The Leading Causes of Death in the US for 2020 Ahmad, Farida B; Anderson, Robert N
JAMA : the journal of the American Medical Association,
2021-May-11, Letnik:
325, Številka:
18
Journal Article
An analysis of all US Food and Drug Administration (FDA) approvals for protein-based assays through 2008 reveals 109 unique protein targets in plasma or serum, as well as 62 additional tests for ...peptides, protein posttranslational modifications, protein complexes, autoantibodies against endogenous proteins, and blood cell proteins. A further 96 unique protein targets are assayed in plasma by laboratory-developed tests available for clinical use in the US, yielding a total of 205 proteins that include products of approximately 211 genes (excluding immunoglobulins). These tests provide quantitative measurements for approximately 1% of the human protein gene products, defining a practical clinical plasma proteome. The rate of introduction of new protein analytes has remained essentially flat over the past 15 years, averaging 1.5 new proteins per year (median of 1 per year). This rate falls far short of that needed to support projected medical needs and indicates serious deficiencies in the protein biomarker pipeline, from which no proteomics-discovered analytes have yet emerged.
The eutrophication of lowland lakes in Europe by excess nitrogen (N) and phosphorus (P) is severe because of the long history of land‐cover change and agricultural intensification. The ecological and ...socio‐economic effects of eutrophication are well understood but its effect on organic carbon (OC) sequestration by lakes and its change overtime has not been determined. Here, we compile data from ~90 culturally impacted European lakes ~60% are eutrophic, Total P (TP) >30 μg P l−1 and determine the extent to which OC burial rates have increased over the past 100–150 years. The average focussing corrected, OC accumulation rate (C ARFC) for the period 1950–1990 was ~60 g C m−2 yr−1, and for lakes with >100 μg TP l−1 the average was ~100 g C m−2 yr−1. The ratio of post‐1950 to 1900–1950 C AR is low (~1.5) indicating that C accumulation rates have been high throughout the 20th century. Compared to background estimates of OC burial (~5–10 g C m−2 yr−1), contemporary rates have increased by at least four to fivefold. The statistical relationship between C ARFC and TP derived from this study (r2 = 0.5) can be used to estimate OC burial at sites lacking estimates of sediment C‐burial. The implications of eutrophication, diagenesis, lake morphometry and sediment focussing as controls of OC burial rates are considered. A conservative interpretation of the results of the this study suggests that lowland European meso‐ to eutrophic lakes with >30 μg TP l−1 had OC burial rates in excess of 50 g C m−2 yr−1 over the past century, indicating that previous estimates of regional lake OC burial have seriously underestimated their contribution to European carbon sequestration. Enhanced OC burial by lakes is one positive side‐effect of the otherwise negative impact of the anthropogenic disruption of nutrient cycles.
Transposable elements (TEs) constitute the majority of flowering plant DNA, reflecting their tremendous success in subverting, avoiding, and surviving the defenses of their host genomes to ensure ...their selfish replication. More than 85% of the sequence of the maize genome can be ascribed to past transposition, providing a major contribution to the structure of the genome. Evidence from individual loci has informed our understanding of how transposition has shaped the genome, and a number of individual TE insertions have been causally linked to dramatic phenotypic changes. Genome-wide analyses in maize and other taxa have frequently represented TEs as a relatively homogeneous class of fragmentary relics of past transposition, obscuring their evolutionary history and interaction with their host genome. Using an updated annotation of structurally intact TEs in the maize reference genome, we investigate the family-level dynamics of TEs in maize. Integrating a variety of data, from descriptors of individual TEs like coding capacity, expression, and methylation, as well as similar features of the sequence they inserted into, we model the relationship between attributes of the genomic environment and the survival of TE copies and families. In contrast to the wholesale relegation of all TEs to a single category of junk DNA, these differences reveal a diversity of survival strategies of TE families. Together these generate a rich ecology of the genome, with each TE family representing the evolution of a distinct ecological niche. We conclude that while the impact of transposition is highly family- and context-dependent, a family-level understanding of the ecology of TEs in the genome can refine our ability to predict the role of TEs in generating genetic and phenotypic diversity.
