A Study of Helium Ion Induced Secondary Electron Production

The scanning electron microscope (SEM) is a popular instrument used for imaging because of its high resolution images it can generate. However the new scanning helium ion scanning microscope (SHIM) can produce higher resolution and better contrast images than the conventional SEM. In both the microscopes secondary electron (SE) signal is the most widely used imaging mode because of their high yield efficiency and their high spatial resolution. In order to be able to properly evaluate the relative strengths and weaknesses of electron induced SE (eSE) and ion induced SE (iSE) imaging a detailed model able to quantify them is required. Unlike in the case of eSE where there have been considerable amount of experimental and theoretical studies, there have been very few for iSE. A detailed Monte Carlo simulation of helium ion beam interaction with solids , IONiSE (Ion Induced SE) was developed. IONiSE is designed to provide data on questions such as the variation of the incident beam range, and the yield δiSE of iSE, as a function of the He+ ion energy and choice of sample, as well as the behavior of iSE yield with surface topography, spatial resolution of the iSE. This simulation employs a combination of „semi empirical‟ model for secondary electron production, and the SRIM routines that describe ion stopping power, scattering, and transport. This is a parametric model and hence requires that the material dependent parameters be determined by fitting to experimental yield data. This model shows predictable behavior for wide range of elements and it can be applied with equal ease to even complex compounds. The model can also be used for other applications like energy deposition profiles in ion beam lithography, critical dimension metrology using helium ions, ion beam deposition and etching studies and ion beam induced current in semiconductor devices

Deceleration of probe beam by stage bias potential improves resolution of serial block-face scanning electron microscopic images.

Serial block-face scanning electron microscopy (SBEM) is quickly becoming an important imaging tool to explore three-dimensional biological structure across spatial scales. At probe-beam-electron energies of 2.0 keV or lower, the axial resolution should improve, because there is less primary electron penetration into the block face. More specifically, at these lower energies, the interaction volume is much smaller, and therefore, surface detail is more highly resolved. However, the backscattered electron yield for metal contrast agents and the backscattered electron detector sensitivity are both sub-optimal at these lower energies, thus negating the gain in axial resolution. We found that the application of a negative voltage (reversal potential) applied to a modified SBEM stage creates a tunable electric field at the sample. This field can be used to decrease the probe-beam-landing energy and, at the same time, alter the trajectory of the signal to increase the signal collected by the detector. With decelerated low landing-energy electrons, we observed that the probe-beam-electron-penetration depth was reduced to less than 30 nm in epoxy-embedded biological specimens. Concurrently, a large increase in recorded signal occurred due to the re-acceleration of BSEs in the bias field towards the objective pole piece where the detector is located. By tuning the bias field, we were able to manipulate the trajectories of the  primary and secondary electrons, enabling the spatial discrimination of these signals using an advanced ring-type BSE detector configuration or a standard monolithic BSE detector coupled with a blocking aperture

A pharmacological evaluation of ethanol extract of alpinia calcarata rhizome for anti-oxidant, anti-inflammatory and anti-asthmatic properties

Alpinia calcarata rhizome ethanolic extract was tested for anti-asthmatic, antioxidant, and anti-inflammatory properties. Adaptogens normalize leukocytosis after milk consumption. Eosinophils are necessary for allergic illness development. The plant extract significantly reduced allergic asthma-related eosinophil cell count compared to the control group. Eosinophil count decreases cell recruitment and IL-4, IL-5, and IL-13, which affect cell count. Studies on milk-induced leukocytosis and eosinophils verified the plant extract's anti-asthmatic capabilities. In guinea pigs, goats, horses, dogs, and humans, histamine contracts trachea and bronchial muscles. Tracheas in guinea pigs test asthma drugs. The isolated guinea pig trachea contracts dose-dependently after H1 receptor stimulation. Alpinia calcarata reduced histamine-induced trachea constriction in solitary guinea pigs, proving its anti-asthmatic and H1 receptor antagonist capabilities. Hydrogen peroxide scavenging and reduction were used to test antioxidants. A hydrogen peroxide-scavenging Alpinia calcarata rhizome ethanol extract. Hydrogen peroxide scavenged less than ascorbic acid. Increasing Alpinia calcarata rhizome ethanolic extract dramatically lowered power. In vitro, ethanolic Alpinia calcarata rhizome extract stabilized rabbit red blood cell membranes and prevented protein denaturation. The ethanolic Alpinia calcarata rhizome extract was anti-asthmatic. Antioxidant and anti-inflammatory characteristics aid the plant's anti-astatic effects. Most asthma medications are steroidal. The phytochemical study identified steroids and flavonoids. Chemical moieties may make the plant anti-asthmatic. The findings support the conventional and advise more anti-asthmatic active component study

Anti-Urolithiatic Activity of Cassia Auriculata Ethanolic Seed Extract in Wistar Rats

Background: Urolithiasis is a medical condition that, despite substantial research in the field of urology, has yet to find a cure within the allopathic medical approach. The process of stone development, known as nephrolithiasis, can occur within the kidney or any segment of the urinary tract, encompassing the ureters and bladder. Material and Methods: The seeds of Cassia auriculata (Linn.) were obtained in June 2021 from Mettukadai hamlet, located in the Erode District of Tamilnadu, India. The herbarium of the plant was meticulously assembled, verified, and afterwards deposited as a voucher specimen. The voucher specimen was retained within the college premises for future reference. Results: The current investigation involved conducting a preliminary phytochemical analysis on the ethanolic seed extract of Cassia auriculata Linn. The research revealed the existence of many phytochemical constituents, including Alkaloids, Flavanoids, Carbohydrate, Sterols, Phytosterols, Phenols, Terpenoids, Amino acids, and Anthraquinones. The acute toxicity experiments revealed that rats exhibited tolerance to a maximum dose of 2000 mg/kg body weight, and no discernible alterations in behavior were detected across all experimental groups. Hence, fractions equivalent to one-fourth and one-eighth of the maximum tolerated dose of 200 mg/kg body weight were selected for subsequent investigations. Conclusion: In summary, the findings suggest that the application of an ethanolic seed extract derived from Cassia auriculata Linn effectively decreased the progression of urinary stone formation. Additionally, it appears that the efficacy of the treatment impact surpasses that of its preventative counterpart

Age Mosaicism across Multiple Scales in Adult Tissues

Most neurons are not replaced during an animal’s lifetime. This nondividing state is characterized by extreme longevity and age-dependent decline of key regulatory proteins. To study the lifespans of cells and proteins in adult tissues, we combined isotope labeling of mice with a hybrid imaging method (MIMS-EM). Using ^(15)N mapping, we show that liver and pancreas are composed of cells with vastly different ages, many as old as the animal. Strikingly, we also found that a subset of fibroblasts and endothelial cells, both known for their replicative potential, are characterized by the absence of cell division during adulthood. In addition, we show that the primary cilia of beta cells and neurons contains different structural regions with vastly different lifespans. Based on these results, we propose that age mosaicism across multiple scales is a fundamental principle of adult tissue, cell, and protein complex organization

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

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