Loneliness among homeless-experienced older adults with cognitive or functional impairments: qualitative findings from the HOPE HOME study.

BACKGROUND: Loneliness is more common in older adults and those who face structural vulnerabilities, including homelessness. The homeless population is aging in the United States; now, 48% of single homeless adults are 50 and older. We know little about loneliness among older adults who have experienced homelessness. We aimed to describe the loneliness experience among homeless-experienced older adults with cognitive and functional impairments and the individual, social, and structural conditions that shaped these loneliness experiences. METHODS: We purposively sampled 22 older adults from the HOPE HOME study, a longitudinal cohort study among adults aged 50 years or older experiencing homelessness in Oakland, California. We conducted in-depth interviews about participants perceived social support and social isolation. We conducted qualitative content analysis. RESULTS: Twenty participants discussed loneliness experience, who had a median age of 57 and were mostly Black (80%) and men (65%). We developed a typology of participants' loneliness experience and explored the individual, social, and structural conditions under which each loneliness experience occurred. We categorized the loneliness experience into four groups: (1) "lonely- distressed", characterized by physical impairment and severe isolation; (2) "lonely- rather be isolated", reflecting deliberate social isolation as a result of trauma, marginalization and aging-related resignation; (3) "lonely- transient", as a result of aging, acceptance and grieving; and (4) "not lonely"- characterized by stability and connection despite having experienced homelessness. CONCLUSIONS: Loneliness is a complex and heterogenous social phenomenon, with homeless-experienced older adults with cognitive or functional impairments exhibiting diverse loneliness experiences based on their individual life circumstances and needs. While the most distressing loneliness experience occurred among those with physical impairment and mobility challenges, social and structural factors such as interpersonal and structural violence during homelessness shaped these experiences.

Quantifying the Relevance of Long-Range Forces for Crystal Nucleation in Water.

Understanding nucleation from aqueous solutions is of fundamental importance in a multitude of fields, ranging from materials science to biophysics. The complex solvent-mediated interactions in aqueous solutions hamper the development of a simple physical picture, elucidating the roles of different interactions in nucleation processes. In this work, we make use of three complementary techniques to disentangle the role played by short- and long-range interactions in solvent-mediated nucleation. Specifically, the first approach we utilize is the local molecular field (LMF) theory to renormalize long-range Coulomb electrostatics. Second, we use well-tempered metadynamics to speed up rare events governed by short-range interactions. Third, the deep learning-based State Predictive Information Bottleneck approach is employed in analyzing the reaction coordinate of the nucleation processes obtained from the LMF treatment coupled with well-tempered metadynamics. We find that the two-step nucleation mechanism can largely be captured by the short-range interactions, while the long-range interactions further contribute to the stability of the primary crystal state under ambient conditions. Furthermore, by analyzing the reaction coordinate obtained from the combined LMF-metadynamics treatment, we discern the fluctuations on different time scales, highlighting the need for long-range interactions when accounting for metastability.

Barriers and Facilitators to Resolving Older Adult Homelessness through Stays with Family: Qualitative findings from the HOPE HOME Study.

Living with family and friends is a common strategy used to prevent or exit homelessness, but little is known about structural barriers that impede family and friends' ability to provide temporary or permanent housing for older homeless adults. We conducted semi-structured interviews with 46 homeless participants from the HOPE HOME study, a cohort of 350 community-recruited homeless adults age 50 or older in Oakland, CA, who reported having stayed with housed family/friends for 1 or more nights in the prior 6 months. We conducted semi-structured interviews with 19 hosts of homeless participants and 11 stakeholders in housing and homelessness. We found that homeless older adults and hosts perceived staying with family or friends as a form of temporary housing rather than as a permanent exit to homelessness. Structural barriers to family and friends providing housing for temporary stays or permanent exits from homelessness included housing regulations restricting visitors and changing rent obligations; decreased eligibility and priority for shelter and permanent housing; geographic and transportation challenges; and environments inconducive to older adults. We suggest four areas for policy reform: providing subsidies to hosts and homeless individuals, removing disincentives for homeless older adults to stay with family, changing lease regulations, and expanding the supply of affordable housing.