Wrist-worn accelerometers are increasingly being used for the assessment of physical activity in population studies, but little is known about their value for sleep assessment. We developed a novel ...method of assessing sleep duration using data from 4,094 Whitehall II Study (United Kingdom, 2012-2013) participants aged 60-83 who wore the accelerometer for 9 consecutive days, filled in a sleep log and reported sleep duration via questionnaire. Our sleep detection algorithm defined (nocturnal) sleep as a period of sustained inactivity, itself detected as the absence of change in arm angle greater than 5 degrees for 5 minutes or more, during a period recorded as sleep by the participant in their sleep log. The resulting estimate of sleep duration had a moderate (but similar to previous findings) agreement with questionnaire based measures for time in bed, defined as the difference between sleep onset and waking time (kappa = 0.32, 95%CI:0.29,0.34) and total sleep duration (kappa = 0.39, 0.36,0.42). This estimate was lower for time in bed for women, depressed participants, those reporting more insomnia symptoms, and on weekend days. No such group differences were found for total sleep duration. Our algorithm was validated against data from a polysomnography study on 28 persons which found a longer time window and lower angle threshold to have better sensitivity to wakefulness, while the reverse was true for sensitivity to sleep. The novelty of our method is the use of a generic algorithm that will allow comparison between studies rather than a "count" based, device specific method.
The human plasma proteome holds the promise of a revolution in disease diagnosis and therapeutic monitoring provided that major challenges in proteomics and related disciplines can be addressed. ...Plasma is not only the primary clinical specimen but also represents the largest and deepest version of the human proteome present in any sample: in addition to the classical "plasma proteins," it contains all tissue proteins (as leakage markers) plus very numerous distinct immunoglobulin sequences, and it has an extraordinary dynamic range in that more than 10 orders of magnitude in concentration separate albumin and the rarest proteins now measured clinically. Although the restricted dynamic range of conventional proteomic technology (two-dimensional gels and mass spectrometry) has limited its contribution to the list of 289 proteins (tabulated here) that have been reported in plasma to date, very recent advances in multidimensional survey techniques promise at least double this number in the near future. Abundant scientific evidence, from proteomics and other disciplines, suggests that among these are proteins whose abundances and structures change in ways indicative of many, if not most, human diseases. Nevertheless, only a handful of proteins are currently used in routine clinical diagnosis, and the rate of introduction of new protein tests approved by the United States Food and Drug Administration (FDA) has paradoxically declined over the last decade to less than one new protein diagnostic marker per year. We speculate on the reasons behind this large discrepancy between the expectations arising from proteomics and the realities of clinical diagnostics and suggest approaches by which protein-disease associations may be more effectively translated into diagnostic tools in the future.
The Huihui Yaofang was an encyclopaedia of Near Eastern medicine compiled under the Mongol Yuan Dynasty for the benefit of themselves and Chinese medical establishments. We translate the surviving ...material and context it in the history and ethnobiology of the medicine described.
We have studied the physiological and genetic responses of Arabidopsis thaliana L. (Arabidopsis) to gold. The root lengths of Arabidopsis seedlings grown on nutrient agar plates containing 100 mg/L ...gold were reduced by 75%. Oxidized gold was subsequently found in roots and shoots of these plants, but gold nanoparticles (reduced gold) were only observed in the root tissues. We used a microarray-based study to monitor the expression of candidate genes involved in metal uptake and transport in Arabidopsis upon gold exposure. There was up-regulation of genes involved in plant stress response such as glutathione transferases, cytochromes P450, glucosyl transferases and peroxidases. In parallel, our data show the significant down-regulation of a discreet number of genes encoding proteins involved in the transport of copper, cadmium, iron and nickel ions, along with aquaporins, which bind to gold. We used Medicago sativa L. (alfalfa) to study nanoparticle uptake from hydroponic culture using ionic gold as a non-nanoparticle control and concluded that nanoparticles between 5 and 100 nm in diameter are not directly accumulated by plants. Gold nanoparticles were only observed in plants exposed to ionic gold in solution. Together, we believe our results imply that gold is taken up by the plant predominantly as an ionic form, and that plants respond to gold exposure by up-regulating genes for plant stress and down-regulating specific metal transporters to reduce gold uptake.
