Integrated Early Childhood Development in Cambodia: Protocol of a Cluster Stepped-Wedge Trial.

OBJECTIVES: Limited evidence is available on mechanisms linking integrated, multisector interventions with early childhood development. The Integrated Early Childhood Development program aims to improve children's development by promoting targeted caregiving behaviors beginning prenatally through age 5 years, in partnership with the Royal Government of Cambodia. METHODS: This cluster stepped-wedge trial is being conducted in Cambodia among 3 cohorts, encompassing 339 villages and 1790 caregivers who are pregnant or caring for a child aged <5 years. The 12- to 15-month intervention is delivered to each cohort using a staggered stepped-wedge design. Among all cohorts, enrollment evaluations will be followed by 3 data collection waves. Targeted caregiving interventions are provided through community, group, and home-visiting platforms. Child development is measured using the Caregiver Reported Early Development Instrument and the Early Childhood Development Index 2030. The evaluation assesses mediation through targeted caregiving behaviors: responsive caregiving, nutrition, health and hygiene, and household stability and support; moderation by household wealth, caregiver education, and child birth weight; and sustainability after the intervention concludes. CONCLUSIONS: This protocol article describes the plans for a cluster randomized controlled trial to measure the impact of an integrated, multisector intervention on children's development. By partnering with the Royal Government of Cambodia and addressing intervention pathways and moderators, this trial will provide guidance for policies and programs to promote early childhood development using principles of implementation science and equity, including increased investment for vulnerable families.

Retention and Predictors of Attrition Among HIV-infected Children on Antiretroviral Therapy in Côte d'Ivoire Between 2012 and 2016.

BACKGROUND: An estimated 21,000 children 0-14 years of age were living with HIV in Côte d'Ivoire in 2020, of whom only 49% have been diagnosed and are receiving antiretroviral therapy (ART). Retention in HIV care and treatment is key to optimize clinical outcomes. We evaluated pediatric retention in select care and treatment centers (CTCs) in Côte d'Ivoire. METHODS: We retrospectively reviewed medical records using 2-stage cluster sampling for children under 15 years initiated on ART between 2012 and 2016. Kaplan-Meier time-to-event analysis was done to estimate cumulative attrition rates per total person-years of observation. Cox proportional hazard regression was performed to identify factors associated with attrition. RESULTS: A total of 1198 patient records from 33 CTCs were reviewed. Retention at 12, 24, 36, 48 and 60 months after ART initiation was 91%, 84%, 74%, 72% and 70%, respectively. A total of 309 attrition events occurred over 3169 person-years of follow-up [266 children were lost to follow-up (LTFU), 29 transferred to another facility and 14 died]. LTFU determinants included attending a "public-private" CTC [adjusted hazard ratio (aHR) 6.05; 95% confidence interval (CI): 4.23-8.65], receiving care at a CTC without an on-site laboratory (aHR: 4.01; 95% CI: 1.70-9.46) or attending a CTC without an electronic medical record (EMR) system (aHR: 2.22; 95% CI: 1.59-3.12). CONCLUSIONS: In Cote d'Ivoire, patients attending a CTC that is public-private, does not have on-site laboratory or EMR system were likely to be LTFU. Decentralization of laboratory services and scaling use of EMR systems could help to improve pediatric retention.

What are the prospects for the hormonal IUD in the public sector? A mixed-method study of the user population in Zambia.