Loneliness among older adults who have experienced homelessness: qualitative findings from the HOPE HOME study.

Background: Loneliness is more common in older adults and those who face structural vulnerabilities, including homelessness. The homeless population is aging. We know little about loneliness among older adults who have experienced homelessness. We aimed to describe the loneliness experience among older adults who have experienced homelessness and the individual, social, and structural conditions that shaped these loneliness experiences. Methods: We purposively sampled 22 older adults from the HOPE HOME study, a longitudinal cohort study among adults aged 50 years or older experiencing homelessness in Oakland, California. We conducted in-depth interviews about participants' perceived social support and social isolation. We conducted qualitative content analysis. Results: Twenty participants discussed loneliness experience, who had a median age of 57 and were mostly Black (80%) and men (65%). We developed a typology of participants' loneliness experience and explored the individual, social, and structural conditions under which each loneliness experience occurred. We categorized the loneliness experience into four groups: 1) "lonely - distressed", characterized by physical impairment and severe isolation; 2) "lonely - rather be isolated", reflecting deliberate social isolation as a result of trauma, marginalization and aging-related resignation; 3) "lonely - transient", as a result of aging, acceptance and grieving; and 4) "not lonely" - characterized by stability and connection despite having experienced homelessness. Conclusions: Loneliness is a complex and heterogenous social phenomenon, with older adults who have experienced homelessness exhibiting diverse loneliness experiences based on their individual life circumstances and needs. While the most distressing loneliness experience occurred among those with physical impairment and mobility challenges, social and structural factors such as interpersonal and structural violence during homelessness shaped these experiences.

Local Molecular Field Theory for Coulomb Interactions in Aqueous Solutions.

Coulomb interactions play a crucial role in a wide array of processes in aqueous solutions but present conceptual and computational challenges to both theory and simulations. We review recent developments in an approach addressing these challenges─local molecular field (LMF) theory. LMF theory exploits an exact and physically suggestive separation of intermolecular Coulomb interactions into strong short-range and uniformly slowly varying long-range components. This allows us to accurately determine the averaged effects of the long-range components on the short-range structure using effective single particle fields and analytical corrections, greatly reducing the need for complex lattice summation techniques used in most standard approaches. The simplest use of these ideas in aqueous solutions leads to the short solvent (SS) model, where both solvent-solvent and solute-solvent Coulomb interactions have only short-range components. Here we use the SS model to give a simple description of pairing of nucleobases and biologically relevant ions in water.

Neurocognitive health of older adults experiencing homelessness in Oakland, California.

Background and objectives: The homeless population in the US is aging. Cognitive impairment is prevalent in this population, yet little is known about the neurologic etiologies of such impairment. Addressing this gap in knowledge is important because homeless older adults with cognitive impairment due to neurodegenerative disease may need lifelong tailored support to obtain and maintain housing. In this study, we characterized the neurocognitive health of a sample of adults who experienced homelessness for the first time after age 50 using gold standard behavioral neurology examination practices. Methods: We conducted a descriptive cross-sectional study of older adults who first experienced homelessness after age 50. We recruited our sample purposively from an ongoing longitudinal cohort study of adults who were aged 50 and over and homeless when they entered the cohort. For this sub study, we enrolled a convenience sample from those who reported their first episode of homelessness after age 50. We did not exclude individuals based on history of substance use. Neurologists conducted a structured neurocognitive history intake, neurological examination, neuropsychological evaluation, and functional assessment between November 2020 and February 2021. We screened all participants for neurocognitive disorders using gold standard clinical research diagnostic criteria. Results: We evaluated 25 participants, most were men (76%) and Black (84%), with a median age of 61 years. The most common neurocognitive complaints included deficits in recent episodic memory (n = 15, 60%), executive functions (n = 13, 52%), and behavior/mood, with apathy being the most common complaint (n = 20, 80%). Neuropsychological testing revealed a high prevalence of socioemotional deficits (n = 20, 80%). Common neurological examination deficits included difficulties with coordination, such as impaired Luria task (n = 16, 64%), signs of distal peripheral neuropathy (n = 8, 32%), anosmia/hyposmia (n = 4, 21%), and signs of mild Parkinsonism (n = 5, 20%). The most common diagnoses were MCI (n = 7, 28%), bvFTD (n = 4, 16%), AD (n = 4, 16%), and DLB (n = 2, 8%). Discussion: Our findings suggest that neurocognitive concerns and examination deficits are common among older homeless adults. Specific neurocognitive disorders may be overrepresented in this population, particularly frontotemporal disorders. Longitudinal studies involving brain biomarkers are needed to characterize the neurocognitive health of this vulnerable population more precisely.

