Immunologic Risk Prediction Model for Kidney Graft Function

Clinicians lack appropriate non-invasive methods to be able to predict, diagnose, and reduce the risk of rejection in the years following kidney transplantation. Protocol biopsies and monitoring of serum creatinine levels are the most common methods of monitoring graft function after transplant; however, they have several negative aspects. Use of traditional factors regarding donors and recipients such as Human Leukocyte Antigen (HLA) DNA typing, pre-transplant anti-HLA antibody levels, and basic demographics (age, ethnicity/race, gender), has proved inadequate for post-transplant graft monitoring past the first few years. We propose that by utilizing immunologic factors available to clinicians across the United States, development of a non-invasive model for predicting renal graft outcome will provide a useful tool for post-transplant patient monitoring. We advocate an expanded model which incorporates both the traditional factors, as well as new factors, which have shown promise in predicting kidney outcome and are widely available for testing using commercial kits. These additional factors include major histocompatibility complex class I chain-related gene A (MICA) typing of donor and recipient, degree of matching for killer cell immunoglobulin-like receptors (KIRs) between donor and recipient, detection of MICA antibodies, and soluble CD30 level (sCD30). This proposed graft-function prediction model is the first to include all of these factors. Using multi-center data from adult recipients of standard-criteria deceased-donor (SCD) kidneys, we were able to construct models, containing the traditional factors only, for prediction of outcome at 1 year and 3 years post-transplant. Using single-center data from adult recipients of standard-criteria deceased-donor kidneys, we developed comparison models containing traditional factors only, as well as, expanded models containing the new suggested variables for prediction of outcome post-transplant. These additional variables, when incorporated into the expanded models provided greater positive predictive values, greater negative predictive values, and lower false negative rates for graft outcome at 1 year and at 3 years post-transplant than the models utilizing traditional factors only. Our results indicate that evaluation of sCD30, MICA and KIR as part of routine protocol testing, is helpful to clinicians for predicting risk of kidney graft rejection

D2 Strategy for the Development of the Mentorship Programme

After three rounds of the CESSDA Mentorship Programme and with experiences from twenty mentorships, it is time to evaluate the programme and see how it can be further developed. The overall conclusion is that the programme has fulfilled its purpose but could benefit from more flexibility. Experience shows that circumstances can change quickly, from delayed decisions on institutionalising to pandemics, which requires an ability to quickly adjust established plans and reallocate resources. It would also be an advantage for the programme to have a wider range of experts to choose from when appointing mentors. Until now, the programme has only been open to CESSDA partners and new members. It would benefit from being open to all CESSDA SPs, regardless of their level of maturity. More mature SPs who want to develop new services could then seek support from, and collaboration with, colleagues with more expertise in the field. The new concept of the Mentorship programme is intended to be an asset to CESSDA and all its member and partner SPs by facilitating the exchange of general and specialised expertise. To achieve that, the programme needs a solid foundation and sustainability of mentorship within CESSDA ERIC

Early life Stress and Social Isolation as a Two-Hit Model for Examining Extinction Learning in Fear and Motivational Contexts

An essential component of understanding mental health is uncovering individual risk factors increasing vulnerability to stress-related disorders. Stress can distinctly alter the developing brain, impacting the ability to respond appropriately to future stress and reward learning. Adulthood stress, through factors like social isolation, may impact behaviors related to motivation. These two factors, early life stress (ELS) and social isolation, critically interact; ELS leaves individuals particularly vulnerable to the effects of adulthood social isolation while social enrichment may ameliorate behavioral deficits demonstrated by ELS. Prior work from our lab using a brief wet bedding stressor on postnatal day 5 (P5) was sufficient to produce persistent fear in adults in a conditioned suppression paradigm (Bercum et al. 2021; 2023). However, the previous study did not compare sex differences, nor did they separately compare the effects of reward versus fear extinction. In our study, male and female pups were exposed to early life stress (ELS) from P2-P10 using a limited bedding approach and brief saturated bedding. We separated cohorts into either paired or isolated housing. In adulthood, we conducted a series of assays to examine the effects of ELS and socialization within-subject: (1) instrumental reward learning, (2) fear acquisition, (3) fear extinction, (4) fear renewal, (5) conditioned suppression, (6) reward extinction. We observed sex-related differences based on ELS exposure and/or socialization. During fear learning and extinction, female ELS rats showed elevated fear relative to female controls, while males in ELS and control groups were similar. In both sexes, socialized animals displayed unimpaired extinction learning while isolated animals demonstrated spontaneous recovery and heightened fear behavior. Our data suggest that experiencing ELS paired with social isolation may have distinct and sex-dependent impacts on adult vulnerability to stress disorders while socialization offers a rescuing effect.</p

