Multiple sclerosis (MS) is characterized by focal inflammatory activity in the central nervous system and a diffuse, compartmentalized inflammation that is the primary driver of neuroaxonal damage and worsening disability. It is now recognized that higher-efficacy disease-modifying therapies (HE-DMT) are often required to treat the complex neuropathological changes that occur during the disease course and improve long-term outcomes. The optimal use of HE-DMTs in practice was addressed by a Canadian panel of 12 MS experts who used the Delphi method to develop 27 consensus recommendations. The HE-DMTs that were considered were the monoclonal antibodies (natalizumab, ocrelizumab, ofatumumab) and the immune reconstitution agents (alemtuzumab, cladribine). The issues addressed included defining aggressive/severe disease, patient selection of the most appropriate candidates for HE-DMTs, baseline investigations and efficacy monitoring, defining suboptimal treatment response, use of serum neurofilament-light chain in evaluating treatment response, safety monitoring, aging and immunosenescence and when to consider de-escalating or discontinuing treatment. The goals of the consensus recommendations were to provide guidelines to clinicians on their use of HE-DMTs in practice and to improve long-term outcomes in persons with MS.

The Society for Healthcare Epidemiology of America, the Association of Professionals in Infection Control and Epidemiology, the Infectious Diseases Society of America, and the Pediatric Infectious Diseases Society represent the core expertise regarding healthcare infection prevention and infectious diseases and have written multisociety statement for healthcare facility leaders, regulatory agencies, payors, and patients to strengthen requirements and expectations around facility infection prevention and control (IPC) programs. Based on a systematic literature search and formal consensus process, the authors advocate raising the expectations for facility IPC programs, moving to effective programs that are:

• Foundational and influential parts of the facility’s operational structure

• Resourced with the correct expertise and leadership

• Prioritized to address all potential infectious harms

This document discusses the IPC program’s leadership—a dyad model that includes both physician and infection preventionist leaders—its reporting structure, expertise, and competencies of its members, and the roles and accountability of partnering groups within the healthcare facility. The document outlines a process for identifying minimum IPC program medical director support. It applies to all types of healthcare settings except post-acute long-term care and focuses on resources for the IPC program. Long-term acute care hospital (LTACH) staffing and antimicrobial stewardship programs will be discussed in subsequent documents.

Objectives/Goals: Ischemic stroke treatments assist in restoring blood flow, but do not guarantee good outcomes. Since extracellular vesicles (EVs) able to cross the blood brain barrier, total (nonspecific) and astrocyte enriched EVs (TEVs, AEVs, respectively) from plasma may emerge as plasma biomarkers for prognostication and targeted therapeutics. Methods/Study Population: “Blood and Clot Thrombectomy Registry and Collaboration” (BACTRAC; NCT03153683) is a human stroke biobank at the University of Kentucky that collects samples at the time of mechanical thrombectomy during emergent large vessel occlusions (ELVO; ischemic stroke). EVs were isolated, via size exclusion chromatography, from unbanked plasma and concentrated resulting in TEVs. AEVs were immunoprecipitated with anti-EAAT1 (GLAST), an astrocyte-specific transmembrane glycoprotein. Isolated protein was sent to Olink and ran on their metabolic panel. Demographics and medical histories of the subjects were exported from REDcap and investigators were blinded during EV analysis. Results/Anticipated Results: ELVO subjects (8 females/ 5 males) were an average age of 71.1 ± 11.7 years. Lower TEV enolase 2, a neuronal glycolysis enzyme, associated with increased stroke severity (NIHSS; rs =  -0.7819, p = 0.0476). Higher systemically TEV quinoid dihydropteridine reductase (QDPR), essential co-factor enzyme, was associated with more severe strokes (NIHSS; rs =  0.8486, p = 0.0123) and lower cognition (MoCA; r2 =  0.7515, p = 0.0254). Interestingly, higher intracranial AEVs QDPR was associated with lower infarct volumes (rs =  -0.7333, p = 0.0202), less severe strokes (NIHSS; rs =  -0.6095, p = 0.0388), and better cognition (MoCA; r2 =  0.6095, p = 0.0388). Increased AEV nicotinamide adenine dinucleotide kinase another essential co-factor enzyme, intracranially also correlated to higher cognition (MoCA; rs =  0.8356, p = 0.0298). Discussion/Significance of Impact: Plasma TEV and AEV metabolic proteins correlate with the progression of stroke outcomes and should be investigated as target therapies during MT to improve outcomes.

