Interactions between animals structure food webs and regulate ecosystem function and productivity. Quantifying subsurface behavioural interactions among marine organisms is challenging, but ...technological advances are promoting novel opportunities.
Here, we present a framework to estimate when there is a high likelihood that aquatic animal subsurface interactions occur and test for a movement‐related behavioural response to those interactions over short temporal scales (days) using a novel multi‐sensor biologging package on a large marine predator, the Greenland shark (Somniosus microcephalus).
We deployed a recoverable biologging package combining a VEMCO Mobile Transceiver (VMT), accelerometer and a temperature–depth tag to quantitatively assess fine‐scale behaviour during detection events, that is when sharks carrying the novel VMT package (animalR, n = 3) detected sharks independently tagged with transmitters in the system (animalT, n = 29). Concurrently, we developed simulations to estimate the distances between animalR and animalT by accounting for their swim speed, the estimated detection efficiency of the VMT and the number of consecutive transmissions recorded. Accelerometer‐derived activity indices were then used as a means to test for response to potential interactions when animals are expected to be in close proximity.
Based on this approach, the three VMT‐equipped Greenland sharks exhibited higher body acceleration and greater depth changes during detections, suggesting a potential behavioural response to the presence of other sharks. A generalized additive model indicated a moderate increasing relationship in activity associated with a greater number of animalT detections.
Through the proposed framework, detection events with varying probabilities of interaction likelihoods can be derived and those data isolated and explicitly tested using acceleration data to quantify behavioural interactions. Through inputting known parameters for a species of interest, the framework presented is applicable for all aquatic taxa and can guide future study design.
There exists a disparity in our ability to monitor interactions among aquatic species that do not surface. The authors present a new framework to quantify behavioural interactions among such marine organisms using a novel transceiver‐accelerometer package where events with varying probabilities of interaction likelihoods are tested against acceleration data to quantify behavioral responses.
Cardiovascular disease (CVD) and heart failure (HF) are major causes of mortality in low-income populations and differ by sex. Risk assessment that incorporates cardiac biomarkers is common. However, ...research evaluating the utility of biomarkers rarely includes controlled substances, which may influence biomarker levels and thus influence CVD risk assessment.
We identified the effects of multiple substances on soluble "suppression of tumorigenicity 2" (sST2), a biomarker of adverse cardiac remodelling, in 245 low-income women. Adjusting for CVD risk factors, we examined associations between substance use and sST2 over six monthly visits.
Median age was 53 years and 74% of participants were ethnic minority women. An sST2 level > 35 ng/mL (suggesting cardiac remodelling) during ≥1 study visit was observed in 44% of participants. In adjusted analysis, higher sST2 levels were significantly and positively associated with the presence of cocaine (Adjusted Linear Effect ALE:1.10; 95% CI:1.03-1.19), alcohol (ALE:1.10; 95% CI:1.04-1.17), heroin (ALE:1.25; 95% CI:1.10-1.43), and the interaction between heroin and fentanyl use.
Results suggest that the use of multiple substances influences the level of sST2, a biomarker often used to evaluate cardiovascular risk. Incorporating substance use alongside cardiac biomarkers may improve CVD risk assessment in vulnerable women.
Cocaine use has been linked to stroke in several studies. However, few studies have considered the influence of cocaine use on stroke mechanisms such as small vessel disease (SVD). We conducted a ...study to assess associations between the toxicology-confirmed use of multiple drugs, including cocaine, and a marker of SVD, white matter hyperintensities (WMH).
We conducted a nested case-control study (n = 30) within a larger cohort study (N = 245) of homeless and unstably housed women recruited from San Francisco community venues. Participants completed six monthly study visits consisting of an interview, blood draw, vital sign assessment and baseline brain MRI. We examined associations between toxicology-confirmed use of multiple substances, including cocaine, methamphetamine, heroin, alcohol and tobacco, and WMH identified on MRI.
Mean study participant age was 53 years, 70% of participants were ethnic minority women and 86% had a history of cocaine use. Brain MRIs indicated the presence of WMH (i.e., Fazekas score>0) in 54% (18/30) of imaged participants. The odds of WMH were significantly higher in women who were toxicology-positive for cocaine (Odd Ratio=7.58, p=0.01), but not in women who were toxicology-positive for other drugs or had several other cerebrovascular risk factors.
Over half of homeless and unstably housed women showed evidence of WMH. Cocaine use is highly prevalent and a significant correlate of WMH in this population, while several traditional CVD risk factors are not. Including cocaine use in cerebrovascular risk calculators may improve stroke risk prediction in high-risk populations and warrants further investigation.
