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يندرج الكتاب ضمن سلسلة \"A Very Short Introduction\" الصادرة عن Oxford University Press (عام 2020)، ويقدم عرضا مركزا وميسرا لظاهرة الخرف على المستوى الطبي والعلمي والاجتماعي. تبدأ المؤلفة بتعريف الخرف وأنواعه المختلفة، وتستعرض التحديات العلمية والبيئية التي تقف أمام فهم أسباب المرض المتعدد والعوامل المؤهبة له، مثل العمر، الوراثة، ونمط الحياة؛ مع التركيز على الفرضية التقليدية للبروتينات الشائكة وما بعدها تفصل في العوامل البيولوجية والنفسية المسؤولة عن تطور المرض، ثم تناقش الأساليب التشخيصية والمعرفية المتبعة حاليا، وتشير إلى التقدم البطيء في إيجاد علاج فعال، والفرص البحثية الواعدة في المستقبل تختتم بطرح استراتيجيات للوقاية وتقليل المخاطر من خلال الالتزام بنمط حياة صحي : النشاط العصبي والاجتماعي، التغذية الجيدة، إدارة الأمراض والضغط النفسي، وكل ما يعزز القدرة المعرفية طويلة الأمد ويساهم في تحسين جودة الحياة مع الحالة المشخصة.

Current autism assessment procedures are costly and resource-intensive. The COVID-19 pandemic accelerated the adoption of telemedicine, highlighting the benefits of innovative diagnostic tools. Telemedicine-based pathways could enhance accessibility and equity in autism diagnostics. The Children with Autism Technology Enabled Assessment (CHATA) project aims to develop and pilot an open-source autism diagnostic pathway for children up to 5 years old, delivered through telemedicine. The pathway is designed to be culturally and linguistically adaptable, increasing its applicability to diverse populations and integrating with existing National Health Service digital systems. Initial pathway development was informed by systematic evidence reviews, coproduction, and mixed methods usability. CHATA comprises 2 key elements: online self-completed standardized autism questionnaires and a structured online interview and observation by a trained clinician. Out of 60 families near the top of the local waiting list will be invited to participate in the pilot evaluation, assessed using both the CHATA and usual assessment pathways. Sensitivity and specificity will be calculated by comparing the diagnosis of autism through CHATA with usual care. Quantitative usability assessment will be gathered from all families using the System Usability Scale (where a mean above 68 indicates above-average usability). A subset of CHATA assessments will be reviewed for interrater reliability (measured by the Cohen κ for categorical data [diagnosis present or absent], with values indicating the level of agreement; eg, <0 indicating no agreement, 0.61-0.80 indicating substantial agreement). Qualitative data on acceptability, feasibility, and usability will be gathered from semistructured interviews with a subset of families and health care providers. We will recruit 60 families for the main pilot study (including the usability testing) and 10-15 participants for the qualitative substudy. Data will estimate CHATA's diagnostic accuracy, validity, reliability, usability, and acceptability. Patient and public involvement will be integral throughout. The study will take place in a socio-economically deprived, ethnically diverse inner-London Borough within a community-based child health National health service responsible for the Autism assessment of children and young people up to the age of 13 years. Ethics approval was received in June 2023 (Research Ethics Committee reference 22/LO/0751; IRAS project ID 320499). Data collection commenced in April 2023 and completed in October 2024. Project end date is March 2025. As of November 2024, we had enrolled 57 participants to the pilot study and 12 to the qualitative substudy. The CHATA project aims to establish a novel, culturally sensitive, equitable, and accurate online autism assessment pathway. By addressing geographical and linguistic barriers, this pathway seeks to reduce service costs, shorten waiting times, and promote equity in autism diagnosis. The procedures developed are expected to be generalized to other populations nationwide. DERR1-10.2196/55741.

Objectives/AimsAltered interoception may be a core pathophysiological mechanism in functional neurological disorder (FND). However, there have been inconsistent findings from interoceptive accuracy paradigms, with several studies reporting no significant group differences in comparisons to controls when tested at rest/baseline. This is contrary to evidence for alterations in other interoceptive dimensions including awareness (metacognitive evaluation of interoceptive accuracy) and sensibility (self- reported sensitivity to bodily sensations) in this population. We aimed to measure interoception across several dimensions, with the prediction that individuals with FND would show reduced accuracy, awareness, and sensibility compared to controls.MethodsIndividuals with FND (n=17, 13F:4M, 10 motor symptoms, 7 motor/seizures) and healthy controls (HC, n=17, 13F:4M) completed measures of interoceptive accuracy and awareness (modified heartbeat tracking task [HTT]) and a time estimation task (TET). Participants also completed a validated scale of interoceptive sensibility (Multidimensional Assessment of Interoceptive Awareness-2, MAIA-2).ResultsThe groups were matched for age (p=.51), sex (p=1.00), and body mass index (p=.19). FND and HC groups did not differ in interoceptive accuracy (p=1.00) or awareness (p=.99), although the FND group displayed lower scores on the ‘Not- Distracting’ (p<.001, g=1.42) and ‘Trusting’ (p=.005, g=1.17) subscales of the MAIA-2, relative to controls. There was no relationship in either group between HTT and TET scores. There was a significant positive relationship between HTT accuracy and awareness (confidence) in the control group (r=.61, p=.016) but not in the FND group (r=.11, p=.69). Exploratory correlations revealed a significant positive relationship between interoceptive awareness and the ‘Self-Regulation’ subscale of the MAIA-2 in the FND group (r=.77, p=.002).ConclusionsIndividuals with FND did not differ from HCs on interoceptive accuracy or awareness, measured at rest. The lower levels of ‘Not-Distracting’ and ‘Trusting’ seen in this FND sample replicated our previous study, suggesting that there may be a separation between trait and state interoceptive awareness in FND, reinforcing the need for interoception to be considered within a multidimensional framework. The lack of relationship between interoceptive accuracy and awareness in the FND group also implies that there may be a disconnect between actual performance and subjective confidence. Our future work will explore the possibility that interoceptive impairments in FND may be state dependent, measuring these interoceptive domains with other paradigms, in larger samples, compared to both healthy and clinical controls.

