Understudied and underaddressed: Femicide, an extreme form of violence against women and girls.

Little is known about the prevalence and dynamics of femicide, a persistent form of violence against women and girls, due to challenges associated with its documentation. Research by Abrahams and colleagues comparing rates of femicide in South Africa over 18 years, however, suggests that femicide is preventable.

Federal Retail Pharmacy Program Contributions to Bivalent mRNA COVID-19 Vaccinations Across Sociodemographic Characteristics - United States, September 1, 2022-September 30, 2023.

The Federal Retail Pharmacy Program (FRPP) facilitated integration of pharmacies as partners in national efforts to scale up vaccination capacity during the COVID-19 pandemic emergency response. To evaluate FRPP's contribution to vaccination efforts across various sociodemographic groups, data on COVID-19 bivalent mRNA vaccine doses administered during September 1, 2022-September 30, 2023, were evaluated from two sources: 1) FRPP data reported directly to CDC and 2) jurisdictional immunization information systems data reported to CDC from all 50 states, the District of Columbia, U.S. territories, and freely associated states. Among 59.8 million COVID-19 bivalent vaccine doses administered in the United States during this period, 40.5 million (67.7%) were administered by FRPP partners. The proportion of COVID-19 bivalent doses administered by FRPP partners ranged from 5.9% among children aged 6 months-4 years to 70.6% among adults aged 18-49 years. Among some racial and ethnic minority groups (e.g., Hispanic or Latino, non-Hispanic Black or African American, non-Hispanic Native Hawaiian or other Pacific Islander, and non-Hispanic Asian persons), ≥45% of COVID-19 bivalent vaccine doses were administered by FRPP partners. Further, in urban and rural areas, FRPP partners administered 81.6% and 60.0% of bivalent vaccine doses, respectively. The FRPP partnership administered approximately two thirds of all bivalent COVID-19 vaccine doses in the United States and provided vaccine access for persons across a wide range of sociodemographic groups, demonstrating that this program could serve as a model to address vaccination services needs for routine vaccines and to provide health services in other public health emergencies.

Global, regional, and national prevalence estimates of physical or sexual, or both, intimate partner violence against women in 2018.

BACKGROUND: Intimate partner violence against women is a global public health problem with many short-term and long-term effects on the physical and mental health of women and their children. The Sustainable Development Goals (SDGs) call for its elimination in target 5.2. To monitor governments' progress towards SDG target 5.2, this study aimed to provide global, regional, and country baseline estimates of physical or sexual, or both, violence against women by male intimate partners. METHODS: This study developed global, regional, and country estimates, based on data from the WHO Global Database on Prevalence of Violence Against Women. These data were identified through a systematic literature review searching MEDLINE, Global Health, Embase, Social Policy, and Web of Science, and comprehensive searches of national statistics and other websites. A country consultation process identified additional studies. Included studies were conducted between 2000 and 2018, representative at the national or sub-national level, included women aged 15 years or older, and used act-based measures of physical or sexual, or both, intimate partner violence. Non-population-based data, including administrative data, studies not generalisable to the whole population, studies with outcomes that only provided the combined prevalence of physical or sexual, or both, intimate partner violence with other forms of violence, and studies with insufficient data to allow extrapolation or imputation were excluded. We developed a Bayesian multilevel model to jointly estimate lifetime and past year intimate partner violence by age, year, and country. This framework adjusted for heterogeneous age groups and differences in outcome definition, and weighted surveys depending on whether they were nationally or sub-nationally representative. This study is registered with PROSPERO (number CRD42017054100). FINDINGS: The database comprises 366 eligible studies, capturing the responses of 2 million women. Data were obtained from 161 countries and areas, covering 90% of the global population of women and girls (15 years or older). Globally, 27% (uncertainty interval [UI] 23-31%) of ever-partnered women aged 15-49 years are estimated to have experienced physical or sexual, or both, intimate partner violence in their lifetime, with 13% (10-16%) experiencing it in the past year before they were surveyed. This violence starts early, affecting adolescent girls and young women, with 24% (UI 21-28%) of women aged 15-19 years and 26% (23-30%) of women aged 19-24 years having already experienced this violence at least once since the age of 15 years. Regional variations exist, with low-income countries reporting higher lifetime and, even more pronouncedly, higher past year prevalence compared with high-income countries. INTERPRETATION: These findings show that intimate partner violence against women was already highly prevalent across the globe before the COVID-19 pandemic. Governments are not on track to meet the SDG targets on the elimination of violence against women and girls, despite robust evidence that intimate partner violence can be prevented. There is an urgent need to invest in effective multisectoral interventions, strengthen the public health response to intimate partner violence, and ensure it is addressed in post-COVID-19 reconstruction efforts. FUNDING: UK Department for International Development through the UN Women-WHO Joint Programme on Strengthening Violence against Women Data, and UNDP-UN Population Fund-UNICEF-WHO-World Bank Special Programme of Research, Development, and Research Training in Human Reproduction, a cosponsored programme executed by WHO.

