Characterizing pre-transplant and post-transplant kidney rejection risk by B cell immune repertoire sequencing.

Studying immune repertoire in the context of organ transplant provides important information on how adaptive immunity may contribute and modulate graft rejection. Here we characterize the peripheral blood immune repertoire of individuals before and after kidney transplant using B cell receptor sequencing in a longitudinal clinical study. Individuals who develop rejection after transplantation have a more diverse immune repertoire before transplant, suggesting a predisposition for post-transplant rejection risk. Additionally, over 2 years of follow-up, patients who develop rejection demonstrate a specific set of expanded clones that persist after the rejection. While there is an overall reduction of peripheral B cell diversity, likely due to increased general immunosuppression exposure in this cohort, the detection of specific IGHV gene usage across all rejecting patients supports that a common pool of immunogenic antigens may drive post-transplant rejection. Our findings may have clinical implications for the prediction and clinical management of kidney transplant rejection

Phasic oxygen dynamics confounds fast choline-sensitive biosensor signals in the brain of behaving rodents

Cholinergic fast time-scale modulation of cortical physiology is critical for cognition, but direct local measurement of neuromodulators in vivo is challenging. Choline oxidase (ChOx)-based electrochemical biosensors have been used to capture fast cholinergic signals in behaving animals. However, these transients might be biased by local field potential and O2-evoked enzymatic responses. Using a novel Tetrode-based Amperometric ChOx (TACO) sensor, we performed highly sensitive and selective simultaneous measurement of ChOx activity (COA) and O2. In vitro and in vivo experiments, supported by mathematical modeling, revealed that non-steady-state enzyme responses to O2 give rise to phasic COA dynamics. This mechanism accounts for most of COA transients in the hippocampus, including those following locomotion bouts and sharp-wave/ripples. Our results suggest that it is unfeasible to probe phasic cholinergic signals under most behavioral paradigms with current ChOx biosensors. This confound is generalizable to any oxidase-based biosensor, entailing rigorous controls and new biosensor designs

Negations in uncertainty lexicon affect attention, decision-making and trust

The Intergovernmental Panel on Climate Change (IPCC) currently communicates uncertainty using a lexicon that features four negative verbal probabilities to convey extremely low to medium probabilities (e.g., unlikely). We compare a positive probability lexicon with the IPCC lexicon in a series of psychology experiments. We find that although the positive and negative lexicons convey a similar level of probability, the positive lexicon directs more attention towards the outcome occurrence, and encourages more cautious decisions: in our role-playing experiment it reduced the number of Type 2 errors, i.e. failures to make needed precautionary interventions. Whilst participants considered the negative lexicon more useful in making a decision, they trusted the positive lexicon more and blamed information providers less after making an incorrect decision. Our results suggest that the negative verbal framing of probabilities used by the IPCC is not neutral and has implications for how climate information is interpreted by decision-makers

Determinants of satisfaction with information and additional information-seeking behaviour for the pertussis vaccination given during pregnancy

Objectives: Information search and processing is critical to the vaccine decision-making process. However, the role of drivers of information satisfaction and search is not fully understood. Here, we investigated the predictive potential of psychosocial characteristics related to satisfaction with information and additional information-seeking about the pertussis vaccine currently recommended during pregnancy. Design: Cross-sectional online questionnaire study. Methods: A UK based sample of 314 women who had given birth during the previous six months was recruited to participate. The questionnaire included measures of the psycho-social predictors: trust, coping strategies, attitude towards vaccine information-seeking behaviour and risk perception of vaccination during pregnancy, and measures of two outcome variables: satisfaction with information received from a health care professional and whether participants engaged in vaccine information-seeking behaviour. Results: Trust in health care professionals, a perceived behavioural control of own vaccine information-seeking behaviour, and an engaged problem-focused strategy for coping with stress were significant predictors of satisfaction with official information given by a health care professional. 40% of women sought out additional information about vaccination however, none of the psychosocial factors measured significantly predicted the behaviour. Conclusions: We found that high trust in health care professionals, a perceived ability to seek out accurate information about vaccines and actively focusing on problems as a means of coping with stress, drives satisfaction in official vaccine information. We also developed measures of these variables that could be used in further research