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We study magic angle graphene in the presence of both strain and particle-hole symmetry breaking due to nonlocal interlayer tunneling. We perform a self-consistent Hartree-Fock study that incorporates these effects alongside realistic interaction and substrate potentials and explore a comprehensive set of competing orders including those that break translational symmetry at arbitrary wave vectors. We find that at all nonzero integer fillings very small strains, comparable to those measured in scanning tunneling experiments, stabilize a fundamentally new type of time-reversal-symmetric and spatially nonuniform order. This order, which we dub the "incommensurate Kekulé spiral"(IKS) order, spontaneously breaks both the emergent valley-charge conservation and moiré translation symmetries but preserves a modified translation symmetry T^′-which simultaneously shifts the spatial coordinates and rotates the U(1) angle which characterizes the spontaneous intervalley coherence. We discuss the phenomenological and microscopic properties of this order. We argue that our findings are consistent with all experimental observations reported so far, suggesting a unified explanation of the global phase diagram in terms of the IKS order.

In this study, we consider the introduction of new mobility services and technologies into the megacity of Beijing, China, as per developed strategy and action plans, in order to investigate their potential contribution to sustainable mobility. This includes population relocation (decentralization), the construction of new rail lines, the introduction of shared bike services as a feeder to subway stations, the electrification of passenger vehicles and the adoption of automated and shared vehicles. The well-established, system dynamics-based MARS model is adapted to Beijing and further improved via the inclusion of these new services, technologies and policies. We find that decentralization can have a profound effect on overall sustainability if not considered in conjunction with other policies and that new rail lines and shared bikes may only have benefits in specific zones. Shared and automated vehicles could increase VKT by 60% and reduce active and public transport trips by a quarter. As such, nuanced integrated policy approaches will be required that are similar to those currently in place, such as imposed car shedding and taxi fleet control.

Aim: Late-onset Pompe disease is characterized by progressive loss of muscular and respiratory function. Until recently, standard of care was enzyme replacement therapy (ERT) with alglucosidase alfa. Secondgeneration ERTs avalglucosidase alfa (aval) and cipaglucosidase alfa with miglustat (cipa+mig) are now available. Without head-to-head trials comparing aval with cipa+mig, an indirect treatment comparison is informative and timely for understanding potential clinical differentiation. Materials & methods: A systematic literature review was performed to identify relevant studies on cipa+mig and aval. Using patient-level and aggregate published data from randomized controlled trials (RCTs) and phase I/II and open-label extension (OLE) trials, a multi-level network meta-regression was conducted, adjusting for various baseline covariates, including previous ERT duration, to obtain relative effect estimates on 6- minute walk distance (6MWD, meters [m]) and forced vital capacity (FVC, % predicted [pp]). Analyses of two networks were conducted: Network A, including only RCTs, and network B, additionally including single-arm OLE and phase I/II studies. Results: Network B (full evidence analysis) showed that cipa+mig was associated with a relative increase in 6MWD (mean difference 28.93 m, 95% credible interval [8.26– 50.11 m]; Bayesian probability 99.7%) and FVC (2.88 pp [1.07–4.71 pp]; >99.9%) compared with aval. The comparison between cipa+mig and aval became more favorable for cipa+mig with increasing previous ERT duration for both end points. Analysis of network A showed that cipa+mig was associated with a relative decrease in 6MWD(-10.02m[-23.62 to 4.00 m]; 91.8%) and FVC (-1.45 pp [-3.01 to 0.07 pp]; 96.8%) compared with aval. Conclusion: Cipa+mig showed a favorable effect versus aval when all available evidence was used in the analysis.

IntroductionEarly diagnosis of oral squamous cell carcinoma can greatly improve treatment success rate and patient survival. Although Optical Coherence Tomography (OCT) based Angiography (OCTA) is a promising in vivo technique in oral imaging, there is a need for objective assessment of oral microvasculature.MethodsThis study aimed to demonstrate a comprehensive methodology of quantitative assessing OCTA intraoral scanning results to provide measurable, reproducible data and to avoid subjective visual interpretations. Data were collected from 37 healthy subjects in total across four intraoral sites—buccal mucosa (n = 32), labial mucosa (n = 24), floor of the mouth (n = 13), and hard palate (n = 8)—using a non-invasive swept-source OCT system. Four quantitative metrics—vessel area density, vessel skeleton density, vessel diameter index, and a newly proposed weighted Tortuosity Index—were used to assess OCTA images in oral applications.ResultsThe quadruple quantitative assessment’s repeatability was evaluated to be reliable. Analysis of a benign ulcer case revealed differences in these metrics compared to healthy cases.Discussion/ConclusionIn conclusion, we demonstrated a comprehensive method to quantify microvasculature in the oral cavity, showing considerable promise for early diagnosis and clinical management of oral diseases.

**Background:** Pompe disease is a rare lysosomal storage disorder, leading to accumulation of glycogen characterized by muscle weakness, fatigue, pain, and, in the longer term, a requirement for ventilatory and ambulatory support, and early mortality if untreated. Clinical evidence suggests that enzyme replacement therapy improves health outcomes for adults with late-onset Pompe disease (LOPD). PROPEL was a Phase 3, double-blind, randomized controlled trial, which evaluated cipaglucosidase alfa plus miglustat, vs alglucosidase alfa plus placebo in 123 adult patients with LOPD (clinicaltrials.gov: NCT03729362). **Objectives:** To analyze EQ-5D health-related quality of life (HRQoL) utility data from PROPEL. **Methods:** Multilevel modeling techniques (mixed regression methods) were used to analyze PROPEL EQ-5D-3L estimates and predict utility values for 7 health states previously identified in an economic evaluation for LOPD. In PROPEL, EQ-5D-5L values were assessed at screening and at weeks 12, 26, 38, and 52. EQ-5D-5L utility values were mapped to EQ-5D-3L values using the van Hout algorithm as recommended by the EuroQoL and the National Institute of Health and Care Excellence position statement at time of analysis. UK population tariffs were applied for all EQ-5D utility valuations. Utility values were predicted according to 6-minute walk distance (6MWD) and percent predicted sitting forced vital capacity. **Results:** The mixed model predicted that EQ-5D-3L utility values for patients who could walk >75 m with LOPD ranged between 0.55 and 0.67 according to patient 6MWD and respiratory function. In this analysis, patients with a 6MWD ≤75 m, consistent with a health state requiring wheelchair support in the economic analysis, had a predicted utility value of 0.49. There were few patients in PROPEL who could walk ≤75 m at any time point in the study, hence, these utility estimates should be interpreted with caution. EQ-5D-3L utility estimates from PROPEL were consistent with previously reported EQ-5D-3L values in LOPD. **Conclusions:** Overall, the results from our analysis indicate that important HRQoL losses are associated with reductions in mobility and respiratory function for patients with Pompe disease. The study provides important evidence of HRQoL utility values for patients with advanced LOPD, a population for whom published data are limited.