Use of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among U.S. infants. In July 2023, the Food and Drug Administration approved nirsevimab, a long-acting monoclonal antibody, for passive immunization to prevent RSV-associated lower respiratory tract infection among infants and young children. Since October 2021, the Advisory Committee on Immunization Practices (ACIP) Maternal and Pediatric RSV Work Group has reviewed evidence on the safety and efficacy of nirsevimab among infants and young children. On August 3, 2023, ACIP recommended nirsevimab for all infants aged <8 months who are born during or entering their first RSV season and for infants and children aged 8-19 months who are at increased risk for severe RSV disease and are entering their second RSV season. On the basis of pre-COVID-19 pandemic patterns, nirsevimab could be administered in most of the continental United States from October through the end of March. Nirsevimab can prevent severe RSV disease among infants and young children at increased risk for severe RSV disease.

Interim Recommendations for Use of Bivalent mRNA COVID-19 Vaccines for Persons Aged ≥6 Months - United States, April 2023.

Throughout the national public health emergency declared in response to the COVID-19 pandemic, CDC, guided by the Advisory Committee on Immunization Practices (ACIP), has offered evidence-based recommendations for the use of COVID-19 vaccines in U.S. populations after each regulatory action by the Food and Drug Administration (FDA). During August 2022-April 2023, FDA amended its Emergency Use Authorizations (EUAs) to authorize the use of a single, age-appropriate, bivalent COVID-19 vaccine dose (i.e., containing components from the ancestral and Omicron BA.4/BA.5 strains in equal amounts) for all persons aged ≥6 years, use of bivalent COVID-19 vaccine doses for children aged 6 months-5 years, and additional bivalent doses for immunocompromised persons and adults aged ≥65 years (1). ACIP voted in September 2022 on the use of the bivalent vaccine, and CDC made recommendations after the September vote and subsequently, through April 2023, with input from ACIP. This transition to a single bivalent COVID-19 vaccine dose for most persons, with additional doses for persons at increased risk for severe disease, facilitates implementation of simpler, more flexible recommendations. Three COVID-19 vaccines are currently available for use in the United States and recommended by ACIP: 1) the bivalent mRNA Pfizer-BioNTech COVID-19 vaccine, 2) the bivalent mRNA Moderna COVID-19 vaccine, and 3) the monovalent adjuvanted, protein subunit-based Novavax COVID-19 vaccine.* As of August 31, 2022, monovalent mRNA vaccines based on the ancestral SARS-CoV-2 strain are no longer authorized for use in the United States (1).

Coverage with Influenza, Respiratory Syncytial Virus, and Updated COVID-19 Vaccines Among Nursing Home Residents - National Healthcare Safety Network, United States, December 2023.

