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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. © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Studies have investigated the effects of heat and temperature variability (TV) on mortality. However, few assessed whether TV modifies the heat-mortality association. Data on daily temperature and mortality in the warm season were collected from 717 locations across 36 countries. TV was calculated as the standard deviation of the average of the same and previous days’ minimum and maximum temperatures. We used location-specific quasi-Poisson regression models with an interaction term between the cross-basis term for mean temperature and quartiles of TV to obtain heat-mortality associations under each quartile of TV, and then pooled estimates at the country, regional, and global levels. Results show the increased risk in heat-related mortality with increments in TV, accounting for 0.70% (95% confidence interval [CI]: −0.33 to 1.69), 1.34% (95% CI: −0.14 to 2.73), 1.99% (95% CI: 0.29–3.57), and 2.73% (95% CI: 0.76–4.50) of total deaths for Q1–Q4 (first quartile–fourth quartile) of TV. The modification effects of TV varied geographically. Central Europe had the highest attributable fractions (AFs), corresponding to 7.68% (95% CI: 5.25–9.89) of total deaths for Q4 of TV, while the lowest AFs were observed in North America, with the values for Q4 of 1.74% (95% CI: −0.09 to 3.39). TV had a significant modification effect on the heat-mortality association, causing a higher heat-related mortality burden with increments of TV. Implementing targeted strategies against heat exposure and fluctuant temperatures simultaneously would benefit public health. © 2022 The Author(s)

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° degrees 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, 1753392 deaths (95% CI 1159 901–2357 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.

There is conflicting evidence on the influence of weather on COVID-19 transmission. Our aim is to estimate weather-dependent signatures in the early phase of the pandemic, while controlling for socio-economic factors and non-pharmaceutical interventions. We identify a modest non-linear association between mean temperature and the effective reproduction number (Re) in 409 cities in 26 countries, with a decrease of 0.087 (95% CI: 0.025; 0.148) for a 10 °C increase. Early interventions have a greater effect on Re with a decrease of 0.285 (95% CI 0.223; 0.347) for a 5th - 95th percentile increase in the government response index. The variation in the effective reproduction number explained by government interventions is 6 times greater than for mean temperature. We find little evidence of meteorological conditions having influenced the early stages of local epidemics and conclude that population behaviour and government interventions are more important drivers of transmission., This work was generated using Copernicus Climate Change Service (C3S) and Copernicus Atmosphere Monitoring Service (CAMS) information [2020]. The authors would like to thank the European Centre for Medium-Range Weather Forecasts (ECMWF) that implements the C3S and CAMS on behalf of the European Union. D.R. was supported by a postdoctoral research fellowship of the Xunta de Galicia (Spain). A.G. was funded by the Medical Research Council-UK (Grant ID: MR/R013349/1), the Natural Environment Research Council UK (Grant ID: NE/R009384/1) and the European Union’s Horizon 2020 Project Exhaustion (Grant ID: 820655). R.L. was supported by a Royal Society Dorothy Hodgkin Fellowship. S.A. and S.M. were funded by the Wellcome Trust (grant 210758/Z/18/Z210758/Z/18/Z). The following funding sources are acknowledged as providing funding for the MCC Collaborative Research Network authors: J.K. and A.U. were supported by the Czech Science Foundation, project 18-22125S. S.T. was supported by the Shanghai Municipal Science and Technology Commission (Grant 18411951600). N.S. is supported by the NIEHS-funded HERCULES Center (P30ES019776). H.K. was supported by the National Research Foundation of Korea (BK21 Center for Integrative Response to Health Disasters, Graduate School of Public Health, Seoul National University). A.S., F.D.R. and S.R. were funded by the European Union’s Horizon 2020 Project Exhaustion (Grant ID: 820655). Each member of the CMMID COVID-19 Working Group contributed to processing, cleaning and interpretation of data, interpreted findings, contributed to the manuscript and approved the work for publication. The following funding sources are acknowledged as providing funding for the CMMID COVID-19 working group authors. This research was partly funded by the Bill & Melinda Gates Foundation (INV-001754: M.Q; INV-003174: K.P., M.J., Y.L., J.L.; NTD Modelling Consortium OPP1184344: C.A.B.P., G.M.; OPP1180644: S.R.P.; OPP1183986: E.S.N.). BMGF (OPP1157270: K.E.A.). DFID/Wellcome Trust (Epidemic Preparedness Coronavirus research programme 221303/Z/20/Z: C.A.B.P.). EDCTP2 (RIA2020EF-2983-CSIGN: H.P.G.). ERC Starting Grant (#757699: M.Q.). This project has received funding from the European Union’s Horizon 2020 research and innovation programme—project EpiPose (101003688: K.P., M.J., P.K., R.C.B., W.J.E., Y.L.). This research was partly funded by the Global Challenges Research Fund (GCRF) project ‘RECAP’ managed through RCUK and ESRC (ES/P010873/1: A.G., C.I.J., T.J.). HDR UK (MR/S003975/1: R.M.E.). MRC (MR/N013638/1: N.R.W.; MR/V027956/1: W.W.). Nakajima Foundation (A.E.). This research was partly funded by the National Institute for Health Research (NIHR) using UK aid from the UK Government to support global health research. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the UK Department of Health and Social Care (16/136/46: B.J.Q.; 16/137/109: B.J.Q., F.Y.S., M.J., Y.L.; Health Protection Research Unit for Immunisation NIHR200929: N.G.D.; Health Protection Research Unit for Modelling Methodology HPRU-2012-10096: T.J.; NIHR200908: R.M.E.; NIHR200929: F.G.S., M.J.; PR-OD-1017-20002: A.R., W.J.E.). Royal Society (Dorothy Hodgkin Fellowship: R.L.; RP\EA\180004: P.K.). UK DHSC/UK Aid/NIHR (PR-OD-1017-20001: H.P.G.). UK MRC (MC_PC_19065—Covid 19: Understanding the dynamics and drivers of the COVID-19 epidemic using real-time outbreak analytics: A.G., N.G.D., R.M.E., S.C., T.J., W.J.E., Y.L.; MR/P014658/1: G.M.K.). Authors of this research receive funding from the UK Public Health Rapid Support Team funded by the United Kingdom Department of Health and Social Care (T.J.). Wellcome Trust (206250/Z/17/Z: A.J.K., T.W.R.; 206471/Z/17/Z: O.B.; 208812/Z/17/Z: S.C.; 210758/Z/18/Z: J.D.M., J.H., N.I.B.; UNS110424: F.K.). No funding (A.M.F., A.S., C.J.V.-A., D.C.T., J.W., K.E.A., Y.-W.D.C.). LSHTM, DHSC/UKRI COVID-19 Rapid Response Initiative (MR/V028456/1: Y.L.). Innovation Fund of the Joint Federal Committee (01VSF18015: F.K.). Foreign, Commonwealth and Development Office/Wellcome Trust (221303/Z/20/Z: M.K.).

