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Abstract Climate change is causing widespread impacts on seawater pH through ocean acidification (OA). Kelp forests, in some locations can buffer the effects of OA through photosynthesis. However, the factors influencing this variation remain poorly understood. To address this gap, we conducted a literature review and field deployments of pH and dissolved oxygen (DO) loggers within four habitats: intact kelp forest, moderate kelp cover, sparse kelp cover and barrens at one site in Port Phillip Bay, a wind-wave dominated coastal embayment in Victoria, Australia. Additionally, a wave logger was placed directly in front of the intact kelp forest and barrens habitats. Most studies reported that kelp increased seawater pH and DO during the day, compared to controls without kelp. This effect was more pronounced in densely populated forests, particularly in shallow, sheltered conditions. Our field study was broadly consistent with these observations, with intact kelp habitat having higher seawater pH than habitats with less kelp or barrens and higher seawater DO compared to barrens, particularly in the afternoon and during calmer wave conditions. Although kelp forests can provide local refuges to biota from OA, the benefits are variable through time and may be reduced by declines in kelp density and increased wave exposure.

Abstract Background Incorporating genomic data into risk prediction has become an increasingly popular approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not. Methods Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip. The first risk score, exposure and methylation risk score (eMRS) used cumulative and childhood trauma exposure and DNAm variables; the second, methylation-only risk score (MoRS) was based solely on DNAm data; the third, methylation-only risk scores with adjusted exposure variables (MoRSAE) utilized DNAm data adjusted for the two exposure variables. The potential of these risk scores to predict future PTSD based on pre-deployment data was also assessed. External validation of risk scores was conducted in four independent cohorts. Results The eMRS model showed the highest accuracy (92%), precision (91%), recall (87%), and f1-score (89%) in classifying PTSD using 3730 features. While still highly accurate, the MoRS (accuracy = 89%) using 3728 features and MoRSAE (accuracy = 84%) using 4150 features showed a decline in classification power. eMRS significantly predicted PTSD in one of the four independent cohorts, the BEAR cohort (beta = 0.6839, p=0.006), but not in the remaining three cohorts. Pre-deployment risk scores from all models (eMRS, beta = 1.92; MoRS, beta = 1.99 and MoRSAE, beta = 1.77) displayed a significant (p

Purpose: The optimal management of stage II follicular lymphoma (FL) is unclear. Radiation therapy (RT) alone has been the gold standard treatment, but a proportion of patients relapse. We sought to characterize outcomes and prognostic factors for stage II FL treated with RT alone to identify a high-risk subgroup of patients who may benefit from treatment intensification. Methods: This was a population-based, province-wide, retrospective study. Included patients had grade 1–3A, non-mesenteric, stage IIA or IIAE FL diagnosed between 1986 and 2016 and treated with curative-intent (≥20 Gy) RT alone. Results: 102 patients were included. Median follow-up was 10.4 years (range, 0.3–22.3). Median age was 59 years (range, 33–86). Median greatest disease diameter was 3.6 cm (range, 1.5–11.5). Freedom from progression (FFP) was 60.3% at 5 years and 40.7% at 10 years. Overall survival (OS) was 89.2% at 5 years and 81.8% at 10 years. Greatest disease diameter of >3.6 cm was associated with inferior FFP (10-year FFP 34% vs. 47%, p = 0.013) on univariable analysis and inferior FFP (hazard ratio [HR] 1.87, p = 0.019) and inferior OS (HR 2.12, p = 0.027) on multivariable analysis (MVA). Older age was associated with inferior OS (HR 1.08, unit = 1 year, p 3.6 cm was associated with inferior FFP and OS, representing a novel prognostic indicator in this population that may help in the decision-making process on whether to complement RT with systemic therapy.

Abstract Aims To describe a reflexive account of a mental health nurse as researcher undertaking a mixed methods study as part of a doctoral degree, with women in a secure forensic hospital. Design A discursive paper that draws upon the primary author's experience of dual roles as a mental health nurse and a novice researcher, and relevant literature pertaining to positionality and reflexivity in the context of conducting mixed methods research. Methods A mixed methods study was conducted within a secure forensic hospital in Australia, to identify factors associated with the frequency and duration of seclusion for women and, to explore their experiences of seclusion. Notes and a reflective diary were used to demonstrate the reflexive approach and strategies used throughout the study design and data collection stages of the research. Results Women in the secure forensic hospital setting often have complex histories and experiences and are considered a vulnerable group, which can add additional challenges when undertaking research with this population. As a doctoral student with clinical experience in mental health undertaking research in the forensic hospital setting with women, positionality and the connection with reflexivity requires exploration to understand self and the influence on research. This understanding along with identified strategies to enhance reflexivity, supports the management of the dual nurse as researcher roles to enhance all stages of the research process. Conclusion Doctoral nursing candidates undertaking clinical research in their area of clinical practice and at the location of previous employment, may experience challenges in relation to identity and the dichotomy of roles. Further challenges can be posed when research involves complex populations and/or controversial practices. Support to balance role conflict and maintain reflexivity is critical to understanding the role of self in research and to enhance credibility. Implications for the Profession and/or Clinical Practice Women are a complex, yet minority population in forensic mental health settings, however the numbers of women being admitted to services is increasing. Future research may consider the use of the strategies explored here to enhance the reflexive process, and support future researchers in this field to conduct research that aims to support an often‐misheard population to better support health outcomes. Patient or Public Involvement There was no patient or public contribution to this paper, however the study in which this paper is based on, is grounded in the experience of patients (women).

Abstract Observational studies suggest that posttraumatic stress disorder (PTSD) increases risk for various autoimmune diseases. Insights into shared biology and causal relationships between these diseases may inform intervention approaches to PTSD and co-morbid autoimmune conditions. We investigated the shared genetic contributions and causal relationships between PTSD, 18 autoimmune diseases, and 3 immune/inflammatory biomarkers. Univariate MiXeR was used to contrast the genetic architectures of phenotypes. Genetic correlations were estimated using linkage disequilibrium score regression. Bi-directional, two-sample Mendelian randomization (MR) was performed using independent, genome-wide significant single nucleotide polymorphisms; inverse variance weighted and weighted median MR estimates were evaluated. Sensitivity analyses for uncorrelated (MR PRESSO) and correlated horizontal pleiotropy (CAUSE) were also performed. PTSD was considerably more polygenic (10,863 influential variants) than autoimmune diseases (median 255 influential variants). However, PTSD evidenced significant genetic correlation with nine autoimmune diseases and three inflammatory biomarkers. PTSD had putative causal effects on autoimmune thyroid disease (p = 0.00009) and C-reactive protein (CRP) (p = 4.3 × 10−7). Inferences were not substantially altered by sensitivity analyses. Additionally, the PTSD-autoimmune thyroid disease association remained significant in multivariable MR analysis adjusted for genetically predicted inflammatory biomarkers as potential mechanistic pathway variables. No autoimmune disease had a significant causal effect on PTSD (all p values > 0.05). Although causal effect models were supported for associations of PTSD with CRP, shared pleiotropy was adequate to explain a putative causal effect of CRP on PTSD (p = 0.18). In summary, our results suggest a significant genetic overlap between PTSD, autoimmune diseases, and biomarkers of inflammation. PTSD has a putative causal effect on autoimmune thyroid disease, consistent with existing epidemiologic evidence. A previously reported causal effect of CRP on PTSD is potentially confounded by shared genetics. Together, results highlight the nuanced links between PTSD, autoimmune disorders, and associated inflammatory signatures, and suggest the importance of targeting related pathways to protect against disease and disability.

Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of many tumor types, and durable responses can be observed in select populations. However, patients may exhibit significant immune-related adverse events (irAEs) that may lead to morbidity. There is limited information on whether the presence of specific germline mutations may highlight those at elevated risk of irAEs. We evaluated 117 patients with metastatic solid tumors or hematologic malignancies who underwent genomic analysis through the ongoing Personalized OncoGenomics (POG) program at BC Cancer and received an ICI during their treatment history. Charts were reviewed for irAEs. Whole genome sequencing of a fresh biopsy and matched normal specimens (blood) was performed at the time of POG enrollment. Notably, we found that MHC class I alleles in the HLA-B27 family, which have been previously associated with autoimmune conditions, were associated with grade 3 hepatitis and pneumonitis (q = 0.007) in patients treated with combination PD-1/PD-L1 and CTLA-4 inhibitors, and PD-1 inhibitors in combination with IDO-1 inhibitors. These data highlight that some patients may have a genetic predisposition to developing irAEs.

Abstract High levels of proinflammatory cytokines induce neurotoxicity and catalyze inflammation-driven neurodegeneration, but the specific release mechanisms from microglia remain elusive. Here we show that secretory autophagy (SA), a non-lytic modality of autophagy for secretion of vesicular cargo, regulates neuroinflammation-mediated neurodegeneration via SKA2 and FKBP5 signaling. SKA2 inhibits SA-dependent IL-1β release by counteracting FKBP5 function. Hippocampal Ska2 knockdown in male mice hyperactivates SA resulting in neuroinflammation, subsequent neurodegeneration and complete hippocampal atrophy within six weeks. The hyperactivation of SA increases IL-1β release, contributing to an inflammatory feed-forward vicious cycle including NLRP3-inflammasome activation and Gasdermin D-mediated neurotoxicity, which ultimately drives neurodegeneration. Results from protein expression and co-immunoprecipitation analyses of male and female postmortem human brains demonstrate that SA is hyperactivated in Alzheimer’s disease. Overall, our findings suggest that SKA2-regulated, hyperactive SA facilitates neuroinflammation and is linked to Alzheimer’s disease, providing mechanistic insight into the biology of neuroinflammation.

ABSTRACTIntroduction: Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates plasticity in brain systems underlying arousal and memory and is associated with posttraumatic stress disorder (PTSD). Research in animal models suggests that PACAP modulates entorhinal cortex (EC) input to the hippocampus, contributing to impaired contextual fear conditioning. In PTSD, PACAP is associated with higher activity of the amygdala to threat stimuli and lower functional connectivity of the amygdala and hippocampus. However, PACAP-affiliated structural alterations of these regions have not been investigated in PTSD. Here, we examined whether peripheral PACAP levels were associated with neuronal morphology of the amygdala and hippocampus (primary analyses), and EC (secondary) using Neurite Orientation Dispersion and Density Imaging.Methods: Sixty-four (44 female) adults (19 to 54 years old) with DSM-5 Criterion A trauma exposure completed the Clinician-Administered PTSD Scale (CAPS-5), a blood draw, and magnetic resonance imaging. PACAP38 radioimmunoassay was performed and T1-weighted and multi-shell diffusion-weighted images were acquired. Neurite Density Index (NDI) and Orientation Dispersion Index (ODI) were quantified in the amygdala, hippocampus, and EC. CAPS-5 total score and anxious arousal score were used to test for clinical associations with brain structure.Results: Higher PACAP levels were associated with greater EC NDI (β = 0.0099, q = 0.032) and lower EC ODI (β = −0.0073, q = 0.047), and not hippocampal or amygdala measures. Neither EC NDI nor ODI was associated with clinical measures.Conclusions: Circulating PACAP levels were associated with altered neuronal density of the EC but not the hippocampus or amygdala. These findings strengthen evidence that PACAP may impact arousal-associated memory circuits in PTSD.

Abstract In brain, the striatum is a heterogenous region involved in reward and goal-directed behaviors. Striatal dysfunction is linked to psychiatric disorders, including opioid use disorder (OUD). Striatal subregions are divided based on neuroanatomy, each with unique roles in OUD. In OUD, the dorsal striatum is involved in altered reward processing, formation of habits, and development of negative affect during withdrawal. Using single nuclei RNA-sequencing, we identified both canonical (e.g., dopamine receptor subtype) and less abundant cell populations (e.g., interneurons) in human dorsal striatum. Pathways related to neurodegeneration, interferon response, and DNA damage were significantly enriched in striatal neurons of individuals with OUD. DNA damage markers were also elevated in striatal neurons of opioid-exposed rhesus macaques. Sex-specific molecular differences in glial cell subtypes associated with chronic stress were found in OUD, particularly female individuals. Together, we describe different cell types in human dorsal striatum and identify cell type-specific alterations in OUD.

Summary: Recent findings show that effective integration of novel information in the brain requires coordinated processes of homo- and heterosynaptic plasticity. In this work, we hypothesize that activity-dependent remodeling of the peri-synaptic extracellular matrix (ECM) contributes to these processes. We show that clusters of the peri-synaptic ECM, recognized by CS56 antibody, emerge in response to sensory stimuli, showing temporal and spatial coincidence with dendritic spine plasticity. Using CS56 co-immunoprecipitation of synaptosomal proteins, we identify several molecules involved in Ca2+ signaling, vesicle cycling, and AMPA-receptor exocytosis, thus suggesting a role in long-term potentiation (LTP). Finally, we show that, in the CA1 hippocampal region, the attenuation of CS56 glycoepitopes, through the depletion of versican as one of its main carriers, impairs LTP and object location memory in mice. These findings show that activity-dependent remodeling of the peri-synaptic ECM regulates the induction and consolidation of LTP, contributing to hippocampal-dependent memory.

