Preclinical evaluation and first-in-dog clinical trials of PBMC-expanded natural killer cells for adoptive immunotherapy in dogs with cancer.

BACKGROUND: Natural killer (NK) cells are cytotoxic cells capable of recognizing heterogeneous cancer targets without prior sensitization, making them promising prospects for use in cellular immunotherapy. Companion dogs develop spontaneous cancers in the context of an intact immune system, representing a valid cancer immunotherapy model. Previously, CD5 depletion of peripheral blood mononuclear cells (PBMCs) was used in dogs to isolate a CD5dim-expressing NK subset prior to co-culture with an irradiated feeder line, but this can limit the yield of the final NK product. This study aimed to assess NK activation, expansion, and preliminary clinical activity in first-in-dog clinical trials using a novel system with unmanipulated PBMCs to generate our NK cell product. METHODS: Starting populations of CD5-depleted cells and PBMCs from healthy beagle donors were co-cultured for 14 days, phenotype, cytotoxicity, and cytokine secretion were measured, and samples were sequenced using the 3'-Tag-RNA-Seq protocol. Co-cultured human PBMCs and NK-isolated cells were also sequenced for comparative analysis. In addition, two first-in-dog clinical trials were performed in dogs with melanoma and osteosarcoma using autologous and allogeneic NK cells, respectively, to establish safety and proof-of-concept of this manufacturing approach. RESULTS: Calculated cell counts, viability, killing, and cytokine secretion were equivalent or higher in expanded NK cells from canine PBMCs versus CD5-depleted cells, and immune phenotyping confirmed a CD3-NKp46+ product from PBMC-expanded cells at day 14. Transcriptomic analysis of expanded cell populations confirmed upregulation of NK activation genes and related pathways, and human NK cells using well-characterized NK markers closely mirrored canine gene expression patterns. Autologous and allogeneic PBMC-derived NK cells were successfully expanded for use in first-in-dog clinical trials, resulting in no serious adverse events and preliminary efficacy data. RNA sequencing of PBMCs from dogs receiving allogeneic NK transfer showed patient-unique gene signatures with NK gene expression trends in response to treatment. CONCLUSIONS: Overall, the use of unmanipulated PBMCs appears safe and potentially effective for canine NK immunotherapy with equivalent to superior results to CD5 depletion in NK expansion, activation, and cytotoxicity. Our preclinical and clinical data support further evaluation of this technique as a novel platform for optimizing NK immunotherapy in dogs.

Biogeographic distribution of five Antarctic cyanobacteria using large-scale k-mer searching with sourmash branchwater.

Cyanobacteria form diverse communities and are important primary producers in Antarctic freshwater environments, but their geographic distribution patterns in Antarctica and globally are still unresolved. There are however few genomes of cultured cyanobacteria from Antarctica available and therefore metagenome-assembled genomes (MAGs) from Antarctic cyanobacteria microbial mats provide an opportunity to explore distribution of uncultured taxa. These MAGs also allow comparison with metagenomes of cyanobacteria enriched communities from a range of habitats, geographic locations, and climates. However, most MAGs do not contain 16S rRNA gene sequences, making a 16S rRNA gene-based biogeography comparison difficult. An alternative technique is to use large-scale k-mer searching to find genomes of interest in public metagenomes. This paper presents the results of k-mer based searches for 5 Antarctic cyanobacteria MAGs from Lake Fryxell and Lake Vanda, assigned the names Phormidium pseudopriestleyi FRX01, Microcoleus sp. MP8IB2.171, Leptolyngbya sp. BulkMat.35, Pseudanabaenaceae cyanobacterium MP8IB2.15, and Leptolyngbyaceae cyanobacterium MP9P1.79 in 498,942 unassembled metagenomes from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA). The Microcoleus sp. MP8IB2.171 MAG was found in a wide variety of environments, the P. pseudopriestleyi MAG was found in environments with challenging conditions, the Leptolyngbyaceae cyanobacterium MP9P1.79 MAG was only found in Antarctica, and the Leptolyngbya sp. BulkMat.35 and Pseudanabaenaceae cyanobacterium MP8IB2.15 MAGs were found in Antarctic and other cold environments. The findings based on metagenome matches and global comparisons suggest that these Antarctic cyanobacteria have distinct distribution patterns ranging from locally restricted to global distribution across the cold biosphere and other climatic zones.