Abstract Background The minimal clinically important difference (MCID) is the smallest change in outcome that physicians or patients would consider meaningful and is relevant when evaluating disease progression or the efficacy of interventions. Studies of patients with late-onset Pompe disease (LOPD) have used the 6-min walk distance (6MWD) as an endpoint to assess motor function. However, an MCID for 6MWD (% predicted and meters) has yet to be established in LOPD. The objective of the study was to derive 6MWD MCID (% predicted and meters) with different analysis methods and for subgroups of different disease severity for LOPD. Methods Data from the PROPEL trial were used to calculate 6MWD MCID in the overall PROPEL population and subgroups of baseline severity as assessed by walking distance and body mass index (BMI), using anchor- and distribution-based approaches. Results The 6MWD MCIDs varied widely, depending on the method and subgroup, ranging from 2.27%-8.11% predicted for the overall LOPD population (23.7 m-57.2 m). For patients with baseline 6MWD

Objective To estimate the cost-effectiveness of craniotomy, compared with decompressive craniectomy (DC) in UK patients undergoing evacuation of acute subdural haematoma (ASDH).Design Economic evaluation undertaken using health resource use and outcome data from the 12-month multicentre, pragmatic, parallel-group, randomised, Randomised Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation-ASDH trial.Setting UK secondary care.Participants 248 UK patients undergoing surgery for traumatic ASDH were randomised to craniotomy (N=126) or DC (N=122).Interventions Surgical evacuation via craniotomy (bone flap replaced) or DC (bone flap left out with a view to replace later: cranioplasty surgery).Main outcome measures In the base-case analysis, costs were estimated from a National Health Service and Personal Social Services perspective. Outcomes were assessed via the quality-adjusted life-years (QALY) derived from the EuroQoL 5-Dimension 5-Level questionnaire (cost-utility analysis) and the Extended Glasgow Outcome Scale (GOSE) (cost-effectiveness analysis). Multiple imputation and regression analyses were conducted to estimate the mean incremental cost and effect of craniotomy compared with DC. The most cost-effective option was selected, irrespective of the level of statistical significance as is argued by economists.Results In the cost-utility analysis, the mean incremental cost of craniotomy compared with DC was estimated to be −£5520 (95% CI −£18 060 to £7020) with a mean QALY gain of 0.093 (95% CI 0.029 to 0.156). In the cost-effectiveness analysis, the mean incremental cost was estimated to be −£4536 (95% CI −£17 374 to £8301) with an OR of 1.682 (95% CI 0.995 to 2.842) for a favourable outcome on the GOSE.Conclusions In a UK population with traumatic ASDH, craniotomy was estimated to be cost-effective compared with DC: craniotomy was estimated to have a lower mean cost, higher mean QALY gain and higher probability of a more favourable outcome on the GOSE (though not all estimated differences between the two approaches were statistically significant).Ethics Ethical approval for the trial was obtained from the North West—Haydock Research Ethics Committee in the UK on 17 July 2014 (14/NW/1076).Trial registration number ISRCTN87370545.

Dietary vitamin A deficiency is exceptionally rare in resource-rich countries. A well-known consequence of vitamin A deficiency is xeropthalmia, a spectrum which includes pathologic dryness of the conjunctiva and cornea, which can lead to corneal infection, thinning, or perforation, portending a very poor visual prognosis. This case describes a 10-year-old boy with Lennox-Gastaut syndrome and autism who developed malnutrition and deficiencies of multiple micronutrients, including copper, zinc, and an undetectable vitamin A blood level, secondary to dietary restriction for seizure control. After experiencing 3 months of nonspecific symptoms of ocular surface disease including eye dryness, eye redness, and tearing, he developed rapidly progressive keratomalacia and polymicrobial corneal ulcers. Despite treatment with topical antibiotics, he ultimately suffered bilateral corneal perforation requiring full-thickness corneal transplants. This report aims to raise the awareness of potentially debilitating nutrient deficiencies related to restricted diets, which are becoming increasingly common in numerous chronic pediatric conditions including epilepsy. This report also brings attention to the severe, long-term complications that can arise from nutrient deficiencies. Pediatric providers should consider a diagnosis of vitamin A deficiency in any child with a history of a restricted diet and ophthalmological symptoms.

Abstract Background The construct validity and interpretation of the Patient-Reported Outcome Measurement Information System (PROMIS®) Physical Function short form 20a (PF20a) questionnaire were evaluated for patients with late-onset Pompe disease (LOPD), a rare, autosomal recessive, progressive neuromuscular disorder treatable by enzyme replacement therapy (ERT). Methods In the phase 3 PROPEL study, adults with LOPD underwent testing of physical functioning and had PRO measurements at baseline and at weeks 12, 26, 38, and 52 while receiving experimental or standard-of-care ERT. All patients were pooled for analyses, without comparisons between treatment groups. Associations and correlations between PROMIS PF20a scores and the 6-minute walk distance (6MWD), % predicted forced vital capacity (FVC), manual muscle test (MMT) of the lower extremities, Gait, Stairs, Gowers’ maneuver, Chair (GSGC) score, and Rasch-built Pompe-specific Activity (R-PAct) scale were evaluated by calculating regression coefficients in linear regression models and Pearson correlation coefficients (R); patients’ age, sex, race, ERT prior to study, body mass index, and study treatment were included as covariables. The minimal clinically important difference (MCID) of PROMIS PF20a was determined using distribution- and anchor-based methods. Results 123 patients received at least 1 dose of ERT. In multivariable analyses, PROMIS PF20a scores had strong correlations with R-PAct scores (R = 0.83 at baseline and R = 0.67 when evaluating changes between baseline and 52 weeks) and moderate correlations with the 6MWD (R = 0.57 at baseline and R = 0.48 when evaluating changes between baseline and 52 weeks). Moderate correlations were also observed between PROMIS PF20a and MMT (R = 0.54), GSGC (R=-0.51), and FVC (R = 0.48) at baseline. In multivariable linear regression models, associations were significant between PROMIS PF20a and 6MWD (P = 0.0006), MMT (P = 0.0034), GSGC (P = 0.0278), and R-PAct (P

One of the limitations of currently-used metabolic syndrome (MetS) risk calculations is that they often depend on sample characteristics. To address this, we introduced a novel sample-independent risk quantification method called ‘triangular areal similarity’ (TAS) that employs three-axis radar charts constructed from five MetS factors in order to assess the similarity between standard diagnostic thresholds and individual patient measurements. The method was evaluated using large datasets of Korean (n = 72,332) and American (n = 11,286) demographics further segmented by sex, age, and race. The risk score exhibited a strong positive correlation with the number of abnormal factors and was closely aligned with the current diagnostic paradigm. The proposed score demonstrated high diagnostic accuracy and robustness, surpassing previously reported risk scores. This method demonstrated superior performance and stability when tested on cross-national datasets. This novel sample-independent approach has the potential to enhance the precision of MetS risk prediction.