Temporary stays with housed family and friends among older adults experiencing homelessness: Qualitative findings from the HOPE HOME study.

Background: The proportion of adults age 50 and older experiencing homelessness is growing. People at risk for homelessness may stay with family and friends to prevent homelessness. Moving in with housed family and friends is a strategy used to exit homelessness. Little is known about these stays with family and friends. This study examined the motivations for and challenges of older adults experiencing homelessness staying with or moving in with family or friends. Methods: We purposively sampled 46 participants from the HOPE HOME study, a cohort of 350 community-recruited adults experiencing homelessness age ≥50 in Oakland, CA. Inclusion criteria included having stayed with housed family/friends for ≥1 nights in the prior 6 months. We sampled 19 family/friends who had hosted participants experiencing homelessness. We conducted separate, semi-structured interviews, summarized, memoed and coded data consistent using a grounded theory approach. Results: Older adults experiencing homelessness reported primarily temporary stays. Motivations for stays on the part of participants included a need for environmental, physical, and emotional respite from homelessness. Both individuals experiencing homelessness and hosts cited the mutual benefits of stays. Barriers to stays included feelings of shame, concerns about burdening the hosts, and interpersonal conflicts between older adults experiencing homelessness and host participants. Conclusions: There are potential opportunities and concerns surrounding temporary stays between older adults experiencing homelessness and their family or friends. Policy solutions should support the potential mutual benefits of temporary stays, while addressing interpersonal barriers to strengthen kinship and friendship networks and mediate the negative impacts of homelessness.

Ground-Truthing the Experiences of Homeless Older Adults' Recent Stays with Family and Friends: A Case Study of Participatory Data Analysis.

Many older homeless adults have recently stayed with family or friends, yet little is understood about these experiences. We conducted a multimethod qualitative study of older unhoused adults in Oakland, California. First, we conducted in-depth interviews among older adults experiencing homelessness with recent stays with a housed family member or friend (n=46), hosts (n=19), and program key informants (n=11). Second, we developed thematic summaries in the form of character-based composite stories, which were presented to a Council of Elders with lived experiences of homelessness, to explore reactions, referred to as ground-truthing, a form of participatory data analysis. Predominantly, participants were African American men. Barriers included structural factors (discrimination), policy (lease restrictions), community (violence), interpersonal factors (power dynamics), and individual factors (health problems). Factors enhancing stays included inter-generational support and leveraging resources. Ground-truthing discussions reinforced and expanded upon findings (e.g., importance of neighborhood identity, training needs, how self-improvement affects readiness to live with others).

Influence of Long-Range Forces on the Transition States and Dynamics of NaCl Ion-Pair Dissociation in Water.

We study NaCl ion-pair dissociation in a dilute aqueous solution using computer simulations both for the full system with long-range Coulomb interactions and for a well-chosen reference system with short-range intermolecular interactions. Analyzing results using concepts from Local Molecular Field (LMF) theory and the recently proposed AI-based analysis tool "State predictive information bottleneck" (SPIB), we show that the system with short-range interactions can accurately reproduce the transition rate for the dissociation process, the dynamics for moving between the underlying metastable states, and the transition state ensemble. Contributions from long-range interactions can be largely neglected for these processes because long-range forces from the direct interionic Coulomb interactions are almost completely canceled (>90%) by those from solvent interactions over the length scale where the transition takes place. Thus, for this important monovalent ion-pair system, short-range forces alone are able to capture detailed consequences of the collective solvent motion, allowing the use of physically suggestive and computationally efficient short-range models for the dissociation event. We believe that the framework here should be applicable to disentangling mechanisms for more complex processes such as multivalent ion disassociation, where previous work has suggested that long-range contributions may be more important.

