Climate Change, Disease, and the State: Lessons from History

The Ohio State University Mershon Center for International Security StudiesAndrew T. Price-Smith is director of the Energy, Environment and Security Program, director of the nascent Global Health Program, and associate professor of political science at Colorado College. He held previous appointments at both the Earth Institute and the School of International and Public Affairs of Columbia University, and at the University of South Florida. He also served as interim chair of environmental science at Colorado College from 2009-10. He specializes in analyses of the effects of disease, environmental change, and energy scarcity on the security of nations.Mershon Center for International Security StudiesEvent Web Page, Streaming Video, Event Photo

Health and disease markers correlate with gut microbiome composition across thousands of people.

Variation in the human gut microbiome can reflect host lifestyle and behaviors and influence disease biomarker levels in the blood. Understanding the relationships between gut microbes and host phenotypes are critical for understanding wellness and disease. Here, we examine associations between the gut microbiota and ~150 host phenotypic features across ~3,400 individuals. We identify major axes of taxonomic variance in the gut and a putative diversity maximum along the Firmicutes-to-Bacteroidetes axis. Our analyses reveal both known and unknown associations between microbiome composition and host clinical markers and lifestyle factors, including host-microbe associations that are composition-specific. These results suggest potential opportunities for targeted interventions that alter the composition of the microbiome to improve host health. By uncovering the interrelationships between host diet and lifestyle factors, clinical blood markers, and the human gut microbiome at the population-scale, our results serve as a roadmap for future studies on host-microbe interactions and interventions

ACHE : the Arthroplasty Candidacy Help Engine : using PROMs data to identify thresholds for referral in hip and knee replacement surgery

Background: At present there is no evidence to support the use of the Oxford PROM scores to set pre-operative thresholds for referral for hip and knee replacement surgery. Despite this the practice has been widespread in the NHS. Objectives/Research Questions: Can the Oxford Hip/Knee scores (OKS/OHS) be used to set referral thresholds for hip/knee replacement surgery? Does the choice of threshold affect the cost effectiveness of the procedure? Methods: Thresholds for the Oxford scores were calculated, based on a capacity to benefit model linking pre-operative OKS/OHS to the probability of a good outcome – creating an online ACHE tool. Markov models were constructed to assess how the cost-effectiveness of TKA and THA compared with no arthroplasty varies with pre-operative OKS/OHS over a 10-year time horizon from a UK NHS perspective. Results: The absolute threshold for the OHS was 41 and 42 for the OKS. A model was created that used preoperative Oxford scores to estimate the probability of a good outcome allowed – e.g. an OHS of 35 or an OKS of 30 offers a patient a 70% probability of achieving a good outcome. The economic evaluation demonstrated that TKA and THA cost 99.9% of patients who currently undergo surgery. It is cost-effective to conduct TKA on patients with OKS of 43 (95% credible interval, CrI: 43,44) or less and on patients with THA of 45 or less (95% CrI: 44, 45). Conclusion: Using the ACHE tool the Oxford Hip/Knee Scores can be used to assess an individual patients suitability for hip or knee replacement surgery. On a population level both interventions are highly cost-effective right up to the absolute threshold for intervention. The ACHE tool appears to be a useful evidence based clinical tool to aid referral from primary to secondary care

Meniscal Transplant surgery or Optimised Rehabilitation full randomised trial (MeTeOR2): a study protocol

Introduction: Pain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective. Methods and analysis: The Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT). Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement. Ethics and dissemination: The trial was approved by the London—Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890). Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate. This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. Trial registration number: ISRCTN87336549

Sex-Stratified Genome-Wide Association Study of Multisite Chronic Pain in UK Biobank

Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception

Medication-related costs of rhinitis in Australia : a NostraData cross-sectional study of pharmacy purchases

Peer reviewedPublisher PD

Polygenic risk for schizophrenia and subcortical brain anatomy in the UK Biobank cohort