Glucocorticoid receptor (GR) overexpression has been linked to increased tumour aggressiveness and treatment resistance. GR antagonists have been shown to enhance treatment effectiveness. Emerging research has investigated mifepristone, a GR antagonist, as an anticancer agent with limited research in the context of oral cancer. This study investigated the effect of mifepristone at micromolar (µM) concentrations of 1, 5, 10 and 20 on the proliferation and migration of oral cancer cells, at 24 and 48 h. Scratch and scatter assays were utilised to assess cell migration, MTT assays were used to measure cell proliferation, Western blotting was used to investigate the expression of GR and the activation of underlying Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signalling pathways, and immunofluorescence (IF) was used to determine the localisation of proteins in HaCaT (immortalised human skin keratinocytes), TYS (oral adeno squamous cell carcinoma), and SAS-H1 cells (squamous cell carcinoma of human tongue). Mifepristone resulted in a dose-dependent reduction in the proliferation of HaCaT, TYS, and SAS-H1 cells. Mifepristone at a concentration of 20 µM effectively reduced collective migration and scattering of oral cancer cells, consistent with the suppression of the PI3K-Akt and MAPK signalling pathways, and reduced expression of N-Cadherin. An elongated cell morphology was, however, observed, which may be linked to the localisation pattern of E-Cadherin in response to mifepristone. Overall, this study found that a high concentration of mifepristone was effective in the suppression of migration and proliferation of oral cancer cells via the inhibition of PI3K-Akt and MAPK signalling pathways. Further investigation is needed to define its impact on epithelial–mesenchymal transition (EMT) markers.

Canine pyometra is a hormonally mediated life-threatening uterine disease of canines, associated with bacterial infection and inflammation. The disease is characterized by the accumulation of pus in the uterus and systemic illness. The study was undertaken to assess the relevance of band cells in circulation and Doppler ultrasonography in the prognostic evaluation of medically managed canine pyometra. A significantly higher band of neutrophils were recorded among bitches presented with pyometra, which reduced to the physiologically normal range as treatment progressed in the animals which responded to the treatment. The resistive index, which was lower than the threshold value of 0.72, increased as the treatment progressed in the responsive animals and proved to be a reliable tool as a recovery marker.

BackgroundSocial anxiety disorder (SAD) is a debilitating psychiatric disorder that affects occupational and social functioning. Virtual reality (VR) therapies can provide effective treatment for people with SAD. However, with rapid innovations in immersive VR technology, more contemporary research is required to examine the effectiveness and concomitant user experience outcomes (ie, safety, usability, acceptability, and attrition) of emerging VR interventions for SAD. ObjectiveThe aim of this systematic review was to examine the effectiveness and user experience of contemporary VR interventions among people with SAD. MethodsThe Cochrane Library, Emcare, PsycINFO, PubMed, ScienceDirect, Scopus, and Web of Science databases were searched between January 1, 2012, and April 26, 2022. Deduplicated search results were screened based on title and abstract information. Full-text examination was conducted on 71 articles. Studies of all designs and comparator groups were included if they appraised the effectiveness and user experience outcomes of any immersive VR intervention among people with SAD. A standardized coding sheet was used to extract data on key participant, intervention, comparator, outcome, and study design items. ResultsThe findings were tabulated and discussed using a narrative synthesis. A total of 18 studies met the inclusion criteria. ConclusionsThe findings showed that VR exposure therapy–based interventions can generally provide effective, safe, usable, and acceptable treatments for adults with SAD. The average attrition rate from VR treatment was low (11.36%) despite some reported user experience difficulties, including potential simulator sickness, exposure-based emotional distress, and problems with managing treatment delivered in a synchronous group setting. This review also revealed several research gaps, including a lack of VR treatment studies on children and adolescents with SAD as well as a paucity of standardized assessments of VR user experience interactions. More studies are required to address these issues. Trial RegistrationPROSPERO CRD42022353891; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=353891

ABSTRACTDue to an alarming threat of air pollution and climate change, governments around the world are now actively promoting electric vehicles. The case for vehicle electrification is even more important in big cities of developing countries, where motorcycle is a dominant mode of travel. To promote electric motorcycles successfully, we need to understand the factors that would drive the consumer choices when buying a motorcycle. This study chose Bandung in Indonesia as the case study location, where nearly 75% of vehicles are motorcycles. This study conducted a survey of preferences from over 700 residents and included battery charging methods such as plug-in/battery swap at home/office, superfast charging at stations, and deployed an innovative modelling approach constraining the mixture of distributions for monetary attributes. The study found that quick recharge in 10 minutes and battery swap at station are preferred over the base method of plug-in at home/work. The battery swap at home has been perceived the same as plug-in home/work and the respondents are indifferent to this option.

Forest products and forest-based activities in Ethiopia play a substantial economic contribution to the livelihoods of rural households. Despite its pivotal role, empirical data are inadequate on forests' monetary contribution across a range of ecological locations and social situation, particularly for rural agrarian communities of the developing nations, like Ethiopia. We estimated the economic contributions of forest products and forest-based activities to forest-dependent rural households’ income and highlighted key socioeconomic characteristics in Wolaita, Ethiopia. We collected demographic, socioeconomic, and forest use data using a semi-structured questionnaire survey of 384 households, and surveyed markets to determine the prices of forest products for the valuation of forest use in three districts. We used descriptive statistics, the Chi-square test, the two-sample t-test, and one-way ANOVA to analyze the data. Findings showed that all respondents were engaged in one way or another in forest-based activities, while 84.6 % were involved in farming. The annual average income from forest products was 252.7US per household, contributing to 28.1 % of the total yearly average income (989.4US$), and 38.3 % relative forest income (RFI). Annual mean household income from crops was 648.1US$. Average annual household income from grazing, charcoal, firewood, woodcutting, cut-and-carry, NTFP, seed selling, medicinal plants, and seedling selling was 77.3 %, 58.4 %, 50.2 %, 24.1 %, 18.5 %, 12.7 %, 7.1 %, 6.8 % and 5.4 % of the total annual mean income, respectively revealing a significant difference (p

The successful and fast start-up of proton exchange membrane fuel cells (PEMFCs) at subfreezing temperatures (cold start) is very important for the use of PEMFCs as energy sources for automotive applications. The effective thermal management of PEMFCs is of major importance. When hydrogen is stored in hydride-forming intermetallics, significant amounts of heat are released due to the exothermic nature of the reaction. This excess of heat can potentially be used for PEMFC thermal management and to accelerate the cold start. In the current work, this possibility is extensively studied. Three hydride-forming intermetallics are introduced and their hydrogenation behavior is evaluated. In addition, five thermal management scenarios of the metal hydride beds are studied in order to enhance the kinetics of the hydrogenation. The optimum combination of the intermetallic, hydrogenation behavior, weight and complexity of the thermal management system was chosen for the study of thermal coupling with the PEMFCs. A 1D GT-SUITE model was built to stimulate the thermal coupling of a 100 kW fuel cell stack with the metal hydride. The results show that the use of the heat from the metal hydride system was able to reduce the cold start by up to 8.2%.