Nursing home residents are at risk for becoming infected with and experiencing severe complications from respiratory viruses, including SARS-CoV-2, influenza, and respiratory syncytial virus (RSV). Fall 2023 is the first season during which vaccines are simultaneously available to protect older adults in the United States against all three of these respiratory viruses. Nursing homes are required to report COVID-19 vaccination coverage and can voluntarily report influenza and RSV vaccination coverage among residents to CDC's National Healthcare Safety Network. The purpose of this study was to assess COVID-19, influenza, and RSV vaccination coverage among nursing home residents during the current 2023-24 respiratory virus season. As of December 10, 2023, 33.1% of nursing home residents were up to date with vaccination against COVID-19. Among residents at 20.2% and 19.4% of facilities that elected to report, coverage with influenza and RSV vaccines was 72.0% and 9.8%, respectively. Vaccination varied by U.S. Department of Health and Human Services region, social vulnerability index level, and facility size. There is an urgent need to protect nursing home residents against severe outcomes of respiratory illnesses by continuing efforts to increase vaccination against COVID-19 and influenza and discussing vaccination against RSV with eligible residents during the ongoing 2023-24 respiratory virus season.

Use of Updated COVID-19 Vaccines 2023-2024 Formula for Persons Aged ≥6 Months: Recommendations of the Advisory Committee on Immunization Practices - United States, September 2023.

COVID-19 vaccines protect against severe COVID-19-associated outcomes, including hospitalization and death. As SARS-CoV-2 has evolved, and waning vaccine effectiveness has been noted, vaccine formulations and policies have been updated to provide continued protection against severe illness and death from COVID-19. Since September 2022, bivalent mRNA COVID-19 vaccines have been recommended in the United States, but the variants these vaccines protect against are no longer circulating widely. On September 11, 2023, the Food and Drug Administration (FDA) approved the updated (2023-2024 Formula) COVID-19 mRNA vaccines by Moderna and Pfizer-BioNTech for persons aged ≥12 years and authorized these vaccines for persons aged 6 months-11 years under Emergency Use Authorization (EUA). On October 3, 2023, FDA authorized the updated COVID-19 vaccine by Novavax for use in persons aged ≥12 years under EUA. The updated COVID-19 vaccines include a monovalent XBB.1.5 component, which is meant to broaden vaccine-induced immunity and provide protection against currently circulating SARS-CoV-2 XBB-sublineage variants including against severe COVID-19-associated illness and death. On September 12, 2023, the Advisory Committee on Immunization Practices recommended vaccination with updated COVID-19 vaccines for all persons aged ≥6 months. These recommendations will be reviewed as new evidence becomes available or new vaccines are approved and might be updated.

COVID-19 Surveillance After Expiration of the Public Health Emergency Declaration - United States, May 11, 2023.

On January 31, 2020, the U.S. Department of Health and Human Services (HHS) declared, under Section 319 of the Public Health Service Act, a U.S. public health emergency because of the emergence of a novel virus, SARS-CoV-2.* After 13 renewals, the public health emergency will expire on May 11, 2023. Authorizations to collect certain public health data will expire on that date as well. Monitoring the impact of COVID-19 and the effectiveness of prevention and control strategies remains a public health priority, and a number of surveillance indicators have been identified to facilitate ongoing monitoring. After expiration of the public health emergency, COVID-19-associated hospital admission levels will be the primary indicator of COVID-19 trends to help guide community and personal decisions related to risk and prevention behaviors; the percentage of COVID-19-associated deaths among all reported deaths, based on provisional death certificate data, will be the primary indicator used to monitor COVID-19 mortality. Emergency department (ED) visits with a COVID-19 diagnosis and the percentage of positive SARS-CoV-2 test results, derived from an established sentinel network, will help detect early changes in trends. National genomic surveillance will continue to be used to estimate SARS-CoV-2 variant proportions; wastewater surveillance and traveler-based genomic surveillance will also continue to be used to monitor SARS-CoV-2 variants. Disease severity and hospitalization-related outcomes are monitored via sentinel surveillance and large health care databases. Monitoring of COVID-19 vaccination coverage, vaccine effectiveness (VE), and vaccine safety will also continue. Integrated strategies for surveillance of COVID-19 and other respiratory viruses can further guide prevention efforts. COVID-19-associated hospitalizations and deaths are largely preventable through receipt of updated vaccines and timely administration of therapeutics (1-4).