Low vitamin D associated with high parathyroid hormone (PTH) is common in HIV infection. We determined the association between total 25(OH)D and PTH in adolescents living with HIV, in Zambia and Zimbabwe. Adolescents (11–19 years) perinatally infected with HIV and established on antiretroviral therapy for ≥ 6 months were recruited into a cross-sectional study. Socio-demographic and clinical characteristics were recorded, anthropometry measured and fasted serum concentrations of 1,25(OH)2D, total 25(OH)D and intact PTH measured. The association between total 25(OH)D and PTH was examined using natural cubic spline regression. 842 participants (female: 53·2%) with a median age of 15·5 (IQR: 13·2–17·9) years were enrolled. Median antiretroviral therapy duration was 9·8 (IQR: 6·3–12·3) years, and 165/841 had an HIV viral-load >60 copies/ml. Stunting (height-for-age z-score <–2) and underweight (weight-for-age z-score <–2) were observed in 29·9 and 30·0%, respectively. Three-quarters reported daily Ca intakes <150 mg/d. The mean (sd) concentrations of total 25(OH)D and 1,25(OH)2D were 66·1(16·5) nmol/l and 210·6 (70·4) pmol/l, respectively, and median PTH level was 4·3 (IQR: 3·3–5·5) pmol/l. There was an inverse non-linear relationship between total 25(OH)D and PTH, 25(OH)D levelling off at 74·6 nmol/l (95 % CI: 74·5, 75·2). Results were consistent in those taking tenofovir disoproxil fumarate and virally unsuppressed participants. In this population with extremely low habitual Ca intakes, the lack of association between 25(OH)D and PTH when 25(OH)D exceeded 75 nmol/l potentially suggests that levels of 25(OH)D >75 nmol/l may need to be achieved to improve bone health; investigation is needed in future research studies.

The fossil record of dinosaurs in Scotland mostly comprises isolated highly fragmentary bones from the Great Estuarine Group in the Inner Hebrides (Bajocian–Bathonian). Here we report the first definite dinosaur body fossil ever found in Scotland (historically), having been discovered in 1973, but not collected until 45 years later. It is the first and most complete partial dinosaur skeleton currently known from Scotland. NMS G.2023.19.1 was recovered from a challenging foreshore location in the Isle of Skye, and transported to harbour in a semi-rigid inflatable boat towed by a motor boat. After manual preparation, micro-CT scanning was carried out, but this did not aid in identification. Among many unidentifiable elements, a neural arch, two ribs and part of the ilium are described herein, and their features indicate that this was a cerapodan or ornithopod dinosaur. Histological thin sections of one of the ribs support this identification, indicating an individual at least eight years of age, growing slowly at the time of death. If ornithopodan, as our data suggest, it could represent the world's oldest body fossil of this clade.

Most Australian school students take a packed lunch to school(1). However, parents have reported many barriers to packing a healthy lunch(2). Subsequently, foods eaten during school hours are not consistent with the Australian Dietary Guidelines, with discretionary foods providing about 44% of energy consumed during this time(3). In addition, some children go to school without any food for lunch or money to buy lunch. The Tasmanian School Lunch Project provides free nutritious cooked lunches for Kinder to Year 10 students attending 30 government schools (15 commenced 2022, 15 commenced 2023) in areas of high socioeconomic disadvantage. The lunches were provided 1-3 days/week. The menu and recipes were designed by dietitians. This analysis aimed to describe parents’ perceptions of the School Lunch Project during the first year. Six of the 15 schools that commenced in term 2 2022 were invited, and agreed, to participate in the evaluation. During term 3 or 4 2022, parents completed online or written surveys (n = 159) and/or participated in discussion groups (n = 26) to share their thoughts on the menu, their concerns, likes, and willingness to pay. Survey data were analysed descriptively and open-ended survey responses and discussion group data thematically. During 2022, 78,832 nutritious cooked lunches were provided to 1,678 students. Most parents felt there was enough variety on the menu (66%) and the right amount of food was served (69%). Most students (79%) ate the lunches every day they were provided yet 52% of parents continued to provide a packed lunch. Parents enjoyed that their child was having a healthy lunch (66%) and trying new foods (74%). Some parents in the discussion groups indicated positive flow on effects at home with students trying new foods and sitting down together as a family to eat the evening meal. Half the parents (50%) had no concerns about the school providing lunches. The most commonly reported concerns were their child might not like the food (36%) or their child does not try new foods (8.6%). These concerns were also raised in the discussion groups. Most parents (93%) were prepared to pay for the lunches in future (median $3, range $1-$12) and 85% thought there should be a family discount. Parents acknowledged some payment was necessary for the sustainability of the program but some expressed concern for those who may struggle to pay. More direct communication with families about the meals offered, the availability of bread (from term 4 2022) for students who choose not to eat the cooked lunch or want more to eat, and allowing families time to adjust to the new lunch system, may address some of the concerns raised. Further data on parents’ perceptions of the school lunches will be collected during term 3 2023.