Purpose The retina provides biomarkers of neuronal and vascular health that offer promising insights into cognitive ageing, mild cognitive impairment and dementia. This article described the rationale and methodology of eye and vision assessments with the aim of supporting the study of dementia in the UK Biobank Repeat Imaging study.Participants UK Biobank is a large-scale, multicentre, prospective cohort containing in-depth genetic, lifestyle, environmental and health information from half a million participants aged 40–69 enrolled in 2006–2010 across the UK. A subset (up to 60 000 participants) of the cohort will be invited to the UK Biobank Repeat Imaging Study to collect repeated brain, cardiac and abdominal MRI scans, whole-body dual-energy X-ray absorptiometry, carotid ultrasound, as well as retinal optical coherence tomography (OCT) and colour fundus photographs.Findings to date UK Biobank has helped make significant advances in understanding risk factors for many common diseases, including for dementia and cognitive decline. Ophthalmic genetic and epidemiology studies have also benefited from the unparalleled combination of very large numbers of participants, deep phenotyping and longitudinal follow-up of the cohort, with comprehensive health data linkage to disease outcomes. In addition, we have used UK Biobank data to describe the relationship between retinal structures, cognitive function and brain MRI-derived phenotypes.Future plans The collection of eye-related data (eg, OCT), as part of the UK Biobank Repeat Imaging study, will take place in 2022–2028. The depth and breadth and longitudinal nature of this dataset, coupled with its open-access policy, will create a major new resource for dementia diagnostic discovery and to better understand its association with comorbid diseases. In addition, the broad and diverse data available in this study will support research into ophthalmic diseases and various other health outcomes beyond dementia.

Pre-death grief in the context of dementia caregiving is a significant risk factor for depression, burden, anxiety, and adjustment difficulties. The Two-Track Model of Dementia Grief (TTM-DG) provides a bifocal perspective addressing the nature of the emotional attachment to a loved one living with cognitive impairment, along with a medico-psychiatric perspective associated with stress, trauma, and change in life. The aims of the present study were to empirically validate the components of the model as to identify salutary and risk factors for maladaptive grief responses. Participants were 62 spouses of people living with cognitive impairment, and a control group of 32 spouses. All completed a battery of self-report questionnaires. Structural Equation Modeling yielded six variables consistent with the TTM-DG: partner’s behavioral disorders; caregiver’s burden; social support; physical health; attachment anxiety; and dementia grief as an outcome measure. Additional findings addressed participants at risk for grief difficulties. The findings provide empirical support for the utility of the TTM-DG in the identification of risk factors associated with maladaptive responses and pre-death grief following a spousal cognitive decline. The TTM-DG can assist in the formulation of evidence-based evaluations and interventions to assist spouses caring for their loved ones living with dementia.

The Peregrine Ion Trap Mass Spectrometer (PITMS) is a mass spectrometer instrument that operated during the Astrobotic Peregrine Mission-1 as part of the NASA Commercial Lunar Payload Services initiative. This paper describes the instrument and investigation design, development, and planning conducted by the PITMS team, consisting of a successful partnership between NASA Goddard Space Flight Center (GSFC), The Open University, NASA, and ESA. PITMS was designed to measure the abundance and temporal variability of volatile species in the near-surface lunar exosphere from a landed platform on the lunar surface. The PITMS instrument consisted of a European Space Agency–provided Exospheric Mass Spectrometer (including sensor, electronics, controller, and power supply boards) and a GSFC wrapper that provided structural elements, thermal control, and a deployable dust cover. PITMS was designed to operate as a passive sampler, where ambient gases would enter PITMS through an aperture, diffuse around the mass analyzer cavity, become ionized by electron impact and trapped in an RF field, and then sequentially be released to a detector to build a mass spectrum. PITMS was capable of measuring species with a mass-to-charge ratio ( m / z ) from 10 to 150 Da, with a mass resolution of approximately 0.5 amu. The PITMS science investigation was planned to be operated by GSFC with an international team of scientists. Though the mission did not achieve its lunar landing, information about the PITMS instrument and planning is provided to be able to understand and effectively use data that will be forthcoming from the investigation.

Induced innovation is a multi-faceted process characterized by interaction between demand-pull forces, path-dependent self-reinforcing change, and the cost reduction of technology that occurs with cumulative deployment. By endogenously including induced innovation in energy models, policy analysts and modellers could enable a mission-oriented approach to policymaking that envisions the opportunities of accelerating the low-carbon energy transition while avoiding the risks of inaction. While the integrated assessment models used in the intergovernmental panel on climate change (IPCC-IAMs) account for induced innovation, their assumptions of general equilibrium and optimality may reveal weaknesses that produce unsatisfactory results for policymakers. In this paper, we develop a menu of options for modelling induced innovation in the energy transition with non-equilibrium, non-optimal models by a three step methodology: a modelling survey questionnaire, a review of the literature, and an analysis of case studies from modelling applications within the economics of energy innovation and system transition (EEIST) programme. The survey questionnaire allows us to compare 24 models from EEIST partner institutions developed to inform energy and decarbonisation policy decisions. We find that only six models, future technological transformations, green investment barriers mode, stochastic e xperience c urves, economy-energy-environment macro-econometric, M3E3 and Dystopian Schumpeter meeting Keynes, represent endogenous innovation—in the form of learning curves, R&D, and spillover effects. The review of the literature and analysis of case studies allow us to form a typology of different models of induced innovation alongside the IPCC-IAMs and develop a decision tree to guide policy analysts and modellers in the choice of the most appropriate models to answer specific policy questions. The paper provides evidence for integrating narrow and systemic approaches to modelling-induced innovation in the context of low-carbon energy transition, and promotes cooperation instead of competition between different but complementary approaches. These findings are consistent with the implementation of risk-opportunity analysis as a policy appraisal method to evaluate low-carbon transition pathways.