BackgroundThe relationship between dissociation and recovery from psychosis is a new topic, which could attract the interest of the researchers in the field of dissociation due to its relevance to their daily clinical practice. This review brings together a diversity of international research and theoretical views on the phenomenology of dissociation, psychosis and recovery and provides a synthesis by narrative and tabulation of the existing knowledge related to these concepts.AimsThe objective was to make a synthesis by narrative and tabulation about what is known on the topic.MethodsThe systematic search was conducted according to the PRISMA-statement in the databases Medline, PsycInfo, PubMed and Google Scholar. 2110 articles were selected according to the inclusion and exclusion criteria detailed in the methods, and 19 records were included in the review.OutcomesNone of the included publications put together, in the same conceptualisation or hypothesis, dissociation and the recovery from an episode of psychosis, therefore this matter remains unstudied at this time.ConclusionThe process of reviewing the existing scientific literature in the field of dissociation and recovery from psychosis has been very useful for charting the direction that future research will take.

Abstract Palladium films hold signicance due to their remarkable affinity for hydrogen diffusion, rendering them valauble for the seperation and purification of hydrogen in membrane reactors. However, palladium is expensive, and its films can become brittle after only a few cycles of hydrogen separation. Alloying with silver has been shown to overcome the problem of palladium embrittlement. Palladium‐silver films have been produced via several methods but all have drawbacks, such as difficulties controlling the alloy composition. This study explores two promising jet printing methods: Inkjet and Aerosoljet. Both methods offer potential advantages such as direct patterning, which reduces waste, enables thin film production, and allows for the control of alloy composition. For the first time, palladium‐silver alloys have been produced via inkjet printing using a palladium‐silver metal organic decomposition (MOD) ink, which alloys at a temperature of 300 °C with nitrogen. Similarly, this study also demonstrates a pioneering approach for Aerosol Jet printing, showing the potential of a novel room‐temperature method, for the deposition of palladium‐silver MOD inks. This low temperature approach is considered an important development as palladium‐silver MOD inks are originally designed for deposition on heated substrates.

Abstract Adolescents and young adults (AYA) with lymphoma experience treatment‐related effects in the short and long term that impact their quality of life and survivorship experience. The effort to improve outcomes for AYA lymphoma survivors requires understanding the available literature, identifying current knowledge deficits, designing better clinical trials incorporating the patient perspective, using novel tools to bridge data gaps and building survivorship guidelines that translate research to clinical practice. This review article summarizes the current state of lymphoma treatment‐related outcomes in AYAs and provides future direction.

Abstract Calls for using marine protected areas (MPAs) to achieve goals for nature and people are increasing globally. While the conservation and fisheries impacts of MPAs have been comparatively well‐studied, impacts on other dimensions of human use have received less attention. Understanding how humans engage with MPAs and identifying traits of MPAs that promote engagement is critical to designing MPA networks that achieve multiple goals effectively, equitably and with minimal environmental impact. In this paper, we characterize human engagement in California's MPA network, the world's largest MPA network scientifically designed to function as a coherent network (124 MPAs spanning 16% of state waters and 1300 km of coastline) and identify traits associated with higher human engagement. We assemble and compare diverse indicators of human engagement that capture recreational, educational and scientific activities across California's MPAs. We find that human engagement is correlated with nearby population density and that site “charisma” can expand human engagement beyond what would be predicted based on population density alone. Charismatic MPAs tend to be located near tourist destinations, have long sandy beaches and be adjacent to state parks and associated amenities. In contrast, underutilized MPAs were often more remote and lacked both sandy beaches and parking lot access. Synthesis and applications: These results suggest that achieving MPA goals associated with human engagement can be promoted by developing land‐based amenities that increase access to coastal MPAs or by locating new MPAs near existing amenities during the design phase. Alternatively, human engagement can be limited by locating MPAs in areas far from population centres, coastal amenities or sandy beaches. Furthermore, managers may want to prioritize monitoring, enforcement, education and outreach programmes in MPAs with traits that predict high human engagement. Understanding the extent to which human engagement impacts the conservation performance of MPAs is a critical next step to designing MPAs that minimize tradeoffs among potentially competing objectives. Read the free Plain Language Summary for this article on the Journal blog.

Abstract SARS-CoV-2 variants and seasonal coronaviruses continue to cause disease and coronaviruses in the animal reservoir pose a constant spillover threat. Importantly, understanding of how previous infection may influence future exposures, especially in the context of seasonal coronaviruses and SARS-CoV-2 variants, is still limited. Here we adopted a step-wise experimental approach to examine the primary immune response and subsequent immune recall toward antigenically distinct coronaviruses using male Syrian hamsters. Hamsters were initially inoculated with seasonal coronaviruses (HCoV-NL63, HCoV-229E, or HCoV-OC43), or SARS-CoV-2 pango B lineage virus, then challenged with SARS-CoV-2 pango B lineage virus, or SARS-CoV-2 variants Beta or Omicron. Although infection with seasonal coronaviruses offered little protection against SARS-CoV-2 challenge, HCoV-NL63-infected animals had an increase of the previously elicited HCoV-NL63-specific neutralizing antibodies during challenge with SARS-CoV-2. On the other hand, primary infection with HCoV-OC43 induced distinct T cell gene signatures. Gene expression profiling indicated interferon responses and germinal center reactions to be induced during more similar primary infection-challenge combinations while signatures of increased inflammation as well as suppression of the antiviral response were observed following antigenically distant viral challenges. This work characterizes and analyzes seasonal coronaviruses effect on SARS-CoV-2 secondary infection and the findings are important for pan-coronavirus vaccine design.

Circulating α1-acid glycoprotein (AGP) and C-reactive protein (CRP) are commonly measured to assess inflammation, but these biomarkers fail to reveal the complex molecular biology of inflammation. We mined the maternal plasma proteome to detect proteins that covary with AGP and CRP. In 435 gravida predominantly in ®) with AGP and CRP, quantified by immunoassay. We defined a plasma inflammasome as protein correlates meeting a false discovery rate

Abstract Severe stress exposure increases the risk of stress-related disorders such as major depressive disorder (MDD). An essential characteristic of MDD is the impairment of social functioning and lack of social motivation. Chronic social defeat stress is an established animal model for MDD research, which induces a cascade of physiological and behavioral changes. Current markerless pose estimation tools allow for more complex and naturalistic behavioral tests. Here, we introduce the open-source tool DeepOF to investigate the individual and social behavioral profile in mice by providing supervised and unsupervised pipelines using DeepLabCut-annotated pose estimation data. Applying this tool to chronic social defeat in male mice, the DeepOF supervised and unsupervised pipelines detect a distinct stress-induced social behavioral pattern, which was particularly observed at the beginning of a novel social encounter and fades with time due to habituation. In addition, while the classical social avoidance task does identify the stress-induced social behavioral differences, both DeepOF behavioral pipelines provide a clearer and more detailed profile. Moreover, DeepOF aims to facilitate reproducibility and unification of behavioral classification by providing an open-source tool, which can advance the study of rodent individual and social behavior, thereby enabling biological insights and, for example, subsequent drug development for psychiatric disorders.

