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Background: Exposure to cold spells is associated with mortality. However, little is known about the global mortality burden of cold spells., Methods: A three-stage meta-analytical method was used to estimate the global mortality burden associated with cold spells by means of a time series dataset of 1960 locations across 59 countries (or regions). First, we fitted the location-specific, cold spell-related mortality associations using a quasi-Poisson regression with a distributed lag non-linear model with a lag period of up to 21 days. Second, we built a multivariate meta-regression model between location-specific associations and seven predictors. Finally, we predicted the global grid-specific cold spell-related mortality associations during 2000-19 using the fitted meta-regression model and the yearly grid-specific meta-predictors. We calculated the annual excess deaths, excess death ratio (excess deaths per 1000 deaths), and excess death rate (excess deaths per 100 000 population) due to cold spells for each grid across the world., Findings: Globally, 205 932 (95% empirical CI [eCI] 162 692-250 337) excess deaths, representing 3·81 (95% eCI 2·93-4·71) excess deaths per 1000 deaths (excess death ratio), and 3·03 (2·33-3·75) excess deaths per 100 000 population (excess death rate) were associated with cold spells per year between 2000 and 2019. The annual average global excess death ratio in 2016-19 increased by 0·12 percentage points and the excess death rate in 2016-19 increased by 0·18 percentage points, compared with those in 2000-03. The mortality burden varied geographically. The excess death ratio and rate were highest in Europe, whereas these indicators were lowest in Africa. Temperate climates had higher excess death ratio and rate associated with cold spells than other climate zones., Interpretation: Cold spells are associated with substantial mortality burden around the world with geographically varying patterns. Although the number of cold spells has on average been decreasing since year 2000, the public health threat of cold spells remains substantial. The findings indicate an urgency of taking local and regional measures to protect the public from the mortality burdens of cold spells., Funding: Australian Research Council, Australian National Health and Medical Research Council, EU's Horizon 2020 Project Exhaustion., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Increased mortality risk is associated with short-term temperature variability. However, to our knowledge, there has been no comprehensive assessment of the temperature variability-related mortality burden worldwide. In this study, using data from the MCC Collaborative Research Network, we first explored the association between temperature variability and mortality across 43 countries or regions. Then, to provide a more comprehensive picture of the global burden of mortality associated with temperature variability, global gridded temperature data with a resolution of 0·5° × 0·5° were used to assess the temperature variability-related mortality burden at the global, regional, and national levels. Furthermore, temporal trends in temperature variability-related mortality burden were also explored from 2000-19., Methods: In this modelling study, we applied a three-stage meta-analytical approach to assess the global temperature variability-related mortality burden at a spatial resolution of 0·5° × 0·5° from 2000-19. Temperature variability was calculated as the SD of the average of the same and previous days' minimum and maximum temperatures. We first obtained location-specific temperature variability related-mortality associations based on a daily time series of 750 locations from the Multi-country Multi-city Collaborative Research Network. We subsequently constructed a multivariable meta-regression model with five predictors to estimate grid-specific temperature variability related-mortality associations across the globe. Finally, percentage excess in mortality and excess mortality rate were calculated to quantify the temperature variability-related mortality burden and to further explore its temporal trend over two decades., Findings: An increasing trend in temperature variability was identified at the global level from 2000 to 2019. Globally, 1 753 392 deaths (95% CI 1 159 901-2 357 718) were associated with temperature variability per year, accounting for 3·4% (2·2-4·6) of all deaths. Most of Asia, Australia, and New Zealand were observed to have a higher percentage excess in mortality than the global mean. Globally, the percentage excess in mortality increased by about 4·6% (3·7-5·3) per decade. The largest increase occurred in Australia and New Zealand (7·3%, 95% CI 4·3-10·4), followed by Europe (4·4%, 2·2-5·6) and Africa (3·3, 1·9-4·6)., Interpretation: Globally, a substantial mortality burden was associated with temperature variability, showing geographical heterogeneity and a slightly increasing temporal trend. Our findings could assist in raising public awareness and improving the understanding of the health impacts of temperature variability., Funding: Australian Research Council, Australian National Health & Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Heat exposure is a risk factor for urologic diseases. However, there are limited existing studies that have examined the relationship between high temperatures and urologic disease. The aim of this study was to examine the associations between heat exposure and hospitalizations for urologic diseases in Queensland, Australia, during the hot seasons of 1995-2016 and to quantify the attributable risks., Methods: We