CD22 Controls Germinal Center B Cell Receptor Signaling, Which Influences Plasma Cell and Memory B Cell Output.

Germinal center reactions are established during a thymus-dependent immune response. Germinal center (GC) B cells are rapidly proliferating and undergo somatic hypermutation in Ab genes. This results in the production of high-affinity Abs and establishment of long-lived memory cells. GC B cells show lower BCR-induced signaling when compared with naive B cells, but the functional relevance is not clear. CD22 is a member of the Siglec family and functions as an inhibitory coreceptor on B cells. Interestingly, GC B cells downregulate sialic acid forms that serve as high-affinity ligands for CD22, indicating a role for CD22 ligand binding during GC responses. We studied the role of CD22 in the GC with mixed bone marrow chimeric mice and found a disadvantage of CD22-/- GC B cells during the GC reaction. Mechanistic investigations ruled out defects in dark zone/light zone distribution and affinity maturation. Rather, an increased rate of apoptosis in CD22-/- GC B cells was responsible for the disadvantage, also leading to a lower GC output in plasma cells and memory B cells. CD22-/- GC B cells showed a clearly increased calcium response upon BCR stimulation, which was almost absent in wild-type GC B cells. We conclude that the differential expression of the low-affinity cis CD22 ligands in the GC normally results in a strong attenuation of BCR signaling in GC B cells, probably due to higher CD22-BCR interactions. Therefore, attenuation of BCR signaling by CD22 is involved in GC output and B cell fate.

A liquid-culture-based screening approach to study compounds affecting inflammatory processes in Caenorhabditis elegans.

Discovery of biomedical drugs makes use of novel biological sources of limited availability and is often in need of fast, small-scale initial screening approaches. Here, we present a screening, based on the reporter Caenorhabditis elegans strain IG692, for identification of anti- and pro-inflammatory properties. The elaborated workflow is based on cultivation in fluid and by this, allows fast and reproducible seeding in 96 well plates. LPS and dexamethasone served as reliable controls, comparable to application in the human cell line THP-1. This in vivo approach offers a first step for selection of e.g. natural products or for repurposing of compounds from drug libraries and by this can serve as a tool in drug discovery for inflammatory human diseases.

Plasma autoantibodies to glial fibrillary acidic protein (GFAP) react with brain areas according to Braak staging of Parkinson's disease.

Idiopathic Parkinson's disease (PD) is characterized by a progredient degeneration of the brain, starting at deep subcortical areas such as the dorsal motor nucleus of the glossopharyngeal and vagal nerves (DM) (stage 1), followed by the coeruleus-subcoeruleus complex; (stage 2), the substantia nigra (SN) (stage 3), the anteromedial temporal mesocortex (MC) (stage 4), high-order sensory association areas and prefrontal fields (HC) (stage 5) and finally first-order sensory association areas, premotor areas, as well as primary sensory and motor field (FC) (stage 6). Autoimmunity might play a role in PD pathogenesis. Here we analyzed whether anti-brain autoantibodies differentially recognize different human brain areas and identified autoantigens that correlate with the above-described dissemination of PD pathology in the brain. Brain tissue was obtained from deceased individuals with no history of neurological or psychiatric disease and no neuropathological abnormalities. Tissue homogenates from different brain regions (DM, SN, MC, HC, FC) were subjected to SDS-PAGE and Western blot. Blots were incubated with plasma samples from 30 PD patients and 30 control subjects and stained with anti-IgG antibodies to detect anti-brain autoantibodies. Signals were quantified. Prominent autoantigens were identified by 2D-gel-coupled mass spectrometry sequencing. Anti-brain autoantibodies are frequent and occur both in healthy controls and individuals with PD. Glial fibrillary acidic protein (GFAP) was identified as a prominent autoantigen recognized in all plasma samples. GFAP immunoreactivity was highest in DM areas and lowest in FC areas with no significant differences in anti-GFAP autoantibody titers between healthy controls and individuals with PD. The anti-GFAP autoimmunoreactivity of different brain areas correlates with the dissemination of histopathological neurodegeneration in PD. We hypothesize that GFAP autoantibodies are physiological but might be involved as a cofactor in PD pathogenesis secondary to a leakage of the blood-brain barrier.