BACKGROUND: Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM2·5 and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM2·5 and mortality across various regions of the world. METHODS: For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000-16. Daily concentrations of wildfire-related PM2·5 were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0·25° × 0·25° resolution. The association between wildfire-related PM2·5 exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM2·5 exposure was calculated. FINDINGS: 65·6 million all-cause deaths, 15·1 million cardiovascular deaths, and 6·8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 μg/m3 increase in the 3-day moving average (lag 0-2 days) of wildfire-related PM2·5 exposure were 1·019 (95% CI 1·016-1·022) for all-cause mortality, 1·017 (1·012-1·021) for cardiovascular mortality, and 1·019 (1·013-1·025) for respiratory mortality. Overall, 0·62% (95% CI 0·48-0·75) of all-cause deaths, 0·55% (0·43-0·67) of cardiovascular deaths, and 0·64% (0·50-0·78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM2·5 exposure during the study period. INTERPRETATION: Short-term exposure to wildfire-related PM2·5 was associated with increased risk of mortality. Urgent action is needed to reduce health risks from the increasing wildfires. FUNDING: Australian Research Council, Australian National Health & Medical Research Council. Copyright © 2021 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: Minimum mortality temperature (MMT) is an important indicator to assess the temperature-mortality association, indicating long-term adaptation to local climate. Limited evidence about the geographical variability of the MMT is available at a global scale. Methods: We collected data from 658 communities in 43 countries under different climates. We estimated temperature-mortality associations to derive the MMT for each community using Poisson regression with distributed lag nonlinear models. We investigated the variation in MMT by climatic zone using a mixed-effects meta-analysis and explored the association with climatic and socioeconomic indicators. Results: The geographical distribution of MMTs varied considerably by country between 14.2 and 31.1 ºC decreasing by latitude. For climatic zones, the MMTs increased from alpine (13.0 ºC) to continental (19.3 ºC), temperate (21.7 ºC), arid (24.5 ºC), and tropical (26.5 ºC). The MMT percentiles (MMTPs) corresponding to the MMTs decreased from temperate (79.5th) to continental (75.4th), arid (68.0th), tropical (58.5th), and alpine (41.4th). The MMTs indreased by 0.8 ºC for a 1 ºC rise in a community's annual mean temperature, and by 1 ºC for a 1 ºC rise in its SD. While the MMTP decreased by 0.3 centile points for a 1 ºC rise in a community's annual mean temperature and by 1.3 for a 1 ºC rise in its SD. Conclusions: The geographical distribution of the MMTs and MMTPs is driven mainly by the mean annual temperature, which seems to be a valuable indicator of overall adaptation across populations. Our results suggest that populations have adapted to the average temperature, although there is still more room for adaptation. Copyright © 2021 The Authors.