obtained 238 427 hospitalized cases with urologic diseases from Queensland Health between 1 December 1995 and 31 December 2016. Meteorological data were collected from the Scientific Information for Land Owners-a publicly accessible database of Australian climate data that provides daily data sets for a range of climate variables. A time-stratified, case-crossover design fitted with the conditional quasi-Poisson regression model was used to estimate the associations between temperature and hospitalizations for urologic diseases at the postcode level during each hot season (December-March). Attributable rates of hospitalizations for urologic disease due to heat exposure were calculated. Stratified analyses were performed by age, sex, climate zone, socio-economic factors and cause-specific urologic diseases., Results: We found that a 1°C increase in temperature was associated with a 3.3% [95% confidence interval (CI): 2.9%, 3.7%] increase in hospitalization for the selected urologic diseases during the hot season. Hospitalizations for renal failure showed the strongest increase 5.88% (95% CI: 5.25%, 6.51%) among the specific causes of hospital admissions considered. Males and the elderly (≥60 years old) showed stronger associations with heat exposure than females and younger groups. The sex- and age-specific associations with heat exposure were similar across specific causes of urologic diseases. Overall, nearly one-fifth of hospitalizations for urologic diseases were attributable to heat exposure in Queensland., Conclusions: Heat exposure is associated with increased hospitalizations for urologic disease in Queensland during the hot season. This finding reinforces the pressing need for dedicated public health-promotion campaigns that target susceptible populations, especially for those more predisposed to renal failure. Given that short-term climate projections identify an increase in the frequency, duration and intensity of heatwaves, this public health advisory will be of increasing urgency in coming years., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: In the context of climate change and deforestation, Brazil is facing more frequent and unprecedented wildfires. Wildfire-related PM 2·5 is associated with multiple adverse health outcomes; however, the magnitude of these associations in the Brazilian context is unclear. We aimed to estimate the association between daily exposure to wildfire-related PM 2·5 and cause-specific hospital admission and attributable health burden in the Brazilian population using a nationwide dataset from 2000 to 2015., Methods: In this nationwide time-series analysis, data for daily all-cause, cardiovascular, and respiratory hospital admissions were collected through the Brazilian Unified Health System from 1814 municipalities in Brazil between Jan 1, 2000, and Dec 31, 2015. Daily concentrations of wildfire-related PM 2·5 were estimated using the 3D chemical transport model GEOS-Chem at a 2·0° latitude by 2·5° longitude resolution. A time-series analysis was fitted using quasi-Poisson regression to quantify municipality-specific effect estimates, which were then pooled at the regional and national levels using random-effects meta-analyses. Analyses were stratified by sex and ten age groups. The attributable fraction and attributable cases of hospital admissions due to wildfire-related PM 2·5 were also calculated., Findings: At the national level, a 10 μg/m 3 increase in wildfire-related PM 2·5 was associated with a 1·65% (95% CI 1·51-1·80) increase in all-cause hospital admissions, a 5·09% (4·73-5·44) increase in respiratory hospital admissions, and a 1·10% (0·78-1·42) increase in cardiovascular hospital admissions, over 0-1 days after the exposure. The effect estimates for all-cause hospital admission did not vary by sex, but were particularly high in children aged 4 years or younger (4·88% [95% CI 4·47-5·28]), children aged 5-9 years (2·33% [1·77-2·90]), and people aged 80 years and older (3·70% [3·20-4·20]) compared with other age groups. We estimated that 0·53% (95% CI 0·48-0·58) of all-cause hospital admissions were attributable to wildfire-related PM 2·5 , corresponding to 35 cases (95% CI 32-38) per 100 000 residents annually. The attributable rate was greatest for municipalities in the north, south, and central-west regions, and lowest in the northeast region. Results were consistent for all-cause and respiratory diseases across regions, but remained inconsistent for cardiovascular diseases., Interpretation: Short-term exposure to wildfire-related PM 2·5 was associated with increased risks of all-cause, respiratory, and cardiovascular hospital admissions, particularly among children (0-9 years) and older people (≥80 years). Greater attention should be paid to reducing exposure to wildfire smoke, particularly for the most susceptible populations., Funding: Australian Research Council and Australian National Health and Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Exposure to cold or hot temperatures is associated with premature deaths. We aimed to evaluate the global, regional, and national mortality burden associated with non-optimal ambient temperatures., Methods: In this modelling study, we collected time-series data on mortality and ambient temperatures from 750 locations in 43 countries and five meta-predictors at a grid size of 0·5° × 0·5° across the globe. A three-stage analysis strategy was used. First, the temperature-mortality association was fitted for each location by use of a time-series regression. Second, a multivariate meta-regression model was built between location-specific estimates and meta-predictors. Finally, the grid-specific temperature-mortality