Interim Recommendations from the Advisory Committee on Immunization Practices for the Use of Bivalent Booster Doses of COVID-19 Vaccines - United States, October 2022.

Four COVID-19 vaccines are currently approved for primary series vaccination in the United States under a Biologics License Application or authorized under an emergency use authorization (EUA) by the Food and Drug Administration (FDA), and recommended for primary series vaccination by the Advisory Committee on Immunization Practices (ACIP): 1) the 2- or 3-dose monovalent mRNA BNT162b2 (Pfizer-BioNTech, Comirnaty) COVID-19 vaccine; 2) the 2- or 3-dose monovalent mRNA mRNA-1273 (Moderna, Spikevax) COVID-19 vaccine; 3) the single-dose adenovirus vector-based Ad26.COV.S (Janssen [Johnson & Johnson]) COVID-19 vaccine; and 4) the 2-dose adjuvanted, protein subunit-based NVX-CoV2373 (Novavax) COVID-19 vaccine. The number of doses recommended is based on recipient age and immunocompromise status (1). For additional protection, FDA has amended EUAs to allow for COVID-19 booster doses in eligible persons (1). Because COVID-19 vaccines have demonstrated decreased effectiveness during the period when the Omicron variant (B.1.1.529) of SARS-CoV-2 predominated, bivalent booster doses (i.e., vaccine with equal components from the ancestral and Omicron strains) were considered for the express purpose of improving protection conferred by COVID-19 vaccine booster doses (2). During September-October 2022, FDA authorized bivalent mRNA vaccines for use as a booster dose in persons aged ≥5 years who completed any FDA-approved or FDA-authorized primary series and removed EUAs for monovalent COVID-19 booster doses (1). Pfizer-BioNTech and Moderna bivalent booster vaccines each contain equal amounts of spike mRNA from the ancestral and Omicron BA.4/BA.5 strains. After the EUA amendments, ACIP and CDC recommended that all persons aged ≥5 years receive 1 bivalent mRNA booster dose ≥2 months after completion of any FDA-approved or FDA-authorized monovalent primary series or monovalent booster doses.

Interim Recommendation of the Advisory Committee on Immunization Practices for Use of the Novavax COVID-19 Vaccine in Persons Aged ≥18 years - United States, July 2022.

The NVX-CoV2373 (Novavax) COVID-19 vaccine is a recombinant spike (rS) protein nanoparticle vaccine with Matrix-M adjuvant to protect against infection with SARS-CoV-2, the virus that causes COVID-19. On July 13, 2022, the Food and Drug Administration (FDA) issued Emergency Use Authorization (EUA) for the Novavax vaccine for primary COVID-19 immunization of unvaccinated adults aged ≥18 years, administered as 2 doses (5 µg rS and 50 µg Matrix-M adjuvant in each dose) 3 weeks apart (1). On July 19, 2022, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use of the Novavax vaccine in persons aged ≥18 years for the prevention of COVID-19.* In the per-protocol† efficacy analysis, vaccine efficacy (VE) against reverse transcription-polymerase chain reaction (RT-PCR)-confirmed symptomatic COVID-19 was 89.6% (95% CI = 82.4%-93.8%). The Alpha variant (B.1.1.7) of SARS-CoV-2 was the predominant circulating variant during the period of case accrual for VE assessments. Cases of myocarditis or pericarditis were reported in temporal association with vaccination, suggesting a possible causal relationship. The ACIP recommendation for the use of the Novavax COVID-19 vaccine is interim and will be updated as additional information becomes available. The adjuvanted, protein subunit-based Novavax COVID-19 vaccine provides an additional option for unvaccinated adults, increasing flexibility for the public and for vaccine providers. Vaccination is important for protection against COVID-19.