Research has shown differences in subcortical brain volumes between participants with schizophrenia and healthy controls. However, none of these differences have been found to associate with schizophrenia polygenic risk. Here, in a large sample (n = 14,701) of unaffected participants from the UK Biobank, we test whether schizophrenia polygenic risk scores (PRS) limited to specific gene-sets predict subcortical brain volumes. We compare associations with schizophrenia PRS at the whole genome level (‘genomic’, including all SNPs associated with the disorder at a p-value threshold < 0.05) with ‘genic’ PRS (based on SNPs in the vicinity of known genes), ‘intergenic’ PRS (based on the remaining SNPs), and genic PRS limited to SNPs within 7 gene-sets previously found to be enriched for genetic association with schizophrenia (‘abnormal behaviour,’ ‘abnormal long-term potentiation,’ ‘abnormal nervous system electrophysiology,’ ‘FMRP targets,’ ‘5HT2C channels,’ ‘CaV2 channels’ and ‘loss-of-function intolerant genes’). We observe a negative association between the ‘abnormal behaviour’ gene-set PRS and volume of the right thalamus that survived correction for multiple testing (ß = −0.031, pFDR = 0.005) and was robust to different schizophrenia PRS p-value thresholds. In contrast, the only association with genomic PRS surviving correction for multiple testing was for right pallidum, which was observed using a schizophrenia PRS p-value threshold < 0.01 (ß = −0.032, p = 0.0003, pFDR = 0.02), but not when using other PRS P-value thresholds. We conclude that schizophrenia PRS limited to functional gene sets may provide a better means of capturing differences in subcortical brain volume than whole genome PRS approaches

Does flip-flop style footwear modify ankle biomechanics and foot loading patterns?

Background Flip-flops are an item of footwear, which are rubber and loosely secured across the dorsal fore-foot. These are popular in warm climates; however are widely criticised for being detrimental to foot health and potentially modifying walking gait. Contemporary alternatives exist including FitFlop, which has a wider strap positioned closer to the ankle and a thicker, ergonomic, multi-density midsole. Therefore the current study investigated gait modifications when wearing flip-flop style footwear compared to barefoot walking. Additionally walking in a flip-flop was compared to that FitFlop alternative. Methods Testing was undertaken on 40 participants (20 male and 20 female, mean ± 1 SD age 35.2 ± 10.2 years, B.M.I 24.8 ± 4.7 kg.m−2). Kinematic, kinetic and electromyographic gait parameters were collected while participants walked through a 3D capture volume over a force plate with the lower limbs defined using retro-reflective markers. Ankle angle in swing, frontal plane motion in stance and force loading rates at initial contact were compared. Statistical analysis utilised ANOVA to compare differences between experimental conditions. Results The flip-flop footwear conditions altered gait parameters when compared to barefoot. Maximum ankle dorsiflexion in swing was greater in the flip-flop (7.6 ± 2.6°, p = 0.004) and FitFlop (8.5 ± 3.4°, p &lt; 0.001) than barefoot (6.7 ± 2.6°). Significantly higher tibialis anterior activation was measured in terminal swing in FitFlop (32.6%, p &lt; 0.001) and flip-flop (31.2%, p &lt; 0.001) compared to barefoot. A faster heel velocity toward the floor was evident in the FitFlop (−.326 ± .068 m.s−1, p &lt; 0.001) and flip-flop (−.342 ± .074 m.s−1, p &lt; 0.001) compared to barefoot (−.170 ± .065 m.s−1). The FitFlop reduced frontal plane ankle peak eversion during stance (−3.5 ± 2.2°) compared to walking in the flip-flop (−4.4 ± 1.9°, p = 0.008) and barefoot (−4.3 ± 2.1°, p = 0.032). The FitFlop more effectively attenuated impact compared to the flip-flop, reducing the maximal instantaneous loading rate by 19% (p &lt; 0.001). Conclusions Modifications to the sagittal plane ankle angle, frontal plane motion and characteristics of initial contact observed in barefoot walking occur in flip-flop footwear. The FitFlop may reduce risks traditionally associated with flip-flop footwear by reducing loading rate at heel strike and frontal plane motion at the ankle during stance