Abstract Background Trigeminal ganglia (TG) neurons are an important site of lifelong latent varicella-zoster virus (VZV) infection. Although VZV-specific T-cells are considered pivotal to control virus reactivation, their protective role at the site of latency remains uncharacterized. Methods Paired blood and TG specimens were obtained from ten latent VZV-infected adults, of which nine were co-infected with herpes simplex virus type 1 (HSV-1). Short-term TG-derived T-cell lines (TG-TCL), generated by mitogenic stimulation of TG-derived T-cells, were probed for HSV-1- and VZV-specific T-cells using flow cytometry. We also performed VZV proteome-wide screening of TG-TCL to determine the fine antigenic specificity of VZV reactive T-cells. Finally, the relationship between T-cells and latent HSV-1 and VZV infections in TG was analyzed by reverse transcription quantitative PCR (RT-qPCR) and in situ analysis for T-cell proteins and latent viral transcripts. Results VZV proteome-wide analysis of ten TG-TCL identified two VZV antigens recognized by CD8 T-cells in two separate subjects. The first was an HSV-1/VZV cross-reactive CD8 T-cell epitope, whereas the second TG harbored CD8 T-cells reactive with VZV specifically and not the homologous peptide in HSV-1. In silico analysis showed that HSV-1/VZV cross reactivity of TG-derived CD8 T-cells reactive with ten previously identified HSV-1 epitopes was unlikely, suggesting that HSV-1/VZV cross-reactive T-cells are not a common feature in dually infected TG. Finally, no association was detected between T-cell infiltration and VZV latency transcript abundance in TG by RT-qPCR or in situ analyses. Conclusions The low presence of VZV- compared to HSV-1-specific CD8 T-cells in human TG suggests that VZV reactive CD8 T-cells play a limited role in maintaining VZV latency.

BackgroundMood disorders such as major depressive and bipolar disorders, along with posttraumatic stress disorder (PTSD), schizophrenia (SCZ), and other psychotic disorders, constitute serious mental illnesses (SMI) and often lead to inpatient psychiatric care for adults. Risk factors associated with increased hospitalization rate in SMI (H-SMI) are largely unknown but likely involve a combination of genetic, environmental, and socio-behavioral factors. We performed a genome-wide association study in an African American cohort to identify possible genes associated with hospitalization due to SMI (H-SMI).MethodsPatients hospitalized for psychiatric disorders (H-SMI; n=690) were compared with demographically matched controls (n=4467). Quality control and imputation of genome-wide data were performed following the Psychiatric Genetic Consortium (PGC)-PTSD guidelines. Imputation of the Human Leukocyte Antigen (HLA) locus was performed using the HIBAG package.ResultsGenome-wide association analysis revealed a genome-wide significant association at 6p22.1 locus in the ubiquitin D (UBD/FAT10) gene (rs362514, p=9.43x10-9) and around the HLA locus. Heritability of H-SMI (14.6%) was comparable to other psychiatric disorders (4% to 45%). We observed a nominally significant association with 2 HLA alleles: HLA-A*23:01 (OR=1.04, p=2.3x10-3) and HLA-C*06:02 (OR=1.04, p=1.5x10-3). Two other genes (VSP13D and TSPAN9), possibly associated with immune response, were found to be associated with H-SMI using gene-based analyses.ConclusionWe observed a strong association between H-SMI and a locus that has been consistently and strongly associated with SCZ in multiple studies (6p21.32-p22.1), possibly indicating an involvement of the immune system and the immune response in the development of severe transdiagnostic SMI.

Background Cardiac rehabilitation (CR) is an evidence‐based, guideline‐recommended intervention for patients recovering from a cardiac event, surgery or procedure that improves morbidity, mortality, and functional status. CR is traditionally provided in‐center, which limits access and engagement, most notably among underrepresented racial and ethnic groups due to barriers including cost, scheduling, and transportation access. This study is designed to evaluate the Corrie Hybrid CR, a technology‐based, multicomponent health equity‐focused intervention as an alternative to traditional in‐center CR among patients recovering from a cardiac event, surgery, or procedure compared with usual care alone. Methods The mTECH‐Rehab (Impact of a Mobile Technology Enabled Corrie CR Program) trial will randomize 200 patients who either have a diagnosis of type 1 myocardial infarction or who undergo coronary artery bypass grafting surgery, percutaneous coronary intervention, heart valve repair, or replacement presenting to 4 hospitals in a large academic health system in Maryland, United States, to the Corrie Hybrid CR program combined with usual care CR (intervention group) or usual care CR alone (control group) in a parallel arm, randomized controlled trial. The Corrie Hybrid CR program leverages 5 components: (1) a patient‐facing mobile application that encourages behavior change, patient empowerment, and engagement with guideline‐directed therapy; (2) Food and Drug Administration‐approved smart devices that collect health metrics; (3) 2 upfront in‐center CR sessions to facilitate personalization, self‐efficacy, and evaluation for the safety of home exercise, followed by a combination of in‐center and home‐based sessions per participant preference; (4) a clinician dashboard to track health data; and (5) weekly virtual coaching sessions delivered over 12 weeks for education, encouragement, and risk factor modification. The primary outcome is the mean difference between the intervention versus control groups in distance walked on the 6‐minute walk test (ie, functional capacity) at 12 weeks post randomization. Key secondary and exploratory outcomes include improvement in a composite cardiovascular health metric, CR engagement, quality of life, health factors (including low‐density lipoprotein‐cholesterol, hemoglobin A1c, weight, diet, smoking cessation, blood pressure), and psychosocial factors. Approval for the study was granted by the local institutional review board. Results of the trial will be published once data collection and analysis have been completed. Conclusions The Corrie Hybrid CR program has the potential to improve functional status, cardiovascular health, and CR engagement and advance equity in access to cardiac rehabilitation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05238103.

Peripheral T-cell lymphomas (PTCL) encompass over 30 different entities and although they share post-thymic T- or NK-cell derivation, the disease biology and genomic landscape are very diverse across subtypes. In Western populations, nodal PTCL are the most frequently encountered entities in clinical practice and although important achievements have been made in deciphering the underlying biology and in therapeutic advances, there are still large gaps in disease understanding and clinical scenarios in which controversy over best practice continues. CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)- based chemotherapy continues to be the ‘standard’ treatment, with the addition of brentuximab vedotin (BV) in the combination CHP (cyclosphosphamide, doxorubicin, prednisone)-BV representing a new treatment paradigm in CD30+ PTCL although its benefit is less certain in the non-anaplastic large cell lymphoma subtypes. Given the high risk of relapse, consolidative autologous stem cell transplant is considered in nodal PTCL, outside of ALK-positive anaplastic large cell lymphoma; however, in the absence of a randomized controlled trials, practices vary. Beyond CHP-BV, most study activity has focused on adding a novel agent to CHOP (i.e., CHOP + drug X). However, with high complete remission rates observed with some novel therapy combinations, these regimens are being tested in the front-line setting, with a particular rationale in follicular helper T-cell lymphomas which have a clear sensitivity to epigenetic modifying therapies. This is well exemplified in the relapsed/refractory setting in which rational combination therapies are being developed for specific subtypes or guided by underlying biology. Taken together, we have finally moved into an era of a more personalized approach to the management of nodal PTCL.