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. © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991–2018. Across all study countries, we find that 37.0% (range 20.5–76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.

Objective To evaluate the short term associations between nitrogen dioxide (NO 2) and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide, using a uniform analytical protocol. Design Two stage, time series approach, with overdispersed generalised linear models and multilevel meta-analysis. Setting 398 cities in 22 low to high income countries/regions. Main outcome measures Daily deaths from total (62.8 million), cardiovascular (19.7 million), and respiratory (5.5 million) causes between 1973 and 2018. Results On average, a 10 μg/m 3 increase in NO 2 concentration on lag 1 day (previous day) was associated with 0.46% (95% confidence interval 0.36% to 0.57%), 0.37% (0.22% to 0.51%), and 0.47% (0.21% to 0.72%) increases in total, cardiovascular, and respiratory mortality, respectively. These associations remained robust after adjusting for co-pollutants (particulate matter with aerodynamic diameter ≤10 μm or ≤2.5 μm (PM 10 and PM 2.5, respectively), ozone, sulfur dioxide, and carbon monoxide). The pooled concentration-response curves for all three causes were almost linear without discernible thresholds. The proportion of deaths attributable to NO 2 concentration above the counterfactual zero level was 1.23% (95% confidence interval 0.96% to 1.51%) across the 398 cities. Conclusions This multilocation study provides key evidence on the independent and linear associations between short term exposure to NO 2 and increased risk of total, cardiovascular, and respiratory mortality, suggesting that health benefits would be achieved by tightening the guidelines and regulatory limits of NO 2. ©

Objective: To evaluate the short term associations between nitrogen dioxide (NO₂) and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide, using a uniform analytical protocol. Design: Two stage, time series approach, with overdispersed generalised linear models and multilevel meta-analysis. Setting: 398 cities in 22 low to high income countries/regions. Main outcome measures: Daily deaths from total (62.8 million), cardiovascular (19.7 million), and respiratory (5.5 million) causes between 1973 and 2018. Results: On average, a 10 μg/m³ increase in NO₂ concentration on lag 1 day (previous day) was associated with 0.46% (95% confidence interval 0.36% to 0.57%), 0.37% (0.22% to 0.51%), and 0.47% (0.21% to 0.72%) increases in total, cardiovascular, and respiratory mortality, respectively. These associations remained robust after adjusting for co-pollutants (particulate matter with aerodynamic diameter ≤10 μm or ≤2.5 μm (PM₁₀ and PM2.5, respectively), ozone, sulfur dioxide, and carbon monoxide). The pooled concentration-response curves for all three causes were almost linear without discernible thresholds. The proportion of deaths attributable to NO₂ concentration above the counterfactual zero level was 1.23% (95% confidence interval 0.96% to 1.51%) across the 398 cities. Conclusions: This multilocation study provides key evidence on the independent and linear associations between short term exposure to NO₂ and increased risk of total, cardiovascular, and respiratory mortality, suggesting that health benefits would be achieved by tightening the guidelines and regulatory limits of NO₂.