Pluripotency of a founding field: rebranding developmental biology.

The field of developmental biology has declined in prominence in recent decades, with off-shoots from the field becoming more fashionable and highly funded. This has created inequity in discovery and opportunity, partly due to the perception that the field is antiquated or not cutting edge. A 'think tank' of scientists from multiple developmental biology-related disciplines came together to define specific challenges in the field that may have inhibited innovation, and to provide tangible solutions to some of the issues facing developmental biology. The community suggestions include a call to the community to help 'rebrand' the field, alongside proposals for additional funding apparatuses, frameworks for interdisciplinary innovative collaborations, pedagogical access, improved science communication, increased diversity and inclusion, and equity of resources to provide maximal impact to the community.

Functional Hearing Preservation in Cochlear Implantation: The Miami Cocktail Effect.

OBJECTIVE: To investigate if pharmacological treatment with prednisone and L-N-acetylcysteine (STE + NAC) influence functional hearing preservation in cochlear implant (CI) surgery. STUDY DESIGNS: Preimplantation and postimplantation longitudinal case-control study. SETTING: Tertiary referral center. PATIENTS: Pediatric and adult recipients of CI with preimplantation functional hearing defined as an average of air-conducted thresholds at 125, 250, and 500 Hz (low-frequency pure-tone average [LFPTA]) <80 dB. INTERVENTIONS: Preimplantation and postimplantation audiometry. Weight-adjusted oral prednisone and L-N-acetylcysteine starting 2 days before surgery (Miami cocktail). Prednisone was continued for 3 days and L-N-acetylcysteine for 12 days after surgery, respectively. Cochlear implantation with conventional length electrodes. MAIN OUTCOME MEASURES: Proportion of patients with LFPTA <80 dB, and LFPTA change at 1-year postimplantation. RESULTS: All 61 patients received intratympanic and intravenous dexamethasone intraoperatively, with 41 patients receiving STE + NAC and 20 patients not receiving STE + NAC. At 1-year postimplantation, the proportion of functional hearing preservation was 83% in the STE + NAC group compared with 55% of subjects who did not receive STE + NAC ( p = 0.0302). The median LFPTA change for STE + NAC-treated and not treated subjects was 8.33 dB (mean, 13.82 ± 17.4 dB) and 18.34 dB (mean, 26.5 ± 23.4 dB), respectively ( p = 0.0401, Wilcoxon rank test). Perioperative STE + NAC treatment resulted in 10 dB of LFPTA better hearing than when not receiving this treatment. Better low-frequency preimplantation hearing thresholds were predictive of postimplantation functional hearing. No serious side effects were reported. CONCLUSION: Perioperative STE + NAC, "The Miami Cocktail," was safe and superior to intraoperative steroids alone in functional hearing preservation 1-year after cochlear implantation.

An artificial intelligence approach of feature engineering and ensemble methods depicts the rumen microbiome contribution to feed efficiency in dairy cows.

