Multisystemic factors predicting street migration of children in Kenya: A multilevel longitudinal study of families and villages.

BACKGROUND: Street-migration of children is a global problem with sparse multi-level or longitudinal data. Such data are required to inform robust street-migration prevention efforts. OBJECTIVE: This study analyzes longitudinal cohort data to identify factors predicting street-migration of children - at caregiver- and village-levels. PARTICIPANTS AND SETTING: Kenyan adult respondents (n = 575; 20 villages) actively participated in a community-based intervention, seeking to improve factors previously identified as contributing to street-migration by children. METHODS: At two time points, respondents reported street-migration of children, and variables across economic, social, psychological, mental, parenting, and childhood experience domains. Primary study outcome was newly reported street-migration of children at T2 "incident street-migration", compared to households that reported no street-migration at T1 or T2. For caregiver-level analyses, we assessed bivariate significance between variables (T1) and incident street-migration. Variables with significant bivariate associations were included in a hierarchical logistical regression model. For community-level analyses, we calculated the average values of variables at the village-level, after excluding values from respondents who indicated an incident street-migration case to reduce potential outlier influence. We then compared variables between the 5 villages with the highest incidence to the 15 villages with fewer incident cases. RESULTS: In regression analyses, caregiver childhood experiences, psychological factors and parenting behaviors predicted future street-migration. Lower village-aggregated depression and higher village-aggregated collective efficacy and social curiosity appeared significantly protective. CONCLUSIONS: While parenting and economic strengthening approaches may be helpful, efforts to prevent street migration by children should also strengthen community-level mental health, collective efficacy, and communal harmony.

A social innovation to empower community-led monitoring and mobilization for HIV prevention in rural Kenya: experimenting to reduce the HIV prevention policy-implementation gap.

Introduction: Strong policy guidance has recently emerged identifying focal points at multiple levels and across sectors to end the persistent HIV pandemic and related inequities. Reducing the policy-implementation gap, as with the evidence-policy gap, requires strategic alignment between interventional research and policy realms. Global- and national-level HIV policy indicate a need for community-led efforts to reduce HIV stigma, and increase uptake of HIV prevention tools. Methods: This study assesses a process-driven approach to facilitating community-led efforts to reduce HIV stigma, and build a generative context for community-led HIV prevention. The study intervention combines an adapted group-based microfinance process, a novel psychological curriculum, and leadership development at a scale now involving over 10,000 rural Kenyans across 39 villages. Results: Consistent with interventional goals, and current relevant psychosocial theories, we find collective emotion, and HIV stigma (blame and discrimination) significantly improve with more time participating in the in the program and novel curriculum. Further, HIV stigma predicts subsequent reporting of ever being tested for HIV, and the intervention led to the development of "HIV prevention resource committees" - groups of participants committed to undergo training to reduce HIV stigma and prevent HIV within their communities. Discussion: Implications for further research to reduce the HIV policy-implementation gap are discussed, directly within this interventional context and more generally.

Enabling structural resilience of street-involved children and youth in Kenya: reintegration outcomes and the Flourishing Community model.

Introduction: Millions of children and youth live on city streets across the globe, vulnerable to substance use, abuse, material and structural neglect. Structural resilience, the re-establishment of access to structural goods within a society such as housing, education, and healthcare following some interruption, provides an orientation for research and interventional efforts with street-involved children and youth (SICY). Further, a structural resilience framework supports organizing interactions between levels and sectors of a socio-ecology. Methods: Following the expressed interests of Kenyan SICY, and consistent with emerging policy interests at national and global levels, we assess reintegration trajectories of Kenyan SICY (n = 227) participating in a new program intervention and model. The intervention combines two coordinated, parallel programs - one focused on the rescue, rehabilitation, reintegration and resocialization of SICY, and the other focused on empowering families and communities to provide better care for children and youth who are reintegrating from life on the streets to the broader community. Data were collected and analyzed from multiple stages across SICY involvement with the intervention. Results: We found 79% of SICY participants reintegrated with the broader community, and 50% reintegrated with families of origin and returned to school. Twenty-five percent of participants reintegrated to a boarding school, polytechnical school, or began a business. Probability of reintegrating successfully was significantly improved among participants whose families participated in the family- and community-oriented program, who were younger, with less street-exposure, expressed more personal interests, and desired to reintegrate with family. Discussion: To our knowledge, these are the first quantitative data published of successful reintegration of SICY to the broader, non-institutionalized community in any low- or middle-income country. Future research should (1) identify factors across socio-ecological levels and sectors contributing to health and developmental outcomes of reintegrated children and youth, (2) mechanisms to support SICY for whom the interventional strategy did not work, (3) methods to prevent street-migration by children and youth, and (4) system development to coordinate follow-up and relevant investment by institutions, organizations and community leaders to continue reintegration work.