BackgroundDifferences in affective processing have previously been shown in functional neurological disorder (FND); however, the mechanistic relevance is uncertain. We tested the hypotheses that highly arousing affective stimulation would result in elevated subjective functional neurological symptoms (FNS), and this would be associated with elevated autonomic reactivity. The possible influence of cognitive detachment was also explored.MethodIndividuals diagnosed with FND (motor symptoms/seizures; n=14) and healthy controls (n=14) viewed Positive, Negative and Neutral images in blocks, while passively observing the stimuli (‘Watch’) or detaching themselves (‘Distance’). The FND group rated their primary FNS, and all participants rated subjective physical (arousal, pain, fatigue) and psychological states (positive/negative affect, dissociation), immediately after each block. Skin conductance (SC) and heart rate (HR) were monitored continuously.ResultsFNS ratings were higher after Negative compared with Positive and Neutral blocks in the FND group (p=0.002, ηp 2=0.386); however, this effect was diminished in the Distance condition relative to the Watch condition (p=0.018, ηp 2=0.267). SC and/or HR correlated with FNS ratings in the Negative-Watch and Neutral-Distance conditions (r values=0.527–0.672, p values=0.006–0.035). The groups did not differ in subjective affect or perceived arousal (p values=0.541–0.919, ηp 2=<0.001–0.015).ConclusionsEmotionally significant events may exert an influence on FNS which is related to autonomic activation rather than altered subjective affect or perceived arousal. This influence may be modulated by cognitive detachment. Further work is needed to determine the relevance and neural bases of these processes in specific FND phenotypes.

Objectives/AimsBiopsychosocial perspectives have highlighted the multifactorial and diverse aetiology of functional neurological disorder (FND). We aimed to assess a range of potential predisposing, precipitating and perpetuating factors in FND, and to explore relationships between aetiological factors and current functioning or health-related quality- of-life (HRQoL).MethodsSeventeen participants with FND (motor symptoms and/or seizures) and 17 healthy controls (HCs) underwent an in-depth interview and completed validated questionnaires, including the Traumatic Experiences Checklist (TEC), Toronto Alexithymia Scale-20, Multiscale Dissociation Inventory, Somatoform Dissociation Questionnaire-20, Autistic Spectrum Quotient, Patient Health Questionnaire-9 and -15, Generalised Anxiety Disorder-7, Brief Illness Perception Questionnaire (B-IPQ), Short Form Survey-36 (SF-36) and the Work & Social Adjustment Scale.ResultsThe groups did not differ in sex (p=1.00) or age (p=.51). The most commonly reported FND symptom precipitants were physical activity/exertion (59%), stress/emotion (59%), sensory (47%) and fatigue (41%). Perceived causes of FND (B-IPQ) were physical (e.g., injury, illness, 65%), stress/emotions (53%), psychosocial trauma (47%) and work-related (29%). There was a trend towards higher rates of adverse life events (TEC) in the FND group compared to HCs (p=.06), and the FND group reported greater impact of events (p=.03). The most frequent adverse experiences in the FND group were: looking after parents/siblings as a child (41%), family problems (41%), parental divorce (41%), intense pain (41%), emotional neglect (41%), and sexual abuse (non-familial, 41%). The most common adverse experiences in HCs were: bereavement (35%) and parental divorce (41%). The FND group had higher scores for alexithymia (p=.002), somatoform dissociation (p<.001), aspects of psychological dissociation (disengagement p=.003, depersonalisation p=.001, derealisation p=.002, memory disturbance p=.01), anxiety (p<.001), depression (p<.001), and physical symptoms (p<.001). No significant differences were observed for autistic spectrum traits (p=.22) and some types of psychological dissociation (emotional constriction p=.38, identity disturbance p=.17). FND participants reported worse HRQoL than HCs in all SF-36 domains (p-values .01- <.001). Work/social functioning was impaired in the FND group relative to HCs (p<.001). Poorer work/social functioning was associated with higher depression scores (p=.016). Worse HRQoL in several domains was associated with higher somatoform dissociation and/or anxiety scores (p-values .044-.005). Lower general health HRQoL scores were associated with higher TEC total (p=.020) and impact (p=.011) scores.ConclusionsIndividuals with FND report diverse aetiological factors, including psychosocial, physical and environmental stressors. Alexithymia, dissociative tendencies, emotional distress, and physical symptom burden are also possible predisposing and/or perpetuating factors. Somatoform dissociation, anxiety and adverse experiences may be related to HRQoL in FND.

