Human determinants of age-dependent patterns of death from infection.

Regardless of microbial virulence (i.e., the global infection-fatality ratio), age generally drives the prevalence of death from infection in unvaccinated humans. Four mortality patterns are recognized: the common U- and L-shaped curves of endemic infections and the unique W- and J-shaped curves of pandemic infections. We suggest that these patterns result from different sets of human genetic and immunological determinants. In this model, it is the interplay between (1) monogenic genotypes affecting immunity to primary infection that preferentially manifest early in life and related genotypes or their phenocopies, including auto-antibodies, which manifest later in life and (2) the occurrence and persistence of adaptive, acquired immunity to primary or cross-reactive infections, which shapes the age-dependent pattern of human deaths from infection.

Renal NF-κB activation impairs uric acid homeostasis to promote tumor-associated mortality independent of wasting.

Tumor-induced host wasting and mortality are general phenomena across species. Many groups have previously demonstrated endocrinal impacts of malignant tumors on host wasting in rodents and Drosophila. Whether and how environmental factors and host immune response contribute to tumor-associated host wasting and survival, however, are largely unknown. Here, we report that flies bearing malignant yki3SA-gut tumors exhibited the exponential increase of commensal bacteria, which were mostly acquired from the environment, and systemic IMD-NF-κB activation due to suppression of a gut antibacterial amidase PGRP-SC2. Either gut microbial elimination or specific IMD-NF-κB blockade in the renal-like Malpighian tubules potently improved mortality of yki3SA-tumor-bearing flies in a manner independent of host wasting. We further indicate that renal IMD-NF-κB activation caused uric acid (UA) overload to reduce survival of tumor-bearing flies. Therefore, our results uncover a fundamental mechanism whereby gut commensal dysbiosis, renal immune activation, and UA imbalance potentiate tumor-associated host death.

Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.

This article presents global cancer statistics by world region for the year 2022 based on updated estimates from the International Agency for Research on Cancer (IARC). There were close to 20 million new cases of cancer in the year 2022 (including nonmelanoma skin cancers [NMSCs]) alongside 9.7 million deaths from cancer (including NMSC). The estimates suggest that approximately one in five men or women develop cancer in a lifetime, whereas around one in nine men and one in 12 women die from it. Lung cancer was the most frequently diagnosed cancer in 2022, responsible for almost 2.5 million new cases, or one in eight cancers worldwide (12.4% of all cancers globally), followed by cancers of the female breast (11.6%), colorectum (9.6%), prostate (7.3%), and stomach (4.9%). Lung cancer was also the leading cause of cancer death, with an estimated 1.8 million deaths (18.7%), followed by colorectal (9.3%), liver (7.8%), female breast (6.9%), and stomach (6.8%) cancers. Breast cancer and lung cancer were the most frequent cancers in women and men, respectively (both cases and deaths). Incidence rates (including NMSC) varied from four-fold to five-fold across world regions, from over 500 in Australia/New Zealand (507.9 per 100,000) to under 100 in Western Africa (97.1 per 100,000) among men, and from over 400 in Australia/New Zealand (410.5 per 100,000) to close to 100 in South-Central Asia (103.3 per 100,000) among women. The authors examine the geographic variability across 20 world regions for the 10 leading cancer types, discussing recent trends, the underlying determinants, and the prospects for global cancer prevention and control. With demographics-based predictions indicating that the number of new cases of cancer will reach 35 million by 2050, investments in prevention, including the targeting of key risk factors for cancer (including smoking, overweight and obesity, and infection), could avert millions of future cancer diagnoses and save many lives worldwide, bringing huge economic as well as societal dividends to countries over the forthcoming decades.

Breast cancer statistics 2024.

This is the American Cancer Society's biennial update of statistics on breast cancer among women based on high-quality incidence and mortality data from the National Cancer Institute and the Centers for Disease Control and Prevention. Breast cancer incidence continued an upward trend, rising by 1% annually during 2012-2021, largely confined to localized-stage and hormone receptor-positive disease. A steeper increase in women younger than 50 years (1.4% annually) versus 50 years and older (0.7%) overall was only significant among White women. Asian American/Pacific Islander women had the fastest increase in both age groups (2.7% and 2.5% per year, respectively); consequently, young Asian American/Pacific Islander women had the second lowest rate in 2000 (57.4 per 100,000) but the highest rate in 2021 (86.3 per 100,000) alongside White women (86.4 per 100,000), surpassing Black women (81.5 per 100,000). In contrast, the overall breast cancer death rate continuously declined during 1989-2022 by 44% overall, translating to 517,900 fewer breast cancer deaths during this time. However, not all women have experienced this progress; mortality remained unchanged since 1990 in American Indian/Alaska Native women, and Black women have 38% higher mortality than White women despite 5% lower incidence. Although the Black-White disparity partly reflects more triple-negative cancers, Black women have the lowest survival for every breast cancer subtype and stage except localized disease, with which they are 10% less likely to be diagnosed than White women (58% vs. 68%), highlighting disadvantages in social determinants of health. Progress against breast cancer could be accelerated by mitigating racial, ethnic, and social disparities through improved clinical trial representation and access to high-quality screening and treatment.

