"What Matters to You?": A Participant-Centered Approach to Needs Identification and Referral to Community Resources.

OBJECTIVE: Referral to social and health services is a core process of the Special Supplemental Nutrition Program for Women, Infants and Children (WIC). We evaluate the feasibility and acceptability of a referral innovation implemented at two New York City WIC sites. This program aimed to improve retention by increasing WIC's perceived value by addressing unmet needs of WIC families. The two main components were needs assessment via conversation and a closed-loop referral process for WIC families with children aged 6-9 months and 18-21 months. DESIGN: Referral outcomes from Unite Us and program data were tracked and assessed using descriptive univariate analyses. We conducted 29 in-depth interviews with caregivers and six focus groups with WIC and CBO staff. Qualitative data were analyzed using thematic framework analysis. RESULTS: From February 2020 through January 2021, 1,675 WIC caregivers participated in a conversation about their family's needs. Four hundred sixty-one caregivers were referred to at least one service. 95 received services or benefits. In interviews, caregivers viewed referrals to other services positively but were not aware WIC could address needs holistically. In focus groups, WIC staff liked the conversation script but highlighted barriers to making referrals. CBO partners valued network participation as it increased their reach to new families. CONCLUSIONS AND IMPLICATIONS: Our approach facilitated targeted referrals for WIC participants. It is an acceptable enhancement of the WIC referral process with potential to strengthen WIC as a community provider.

Investigating the phylogenetic history of toxin tolerance in mushroom-feeding Drosophila.

Understanding how and when key novel adaptations evolved is a central goal of evolutionary biology. Within the immigrans-tripunctata radiation of Drosophila, many mushroom-feeding species are tolerant of host toxins, such as cyclopeptides, that are lethal to nearly all other eukaryotes. In this study, we used phylogenetic and functional approaches to investigate the evolution of cyclopeptide tolerance in the immigrans-tripunctata radiation of Drosophila. First, we inferred the evolutionary relationships among 48 species in this radiation using 978 single copy orthologs. Our results resolved previous incongruities within species groups across the phylogeny. Second, we expanded on previous studies of toxin tolerance by assaying 16 of these species for tolerance to α-amanitin and found that six of them could develop on diet with toxin. Finally, we asked how α-amanitin tolerance might have evolved across the immigrans-tripunctata radiation, and inferred that toxin tolerance was ancestral in mushroom-feeding Drosophila and subsequently lost multiple times. Our findings expand our understanding of toxin tolerance across the immigrans-tripunctata radiation and emphasize the uniqueness of toxin tolerance in this adaptive radiation and the complexity of biochemical adaptations.

Investigating the phylogenetic history of toxin tolerance in mushroom-feeding Drosophila.

Understanding how and when key novel adaptations evolved is a central goal of evolutionary biology. Within the immigrans-tripunctata radiation of Drosophila , many mushroom-feeding species are tolerant of host toxins, such as cyclopeptides, that are lethal to nearly all other eukaryotes. In this study, we used phylogenetic and functional approaches to investigate the evolution of cyclopeptide tolerance in the immigrans-tripunctata radiation of Drosophila . We first inferred the evolutionary relationships among 48 species in this radiation using 978 single copy orthologs. Our results resolved previous incongruities within species groups across the phylogeny. Second, we expanded on previous studies of toxin tolerance by assaying 16 of these species for tolerance to α-amanitin and found that six of these species could develop on diet with toxin. Third, we examined fly development on a diet containing a natural mix of toxins extracted from the Death Cap Amanita phalloides mushroom. Both tolerant and susceptible species developed on diet with this mix, though tolerant species survived at significantly higher concentrations. Finally, we asked how cyclopeptide tolerance might have evolved across the immigrans-tripunctata radiation and inferred that toxin tolerance was ancestral and subsequently lost multiple times. Our results suggest the evolutionary history of cyclopeptide tolerance is complex, and simply describing this trait as present or absent does not fully capture the occurrence or impact on this adaptive radiation. More broadly, the evolution of novelty can be more complex than previously thought, and that accurate descriptions of such novelties are critical in studies examining their evolution.

Partial RAG deficiency in humans induces dysregulated peripheral lymphocyte development and humoral tolerance defect with accumulation of T-bet+ B cells.

The recombination-activating genes (RAG) 1 and 2 are indispensable for diversifying the primary B cell receptor repertoire and pruning self-reactive clones via receptor editing in the bone marrow; however, the impact of RAG1/RAG2 on peripheral tolerance is unknown. Partial RAG deficiency (pRD) manifesting with late-onset immune dysregulation represents an 'experiment of nature' to explore this conundrum. By studying B cell development and subset-specific repertoires in pRD, we demonstrate that reduced RAG activity impinges on peripheral tolerance through the generation of a restricted primary B cell repertoire, persistent antigenic stimulation and an inflammatory milieu with elevated B cell-activating factor. This unique environment gradually provokes profound B cell dysregulation with widespread activation, remarkable extrafollicular maturation and persistence, expansion and somatic diversification of self-reactive clones. Through the model of pRD, we reveal a RAG-dependent 'domino effect' that impacts stringency of tolerance and B cell fate in the periphery.