Genetic selection has remarkably helped U.S. dairy farms to decrease their carbon footprint by more than doubling milk production per cow over time. Despite the environmental and economic benefits of improved feed and milk production efficiency, there is a critical need to explore phenotypical variance for feed utilization to advance the long-term sustainability of dairy farms. Feed is a major expense in dairy operations, and their enteric fermentation is a major source of greenhouse gases in agriculture. The challenges to expanding the phenotypic database, especially for feed efficiency predictions, and the lack of understanding of its drivers limit its utilization. Herein, we leveraged an artificial intelligence approach with feature engineering and ensemble methods to explore the predictive power of the rumen microbiome for feed and milk production efficiency traits, as rumen microbes play a central role in physiological responses in dairy cows. The novel ensemble method allowed to further identify key microbes linked to the efficiency measures. We used a population of 454 genotyped Holstein cows in the U.S. and Canada with individually measured feed and milk production efficiency phenotypes. The study underscored that the rumen microbiome is a major driver of residual feed intake (RFI), the most robust feed efficiency measure evaluated in the study, accounting for 36% of its variation. Further analyses showed that several alpha-diversity metrics were lower in more feed-efficient cows. For RFI, [Ruminococcus] gauvreauii group was the only genus positively associated with an improved feed efficiency status while seven other taxa were associated with inefficiency. The study also highlights that the rumen microbiome is pivotal for the unexplained variance in milk fat and protein production efficiency. Estimation of the carbon footprint of these cows shows that selection for better RFI could reduce up to 5 kg of diet consumed per cow daily, potentially reducing up to 37.5% of CH4. These findings shed light that the integration of artificial intelligence approaches, microbiology, and ruminant nutrition can be a path to further advance our understanding of the rumen microbiome on nutrient requirements and lactation performance of dairy cows to support the long-term sustainability of the dairy community.

Acipenserid herpesvirus 2 genome and partial validation of a qPCR for its detection in white sturgeon Acipenser transmontanus.

White sturgeon Acipenser transmontanus is the primary species used for caviar and sturgeon meat production in the USA. An important pathogen of white sturgeon is acipenserid herpesvirus 2 (AciHV-2). In this study, 4 archived isolates from temporally discrete natural outbreaks spanning the past 30 yr were sequenced via Illumina and Oxford Nanopore Technologies platforms. Assemblies of approximately 134 kb were obtained for each isolate, and the putative ATPase subunit of the terminase gene was selected as a potential quantitative PCR (qPCR) target based on sequence conservation among AciHV-2 isolates and low sequence homology with other important viral pathogens. The qPCR was repeatable and reproducible, with a linear dynamic range covering 5 orders of magnitude, an efficiency of approximately 96%, an R2 of 0.9872, and an analytical sensitivity of 103 copies per reaction after 35 cycles. There was no cross-reaction with other known viruses or closely related sturgeon species, and no inhibition by sturgeon DNA. Clinical accuracy was assessed from white sturgeon juveniles exposed to AciHV-2 by immersion. Viral culture (gold standard) and qPCR were in complete agreement for both cell culture negative and cell culture positive samples, indicating that this assay has 100% relative accuracy compared to cell culture during an active outbreak. The availability of a whole-genome sequence for AciHV-2 and a highly specific and sensitive qPCR assay for detection of AciHV-2 in white sturgeon lays a foundation for further studies on host-pathogen interactions while providing a specific and rapid test for AciHV-2 in captive and wild populations.

A cost-utility study of elective haemorrhoidectomies in Canada.

AIM: The aim was to estimate the 10-year cost-utility of haemorrhoidectomy surgery with preference-based measures of health using Canadian health utility measures and costs. METHODS: Patients undergoing elective haemorrhoidectomies by general and colorectal surgeons in British Columbia, Vancouver, between September 2015 and November 2022, completed preoperatively and postoperatively the EuroQol five-dimension five-level health-related quality of life questionnaire (EQ-5D-5L). Quality-adjusted life years (QALYs) attributable to surgery were calculated by discounting preoperative and postoperative health utility values derived from the EQ-5D-5L. Costs were measured from a health system perspective which incorporated costs of hospital stay and specialists' fees. Results are presented in 2021 Canadian dollars. RESULTS: Of 94 (47%) patients who completed both the preoperative and postoperative questionnaires, the mean gain in QALYs 10 years after surgery was 1.0609, assuming a 3.5% annual discounting rate. The average cost of the surgery was $3166. The average cost per QALY was $2985 when benefits of the surgery were assumed to accrue for 10 years. The cost per QALY was higher for women ($3821) compared with men ($2485). Participants over the age of 70 had the highest cost per QALY ($8079/QALY). CONCLUSIONS: Haemorrhoidectomies have been associated with significant gains in health status and are inexpensive relative to the associated gains in quality of life based on patients' perspectives of their improvement in health and well-being.