association between 2000 and 2019 was predicted by use of the fitted meta-regression and the grid-specific meta-predictors. Excess deaths due to non-optimal temperatures, the ratio between annual excess deaths and all deaths of a year (the excess death ratio), and the death rate per 100 000 residents were then calculated for each grid across the world. Grids were divided according to regional groupings of the UN Statistics Division., Findings: Globally, 5 083 173 deaths (95% empirical CI [eCI] 4 087 967-5 965 520) were associated with non-optimal temperatures per year, accounting for 9·43% (95% eCI 7·58-11·07) of all deaths (8·52% [6·19-10·47] were cold-related and 0·91% [0·56-1·36] were heat-related). There were 74 temperature-related excess deaths per 100 000 residents (95% eCI 60-87). The mortality burden varied geographically. Of all excess deaths, 2 617 322 (51·49%) occurred in Asia. Eastern Europe had the highest heat-related excess death rate and Sub-Saharan Africa had the highest cold-related excess death rate. From 2000-03 to 2016-19, the global cold-related excess death ratio changed by -0·51 percentage points (95% eCI -0·61 to -0·42) and the global heat-related excess death ratio increased by 0·21 percentage points (0·13-0·31), leading to a net reduction in the overall ratio. The largest decline in overall excess death ratio occurred in South-eastern Asia, whereas excess death ratio fluctuated in Southern Asia and Europe., Interpretation: Non-optimal temperatures are associated with a substantial mortality burden, which varies spatiotemporally. Our findings will benefit international, national, and local communities in developing preparedness and prevention strategies to reduce weather-related impacts immediately and under climate change scenarios., Funding: Australian Research Council and the Australian National Health and Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Liao ning virus (LNV) is a member of the genus Seadornavirus, family Reoviridae and has been isolated from kinds of vectors in Asia and Australia. However, there are no systematic studies describe the molecular genetic evolution and migration of LNVs. With the development of bioinformatics, viral genetic data combining the information of virus isolation time and locations could be integrated to infer the virus evolution and spread in nature., Methods: Here, a phylogenetic and phylogeographic analysis using Bayesian Markov chain Monte Carlo simulations was conducted on the LNVs isolated from a variety of vectors during 1990-2014 to identify the evolution and migration patterns of LNVs., Results: The results demonstrated that the LNV could be divided into 3 genotypes, of which genotype 1 mainly composed of LNVs isolated from Australia during 1990 to 2014 and the original LNV strain (LNV-NE97-31) isolated from Liaoning province in northern China in 1997, genotype 2 comprised of the isolates all from Xinjiang province in western China and genotype 3 consisted the isolates from Qinghai and Shanxi province of central China. LNVs emerged about 272 years ago and gradually evolved into three lineages in the order genotype 1, genotype 2 and genotype 3. Following phylogeographic analysis, it shows genotype 1 LNVs transmitted from Australia (113°E-153°E,10°S-42°S) to Liaoning province (118°E-125°E,38°N-43°N) in Northeast Asian continent then further spread across the central part of China to western China (75°E-95°E,35°N-50°N)., Conclusion: LNVs were initially isolated from Liaoning province of China in the Northeast Asia, however, the present study revealed that LNVs were first appeared in Australia in the South Pacific region and transmitted to mainland China then rapidly spread across China and evolved three different genotypes. The above results suggested that LNV had the characteristics of long-distance transmission and there were great genetic diversity existed in the LNV population. Notably, current information of 80 strains of LNVs are limited. It is of great importance to strengthen the surveillance of LNVs to explore its real origin in nature and monitoring of the LNVs' population variation and maintain vigilance to avoid LNV breaking through the species barrier and further clarify its relationship to human and animal infection.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by the loss of upper and lower motor neurons. ALS exhibits high phenotypic variability including age and site of onset, and disease duration. To uncover epigenetic and transcriptomic factors that may modify an ALS phenotype, we used a cohort of Australian monozygotic twins (n = 3 pairs) and triplets (n = 1 set) that are discordant for ALS and represent sporadic ALS and the two most common types of familial ALS, linked to C9orf72 and SOD1. Illumina Infinium HumanMethylation450K BeadChip, EpiTYPER and RNA-Seq analyses in these ALS-discordant twins/triplets and control twins (n = 2 pairs), implicated genes with consistent longitudinal differential DNA methylation and/or gene expression. Two identified genes, RAD9B and C8orf46, showed significant differential methylation in an extended cohort of >1000 ALS cases and controls. Combined longitudinal methylation-transcription analysis within a single twin set implicated CCNF, DPP6, RAMP3, and CCS, which have been previously associated with ALS. Longitudinal transcriptome data showed an 8-fold enrichment of immune function genes and under-representation of transcription and protein modification genes in ALS. Examination of these changes in a large Australian sporadic ALS cohort suggest a broader role in ALS. Furthermore, we observe that increased methylation age is a signature of ALS in older patients.