Cameras Optional? Examining Student Camera Use from a Learner-Centered Perspective.

In this paper, we offer a holistic look at undergraduate and graduate students' experiences with using cameras for synchronous online learning via Zoom. Analysis of the data using the American Psychological Association's learner-centered psychological principles revealed that social, cognitive, metacognitive, motivational, affective, and individual difference factors influenced student camera use and the level of influence of each of these factors varied from student to student, time to time, and space to space within a class. Findings suggest that there is a multifaceted, dynamic relationship between the student, video conferencing technology, and instructor's pedagogical actions that shapes camera use. Based on the findings, we offer suggestions for online synchronous course design, teaching, and research.

Child maltreatment, social capital, maternal mental health and duration of program involvement: Assessment from a community-based empowerment program in Kenya.

Multisystem, multi-level interventions are required to enable resilient, nurturing environments for children facing adversity. This study assesses parenting behavior associated with participation in a community-based, adapted microfinance program, and mediated by program-affiliated social capital, maternal depression and self-esteem among Kenyan women. Participants in the intervention, Kuja Pamoja kwa Jamii (KPJ, Swahili for "Come Together to Belong"), gather weekly to engage in trainings and group-based microfinance. Groups selected for the study had participated in the program for 0-15 months at the time of the first interview. Women (n = 400) completed surveys in June 2018 and June 2019. Measures included duration of program exposure, group-affiliated social capital (i.e. trust, belonging, cohesion, and expectation of mutual benefit), depression, self-esteem, and conflict tactics. We used regression analyses and generalized structural equation models to explore associations between program exposure, social capital, psychosocial variables and child maltreatment. Each standard deviation increase in duration of program exposure decreased odds of child physical abuse by 40% and child neglect by 35%. Each standard deviation in the social capital index predicted a significant reduction in odds of child physical abuse (aOR: 0.67), and child neglect (aOR: 0.71). Self-esteem and depression fully mediated observed associations between social capital and child maltreatment. Findings recommend further investigation of the potential for adapted microfinance programs to deliver parenting interventions, improve mental health and foster resilience-enabling social capital. A randomized control trial is required to validate the potential of the assessed intervention to improve parenting behaviors and supportive social conditions.

Flourishing Communities: A new model to promote sustainable community leadership and transformation in semi-rural Kenya.

Communities often face numerous challenges and opportunities - situations that may be reduced to specific domains by researchers, policy makers and interventionists. This study informs and animate a new "flourishing community" model that seeks to build collective capacity to respond to challenges and opportunities. Our work is a response to children living on the streets, whose families face myriad challenges. The Sustainable Development Goals make explicit the need for new, integrative models that acknowledge the interplay of challenges and opportunities within communities through the flow of everyday life. Flourishing communities are generative, supportive, resilient, compassionate, curious, responsive, self-determined, and build resources across economic, social, educational, and health domains. Integrating theoretical models - specifically, community-led development, multi-systemic resilience, and the "broaden and build" cycle of attachment - provide a testable framework to understand and explore hypothesized relationships between survey-collected, cross-sectional variables with 335 participants. Higher collective efficacy, a common byproduct of group-based microlending activities, was correlated with higher sociopolitical control. This correlation was mediated by higher positive emotion, meaning in life, spirituality, curiosity, and compassion. Further research is required to understand replicability, cross-sectoral impact, mechanisms of integrating health and development domains, and implementation challenges of the flourishing community model. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement.

Recently Designed Multivalent Spike Binders Cannot Bind Multivalently─How Do They Achieve Enhanced Avidity to SARS-CoV-2?

The trimeric spike protein of SARS-CoV-2 has been targeted by antibody mimics that bind near or at the receptor-binding domain to neutralize the virus. Several independent studies have reported enhanced binding avidity for dimers and trimers, where binding domains are connected by short peptides. The enhanced avidity of the multivalent constructs was attributed to their simultaneously binding two or three sites within a single spike trimer. We argue here that the 15-20 amino acid peptide linkers, when considered as worm-like-chains, are too short to span the binding sites within a single spike. The enhanced avidity of the multivalent constructs may be explained by a rebinding mechanism, which does not involve multivalent binding.

Partner Cooperation, Conflict, Maternal Mental Health, and Parenting Behaviors in Rural Kenya: Towards a Two-Generational Understanding of Gender Transformation Benefits.