Forensic anthropologists and estimates of skeletal completeness: The impacts of training and experience.

Forensic anthropologists engage with numerous and diverse stakeholders in their casework. Regarding the recovery of human remains, these stakeholders may be interested in quantifying or qualifying the amount of remains recovered. How forensic anthropologists respond to such questions, whether verbally or in written reporting, has the potential to impact the trajectory of a case. However, communications about skeletal completeness are rarely discussed within the field. Current data-collection procedures recommend the use of inventories. This approach may be less feasible for complicated assemblages involving commingling or high degrees of fragmentation. Numerous methods exist to quantify the amount of skeletal remains present in complex or larger assemblages, but it remains unclear to what extent forensic anthropologists utilize these methods and whether factors like degree of expertise influence analysts' ability to report skeletal completeness consistently and precisely. A study was designed to examine differences between public and professional perceptions of skeletal completeness, presenting images of incomplete bones and skeletal remains. Survey participants were asked to assess the completeness of the remains in each image. Few patterns were observed regarding photographs of skeletal assemblages, but distinct differences were observed among individual bones between respondents with different degrees of expertise. These responses reflect potentially unexamined assumptions underlying assessments of incomplete bones and skeletal assemblages. This highlights the necessity of standardizing how we report estimates of completeness within the forensic anthropology community and how we discuss these results with external stakeholders. Completeness estimates must be either removed from reports and bench notes or annotated and cited clearly, as is standard with other aspects of forensic anthropological analysis. Several methods are summarized, with recommendations for integrating them into casework.

Novel Ameloblastin Variants, Contrasting Amelogenesis Imperfecta Phenotypes.

Amelogenesis imperfecta (AI) comprises a group of rare, inherited disorders with abnormal enamel formation. Ameloblastin (AMBN), the second most abundant enamel matrix protein (EMP), plays a critical role in amelogenesis. Pathogenic biallelic loss-of-function AMBN variants are known to cause recessive hypoplastic AI. A report of a family with dominant hypoplastic AI attributed to AMBN missense change p.Pro357Ser, together with data from animal models, suggests that the consequences of AMBN variants in human AI remain incompletely characterized. Here we describe 5 new pathogenic AMBN variants in 11 individuals with AI. These fall within 3 groups by phenotype. Group 1, consisting of 6 families biallelic for combinations of 4 different variants, have yellow hypoplastic AI with poor-quality enamel, consistent with previous reports. Group 2, with 2 families, appears monoallelic for a variant shared with group 1 and has hypomaturation AI of near-normal enamel volume with pitting. Group 3 includes 3 families, all monoallelic for a fifth variant, which are affected by white hypoplastic AI with a thin intact enamel layer. Three variants, c.209C>G; p.(Ser70*) (groups 1 and 2), c.295T>C; p.(Tyr99His) (group 1), and c.76G>A; p.(Ala26Thr) (group 3) were identified in multiple families. Long-read AMBN locus sequencing revealed these variants are on the same conserved haplotype, implying they originate from a common ancestor. Data presented therefore provide further support for possible dominant as well as recessive inheritance for AMBN-related AI and for multiple contrasting phenotypes. In conclusion, our findings suggest pathogenic AMBN variants have a more complex impact on human AI than previously reported.

Analysis of fibrinolytic shutdown in trauma patients with traumatic brain injury.

