America\u27s Energy Dependency: Will Government Regulation of Caffeine Bring the Caffeine Companies to a Crash?

In light of Americans’ growing love affair with caffeinated products, this Note considers not only the possibility of future regulation of those products, but also the effect that regulation would have on caffeinated product-producing companies. While there is no certainty that such regulation is in our future, the regulation of market-similar products like tobacco and alcohol, and regulations abroad on heavily caffeinated drinks, suggest American regulation of caffeinated products to be a distinct possibility. This would be a serious concern for caffeine companies, who could face reduced access to target markets as a result of FDA-imposed limitations, whether by age restriction or another similar measure. In light of this potential regulation, the next question then becomes: what can companies do to help combat foreseeable FDA regulation or governmental legislation of the caffeine industry? Can businesses in this industry predict the market effect of regulation, and thereby take effective action, by comparing regulation of market-similar products such as tobacco and alcohol? Part I of this Note discusses the medical effects of caffeine on humans, both adults and children. Part II discusses the probability of future government regulation and the subtle hints of impending regulation. Part II also briefly examines other countries’ laws and regulations of caffeine consumption. Part III discusses and predicts the effects regulation would have on producers of caffeinated products by contrasting the caffeine industry with the tobacco industry, and looks at the effects of tobacco regulations placed on tobacco producers. Part IV discusses the effects of future regulation on caffeine-dependent Americans. Part V discusses the potential avenues businesses may take to fend off diminishing profits that would result from government regulation. Finally, this Note concludes that while businesses’ financial statements will be hurt by government regulation, businesses will be able to defend their profit model by incorporating the proffered solutions discussed in Part V

America\u27s Energy Dependency: Will Government Regulation of Caffeine Bring the Caffeine Companies to a Crash?

In light of Americans’ growing love affair with caffeinated products, this Note considers not only the possibility of future regulation of those products, but also the effect that regulation would have on caffeinated product-producing companies. While there is no certainty that such regulation is in our future, the regulation of market-similar products like tobacco and alcohol, and regulations abroad on heavily caffeinated drinks, suggest American regulation of caffeinated products to be a distinct possibility. This would be a serious concern for caffeine companies, who could face reduced access to target markets as a result of FDA-imposed limitations, whether by age restriction or another similar measure. In light of this potential regulation, the next question then becomes: what can companies do to help combat foreseeable FDA regulation or governmental legislation of the caffeine industry? Can businesses in this industry predict the market effect of regulation, and thereby take effective action, by comparing regulation of market-similar products such as tobacco and alcohol? Part I of this Note discusses the medical effects of caffeine on humans, both adults and children. Part II discusses the probability of future government regulation and the subtle hints of impending regulation. Part II also briefly examines other countries’ laws and regulations of caffeine consumption. Part III discusses and predicts the effects regulation would have on producers of caffeinated products by contrasting the caffeine industry with the tobacco industry, and looks at the effects of tobacco regulations placed on tobacco producers. Part IV discusses the effects of future regulation on caffeine-dependent Americans. Part V discusses the potential avenues businesses may take to fend off diminishing profits that would result from government regulation. Finally, this Note concludes that while businesses’ financial statements will be hurt by government regulation, businesses will be able to defend their profit model by incorporating the proffered solutions discussed in Part V

Influence of Temperature on the Conformational Guided Physical Properties of Ultrathin Films of PLLA

Poly (L lactic acid) (PLLA) ultrathin films of various thicknesses were prepared by spin coating method and investigated by using vibrational spectroscopic techniques such as FTIR and Raman. The analysis has been done in two parts: first one is verification of structural mode to understand the visibility of characteristic band to confirm the PLLA structure; where interestingly, as the thickness of the film increased, the structural features were found to be more explicit. The second part of the study was to observe the features of the film having been annealed for 1 h in two separate temperatures, one at specific annealing temperature 120 °C and the other at 160 °C to enable PLLA chains to reorient to get crystallized from its soften state at two such specific temperatures. The isothermal crystallization behavior of PLLA film at 120 °C and 160 °C from the melt was monitored by FTIR as well as Raman spectroscopies. More importantly, the band at 921 cm-1 corresponds to α crystalline phase of PLLA has been observed even in this ultrathin film with the effective application of temperature as selected in this study.Defence Science Journal, Vol. 64, No. 3, May 2014, pp. 309-313, DOI:http://dx.doi.org/10.14429/dsj.64.732

