Significant range extensions for two fish species at Pitcairn Island, South Pacific

A baited videographic survey at Pitcairn Island has significantly extended the known range for two reef-fish species: blue-lined triggerfish Xanthichthys caeruleolineatus and greater amberjack Seriola dumerili, with an additional minor extension noted for giant trevally Caranx ignobilis. This highlights the importance of further research in this remote, poorly studied island group and provides evidence supplementing the understanding of oceanographic patterns in the South Pacific

Perceptual Context in Cognitive Hierarchies

Cognition does not only depend on bottom-up sensor feature abstraction, but also relies on contextual information being passed top-down. Context is higher level information that helps to predict belief states at lower levels. The main contribution of this paper is to provide a formalisation of perceptual context and its integration into a new process model for cognitive hierarchies. Several simple instantiations of a cognitive hierarchy are used to illustrate the role of context. Notably, we demonstrate the use context in a novel approach to visually track the pose of rigid objects with just a 2D camera

Alternative reconstruction after pancreaticoduodenectomy

<p>Abstract</p> <p>Background</p> <p>Pancreaticoduodenectomy is the procedure of choice for tumors of the head of the pancreas and periampulla. Despite advances in surgical technique and postoperative care, the procedure continues to carry a high morbidity rate. One of the most common morbidities is delayed gastric emptying with rates of 15%–40%. Following two prolonged cases of delayed gastric emptying, we altered our reconstruction to avoid this complication altogether. Subsequently, our patients underwent a classic pancreaticoduodenectomy with an undivided <it>Roux-en-Y </it>technique for reconstruction.</p> <p>Methods</p> <p>We reviewed the charts of our last 13 Whipple procedures evaluating them for complications, specifically delayed gastric emptying. We compared the outcomes of those patients to a control group of 15 patients who underwent the Whipple procedure with standard reconstruction.</p> <p>Results</p> <p>No instances of delayed gastric emptying occurred in patients who underwent an undivided <it>Roux-en-Y </it>technique for reconstruction. There was 1 wound infection (8%), 1 instance of pneumonia (8%), and 1 instance of bleeding from the gastrojejunal staple line (8%). There was no operative mortality.</p> <p>Conclusion</p> <p>Use of the undivided <it>Roux-en-Y </it>technique for reconstruction following the Whipple procedure may decrease the incidence of delayed gastric emptying. In addition, it has the added benefit of eliminating bile reflux gastritis. Future randomized control trials are recommended to further evaluate the efficacy of the procedure.</p

Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome.

Consistent evidence is accumulating to link lower socioeconomic position (SEP) and poorer health, and the inflammatory system stands out as a potential pathway through which socioeconomic environment is biologically embedded. Using bloodderived genome-wide transcriptional profiles from 268 Italian participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we evaluated the association between early life, young and later adulthood SEP and the expression of 845 genes involved in human inflammatory responses. These were examined individually and jointly using several inflammatory scores. Our results consistently show that participants whose father had a manual (as compared to nonmanual) occupation exhibit, later in life, a higher inflammatory score, hence indicating an overall increased level of expression for the selected inflammatory-related genes. Adopting a life course approach, these associations remained statistically significant upon adjustment for later-in-life socioeconomic experiences. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated, and were replicated in an independent study. Our study provides additional evidence that childhood SEP is associated with a sustainable upregulation of the inflammatory transcriptome, independently of subsequent socioeconomic experiences. Our results support the hypothesis that early social inequalities impacts adult physiology

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.

BackgroundT cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.MethodsPatients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 1010 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72.ResultsFourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14&nbsp;weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48&nbsp;weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed.ConclusionThese findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity

The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules

Recent studies have demonstrated that the CD3-ζ subunit of the T cell antigen receptor (TCR) complex is involved in signal transduction. However, the function of the remaining invariant subunits, CD3-γ, -δ, and , is still poorly understood. To examine their role in TCR function, we have constructed TCR/CD3 complexes devoid of functional ζ subunit and showed that they are still able to trigger the production of interleukin-2 in response to antigen or superantigen. These data, together with previous results, indicate that the TCR/CD3 complex is composed of at least two parallel transducing units, made of the γδ and ζ chains, respectively, Furthermore, the analysis of partially truncated ζ chains has led us to individualize a functional domain that may have constituted the building block of most of the transducing subunits associated with antigen receptors and some Fc receptors

SARS Coronavirus-2 Microneutralisation and Commercial Serological Assays Correlated Closely for Some but Not All Enzyme Immunoassays