Land use/land cover (LULC) changes influence the ecological function, consequence on ecosystem services, which are tightly linked to human wellbeing. However, quantification of the LULC changes and identifying the underlying factors remain patchy particularly in developing nations, despite this information is crucial to propose a feasible restoration action. Therefore, this study investigates the land use/land cover changes and its drivers in central Rift Valley, Ethiopia. GIS and Remote sensors i.e. Landsat 5 (TM), and Landsat 8 (OLI/TIRs) imagery sensors acquired from USGS, and field observation were used. Using the supervised classification method and the support of ArcGIS 10.5 and ERDAS IMAGINE 2014, all images were classified into various land cover types. Focus group discussions, key informant interviews, and structured questionnaire surveys were used to investigate the drivers of LULC change. NDVI was used to detect the vegetation cover change. Woodland, grassland, and barren lands were the major LULC types identified in this study. After 28 years, the woodland cover increased from 20.6% to 40.2% whereas the barren land decreased from 43.4% to 22.6%. Grassland showed very slight increment, i.e. from 35.9% to 36.9%. This implies that area enclosure plays a significant role in the restoration of degraded lands. The highest NDVI values (0.6) were determined in the year 2022 at the end of the classification. Focus group discussants and key informants confirmed that human-induced factors were the major drivers of LULC changes in the study area. Our findings indicated that human interventions are the key determinants of land use/land cover dynamics, and as a result, enforcement of the law and public education campaigns to change human behavior in support of the area enclosure approach are essential to restoring degraded land for the benefit and wellbeing of humans and nature while also advancing the achievement of the global goals.

BackgroundCerebrospinal fluid rhinorrhoea (CSFR) is a common complication following endonasal skull base surgery, a technique that is fundamental to the treatment of pituitary adenomas and many other skull base tumours. The CRANIAL study explored CSFR incidence and related risk factors, particularly skull base repair techniques, via a multicentre prospective observational study. We sought to use machine learning to leverage this complex multicentre dataset for CSFR prediction and risk factor analysis.MethodsA dataset of 865 cases - 725 transsphenoidal approach (TSA) and 140 expanded endonasal approach (EEA) - with cerebrospinal fluid rhinorrhoea as the primary outcome, was used. Relevant variables were extracted from the data, and prediction variables were divided into two categories, preoperative risk factors; and repair techniques, with 6 and 11 variables respectively. Three types of machine learning models were developed in order to predict CSFR: logistic regression (LR); decision tree (DT); and neural network (NN). Models were validated using 5-fold cross-validation, compared via their area under the curve (AUC) evaluation metric, and key prediction variables were identified using their Shapley additive explanations (SHAP) score.ResultsCSFR rates were 3.9% (28/725) for the transsphenoidal approach and 7.1% (10/140) for the expanded endonasal approach. NNs outperformed LR and DT for CSFR prediction, with a mean AUC of 0.80 (0.70-0.90) for TSA and 0.78 (0.60-0.96) for EEA, when all risk factor and intraoperative repair data were integrated into the model. The presence of intraoperative CSF leak was the most prominent risk factor for CSFR. Elevated BMI and revision surgery were also associated with CSFR for the transsphenoidal approach. CSF diversion and gasket sealing appear to be strong predictors of the absence of CSFR for both approaches.ConclusionNeural networks are effective at predicting CSFR and uncovering key CSFR predictors in patients following endonasal skull base surgery, outperforming traditional statistical methods. These models will be improved further with larger and more granular datasets, improved NN architecture, and external validation. In the future, such predictive models could be used to assist surgical decision-making and support more individualised patient counselling.

Land degradation is a common environmental problem affecting the ecological functions and ecosystem services leading to biodiversity loss and impoverishment of rural livelihood. This study explores people's attitudes and perceptions in central rift valley, Ethiopia. We interviewed 384 households using semi-structured questionnaires, conducted focus group discussions, and key informant interviews. The results showed that 92.1% of the respondents were aware of the role of area enclosure in degraded land restoration; 94.5% had a positive opinion of the establishment of new enclosures; 94.5% agreed to maintain the existing enclosures whereas 88.1% support the expansion. The benefits gained from the enclosure increased significantly with increased vegetation cover (OR = 41.961, P

Here, the authors design a multiplex serology platform to quantitatively measure antibodies against 20 infectious agents in UK Biobank participants and confirm associations of antibody responses with sociodemographic characteristics, HLA genetic variants, and disease outcomes.

Abstract Anthropogenic land-use changes pose significant threats to the diversity and occurrence of wildlife species around the world. We investigated how land-use and environmental factors affect the richness and occurrence of carnivore species in the Faragosa-Fura Landscape of the Southern Rift Valley of Ethiopia. We used the line transect method to collect data, combining three complementary field survey techniques: sign survey, camera trapping, and opportunistic sighting surveys. We confirmed the presence of 12 carnivore species belonging to six families, including the vulnerable Felidae species Panthera pardus. More species were found in the family’s Felidae and Herpestidae, while Hyaenidae and Mustelidae were composed of a single species each. The two large-sized species identified were Panthera pardus and Crocuta crocuta. The species richness was the highest in wetlands, while it was the lowest in the settlement. The occurrence of most carnivores was negatively associated with agricultural land and settlements, while they were positively associated with wetlands and altitude. Genetta genetta had the highest occurrence, while Panthera pardus had the lowest in the area. We concluded that of the studied habitats, wetlands are the most important, and anthropogenic land-uses have a negative impact on species richness. Our findings provide valuable baseline data for stakeholders making critical conservation decisions as well as researchers conducting related ecological studies in a human-dominated landscape. Based on our findings, we propose a basic approach for integrating land management and wildlife conservation. Article Highlights Twelve carnivore species belonging to six families were identified; only two were large-sized. The species richness was the highest in wetlands, while it was the lowest in settlements and agricultural land. Most species tended to have positive associations with higher altitudes and wetlands and negative associations with settlements, agricultural land, and roads. Our finding highlights valuable baseline data for critical conservation decisions as well as researchers in a human-dominated landscape.

