Should I stay or should I go?: consistency and switching of delivery locations among new mothers in 39 Sub-Saharan African and South/Southeast Asian countries.

The objective of this article is to assess the extent and determinants of switching delivery location between women's first and second deliveries. We used Demographic and Health Survey data from 39 low- and middle-income countries on delivery locations from >30 000 women who had their first two deliveries in the 5-year survey recall period. Each delivery was characterized as occurring at home or in a health facility, facilities were classified as public- or private-sector. The extent of switching was estimated for each country, region and overall. Multivariable logistic regression models assessed determinants of switching (home to facility or facility to home), using four dimensions (perceived/biological need, socioeconomic characteristics, utilization of care and availability of care). Overall, 49.0% of first and 44.5% of second deliveries occurred in health facilities. Among women who had their first delivery at home, 11.8% used a facility for their second (7.0% public-sector and 4.8% private-sector). Among women who had their first delivery in a facility, 21.6% switched to a home location for their second. The extent of switching varied by country; but the overall net effect was either non-existent (n = 20) or away from facilities (n = 17) in all but two countries-Cambodia and Burkina Faso. Four factors were associated with switching to a facility after a home delivery: higher education, urban residence, non-poor household status and multiple gestation. Majority of women consistently used the same delivery location for their first two deliveries. We found some evidence that where switching occurred, women were being lost from facility care during this important transition, and that all four included dimensions were important determinants of women's pattern of delivery care use. The relative importance of these factors should be understood in each specific context to improve retention in and provision of quality intrapartum care for women and their newborns

Why not? Understanding the spatial clustering of private facility-based delivery and financial reasons for homebirths in Nigeria.

BACKGROUND: In Nigeria, the provision of public and private healthcare vary geographically, contributing to variations in one's healthcare surroundings across space. Facility-based delivery (FBD) is also spatially heterogeneous. Levels of FBD and private FBD are significantly lower for women in certain south-eastern and northern regions. The potential influence of childbirth services frequented by the community on individual's barriers to healthcare utilization is under-studied, possibly due to the lack of suitable data. Using individual-level data, we present a novel analytical approach to examine the relationship between women's reasons for homebirth and community-level, health-seeking surroundings. We aim to assess the extent to which cost or finance acts as a barrier for FBD across geographic areas with varying levels of private FBD in Nigeria. METHOD: The most recent live births of 20,467 women were georeferenced to 889 locations in the 2013 Nigeria Demographic and Health Survey. Using these locations as the analytical unit, spatial clusters of high/low private FBD were detected with Kulldorff statistics in the SatScan software package. We then obtained the predicted percentages of women who self-reported financial reasons for homebirth from an adjusted generalized linear model for these clusters. RESULTS: Overall private FBD was 13.6% (95%CI = 11.9,15.5). We found ten clusters of low private FBD (average level: 0.8, 95%CI = 0.8,0.8) and seven clusters of high private FBD (average level: 37.9, 95%CI = 37.6,38.2). Clusters of low private FBD were primarily located in the north, and the Bayelsa and Cross River States. Financial barrier was associated with high private FBD at the cluster level - 10% increase in private FBD was associated with + 1.94% (95%CI = 1.69,2.18) in nonusers citing cost as a reason for homebirth. CONCLUSIONS: In communities where private FBD is common, women who stay home for childbirth might have mild increased difficulties in gaining effective access to public care, or face an overriding preference to use private services, among other potential factors. The analytical approach presented in this study enables further research of the differentials in individuals' reasons for service non-uptake across varying contexts of healthcare surroundings. This will help better devise context-specific strategies to improve health service utilization in resource-scarce settings

Who Meets the Contraceptive Needs of Young Women in Sub-Saharan Africa?

PURPOSE: Despite efforts to expand contraceptive access for young people, few studies have considered where young women (age 15-24) in low- and middle-income countries obtain modern contraceptives and how the capacity and content of care of sources used compares with older users. METHODS: We examined the first source of respondents' current modern contraceptive method using the most recent Demographic and Health Survey since 2000 for 33 sub-Saharan African countries. We classified providers according to sector (public/private) and capacity to provide a range of short- and long-term methods (limited/comprehensive). We also compared the content of care obtained from different providers. RESULTS: Although the public and private sectors were both important sources of family planning (FP), young women (15-24) used more short-term methods obtained from limited-capacity, private providers, compared with older women. The use of long-term methods among young women was low, but among those users, more than 85% reported a public sector source. Older women (25+) were significantly more likely to utilize a comprehensive provider in either sector compared with younger women. Although FP users of all ages reported poor content of care across all providers, young women had even lower content of care. CONCLUSIONS: The results suggest that method and provider choice are strongly linked, and recent efforts to increase access to long-term methods among young women may be restricted by where they seek care. Interventions to increase adolescents' access to a range of FP methods and quality counseling should target providers frequently used by young people, including limited-capacity providers in the private sector