Literature suggests that female athletes receive less coverage in media than male athletes and that representation more often focuses on femininity than athleticism. Yet factors other than gender may ...influence media representation. Race and gender of target readers may impact representation of female athletes. This study reports the results of a content analysis of representations of white and black female athletes in 92 magazines. Representations of black female and white female athletes in Sports Illustrated, Sports Illustrated for Women and Her Sports from two different time periods, 2000-2002 and 2004-2008, were compared. Results reveal that the race of the female athlete and the gender of the reading audience affect the depiction of the athlete as primarily athletic or feminine. Keywords: Female athlete, Race, Magazine Images, Content Analysis, Representation
Cancer vaccines strive to induce robust, antigen‐targeted, T‐cell‐mediated immune responses but have struggled to produce meaningful regression in solid tumors. An autologous cell vaccine, ...SQZ‐PBMC‐HPV, was developed by SQZ Biotechnologies using microfluidic squeezing technology to load PBMCs with HPV16 E6 and E7 antigens in HLA‐A*02+ patients. The SQZ‐PBMC‐HPV‐101 Phase 1 trial (NCT04084951) enrolled patients with incurable HPV16+ cancers. Here, we present a post hoc analysis of the relationship between Posttreatment CD8+ T cell infiltration and patient outcomes. SQZ‐PBMC‐HPV was administered as monotherapy every 3 weeks. Tumor samples were collected pre‐dose and post‐dose 4 weeks after treatment start. Biomarkers including CD8, MHC‐I, E6, E7, GZMB, and Ki67 were evaluated by immunohistochemistry, immunofluorescence, and RNA in situ hybridization, and were correlated with clinical response, survival, and drug product composition. Eighteen patients had paired pre‐ and post‐dose biopsies. Six (33%) had an increase in CD8+ T cell density in tumor parenchyma between screening and C2D8. Patients with increased CD8+ T cell density had improved disease control rate (66.7% vs 16.7%) and median overall survival (606.5 days vs 170.0 days, p = 0.0078). Drug product was significantly enriched for higher T cells and lower monocytes in the increased CD8+ T cell density group. In patients with incurable HPV16+ solid tumors treated with SQZ‐PBMC‐HPV, an increase in CD8+ T cell density within the tumor parenchyma was associated with superior disease control rate and overall survival. The product composition for patients with increased CD8+ T cell density was enriched for T cells.
Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up ...analysis of 822 variants with P < 1 × 10
in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10
) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.
In the largest E3 ligase subfamily, Cul3 binds a BTB domain, and an associated protein-interaction domain such as MATH recruits substrates for ubiquitination. Here, we present biochemical and ...structural analyses of the MATH-BTB protein, SPOP. We define a SPOP-binding consensus (SBC) and determine structures revealing recognition of SBCs from the phosphatase Puc, the transcriptional regulator Ci, and the chromatin component MacroH2A. We identify a dimeric SPOP-Cul3 assembly involving a conserved helical structure C-terminal of BTB domains, which we call “3-box” due to its facilitating Cul3 binding and its resemblance to F-/SOCS-boxes in other cullin-based E3s. Structural flexibility between the substrate-binding MATH and Cul3-binding BTB/3-box domains potentially allows a SPOP dimer to engage multiple SBCs found within a single substrate, such as Puc. These studies provide a molecular understanding of how MATH-BTB proteins recruit substrates to Cul3 and how their dimerization and conformational variability may facilitate avid interactions with diverse substrates.
Modelling suggests that achieving the World Health Organization’s elimination targets for hepatitis C virus (HCV) is possible by scaling up use of direct-acting antiviral (DAA) therapy. However, poor ...linkage to health services and retention in care presents a major barrier, in particular among people who inject drugs (PWID). We identify and assess the cost-effectiveness of additional health system interventions required to achieve HCV elimination targets in Australia, a setting where all people living with HCV have access to DAA therapy.
We used a dynamic HCV transmission and liver-disease progression mathematical model among current and former PWID, capturing testing, treatment and other features of the care cascade. Interventions tested were: availability of point-of-care RNA testing; increased testing of PWID; using biomarkers in place of liver stiffness measurement; and scaling up primary care treatment delivery.
The projected treatment uptake in Australia reduced the number of people living with HCV from approximately 230,000 in 2015 to approximately 24,000 by 2030 and reduced incidence by 45%. However, the majority (74%) of remaining infections were undiagnosed and among PWID. Scaling up primary care treatment delivery and using biomarkers in place of liver stiffness measurement only reduced incidence by a further 1% but saved AU$32 million by 2030, with no change to health outcomes. Additionally replacing HCV antibody testing with point-of-care RNA testing increased healthcare cost savings to AU$62 million, increased incidence reduction to 64% and gained 11,000 quality-adjusted life years, but critically, additional screening of PWID was required to achieve HCV elimination targets.
Even with unlimited and unrestricted access to HCV DAA treatment, interventions to improve the HCV cascade of care and target PWID will be required to achieve elimination targets.
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