At-home sampling is key to large scale seroprevalence studies. Dried blood spot (DBS) self-sampling removes the need for medical personnel for specimen collection but facilitates specimen referral to an appropriately accredited laboratory for accurate sample analysis. To establish a highly sensitive and specific antibody assay that would facilitate self-sampling for prevalence and vaccine-response studies. Paired sera and DBS eluates collected from 439 sero-positive, 382 sero-negative individuals and DBS from 34 vaccine recipients were assayed by capture ELISAs for IgG and IgM antibody to SARS-CoV-2. IgG and IgM combined on DBS eluates achieved a diagnostic sensitivity of 97.9% (95%CI 96.6 to 99.3) and a specificity of 99.2% (95% CI 98.4 to 100) compared to serum, displaying limits of detection equivalent to 23 and 10 WHO IU/ml, respectively. A strong correlation (r = 0.81) was observed between serum and DBS reactivities. Reactivity remained stable with samples deliberately rendered inadequate, ( p  = 0.234) and when samples were accidentally damaged or ‘invalid’. All vaccine recipients were sero-positive. This assay provides a secure method for self-sampling by DBS with a sensitivity comparable to serum. The feasibility of DBS testing in sero-prevalence studies and in monitoring post-vaccine responses was confirmed, offering a robust and reliable tool for serological monitoring at a population level.

IntroductionGlioblastoma (GBM) is the most common adult primary malignant brain tumour. The condition is incurable and, despite aggressive treatment at first presentation, almost all tumours recur after a median of 7 months. The aim of treatment at recurrence is to prolong survival and maintain health-related quality of life (HRQoL). Chemotherapy is typically employed for recurrent GBM, often using nitrosourea-based regimens. However, efficacy is limited, with reported median survivals between 5 and 9 months from recurrence. Although less commonly used in the UK, there is growing evidence that re-irradiation may produce survival outcomes at least similar to nitrosourea-based chemotherapy. However, there remains uncertainty as to the optimum approach and there is a paucity of available data, especially with regards to HRQoL. Brain Re-Irradiation Or Chemotherapy (BRIOChe) aims to assess re-irradiation, as an acceptable treatment option for recurrent IDH-wild-type GBM.Methods and analysisBRIOChe is a phase II, multi-centre, open-label, randomised trial in patients with recurrent GBM. The trial uses Sargent’s three-outcome design and will recruit approximately 55 participants from 10 to 15 UK radiotherapy sites, allocated (2:1) to receive re-irradiation (35 Gy in 10 daily fractions) or nitrosourea-based chemotherapy (up to six, 6-weekly cycles). The primary endpoint is overall survival rate for re-irradiation patients at 9 months. There will be no formal statistical comparison between treatment arms for the decision-making primary analysis. The chemotherapy arm will be used for calibration purposes, to collect concurrent data to aid interpretation of results. Secondary outcomes include HRQoL, dexamethasone requirement, anti-epileptic drug requirement, radiological response, treatment compliance, acute and late toxicities, progression-free survival.Ethics and disseminationBRIOChe obtained ethical approval from Office for Research Ethics Committees Northern Ireland (reference no. 20/NI/0070). Final trial results will be published in peer-reviewed journals and adhere to the ICMJE guidelines.Trial registration numberISRCTN60524.

In this period of rapid human‐induced environmental change, it is vital that influences of habitat on the distribution and productivity of threatened species are understood. Ground‐nesting birds are declining more rapidly across Europe than any other group, with large‐bodied birds at the greatest risk of extinction. Productivity and adult survival cannot both be maximised concurrently, and individuals will make decisions during the nest‐placement phase which will favour one outcome or the other; however, under conditions of accelerating change, these decision processes may become decoupled from positive fitness outcomes. The Eurasian curlew Numenius arquata is Europe's largest wader and is showing steep declines in breeding productivity. Curlews are known to use a diverse range of habitats for nesting, where anthropogenic or natural features may influence distribution. There is an urgent need to understand the spatial scales of these impacts, and whether habitat characteristics have a positive or negative impact on nest survival. In our study site in southern England, curlew showed a marked preference for nesting in wetter habitats, primarily mire, and a weaker selection of dry heathland. Nest survival improved in wetter habitats, and the area of mire round a nest site was positively associated with increased levels of nesting success, whilst area of scrub had a negative association. Woodland significantly excluded curlew from potentially suitable breeding habitat, with an impact observed up to 2 km from the nest site, but nest survival did not improve with distance from woodland. Curlews strongly avoided nesting near a major road passing through the study site, despite seemingly suitable habitat nearby. Understanding landscape effects will assist in planning future habitat management for curlew, impacts of forestry and avoidance of additional pressures on a species of high conservation concern.