Objective To assess short term mortality risks and excess mortality associated with exposure to ozone in several cities worldwide. Design Two stage time series analysis. Setting 406 cities in 20 countries, with overlapping periods between 1985 and 2015, collected from the database of Multi-City Multi-Country Collaborative Research Network. Population Deaths for all causes or for external causes only registered in each city within the study period. Main outcome measures Daily total mortality (all or non-external causes only). Results A total of 45 165 171 deaths were analysed in the 406 cities. On average, a 10 μg/m 3 increase in ozone during the current and previous day was associated with an overall relative risk of mortality of 1.0018 (95% confidence interval 1.0012 to 1.0024). Some heterogeneity was found across countries, with estimates ranging from greater than 1.0020 in the United Kingdom, South Africa, Estonia, and Canada to less than 1.0008 in Mexico and Spain. Short term excess mortality in association with exposure to ozone higher than maximum background levels (70 μg/m 3) was 0.26% (95% confidence interval 0.24% to 0.28%), corresponding to 8203 annual excess deaths (95% confidence interval 3525 to 12 840) across the 406 cities studied. The excess remained at 0.20% (0.18% to 0.22%) when restricting to days above the WHO guideline (100 μg/m 3), corresponding to 6262 annual excess deaths (1413 to 11 065). Above more lenient thresholds for air quality standards in Europe, America, and China, excess mortality was 0.14%, 0.09%, and 0.05%, respectively. Conclusions Results suggest that ozone related mortality could be potentially reduced under stricter air quality standards. These findings have relevance for the implementation of efficient clean air interventions and mitigation strategies designed within national and international climate policies. © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to.

BACKGROUND The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias. METHODS We evaluated the associations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 μm or less (PM10) and fine PM with an aerodynamic diameter of 2.5 μm or less (PM2.5) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions. Daily data on mortality and air pollution were collected from 652 cities in 24 countries or regions. We used overdispersed generalized additive models with random-effects meta-analysis to investigate the associations. Two-pollutant models were fitted to test the robustness of the associations. Concentration–response curves from each city were pooled to allow global estimates to be derived. RESULTS On average, an increase of 10 μg per cubic meter in the 2-day moving average of PM10 concentration, which represents the average over the current and previous day, was associated with increases of 0.44% (95% confidence interval [CI], 0.39 to 0.50) in daily all-cause mortality, 0.36% (95% CI, 0.30 to 0.43) in daily cardiovascular mortality, and 0.47% (95% CI, 0.35 to 0.58) in daily respiratory mortality. The corresponding increases in daily mortality for the same change in PM2.5 concentration were 0.68% (95% CI, 0.59 to 0.77), 0.55% (95% CI, 0.45 to 0.66), and 0.74% (95% CI, 0.53 to 0.95). These associations remained significant after adjustment for gaseous pollutants. Associations were stronger in locations with lower annual mean PM concentrations and higher annual mean temperatures. The pooled concentration–response curves showed a consistent increase in daily mortality with increasing PM concentration, with steeper slopes at lower PM concentrations. CONCLUSIONS Our data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.) Copyright © 2019 Massachusetts Medical Society.

Yasutaka Tashiro,1 Ken Okazaki,1 Munenori Uemura,2 Kazutaka Toyoda,2 Kanji Osaki,1 Hirokazu Matsubara,1 Makoto Hashizume,2 Yukihide Iwamoto1 1Department of Orthopaedic Surgery, 2Department of Advanced Medical Initiatives, Kyushu University Hospital, Fukuoka, Japan Purpose: The purpose of this study was to assess the differences in bone tunnel apertures between the trans-accessory medial portal (trans-AMP) technique and the transtibial (TT) technique in double-bundle anterior cruciate ligament reconstruction. The extent of ovalization and the frequency of overlap of the two tunnel apertures were compared. Methods: The simulation of femoral tunnel drilling with the TT and the trans-AMP techniques was performed using three-dimensional computer aided design models from two volunteers. The incidence angle of drilling against the intercondylar wall, the femoral tunnel position, the ovalization, and the overlap were analyzed. The aperture and location of the tunnels were also examined in real anterior cruciate ligament reconstruction cases (n=36). Results: The surgical simulation showed that a lower drill incident angle induced by the TT technique made the apertures of two tunnels more ovalized, located anteromedial tunnels in a shallower position to prevent posterior wall blow out, and led to a higher frequency of tunnel overlap. The trans-AMP group had tunnel places within the footprint and had less ovalization and overlap. The results of analysis for tunnels in the clinical cases were consistent with results from the surgical simulation. Conclusion: In the TT technique, the shallow anteromedial tunnel location and more ovalized tunnel aperture can lead to a higher frequency of tunnel overlap. Compared with the TT technique, the trans-AMP technique was more useful in preparing femoral tunnels anatomically and avoiding tunnel ovalization and overlapping in double-bundle anterior cruciate ligament reconstruction. Keywords: anterior cruciate ligament, transtibial, transaccessory medial portal, computer aided design, surgical simulation, tunnel aperture