BACKGROUND: Coagulation profiles following major trauma vary depending on injury pattern and degree of shock. The physiologic mechanisms involved in coagulation function at any given time are varied and remain poorly understood. Thromboelastography (TEG) has been used evaluate coagulation profiles in the trauma population with some reports demonstrating a spectrum of fibrinolysis to fibrinolytic shutdown on initial presentation. The objective of this study was to evaluate the fibrinolytic profile of patients with TBI using thromboelastography (TEG). We hypothesized that patients with TBI would demonstrate low fibrinolytic activity. METHODS: All trauma activations at an ACS-verified level 1 trauma center received a TEG analysis upon arrival from December 2019 to June 2021. A retrospective review of the results and outcomes was conducted, and TBI patients were compared to patients without TBI. Linear regression was used to evaluate the effect of patient and injury factors on fibrinolysis. Hyperfibrinolysis was defined as LY30 â€‹> â€‹7.7%, physiologic fibrinolysis as LY30 0.6-7.7%, and fibrinolytic shutdown as LY30 â€‹< â€‹0.6%. RESULTS: A total of 1369 patients received an admission TEG analysis. Patients with TBI had a significantly higher median ISS (16 vs. 8, p â€‹< â€‹0.001), lower median admission Glasgow Coma Scale (14 vs. 15, p â€‹< â€‹0.001), longer intensive care unit length of stay (3 vs. 2 days, p â€‹< â€‹0.0001), increased ventilator days (216 vs. 183, p â€‹< â€‹0.001), higher mortality (14.6% vs. 5.1%, p â€‹< â€‹0.001), but lower shock index (0.6 vs. 0.7, p â€‹< â€‹0.0001) compared to those without TBI. Median LY30 was found to be decreased in the TBI group (0.1 vs. 0.2, p â€‹= â€‹0.0006). Patients with TBI were found to have a higher rate of fibrinolytic shutdown compared those without TBI (68.7% vs. 63.5%, p â€‹= â€‹0.054). ISS, sex, and shock index were found to be predictive of LY30 on linear regression, but TBI was not (Β: 0.09, SE: 0.277, p â€‹= â€‹0.745). The rate of DVT/PE did not appear to be elevated in patients with TBI (0.8%) and without TBI (1.2%). CONCLUSIONS: Trauma patients with and without TBI were found to have high rates of fibrinolytic shutdown. Although there was a high incidence of fibrinolytic shutdown, it did not appear to have an impact on the rate of thrombotic complications. The clinical significance of these results is unclear and differs significantly from recent reports which demonstrated that TBI is associated with a 25% rate of fibrinolytic shutdown. Further investigation is needed to better define the fibrinolytic pathway in patients with trauma and TBI to develop optimal treatment algorithms.

Missing a "Missing Self" Mechanism: Modeling and Detection of Ly49 Expression in Canine NK Cells.

NK cells are a key focus in immuno-oncology, based on their ability to eliminate malignant cells without prior sensitization. Dogs are valuable models for translational immunotherapy studies, especially for NK cells, where critical species differences exist between mice and humans. Given that the mechanism for recognition of "self" by canine NK cells is currently unknown, we sought to evaluate expression of Ly49 in canine NK cells using in silico and high-throughput techniques. We interrogated the identified polymorphism/mutation in canine Ly49 and assessed the potential impact on structure using computational modeling of three-dimensional protein structure and protein-protein docking of canine Ly49 with MHC class I (MHC-I). Bulk and single-cell RNA-sequencing analysis was performed to detect gene expression of Ly49/KLRA1 in resting and activated NK cells. Tertiary protein structure demonstrated significant structural similarity to the known murine system. Molecular docking of canine Ly49 with MHC-I was favorable, converging at a single low-energy conformation. RNA sequencing revealed expression of Ly49/KLRA1 in both resting and activated NK cells and demonstrated almost exclusive expression of the gene in the NK cluster at the single-cell level. Despite prior reports of a mutated, nonfunctional canine Ly49, our data support that the protein product is predicted to bind to MHC-I in a comparable conformation to the murine system and is expressed in canine NK cells with upregulation following activation. Taken together, these data suggest that Ly49 is capable of recognizing MHC-I and therefore regulating NK cell function in dogs.

