Changes in NDVI and human population in protected areas on the Tibetan Plateau

Understanding the Tibetan Plateau’s role in environmental change has gained increasing scientific attention in light of warming and changes in landmanagement. We examine changes in greenness over the Tibetan Plateau using the Normalized Difference Vegetation Index (NDVI) from the Global Inventory Monitoring and Modeling Study (GIMMS3g) to identify significant changes over the entire plateau, six ecoregions, and protected areas based on a multiyear time series of July imagery from 1982 to 2015. We also test whether there have been changes in human populations in protected areas. There has been relatively little change in mean NDVI over the Tibetan Plateau or ecoregions, however, there were significant changes at the pixel level. There are sixty-nine protected areas on the Tibetan Plateau; sixtytwo protected areas had no significant change in mean NDVI and seven protected areas experienced a significant increase in NDVI. There has been an increase in population within protected areas from 2000 to 2015; however, mean populations significantly increased in two protected areas and significantly decreased in four protected areas. Results suggest a slow greening of the Tibetan Plateau, ecoregions, and protected areas, with a more rapid greening in northern Tibet at the pixel level. Most protected areas are experiencing minor changes in NDVI independent of human population

Residual meningioma: Volumetric growth and progression following surgical resection

Introduction: Meningiomas are the most common primary brain tumour, with the primary management strategy being surgery. A residual tumour is identified in approximately 25% of operated meningioma. They have a higher progression rate than if no residual is present. The precise growth rates of these tumours on long-term follow up, using accurate and verified 3D volume measuring tools, remains unclear. This uncertainty has implications for patient management, and stratification of treatment paradigms. Previous literature has used small sample sizes, and different definitions to define an increase in meningioma volume after surgery. There is a need for a large study delineating the volumetric growth of residual meningioma, using uniform progression definitions. The aims of this thesis were to conduct a systematic review, followed by a highly powered study measuring the volumetric growth of residual meningioma. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using six scientific databases. After audit approval, a retrospective cohort study of 236 patients with residual meningioma was completed, analysing the tumour volume using manual segmentation at every MRI follow up scan, and conducted non-linear regression analysis of the growth trajectories of residual tumour. Results: The systematic review revealed only four studies available in the literature, with variable growth rates and factors associated with growth identified. The retrospective study revealed a low rate of tumour growth after surgery, both in absolute and relative tumour volume (0.11cm3 and 4.3% per year respectively). More than half patients (55.9%) on long-term follow up demonstrated sufficient volumetric growth to satisfy a definition of tumour progression, and most patients were managed conservatively for this (73.7%). Multivariable analysis revealed skull base location (Hazard ratio [HR] 1.58, 95% Confidence interval (CI) 1.02-2.44), adjuvant fRT (HR 1.72, 95% CI 1.03-2.89) and elevated Ki-67 index (HR 3.62, 95% CI 1.25-10.48) to be associated with high volumetric growth. Regression analysis revealed that most residual tumours exhibit exponential, logistic, and gompertz growth patterns. Conclusions: Residual meningioma is a commonly encountered clinical entity, but volumetric growth rates are scarcely reported. In our retrospective cohort of 236 meningiomas, the absolute and relative growth rate was low, yet over a long period of follow up most met a Response Assessment in Neuro-Oncology (RANO) definition of progression. Further clinical studies of WHO grade 2 meningiomas, and studies that use a uniform growth definition are required to delineate growth rates, and substantiate the findings of this work