Predominantly nodal is the most common clinical presentation of peripheral T- (and NK-) cell lymphomas (PTCL), which comprise three main groups of diseases: (i) systemic anaplastic large cell lymphomas (ALCL), whether positive or negative for anaplastic lymphoma kinase (ALK); (ii) follicular helper T-cell lymphomas (TFHL); and (iii) PTCL, not otherwise specified (NOS). Recent advances in the genomic and molecular characterization of PTCL, with enhanced understanding of pathobiology, have translated into significant updates in the latest 2022 classifications of lymphomas. ALK-negative ALCL is now recognized to be genetically heterogeneous, with identification of DUSP22 rearrangements in approximately 20-30% of cases, correlated with distinctive pathological and biological features. The notion of cell-of-origin as an important determinant of the classification of nodal PTCL is best exemplified by TFHL, considered as one disease or a group of related entities, sharing oncogenic pathways with frequent recurrent epigenetic mutations as well as a relationship to clonal hematopoiesis. Data are emerging to support that a similar cell-of-origin concept might be relevant to characterize meaningful subgroups within PTCL, NOS, based on cytotoxic and/or Th1 versus Th2 signatures. The small group of primary nodal Epstein-Barr virus-positive lymphomas of T- or NK-cell derivation, formerly considered PTCL, NOS, is now classified separately, due to distinctive features, and notably an aggressive course. This review summarizes current knowledge of the pathology and biology of nodal-based PTCL entities, with an emphasis on recent findings and underlying oncogenic mechanisms.

Background: Posttraumatic stress disorder (PTSD) and depression are associated with increased risk for cardiovascular disease (CVD), which is the leading cause of death and disability worldwide. Epidemiological studies have revealed these illnesses to be highly comorbid, particularly among women. In the current study, we explored associations between indices of cardiovascular health, PTSD, and depression among a sample of trauma-exposed individuals assigned female at birth. Methods: Participants were N = 49 individuals without CVD who reported lifetime Criterion A trauma exposure. Blood pressure (BP), heart rate (HR), and high-frequency heart rate variability (HF-HRV) were collected during a 5-minute resting period. Symptoms of CVD (e.g. extremity pain and swelling, shortness of breath), PTSD, and depression were assessed, along with an exploratory measure of anhedonia. Results: Trauma exposure was positively correlated with systolic BP (r = .32, p = .029) and diastolic BP (r = .30, p = .040). The number of reported CVD symptoms was positively correlated with symptoms of PTSD (r = .41, p = .004), depression (r = .40, p = .005) and anhedonia (r = .38, p = .007). CVD symptoms were also significantly associated with PTSD (β = .41, t = 2.43, p = .023), depression (β = .40, t = 2.76, p = .009), and anhedonia (β = .38, t = 2.51, p = .017) after controlling for age and trauma exposure. These associations were not moderated by HF-HRV in our sample. Conclusions: Our results support the association between PTSD and depressive symptoms and worse cardiovascular functioning among an often-overlooked population that is particularly vulnerable to these illnesses. Future studies should investigate residual impacts of PTSD and depression treatment on CVD risk among trauma-exposed individuals, particularly women.

Baseline data for reference conditions are needed to determine the impacts of human pressures on the structure and functioning of marine ecosystems. However, baseline data are seldom available, and a comprehensive understanding of what good ecological condition is or how to measure it is often lacking. In the absence of true baselines, well established and effective marine protected areas (MPAs) can be used to approximate reference conditions. Thus, the aim of this study was to use effective no-take MPAs to identify suitable indicators that can be used for condition assessments of rocky reefs in South Africa. To achieve this, we tested the response of two types of metrics (compositional and size-based), using in situ fish and benthic community data, to three levels of human pressures in two ecoregions in South Africa. Results showed that traditionally-used structural metrics, such as total abundance or species richness, were less responsive than size-based metrics, including total biomass, average length and proportion of mature fish. Rocky reef ecosystems exposed to low anthropogenic pressure were characterised by a higher biomass, average length and proportion of mature and large (>30 cm) fish than reefs with moderate and high pressures. Benthic communities appeared more resilient than fish communities to the typical human pressures in the study region. Overall, the greatest effect of pressure was observed in the heavily impacted sub-tropical Natal Shelf Ecoregion, while rocky reefs in the warm-temperate Agulhas Shelf Ecoregion appeared to be in better condition than expected. This study identified assemblage patterns and indicators that appeared responsive and sensitive to different levels of human pressure, which can be used to infer good and poor ecological condition of rocky reef ecosystems. These results indicate which species (e.g., target species) and traits (e.g., size) are most vulnerable to local human pressures and will be suitable for condition assessments.

Abstract The authors sought to characterize adverse posttraumatic neuropsychiatric sequelae (APNS) symptom trajectories across ten symptom domains (pain, depression, sleep, nightmares, avoidance, re-experiencing, anxiety, hyperarousal, somatic, and mental/fatigue symptoms) in a large, diverse, understudied sample of motor vehicle collision (MVC) survivors. More than two thousand MVC survivors were enrolled in the emergency department (ED) and completed a rotating battery of brief smartphone-based surveys over a 2-month period. Measurement models developed from survey item responses were used in latent growth curve/mixture modeling to characterize homogeneous symptom trajectories. Associations between individual trajectories and pre-trauma and peritraumatic characteristics and traditional outcomes were compared, along with associations within and between trajectories. APNS across all ten symptom domains were common in the first two months after trauma. Many risk factors and associations with high symptom burden trajectories were shared across domains. Both across and within traditional diagnostic boundaries, APNS trajectory intercepts, and slopes were substantially correlated. Across all domains, symptom severity in the immediate aftermath of trauma (trajectory intercepts) had the greatest influence on the outcome. An interactive data visualization tool was developed to allow readers to explore relationships of interest between individual characteristics, symptom trajectories, and traditional outcomes ( http://itr.med.unc.edu/aurora/parcoord/ ). Individuals presenting to the ED after MVC commonly experience a broad constellation of adverse posttraumatic symptoms. Many risk factors for diverse APNS are shared. Individuals diagnosed with a single traditional outcome should be screened for others. The utility of multidimensional categorizations that characterize individuals across traditional diagnostic domains should be explored.