Best Practices for Chiropractic Management of Patients with Chronic Musculoskeletal Pain: A Clinical Practice Guideline.

Objective: To develop an evidence-based clinical practice guideline (CPG) through a broad-based consensus process on best practices for chiropractic management of patients with chronic musculoskeletal (MSK) pain. Design: CPG based on evidence-based recommendations of a panel of experts in chronic MSK pain management. Methods: Using systematic reviews identified in an initial literature search, a steering committee of experts in research and management of patients with chronic MSK pain drafted a set of recommendations. Additional supportive literature was identified to supplement gaps in the evidence base. A multidisciplinary panel of experienced practitioners and educators rated the recommendations through a formal Delphi consensus process using the RAND Corporation/University of California, Los Angeles, methodology. Results: The Delphi process was conducted January-February 2020. The 62-member Delphi panel reached consensus on chiropractic management of five common chronic MSK pain conditions: low-back pain (LBP), neck pain, tension headache, osteoarthritis (knee and hip), and fibromyalgia. Recommendations were made for nonpharmacological treatments, including acupuncture, spinal manipulation/mobilization, and other manual therapy; modalities such as low-level laser and interferential current; exercise, including yoga; mind-body interventions, including mindfulness meditation and cognitive behavior therapy; and lifestyle modifications such as diet and tobacco cessation. Recommendations covered many aspects of the clinical encounter, from informed consent through diagnosis, assessment, treatment planning and implementation, and concurrent management and referral. Appropriate referral and comanagement were emphasized. Conclusions: These evidence-based recommendations for a variety of conservative treatment approaches to the management of common chronic MSK pain conditions may advance consistency of care, foster collaboration between provider groups, and thereby improve patient outcomes.

Heterogeneity in human hippocampal CaMKII transcripts reveals allosteric hub-dependent regulation.

Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in Ca2+ signaling throughout the body. In the hippocampus, CaMKII is required for learning and memory. Vertebrate genomes encode four CaMKII homologs: CaMKIIα, CaMKIIß, CaMKIIγ, and CaMKIIδ. All CaMKIIs consist of a kinase domain, a regulatory segment, a variable linker region, and a hub domain, which is responsible for oligomerization. The four proteins differ primarily in linker length and composition because of extensive alternative splicing. Here, we report the heterogeneity of CaMKII transcripts in three complex samples of human hippocampus using deep sequencing. We showed that hippocampal cells contain a diverse collection of over 70 CaMKII transcripts from all four CaMKII-encoding genes. We characterized the Ca2+/CaM sensitivity of hippocampal CaMKII variants spanning a broad range of linker lengths and compositions. The effect of the variable linker on Ca2+/CaM sensitivity depended on the kinase and hub domains. Moreover, we revealed a previously uncharacterized role for the hub domain as an allosteric regulator of kinase activity, which may provide a pharmacological target for modulating CaMKII activity. Using small-angle x-ray scattering and single-particle cryo-electron microscopy (cryo-EM), we present evidence for extensive interactions between the kinase and the hub domains, even in the presence of a 30-residue linker. Together, these data suggest that Ca2+/CaM sensitivity in CaMKII is homolog dependent and includes substantial contributions from the hub domain. Our sequencing approach, combined with biochemistry, provides insights into understanding the complex pool of endogenous CaMKII splice variants.

In vitro evaluation of the metabolic stability of nine fragrance chemicals in trout and human hepatocytes.