Riki Toita,1,2 Masaharu Murata,1–3 Kana Abe,3 Sayoko Narahara,1 Jing Shu Piao,2 Jeong-Hun Kang,4 Kenoki Ohuchida,2,5 Makoto Hashizume1–31Innovation Center for Medical Redox Navigation, Kyushu University, 2Department of Advanced Medical Initiatives, Kyushu University, 3Center for Advanced Medical Innovation, Kyushu University, Fukuoka, 4Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institutes, Suita, 5Department of Surgery and Oncology, Kyushu University, Fukuoka, JapanAbstract: This study describes the applications of a naturally occurring small heat shock protein (Hsp) that forms a cage-like structure to act as a drug carrier. Mutant Hsp cages (HspG41C) were expressed in Escherichia coli by substituting glycine 41 located inside the cage with a cysteine residue to allow conjugation with a fluorophore or a drug. The HspG41C cages were taken up by various cancer cell lines, mainly through clathrin-mediated endocytosis. The cages were detected in acidic organelles (endosomes/lysosomes) for at least 48 hours, but none were detected in the mitochondria or nuclei. To generate HspG41C cages carrying doxorubicin (DOX), an anticancer agent, the HspG41C cages and DOX were conjugated using acid-labile hydrazone linkers. The release of DOX from HspG41C cages was accelerated at pH 5.0, but was negligible at pH 7.2. The cytotoxic effects of HspG41C–DOX against Suit-2 and HepG2 cells were slightly weaker than those of free DOX, but the effects were almost identical in Huh-7 cells. Considering the relatively low release of DOX from HspG41C–DOX, HspG41C–DOX exhibited comparable activity towards HepG2 and Suit-2 cells and slightly stronger cytotoxicity towards Huh-7 cells than free DOX. Hsp cages offer good biocompatibility, are easy to prepare, and are easy to modify; these properties facilitate their use as nanoplatforms in drug delivery systems and in other biomedical applications.Keywords: anticancer activity, biomedical application, doxorubicin, drug delivery system, protein nanocapsules, small heat shock protein

Masaharu Murata,1,2 Sayoko Narahara,1,2 Kaori Umezaki,1 Riki Toita,1,2 Shigekazu Tabata,1 Jing Shu Piao,1 Kana Abe,1 Jeong-Hun Kang,3 Kenoki Ohuchida,1,4 Lin Cui,4 Makoto Hashizume1,21Department of Advanced Medical Initiatives, Faculty of Medical Science, Kyushu University, Fukuoka, Japan; 2Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan; 3Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan; 4Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanAbstract: Protein nanocages are self-organized complexes of oligomers whose three-dimensional architecture can been determined in detail. These structures possess nanoscale inner cavities into which a variety of molecules, including therapeutic or diagnostic agents, can be encapsulated. These properties yield these particles suitable for a new class of drug delivery carrier, or as a bioimaging reagent that might respond to biochemical signals in many different cellular processes. We report here the design, synthesis, and biological characterization of a hepatocyte-specific nanocage carrying small heat-shock protein. These nanoscale protein cages, with a targeting peptide composed of a preS1 derivative from the hepatitis B virus on their surfaces, were prepared by genetic engineering techniques. PreS1-carrying nanocages showed lower cytotoxicity and significantly higher specificity for human hepatocyte cell lines than other cell lines in vitro. These results suggested that small heat-shock protein-based nanocages present great potential for the development of effective targeted delivery of various agents to specific cells.Keywords: protein nanocages, drug delivery system, hepatocyte cell lines specific, hepatitis B virus

九州大学医学部とタイ国チュラロンコン大学医学部を結び、遠隔内視鏡手術の実証実験を実施し、ブロードバンドネットワークによる遠隔医療の効果が示された。筆者は、ネットワーク、映像系システム、蓄積システムの設計、構築に寄与した。

Introduction : The aim of this study was to describe the extent of self-reported non-communicable diseases (NCDs) among highly active antiretroviral therapy (HAART) recipients in Kagera region in Tanzania and their effect on health-related quality of life (HRQOL). This study was conducted 2 years after HAART administration was started in Kagera region. Methods : The SF-36 questionnaire was used to collect the HRQOL data of 329 HAART recipients. Questions on the NCDs, socio-demographic characteristics and treatment information were validated and added to the SF-36. Bivariate analyses involving socio-demographic characteristics and SF-36 scores of the recipients were performed. Multiple logistic regression was employed to compute adjusted odds ratios for different explanatory variables on physical functioning and mental health scores. Results : Respondents who reported having 1 or more NCDs were 57.8% of all the respondents. Arthritis was the commonest NCD (57.8%). Respondents with the NCDs were more likely to have HRQOL scores below the mean of the general Tanzanian population. The population attributable fraction (PAF) for the NCDs on physical functioning was 0.28 and on mental health was 0.22. Conclusion : Self-reported NCDs were prevalent among the HAART recipients in Kagera region. They accounted for 28% of the physical functioning scores and 22% of the mental health scores that were below the mean of the general Tanzanian population. Therefore, the integration of NCD care is important in the management of HIV/AIDS.