Biomedical research has grown increasingly cooperative through the sharing of consortia-level epigenetic data. Since consortia preprocess data prior to distribution, new processing pipelines can lead to different versions of the same dataset. Similarly, analytic frameworks evolve to incorporate cutting-edge methods and best practices. However, it remains unknown how different data and analytic versions alter the results of epigenome-wide analyses, which could influence the replicability of epigenetic associations. Thus, we assessed the impact of these changes using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. We analysed DNA methylation from two data versions, processed using separate preprocessing and analytic pipelines, examining associations between seven childhood adversities or prenatal smoking exposure and DNA methylation at age 7. We performed two sets of analyses: (1) epigenome-wide association studies (EWAS); (2) Structured Life Course Modelling Approach (SLCMA), a two-stage method that models time-dependent effects. SLCMA results were also compared across two analytic versions. Data version changes impacted both EWAS and SLCMA analyses, yielding different associations at conventional p-value thresholds. However, the magnitude and direction of associations was generally consistent between data versions, regardless of p-values. Differences were especially apparent in analyses of childhood adversity, while smoking associations were more consistent using significance thresholds. SLCMA analytic versions similarly altered top associations, but time-dependent effects remained concordant. Alterations to data and analytic versions influenced the results of epigenome-wide analyses. Our findings highlight that magnitude and direction are better measures for replication and stability than p-value thresholds.

A revision of figure 3-4 is required, in response to the correspondence from Paris Alidoost Salima (PhD coral researcher: Islamic Azad University) notifying authors that the caption in monograph does not match published plates. Additionally, authors retract Paraconotrochus capensis (Gardiner, 1904) as a synonym of Monohedotrochus capensis comb. nov - as Cairns and Parker (1992) based this new combination on Duncania capensis Gardiner, 1904

T cells are considered important for controlling skin infections. Here, the authors report that varicella-zoster virus-specific T cells preferentially persist as tissue-resident-memory T cells in rash-involved skin after recovery from zoster.

Abstract Repeated excessive alcohol consumption is a risk factor for alcohol use disorder (AUD). Although AUD has been more common in men than women, women develop more severe behavioral and physical impairments. However, relatively few new therapeutics targeting development of AUD, particularly in women, have been validated. To gain a better understanding of molecular mechanisms underlying alcohol intake, we conducted a genome-wide RNA-sequencing analysis in female mice exposed to different modes (acute vs chronic) of ethanol drinking. We focused on transcriptional profiles in the amygdala including the central and basolateral subnuclei, brain areas previously implicated in alcohol drinking and seeking. Surprisingly, we found that both drinking modes triggered similar changes in gene expression and canonical pathways, including upregulation of ribosome-related/translational pathways and myelination pathways, and downregulation of chromatin binding and histone modification. In addition, analyses of hub genes and upstream regulatory pathways revealed that voluntary ethanol consumption affects epigenetic changes via histone deacetylation pathways, oligodendrocyte and myelin function, and the oligodendrocyte-related transcription factor, Sox17. Furthermore, a viral vector-assisted knockdown of Sox17 gene expression in the amygdala prevented a gradual increase in alcohol consumption during repeated accesses. Overall, these results suggest that the expression of oligodendrocyte-related genes in the amygdala is sensitive to voluntary alcohol drinking in female mice. These findings suggest potential molecular targets for future therapeutic approaches to prevent the development of AUD, due to repeated excessive alcohol consumption, particularly in women.

Follicular lymphoma can transform to a more aggressive histology. Here, the authors use bulk and single cell analysis to create a 26 marker panel which could be used to profile FL samples and predict the risk of transformation using flow cytometry.

Abstract Exposure to stress triggers biological changes throughout the body. Accumulating evidence indicates that alterations in immune system function are associated with the development of stress-associated illnesses such as major depressive disorder and post-traumatic stress disorder, increasing interest in identifying immune markers that provide insight into mental health. Recombination events during T-cell receptor rearrangement and T-cell maturation in the thymus produce circular DNA fragments called T-cell receptor excision circles (TRECs) that can be utilized as indicators of thymic function and numbers of newly emigrating T-cells. Given data suggesting that stress affects thymus function, we examined whether blood levels of TRECs might serve as a quantitative peripheral index of cumulative stress exposure and its physiological correlates. We hypothesized that chronic stress exposure would compromise thymus function and produce corresponding decreases in levels of TRECs. In male mice, exposure to chronic social defeat stress (CSDS) produced thymic involution, adrenal hypertrophy, and decreased levels of TRECs in blood. Extending these studies to humans revealed robust inverse correlations between levels of circulating TRECs and childhood emotional and physical abuse. Cell-type specific analyses also revealed associations between TREC levels and blood cell composition, as well as cell-type specific methylation changes in CD4T + and CD8T + cells. Additionally, TREC levels correlated with epigenetic age acceleration, a common biomarker of stress exposure. Our findings demonstrate alignment between findings in mice and humans and suggest that blood-borne TRECs are a translationally-relevant biomarker that correlates with, and provides insight into, the cumulative physiological and immune-related impacts of stress exposure in mammals.

On-Chip integration of laser systems led to impressive development in many field of application like LIDAR or AR/VR to cite a few. Here the authors harness Pockels effect in an integrated semiconductor platform achieving fast on-chip configurability of a narrow linewidth laser.

Background:. Immediate expander/implant-based breast reconstruction after mastectomy has become more sought after by patients. Although many patients choose this technique due to good aesthetic outcomes, lack of donor site morbidity, and shorter procedure times, it is not without complications. The most reported complications include seroma, infection, hematoma, mastectomy flap necrosis, wound dehiscence, and implant exposure, with an overall complication rate as high as 45%. Closed incision negative pressure therapy (ciNPT) has shown value in wound healing and reducing complications; however, the current literature is inconclusive. We aimed to examine if ciNPT improves outcomes for patients receiving this implant-based reconstruction. Methods:. This is a retrospective single-institution study evaluating the ciNPT device, 3M Prevena Restor BellaForm, on breast reconstruction patients. The study was performed between July 1, 2019 and October 30, 2020, with 125 patients (232 breasts). Seventy-seven patients (142 breasts) did not receive the ciNPT dressing, and 48 patients (90 breasts) received the ciNPT dressing. Primary outcomes were categorized by major or minor complications. Age, BMI, and final drain removal were summarized using medians and quartiles, and were compared with nonparametric Mann-Whitney test. Categorical variables were compared using chi-square or Fisher exact test. Results:. There was a statistically significant reduction in major complications in the ciNPT group versus the standard dressing group (P = 0.0247). Drain removal time was higher in the ciNPT group. Conclusion:. Our study shows that ciNPT may help reduce major complication rates in implant-based breast reconstruction patients.