Interim Recommendations of the Advisory Committee on Immunization Practices for Use of Moderna and Pfizer-BioNTech COVID-19 Vaccines in Children Aged 6 Months-5 Years - United States, June 2022.

On June 17, 2022, the Food and Drug Administration (FDA) issued Emergency Use Authorization (EUA) amendments for the mRNA-1273 (Moderna) COVID-19 vaccine for use in children aged 6 months-5 years, administered as 2 doses (25 µg [0.25 mL] each), 4 weeks apart, and BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine for use in children aged 6 months-4 years, administered as 3 doses (3 µg [0.2 mL] each), at intervals of 3 weeks between doses 1 and 2 and ≥8 weeks between doses 2 and 3. On June 18, 2022, the Advisory Committee on Immunization Practices (ACIP) issued separate interim recommendations for use of the Moderna COVID-19 vaccine in children aged 6 months-5 years and the Pfizer-BioNTech COVID-19 vaccine in children aged 6 months-4 years for the prevention of COVID-19.* Both the Moderna and Pfizer-BioNTech COVID-19 vaccines met the criteria for immunobridging, which is the comparison of neutralizing antibody levels postvaccination in young children with those in young adults in whom efficacy had been demonstrated. Descriptive efficacy analyses were also conducted for both Moderna and Pfizer-BioNTech COVID-19 vaccines during the period when the Omicron variant of SARS-CoV-2 (the virus that causes COVID-19) predominated. No specific safety concerns were identified among recipients of either vaccine. ACIP recommendations for the use of the Moderna COVID-19 vaccine and the Pfizer-BioNTech COVID-19 vaccine in children aged 6 months-5 years and 6 months-4 years, respectively, are interim and will be updated as additional information becomes available. Vaccination is important for protecting children aged 6 months-5 years against COVID-19.

The Advisory Committee on Immunization Practices' Recommendation for Use of Moderna COVID-19 Vaccine in Adults Aged ≥18 Years and Considerations for Extended Intervals for Administration of Primary Series Doses of mRNA COVID-19 Vaccines - United States, February 2022.

The mRNA-1273 (Moderna) COVID-19 vaccine is a lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccine encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2, the virus that causes COVID-19. During December 2020, the vaccine was granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA), and the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for use among persons aged ≥18 years (1), which was adopted by CDC. During December 19, 2020-January 30, 2022, approximately 204 million doses of Moderna COVID-19 vaccine were administered in the United States (2) as a primary series of 2 intramuscular doses (100 µg [0.5 mL] each) 4 weeks apart. On January 31, 2022, FDA approved a Biologics License Application (BLA) for use of the Moderna COVID-19 vaccine (Spikevax, ModernaTX, Inc.) in persons aged ≥18 years (3). On February 4, 2022, the ACIP COVID-19 Vaccines Work Group conclusions regarding recommendations for the use of the Moderna COVID-19 vaccine were presented to ACIP at a public meeting. The Work Group's deliberations were based on the Evidence to Recommendation (EtR) Framework,* which incorporates the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach† to rank evidence quality. In addition to initial clinical trial data, ACIP considered new information gathered in the 12 months since issuance of the interim recommendations, including additional follow-up time in the clinical trial, real-world vaccine effectiveness studies, and postauthorization vaccine safety monitoring. ACIP also considered comparisons of mRNA vaccine effectiveness and safety in real-world settings when first doses were administered 8 weeks apart instead of the original intervals used in clinical trials (3 weeks for BNT162b2 [Pfizer-BioNTech] COVID-19 vaccine and 4 weeks for Moderna COVID-19 vaccine). Based on this evidence, CDC has provided guidance that an 8-week interval might be optimal for some adolescents and adults. The additional information gathered since the issuance of the interim recommendations increased certainty that the benefits of preventing symptomatic and asymptomatic SARS-CoV-2 infection, hospitalization, and death outweigh vaccine-associated risks of the Moderna COVID-19 vaccine. On February 4, 2022, ACIP modified its interim recommendation to a standard recommendation§ for use of the fully licensed Moderna COVID-19 vaccine in persons aged ≥18 years.