Lacosamide add-on therapy for focal epilepsy

BACKGROUND: This is an updated version of the Cochrane review published in 2015. Around half of people with epilepsy will not achieve seizure freedom on their first antiepileptic drug; many will require add‐on therapy. Around a third of people fail to achieve complete seizure freedom despite multiple antiepileptic drugs. Lacosamide has been licenced as an add‐on therapy for drug‐resistant focal epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of lacosamide as an add‐on therapy for children and adults with drug‐resistant focal epilepsy. SEARCH METHODS: We searched the following databases (22 August 2019): the Cochrane Register of Studies (CRS Web), including the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 20 August 2019), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP), with no language restrictions. We contacted UCB Pharma (sponsors of lacosamide). SELECTION CRITERIA: Randomised controlled trials of add‐on lacosamide in people with drug‐resistant focal epilepsy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology, assessing the following outcomes: 50% or greater reduction in seizure frequency; seizure freedom; treatment withdrawal; adverse events; quality of life; and cognitive changes. The primary analyses were intention‐to‐treat. We estimated summary risk ratios (RR) for each outcome presented with 99% confidence intervals (CI), except for 50% or greater seizure reduction, seizure freedom and treatment withdrawal which were presented with 95% CIs. We performed subgroup analyses according to lacosamide dose and sensitivity analyses according to population age, whereby data from children were excluded from the meta‐analysis. MAIN RESULTS: We included five trials (2199 participants). The risk of bias for all studies was low to unclear. All studies were placebo‐controlled and assessed doses from 200 mg to 600 mg per day. One study evaluated lacosamide in children; all other studies were in adults. Trial duration ranged from 24 to 26 weeks. All studies used adequate methods of randomisation and were double‐blind. Overall, the certainty of the evidence for the outcomes was judged as moderate to high, with the exception of seizure freedom which was low. The RR for a 50% or greater reduction in seizure frequency for all doses of lacosamide compared with placebo was 1.79 (95% CI 1.55 to 2.08; 5 studies; 2199 participants; high‐certainty evidence). The RR for seizure freedom for all doses of lacosamide compared with placebo was 2.27 (95% CI 1.35 to 3.83; 5 studies; 2199 participants; low‐certainty evidence). The RR for treatment withdrawal for all doses of lacosamide compared with placebo was 1.57 (95% CI 1.24 to 1.98; 5 studies; 2199 participants; moderate‐certainty evidence). The estimated effect size for most outcomes did not change considerably following sensitivity analysis. For seizure freedom, however, the RR nearly doubled upon the exclusion of data from children (RR 4.04, 95% CI 1.52 to 10.73). Adverse events associated with lacosamide included: abnormal co‐ordination (RR 6.12, 99% CI 1.35 to 27.77), blurred vision (RR 4.65, 99% CI 1.24 to 17.37), diplopia (RR 5.59, 99% CI 2.27 to 13.79), dizziness (RR 2.96, 99% CI 2.09 to 4.20), nausea (RR 2.35, 99% CI 1.37 to 4.02), somnolence (RR 2.04, 99% CI 1.22 to 3.41), vomiting (RR 2.94, 99% CI 1.54 to 5.64), and number of participants experiencing one or more adverse events (RR 1.12, 99% CI 1.01 to 1.24). Adverse events that were not significant were: vertigo (RR 3.71, 99% CI 0.86 to 15.95), rash (RR 0.58, 99% CI 0.17 to 1.89), nasopharyngitis (RR 1.41, 99% CI 0.87 to 2.28), headache (RR 1.34, 99% CI 0.90 to 1.98), fatigue (RR 2.11, 99% CI 0.92 to 4.85), nystagmus (RR 1.47, 99% CI 0.61 to 3.52), and upper respiratory tract infection (RR 0.70, 99% CI 0.43 to 1.15). AUTHORS' CONCLUSIONS: Lacosamide is effective and well‐tolerated in the short term when used as add‐on treatment for drug‐resistant focal epilepsy. Lacosamide increases the number of people with 50% or greater reduction in seizure frequency and may increase seizure freedom, compared to placebo. Higher doses of lacosamide may be associated with higher rates of adverse events and treatment withdrawal. Additional evidence is required assessing the use of lacosamide in children and on longer‐term efficacy and tolerability

Diagnostic utility of Brain Injury Guidelines (BIG): systematic review and meta-analysis for prediction of neurosurgical intervention in traumatic brain injury