BACKGROUND: The levonorgestrel-releasing intrauterine device (IUD)-also known as the hormonal IUD-is a highly effective contraceptive method that has not been widely available in the public sector in Zambia. Early introduction efforts can provide critical insights into the characteristics of users, reasons for method choice, and experiences getting their method. METHODS: We conducted a survey with 710 public sector clients who received a hormonal IUD, copper IUD, implant or injectable in two provinces of Zambia, and additional in-depth interviews with 29 women. We performed descriptive analyses of survey data and fitted multivariable logistic regression models to assess factors associated with hormonal IUD use. Qualitative interviews were analyzed thematically. RESULTS: Factors associated with hormonal IUD use included full-time or self-employment (relative to both implant and copper IUD use), as well as being older, wealthier, and partner not being aware of method use (relative to implant use only). Common reasons for choosing long-acting methods were duration, perception that the method was "right for my body," and convenience. In addition, a portion of hormonal IUD acceptors mentioned effectiveness, potential for discreet use, few or manageable side effects, and treatment for heavy or painful periods. Between 83 and 95% of women said that they were counseled about menstrual changes and/or non-bleeding side effects; however, more hormonal IUD acceptors recalled being counseled on the possibility of experiencing reduced bleeding (88%) than amenorrhea (43%). Qualitative interviews indicate that women seek methods with minimal or tolerable side effects. While most women reported their partner was aware of method use, men may be more consistently involved in the decision to use contraception rather than in the choice of a particular method. Qualitative results show an appreciation of the lifestyle benefits of reduced bleeding (especially lighter bleeding), although amenorrhea can be cause for concern. CONCLUSIONS: Initial efforts to introduce the hormonal IUD can provide valuable learnings that can inform broader method introduction to expand choice and better suit women's needs in Zambia and elsewhere. Scale-up plans should include emphasis on high quality counseling and demand generation. The government of Zambia is committed to increasing access to high-quality contraception and making more choices available to users. To date, the hormonal IUD, a highly effective, long-lasting contraceptive has not been widely available in the country. A study in pilot introduction settings provided insights into why women chose the methods, their characteristics, and their experiences getting their methods. The 710 women in the study received family planning services in public sector settings in two provinces in Zambia. Women in the study who received a hormonal IUD, copper IUD, implant, or injectable completed a quantitative survey; in-depth interviews were also conducted with 29 women. Results showed common reasons for choosing the long-acting methods (hormonal IUD, copper IUD or implants) were their duration, perception that the method was "right for my body," and convenience. In addition, some hormonal IUD acceptors indicated that they were attracted to the method's effectiveness, potential for discreet use, few or manageable side effects, and treatment for heavy or painful periods. Qualitative interviews with women also showed that women want contraceptive methods that lead to minimal or tolerable side effects. Male partners were typically aware of contraceptive use; however, men were less involved with decisions about the particular method women selected. Use of the hormonal IUD can lead to reduced menstrual bleeding, and in the interviews, women indicated that they liked reduced bleeding (especially lighter bleeding), although amenorrhea (paused bleeding) can be cause for concern. The results can help inform broader method introduction.

What Goes In Must Come Out: A Mixed-Method Study of Access to Contraceptive Implant Removal Services in Ghana.

BACKGROUND: Access to quality removal services is a key component of informed choice in contraceptive implant use; however, limited data exist on users' access to removal services. In Ghana, implants are available across the country and are the most commonly used contraceptive method among married women. METHODS: From October 2017 and January 2018, we conducted a phone survey with a stratified random sample of 1,159 women who had obtained an implant from a public-sector Ghana Health Service clinic in 2 regions and 1,073 women who had an implant inserted through Marie Stopes International Ghana (MSIG) mobile outreach in 2 other regions. We also interviewed 50 women just after receiving an implant removal from MSIG. We conducted follow-up in-depth interviews with 20 implant acceptors and 15 implant providers across the 4 study regions. RESULTS: More than four-fifths of women in both service delivery contexts knew that their implant could be removed before its labeled duration. Nearly half of public sector clients and one-third of outreach clients reported that their provider only told them of removal access at the place of insertion. Among women obtaining their implant in the public and outreach sectors, respectively, 32% and 21% reported ever wanting it removed and 61% and 55% who attempted removal obtained a removal on the first attempt. An additional 17% in each context were successful in having their implant removed within 1 week of the first attempt. Most women obtained removal from the same place they received their insertion (81% public, 70% outreach). Most women reported their overall removal experience was very or somewhat easy (74% public, 68% outreach). Challenges included cost, provider availability, interactions with providers, and difficult removals. CONCLUSIONS: Access to implant removal is not universal in Ghana. Strengthening removal services in both the public and outreach sectors is needed to ensure comprehensive access.

