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Hair is a ubiquitous and robust mammalian tissue with biological, clinical, forensic, social, and economic significance. The hair shaft proteome reflects both structural proteins, dominated by cuticular intermediate filament keratins and associated proteins, and proteins involved in the final cellular processes of terminally differentiating corneocytes prior to cornification. These distinct biological processes involve cell maintenance, biosynthesis, senescence, and xenobiotic response. Because growth occurs rapidly and predictably, there is also temporal organization. The hair shaft proteome also contains genetic and phylogenetic information in the amino acid sequence. Chemically the shaft is highly robust, the result of a highly structured protein matrix with abundant isopeptide and disulfide intermolecular bonds. Sample processing is therefore a challenge that requires robust chemistries but also minimizes the introduction of additional chemical modifications. This protocol depends on the combination of sodium dodecanoate and high levels of reductant to denature the matrix. The result is a proteome that is both readily accessible and can provide biological information to geneticists, developmental biologists, toxicologists, human and wildlife forensic scientists, scientists in the cosmetics industry, and wildlife ecologists.

Background: Long-term care services are funded primarily by Medicaid long-term services and support in the United States, where eligibility is based on care needs of the individual with intellectual and developmental disability alone. Impact of Medicaid waiver services on self-reported caregiver needs is not well understood. Method: Caregivers (n = 405) of individuals with intellectual and developmental disabilities across four states (NY, OH, TX, and PA) completed an online survey. Results: Caregivers reported a moderate degree of burden and susceptibility of stress-induced health breakdown. Despite controlling for the activities of daily living of the care recipient, caregivers of individuals with Medicaid Waiver services reported greater difficulty managing medications (p = 0.013) and finding paid help (p < 0.001) than caregivers of individuals without services.

Health emerges from coordinated psychobiological processes powered by mitochondrial energy transformation. But how do mitochondria regulate the multisystem responses that shape resilience and disease risk across the lifespan? The Mitochondrial Stress, Brain Imaging, and Epigenetics (MiSBIE) study was established to address this question and determine how mitochondria influence the interconnected neuroendocrine, immune, metabolic, cardiovascular, cognitive, and emotional systems among individuals spanning the spectrum of mitochondrial energy transformation capacity, including participants with rare mitochondrial DNA (mtDNA) lesions causing mitochondrial diseases (MitoDs). This interdisciplinary effort is expected to generate new insights into the pathophysiology of MitoDs, provide a foundation to develop novel biomarkers of human health, and integrate our fragmented knowledge of bioenergetic, brain-body, and mind-mitochondria processes relevant to medicine and public health.

Support for school-age children with speech, language and communication needs (SLCN) usually takes place within the school setting. Successful outcomes for children with SLCN rely on effective collaborative working between speech and language therapists (SLTs), school staff and families. We need to understand the current evidence regarding the joint working practices, relationships and collaboration experiences of SLT and teaching staff within mainstream primary schools, in order to identify whether sufficient research exists for a systematic review within this field, and to inform practice. The purpose of this scoping review was to identify what research currently exists regarding collaboration, roles and relationships of SLTs and teaching staff within mainstream UK primary schools, and clarify the nature, participants and concepts described within this literature. A scoping review framework was used, consisting of identification of the review objectives, identification of relevant studies, study selection and iterative searches, data charting and reporting of the results. Information regarding research question, participants, data collection and analysis and terms used for key concepts was extracted. This scoping review identified 14 papers, however, collaboration was the primary focus of only 5 of these. Clarity and perceptions of roles were key themes within six of the papers. Whilst facilitators and barriers to collaboration are discussed in all 14 papers, only 4 studies aimed to investigate barriers and facilitators. Teaching assistant (TA) views are underrepresented within the research. Drawing conclusions from the body of research is challenging due to the varied ways in which the key concept 'collaboration' is used. Currently, there is insufficient literature to carry out a systematic review. This scoping review highlights the need for research that considers collaboration within the complex social network of school staff (including TAs) and SLTs, in order to ensure that future guidance is rooted in research.