Background The Brain Injury Guidelines (BIG) categorize the severity of Traumatic Brain Injury (TBI). The efficacy of BIG in predicting radiological deterioration and the necessity for neurosurgical intervention remains uncertain, as there is a lack of examination of pooled data from current literature despite validation in numerous single and multi-institutional studies. The aim of this study was to analyze existing studies to determine the diagnostic accuracy of BIG scoring criteria. Methods A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPEROID CRD42021277542). Three databases were searched, and articles published from 2000 to October 2022 were included (last search date: 25 November 2022). Pooled sensitivity and specificity were calculated using random effects meta-analysis. Results Of the 1130 articles identified, 13 were included in the analysis (9032 patients – 1433 BIG1, 2136 BIG2 & 3189 BIG3). A total of 2274 patients were not classified under either group. Pooled sensitivity for predicting neurosurgical intervention was 1.00 (95%CI:1.00–1.00), and 0.98 for radiological deterioration (95% CI: 0.927–0.996). The specificity in predicting radiological deterioration was 0.18 (95% CI: 0.16–0.21) and 0.05 for neurosurgical intervention (95% CI 0.05–0.05). Conclusions The BIG score is highly sensitive at excluding TBI cases that do not require neurosurgical intervention; however, BIG-2 and BIG-3 might not be useful for ruling in TBI patients who require neurosurgical intervention

Ultra-Processed Food Intake Is Associated with Non-Alcoholic Fatty Liver Disease in Adults: A Systematic Review and Meta-Analysis

Non-alcoholic fatty liver disease (NAFLD) is associated with overweight/obesity, metabolic syndrome and type 2 diabetes (T2D) due to chronic caloric excess and physical inactivity. Previous meta-analyses have confirmed associations between ultra-processed food (UPF) intake and obesity and T2D. We aim to ascertain the contribution of UPF consumption to the risk of developing NAFLD. We performed a systematic review and meta-analysis (PROSPERO (CRD42022368763)). All records registered on Ovid Medline and Web of Science were searched from inception until December 2022. Studies that assessed UPF consumption in adults, determined according to the NOVA food classification system, and that reported NAFLD determined by surrogate (steatosis) scores, imaging or liver biopsy were included. The association between UPF consumption and NAFLD was assessed using random-effects meta-analysis methods. Study quality was assessed, and evidence credibility evaluated, using the Newcastle Ottawa Scale and NutriGrade systems, respectively. A total of 5454 records were screened, and 112 records underwent full text review. From these, 9 studies (3 cross-sectional, 3 case-control and 3 cohort), analysing 60,961 individuals, were included in the current review. Both moderate (vs. low) (pooled relative risk 1.03 (1.00–1.07) (p = 0.04) (I2 = 0%)) and high (vs. low) (1.42 (1.16–1.75) (&lt;0.01) (I2 = 89%)) intake of UPF significantly increased the risk of NAFLD. Funnel plots demonstrate low risk of publication bias. Consumption of UPF is associated with NAFLD with a dose–response effect. Public health measures to reduce overconsumption of UPF are imperative to reduce the burden of NAFLD, and the related conditions, obesity and T2D.</jats:p

A survey of foot disinfection practices for control of bovine digital dermatitis; evaluating solution depth, footbath hygiene, and the potential of footbaths as infection reservoirs for Treponema species

Bovine digital dermatitis remains a widespread endemic disease of dairy cattle worldwide. Footbathing is commonly used as a control measure and has significant economic and environmental impact. There are few studies documenting footbathing practices on dairy farms, or evaluating their suitability for achieving foot disinfection. This study describes footbathing practices on 32 farms observed in the United Kingdom, Ireland, and the Netherlands. We measured solution depth throughout footbathing and observed levels below 7cm on 9/32 farms, which leads to inadequate foot coverage. Solution depth was associated with the number of cow passages, decreasing by 1.2cm for every 100 cow passages. We also describe levels of organic matter content (g/L) throughout footbathing as a proxy for footbath hygiene. Our data indicates that almost half of footbaths (15/32) became contaminated above the 20g/L threshold to which veterinary biocides are tested for efficacy, and that organic matter content is associated with the number of cow passages per liter of footbathing solution provided. A multivariable mixed model predicted that one liter of footbathing solution per cow should be sufficient to prevent excess contamination. As a further measure of hygiene, we tested a subset of footbath samples to quantify the amount of DNA present from the Treponema species which are considered instrumental in the etiology of digital dermatitis. We did not detect Treponema DNA in footbath samples, suggesting they are unlikely to act as infection reservoirs for this disease. Multivariable mixed models including farm identity as a random effect demonstrated that for both change in solution depth and organic matter content the effect of farm-level factors was large. Because of the magnitude of this farm effect, applying model predictions will not translate to adequate solution depth and hygiene on all farms. Our data highlights the importance of footbath auditing on individual farms