The non-archosauriform archosauromorph Dinocephalosaurus orientalis was first described from the Upper Member of the Guanling Formation (late Anisian, Middle Triassic) of Guizhou Province by Li in 2003 on the basis of a complete articulated skull and the first three cervical vertebrae exposed in dorsal to right lateral view. Since then, additional specimens have been discovered in southwestern China. Here, five newly discovered specimens are described for the first time, and redescriptions of the holotype IVPP V13767 and another referred specimen, IVPP V13898, are provided. Together, these permit the description of the complete skeleton of this remarkable long-necked marine reptile. The postcranial skeleton is as much as 6 metres long, and characterised by its long tail and even longer neck. The appendicular skeleton exhibits a high degree of skeletal paedomorphosis recalling that of many sauropterygians, but the skull and neck are completely inconsistent with sauropterygian affinities. The palate does not extend back over the basisphenoid region and lacks any development of the closed condition typical of sauropterygians. The arrangement of cranial elements, including the presence of narial fossae, is very similar to that seen in another long-necked archosauromorph, Tanystropheus hydroides, which at least in part represents a convergence related to an aquatic piscivorous lifestyle. The long and low cervical vertebrae support exceptionally elongate cervical ribs that extend across multiple intervertebral joints and contribute to a ‘stiffening bundle of ribs’ extending along the entire ventral side of the neck, as in many other non-crocopodan archosauromorphs. The functional significance of the extraordinarily elongate neck is hard to discern but it presumably played a key role in feeding, and it is probably analogous to the elongate necks seen in pelagic, long-necked plesiosaurs. Dinocephalosaurus orientalis was almost certainly a fully marine reptile and even gave birth at sea.

To improve contact tracing for healthcare workers, we built and configured a Bluetooth low-energy system. We predicted close contacts with great accuracy and provided an additional contact yield of 14.8%. This system would decrease the effective reproduction number by 56% and would unnecessarily quarantine 0.74% of employees weekly.

This study investigated sex differences in Fe status, and associations between Fe status and endurance and musculoskeletal outcomes, in military training. In total, 2277 British Army trainees (581 women) participated. Fe markers and endurance performance (2·4 km run) were measured at the start (week 1) and end (week 13) of training. Whole-body areal body mineral density (aBMD) and markers of bone metabolism were measured at week 1. Injuries during training were recorded. Training decreased Hb in men and women (mean change (–0·1 (95 % CI –0·2, –0·0) and –0·7 (95 % CI –0·9, –0·6) g/dl, both P < 0·001) but more so in women (P < 0·001). Ferritin decreased in men and women (–27 (95 % CI –28, –23) and –5 (95 % CI –8, –1) µg/l, both P ≤ 0·001) but more so in men (P < 0·001). Soluble transferrin receptor increased in men and women (2·9 (95 % CI 2·3, 3·6) and 3·8 (95 % CI 2·7, 4·9) nmol/l, both P < 0·001), with no difference between sexes (P = 0·872). Erythrocyte distribution width increased in men (0·3 (95 % CI 0·2, 0·4)%, P < 0·001) but not in women (0·1 (95 % CI –0·1, 0·2)%, P = 0·956). Mean corpuscular volume decreased in men (–1·5 (95 % CI –1·8, –1·1) fL, P < 0·001) but not in women (0·4 (95 % CI –0·4, 1·3) fL, P = 0·087). Lower ferritin was associated with slower 2·4 km run time (P = 0·018), sustaining a lower limb overuse injury (P = 0·048), lower aBMD (P = 0·021) and higher beta C-telopeptide cross-links of type 1 collagen and procollagen type 1 N-terminal propeptide (both P < 0·001) controlling for sex. Improving Fe stores before training may protect Hb in women and improve endurance and protect against injury.