"We're Going to Leave You for Last, Because of How You Are": Transgender Women's Experiences of Gender-Based Violence in Healthcare, Education, and Police Encounters in Latin America and the Caribbean.

Transgender (trans) women experience gender-based violence (GBV) throughout their lives, which impedes their access to services and contributes to poor health outcomes and quality of life. To inform policies and health programs, trans women worked with the United States Agency for International Development (USAID)- and President's Emergency Plan for AIDS Relief (PEPFAR)-supported LINKAGES project, the United Nations Development Programme, The University of the West Indies, and local organizations to document experiences of GBV and transphobia in healthcare, education, and police encounters. Trans women conducted 74 structured interviews with other trans women in El Salvador, Trinidad and Tobago, Barbados, and Haiti in 2016. We conducted qualitative applied thematic analysis to understand the nature and consequences of GBV and transphobia and descriptive quantitative analysis to identify the proportion who experienced GBV in each context. A high proportion experienced GBV in education (85.1%), healthcare (82.9%), from police (80.0%), and other state institutions (66.1%). Emotional abuse was the most common in all contexts and included gossiping, insults, and refusal to use their chosen name. Participants also experienced economic, physical, and sexual violence, and other human rights violations based on their gender identity and expression. At school, participants were physically threatened and assaulted, harassed in bathrooms, and denied education. In healthcare, participants were given lower priority and received substandard care. Healthcare workers and police blamed participants for their health and legal problems, and denied them services. From police, participants also experienced physical and sexual assault, theft, extortion for sex or money, and arbitrary arrest and detention. Participants had difficulty obtaining identification documents that matched their gender identity, sometimes being forced to alter their appearance or being denied an identification card. Service providers not only failed to meet the specific needs of trans women but also discriminated against them when they sought services, exacerbating their economic, health, and social vulnerability. Although international and regional resolutions call for the legal protection of transgender people, states do not meet these obligations. To respect, promote, and fulfill trans women's human rights, governments should enact and enforce antidiscrimination and gender-affirming laws and policies. Governments should also sensitize providers to deliver gender-affirming services.

Experiences of gender-based violence among female sex workers, men who have sex with men, and transgender women in Latin America and the Caribbean: a qualitative study to inform HIV programming.

BACKGROUND: Female sex workers, MSM, and transgender women-collectively referred to as key populations (KPs)-are disproportionately affected by gender-based violence (GBV) and HIV, yet little is known about the violence they face, its gender-based origins, and responses to GBV. The purpose of this study was to understand the nature and consequences of GBV experienced, to inform HIV policies and programming and to help protect KPs' human rights. METHODS: Using a participatory approach, FSWs, MSM, and transgender women in Barbados, El Salvador, Trinidad and Tobago, and Haiti conducted 278 structured interviews with peers to understand their experiences of and responses to GBV. Responses to open-ended questions were coded in NVivo and analyzed using an applied thematic analysis. RESULTS: Nearly all participants experienced some form of GBV. Emotional and economic GBV were the most commonly reported but approximately three-quarters of participants reported sexual and physical GBV and other human rights violations. The most common settings for GBV were at home, locations where sex work took place such as brothels, bars and on the street; public spaces such as parks, streets and public transport, health care centers, police stations and-for transgender women and MSM-religious settings and schools. The most common perpetrators of violence included: family, friends, peers and neighbors, strangers, intimate partners, sex work clients and other sex workers, health care workers, police, religious leaders and teachers. Consequences included emotional, physical, and sexual trauma; lack of access to legal, health, and other social services; and loss of income, employment, housing, and educational opportunities. Though many participants disclosed experiences of GBV to friends, colleagues and family, they rarely sought services following violence. Furthermore, less than a quarter of participants believed that GBV put them at risk of HIV. CONCLUSIONS: Our study found that across the four study countries, FSWs, MSM, and transgender women experienced GBV from state and non-state actors throughout their lives, and much of this violence was directly connected to rigid and harmful gender norms. Through coordinated interventions that address both HIV and GBV, this region has the opportunity to reduce the national burden of HIV while also promoting key populations' human rights.

