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Modelling studies suggest that the climate and the hydrological cycle are sensitive to the concentrations of ice-nucleating particles (INPs). However, the concentrations, composition, and sources of INPs in the atmosphere remain uncertain. Here, we report daily concentrations of INPs in the immersion freezing mode and tracers of mineral dust (Al, Fe, Ti, and Mn), sea spray aerosol (Na+ and Cl−), and anthropogenic aerosol (Zn, Pb, NO3-, NH4+, and non-sea-salt SO42-) at Alert, Canada, during a 3-week campaign in March 2016. In total, 16 daily measurements of INPs are reported. The average INP concentrations measured in the immersion freezing mode were 0.005±0.002, 0.020±0.004, and 0.186±0.040 L−1 at −15, −20, and −25 ∘C, respectively. These concentrations are within the range of concentrations measured previously in the Arctic at ground level or sea level. Mineral dust tracers all correlated with INPs at −25 ∘C (correlation coefficient, R, ranged from 0.70 to 0.76), suggesting that mineral dust was a major contributor to the INP population at −25 ∘C. Particle dispersion modelling suggests that the source of the mineral dust may have been long-range transport from the Gobi Desert. Sea spray tracers were anti-correlated with INPs at −25 ∘C (R=-0.56). In addition, INP concentrations at −25 ∘C divided by mass concentrations of aluminum were anti-correlated with sea spray tracers (R=-0.51 and −0.55 for Na+ and Cl−, respectively), suggesting that the components of sea spray aerosol suppressed the ice-nucleating ability of mineral dust in the immersion freezing mode. Correlations between INPs and anthropogenic aerosol tracers were not statistically significant. These results will improve our understanding of INPs in the Arctic during spring.

Background Contingency management (CM) that is delivered by peer recovery support specialists and incentivizes harm reduction goals among people not seeking treatment for stimulant use has not been tested. The Peers Expanding Engagement in Stimulant Harm Reduction with Contingency Management (PEER-CM) study compares the effectiveness of two peer-facilitated CM interventions: (1) an experimental approach incentivizing achievement of client-identified harm reduction goals and (2) an enhanced standard of care approach incentivizing peer visit attendance. Methods Applying a hybrid type 1 effectiveness-implementation framework and stepped-wedge design across 14 community-based peer services sites across Oregon, the PEER-CM study trains peers to conduct CM. All sites implement the standard CM approach of incentivizing peer visit attendance. Every 2 months, two sites are randomly assigned to initiate the experimental CM condition of incentives for achieving client-directed harm reduction activities. Peers monitor progress and manage incentives. In the experimental approach, peers facilitate client progress on goal-related activities (selected from a standardized list of goals) to support the primary study outcome of reducing opioid overdoses and stimulant overamping. The intended study enrollment is approximately 80 clients per site (N = 1,120). Peer specialists participate in skills-focused coaching-to-criterion coaching process to document proficient CM delivery skills. This includes a series of group coaching sessions and an individual assessment with a standardized patient, observed and rated according to core dimensions of the Contingency Management Competence Scale. Results The primary study outcome is time until peer-reported fatal or first participant-reported non-fatal overdose or overamp (acute stimulant toxicity). Secondary outcomes include achievement of client-identified harm reduction goals and engagement in substance use disorder treatment. We will also demonstrate the feasibility of our coaching-to-criterion process by documenting peer proficiency in CM skills. Qualitative interviews with peers and their clients will explore the optimal context and implementation strategies for peer-facilitated CM. Conclusion PEER-CM is among the first trials to test the effectiveness of peer-facilitated CM for achieving harm reduction goals and reducing overdose in non-treatment-seeking people who use stimulants. The findings will generate evidence for peer-facilitated delivery of CM and application of CM to client-identified harm reduction goals. Trial Registration : This study is registered at ClinicalTrials.gov (NCT 05700994).