Abstract Visual components of trauma memories are often vividly re-experienced by survivors with deleterious consequences for normal function. Neuroimaging research on trauma has primarily focused on threat-processing circuitry as core to trauma-related dysfunction. Conversely, limited attention has been given to visual circuitry which may be particularly relevant to posttraumatic stress disorder (PTSD). Prior work suggests that the ventral visual stream is directly related to the cognitive and affective disturbances observed in PTSD and may be predictive of later symptom expression. The present study used multimodal magnetic resonance imaging data (n = 278) collected two weeks after trauma exposure from the AURORA study, a longitudinal, multisite investigation of adverse posttraumatic neuropsychiatric sequelae. Indices of gray and white matter were combined using data fusion to identify a structural covariance network (SCN) of the ventral visual stream 2 weeks after trauma. Participant’s loadings on the SCN were positively associated with both intrusion symptoms and intensity of nightmares. Further, SCN loadings moderated connectivity between a previously observed amygdala-hippocampal functional covariance network and the inferior temporal gyrus. Follow-up MRI data at 6 months showed an inverse relationship between SCN loadings and negative alterations in cognition in mood. Further, individuals who showed decreased strength of the SCN between 2 weeks and 6 months had generally higher PTSD symptom severity over time. The present findings highlight a role for structural integrity of the ventral visual stream in the development of PTSD. The ventral visual stream may be particularly important for the consolidation or retrieval of trauma memories and may contribute to efficient reactivation of visual components of the trauma memory, thereby exacerbating PTSD symptoms. Potentially chronic engagement of the network may lead to reduced structural integrity which becomes a risk factor for lasting PTSD symptoms.

Optical absorption and nonlinear index are important performance drivers in devices like microcombs. Here the authors use resonance-enhanced nonlinear spectroscopy to characterize absorption limits and nonlinear index for some integrated photonic materials.

Despite its remoteness, human activity has impacted the deep sea and changes to the structure and function of deep-sea ecosystems are already noticeable. In terrestrial and shallow water marine environments, demonstrating how ecosystems support human well-being has been instrumental in setting policy and management objectives for sustainable resource use. Foundational to this approach is a framework of ecosystem service (ES) classification and a synthesis of the knowledge base, which can then be used to structure decision-support tools such as ecosystem accounts or Environmental Impact Assessments. At present, no such framework exists for the deep sea. There is thus an urgent need to determine and assess the ES provided by deep-sea habitats and species before (potentially irreversible) decisions are made about deep-sea habitat use and governance. As a first step towards the incorporation of ES in such decision-making, we undertake two systematic reviews of the scientific literature based on the principles of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) systematic process. This was to define a comparative ES framework and synthesise the current evidence base for how deep-sea habitats support ecosystem services. Our framework proposes four supporting services, three regulating services, four provisioning services and three cultural services for which there is an established and growing body of evidence for the role of deep-sea habitats. The ES framework presented here provides a structure for deep-sea ecosystem services. In its next phase of development, this could provide the foundation for the development of habitat-ecosystem service matrices, which are a critical component for truly accounting for ES in decision-making, particularly spatial management. This framework has significant implications for deep-sea management, conservation and policy, as it provides an ecosystem services-based tool that can be used in any deep-sea ecosystems management across the planet, and it also shows how critical these data gaps are for today’s decisions and how seriously they should be considered in decision-making processes.

South Africa has taken an iterative approach to marine ecosystem mapping over 18 years that has provided a valuable foundation for ecosystem assessment, planning and decision-making, supporting improved ecosystem-based management and protection. Iterative progress has been made in overcoming challenges faced by developing countries, especially in the inaccessible marine realm. Our aim is to report on the approach to produce and improve a national marine ecosystem map to guide other countries facing similar challenges, and to illustrate the impact of even the simplest ecosystem map. South Africa has produced four map versions, from a rudimentary map of 34 biozones informed by bathymetry data, to the latest version comprising 163 ecosystem types informed by 83 environmental and biodiversity datasets that aligns with the IUCN Global Ecosystem Typology. Data were unlocked through academic and industry collaborations; multi-disciplinary, multi-realm and multi-generational networks of practitioners; and targeted research to address key gaps. To advance toward a more transparent, reproducible and data-driven approach, limitations, barriers and opportunities for improvement were identified. Challenges included limited human and data infrastructure capacity to collate, curate and assimilate many data sources, covering a variety of ecosystem components, methods and scales. Five key lessons that are of relevance for others working to advance ecosystem classification and mapping, were distilled. These include (1) the benefits of iterative improvement; (2) the value of fostering relationships among a co-ordinated network of practitioners including early-career researchers; (3) strategically prioritizing and leveraging resources to build and curate key foundational biodiversity datasets and understand drivers of biodiversity pattern; (4) the need for developing, transferring and applying capacity and tools that enhance data quality, analytical workflows and outputs; and (5) the application of new technology and emerging statistical tools to improve the classification and prediction of biodiversity pattern. South Africa’s map of marine ecosystem types has been successfully applied in spatial biodiversity assessment, prioritization to support protected area expansion and marine spatial planning. These successes demonstrate the value of a co-ordinated network of practitioners who continually build an evidence base and iteratively improve ecosystem mapping while simultaneously growing ecological knowledge and informing changing priorities and policy.

Disclosures: EMS serves as a consultant to Corrie Health. Under a license agreement between Corrie Health and the Johns Hopkins University, the University owns equity in Corrie Health and the University, FAM, and SSM are entitled to royalty distributions related to technology described in the study discussed in this publication. Additionally, FAM and SSM are founders of and hold equity in Corrie Health. ML and JS have equity ownership in Corrie Health. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies. Therapeutic Area: Cardiac Rehabilitation; Secondary Prevention of CVD; Digital Health Background: Low participation in cardiac rehabilitation (CR) is a missed opportunity to improve outcomes in secondary prevention of cardiovascular disease. To increase participation in CR, a multidisciplinary team launched a 12-week hybrid CR program utilizing in-center and virtual CR sessions via an evidence-based digital health platform. Our early experience with >40 participants provides valuable lessons learned for creating a scalable hybrid CR program. Methods: We established a 5-phase approach from recruitment to graduation. Phase 1 - Pre-Bedside: We used the electronic medical record system, Epic, to identify low to moderate risk CR-eligible inpatients. Phase 2 - Bedside: Patient navigators approached inpatients to inform them about hybrid CR, conduct further screening, and for enrollment. Patients were coached how to use the digital health platform including a smartphone application, smartwatch, and blood pressure monitor. Phase 3 - Pre-CR: During hospitalization and after discharge, patients tracked medication use and vital signs, engaged with educational videos, and entered lab values (ex. LDL). Coaches conducted weekly check-in sessions to review progress, safety, and address any technical issues. Phase 4 - CR: Patients completed 2 in-center safety assessments prior to starting home-exercise. Phase 5 - Graduation: Patients received a graduation coaching session at week 12 to celebrate and plan for sustainable healthy lifestyle habits. Results: We identified multiple areas for improvement and enhanced our program. Phase 1: We streamlined patient identification using Epic reports and auto-referral ordersets for eligible patients. Phase 2: We developed flexible onboarding methods with instructional videos tailored for different levels of digital literacy. We also found that assembling a diverse CR team was key for recruiting patients traditionally underrepresented in CR. Phase 3: We created a structured weekly coaching curriculum to promote engagement. Phase 4: We refined low to moderate risk criteria to adjust for lack of exercise data during hospitalization and implemented 2 in-person safety assessments. Phase 5: Some patients expressed interest in advocacy after graduating, possibly through social media support groups. Conclusion: Drawing on lessons learned, we developed a hybrid CR program that adapted to patients’ experiences and provided a scalable solution for patients who cannot attend CR on a regular basis.