Engaging primary care clinicians in the selection of implementation strategies for toddler social-emotional health promotion in community health centers.

BACKGROUND: Social-emotional risk for subsequent behavioral health problems can be identified at toddler age, a period where prevention has a heightened impact. This study aimed to meaningfully engage pediatric clinicians, given the emphasis on health promotion and broad reach of primary care, to prepare an Implementation Research Logic Model to guide the implementation of a screening and referral process for toddlers with elevated social-emotional risk. METHOD: Using an adaptation of a previously published community partner engagement method, six pediatricians from community health centers (CHCs) comprised a Clinical Partner Work Group. The group was engaged in identifying determinants (barriers/facilitators), selecting and specifying strategies, strategy-determinant matching, a modified Delphi approach for strategy prioritization, and user-centered design methods. The data gathered from individual interviews, two group sessions, and a follow-up survey resulted in a completed Implementation Research Logic Model. RESULTS: The Clinical Partner Work Group identified 16 determinants, including barriers (e.g., patient access to electronic devices) and facilitators (e.g., clinician buy-in). They then selected and specified 14 strategies, which were prioritized based on ratings of feasibility, effectiveness, and priority. The highest-rated strategies (e.g., integration of the screener into the electronic health record) provided coverage of all identified barriers and comprised the primary implementation strategy "package" to be used and tested. CONCLUSIONS: Clinical partners provided important context and insights for implementation strategy selection and specification to support the implementation of social-emotional risk screening and referral in pediatric primary care. The methodology described herein can improve partner engagement in implementation efforts and increase the likelihood of success. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Retrospective Psychometrics and Effect Heterogeneity in Integrated Data Analysis: Commentary on the Special Issue.

The current special issue of Prevention Science indicates that momentum in using individual participant data (IPD) and integrative data analysis (IDA) to combine and synthesize findings in prevention science has accelerated over the past decade. In this commentary, we focus on two general themes involving methods for harmonizing measures and findings of effect heterogeneity. We describe methods for harmonization as retrospective psychometrics, requiring that we attend to the assumptions necessary for accurate measurement, but adjust our methods given the constraints of working with existing datasets that often involve different measures in different studies. We point to novel approaches for increasing confidence that semantic matching and empirical modeling used in these studies will yield accurate and valid measurements that can be combined in IDA. We also review findings about effect heterogeneity, emphasizing the importance of using etiologic and action theories to identify and evaluate sources of such effects. We note that all of the papers in this issue deserve careful attention, as they illustrate how prevention scientists are approaching the complexities of IDA and exploring novel methods for overcoming its challenges.

Substance Use Outcomes Among Sexual and Gender Minority Individuals Living with HIV Following Residential Substance Use Treatment in Washington, DC.

This study explored how sexual or gender minority (SGM) status influenced substance use (SU) treatment outcomes in a predominantly African American and unemployed sample of people with HIV. N = 60 participants were enrolled in an abstinence-focused inpatient SU treatment center, followed by outpatient treatment sessions. At 12-months follow-up, the survival rate (i.e. those who did not reuse substances) was 37.6% (non-SGM group) vs. 4.8% (SGM group). The impact of SGM status on reuse was .54 log odds, p = .11, which translates to a 71.8% increase in the hazard of reusing substances for SGM vs. non-SGM individuals. For both groups, frequency of reuse remained stable and problems associated with SU decreased over time. Results suggest a potentially clinically relevant finding that SGM individuals have possible heigh-tened risk of SU after a mixed inpatient-outpatient program. ClinicalTrials.gov trial registration number: NCT01351454.

