Geographical variation in relative risks associated with cold waves in Spain: The need for a cold wave prevention plan

In general, there are few studies that analyse the impact of low temperatures on mortality and fewer still that use cold-wave-definition thresholds based on epidemiological and non-climatological criteria. Such a threshold definition, which took into account population features such as socio-economic and demographic characteristics, made it possible for a specific threshold temperature to be obtained for each of Spain's 52 provincial capitals in this study. Using generalised linear models with the Poisson regression link, and controlling for trend, autocorrelations and seasonalities of the series, and influenza epidemics, we obtained the impact of low temperatures on mortality in each provincial capital by calculating the relative risks (RRs) and attributable risks (ARs) for natural as well as circulatory and respiratory causes. The study showed higher minimum temperature thresholds in coastal areas, and an overall impact of cold on mortality in Spain due to natural causes RR=1.13 (95% CI: 1.11-1.16), circulatory causes RR=1.18 (95% CI: 1.15-1.22) and respiratory causes RR=1.24 (95% CI: 1.20-1.29) slightly greater than that obtained to date for heat. From a public health standpoint, there is a need for specific cold wave prevention plans at a regional level which would enable mortality attributable to low temperatures to be reduced. These plans have shown themselves to be effective in decreasing heat-related mortality, and we feel that they are essential for reducing cold-related effects on morbidity and mortality.This study was supported by grants: FIS ENPY 1001/13 & SEPY 1037/14 from Spain's Health Research FundS

Short-term effect of heat waves on hospital admissions in Madrid: Analysis by gender and comparision with previous findings

Global warming affects health through multiple exposures and pathways, in and is turn deeply influenced by climate change. Every year, several million deaths are caused by environmental factors, many of which are aggravated by climate change or its drivers (WHO, 2016). The adverse effects of climate change on health are varied, complex and far-reaching. Essentially, climate change acts as a multiplier for global health threats, compounding many of the health issues communities already face. Disproportionately affect the health of vulnerable groups and people in lower income countries, thus exacerbating inequalities and gender differences (Watts et al., 2018)

Mortality attributable to extreme temperatures in Spain: A comparative analysis by city

BACKGROUND: The Low Temperature Days (LTD) have attracted far less attention than that of High Temperature Days (HTD), though its impact on mortality is at least comparable. This lower degree of attention may perhaps be due to the fact that its influence on mortality is less pronounced and longer-term, and that there are other concomitant infectious winters factors. In a climate-change scenario, the studies undertaken to date report differing results. The aim of this study was to analyse mortality attributable to both thermal extremes in Spain's 52 provinces across the period 2000-2009, and estimate the related economic cost to show the benefit or "profitability" of implementing prevention plans against LTD. METHODS: Previous studies enabled us: to obtain the maximum daily temperature above which HTD occurred and the minimum daily temperature below which LTD occurred in the 52 provincial capitals analysed across the same study period; and to calculate the relative and attributable risks (%) associated with daily mortality in each capital. These measures of association were then used to make different calculations to obtain the daily mean mortality attributable to both thermal extremes. To this end, we obtained a summary of the number of degrees whereby the temperature exceeded (excess °C) or fell short (deficit °C) of the threshold temperature for each capital, and calculated the respective number of extreme temperatures days. The economic estimates rated the prevention plans as being 68% effective. RESULTS: Over the period considered, the number of HTD (4373) was higher than the number of LTD (3006) for Spain as a whole. Notwithstanding this, in every provincial capital the mean daily mortality attributable to heat was lower (3deaths/day) than that attributable to cold (3.48deaths/day). In terms of the economic impact of the activation of prevention plans against LTD, these could be assumed to avoid 2.37 deaths on each LTD, which translated as a saving of €0.29M. Similarly, in the case of heat, 2.04 deaths could be assumed to be avoided each day on which the prevention plan against HTD was activated, amounting to a saving of €0.25M. While the economic cost of cold-related mortality across the ten-year period 2000-2009 was €871.7M, that attributable to heat could be put at €1093.2M. CONCLUSION: The effect of extreme temperatures on daily mortality was similar across the study period for Spain overall. The lower number of days with LTD meant, however, that daily cold-related mortality was higher than daily heat-related mortality, thereby making prevention plans against LTD more "profitable" prevention plans against HTD in terms of avoidable mortality.This study was supported by grants FIS ENPY 1001/13 & SEPY 1037/14 from Spain's Health Research Fund.S

Geographical variation in relative risks associated with heat: Update of Spain's Heat Wave Prevention Plan

A decade after the implementation of prevention plans designed to minimise the impact of high temperatures on health, some countries have decided to update these plans in order to improve the weakness detected in these ten years of operation. In the case of Spain, this update has fundamentally consisted of changing the so-called "threshold" or "trigger" temperatures used to activate the plan, by switching from temperature values based on climatological criteria to others obtained by epidemiological studies conducted on a provincial scale. This study reports the results of these "trigger" temperatures for each of Spain's 52 provincial capitals, as well as the impact of heat on mortality by reference to the relative risks (RRs) and attributable risks (ARs) calculated for natural as well as circulatory and respiratory causes. The results obtained for threshold temperatures and RRs show a more uniform behaviour pattern than those obtained using temperature values based on climatological criteria; plus a clear decrease in RRs of heat-associated mortality due to the three causes considered, at both a provincial and regional level as well as for Spain as a whole. The updating of prevention plans is regarded as crucial for optimising the operation of these plans in terms of reducing the effect of high temperatures on population health.This study was supported by grants FIS ENPY 1001/13 & SEPY 1037/14 from Spain's Health Research Fund.S

Population vulnerability to extreme cold days in rural and urban municipalities in ten provinces in Spain

Background: The objective was to analyze whether there are differences in vulnerability to Extreme Cold Days (ECD) between rural and urban populations in Spain. Methodology: Time series analysis carried out from January 1, 2000, through December 31, 2013. Municipalities with over 10,000 inhabitants were included from 10 Spanish provinces, classified into 42 groups by isoclimate and urban/rural character as defined by Eurostat criteria. The statistical strategy was carried out in two phases. First: It was analyzed the relationship between minimum daily temperature (Tmin) (source: AEMET) and the rate of daily winter mortality due to natural causes —CIE-10: A00 – R99— (source: National Statistics Institute). Then, It was determinated the threshold of Tmin that defines the ECD and its percentile in the series of winter Tmin (Pthreshold), which is a measure of vulnerability to ECD so that the higher the percentile, the higher the vulnerability. Second: possible explanatory variables of vulnerability were explored using Mixed Generalized Models, using 13 independent variables related to meteorology, environment, socioeconomics, demographics and housing quality. Results: The average Pthreshold was 18 %. The final model indicated that for each percentage point increase in unemployment, the vulnerability to ECD increased by 0.4 (0.2, 0.6) points. Also, with each point increase in rurality index, this vulnerability decreased by −6.1 (−2.1, −10.0) points. Although less determinant, other factors that could contribute to explaining vulnerability at the province level included minimum winter daily temperatures and the percentage of housing with poor insulation. Conclusions: The vulnerability to ECD was greater in urban zones than in rural zones. Socioeconomic status is a key to understanding how this vulnerability is distributed. These results suggest the need to implement public health prevention plans to address ECD at the state level. These plans should be based on threshold temperatures determined at the smallest scale possibleThe authors wish to thank the funding provided by the ENPY107/18, ENPY 376/18, ENPY 304/20 projects of the Carlos III Health Institute III (ISCIII

Determination of heat wave definition temperatures in Spain at an isoclimatic level: time trend of heat wave duration and intensity across the decade 2009–2018

Background: In line with WHO guidelines for the implementation of public health prevention plans targeted at the impacts of high temperatures, a heat wave defnition temperature (Tthreshold) was calculated for 182 so called “isoclimatic zones” (IZ) in Spain. As the dependent variable for determining this Tthreshold, we analysed daily all-cause mortality data (ICD-10: A00-R99) for each IZ across the period 2009–2018. The independent variable used was the mean value of the maximum daily temperature of the summer months recorded at meteorological observatories in each IZ. We used Box–Jenkins models to ascertain mortality anomalies, and scatterplots to link these anomalies to the temperatures at which they occurred, thereby determining the Tthreshold for each IZ. We then calculated how many heat waves had occurred in each IZ, as well as their intensity, and analysed their time trend over this period. Results: The results showed that in 52.5% of the IZ, the percentile of the maximum temperatures series of the summer months to which Tthreshold corresponded was below the 95th percentile of the meteorological heat wave defnition in Spain: indeed, it only coincided in 30.7% of cases. The geographical distribution of these percentiles displayed great heterogeneity as a consequence of the local factors that infuence the temperature–mortality relationship. The trend in the number of heat waves analysed indicated an overall increase in Spain at a rate of 3.9 heat waves per decade, and a similar rise in mean annual intensity of 9.5 °C/decade. These time-trend values were higher than those yielded by analysing the trend in meteorological heat waves based on the 95th percentile. Conclusions: The results obtained in this study indicate the need to use a heat wave defnition based on epidemiological temperature–mortality studies, rather than on values based on meteorological percentiles. This could be minimising estimated health impacts in analyses of future impacts attributable to heat.Acknowledgements and funding The authors would like to express their gratitude for the following grants from the Carlos III Institute of Health (Instituto de Salud Carlos III/ISCIII) for the ENPY 304/20, and ENPY 436/21 projects.S

Gender differences in adaptation to heat in Spain (1983-2018)

In Spain the average temperature has increased by 1.7 °C since pre-industrial times. There has been an increase in heat waves both in terms of frequency and intensity, with a clear impact in terms of population health. The effect of heat waves on daily mortality presents important territorial differences. Gender also affects these impacts, as a determinant that conditions social inequalities in health. There is evidence that women may be more susceptible to extreme heat than men, although there are relatively few studies that analyze differences in the vulnerability and adaptation to heat by sex. This could be related to physiological causes. On the other hand, one of the indicators used to measure vulnerability to heat in a population and its adaptation is the minimum mortality temperature (MMT) and its temporal evolution. The aim of this study was to analyze the values of MMT in men and women and its temporal evolution during the 1983-2018 period in Spain's provinces. An ecological, longitudinal retrospective study was carried out of time series data, based on maximum daily temperature and daily mortality data corresponding to the study period. Using cubic and quadratic fits between daily mortality rates and the temperature, the minimum values of these functions were determined, which allowed for determining MMT values. Furthermore, we used an improved methodology that provided for the estimation of missing MMT values when polynomial fits were inexistent. This analysis was carried out for each year. Later, based on the annual values of MMT, a linear fit was carried out to determine the rate of evolution of MMT for men and for women at the province level. Average MMT for all of Spain's provinces was 29.4 °C in the case of men and 28.7 °C in the case of women. The MMT for men was greater than that of women in 86 percent of the total provinces analyzed, which indicates greater vulnerability among women. In terms of the rate of variation in MMT during the period analyzed, that of men was 0.39 °C/decade, compared to 0.53 °C/decade for women, indicating greater adaptation to heat among women, compared to men. The differences found between men and women were statistically significant. At the province level, the results show great heterogeneity. Studies carried out at the local level are needed to provide knowledge about those factors that can explain these differences at the province level, and to allow for incorporating a gender perspective in the implementation of measures for adaptation to high temperatures.The authors wish to thank the funding provided by the ENPY 304/20, ENPY 376/18 and ENPY 107/18 projects of the Carlos III Health Institute III (ISCIII). They also wish to thank the UNED for funding this publication in open access.S

A bicyclic α-iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration

I2 receptors (I2-IR) are widely distributed in the central nervous system. I2-IR ligands are associated with a neuroprotective effect but, as I2-IR structure remains unknown, the discovery of better and more selective ligands is necessary to understand the pharmacological and molecular implications of I2-IR. Recently, we described a new imidazoline-structure family which showed high affinity and selectivity for I2-IR. In vivo studies in mice indicated a neuroprotective role and revealed beneficial effects in behaviour and cognition with a murine model of neurodegeneration, senescence-accelerated prone mouse (SAMP8). Herein, we report a novel non-imidazoline-structure of bicyclic α-iminophosphonates family with high affinities for I2-IR. In vivo studies in 5X-FAD mice (a transgenic representative model of AD) and SAMP8 mice (a model of neurodegeneration linked to aging) showed an improvement in behaviour and cognition, a reduction of AD hallmarks and of neuroinflammation markers for the mice treated with the lead compound B06. After evaluating several pathways associated with neurodegeneration, we demonstrated that CaN pathway plays a critical role on the neuroprotective effects of I2-IR ligands on SAMP8 mice model. To rule out warnings of the novel family, we calculated DMPK and physicochemical properties for the novel bicyclic α-iminophosphonates. As well, we carried out drug metabolism, safety studies and in vivo pharmacokinetics for lead compound B06. In summary, we present a novel family of I2-IR ligands, its effectiveness in in vivo models and the possible neuroprotective molecular mechanism mediated by them. This highlights that the modulation of I2-IR by bicyclic α-iminophosphonates may open a new therapeutic venue for unmet neurodegenerative conditions

Bats' Conquest of a Formidable Foraging Niche: The Myriads of Nocturnally Migrating Songbirds

Along food chains, i.e., at different trophic levels, the most abundant taxa often represent exceptional food reservoirs, and are hence the main target of consumers and predators. The capacity of an individual consumer to opportunistically switch towards an abundant food source, for instance, a prey that suddenly becomes available in its environment, may offer such strong selective advantages that ecological innovations may appear and spread rapidly. New predator-prey relationships are likely to evolve even faster when a diet switch involves the exploitation of an unsaturated resource for which few or no other species compete. Using stable isotopes of carbon and nitrogen as dietary tracers, we provide here strong support to the controversial hypothesis that the giant noctule bat Nyctalus lasiopterus feeds on the wing upon the multitude of flying passerines during their nocturnal migratory journeys, a resource which, while showing a predictable distribution in space and time, is only seasonally available. So far, no predator had been reported to exploit this extraordinarily diverse and abundant food reservoir represented by nocturnally migrating passerines