Increasing partner cooperation is an established approach to reducing intimate partner violence. This strategy, known in the literature as "gender transformation," benefits mental and physical health of women and men. Less is known about the potential for gender transformation strategies to improve the nurturing context for children. We hypothesize that increasing partner cooperation, a common benefit of community-based empowerment programs, would decrease child maltreatment through reducing intimate partner conflict and improving maternal mental health. This study utilizes cohort data from women (n = 400) participating in a combined group-based microfinance program to assess potential mechanisms by which partner cooperation at T1 (June 2018) predicts less children maltreatment at T2 (June 2019). As hypothesized, partner cooperation predicts less subsequent child maltreatment-frequency of neglect, corporal punishment, physical assault, and psychological abuse in the past month. This association is mediated completely by subsequent more partner cooperation and less intimate partner conflict, maternal loneliness, and depression. Implications of this study include potential for combining multiple development areas-women's empowerment, intimate partner cooperation, mental health, and child nurturing contexts. Future study should assess these pathways in a cluster-based randomized trial, and explore how findings may inform policy and practice where these domains are less integrated.

Adverse childhood experiences, adult anxiety and social capital among women in rural Kenya.

Hundreds of millions of people suffer anxiety disorders globally, demonstrating need for scalable and effective interventions. Adverse childhood experiences contribute to this mental health burden. The stress-buffering hypothesis, which posits social factors moderate prior adversity and subsequent mental health outcomes, provides one theoretical avenue to consider observations that group-based microfinance programs improve social capital. We investigate associations between adverse childhood experiences, generalized anxiety among adults and social capital associated with participation in a group-based microfinance program in rural Kenya. Adult participants (n = 400 women) responded to standardized measures of childhood adversity in June 2018, group-affiliated social capital and generalized anxiety in June 2019. Cumulative adverse childhood experiences predicted higher anxiety, which was statistically moderated by the presence of group-affiliated interpersonal trust. This study is the first to find social capital associated with participation in a group-based microfinance program statistically moderates expected associations between adverse childhood experiences and adult generalized anxiety. Future study should be conducted using a cluster-randomized control design to further assess the potential of this intervention method to ameliorate associations between past adversity and current mental health.

FtsZ at mid-cell is essential in Escherichia coli until the late stage of constriction.

There has been recent debate as to the source of constriction force during cell division. FtsZ can generate a constriction force on tubular membranes in vitro, suggesting it may generate the constriction force in vivo. However, another study showed that mutants of FtsZ did not affect the rate of constriction, whereas mutants of the PG assembly did, suggesting that PG assembly may push the constriction from the outside. Supporting this model, two groups found that cells that have initiated constriction can complete septation while the Z ring is poisoned with the FtsZ targeting antibiotic PC190723. PC19 arrests treadmilling but leaves FtsZ in place. We sought to determine if a fully assembled Z ring is necessary during constriction. To do this, we used a temperature-sensitive FtsZ mutant, FtsZ84. FtsZ84 supports cell division at 30 °C, but it disassembles from the Z ring within 1 min upon a temperature jump to 42 °C. Following the temperature jump we found that cells in early constriction stop constricting. Cells that had progressed to the later stage of division finished constriction without a Z ring. These results show that in Escherichia coli, an assembled Z ring is essential for constriction except in the final stage, contradicting the simplest interpretation of previous studies using PC19.

Impact of the Injectable Opioid Drug Shortage on Analgesia and Sedation Management in the Medical Intensive Care Unit: A Retrospective Cohort Study.

Objectives: The purpose of this study was to assess the impact of the injectable opioid drug shortage on analgesia and sedation management in the medical intensive care unit (MICU). Methods: A single-center, retrospective cohort study was conducted of mechanically ventilated patients during the injectable opioid shortage. Outcomes were compared between a cohort of patients during the intravenous (IV) opioid shortage (01/01/18-03/31/18) and a control cohort (01/01/17-03/31/17). Total IV opioids and alternative sedative administration were assessed. Richmond Agitation Sedation Score (RASS) and Clinical Pain Observation Score (CPOT) assessments were also evaluated. The primary outcome was percentage of RASS within goal. Secondary outcomes included duration of mechanical ventilation, hospital/ICU length of stay, and mortality. Results: One hundred patients were included (50 patients per cohort). In the shortage cohort, 23.2% fewer IV opioids were used (40 501.8 vs 52 713.8 oral morphine equivalents [OME]). No statistical differences were found in percentage of patients within goal RASS between the shortage and control (median 63.7% vs 74.8%; P = .094) or CPOT (median 49.7% vs 47.7%; P = .575). More patients received enteral opioids and propofol on day 1 in the shortage cohort when compared to the control (22% vs 4%; P = .007 and 76% vs 56%; P = .035) but there were no differences in benzodiazepine, dexmedetomidine, or antipsychotic use. No differences in mechanical ventilation, hospital/ICU length of stay, or mortality were found. Conclusions: Use of less IV opioids during the injectable opioid shortage did not affect achievement of goal RASS and CPOT scores or increase prescribing of sedative medications such as benzodiazepines in the MICU.