Background Novel strategies are needed to engage people who use stimulants into the continuum of addiction care. Contingency management (CM) is the most effective intervention for stimulant use disorder and may engage non-treatment-seeking populations, especially when delivered by peer recovery support specialists (peers). We describe development and training for a novel peer-delivered CM program for stimulant use harm reduction and treatment engagement. Methods We used a community based participatory research (CBPR) process to develop a CM program focused on self-identified goals for harm reduction and treatment engagement. A steering committee of peers guided study design, CM rewards, schedule, and incentivized goals. Peers completed coaching-to-criterion of six CM skills based on the CM Competence Scale (CMCS), then completed a one-on-one roleplay with a standardized patient. Coaches rated peer performance of each CMCS skill according to its Likert scale (1 = Very Poor to 7 = Excellent) and an a priori rating criterion of 4 (‘adequate’). Roleplays included feedback and a ‘replay’ of skills, if necessary. Results The steering committee devised two CM interventions: an enhanced standard-of-care incentivizing peer visits ($20 for weekly peer visits) and an intervention that additionally incentivized self-directed goals ($20 for weekly peer visits and $30 for completed goal-related activities). Self-identified goal-related activities were chosen through a collaborative process and organized into 6 domains: (1) overdose/overamping prevention (2) substance use supports/treatment (3) daily living/housing (4) education/employment (5) mental/physical/spiritual health (6) social relationships. Forty-seven peers across nine peer-led organizations (three rural and six urban organizations across Oregon) completed CM training. All 47 peers met the a priori criterion in their roleplay, with seventeen (36%) requiring a ‘replay’ of a skill. Mean CMSC summary scores were 28.51 (SD 4.73) on the first attempt and 29.62 (SD 4.01) on the second attempt. Conclusions PEER-CM (Peers Expanding Engagement in Stimulant Harm Reduction with Contingency Management) is among the first trials to use peer-delivered CM for stimulant use, incentivizing peer engagement and self-identified goals for harm reduction and treatment engagement. A CBPR approach strengthened the study design by incorporating peer guidance. Peers in this large, multisite sample demonstrated adequate CM delivery skills with acceptable fidelity following training. Trial Registration This study is registered at ClinicalTrials.gov (NCT 05700994). Registered 26 January, 2023.

Lymph node (LN)‐resident dendritic cells (DCs) are a promising target for vaccination given their professional antigen‐presenting capabilities and proximity to a high concentration of immune cells. Direct intra‐LN injection has been shown to greatly enhance the immune response to vaccine antigens compared to traditional intramuscular injection, but it is infeasible to implement clinically in a vaccination campaign context. Employing the passive lymphatic flow of antigens to target LNs has been shown to increase total antigen uptake by DCs more than inflammatory adjuvants, which recruit peripheral DCs. Herein, we describe a novel vaccination platform in which two complementary multi‐arm poly(ethylene glycol) (PEG) polymers—one covalently bound to the model antigen ovalbumin (OVA)—are injected subcutaneously into two distinct sites. These materials then drain to the same LN through different lymphatic vessels and, upon meeting in the LN, rapidly crosslink. This system improves OVA delivery to, and residence time within, the draining LN compared to all control groups. The crosslinking of the two PEG components also improves humoral immunity without the need for any pathogen‐mimicking adjuvants. Further, we observed a significant increase in non‐B/T lymphocytes in LNs cross‐presenting the OVA peptide SIINFEKL on MHC I over a dose‐matched control containing alum, the most common clinical adjuvant, as well as an increase in DC activation in the LN. These data suggest that this platform can be used to deliver antigens to LN‐resident immune cells to produce a stronger humoral and cellular immune response over materials‐matched controls without the use of traditional adjuvants.

Substantial evidence supports the familial aggregation of exceptional longevity. The existence of rare families demonstrating clustering for this phenotype suggests that a genetic etiology may be an important component. Previous attempts at localizing loci predisposing for exceptional longevity have been limited to association studies of candidate gene polymorphisms. In this study, a genome-wide scan for such predisposing loci was conducted by using 308 individuals belonging to 137 sibships demonstrating exceptional longevity. By using nonparametric analysis, significant evidence for linkage was noted for chromosome 4 at D4S1564 with a MLS of 3.65 (P = 0.044). The analysis was corroborated by a parametric analysis (P = 0.052). These linkage results indicate the likelihood that there exists a gene, or genes, that exerts a substantial influence on the ability to achieve exceptional old age. Identification of the genes in humans that allow certain individuals to live to extreme old age should lead to insights on cellular pathways that are important to the aging process.

Although survival to old age is known to have strong environmental and behavioral components, mortality differences between social groups tend to diminish or even disappear at older ages. Hypothesizing that surviving to extreme old age entails a substantial familial predisposition for longevity, we analyzed the pedigrees of 444 centenarian families in the United States. These pedigrees included 2,092 siblings of centenarians, whose survival was compared with 1900 birth cohort survival data from the U.S. Social Security Administration. Siblings of centenarians experienced a mortality advantage throughout their lives relative to the U.S. 1900 cohort. Female siblings had death rates at all ages about one-half the national level; male siblings had a similar advantage at most ages, although diminished somewhat during adolescence and young adulthood. Relative survival probabilities for these siblings increase markedly at older ages, reflecting the cumulative effect of their mortality advantage throughout life. Compared with the U.S. 1900 cohort, male siblings of centenarians were at least 17 times as likely to attain age 100 themselves, while female siblings were at least 8 times as likely.