IntroductionCurriculum-based sexual and reproductive health education (CBSRHE) is one of the preventive strategies targeting youth in higher institutions to protect them from sexual and reproductive health problems, despite never assessing the effect in Ethiopia. Therefore, this study aimed to assess the effect of CBSRHE on knowledge and attitude about SRH services to have safer sexual behaviors among first-year students of Arba Minch University.MethodWe conducted a quasi-experimental study among purposively selected campuses. The campuses were allocated to (i) an intervention arm consisting of curriculum-based sexual and reproductive health, or (ii) a control arm for those who were free from intervention. Data was collected, at baseline and immediately after the intervention ended by using a structured self-administered questionnaire. To compare differences in the change from baseline to post-intervention between the two arms we use the chi-square test and independent-samples t-test. To see the effect of the CBSRHE by controlling the effect confounding inverse probability-weighted analysis was conducted.ResultA total of 832 and 820 students participated in a baseline and post-test respectively. The proportion of youth who practice receptive penetrative sex decreases from 40.9% to 28.3% in the intervention arm compared to 37.6% to 37.3% in the non-intervention arm between baseline and end line, with statistically significant differences between groups. However, there are statistically significant differences between the intervention and control groups in terms of changes in contraception utilization (X2 = 1.21; P>0.05). Furthermore, there were significant improvements in knowledge and attitude among the intervention arm a comprehensive knowledge of HIV/AIDS (ATE = 0.22,95% CI, 0.14 to 0.29; p < 0.01), an average change of attitude toward HIV/AIDS(ATE = 1.32, 95% CI, 1.18 to 1.47; p < 0.01), comprehensive condom knowledge score (ATE = 0.23, 95% CI, 0.13 to 0.33; p < 0.01) and the average change of attitude toward condom score (ATE = 1.83, 95% CI, 1.19 to 2.77; p < 0.01).Conclusion and recommendationIt was found that there was a significant difference in knowledge and attitude toward a disk sexual behaviors among r one student. This implies that the educational authority o the country can gain through the adoption of courses to all universities across the country, besides doing further comparative studies to determine the long-term effect of the course supported with models and/or theories like the theory of change.

Metabolic syndrome (MetS) is a chronic disease caused by obesity, high blood pressure, high blood sugar, and dyslipidemia and may lead to cardiovascular disease or type 2 diabetes. Therefore, the detection and prevention of MetS at an early stage are imperative. Individuals can detect MetS early and manage it effectively if they can easily monitor their health status in their daily lives. In this study, a predictive model for MetS was developed utilizing solely noninvasive information, thereby facilitating its practical application in real-world scenarios. The model's construction deliberately excluded three features requiring blood testing, specifically those for triglycerides, blood sugar, and HDL cholesterol. We used a large-scale Korean health examination dataset (n = 70, 370; the prevalence of MetS = 13.6%) to develop the predictive model. To obtain informative features, we developed three novel synthetic features from four basic information: waist circumference, systolic and diastolic blood pressure, and gender. We tested several classification algorithms and confirmed that the decision tree model is the most appropriate for the practical prediction of MetS. The proposed model achieved good performance, with an AUC of 0.889, a recall of 0.855, and a specificity of 0.773. It uses only four base features, which results in simplicity and easy interpretability of the model. In addition, we performed calibrations on the prediction probability and calibrated the model. Therefore, the proposed model can provide MetS diagnosis and risk prediction results. We also proposed a MetS risk map such that individuals could easily determine whether they had metabolic syndrome.

Introduction: In this paper we consider system dynamics (SD) modelling of tradable transport permit schemes (TTPS). TTPS are complex and uncertain, having not yet been implemented beyond experimental trials anywhere in the world, yet have for some time been suggested as an efficient and equitable policy response to reducing car-based travel and its associated externalities.Method: Although there is a large number of econometric models that explore the potential of TTPS, there have been none published (to our knowledge) that have used the SD approach. SD is an appropriate method for developing our understanding of TTPS efficiency and equity as it captures feedbacks and tracks the influence of the TTPS over a period of time. Thus, we have developed an SD model of TTPS, drawing from the literature that already exists. It is a micro-level model that considers heterogeneity within a population on a daily basis over a matter of months. We carry out sensitivity testing of price sensitivity, initial permit price, daily preference and permit allocation and develop combined scenarios of these attributes.Results: Our modelling results suggest a sensitivity of TTPS to heterogeneity across the population, which will influence the final equilibrium price. Trading encourages a redistribution of wealth across the population but may also mean that some travel needs are not met, which may require some allocation according to need or a certain portion of protected permits. The inclusion of non-car users within the allocation further encourages trading behaviours and allows for compensation for externalities of car use.Discussion: Through an analysis of outputs we are able to bring new insights into the governance frameworks required for a successful TTPS. In particular we have shown the importance of allocation considerations in the design of a TTPS when issues of fairness across the population are considered. Although there is no data of existing schemes available for us to calibrate our models, we compare the trends with data from an in-the-field TTPS experiment.

ObjectiveDespite progress in endonasal skull-base neurosurgery, cerebrospinal fluid (CSF) rhinorrhoea remains common and significant. The CRANIAL study sought to determine 1) the scope of skull-base repair methods used, and 2) corresponding rates of postoperative CSF rhinorrhoea in the endonasal transsphenoidal approach (TSA) and the expanded endonasal approach (EEA) for skull-base tumors.MethodsA prospective observational cohort study of 30 centres performing endonasal skull-base neurosurgery in the UK and Ireland (representing 91% of adult units). Patients were identified for 6 months and followed up for 6 months. Data collection and analysis was guided by our published protocol and pilot studies. Descriptive statistics, univariate and multivariable logistic regression models were used for analysis.ResultsA total of 866 patients were included - 726 TSA (84%) and 140 EEA (16%). There was significant heterogeneity in repair protocols across centres. In TSA cases, nasal packing (519/726, 72%), tissue glues (474/726, 65%) and hemostatic agents (439/726, 61%) were the most common skull base repair techniques. Comparatively, pedicled flaps (90/140, 64%), CSF diversion (38/140, 27%), buttresses (17/140, 12%) and gasket sealing (11/140, 9%) were more commonly used in EEA cases. CSF rhinorrhoea (biochemically confirmed or requiring re-operation) occurred in 3.9% of TSA (28/726) and 7.1% of EEA (10/140) cases. A significant number of patients with CSF rhinorrhoea (15/38, 39%) occurred when no intraoperative CSF leak was reported. On multivariate analysis, there may be marginal benefits with using tissue glues in TSA (OR: 0.2, CI: 0.1-0.7, p

In this work we are concerned with how the introduction of connected and automated mobility (CAM) will influence liveability in cities. We engaged with city and transport planners from both Europe and the U.S. and adopted a system dynamics approach to capturing the discussions and exploring potential outcomes. There are two aims in doing this: (1) to identify the concerns of city planners and how they differ from the traditional focus of transport researchers; but also (2) to develop a causal loop diagram (CLD) that can both explore the potential systemic effects of CAM and help to communicate those effects and the underlying mental models. Addressing these aims can inform policy design related to both CAM specifically and urban mobility more generally. In a change from previous related studies, we allowed the participants to establish their concept of liveability in cities and did not define a specific CAM scenario. This broad scope was critical in capturing the high-level view of what really matters to city stakeholders. We have established that a focus on a more holistic understanding of interactions related to sustainability is required rather than on specific transport modes or technology. A key insight that emerged was that quality of life (QoL) was the dominant concern of city planners, regardless of how it is achieved. The specifics of new services or technologies (such as CAM) are secondary concerns - which are important only insofar as they support the higher goal of improving QoL. As a result, we have produced a high level CLD that can be used as a starter for any future research in the area of CAM and liveability in cities and which may resonate better than previous CAM models have with city planners and policy makers—those who will ultimately play a key role in recommending and then implementing changes affecting QoL.