Hexokinase 1 cellular localization regulates the metabolic fate of glucose.

The product of hexokinase (HK) enzymes, glucose-6-phosphate, can be metabolized through glycolysis or directed to alternative metabolic routes, such as the pentose phosphate pathway (PPP) to generate anabolic intermediates. HK1 contains an N-terminal mitochondrial binding domain (MBD), but its physiologic significance remains unclear. To elucidate the effect of HK1 mitochondrial dissociation on cellular metabolism, we generated mice lacking the HK1 MBD (ΔE1HK1). These mice produced a hyper-inflammatory response when challenged with lipopolysaccharide. Additionally, there was decreased glucose flux below the level of GAPDH and increased upstream flux through the PPP. The glycolytic block below GAPDH is mediated by the binding of cytosolic HK1 with S100A8/A9, resulting in GAPDH nitrosylation through iNOS. Additionally, human and mouse macrophages from conditions of low-grade inflammation, such as aging and diabetes, displayed increased cytosolic HK1 and reduced GAPDH activity. Our data indicate that HK1 mitochondrial binding alters glucose metabolism through regulation of GAPDH.

Communicating About Time-Limited Trials.

Time-limited trials (TLTs) are used in the management of critical care patients undergoing potentially nonbeneficial interventions to improve prognostication and build trust and consensus between family and intensivists. When these trials are not well defined and executed, discordant views of the patient's prognosis, conflict, and continuation of nonbeneficial care can arise. The mnemonic TIME (truth about uncertainty in prognosis, interval of time, measurement of improvement, and end or extend) can help facilitate clear communication surrounding TLTs. This framework allows physicians and families to deal more effectively with the inherent uncertainty and required flexibility needed in caring for complex critical care patients. This can lead to patient-centered decision-making that improves patient-physician relationships and goal-concordant care and also potentially reduces nonbeneficial treatments at the end of life.

Spirituality as compensation for low-quality social environments in childhood among young Kenyan men.

This study explores the role of spirituality as a coping mechanism for poor social conditions in childhood, asking whether spirituality moderates poor childhood social conditions and suicide ideation, self-rated health and collective self-esteem among young Kenyan men. Measured outcomes were worse among men who recalled fewer memories of relational warmth and safety in childhood, and better among men who reported higher spirituality. Consistent with the "religion as attachment" framework, spirituality significantly moderated associations between suicide ideation, self-rated health and childhood relational warmth and safety. Contrary to expectations, the association between low childhood warmth and safety and collective self-esteem was exacerbated, rather than compensated for, by higher spirituality. We consider whether "a safe harbor" may exist for people higher in spirituality to accept and critique social arrangements, and whether such a situation might illuminate another way spirituality compensates for poor social environments.

Come together to promote health: case study and theoretical perspectives from a Kenyan community-based program.

Over the past four decades, group-based microfinance programs have spread rapidly throughout south Asia, sub-Saharan Africa and Latin America. Recent evaluations of the programs have identified social capital as a common byproduct of frequent association by members, increasing trust, belonging and normative influence. Concurrently, social capital is increasingly recognized as an important health determinant. We present an overview of a program intervention operating in Kenya that utilizes a microfinance approach to produce social capital, and seeks to leverage that social capital to promote health at three levels-the village, group, and individual. A theory of change is presented for each of these three levels, demonstrating conceptually and with program examples how social capital can be applied to promote health. Related social theories and approaches, further research and program directions are given for each of the three levels. We identify potential to improve a broad range of health outcomes through this innovative model, which requires engagement with health promotion researchers and planners in low- and middle-income countries for further refinement and validation.

Iron and Heart Failure: Diagnosis, Therapies, and Future Directions.

To date, 3 clinical trials have shown symptomatic benefit from the use of intravenous (IV) iron in patients with heart failure (HF) with low serum iron. This has led to recommendations in support of the use of IV iron in this population. However, the systemic and cellular mechanisms of iron homeostasis in cardiomyocyte health and disease are distinct, complex, and poorly understood. Iron metabolism in HF appears dysregulated, but it is still unclear whether the changes are maladaptive and pathologic or compensatory and protective for the cardiomyocytes. The serum markers of iron deficiency in HF do not accurately reflect cellular and mitochondrial iron levels, and the current definition based on the ferritin and transferrin saturation values is broad and inclusive of patients who do not need IV iron. This is particularly relevant in view of the potential risks that are associated with the use of IV iron. Reliable markers of cellular iron status may differentiate subgroups of HF patients who would benefit from cellular and mitochondrial iron chelation rather than IV iron.