Extrapolation from studies in the 1980s suggests that smoking causes 25% of deaths among women and men 35 to 69 years of age in the United States. Nationally representative measurements of the ...current risks of smoking and the benefits of cessation at various ages are unavailable.
We obtained smoking and smoking-cessation histories from 113,752 women and 88,496 men 25 years of age or older who were interviewed between 1997 and 2004 in the U.S. National Health Interview Survey and related these data to the causes of deaths that occurred by December 31, 2006 (8236 deaths in women and 7479 in men). Hazard ratios for death among current smokers, as compared with those who had never smoked, were adjusted for age, educational level, adiposity, and alcohol consumption.
For participants who were 25 to 79 years of age, the rate of death from any cause among current smokers was about three times that among those who had never smoked (hazard ratio for women, 3.0; 99% confidence interval CI, 2.7 to 3.3; hazard ratio for men, 2.8; 99% CI, 2.4 to 3.1). Most of the excess mortality among smokers was due to neoplastic, vascular, respiratory, and other diseases that can be caused by smoking. The probability of surviving from 25 to 79 years of age was about twice as great in those who had never smoked as in current smokers (70% vs. 38% among women and 61% vs. 26% among men). Life expectancy was shortened by more than 10 years among the current smokers, as compared with those who had never smoked. Adults who had quit smoking at 25 to 34, 35 to 44, or 45 to 54 years of age gained about 10, 9, and 6 years of life, respectively, as compared with those who continued to smoke.
Smokers lose at least one decade of life expectancy, as compared with those who have never smoked. Cessation before the age of 40 years reduces the risk of death associated with continued smoking by about 90%.
Aside from age, sex, and family history, risk of developing breast cancer is largely linked to reproductive factors, which characterize exposure to sex hormones. Given that, molecular testing at the ...tumor level is currently possible, clinical characterization of tumor subtypes is routinely conducted to guide treatment decisions. However, despite the vast amount of published data from observational studies on reproductive factor associations and breast cancer risk, relatively fewer reports have been published on associations specific to breast tumor subtypes. We conducted a review of the literature and summarized the results of associations between reproductive factors and risk or odds of three distinct tumor subtypes: estrogen receptor/progesterone receptor positive (hormone receptor positive, HR+ tumors), tumors overexpressing the human epidermal receptor 2 protein (HER2+), and triple negative breast cancer (TNBC), which lacks the three markers. Results show that the most consistent evidence for associations with reproductive risk factors exists for HR+ breast cancers, with nulliparity, current use of menopausal hormone therapy, and prolonged interval between menarche and age at first birth being the strongest risk factors; increased age at first birth and decreased age at menarche were fairly consistently associated with HR+ cancers; and though less consistent, older age at menopause was also positively associated, while lactation was inversely associated with HR+ tumors. Fewer consistent associations have been reported for TNBC. The single protective factor most consistently associated with TNBC was longer duration of breastfeeding. Increased parity, younger age at first birth, older age at menarche, and oral contraceptive use were less consistently shown to be associated with TNBC. No remarkable associations for HER2+ breast cancers were evident, although this was based on relatively scarce data. Findings suggest heterogeneity in reproductive risk factors for the distinct subtypes of breast tumors, which may have implications for recommended prevention strategies.
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