PaLA Virtual Journal Club: Providing Opportunities for Reflection, Improvement, and Connections

A journal club is one means for those in similar professions or practices to read, discuss, and keep up with professional literature with colleagues. Journal clubs are most frequently associated with the medical professions; however, many professionals, including librarians, can benefit from the reading of research and the subsequent discussions and camaraderie that a journal club can elicit. This article describes the launch of a statewide virtual journal club for librarians in Pennsylvania. Now in its third series, the Pennsylvania Library Association (PaLA) College & Research Division (CRD) journal club has given those who’ve participated the opportunity to designate time for professional reading, reflect on personal practice, discuss and exchange theoretical and practical ideas, and connect with librarians across the state

Syntactic development in early foreign language learning: Effects of L1 transfer, input and individual factors

This study explores parallels and differences in the comprehension of wh-questions and relative clauses between early foreign-language (FL) learners and monolingual children. We test for (a) effects of syntactic first-language (L1) transfer, (b) the impact of input on syntactic development, and (c) the impact of individual differences on early FL syntactic development. We compare the results to findings in child second language (L2) naturalistic acquisition and adult FL acquisition. Following work on adult FL acquisition, we carried out a picture-based interpretation task with 243 child FL learners in fourth grade at different regular, partial, and high-immersion schools in Germany plus 68 monolingual English children aged 5 to 8 years as controls. The child FL learners display a strong subject-first preference but do not appear to use the L1 syntax in comprehension. Input differences across different schools affect overall accuracy, with students at high-immersion FL schools catching up to monolingual performance within 4 years of learning. Finally, phonological awareness is implicated in both early FL learning and naturalistic child L2 development. These findings suggest that early FL development resembles child L2 acquisition in speed and effects of individual factors, yet is different from adult FL acquisition due to the absence of L1 transfer effects.Peer reviewedFinal Accepted Versio

Multiple mineral horizons in layered outcrops at Mawrth Vallis, Mars, signify changing geochemical environments on early Mars

Refined calibrations of CRISM images are enabling identification of smaller deposits of unique aqueous materials on Mars that reveal changing environmental conditions at the region surrounding Mawrth Vallis. Through characterization of these clay-sulfate assemblages and their association with the layered, phyllosilicate units of this region, more details of the aqueous geochemical history can be gleaned. A stratigraphy including five distinct mineral horizons is mapped using compositional data from CRISM over CTX and HRSC imagery across 100s of km and from CRISM over HiRISE imagery across 100s of meters. Transitions in mineralogic units were characterized using visible/near-infrared (VNIR) spectral properties and surface morphology. We identified and characterized complex “doublet” type spectral signatures with two bands between 2.2 and 2.3 μm at one stratigraphic horizon. Based on comparisons with terrestrial sites, the spectral “doublet” unit described here may reflect the remnants of a salty, evaporative period that existed on Mars during the transition from formation of Fe-rich phyllosilicates to Al-rich phyllosilicates. Layered outcrops observed at Mawrth Vallis are thicker than in other altered regions of Mars, but may represent processes that were more widespread in wet regions of the planet during its early history. The aqueous geochemical environments supporting the outcrops observed here include: (i) the formation of Fe3+-rich smectites in a warm and wet environment, (ii) overlain by a thin ferrous-bearing clay unit that could be associated with heating or reducing conditions, (iii) followed by a transition to salty and/or acidic alteration phases and sulfates (characterized by the spectral “doublet” shape) in an evaporative setting, (iv) formation of Al-rich phyllosilicates through pedogenesis or acid leaching, and (v) finally persistence of poorly crystalline aluminosilicates marking the end of the warm climate on early Mars. The “doublet” type units described here are likely composed of clay-sulfate assemblages formed in saline, acidic evaporative environments similar to those found in Western Australia and the Atacama desert. Despite the chemically extreme and variable waters present at these terrestrial, saline lake environments, active ecosystems are present; thus, these “doublet” type units may mark exciting areas for continued exploration important to astrobiology on Mars

Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.

Background:Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods:The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results:A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P &lt; .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Conclusions:Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors

The protective effects of social bonding on behavioral and pituitary-adrenal axis reactivity to chronic mild stress in prairie voles.