Subjective Social Standing and Conflict Tactics Among Young Kenyan Men.

Efforts to reduce intimate partner violence in sub-Saharan Africa generally approach the issue through the lens of women's empowerment. These efforts include foci on women's relative power in the relationship, educational background, and earning potential. The social status of men has largely been ignored, reducing the potential to involve them in efforts to demote intimate partner violence. In this study we consider whether a man's perceived social status predicts conflict tactics, and whether these tactics are mediated by loneliness and collective self-esteem from a community-based sample in semi-rural Kenya (n = 263). We find that men who reported lower perceived social status also reported significantly more frequent violent conflicts with their intimate partners. This association was significantly, and completely, mediated by lower collective self-esteem and higher loneliness. There was no direct association between subjective social status and negotiation-based conflict tactics, although there was an indirect association. Men with higher perceived social status reported higher collective self-esteem, and men with higher collective self-esteem reported more negotiation-based conflict tactics. These findings inform efforts to reduce intimate partner violence by involving men, showing potential to reduce violence by building self-esteem among men-particularly those with lower perceived social status.

Evaluation of Emergency Department Management of Opioid-Tolerant Cancer Patients With Acute Pain.

CONTEXT: There are no previously published studies examining opioid doses administered to opioid-tolerant cancer patients during emergency department (ED) encounters. OBJECTIVES: To determine if opioid-tolerant cancer patients presenting with acute pain exacerbations receive adequate initial doses of as needed (PRN) opioids during ED encounters based on home oral morphine equivalent (OME) use. METHODS: We performed a retrospective cohort study of opioid-tolerant cancer patients who received opioids in our ED over a two-year period. The percentage of patients who received an adequate initial dose of PRN opioid (defined as ≥10% of total 24-hour ambulatory OME) was evaluated. Logistic regression was used to establish the relationship between 24-hour ambulatory OME and initial ED OME to assess whether higher home usage was associated with higher likelihood of being undertreated. RESULTS: Out of 216 patients, 61.1% of patients received an adequate initial PRN dose of opioids in the ED. Of patients taking <200 OMEs per day at home, 77.4% received an adequate initial dose; however, only 3.2% of patients taking >400 OMEs per day at home received an adequate dose. Patients with ambulatory 24-hour OME greater than 400 had 99% lower odds of receiving an adequate initial dose of PRN opioid in the ED compared to patients with ambulatory 24-hour OME less than 100 (OR <0.01, CI 0.00-0.02, P < 0.001). CONCLUSIONS: Patients with daily home use less than 200 OMEs generally received adequate initial PRN opioid doses during their ED visit. However, patients with higher home opioid usage were at increased likelihood of being undertreated.

Bereavement Service Preferences of Surviving Family Members: Variation among Next of Kin with Depression and Complicated Grief.

BACKGROUND: Research indicates that bereavement services reduce distress and support adjustment in the bereaved, particularly those experiencing significant levels of depression or grief. However, the service use of bereaved individuals and whether utilization differs among those experiencing depression and complicated grief currently remain unclear. Research is needed to clarify the preferences of the bereaved, including specific bereaved subgroups. OBJECTIVES: The purpose of this study was to explore the bereavement service preferences of bereaved family members whose loved one died in the hospital and identify group differences in service use among individuals with and without depression and complicated grief, considering time since the death of the patient. DESIGN: In this cross-sectional study, self-report data were collected from family members primarily between 3 and 18 months following the death of the patient in the hospital. SETTING: Academic medical center. MEASUREMENTS: We explored helpfulness ratings and actual and projected service utilization of a comprehensive list of hospital and community bereavement services, and compared findings between those with and without depression and complicated grief, considering timing since patient death. RESULTS: Services receiving the highest helpfulness ratings by the entire sample included time alone with the deceased, a quiet room to be alone after the death, sympathy cards from hospital staff, memorial services, chaplain support before/during time of death, an educational grief booklet, grief book recommendations, a check-in phone call from hospital staff, individual counseling, and a relationship-specific support group. Individuals with depression and complicated grief reported a greater willingness to utilize specific services, including a memorial website, support groups, a holiday workshop, and individual/family psychotherapy. CONCLUSION: Findings indicate a difference in the projected service use of the bereaved experiencing depression and/or complicated grief. Follow-up screenings 6-12 months post-bereavement are recommended to identify those in need of formal psychosocial support.