In vitro metabolic stability of nine fragrance chemicals: p-tolyl acetate, cashmeran, ethylene brassylate, celestolide, galaxolide, traseolide, ambretone, tonalide and pentadecanolide, was evaluated in trout and human hepatocytes. The compounds were incubated with trout hepatocytes at 12°C and human hepatocytes at 37°C. Quantification of compound disappearance with time was performed using gas chromatography/mass spectrometry. in vivo hepatic intrinsic clearance values were calculated from the in vitro data. Significant metabolism was observed with trout hepatocytes for five of the nine fragrance chemicals, while all nine were metabolized significantly with human hepatocytes. Previously published models were used to examine expected bioaccumulation and persistence in whole organisms. Calculated half-lives due to metabolism of the nine chemicals are significantly shorter for humans than trout: <1 hour and <1 day, respectively. For all chemicals with demonstrated hepatic metabolism, the models indicate a lack of accumulation. For those where metabolism was demonstrated in trout, calculated bioconcentration factors would not be classified as bioaccumulative under prevailing regulatory systems.

Local Molecular Field Theory for Nonequilibrium Systems.

We provide a framework for extending equilibrium local molecular field (LMF) theory to a statistical ensemble evolving under a time-dependent applied field. In this context, the self-consistency of the original LMF equation is achieved dynamically, which provides an efficient method for computing the equilibrium LMF potential, in addition to providing the nonequilibrium generalization. As a concrete example, we investigate water confined between hydrophobic or charged walls, systems that are very sensitive to the treatment of long-ranged electrostatics. We then analyze confined water in the presence of a time-dependent applied electric field, generated by a sinusoidal or abrupt variation of the magnitudes of uniform charge densities on each wall. Very accurate results are found from the time-dependent LMF formalism even for strong static fields and for time-dependent systems that are driven far from equilibrium where linear response methods fail.

Spatial analysis of individual- and village-level sociodemographic characteristics associated with age at marriage among married adolescents in rural Niger.

BACKGROUND: Niger has the highest prevalence of child marriage in the world. While child marriage in Niger is clearly normative in the sense that it is commonly practiced, the social and contextual factors that contribute to it are still unclear. METHODS: Here, we tested the importance of village-level factors as predictors of young age at marriage for a group of married adolescent girls (N = 1031) in the Dosso district of rural Niger, using multi-level and geographic analyses. We aggregated significant individual level factors to determine whether, independent of a girl's own sociodemographic characteristics, the impact of each factor is associated at the village level. Finally, we tested for spatial dependence and heterogeneity in examining whether the village-level associations we find with age at marriage differ geographically. RESULTS: The mean age of marriage for girls in our study was 14.20 years (SD 1.8). Our statistical results are consistent with other literature suggesting that education is associated with delayed marriage, even among adolescent girls. Younger ages at marriage are also associated with a greater age difference between spouses and with a greater likelihood of women being engaged in agricultural work. Consistent with results at the individual level, at the village level we found that the proportion of girls who do agricultural work and the mean age difference between spouses were both predictive of a lower age at marriage for individual girls. Finally, mapping age at marriage at the village level revealed that there is geographical variation in age at marriage, with a cluster of hot spots in the Hausa-dominated eastern area where age at marriage is particularly low and a cluster of cold spots in the Zarma-dominated western areas where age at marriage is relatively high. CONCLUSIONS: Our findings suggest that large-scale approaches to eliminating child marriage in these communities may be less successful if they do not take into consideration geographically and socially determined contextual factors at the village level.

Social normative and social network factors associated with adolescent pregnancy: a cross-sectional study of 176 villages in rural Honduras.