The workforce of the medical specialty of Rehabilitation Medicine (RM) in the UK is 10 times less than the European average for the specialty of Physical and Rehabilitation Medicine (PRM). This can be explained partly by the difference in the scope of practice within the specialty between the UK and other European countries and USA. This opinion paper aims to compare the rehabilitation needs in chronic medical conditions and compare the scope of practice between countries within Europe and other regions of the world. The potential advantages of a broader remit specialty to improve rehabilitation care for patients by involving rehabilitation physicians in various medical conditions is explored. Recommendations have been put forward in the Rehabilitation Medicine Expansion Proposal (RMEP), which is likely to make the medical specialty of RM/ PRM more satisfying for the doctors working in the specialty and a more attractive career choice for those entering training in the specialty. There is a need for an international universal framework for the scope of the specialty to have a greater impact on improving the lives of those with chronic medical conditions.

Lifestyle factors are known to be influential determinants of health. According to the World Health Organization (WHO), approximately one third of deaths involve unhealthy lifestyle habits. Among lifestyle risk factors for head and neck cancers (HNC), alcohol consumption and smoking have an undeniable role in the multifactorial aetiology of the disease. In recent years, the promotion of healthy lifestyle choices has gained significant attention as contributory to improving health and disease prevention. Interventions to tackle these risk factors are vitally important in disease prevention and progression. However, in order to effectively prevent the disease and reduce the risk factors, it is crucial to identify what upstream reasons lead to the adoption of these lifestyle risk factors in the first place. Stress being a constant aspect of modern-day life is known to contribute to alcohol and smoking practices. In this review paper, relevant literature was searched in PubMed database for stress, lifestyle factors, HNC and cancer to explore the role of stress and its associated biological pathways as an upstream factor in the adoption of lifestyle risk factors that cause HNC. It highlights the importance of stress pathways and the Hypothalamus Pituitary Adrenal (HPA) axis as a locus of interaction between stress, alcohol, smoking and cancer. Despite their widely accepted harmful effects, alcohol and smoking remain deeply rooted in contemporary life. A greater understanding of the impact of stress on lifestyle choices and an exploration of the mechanisms resulting in stress, alcohol- and smoking- related cancer may highlight opportunities for improved prevention measures through the modification of unhealthy lifestyle choices.

The treatment landscape for lysosomal storage disorders (LSDs) is rapidly evolving. An increase in the number of preclinical and clinical studies in the last decade has demonstrated that pharmacological chaperones are a feasible alternative to enzyme replacement therapy (ERT) for individuals with LSDs. A systematic search was performed to retrieve and critically assess the evidence from preclinical and clinical applications of pharmacological chaperones in the treatment of LSDs and to elucidate the mechanisms by which they could be effective in clinical practice. Publications were screened according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) reporting guidelines. Fifty-two articles evaluating 12 small molecules for the treatment of seven LSDs are included in this review. Overall, a substantial amount of preclinical and clinical data support the potential of pharmacological chaperones as treatments for Fabry disease, Gaucher disease, and Pompe disease. Most of the available clinical evidence evaluated migalastat for the treatment of Fabry disease. There was a lack of consistency in the terminology used to describe pharmacological chaperones in the literature. Therefore, the new small molecule chaperone (SMC) classification system is proposed to inform a standardized approach for new, emerging small molecule therapies in LSDs.

It is unclear how maternal glycemic status and maternal iodine status influence birth weight among individuals with mild-to-moderate iodine deficiency (ID). We studied the association between birth weight and both maternal glucose levels and iodine intake among pregnant women with mild-to-moderate ID. Glucose values were assessed using a glucose challenge test (GCT) and non-fasting glucose levels that were determined before delivery; individuals’ iodine statuses were assessed using an iodine food frequency questionnaire; and serum thyroglobulin (Tg) and urinary iodine concentrations (UIC) were used to assess each group’s iodine status. Thyroid antibodies and free thyroxine (FT4) levels were measured. Obstetric and anthropometric data were also collected. Large-for-gestational age (LGA) status was predicted using a Cox proportional hazards model with multiple confounders. Tg > 13 g/L was independently associated with LGA (adjusted hazard ratio = 3.4, 95% CI: 1.4–10.2, p = 0.001). Estimated iodine intake correlated with FT4 among participants who reported consuming iodine-containing supplements (ICS) after adjusting for confounders (β = 0.4, 95% CI: 0.0002–0.0008, p = 0.001). Newborn weight percentiles were inversely correlated with maternal FT4 values (β = −0.2 95% CI:−0.08–−56.49, p = 0.049). We conclude that in mild-to-moderate ID regions, insufficient maternal iodine status may increase LGA risk. Iodine status and ICS intake may modify the effect that maternal dysglycemia has on offspring weight.

In Ethiopia, most of the studies on mammals have focused on single species and protected areas. This survey investigated the impacts of habitats and seasons on the medium and large-sized mammals’ diversity and distribution in a human-dominated landscape. This survey was conducted using 36 systematically distributed transect lines within stratified habitat types. A total of 685 records belonging to 21 species, six orders, and 13 families were identified, including globally vulnerable Panthera leo, Panthera pardus, and Hippopotamus amphibious. Overall, Papio anubis and Chlorocebus aethiops were the dominant species recorded in the area. Except for three species, all species encountered in the three habitats are subsets of the species recorded in the grassland. The species record frequency was highest in the forest. The dry season characterized by a higher frequency of records but by lower species richness than the wet season. In general, the study area is potential for mammalian species conservation in Ethiopia.