Evaluation of a pilot program for task sharing short and long-acting contraceptive methods in Burkina Faso.

Background: The Family Health Directorate of the Ministry of Health (MoH/FHD) and Marie Stopes Burkina Faso (MS BF), with implementing partners, Association Burkinabé pour le Bien-être Familial (ABBEF) and Equilibres & Populations (Equipop) collaborated to conduct a pilot project in Burkina Faso focused on "increasing access to family planning (FP) services through task-sharing short- and long-acting family planning methods to primary care cadres." Four cadres of providers were trained to provide intrauterine devices (IUDs) and implants, while community health workers (CHWs) were trained to provide pills and subcutaneous injectables. FHI 360 and the Institut Supérieur des Sciences de la Population (ISSP) evaluated the project's impact on method uptake, client satisfaction, safety, acceptability and the feasibility of task sharing. Methods: The evaluation employed service statistics, client exit interviews (quantitative) and in-depth interviews (qualitative). New FP clients, community representatives, MoH officials, and pilot project-trained FP providers from Dandé and Tougan districts participated in these interviews. Results: Providers, community representatives and government officials all spoke favorably of the pilot project and considered it a boon to women and the communities in which they lived. FP clients were satisfied with their methods and the services they received from their respective providers, and they reported no safety concerns. However, service statistics did not show a clear and steady increase in method uptake for the four methods beyond spikes coinciding with pre-existing free contraceptive weeks. Conclusions: Results of the evaluation were largely positive. These evaluation findings are being used to guide decisions about scale-up.

Comparative Study of Different Methods for the Prediction of Drug-Polymer Solubility.

In this study, a comparison of different methods to predict drug-polymer solubility was carried out on binary systems consisting of five model drugs (paracetamol, chloramphenicol, celecoxib, indomethacin, and felodipine) and polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios. The drug-polymer solubility at 25 °C was predicted using the Flory-Huggins model, from data obtained at elevated temperature using thermal analysis methods based on the recrystallization of a supersaturated amorphous solid dispersion and two variations of the melting point depression method. These predictions were compared with the solubility in the low molecular weight liquid analogues of the PVP/VA copolymer (N-vinylpyrrolidone and vinyl acetate). The predicted solubilities at 25 °C varied considerably depending on the method used. However, the three thermal analysis methods ranked the predicted solubilities in the same order, except for the felodipine-PVP system. Furthermore, the magnitude of the predicted solubilities from the recrystallization method and melting point depression method correlated well with the estimates based on the solubility in the liquid analogues, which suggests that this method can be used as an initial screening tool if a liquid analogue is available. The learnings of this important comparative study provided general guidance for the selection of the most suitable method(s) for the screening of drug-polymer solubility.

A multi-step transmission electron microscopy sample preparation technique for cracked, heavily damaged, brittle materials.

A new technique for the preparation of heavily cracked, heavily damaged, brittle materials for examination in a transmission electron microscope (TEM) is described in detail. In this study, cross-sectional TEM samples were prepared from indented silicon carbide (SiC) bulk ceramics, although this technique could also be applied to other brittle and/or multiphase materials. During TEM sample preparation, milling-induced damage must be minimized, since in studying deformation mechanisms, it would be difficult to distinguish deformation-induced cracking from cracking occurring due to the sample preparation. The samples were prepared using a site-specific, two-step ion milling sequence accompanied by epoxy vacuum infiltration into the cracks. This technique allows the heavily cracked, brittle ceramic material to stay intact during sample preparation and also helps preserve the true microstructure of the cracked area underneath the indent. Some preliminary TEM results are given and discussed in regards to deformation studies in ceramic materials. This sample preparation technique could be applied to other cracked and/or heavily damaged materials, including geological materials, archaeological materials, fatigued materials, and corrosion samples.