Barriers and facilitators for surgical site infection surveillance for adult cardiac surgery in a high-income setting: an in-depth exploration.

BACKGROUND: Surgical site infection (SSI) surveillance aims to facilitate a reduction in SSIs through identifying infection rates, benchmarking, triggering clinical review and instituting infection control measures. Participation in surveillance is, however, variable suggesting opportunities to improve wider adoption. AIM: To gain an in-depth understanding of the barriers and facilitators for SSI surveillance in a high-income European setting. METHODS: Key informant interviews with 16 surveillance staff, infection prevention staff, nurses and surgeons from nine cardiac hospitals in England. Data were analysed thematically. FINDINGS: SSI surveillance was reported to be resource intensive. Barriers to surveillance included challenges associated with data collection: data being located in numerous places, multiple SSI data reporting schemes, difficulty in finding denominator data, lack of interface between computerized systems, 'labour intensive' or 'antiquated' methods to collect data (e.g., using postal systems for patient questionnaires). Additional reported concerns included: relevance of definitions, perceived variability in data reporting, lack of surgeon engagement, unsupportive managers, low priority of SSIs among staff, and a 'blame culture' around high SSI rates. Facilitators were increased resources, better use of digital technologies (e.g., remote digital wound monitoring), integrating surveillance within routine clinical work, having champions, mandating surveillance, ensuring a closer relationship between surveillance and improved patient outcomes, increasing the focus on post-discharge surveillance, and integration with primary care data. CONCLUSION: Using novel interviews with 'front-line' staff, identified opportunities for improving participation in SSI surveillance. Translating these findings into action will increase surveillance activity and bring patient safety benefits to a larger pool of surgical patients.

"The library is so much more than books": considerations for the design and implementation of teen digital mental health services in public libraries.

Background: Adolescence is a vulnerable developmental period, characterized by high rates of mental health concerns, yet few adolescents receive treatment. Public libraries support adolescents by providing them with access to teen programming, technological resources, and have recently been providing mental health services. Digital mental health (DMH) services may help libraries provide scalable mental health solutions for their adolescent patrons and could be well positioned to address the mental health needs of historically underrepresented racial and ethnic (HURE) adolescents; however, little research has been conducted on the compatibility of DMH services with adolescent patron mental health needs or resource needs of library workers supporting them. Methods: The research team formed a partnership with a public library, which serves a large HURE adolescent population. We conducted needs assessment and implementation readiness interviews with 17 library workers, including leadership, librarians, and workers with specialized areas of practice. Interview questions focused on library infrastructure, as well as library needs and preferences around the design and implementation of DMH services for adolescents. We used the Consolidated Framework for Implementation Research as guiding implementation determinant framework to code and analyze the interview transcripts. Results: Our findings revealed library workers play an important role in guiding patrons to desired resources and share a goal of implementing adolescent DMH resources into the library and elevating marginalized adolescents' voices. Existing library resources, such as the library's role as a safe space for adolescents in the community, close relationships with external and community organizations, and availability of no-cost technological resources, could help facilitate the implementation of DMH services. Barriers related to community buy-in, mental health stigma, and library worker confidence in supporting adolescent mental health could affect service implementation. Conclusions: Our findings suggest public libraries are highly promising settings to deploy DMH services for adolescents. We identified important determinants that may impact the implementation of DMH services in public library settings. Special considerations are needed to design services to meet the mental health needs of HURE adolescent populations and those adolescents' most experiencing health inequities.

Effect of storage periods and conditions on embryonic mortalities and hatchability of artificially incubated ostrich eggs.