Cancer statistics, 2024.

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries (through 2020) and mortality data collected by the National Center for Health Statistics (through 2021). In 2024, 2,001,140 new cancer cases and 611,720 cancer deaths are projected to occur in the United States. Cancer mortality continued to decline through 2021, averting over 4 million deaths since 1991 because of reductions in smoking, earlier detection for some cancers, and improved treatment options in both the adjuvant and metastatic settings. However, these gains are threatened by increasing incidence for 6 of the top 10 cancers. Incidence rates increased during 2015-2019 by 0.6%-1% annually for breast, pancreas, and uterine corpus cancers and by 2%-3% annually for prostate, liver (female), kidney, and human papillomavirus-associated oral cancers and for melanoma. Incidence rates also increased by 1%-2% annually for cervical (ages 30-44 years) and colorectal cancers (ages <55 years) in young adults. Colorectal cancer was the fourth-leading cause of cancer death in both men and women younger than 50 years in the late-1990s but is now first in men and second in women. Progress is also hampered by wide persistent cancer disparities; compared to White people, mortality rates are two-fold higher for prostate, stomach and uterine corpus cancers in Black people and for liver, stomach, and kidney cancers in Native American people. Continued national progress will require increased investment in cancer prevention and access to equitable treatment, especially among American Indian and Alaska Native and Black individuals.

Screening for lung cancer: 2023 guideline update from the American Cancer Society.

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network-validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit-to-radiation-risk ratios from LCS and follow-up examinations. The GDG also examined disease burden data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50-80 years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80 years who are in good health. The ACS recommends annual LCS with low-dose computed tomography for asymptomatic individuals aged 50-80 years who currently smoke or formerly smoked and have a ≥20 pack-year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision-making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States.

Cancer statistics, 2023.

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries and mortality data collected by the National Center for Health Statistics. In 2023, 1,958,310 new cancer cases and 609,820 cancer deaths are projected to occur in the United States. Cancer incidence increased for prostate cancer by 3% annually from 2014 through 2019 after two decades of decline, translating to an additional 99,000 new cases; otherwise, however, incidence trends were more favorable in men compared to women. For example, lung cancer in women decreased at one half the pace of men (1.1% vs. 2.6% annually) from 2015 through 2019, and breast and uterine corpus cancers continued to increase, as did liver cancer and melanoma, both of which stabilized in men aged 50 years and older and declined in younger men. However, a 65% drop in cervical cancer incidence during 2012 through 2019 among women in their early 20s, the first cohort to receive the human papillomavirus vaccine, foreshadows steep reductions in the burden of human papillomavirus-associated cancers, the majority of which occur in women. Despite the pandemic, and in contrast with other leading causes of death, the cancer death rate continued to decline from 2019 to 2020 (by 1.5%), contributing to a 33% overall reduction since 1991 and an estimated 3.8 million deaths averted. This progress increasingly reflects advances in treatment, which are particularly evident in the rapid declines in mortality (approximately 2% annually during 2016 through 2020) for leukemia, melanoma, and kidney cancer, despite stable/increasing incidence, and accelerated declines for lung cancer. In summary, although cancer mortality rates continue to decline, future progress may be attenuated by rising incidence for breast, prostate, and uterine corpus cancers, which also happen to have the largest racial disparities in mortality.

Cancer statistics for American Indian and Alaska Native individuals, 2022: Including increasing disparities in early onset colorectal cancer.