Serological testing for SARS-CoV-2-specific antibodies provides important research and diagnostic information relating to COVID-19 prevalence, incidence and host immune response. A greater understanding of the relationship between functionally neutralising antibodies detected using microneutralisation assays and binding antibodies detected using scalable enzyme immunoassays (EIA) is needed in order to address protective immunity post-infection or vaccination, and assess EIA suitability as a surrogate test for screening of convalescent plasma donors. We assessed whether neutralising antibody titres correlated with signal cut-off ratios in five commercially available EIAs, and one in-house assay based on expressed spike protein targets. Sera from recovered patients or convalescent plasma donors who reported laboratory-confirmed SARS-CoV-2 infection (n = 200), and negative control sera collected prior to the COVID-19 pandemic (n = 100), were assessed in parallel. Performance was assessed by calculating EIA sensitivity and specificity with reference to microneutralisation. Neutralising antibodies were detected in 166 (83%) samples. Compared with this, the most sensitive EIAs were the Cobas Elecsys Anti-SARS-CoV-2 (98%) and Vitros Immunodiagnostic Anti-SARS-CoV-2 (100%), which detect total antibody targeting the N and S1 antigens, respectively. The assay with the best quantitative relationship with microneutralisation was the Euroimmun IgG. These results suggest the marker used (total Ab vs. IgG vs. IgA) and the target antigen are important determinants of assay performance. The strong correlation between microneutralisation and some commercially available assays demonstrates their potential for clinical and research use in assessing protection following infection or vaccination, and use as a surrogate test to assess donor suitability for convalescent plasma donation

Patient preferences for the allocation of deceased donor kidneys for transplantation: a mixed methods study

<p>Abstract</p> <p>Background</p> <p>Deceased donor kidneys are a scarce health resource, yet patient preferences for organ allocation are largely unknown. The aim of this study was to determine patient preferences for how kidneys should be allocated for transplantation.</p> <p>Methods</p> <p>Patients on dialysis and kidney transplant recipients were purposively selected from two centres in Australia to participate in nominal/focus groups in March 2011. Participants identified and ranked criteria they considered important for deceased donor kidney allocation. Transcripts were thematically analysed to identify reasons for their rankings.</p> <p>Results</p> <p>From six groups involving 37 participants, 23 criteria emerged. Most agreed that matching, wait-list time, medical urgency, likelihood of surviving surgery, age, comorbidities, duration of illness, quality of life, number of organs needed and impact on the recipient's life circumstances were important considerations. Underpinning their rankings were four main themes: enhancing life, medical priority, recipient valuation, and deservingness. These were predominantly expressed as achieving equity for all patients, or priority for specific sub-groups of potential recipients regarded as more "deserving".</p> <p>Conclusions</p> <p>Patients believed any wait-listed individual who would gain life expectancy and quality of life compared with dialysis should have access to transplantation. Equity of access to transplantation for all patients and justice for those who would look after their transplant were considered important. A utilitarian rationale based on maximizing health gains from the allocation of a scarce resource to avoid "wastage," were rarely expressed. Organ allocation organisations need to seek input from patients who can articulate preferences for allocation and advocate for equity and justice in organ allocation.</p

Education, biological ageing, all-cause and cause-specific mortality and morbidity : UK biobank cohort study

Background: Socioeconomic position as measured by education may be embodied and affect the functioning of key physiological systems. Links between social disadvantage, its biological imprint, and cause-specific mortality and morbidity have not been investigated in large populations, and yet may point towards areas for public health interventions beyond targeting individual behaviours. Methods: Using data from 366,748 UK Biobank participants with 13 biomarker measurements, we calculated a Biological Health Score (BHS, ranging from 0 to 1) capturing the level of functioning of five physiological systems. Associations between BHS and incidence of cardiovascular disease (CVD) and cancer, and mortality from all, CVD, cancer, and external causes were examined. We explored the role of education in these associations. Mendelian randomisation using genetic evidence was used to triangulate these findings. Findings: An increase in BHS of 0.1 was associated with all-cause (HR = 1.14 [1.12–1.16] and 1.09 [1.07–1.12] in men and women respectively), cancer (HR = 1.11 [1.09–1.14] and 1.07 [1.04–1.10]) and CVD (HR = 1.25 [1.20–1.31] and 1.21 [1.11–1.31]) mortality, CVD incidence (HR = 1.15 [1.13–1.16] and 1.17 [1.15–1.19]). These associations survived adjustment for education, lifestyle-behaviours, body mass index (BMI), co-morbidities and medical treatments. Mendelian randomisation further supported the link between the BHS and CVD incidence (HR = 1.31 [1.21–1.42]). The BHS contributed to CVD incidence prediction (age-adjusted C-statistic = 0.58), other than through education and health behaviours. Interpretation: The BHS captures features of the embodiment of education, health behaviours, and more proximal unknown factors which all complementarily contribute to all-cause, cancer and CVD morbidity and premature death. © 2020 The Author(s)Peer reviewe