Discursive experiences can contribute to shaping lives and their identities. For minoritized youth in Hong Kong, the 2019 protest movement provided many such experiences, although very little has been heard about them. Instead, reporting has focused on the experiences of the dominant Chinese population. This paper aims to highlight the voices of minoritized youth in relation to the social movement that dominated Hong Kong in the second half of 2019. It is well recognized that identity is not fixed and that there are more likely multiple identities that transition from one to the other. Yet little is known about the influences on identity formation and the processes that underlie them. This was the issue addressed here. The paper draws on Lacan’s theory of identity in examining interviews involving minoritized youth and their engagement in Hong Kong’s 2019 protest movement. It shows how individual responses to the movement differed, how the movement challenged identities, and how these challenges were resolved.

Intercropping using mixtures of dryland crop species for grain or seed production was investigated in southern Australia across a range of rainfall zones over three years. The objective was to understand the productivity and profitability of intercropping in extensive, high-input grain cropping systems. Previous research has shown large productivity benefits of mixtures; however, few farmers practice intercropping in Australia, and an analysis of profitability is needed to support future potential adoption. Experimental results showed strong mixture responses (in terms of yield, value and land equivalence), but not all were profitable compared to an equivalent share of monoculture crops (as measured by gross margins). The most promising mixtures were those containing high-value crops (canola) and legumes (field pea or faba bean) at the wetter sites where the additional gross margin over equivalent monoculture crops ranged from $12/ha to $576/ha. Mixtures containing highly competitive crops (wheat or barley) were generally unprofitable. Mixtures involving cereals were doubly disadvantaged by the aggressiveness of these lower-value crops in the mixtures we examined and the high grain separation costs post-harvest. Cost reduction in mixture systems involving high-value crops that are synergistic (grain legumes) should provide enduring opportunities for intercropping in southern Australia.

Abstract Background Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (achondroplasia natural history study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at 1 month increments from birth through 18 years for clinical use and research for achondroplasia patients. Methods All available retrospective anthropometry data including length/height, weight and head circumference from achondroplasia patients were collected at 4 US skeletal dysplasia centers (Johns Hopkins University, AI DuPont Hospital for Children, McGovern Medical School University of Texas Health, University of Wisconsin School of Medicine and Public Health). Weight-for-age values beyond 3 SD above the mean were excluded from the weight-for-height and weight-for-age curves to create a stricter tool for weight assessment in this population. Results Over 37,000 length/height, weight and head circumference measures from 1374 patients with achondroplasia from birth through 75 years of age were compiled in a REDCap database. Stature and weight data from birth through 18 years of age and head circumference from birth through 5 years of age were utilized to construct new length/height-for-age, weight-for-age, head circumference-for-age and weight-for-height curves. Conclusion Achondroplasia-specific growth curves are essential for clinical care of growing infants and children with this condition. In an effort to provide prescriptive, rather than purely descriptive, references for weight in this population, extreme weight values were omitted from the weight-for-age and weight-for-height curves. This well-phenotyped cohort may be studied with other global achondroplasia populations (e.g. Europe, Argentina, Australia, Japan) to gain further insight into environmental or ethnic influences on growth.

The need to move toward marine ecosystem-based management is globally recognized. Few countries effectively account for multiple interacting pressures in their marine assessments, planning and management. Many socio-economic sectors currently operate in South African waters and in most cases, their associated pressures are managed on a sector-by-sector basis and interacting pressures are seldom accounted for in assessments or decision-making. For ecosystem-based management to be effective, a science-based approach to prioritize sectors and pressures needing most urgent action, and to identify affected ecological components is needed. Integrated Ecosystem Assessment (IEA) has hence been put forward as a tool that can organize relevant information and provide context for cross-sectoral management decisions. Consisting of five main stages that form an iterative cycle, the first IEA stage involves scoping of top management priorities in a given area and can be done by way of risk assessment. Through the ODEMM (Options for Delivering Ecosystem-based Marine Management) approach, linkage chains (interactions) among sectors, pressures and affected ecological components for the entirety of the South African marine territory were identified. Subsequently, impact risk scores of each linkage chain were calculated based on the exposure and severity of impacts faced by ecological components from pressures that are associated with each sector. Fishing was the sector with the greatest connectivity (11.65% proportional connectance) in the framework and ranked highest in terms of impact risk (summed), followed by Shipping and Coastal infrastructure. Pressures with the most serious impacts on ecological components, as identified through summed impact risk scores, included Bycatch, Species extraction, and Incidental loss and the ecological components most affected were those primarily associated with Fishing and its associated pressures. These findings align with those of the recent South African National Biodiversity Assessment and corroborate views of local stakeholders. This study also identified key local knowledge gaps, including impacts of underwater noise, invasive species, and climate change, that must be better understood to improve assessment accuracy and guide management prioritization of pressures exerted by most impactful sectors.

Background: Suicide is a leading cause of death, and rates of attempted suicide have increased during the COVID-19 pandemic. The under-diagnosed psychiatric phenotype of dissociation is associated with elevated suicidal self-injury; however, it has largely been left out of attempts to predict and prevent suicide. Objective: We designed an artificial intelligence approach to identify dissociative patients and predict prior suicide attempts in an unbiased, data-driven manner. Method: Participants were 30 controls and 93 treatment-seeking female patients with posttraumatic stress disorder (PTSD) and various levels of dissociation, including some with the PTSD dissociative subtype and some with dissociative identity disorder (DID). Results: Unsupervised learning models identified patients along a spectrum of dissociation. Moreover, supervised learning models accurately predicted prior suicide attempts with an F1 score up to 0.83. DID had the highest risk of prior suicide attempts, and distinct subtypes of dissociation predicted suicide attempts in PTSD and DID. Conclusions: These findings expand our understanding of the dissociative phenotype and underscore the urgent need to assess for dissociation to identify individuals at high-risk of suicidal self-injury.