Theoretical roots of higher education institutions (HEIs) and Stakeholder Analysis date back to mid-1990s and research was focussed on the role of HEIs in society and sustainable development. While various studies have been published about 'triple-helix model' - bringing government, academia, and industry closer, the concept of HEIs and Stakeholder Analysis needs a comprehensive review of the work carried out till date. Bibliometric and content analyses were performed, incorporating citations from Scopus' database during last 25 years. Thematic mapping was carried out and evolving trends were identified. Findings and analysis of this research disclosed that during the last 25 years there has been a growing interest among scholars towards Stakeholder Analysis and HEIs. It was also noted that majority of research pursuits concentrated in western countries such as USA and UK, while Africa, Asia and South America were under-represented. This work will not only lay a foundation for academics to carry out further research, but it will also give new insights to the policymakers which would enable them to device strategies aiming at enhanced participation of universities/HEIs in the local, regional, and national development.

Hemingway's story 'Hills Like White Elephants' is filled with twosomes. Indeed, the title itself presents a pair: 'Hills' like 'White Elephants.' It is a natural temptation, when confronted with such couplings, to choose one or the other: either the Hills or the White Elephants. This temptation passes something crucial by, though--namely, the 'like.' This paper argues--through a healthy dose of psychoanalysis--that in this story Hemingway is attempting to heed these in-between third terms, of which the simile is one, to tarry with them, and to refrain from choosing one of the pair over the other. KEYWORDS: Simile, Lacan, Psychoanalysis, 'For all of us, grave or light, get our thoughts tangled in metaphors, and act fatally on the strength of them.' --George Eliot, Middlemarch In an essay published over sixty [...]

Structured oral examinations (SOEs) result in higher test scores than traditional written assessments, but there lacks reproducible quantitative evidence supporting knowledge acquisition and retention. A modified SOE--called the One2One--whereby students present prepared answers to an instructor was evaluated for effectiveness in large classes despite its resource-intensive nature. This study used a post-assessment survey (Efficacy Assessment Survey, EAS) to measure the effect of the One2One on knowledge acquisition and retention, as well as student perceptions of its usefulness and perceived value. The One2One helped students learn and retain content better than by didactic lecture alone as demonstrated by significantly higher scores on One2One content as compared to control content (p<0.05) on the EAS (t-test) and this knowledge was retained until the end of the semester as measured by regression analysis. A previously identified drawback of SOEs is student-reported anxiety, however students' perception of the SOEs' usefulness and value are understudied. Here, thematic analysis of student feedback identified the One2One as being useful, a driver of learning, and of high professional value, albeit stressful. Though more resource intensive than traditional assessment methods, the One2One is a positively rated, authentic evaluation tool that motivates student learning.

There has been considerable interest exploring how the utility of an outcome impacts the probability with which it is mentally simulated. Earlier studies using varying methodologies have yielded divergent conclusions with different directions of the influence. To directly examine such mental process, we employed a random generation paradigm in which all the outcomes were either equally (i.e., followed a uniform distribution) or unequally (i.e., a binomial distribution) probable. While our results revealed individual differences in how the utility influenced responses, the overall findings suggested that it is the outcomes' probabilities, not their utilities, that guide this process. Notably, an initial utility-independent bias emerged, with individuals displaying a tendency to start with smaller values when all outcomes are equally likely. Our findings offer insights into the benefits of studying the mental sampling processes and provide empirical support for particular sampling models in this domain.

Recent decision making theories have explained behaviour using mental sampling mechanisms where people imagine possible outcomes to guide their choices. Simultaneously, work in other domains has found evidence of particular mental sampling patterns, such as autocorrelations between samples and moderation by prior assumptions, which current decision making theories do not generally consider. Here, we seek to unify this work, developing a new sampling model of preferential choice incorporating these findings in other domains. Our model, based on the Autocorrelated Bayesian Sampler, predicts choice, reaction time, confidence and valuation from a common underlying process. We find a strong correspondence between our model's predictions and empirical choice data, though performance remains below leading explanations for such tasks. Our model does however cover a broader set of response types than existing theories, suggesting the advantages of considering of a wider range of behaviours than are commonly examined in current decision making studies.