Kinetics and 28-day test-retest repeatability and reproducibility of [C-11]UCB-J PET brain imaging

[C-11]UCB-J is a novel radioligand that binds to synaptic vesicle glycoprotein 2A (SV2A). The main objective of this study was to determine the 28-day test-retest repeatability (TRT) of quantitative [C-11]UCB-J brain positron emission tomography (PET) imaging in Alzheimer's disease (AD) patients and healthy controls (HCs). Nine HCs and eight AD patients underwent two 60 min dynamic [C-11]UCB-J PET scans with arterial sampling with an interval of 28 days. The optimal tracer kinetic model was assessed using the Akaike criteria (AIC). Micro-/macro-parameters such as tracer delivery (K-1) and volume of distribution (V-T) were estimated using the optimal model. Data were also analysed for simplified reference tissue model (SRTM) with centrum semi-ovale (white matter) as reference region. Based on AIC, both 1T2k_V-B and 2T4k_V-B described the [C-11]UCB-J kinetics equally well. Analysis showed that whole-brain grey matter TRT for V-T, DVR and SRTM BPND were -2.2% +/- 8.5, 0.4% +/- 12.0 and -8.0% +/- 10.2, averaged over all subjects. [C-11]UCB-J kinetics can be well described by a 1T2k_V-B model, and a 60 min scan duration was sufficient to obtain reliable estimates for both plasma input and reference tissue models. TRT for V-T, DVR and BPND wa

Validation and test-retest repeatability performance of parametric methods for [11C]UCB-J PET

[(11)C]UCB-J is a PET radioligand that binds to the presynaptic vesicle glycoprotein 2A. Therefore, [(11)C]UCB-J PET may serve as an in vivo marker of synaptic integrity. The main objective of this study was to evaluate the quantitative accuracy and the 28-day test–retest repeatability (TRT) of various parametric quantitative methods for dynamic [(11)C]UCB-J studies in Alzheimer’s disease (AD) patients and healthy controls (HC). Eight HCs and seven AD patients underwent two 60-min dynamic [(11)C]UCB-J PET scans with arterial sampling over a 28-day interval. Several plasma-input based and reference-region based parametric methods were used to generate parametric images using metabolite corrected plasma activity as input function or white matter semi-ovale as reference region. Different parametric outcomes were compared regionally with corresponding non-linear regression (NLR) estimates. Furthermore, the 28-day TRT was assessed for all parametric methods. Spectral analysis (SA) and Logan graphical analysis showed high correlations with NLR estimates. Receptor parametric mapping (RPM) and simplified reference tissue model 2 (SRTM2) BP(ND), and reference Logan (RLogan) distribution volume ratio (DVR) regional estimates correlated well with plasma-input derived DVR and SRTM BP(ND). Among the multilinear reference tissue model (MRTM) methods, MRTM1 had the best correspondence with DVR and SRTM BP(ND). Among the parametric methods evaluated, spectral analysis (SA) and SRTM2 were the best plasma-input and reference tissue methods, respectively, to obtain quantitatively accurate and repeatable parametric images for dynamic [(11)C]UCB-J PET. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-021-00874-8

Who pays and how much? A cross-sectional study of out-of-pocket payment for modern contraception in Kenya.

OBJECTIVES: Out-of-pocket (OOP) payment for modern contraception is an understudied component of healthcare financing in countries like Kenya, where wealth gradients in met need have prompted efforts to expand access to free contraception. This study aims to examine whether, among public sector providers, the poor are more likely to receive free contraception and to compare how OOP payment for injectables and implants-two popular methods-differs by public/private provider type and user's sociodemographic characteristics. DESIGN, SETTING AND PARTICIPANTS: Secondary analyses of nationally representative, cross-sectional household data from the 2014 Kenya Demographic and Health Survey. Respondents were women of reproductive age (15-49 years). The sample comprised 5717 current modern contraception users, including 2691 injectable and 1073 implant users with non-missing expenditure values. MAIN OUTCOME: Respondent's self-reported source and payment to obtain their current modern contraceptive method. METHODS: We used multivariable logistic regression to examine predictors of free public sector contraception and compared average expenditure for injectable and implant. Quintile ratios examined progressivity of non-zero expenditure by wealth. RESULTS: Half of public sector users reported free contraception; this varied considerably by method and region. Users of implants, condoms, pills and intrauterine devices were all more likely to report receiving their method for free (p<0.001) compared with injectable users. The poorest were as likely to pay for contraception as the wealthiest users at public providers (OR: 1.10, 95% CI: 0.64 to 1.91). Across all providers, among users with non-zero expenditure, injectable and implant users reported a mean OOP payment of Kenyan shillings (KES) 80 (US$0.91), 95$4.31), 95% CI: KES 327 to 429, respectively. In the public sector, expenditure was pro-poor for injectable users yet weakly pro-rich for implant users. CONCLUSIONS: More attention is needed to targeting subsidies to the poorest and ensuring government facilities are equipped to cope with lost user fee revenue