Abstract Mesothelin (MSLN) is an attractive candidate of targeted therapy for several cancers, and hence there are increasing needs to develop MSLN-targeting strategies for cancer therapeutics. Antibody–drug conjugates (ADCs) targeting MSLN have been demonstrated to be a viable strategy in treating MSLN-positive cancers. However, developing antibodies as targeting modules in ADCs for toxic payload delivery to the tumor site but not to normal tissues is not a straightforward task with many potential hurdles. In this work, we established a high throughput engineering platform to develop and optimize anti-MSLN ADCs by characterizing more than 300 scFv CDR-variants and more than 50 IgG CDR-variants of a parent anti-MSLN antibody as candidates for ADCs. The results indicate that only a small portion of the complementarity determining region (CDR) residues are indispensable in the MSLN-specific targeting. Also, the enhancement of the hydrophilicity of the rest of the CDR residues could drastically increase the overall solubility of the optimized anti-MSLN antibodies, and thus substantially improve the efficacies of the ADCs in treating human gastric and pancreatic tumor xenograft models in mice. We demonstrated that the in vivo treatments with the optimized ADCs resulted in almost complete eradication of the xenograft tumors at the treatment endpoints, without detectable off-target toxicity because of the ADCs’ high specificity targeting the cell surface tumor-associated MSLN. The technological platform can be applied to optimize the antibody sequences for more effective targeting modules of ADCs, even when the candidate antibodies are not necessarily feasible for the ADC development due to the antibodies’ inferior solubility or affinity/specificity to the target antigen.

Background: Moringa stenopetala is used for medicinal and nutritional purposes. This study was, therefore, conducted to assess the contribution of Moringa stenopetala based diet in reducing under nutrition in under-five children in four districts of Southern Ethiopia. Method: A community-based comparative cross-sectional study design was employed from August to September 2016 in randomly selected comparative sites among 732 under five children. Anthropometric measurements of weight and height of children were measured based on the standard measurement protocol. Regarding moringa stenopetala diet, the consumption habit was collected by using a seven days food frequency questionnaire. Amount of moringa stenopetala leaf biomass portion size consumption was measured with local measurement and converted to kilograms. Anthropometric data were analyzed using WHO Anthro software to determine the nutritional status of the child. An independent t-test was conducted to compare the mean difference of WHO-Z score of child nutritional index. Statistical mean significance difference was measured based on p-value less than 0.05 with 95% confidence level. In addition chi-square test with a p-value, less than 0.05 with a 95% confidence level was used to compare the prevalence of stunting, wasting, and underweight in moringa stenopetala based diet and non-moringa stenopetala based diet consuming area. Result: The prevalence of stunting was 19% vs. 28.8%, wasting 4.7% vs. 9.6%, and underweight 12.19% vs 13.71% in moringa stenopetala based diet consuming and non-consuming participants respectively. There was a significant difference in stunting and wasting (p < 0.05) among moringa stenopetala based diet-consuming and non-consuming participants. Conclusion: The present study showed that moringa stenopetala based diet consumption had a significant contribution in reducing under-nutrition in under-five children.

Abstract Local people's perceptions and attitudes toward wildlife have been advocating for the success of biodiversity conservation. However, area‐specific data on local people's perceptions and attitudes toward carnivore populations and conservation in human‐dominated landscapes are scarce. The purpose of this study was to investigate local people's perceptions of carnivore population abundance and trend, as well as their attitudes toward carnivore conservation in the Southern Rift Valley of Ethiopia. We collected data from 352 households' interviews using a semi‐structured questionnaire and photographic sampling of 13 carnivore species in 2020. About 57% of respondents perceived the population abundance trend of carnivores had decreased between 2015 and 2019. The reported decline was higher for lions, caracals, and leopards, while the increase was higher for common genets and mongooses. The reported population abundance of carnivore species varied significantly. Only marginally more people (52%) opposed carnivore conservation, citing livestock predation as the primary reason. Two thirds of respondents opposed the conservation of spotted hyenas, black‐backed jackals, common genets, and mongoose species while supporting the conservation of lions, caracals, African civets, and leopards. Respondents' livestock number was the most important factor significantly affecting all three models (population abundance, population trend, and support for conservation). Age and education status were displayed to have an effect on population abundance and trend models, while gender, land size, and damage to livestock were shown to have an effect on one of the two models. Thus, we recommend that awareness raising of human–carnivore coexistence through adult education programs be targeted at people who oppose conservation, own more livestock, experience more livestock damage, and have not received formal education. Also, effective livestock husbandry practices should be implemented to promote peaceful human–carnivore coexistence.

Objective To investigate features of Guillain-Barré syndrome (GBS) following SARS-CoV-2 vaccines and evaluate for a causal link between the two.Methods We captured cases of GBS after SARS-CoV-2 vaccination through a national, open-access, online surveillance system. For each case, the certainty of GBS was graded using the Brighton criteria, and the relationship to the vaccine was examined using modified WHO Causality Assessment criteria. We compared age distribution of cases with that of prepandemic GBS cases and clinical features with the International GBS Outcome Study (IGOS).Results Between 1 January and 30 June 2021, we received 67 reports of GBS following the ChAdOx1 vaccine (65 first doses) and three reports following the BNT162b2 vaccine (all first doses). The causal association with the vaccine was classified as probable for 56 (80%, all ChAdOx1), possible for 12 (17%, 10 ChAdOx1) and unlikely for two (3%, 1 ChAdOx1). A greater proportion of cases occurred in the 50–59 age group in comparison with prepandemic GBS. Most common clinical variants were sensorimotor GBS (n=55; 79%) and facial diplegia with paraesthesias (n=10; 14%). 10% (n=7/69) of patients reported an antecedent infection, compared with 77% (n=502/652) of the IGOS cohort (p

Abstract Background We present our 9-year consecutive case series of skull base chordomas and chondrosarcomas from a UK tertiary referral centre, discussing treatments offered and outcomes. This was carried out to improve understanding around current treatment and to better inform the management of future patients. Methods Consecutive case series over a 9-year period (2007–2016). Retrospective data analysis from the electronic skull base multidisciplinary team database and the digital patient records at a UK tertiary referral centre Results Twenty-four patients were identified (11 chordomas, 13 chondrosarcomas, mean age 52). Nineteen had proton beam therapy (PBT) postoperatively; two had intensity-modulated radiotherapy; two had no further treatment. One patient was lost to follow-up. All chordomas were resected via a transnasal endoscopic approach. Of the 19 patients undergoing resection with PBT, 13 were disease free at latest follow-up, and six patients had local recurrence, of which two died (mean follow up 7.4 years). Of the three patients treated with surgery then IMRT/TomoTherapy, one died 4 years post-treatment, and the other two are alive after 4 and 5 years of follow-up respectively. Of the two patients treated with surgery alone, one was lost to follow-up, and the other is alive after more than 8 years. Chondrosarcoma 5-year survival was 91.6%, and chordoma 4-year survival was 75%. Conclusion Skull base chordomas and chondrosarcomas can be challenging to resect, and most cases require adjuvant therapy to achieve control. Where complete resection is not possible, it is critical to undertake sufficient resection to permit high-dose radiation.