Positive social interactions may protect against stress. This study investigated the beneficial effects of pairing with a social partner on behaviors and neuroendocrine function in response to chronic mild stress (CMS) in 13 prairie vole pairs. Following 5 days of social bonding, male and female prairie voles were exposed to 10 days of CMS (mild, unpredictable stressors of varying durations, for instance, strobe light, white noise, and damp bedding), housed with either the social partner (paired group) or individually (isolated group). Active and passive behavioral responses to the forced swim test (FST) and tail-suspension test (TST), and plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone, were measured in all prairie voles following the CMS period. Both female and male prairie voles housed with a social partner displayed lower durations of passive behavioral responses (immobility, a maladaptive behavioral response) in the FST (mean ± SEM; females: 17.3 ± 5.4 s; males: 9.3 ± 4.6 s) and TST (females: 56.8 ± 16.4 s; males: 40.2 ± 11.3 s), versus both sexes housed individually (females, FST: 98.6 ± 12.9 s; females, TST: 155.1 ± 19.3 s; males, FST: 92.4 ± 14.1 s; males, TST: 158.9 ± 22.0 s). Female (but not male) prairie voles displayed attenuated plasma stress hormones when housed with a male partner (ACTH: 945 ± 24.7 pg/ml; corticosterone: 624 ± 139.5 ng/ml), versus females housed individually (ACTH: 1100 ± 23.2 pg/ml; corticosterone: 1064 ± 121.7 ng/ml). These results may inform understanding of the benefits of social interactions on stress resilience. Lay Summary: Social stress can lead to depression. The study of social bonding and stress using an animal model will inform understanding of the protective effects of social bonds. This study showed that social bonding in a rodent model can protect against behavioral responses to stress, and may also be protective against the elevation of stress hormones. This study provides evidence that bonding and social support are valuable for protecting against stress in humans

Advancing participatory energy systems modelling

Energy system models are important tools to guide our understanding of current and future carbon dioxide emissions as well as to inform strategies for emissions reduction. These models offer a vital evidence base that increasingly underpins energy and climate policies in many countries. In light of this important role in policy formation, there is growing interest in, and demands for, energy modellers to integrate more diverse perspectives on possible and preferred futures into the modelling process. The main purpose of this is to ensure that the resultant policy decisions are both fairer and better reflect people's concerns and preferences. However, while there has been a focus in the literature on efforts to bring societal dimensions into modelling tools, there remains a limited number of examples of well-structured participatory energy systems modelling processes and no available how-to guidance. This paper addresses this gap by providing good practice guidance for integrating stakeholder and public involvement in energy systems modelling based on the reflections of a diverse range of experts from this emergent field. The framework outlined in this paper offers multiple entry points for modellers to incorporate participatory elements either throughout the process or in individual stages. Recognising the messiness of both fields (energy systems modelling and participatory research), the good practice principles are not comprehensive or set in stone, but rather pose important questions to steer this process. Finally, the reflections on key issues provide a summary of the crucial challenges and important areas for future research in this critical field

Assessing knowledge about acupuncture: A survey of people with back pain in the UK.

OBJECTIVES: Despite the prevalence of acupuncture treatment in the UK, and the increasing evidence of safety and effectiveness, the information presented to patients by practitioners frequently contains inaccuracies. As knowledge of treatment affects both patient decision-making and treatment outcomes, this study aimed to establish what is known about acupuncture in a sample of people who had, and had not, previously experienced acupuncture. DESIGN: A 15-item questionnaire was constructed to assess knowledge of acupuncture. SETTING: Online survey of people with a history of back pain. RESULTS: 202 participants completed the questionnaire. 66.8% of the sample was female and 33.2% male, with a mean age of 35 years (range 18-74 years). 87.6% had back pain in the past six months, 44.1% currently. 21.8% had previously received acupuncture, and 69.8% had previously read or heard information about acupuncture. On average participants answered 11.03 of 15 questions about acupuncture correctly (SD=2.64). Items relating to common concerns about acupuncture, acupuncture efficacy, and types of acupuncture were correctly answered by ≥80% of participants. Participants possessed less knowledge of accessibility, Government legislation, and methods of administration. CONCLUSIONS: The study identified key gaps in knowledge about acupuncture among patients. In particular, many participants were unaware that acupuncture is available from the UK National Health Service and that acupuncturists are not subject to statutory regulation in the UK. These knowledge gaps should be addressed in order to increase people's understanding of and access to acupuncture