A framework to model global, regional, and national estimates of intimate partner violence.

BACKGROUND: Accurate and reliable estimates of violence against women form the backbone of global and regional monitoring efforts to eliminate this human right violation and public health problem. Estimating the prevalence of intimate partner violence (IPV) is challenging due to variations in case definition and recall period, surveyed populations, partner definition, level of age disaggregation, and survey representativeness, among others. In this paper, we aim to develop a sound and flexible statistical modeling framework for global, regional, and national IPV statistics. METHODS: We modeled IPV within a Bayesian multilevel modeling framework, accounting for heterogeneity of age groups using age-standardization, and age patterns and time trends using splines functions. Survey comparability is achieved using adjustment factors which are estimated using exact matching and their uncertainty accounted for. Both in-sample and out-of-sample comparisons are used for model validation, including posterior predictive checks. Post-processing of models' outputs is performed to aggregate estimates at different geographic levels and age groups. RESULTS: A total of 307 unique studies conducted between 2000-2018, from 154 countries/areas, and totaling nearly 1.8 million unique women responses informed lifetime IPV. Past year IPV had a similar number of studies (n = 332), countries/areas represented (n = 159), and individual responses (n = 1.8 million). Roughly half of IPV observations required some adjustments. Posterior predictive checks suggest good model fit to data and out-of-sample comparisons provided reassuring results with small median prediction errors and appropriate coverage of predictions' intervals. CONCLUSIONS: The proposed modeling framework can pool both national and sub-national surveys, account for heterogeneous age groups and age trends, accommodate different surveyed populations, adjust for differences in survey instruments, and efficiently propagate uncertainty to model outputs. Describing this model to reproducible levels of detail enables the accurate interpretation and responsible use of estimates to inform effective violence against women prevention policy and programs, and global monitoring of elimination efforts as part of the Sustainable Development Goals.

Separation of intact proteins by capillary electrophoresis.

This work introduces novel and universal workflows for the analysis of intact proteins by capillary electrophoresis and presents guidelines for the targeted selection of appropriate background electrolytes (BGEs) by consideration of the target proteins' isoelectric point (pI). The suitability of neutral dimethyl polysiloxane (PDMS) capillaries with dynamic coatings of cationic cetyltrimethylammonium bromide (CTAB) or anionic sodium dodecyl sulfate (SDS), and bare fused silica (BFS) capillaries were systematically evaluated for the analysis of histidine and seven model proteins in six BGEs with pH values between 3.0 and 9.6. Multiple capillary and BGE combinations were suitable for the analysis of all proteins with molecular weights ranging from 13.7-150 kDa, and pIs between 4.7 and 9.6. The CTAB-PDMS capillary was best suited for low pH BGEs, while the SDS-PDMS and BFS capillary were superior for high pH BGEs. These combinations consistently resulted in sharp peak shapes and rapid migration times. pH values of BGEs closer to the proteins' pI produced poorer peak shapes and decreased effective mobilities due to suppressed ionisation. Plots of mobility vs. pH crossed at approximately the pI of the protein in most cases. The workflow was applied to the analysis of caseins and whey proteins in milk for the separation of the seven most abundant proteins, including the isoforms of A1 and A2 ß-casein and ß-lactoglobulin A and B.

Cullin 3 Is Crucial for Pro-B Cell Proliferation, Interacts with CD22, and Controls CD22 Internalization on B Cells.

