of deposition and, then, become frozen by local rotatable anisotropy as sample thickness increases.
Advances in nanoscale magnetism increasingly require characterization tools providing detailed descriptions of magnetic configurations. Magnetic transmission X-ray microscopy produces element ...specific magnetic domain images with nanometric lateral resolution in films up to ∼100 nm thick. Here we present an imaging method using the angular dependence of magnetic contrast in a series of high resolution transmission X-ray microscopy images to obtain quantitative descriptions of the magnetization (canting angles relative to surface normal and sense). This method is applied to 55-120 nm thick ferromagnetic NdCo5 layers (canting angles between 65° and 22°), and to a NdCo5 film covered with permalloy. Interestingly, permalloy induces a 43° rotation of Co magnetization towards surface normal. Our method allows identifying complex topological defects (merons or ½ skyrmions) in a NdCo5 film that are only partially replicated by the permalloy overlayer. These results open possibilities for the characterization of deeply buried magnetic topological defects, nanostructures and devices.
Abstract Public financing of IVF aims at increasing access to treatment while decreasing the expenses associated with multiple pregnancies. Critics argue that it is associated with lower pregnancy ...rates. This study compared cycles performed during 2009 (before implementation of Quebec’s public IVF programme; period I) to those performed in the year following implementation (period II) in a single IVF centre. First fresh cycles in period I (499 women) and first fresh cycles (815 women) along with their corresponding first vitrified–warmed transfer (271 women) in period II were evaluated. From period I to period II, single-embryo transfer increased from 17.3% to 85.0% ( P < 0.001), multiple ongoing pregnancy rate decreased from 25.8% to 1.6% ( P < 0.001) and ongoing pregnancy rate decreased from 31.9% to 23.3% ( P = 0.001). During period II, the ongoing pregnancy rate per vitrified–warmed embryo transfer was 19.2%, leading to a cumulative ongoing pregnancy rate per initiated cycle of 29.7%, which was not different to the pregnancy rate per fresh cycle during period I (31.9%). To conclude, Quebec’s public IVF programme decreased multiple pregnancy rates while maintaining an acceptable cumulative ongoing pregnancy rate, a more precise outcome to evaluate the impact of public IVF programmes. Public funding of IVF intends to increase access to IVF treatment and reduce the health and economic consequences of multiple pregnancies. However, the success of treatment, as measured by the pregnancy rates, may seem lower as expressed by critics of these public programmes. In order to evaluate the impact of the new public IVF programme in the province of Quebec, we compared the IVF cycles performed during 2009 (period I), the year previous to implementation of the programme, to the cycles performed 1 year following the programme (period II) in a single IVF centre. The first fresh cycles performed in period I were compared with the first fresh cycles in addition to the fresh cryopreserved cycle during period II (a surrogate of cumulative pregnancy rate). The transfer of a single embryo increased (17.3% in period I versus 85.0% in period II), and as a consequence, the multiple pregnancy rate sharply decreased (25.8% in period I versus 1.6% in period II). Although the ongoing pregnancy rate decreased after the transfer of the first fresh embryo (31.9% in period I versus 23.3% in period II), the transfer of one cryopreserved embryo to those women who did not get pregnant during period II resulted in a cumulative pregnancy rate of 29.7% during period II (almost the same as the pregnancy rate of 31.9% during period I). Thus, in this centre, the Quebec public IVF programme attained the objective of decreasing multiple pregnancy rates while maintaining acceptable cumulative pregnancy rate, a more precise outcome to evaluate the impact of public IVF programmes.
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