Mean birth weight of twins is known to be lower than that of singletons, however, southern China lacks a twin-specific birth weight reference. In this paper, we use data from the Birth Certificate System in southern China, collected between January 1 st 2014 and December 31 st 2017 and including 161,076 twins, to calculate sex- and gestational week-specific birth weight percentiles (the 3 rd , 10 th , 25 th , 50 th , 75 th , 90 th , and 97 th ). We applied generalized additive models for location, scale and shape (GAMLSS) when calculating the birth weight percentiles, and calculated percentiles for monochorionic and dichorionic twins separately. We next used data collected between Jan 1st 2018 and Apr 30th 2018, encompassing 12,371 live births, to calculate the SGA and LGA ratios using birth weight references in Australia, South Korea and China (based on birth defects surveillance system) and birth weight percentiles calculated in this study. Compared to dichorionic twins, monochorionic twins had lower birth weights at 25 to 42 weeks of gestation. The calculated SGA and LGA ratios were relatively stable compared to the other references.

Cross-ethnic genetic studies can leverage power from differences in disease epidemiology and population-specific genetic architecture. In particular, the differences in linkage disequilibrium and allele frequency patterns across ethnic groups may increase gene-mapping resolution. Here we use cross-ethnic genetic data in sporadic amyotrophic lateral sclerosis (ALS), an adult-onset, rapidly progressing neurodegenerative disease. We report analyses of novel genome-wide association study data of 1,234 ALS cases and 2,850 controls. We find a significant association of rs10463311 spanning GPX3-TNIP1 with ALS (p = 1.3 × 10 -8 ), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 10 -3 ). Both GPX3 and TNIP1 interact with other known ALS genes (SOD1 and OPTN, respectively). In addition, GGNBP2 was identified using gene-based analysis and summary statistics-based Mendelian randomization analysis, although further replication is needed to confirm this result. Our results increase our understanding of genetic aetiology of ALS.Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.

Background and Aim: Studies in stroke patients suggest that lacunar stroke and intracerebral hemorrhage might be more common in Chinese than Whites. We hypothesized that other manifestations of subclinical cerebral small vessel disease, namely white matter hyperintensities (WMH), lacunes, and microbleeds, are also more common in Chinese than Whites. We compared the community prevalence of these lesions between Han Chinese and White Australians., Methods: Magnetic resonance imaging (1·5-Tesla) was performed on participants of the Shanghai Aging Study (n = 321, mean age 69 ± 6 years) and Tasmanian Study of Cognition and Gait (n = 397, mean age 72 ± 7 years). A single-rater recorded measures of WMH, lacunes, and microbleeds. We compared lesion prevalence between age- and gender-matched subgroups from the two cohorts. Among all subjects (n = 718), we performed multivariable logistic regression to examine if race-ethnicity was independently associated with these lesions., Results: Among age- and gender-matched subjects, confluent WMH were significantly more prevalent in Chinese (38·5%) than Whites (28·4%; P = 0·01). There was no difference in the prevalence of lacunes (Chinese 29·1% vs. Whites 29·5%, P = 0·93) and microbleeds (Chinese 10·1% vs. 9·0%, P = 0·67) between Chinese and Whites. In multivariable logistic regression, Chinese ethnicity was associated with confluent WMH (odds ratio 1·7, 95% confidence interval 1·1-2·6, P = 0·01), but no differences were seen for lacunes and microbleeds. The association between Chinese ethnicity with confluent WMH became insignificant when subjects with history of stroke were excluded., Conclusions: In this population-based cross-national comparison, Han Chinese had a higher prevalence of confluent WMH than White Australians, but had a similar prevalence of lacunes and microbleeds., (© 2014 The Authors. International Journal of Stroke © 2014 World Stroke Organization.)