B lymphocytes are important players of the adaptive immune system. However, not just activation of B cells but also regulation of B cell signaling is important to prevent hyperactivity and dysregulation of the immune response. Different mechanisms and proteins contribute to this balance. One of these is CD22, a member of the Siglec family. It is an inhibitory coreceptor of the BCR and inhibits B cell activation. Upon BCR stimulation, CD22-dependent inhibition of BCR signaling results in a decreased calcium mobilization. Although some CD22 binding partners have already been identified, the knowledge about the CD22 interactome is still incomplete. In this study, quantitative affinity purification-mass spectrometry enabled the delineation of the CD22 interactome in the B cell line DT40. These data will clarify molecular mechanisms and CD22 signaling events after BCR activation and revealed several new CD22-associated proteins. One new identified interaction partner is the E3 ubiquitin ligase cullin 3, which was revealed to regulate CD22 surface expression and clathrin-dependent CD22 internalization after BCR stimulation. Furthermore cullin 3 was identified to be important for B lymphocytes in general. B cell-specific cullin 3-deficient mice show reduced developing B cells in the bone marrow and a severe pro-B cell proliferation defect. Mature B cells in the periphery are also reduced and characterized by increased CD22 expression and additionally by preactivated and apoptotic phenotypes. The findings reveal novel functions of cullin 3 in B lymphocytes, namely regulating CD22 surface expression and internalization after B cell activation, as well as promoting proliferation of pro-B cells.

Knowledge, attitudes and practices of health care providers trained in responding to violence against women: a pre- and post-intervention study.

BACKGROUND: Violence against women is a serious public health concern, and is highly prevalent globally, including in India. Health-care providers [HCPs] can play an important role in addressing and reducing negative consequences of violence against women. We implemented a pre-post intervention study of HCP training in three tertiary care facilities in Maharashtra, India. METHODS: The study used a pre-post intervention design with assessment of HCPs' (n = 201) knowledge, attitudes, perceived preparedness and practice at three time points: before training, after training and at 6 months follow- up. RESULTS: Total median score of knowledge about common signs and symptoms of violence (8.89 vs, 10.00), attitudes towards acceptability of violence (9.05 vs. 10.00), individual (6.74 vs. 10.00) and system level preparedness (6.11 vs. 8.14) improved from pre to post- training. The generalized estimating equation [GEE] model, adjusted for age, sex, site and department, showed an improvement in knowledge, attitudes and preparedness post- training. The change from pre to 6 months follow- up was not significant for attitude. CONCLUSIONS: This package of interventions, including training of HCPs, improved HCPs' knowledge, attitudes and practices, yet changes in attitudes and preparedness did not sustain over time. This study indicates feasibility and positive influence of a multi-component intervention to improve HCP readiness to respond to violence against women in a low-resource setting. Future phases of intervention development include adapting this intervention package for primary and secondary health facilities in this context, and future research should assess these interventions using a rigorous experimental design. Finally, these results can be used to advocate for multi-layered, systems-based approaches to strengthening health response to violence against women.

Characterization of Upconversion Nanoparticles by Single-Particle ICP-MS Employing a Quadrupole Mass Filter with Increased Bandpass.

This work introduces new methods to characterize dispersions of small-diameter or low-mass-fraction nanoparticles (NPs) by single-particle inductively coupled plasma-mass spectrometry (SP ICP-MS). The optimization of ion extraction, ion transport, and the operation of the quadrupole with increased mass bandwidth improved the signal-to-noise ratios significantly and decreased the size detection limits for all NP dispersions investigated. As a model system, 10.9 ± 1.0 nm Au NPs were analyzed to demonstrate the effects of increasing ion transmission. Specifically, increasing the mass bandwidth of the quadrupole improved the size detection limit to 4.2 nm and enabled the resolution of NP signals from ionic background and noise. Subsequently, the methods were applied to the characterization of lanthanide-doped upconversion nanoparticles (UCNPs) by SP ICP-MS. Three different types of UCNPs (90 nm NaYF4: 20% Yb, 2% Er; 20 nm NaGdF4: 20% Yb, 1% Er; 15 nm NaYF4: 20% Yb, 2% Er) were investigated. Y showed the best signal-to-noise ratios with optimized ion extraction and transport parameters only, whereas the signal-to-noise ratios of Gd, Er, and Yb were further improved by increasing the mass bandwidth of a quadrupole mass filter. The novel methods were suitable for detailed characterization of diluted UCNP dispersions including particle stoichiometries and size distributions. A Poisson model was further applied to assess particle-particle interactions in the aqueous dispersions. The methods have considerable potential for the characterization of small-diameter and/or low-mass-fraction nanoparticles.