本稿では、NOTESロボットを使用した遠隔手術の概要と、タイー日本間国際手術実証実験に関して述べた。本実験では、東大の内視鏡手術ロボットと慈恵大のNOTESロボットを使用した実験を実施したが、筆者は実験計画作成、ネットワーク、画像通信設備、テレアノテーション機能などで寄与した。

九州大学医学部とタイ国チュラロンコン大学医学部を結び、遠隔内視鏡手術の実証実験を実施し、ブロードバンドネットワークによる遠隔医療の効果が示された本論文は実際にロボットを使用する医師に対し複数のタスクを指示し、遠隔地からの操作とローカルでの操作の違いを明らかにした。筆者は、ネットワーク、映像系システム、蓄積システムの設計、構築に寄与した。

An optical particle counter (OPC) is used in conjunction with lidar measurements to examine the characteristics of the particle size distribution in cirrus cloud in the tropical tropopause layer (TTL) over Thailand where the TTL is defined as the height at which temperature is lower than −75°C in this paper. Of 11 OPC launches, cirrus cloud was detected at 10–15 km high on 7 occasions, cirrus was detected in the TTL in 6 cases, and simultaneous OPC and lidar measurements were made on two occasions. Comparison of lidar and OPC measurements reveal that the cloud heights of cirrus in the TTL varies by several hundred meters over distances of tens kilometers; hence the height is not always horizontally uniform. The mode radii of particles constituting the clouds are estimated by lidar and OPC measurements to be less than approximately 10 μm. The regression lines of the particle size distribution with and without cirrus cloud exhibit similar features at equivalent radii of

九州大学医学部とタイ国チュラロンコン大学医学部を結び、遠隔内視鏡手術の実証実験を実施し、ブロードバンドネットワークによる遠隔医療の効果が示された。筆者は、ネットワーク、映像系システム、蓄積システムの設計、構築に寄与した。

An optical particle counter (OPC) is used in conjunction with lidar measurements to examine the characteristics of the particle size distribution in cirrus cloud at the tropical tropopause (TT) over Thailand. Of 11 OPC launches, cirrus cloud was detected at 10–15 km high on 7 occasions, cirrus was detected at the TT in 6 cases, and simultaneous OPC and lidar measurements were made on two occasions. Comparison of lidar and OPC measurements reveal that the cloud height of cirrus in the TT varies by several hundred meters over distances of tens kilometers; hence the height is not horizontally uniform. The mode radii of particles constituting the clouds are estimated by lidar and OPC measurements to be less than approximately 10 μm. The regression lines of the particle size distribution with and without cirrus cloud exhibit similar features at equivalent radii of

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991–2018. Across all study countries, we find that 37.0% (range 20.5–76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change.

Objective To assess the effectiveness of an HPV vaccination programme in reducing the risk of cervical abnormalities identified at subsequent screening. Design Retrospective cohort study using administrative health data. Setting General population of Ferrara Province, Italy. Population Female residents born in 1986-1993 and participating in the organized cervical screening programme in 2011-2018, who were eligible for HPV vaccination in catch-up cohorts. Methods Logistic regression to evaluate the potential association between abnormal cervical cytology and one, two, three or at least one dose of HPV vaccine. Main outcome measures Cervical abnormalities, as predicted by low-grade or high-grade cytology, by number of vaccine doses, stratified by age. Results The sample consisted of 7785 women (mean age 27.5 years, SD 2.3). Overall, 391 (5.0%) were vaccinated with ≥1 dose and 893 (11.5%) had abnormal cytology. Women receiving at least one vaccine dose were significantly less likely to have an abnormal cytology (adjusted odds ratio 0.52; 95% confidence interval 0.34-0.79). Similar results were observed for women receiving a single dose, for both bivalent and quadrivalent vaccines, and applying buffer periods (excluding cytological outcomes within 1 month, 6 months and 1 year of the first dose). Conclusions In the context of an organised cervical screening programme in Italy, catch-up HPV vaccination almost halved the risk of cytological abnormalities. Tweetable abstract Among Ferrara women, vaccination against human papillomavirus halved the risk of screening cervical abnormalities.