Ultra‐processed food and non‐communicable diseases in the United Kingdom: A narrative review and thematic synthesis of literature

SummaryThe social and economic constructs of the United Kingdom (UK) provide a fertile food environment for the dramatic expansion in the ultra‐processed food (UPF) market, driving increased UPF consumption. This has coincided with the significant increase in the incidence and prevalence of non‐communicable diseases (NCDs) such as obesity, type 2 diabetes, cardiovascular disease, and cancer, with an inherent impact on morbidity and mortality. Our review aims to assess the current epidemiological and public health trends in the United Kingdom, specifically examining consumption of UPFs and subsequent development of NCDs, summarizing existing meta‐analytical and experimental approaches. First, we address important socioeconomic and psychosocial domains that may contribute to increased availability and consumption of UPF. Additionally, we explore the putative mechanistic basis for the association between UPFs and NCDs: partly attributable to their energy density, the macro‐ and micronutrient composition (including high refined carbohydrate, saturated, and trans fats composition, in addition to low fiber and protein content), and artificially engineered additives and other compounds that adversely affect health in inadequately researched pathophysiological pathways. This review highlights the importance of promoting minimally processed diets to both clinical and political decision makers.</jats:p

National audit of pathways in epileptic seizure referrals (NAPIER) : a national, multicentre audit of first seizure clinics throughout the UK and Ireland

Acknowledgements We would like to thank the following collaborators of the NANSIG Collaborative, who conducted local data collection and analysis: Ajitesh Anand, Alena Abraham, Alex Irving, Amogh Prabhakar, Catinca Ciuculete, Cindy Zheng, Daniel King, Declan Browne, Dipesh Kumar Barua, Dorota Duklas, Farhat Mirza, Fumilola Olaifa, Harmani Daler, Hassan Naveed, Heba Elzeky, Hedley Emsley, Honglin Zhu, Ian Morrison, Irtiza Syed, Isabel Summers, Jack Wellington, Jasmine Wall, John O'Dwyer, Jordan Ford, Karthikeyan Sivaganesh, Katja Lassak, Keara Jamison, Khalid Hamandi, Kourosh Parvi, Lareyna McMenemy, Lewis McColm, Lina Aleknaite, Maithili Srikantha, Maja Kaladjiska, Marie Jasim, Mark McCarron, Martina Mockova, Mohammad Marar, Naghme Adab, Najma Ahmed, Nye Rhys Potter, Pavithira Tharmapoopathy, Prithvi Dixit, Rajiv Mohanraj, Ravanth Baskaran, Richard Davenport, Robert Seah, Rohan Bhate, Rohan Gupta, Sahar Shams, Siddarth Kannan, Tahir Majeed, Timothy Counihan, Tomas Ferriera, Yihui Cheng, Zaib ShamshiPeer reviewedPostprin

Amino acid-dependent cMyc expression is essential for NK cell metabolic and functional responses in mice

Natural killer (NK) cells are lymphocytes with important anti-tumour functions. Cytokine activation of NK cell glycolysis and oxidative phosphorylation (OXPHOS) are essential for robust NK cell responses. However, the mechanisms leading to this metabolic phenotype are unclear. Here we show that the transcription factor cMyc is essential for IL-2/IL-12-induced metabolic and functional responses in mice. cMyc protein levels are acutely regulated by amino acids; cMyc protein is lost rapidly when glutamine is withdrawn or when system L-amino acid transport is blocked. We identify SLC7A5 as the predominant system L-amino acid transporter in activated NK cells. Unlike other lymphocyte subsets, glutaminolysis and the tricarboxylic acid cycle do not sustain OXPHOS in activated NK cells. Glutamine withdrawal, but not the inhibition of glutaminolysis, results in the loss of cMyc protein, reduced cell growth and impaired NK cell responses. These data identify an essential role for amino acid-controlled cMyc for NK cell metabolism and function