When making financial forecasts, individuals often overreact to recent information, as consistently observed in both laboratory studies with naïve participants and professional consensus real-world forecasting. Current models attribute this overreaction to either an overestimation of recent information or memory constraints favoring more accessible information. An alternative explanation suggests individuals accurately integrate all available information into their mental posterior probability distribution for forecasting, but are unable to directly access this distribution, leading to dependence on approximation methods such as sampling. Local sampling algorithms have received recent support in other forecasting contexts and may introduce overreaction as a consequence of a starting point bias. By reanalyzing existing data from a price prediction task with a random walk price series, we observe increasing variability in predicted values and forecast errors as the horizon expands. Employing this heightened variability and overreaction, we differentiate between competing explanations for the observed forecasting behavior.

Therapeutic strategies for early-stage non-small cell lung cancer (NSCLC) are advancing, with immune checkpoint inhibitors (ICIs) and targeted therapies making their way into neoadjuvant and adjuvant settings. With recent advances, there was a need for multidisciplinary lung cancer healthcare providers from across Ontario to convene and review recent data from practical and implementation standpoints. The focus was on the following questions: (1) To what extent do patient (e.g., history of smoking) and disease (e.g., histology, tumor burden, nodal involvement) characteristics influence treatment approaches? (2) What are the surgical considerations in early-stage NSCLC? (3) What is the role of radiation therapy in the context of recent evidence? (4) What is the impact of biomarker testing on treatment planning? Ongoing challenges, treatment gaps, outstanding questions, and controversies with the data were assessed through a pre-meeting survey, interactive cases, and polling questions. By reviewing practice patterns across Ontario cancer centers in the context of evolving clinical data, Health Canada indications, and provincial (Cancer Care Ontario [CCO]) funding approvals, physicians treating lung cancer voiced their opinions on how new approaches should be integrated into provincial treatment algorithms. This report summarizes the forum outcomes, including pre-meeting survey and polling question results, as well as agreements on treatment approaches based on specific patient scenarios.

Background: Very young children from lower socioeconomic status (SES) backgrounds often show poorer language development. Whilst there have been attempts to provide early intervention programmes, these sometimes miss the most disadvantaged groups. Aims: This report presents preliminary feasibility and effectiveness data for a novel language intervention designed for parents of toddlers in the United Kingdom. Methods and Procedures: In total, 43 UK families of 2--4-year-olds were recruited to the study, half of whom completed an 8-week course (Tots Talking) focussed on parent interaction, and half of whom acted as wait-list controls. Results and Outcomes: Results suggest that such programmes are feasible for families with 86% staying in the intervention. In addition, greater changes in underlying communication skills such as joint attention and gesture were evident compared to wait-list controls. Conclusions and Implications: We conclude that pre-verbal skills may be more important to measure as initial outcomes than language or vocabulary change in this population.

Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.

Summary: Background: Perivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. However, it is unknown whether PVS can predict dementia risk and brain atrophy trajectories in participants without dementia, as longitudinal studies on PVS are scarce and current methods for PVS assessment lack robustness and inter-scanner reproducibility. Methods: We developed a robust algorithm to automatically assess PVS count and size on clinical MRI, and investigated 1) their relationship with dementia risk and brain atrophy in participants without dementia, 2) their longitudinal evolution, and 3) their potential use as a screening tool in simulated clinical trials. We analysed 46,478 clinical measurements of cognitive functioning and 20,845 brain MRI scans from 10,004 participants (71.1 ± 9.7 years-old, 56.6% women) from three publicly available observational studies on ageing and dementia (the Alzheimer’s Disease Neuroimaging Initiative, the National Alzheimer’s Coordinating Centre database, and the Open Access Series of Imaging Studies). Clinical and MRI data collected between 2004 and 2022 were analysed with consistent methods, controlling for confounding factors, and combined using mixed-effects models. Findings: Our fully-automated method for PVS assessment showed excellent inter-scanner reproducibility (intraclass correlation coefficients >0.8). Fewer PVS and larger PVS diameter at baseline predicted higher dementia risk and accelerated brain atrophy. Longitudinal trajectories of PVS markers differed significantly in participants without dementia who converted to dementia compared with non-converters. In simulated placebo-controlled trials for treatments targeting cognitive decline, screening out participants at low risk of dementia based on our PVS markers enhanced the power of the trial independently of Alzheimer’s disease biomarkers. Interpretation: These robust cerebrovascular markers predict dementia risk and brain atrophy and may improve risk-stratification of patients, potentially reducing cost and increasing throughput of clinical trials to combat dementia. Funding: US National Institutes of Health.