New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms

Background: Hyperekplexia mutations have provided much information about glycine receptor structure and function. Results: Weidentified and characterized nine new mutations. Dominant mutations resulted in spontaneous activation, whereas recessive mutations precluded surface expression. Conclusion: These data provide insight into glycine receptor activation mechanisms and surface expression determinants. Significance: The results enhance our understanding of hyperekplexia pathology and glycine receptor structure-function. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A

Clinical pharmacogenomic testing of KRAS, BRAF and EGFR mutations by high resolution melting analysis and ultra-deep pyrosequencing

BACKGROUND: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. METHODS: We describe a high resolution melting (HRM) assay for mutation detection in EGFR exons 19-21, KRAS codon 12/13 and BRAF V600 using formalin-fixed paraffin-embedded samples. Somatic variation of KRAS exon 2 was also analysed by massively parallel pyrosequencing of amplicons with the GS Junior 454 platform. RESULTS: We tested 120 routine diagnostic specimens from patients with colorectal or lung cancer. Mutations in KRAS, BRAF and EGFR were observed in 41.9%, 13.0% and 11.1% of the overall samples, respectively, being mutually exclusive. For KRAS, six types of substitutions were detected (17 G12D, 9 G13D, 7 G12C, 2 G12A, 2 G12V, 2 G12S), while V600E accounted for all the BRAF activating mutations. Regarding EGFR, two cases showed exon 19 deletions (delE746-A750 and delE746-T751insA) and another two substitutions in exon 21 (one showed L858R with the resistance mutation T590M in exon 20, and the other had P848L mutation). Consistent with earlier reports, our results show that KRAS and BRAF mutation frequencies in colorectal cancer were 44.3% and 13.0%, respectively, while EGFR mutations were detected in 11.1% of the lung cancer specimens. Ultra-deep amplicon pyrosequencing successfully validated the HRM results and allowed detection and quantitation of KRAS somatic mutations. CONCLUSIONS: HRM is a rapid and sensitive method for moderate-throughput cost-effective screening of oncogene mutations in clinical samples. Rather than Sanger sequence validation, next-generation sequencing technology results in more accurate quantitative results in somatic variation and can be achieved at a higher throughput scale.This work was supported by grants from Spanish Health Ministry (FIS) network RIRAAF (RD 07/0064).Ye

The Opportunistic Pathogen Propionibacterium acnes: Insights into Typing, Human Disease, Clonal Diversification and CAMP Factor Evolution

We previously described a Multilocus Sequence Typing (MLST) scheme based on eight genes that facilitates population genetic and evolutionary analysis of P. acnes. While MLST is a portable method for unambiguous typing of bacteria, it is expensive and labour intensive. Against this background, we now describe a refined version of this scheme based on two housekeeping (aroE; guaA) and two putative virulence (tly; camp2) genes (MLST4) that correctly predicted the phylogroup (IA1, IA2, IB, IC, II, III), clonal complex (CC) and sequence type (ST) (novel or described) status for 91% isolates (n = 372) via cross-referencing of the four gene allelic profiles to the full eight gene versions available in the MLST database (http:// pubmlst.org/pacnes/). Even in the small number of cases where specific STs were not completely resolved, the MLST4 method still correctly determined phylogroup and CC membership. Examination of nucleotide changes within all the MLST loci provides evidence that point mutations generate new alleles approximately 1.5 times as frequently as recombination; although the latter still plays an important role in the bacterium’s evolution. The secreted/cell-associated ‘virulence’ factors tly and camp2 show no clear evidence of episodic or pervasive positive selection and have diversified at a rate similar to housekeeping loci. The co-evolution of these genes with the core genome might also indicate a role in commensal/normal existence constraining their diversity and preventing their loss from the P. acnes population. The possibility that members of the expanded CAMP factor protein family, including camp2, may have been lost from other propionibacteria, but not P. acnes, would further argue for a possible role in niche/host adaption leading to their retention within the genome. These evolutionary insights may prove important for discussions surrounding camp2 as an immunotherapy target for acne, and the effect such treatments may have on commensal lineages

Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer

Summary Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886) we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralising antibody titres (NAbT) using a live virus microneutralization assay against wild-type (WT), Delta, Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titres and T cell responses after the fourth vaccine dose increases compared to those after the third vaccine dose. Patients who received B cell-depleting therapies within 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination