The Scientific Foundations of Forecasting Magnetospheric Space Weather

The magnetosphere is the lens through which solar space weather phenomena are focused and directed towards the Earth. In particular, the non-linear interaction of the solar wind with the Earth's magnetic field leads to the formation of highly inhomogenous electrical currents in the ionosphere which can ultimately result in damage to and problems with the operation of power distribution networks. Since electric power is the fundamental cornerstone of modern life, the interruption of power is the primary pathway by which space weather has impact on human activity and technology. Consequently, in the context of space weather, it is the ability to predict geomagnetic activity that is of key importance. This is usually stated in terms of geomagnetic storms, but we argue that in fact it is the substorm phenomenon which contains the crucial physics, and therefore prediction of substorm occurrence, severity and duration, either within the context of a longer-lasting geomagnetic storm, but potentially also as an isolated event, is of critical importance. Here we review the physics of the magnetosphere in the frame of space weather forecasting, focusing on recent results, current understanding, and an assessment of probable future developments.Peer reviewe

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. Methods: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model—a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates—with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality—which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. Findings: The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2–100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1–290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1–211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4–48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3–37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7–9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. Interpretation: Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. Funding: Bill & Melinda Gates Foundation

Materials and Fabrication Processes for Transient and Bioresorbable High-Performance Electronics

Materials and fabrication procedures are described for bioresorbable transistors and simple integrated circuits, in which the key processing steps occur on silicon wafer substrates, in schemes compatible with methods used in conventional microelectronics. The approach relies on an unusual type of silicon on insulator wafer to yield devices that exploit ultrathin sheets of monocrystalline silicon for the semiconductor, thin fi lms of magnesium for the electrodes and interconnects, silicon dioxide and magnesium oxide for the dielectrics, and silk for the substrates. A range of component examples with detailed measurements of their electrical characteristics and dissolution properties illustrate the capabilities. In vivo toxicity tests demonstrate biocompatibility in sub-dermal implants. The results have signifi cance for broad classes of water-soluble, "transient" electronic devices.1981001sciescopu

Information dimension, information overload and decision quality.

The impact of information load (both under and overload) on decision quality is an important topic, yet results of empirical research are inconsistent. These mixed results may be due to the fact that information load itself is a function of information dimension. A meta-analysis of 31 experiments reported in 18 empirical bankruptcy prediction studies was conducted to test the effect of two information dimensions: information diversity and information repetitiveness. Results indicated that both information dimensions have an adverse impact on decision quality: provision of either diverse or repeated information can be detrimental to prediction accuracy. The findings have implications for information suppliers and researchers who are interested in improving the quality of human decision making

Acupuntura e analgesia: aplicações clínicas e principais acupontos Acupuncture and analgesia: clinical applications and main acupoints

A dor é uma resposta protetora do organismo a estímulos nocivos, que resulta em efeitos indesejáveis quando não controlada. A analgesia pode ser promovida mediante a utilização de vários tipos de fármacos. No entanto, estes podem causar efeitos adversos de acordo com a espécie e condição física do paciente. A acupuntura tem se mostrado eficaz como coanalgésico pela capacidade de diminuir a quantidade de fármacos utilizados para o controle da dor e raramente ser contraindicada. Objetivou-se com este trabalho fazer uma breve revisão sobre as aplicações clínicas e os efeitos fisiológicos da acupuntura nos mecanismos da dor, bem como demonstrar os principais pontos de acupuntura utilizados para analgesia em animais. A pesquisa foi realizada em bases de dados eletrônicas por palavra-chave, durante o período de março a dezembro de 2008.<br>Pain is a protective response of the body to harmful stimulus, which results in undesirable effects if not controlled. Analgesia can be achieved with the use of different types of drugs. However, these drugs can cause adverse effects according to species and patient physical condition. Acupuncture has been proved to be an effective analgesic adjuvant, by the capacity to decrease the amount of drug used for pain control, rarely contra-indicated. The aim of this paper was to review the physiological effects of acupuncture on pain mechanisms, and demonstrate the main acupoints used for animal analgesia. The search was done in electronic search database using key words, in 2008