Academic and community investigators conducting community-engaged research (CEnR) are often met with challenges when seeking Institutional Review Board (IRB) approval. This scoping review aims to identify challenges and recommendations for CEnR investigators and community partners working with IRBs. Peer-reviewed articles that reported on CEnR, specified study-related challenges, and lessons learned for working with IRBs and conducted in the United States were included for review. Fifteen studies met the criteria and were extracted for this review. Four challenges identified (1) Community partners not being recognized as research partners (2) Cultural competence, language of consent forms, and literacy level of partners; (3) IRBs apply formulaic approaches to CEnR; & (4) Extensive delays in IRB preparation and approval potentially stifle the relationships with community partners. Recommendations included (1) Training IRBs to understand CEnR principles to streamline and increase the flexibility of the IRB review process; (2) Identifying influential community stakeholders who can provide support for the study; and (3) Disseminating human subjects research training that is accessible to all community investigator to satisfy IRB concerns. Findings from our study suggest that IRBs can benefit from more training in CEnR requirements and methodologies

Municipal regulations and humane movement policies often restrict or discourage the use of ‘exotic’ species as companion animals. However, confusion arises because the term ‘exotic’ is used in various ways, and because classifying species as exotic or non-exotic does not satisfactorily distinguish suitable from unsuitable companion animals. Even among commonly kept species, some appear to be much more suitable than others. Instead, decisions about suitable companion animal species need to be based on a number of relevant issues. As ethical criteria, we considered that keeping a companion animal should not jeopardize - and ideally should enhance - its welfare, as well as that of its owner; and that keeping a companion animal should not incur any appreciable harm or risk of harm to the community or the environment. These criteria then served as the basis for identifying and organizing the various concerns that may arise over keeping a species for companionship. Concerns include how the animals are procured and transported, how well their needs can be met in captivity, whether the animal poses any danger to others, and whether the animal might cause environmental damage. These concerns were organized into a checklist of questions that form a basis for assigning species to five proposed categories reflecting their suitability as companion animals. This assessment framework could be used in creating policy or regulations, and to create educational and decision-making tools for pet retailers, animal adoption workers, and potential owners, to help prevent animals from being placed in unsuitable circumstances.

Avian endoparasites play important roles in conservation, biodiversity and host evolution. Currently, little is known about the epidemiology of intestinal helminths and protozoans infecting wild birds of Britain and Ireland. This study aimed to determine the rates of parasite prevalence, abundance and infection intensity in wild passerines. Fecal samples (n = 755) from 18 bird families were collected from 13 sites across England, Wales and Ireland from March 2020 to June 2021. A conventional sodium nitrate flotation method allowed morphological identification and abundance estimation of eggs/oocysts. Associations with host family and age were examined alongside spatiotemporal and ecological factors using Bayesian phylogenetically controlled models. Parasites were detected in 20.0% of samples, with corvids and finches having the highest prevalences and intensities, respectively. Syngamus (33%) and Isospora (32%) were the most prevalent genera observed. Parasite prevalence and abundance differed amongst avian families and seasons, while infection intensity varied between families and regions. Prevalence was affected by diet diversity, while abundance differed by host age and habitat diversity. Infection intensity was higher in birds using a wider range of habitats, and doubled in areas with feeders present. The elucidation of these patterns will increase the understanding of parasite fauna in British and Irish birds.

Most farm assurance schemes in the UK at least, in part, aim to provide assurances to consumers and retailers of compliance with welfare standards. Inclusion of welfare outcome assessments into the relevant inspection procedures provides a mechanism to improve animal welfare within assurance schemes. In this study, taking laying hens as an example, we describe a process for dealing with the practical difficulties in achieving this in two UK schemes; Freedom Food and Soil Association. The key challenges arise from selecting the most appropriate measures, defining sampling strategies that are feasible and robust, ensuring assessors can deliver a consistent evaluation and establishing a mechanism to achieve positive change. After a consultation exercise and pilot study, five measures (feather cover, cleanliness, aggressive behaviour, management of sick or injured birds, and beak trimming) were included within the inspection procedures of the schemes. The chosen sampling strategy of assessing 50 birds without handling provided reasonable certainty at a scheme level but less certainty at an individual farm level. Despite the inherent limitations within a time and cost sensitive certification assessment, the approach adopted does provide a foundation for welfare improvement by being able to highlight areas of concern requiring attention, enabling schemes to promote the use of outcome scoring as a management tool, promoting the dissemination of relevant technical information in a timely manner and increasing the scrutiny of standards important for the welfare of the birds.