1. Despite substantial research, the hatching failure of ostrich eggs remains a key concern for many commercial breeding farms.2. This source of reproductive failure needs to be addressed for ostrich farming to become more profitable.3. Information from 2212 eggs were obtained from the ostrich resource flock at the Oudtshoorn Research Farm (2013-2014). Egg data were divided on a daily basis into two groups: Group 1 included eggs stored from 1 to 13 d in cold storage (CS) at a controlled temperature of 17°C and a relative humidity (RH) of 90%. Group 2 was stored for the same time interval as Group 1, but in a cool room (CR) at ambient temperature to simulate the uncontrolled storage conditions prevalent on most breeding farms.4. Overall embryonic mortalities (OEM) were significantly higher for eggs stored for 1 d (0.38 ± 0.04) and for 8 d or more (between 0.31 ± 0.04 and 0.43 ± 0.04) compared to eggs stored for between 2 and 7 d (between 0.20 ± 0.03 and 0.26 ± 0.04).5. The moisture loss during storage (ML) for eggs stored for 13 d in CS during spring was on average slightly higher (1.28%) than that during summer (0.95%). In contrast, the ML of eggs stored in the CR for 13 d was significantly higher, at 1.59% in spring and 2.08% in summer.6. A general reduction in chick weight occurred for all the seasons (winter, spring and summer) as the number of storage days increased. Ostrich eggs should be stored for between 2 and 8 d under controlled storage conditions for improved hatchability.

Detection, survival, and persistence of Staphylococcus capitis NRCS-A in neonatal units in England.

BACKGROUND: The multidrug-resistant Staphylococcus capitis clone, NRCS-A, is increasingly associated with late-onset sepsis in low birthweight newborns in neonatal intensive care units (NICUs) in England and globally. Understanding where this bacterium survives and persists within the NICU environment is key to developing and implementing effective control measures. AIM: To investigate the potential for S. capitis to colonize surfaces within NICUs. METHODS: Surface swabs were collected from four NICUs with and without known NRCS-A colonizations/infections present at the time of sampling. Samples were cultured and S. capitis isolates analysed via whole-genome sequencing. Survival of NRCS-A on plastic surfaces was assessed over time and compared to that of non-NRCS-A isolates. The bactericidal activity of commonly used chemical disinfectants against S. capitis was assessed. FINDINGS: Of 173 surfaces sampled, 40 (21.1%) harboured S. capitis with 30 isolates (75%) being NRCS-A. Whereas S. capitis was recovered from surfaces across the NICU, the NRCS-A clone was rarely recovered from outside the immediate neonatal bedspace. Incubators and other bedside equipment were contaminated with NRCS-A regardless of clinical case detection. In the absence of cleaning, S. capitis was able to survive for three days with minimal losses in viability (<0.5 log10 reduction). Sodium troclosene and a QAC-based detergent/disinfectant reduced S. capitis to below detectable levels. CONCLUSION: S. capitis NRCS-A can be readily recovered from the NICU environment, even in units with no recent reported clinical cases of S. capitis infection, highlighting a need for appropriate national guidance on cleaning within the neonatal care environment.

PrEP Persistence Support and Monitoring in Areas of High HIV Burden in the Midwestern United States.

Monitoring pre-exposure prophylaxis (PrEP) metrics can guide service delivery yet does not occur routinely. We developed a survey to understand current practices for monitoring PrEP at PrEP-providing organizations in Illinois and Missouri. The survey was distributed from September through November 2020; 26 organizations participated. Most respondents indicated ongoing efforts to screen for PrEP eligibility (66.7%), link to care (87.5%), and retain clients in care (70.8%); 70.8% reported collecting data on PrEP initiation, 41.7% on retention in care, and 37.5% on missed visits. Barriers to monitoring PrEP metrics included lack of IT support (69.6%), manual processes (69.6%), and lack of staff resources (65.2%). Most respondents offered clients support for PrEP retention and adherence and wanted to expand interventions for PrEP persistence, yet fewer monitored corresponding metrics. To enhance PrEP implementation, organizations should improve monitoring and evaluation of PrEP metrics along the entire continuum and respond with appropriate services to support clients.