Multi-Response Optimization of WEDM Process Parameters for Machining of Superelastic Nitinol Shape-Memory Alloy Using a Heat-Transfer Search Algorithm

Nitinol, a shape-memory alloy (SMA), is gaining popularity for use in various applications. Machining of these SMAs poses a challenge during conventional machining. Henceforth, in the current study, the wire-electric discharge process has been attempted to machine nickel-titanium (Ni55.8Ti) super-elastic SMA. Furthermore, to render the process viable for industry, a systematic approach comprising response surface methodology (RSM) and a heat-transfer search (HTS) algorithm has been strategized for optimization of process parameters. Pulse-on time, pulse-off time and current were considered as input process parameters, whereas material removal rate (MRR), surface roughness, and micro-hardness were considered as output responses. Residual plots were generated to check the robustness of analysis of variance (ANOVA) results and generated mathematical models. A multi-objective HTS algorithm was executed for generating 2-D and 3-D Pareto optimal points indicating the non-dominant feasible solutions. The proposed combined approach proved to be highly effective in predicting and optimizing the wire electrical discharge machining (WEDM) process parameters. Validation trials were carried out and the error between measured and predicted values was negligible. To ensure the existence of a shape-memory effect even after machining, a differential scanning calorimetry (DSC) test was carried out. The optimized parameters were found to machine the alloy appropriately with the intact shape memory effect

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

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

Effect of multi-walled structure on microstructure and mechanical properties of 1.25Cr-1.0Mo steel fabricated by GMAW-based WAAM using metal-cored wire

Wire-arc additive manufacturing (WAAM) offers multiple benefits, such as high metal deposition, low capital cost, suitable mechanical properties, and reasonable costs. In the present work, Gas metal arc welding (GMAW) based WAAM was employed to manufacture a multi-walled component of 1.25Cr-0.5Mo at optimized parameters using metal-cored wire. The fabricated multi-walled structure was observed with seamless fusion and free from disbonding. The fabricated multi-walled component was studied through microstructure investigations, mechanical properties such as microhardness (MH), tensile test, and impact test at various positions (top side, middle side, and bottom side) of the built structure. Microstructure results have shown a tempered martensite structure in the bottom zone with coarse grains and finer microstructures in the middle and top zones. MH values throughout the component were uniform and thus indicated a similar nature to the multi-walled component. A comparison of tensile properties was carried out among the results of metal-cored wires and multi-walled structures to check the internal eminence of the obtained component. For all sides of the multi-walled structure, all the tensile properties were found to be in the range values of 1.25Cr-0.5Mo metal-cored wire. The results of all three conditions for impact toughness showed far better strength than the requirement. Fracture surface morphologies of tensile and impact test parts showed the presence of large dimples with the homogenous distribution. Thus, all the obtained results have suggested the suitability of the GMAWAM process for the fabrication of a multi-walled structure of 1.25Cr-0.5Mo metal-cored wire for various industrial applications

Trend of clinical drug trials in type 2 diabetes mellitus over last decade

Background: Type 2 diabetes mellitus (Type 2 DM) has been recognized as the recent pandemic; India and China competing each other for the title--"Diabetes Capital of the World." A number of new drugs have been recently available and has lead to a boom in the clinical drug trial industry. We intend to evaluate the trend of clinical drug trials in Type 2 DM over last one decade. Materials and Methods: Clinical drug trial registry of USA was used for getting the data regarding number of drug trials conducted in each country over last decade. India, China, and USA being the countries with highest prevalence of diabetes were included in the analysis. The percentage share of each country in clinical drug trials in Type 2 DM was compared with their percentage share in prevalence of Type 2 DM. Discussion: A significant growth in the drug trials in Type 2 DM was observed during 2005 to 2008, after which there has been a plateau. It was also recognized that India and China which contribute to around 30% of diabetic population of the world contributed in only 9.73% and 5.15% of drug trials in Type 2 DM during 2010, respectively. USA comprising of 15.15% of diabetic population of world was seen to have contributed in 38.36% of clinical drug trials in Type 2 DM. This raises a question of skewing in the data generated from various drug trials conducted in Type 2 DM