Exposure to environmental contaminants can result in profound effects on the host immune system. One class of environmental toxicants, known as dioxins, are persistent environmental contaminants termed “forever chemicals”. The archetype toxicant from this group of chemicals is 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), an immunotoxicant that activates the aryl-hydrocarbon receptor pathway leading to a variety of changes in immune cell responses. Immune cell functions are crucial to the development and maintenance of healthy reproduction. Immune cells facilitate tolerance between at the maternal-fetal interface between the parent and the semi-allogenic fetus and help defend the gravid reproductive tract from infectious assault. Epidemiological studies reveal that exposure to environmental contaminants (such as TCDD) are linked to adverse reproductive health outcomes including endometriosis, placental inflammation, and preterm birth. However, little is known about the molecular mechanisms that underpin how environmental toxicant exposures impact immune functions at the maternal-fetal interface or within the reproductive tract in general. This review presents the most recent published work that studies interactions between dioxin or TCDD exposure, the host immune system, and reproduction.

Autistic/ADHD individuals are increasingly recognised as a valid minority group, with consistent research demonstrating a higher prevalence of co-occurring mental health conditions such as PTSD, anxiety, depression, substance use, and eating disorders among other mental health challenges. Due to this, there is increasing focus on the adaptations required for Autistic and ADHD individuals of current therapeutic approaches such as Schema Therapy. Particular emphasis when creating these adaptations needs to include looking at the developmental experiences, social influences, and continued adversity faced by Autistic and ADHD individuals across the lifespan, and how the narrative around Autism and ADHD within psychotherapy in general needs to change. This paper critically examines the role of attachment, unmet needs, and adverse childhood experiences in Autistic and ADHD individuals and the subsequent impact on schema development and maintenance and mental health. This will include an overview of the current literature in this area, reconsideration of understandings of Autism and ADHD, particular therapeutic considerations and adjustments and importantly discussion around the wider societal changes that need to occur to prevent schema development and reinforcement across the lifespan.

Phenomics is the acquisition of high-dimensional data on an individual-wide scale and is proving transformational in areas of biological research related to human health including medicine and the crop sciences. However, more broadly, a lack of accessible transferrable technologies and research approaches is significantly hindering the uptake of phenomics, in contrast to molecular-omics for which transferrable technologies have been a significant enabler. Aquatic embryos are natural models for phenomics, due to their small size, taxonomic diversity, ecological relevance, and high levels of temporal, spatial and functional change. Here, we present LabEmbryoCam, an autonomous phenotyping platform for timelapse imaging of developing aquatic embryos cultured in a multiwell plate format, and while optimised for embryos, the instrument is extremely versatile. The LabEmbryoCam capitalises on 3D printing, single board computers, consumer electronics and stepper motor enabled motion. We combine these into a compact and modular laboratory insturment to provide X, Y and Z motion of a camera and lens, a web application streamlined for rapid setup of experiments, user email notifications and a humidification chamber to reduce evaporation over prolonged acquisitions. Downstream analyses are provided, enabling automated embryo segmentation, heartrate measurement, motion tracking, and energy proxy trait (EPT) measurement. The LabEmbryoCam is a scalable, and flexible laboratory instrument, that leverages embryonic and early life stage organisms to tackle key global challenges including biological sensitivity assessment, toxicological screening, but also to support broader engagement with the earliest stages of life.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The HBCD study has faced several ethical and legal challenges due to its goal of enrolling pregnant people (including those with substance use disorder) and their newborns. Challenges not fully anticipated at the outset emerged from the rapidly changing legal landscape around reproductive rights in the United States. By embedding scholars in bioethics and law within research teams and engaging them in conversation with each other and other study personnel, we were able to address many challenges proactively and respond promptly to unanticipated challenges. In this paper, we highlight several important ethical and legal challenges that arose from the first phase of funding through the beginning of participant enrollment. We explain the methods used to address these challenges, the ethical and legal tradeoffs that arose, and the resolution of challenges through the design of the study. Based on this experience, we provide recommendations for research teams, sponsors, and reviewers to address legal risks and promote the ethical conduct of studies with pregnant people and caregivers. We highlight the importance of collaboration with bioethics and legal scholars in studies involving complex and evolving legal risks, as well as the necessity of designing robust approaches to informed consent and maintaining participant trust while navigating ethical challenges in research.