BACKGROUND: Adolescent pregnancy and childbirth are common throughout Central America. While gendered beliefs promoting motherhood are a known risk factor, their association with adolescent childbirth within the social networks of Central American communities is unknown. METHODS: This was a cross-sectional study looking at adolescent childbirth amongst women ages 15-20 years (N = 2990) in rural Honduras, using reproductive health data on all individuals ≥15 years of age (N = 24 937 of 31 300 population) including social network contacts, all of whom were interviewed as part of the study. The outcome, adolescent childbirth, was defined as having had a child < age 20 years. Predictors included whether a woman's social contact had an adolescent childbirth and the social contact's reported perception of community support for adolescent childbirth. RESULTS: While girls who identified a father in the village as a social contact had a lower likelihood of adolescent childbirth regardless of whether or not they reported being in a partnership, this finding did not hold for girls who identified mothers. There was an association between a social contact's report of norms supporting adolescent childbirth and a girl's risk of adolescent childbirth; however, village-level aggregate norms attenuated that relationship. Independent significant associations were found between a girl's risk of adolescent childbirth and both a social contact's adolescent childbirth and the village proportion of women who had had an adolescent childbirth. The association between social contacts' adolescent childbirth and a girl's risk of adolescent childbirth across relationships was more robust for stronger relationships and when the social contact was closer in age to the girl. CONCLUSIONS: If, as this evidence suggests, a strong driver of adolescent childbirth is the frequency of the occurrence of adolescent childbirth both within the greater community and within a girl's proximal social network, the challenge for intervention strategies is to encourage norms that prevent adolescent childbirth without stigmatising those who have had an adolescent childbirth. Programmatic efforts to counter prevailing norms that limit a woman's role to motherhood, and that support and encourage strong norms for girls' education may play an important role in addressing this situation.

Short solvent model for ion correlations and hydrophobic association.

Coulomb interactions play a major role in determining the thermodynamics, structure, and dynamics of condensed-phase systems, but often present significant challenges. Computer simulations usually use periodic boundary conditions to minimize corrections from finite cell boundaries but the long range of the Coulomb interactions generates significant contributions from distant periodic images of the simulation cell, usually calculated by Ewald sum techniques. This can add significant overhead to computer simulations and hampers the development of intuitive local pictures and simple analytic theory. In this paper, we present a general framework based on local molecular field theory to accurately determine the contributions from long-ranged Coulomb interactions to the potential of mean force between ionic or apolar hydrophobic solutes in dilute aqueous solutions described by standard classical point charge water models. The simplest approximation leads to a short solvent (SS) model, with truncated solvent-solvent and solute-solvent Coulomb interactions and long-ranged but screened Coulomb interactions only between charged solutes. The SS model accurately describes the interplay between strong short-ranged solute core interactions, local hydrogen-bond configurations, and long-ranged dielectric screening of distant charges, competing effects that are difficult to capture in standard implicit solvent models.

In vitro and in vivo metabolic stability of various fragrance materials and insect repellent in rainbow trout (Oncorhynchus mykiss).

Commercial fragrances consist of several thousand natural and synthetic substances formulated in complex combinations. These ingredients are frequently blended at very low concentrations but they are typically lipophilic and a few of them (e.g., synthetic musks) have been detected in aquatic systems, albeit at low concentrations. Few fragrances have guideline in vivo data on bioaccumulation, so in silico modeling has been widely used to estimate bioconcentration factors (BCFs). This study used in vitro metabolism assays with trout S9 cell fractions and cryopreserved hepatocytes to improve estimates of fish BCFs and to test published methods for extrapolating in vitro metabolic rate data to whole fish and corresponding BCFs. These estimates for several chemicals were compared with new in vivo bioconcentration measurements and previously published data on fragrances and the insect repellent, DEET. In total, 17 (20 including isomers) fragrance chemicals (abalyn, amberwood, amboryl acetate, bisabolene, cedroxide, coniferan, elemol, givescone, maritima, precyclemone B, polysantol, sandela, sanjinol, santalex, timberol and vernaldehyde) and DEET were metabolized at various rates. Only three materials tested did not appear to undergo enzymatic degradation (caryophyllene oxide, galaxolide and ketone patchouli). Even relatively slow rates of metabolism had a large influence on bioconcentration estimates. This work adds valuable information to the evolving body of work supporting the use of in vitro determinations of hepatic clearance to improve modeled predictions of bioaccumulation. It can also be used directly to help prioritize testing of potential bioaccumulative chemicals or serve as a more economical method for screening these chemicals.