Unexpected reversible pyrazine based methylation in a Ru(II) complex bearing a pyrazin-2'-yl-1,2,4-triazolato ligand and its effect on acid/base and photophysical properties.

The regioselective methylation of a ruthenium polypyridyl complex bearing both a 1,2,4-triazolato and a pyrazine moiety is reported. In contrast to previous studies in which methylation of the 1,2,4-triazolato ring was observed, in the present system methylation takes place exclusively at the non-coordinated nitrogen of the pyrazine ring. The monomethylation is confirmed by (1)H NMR spectroscopy and ESI-MS and the electronic properties of the methylated complexes are studied by UV/vis absorption, emission, surface enhanced, resonance and transient resonance Raman spectroscopy. Ligand deuteriation is used to simplify the (1)H NMR spectra and to assign definitively the Raman spectra. Acid-base studies show that the triazolato ring of the N-methylated complexes can be protonated at low pH and that at high pH the N-methyl group can be deprotonated reversibly. Furthermore it is shown that under conditions where the methyl group is deprotonated, demethylation occurs to recover the initial complex.

Real-time PCR detection of Dinophysis species in Irish coastal waters.

Diarrhetic shellfish toxin-producing Dinophysis species occur in Irish coastal waters throughout the year. Dinophysis acuta and Dinophysis acuminata are the most commonly occurring species and are responsible for the majority of closures of Irish mussel farms. This study describes the development of a qualitative real-time polymerase chain reaction (PCR) assay for identification of D. acuta and D. acuminata in Irish coastal waters. DNA sequence information for the D1-D2 region of the large ribosomal sub-unit (LSU) was obtained, following single-cell PCR of D. acuta and D. acuminata cells isolated from Irish coastal locations. PCR primers and hybridization probes, specific for the detection of D. acuta, were designed for real-time PCR on the LightCycler™. The LightCycler™ software melt curve analysis programme determined that D. acuta was identified by a melt-peak at 61°C, while D. acuminata cells produced a melt peak at 48°C. The limit of detection of the real-time PCR assay was determined to be one to ten plasmid copies of the LSU D1-D2 target region for both species and one to five D. acuminata cells. Lugol's preserved water samples were also tested with the assay. The real-time PCR assay identified Dinophysis species in 100% of samples found to contain Dinophysis species by light microscopy and had a greater than 90% correlation with light microscopy for identification of D. acuta and D. acuminata in the samples. The assay can identify and discriminate D. acuta and D. acuminata at low numbers in Irish waters and has the potential to add value to the Irish phytoplankton monitoring programme.

Type II (tositumomab) anti-CD20 monoclonal antibody out performs type I (rituximab-like) reagents in B-cell depletion regardless of complement activation.

Anti-CD20 monoclonal antibodies (mAbs) are classified into type I (rituximab-like) or type II (tositumomab-like) based on their ability to redistribute CD20 molecules in the plasma membrane and activate various effector functions. To compare type I and II mAbs directly in vivo and maximize Fc effector function, we selected and engineered mAbs with the same mouse IgG(2)a isotype and assessed their B-cell depleting activity in human CD20 transgenic mice. Despite being the same isotype, having similar affinity, opsonizing activity for phagocytosis, and in vivo half-life, the type II mAb tositumomab (B1) provided substantially longer depletion of B cells from the peripheral blood compared with the type I mAb rituximab (Rit m2a), and 1F5. This difference was also evident within the secondary lymphoid organs, in particular, the spleen. Failure to engage complement did not explain the efficacy of the type II reagents because type I mAbs mutated in the Fc domain (K322A) to prevent C1q binding still did not display equivalent efficacy. These results give support for the use of type II CD20 mAbs in human B-cell diseases.