American Indian and Alaska Native (AIAN) individuals are diverse culturally and geographically but share a high prevalence of chronic illness, largely because of obstacles to high-quality health care. The authors comprehensively examined cancer incidence and mortality among non-Hispanic AIAN individuals, compared with non-Hispanic White individuals for context, using population-based data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries. Overall cancer rates among AIAN individuals were 2% higher than among White individuals for incidence (2014 through 2018, confined to Purchased/Referred Care Delivery Area counties to reduce racial misclassification) but 18% higher for mortality (2015 through 2019). However, disparities varied widely by cancer type and geographic region. For example, breast and prostate cancer mortality rates are 8% and 31% higher, respectively, in AIAN individuals than in White individuals despite lower incidence and the availability of early detection tests for these cancers. The burden among AIAN individuals is highest for infection-related cancers (liver, stomach, and cervix), for kidney cancer, and for colorectal cancer among indigenous Alaskans (91.3 vs. 35.5 cases per 100,000 for White Alaskans), who have the highest rates in the world. Steep increases for early onset colorectal cancer, from 18.8 cases per 100,000 Native Alaskans aged 20-49 years during 1998 through 2002 to 34.8 cases per 100,000 during 2014 through 2018, exacerbated this disparity. Death rates for infection-related cancers (liver, stomach, and cervix), as well as kidney cancer, were approximately two-fold higher among AIAN individuals compared with White individuals. These findings highlight the need for more effective strategies to reduce the prevalence of chronic oncogenic infections and improve access to high-quality cancer screening and treatment for AIAN individuals. Mitigating the disparate burden will require expanded financial support of tribal health care as well as increased collaboration and engagement with this marginalized population.

Cancer statistics, 2022.

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.

Cancer statistics for African American/Black People 2022.

African American/Black individuals have a disproportionate cancer burden, including the highest mortality and the lowest survival of any racial/ethnic group for most cancers. Every 3 years, the American Cancer Society estimates the number of new cancer cases and deaths for Black people in the United States and compiles the most recent data on cancer incidence (herein through 2018), mortality (through 2019), survival, screening, and risk factors using population-based data from the National Cancer Institute and the Centers for Disease Control and Prevention. In 2022, there will be approximately 224,080 new cancer cases and 73,680 cancer deaths among Black people in the United States. During the most recent 5-year period, Black men had a 6% higher incidence rate but 19% higher mortality than White men overall, including an approximately 2-fold higher risk of death from myeloma, stomach cancer, and prostate cancer. The overall cancer mortality disparity is narrowing between Black and White men because of a steeper drop in Black men for lung and prostate cancers. However, the decline in prostate cancer mortality in Black men slowed from 5% annually during 2010 through 2014 to 1.3% during 2015 through 2019, likely reflecting the 5% annual increase in advanced-stage diagnoses since 2012. Black women have an 8% lower incidence rate than White women but a 12% higher mortality; further, mortality rates are 2-fold higher for endometrial cancer and 41% higher for breast cancer despite similar or lower incidence rates. The wide breast cancer disparity reflects both later stage diagnosis (57% localized stage vs 67% in White women) and lower 5-year survival overall (82% vs 92%, respectively) and for every stage of disease (eg, 20% vs 30%, respectively, for distant stage). Breast cancer surpassed lung cancer as the leading cause of cancer death among Black women in 2019. Targeted interventions are needed to reduce stark cancer inequalities in the Black community.

Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.

Cancer Statistics, 2021.

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.

Cancer statistics, 2020.

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.

Mortality and morbidity ramifications of proposed retractions in healthcare coverage for the United States.

In the absence of universal healthcare in the United States, federal programs of Medicaid and Medicare are vital to providing healthcare coverage for low-income households and elderly individuals, respectively. However, both programs are under threat, with either enacted or proposed retractions. Specifically, raising Medicare age eligibility and the addition of work requirements for Medicaid qualification have been proposed, while termination of continuous enrollment for Medicaid was recently effectuated. Here, we assess the potential impact on mortality and morbidity resulting from these policy changes. Our findings indicate that the policy change to Medicare would lead to over 17,000 additional deaths among individuals aged 65 to 67 and those to Medicaid would lead to more than 8,000 deaths among those under the age of 65. To illustrate the implications for morbidity, we further consider a case study among those people with diabetes who would be likely to lose their health insurance under the policy changes. We project that these insurance retractions would lead to the loss of coverage for over 700,000 individuals with diabetes, including more than 200,000 who rely on insulin.

Physician-patient racial concordance and newborn mortality.

The racial gap in infant mortality is a pressing public-health concern, and [B. N. Greenwood et al., Proc. Natl. Acad. Sci. U.S.A. 117, 21194-21200 (2020), 10.1073/pnas.1913405117] suggest that Black newborns are more likely to survive if cared for by Black physicians after birth, even in models that control for numerous variables, including hospital and physician fixed effects, and the 65 most common comorbidities affecting newborns (as described by International Classification of Disease codes). We acquired the data used in the study, covering Florida hospital discharges from 1992 through the third quarter of 2015, to replicate and extend the analysis. We find that the magnitude of the concordance effect is substantially reduced after controlling for diagnoses indicating very low birth weight (<1,500 g), which are a strong predictor of neonatal mortality but not among the 65 most common comorbidities. In fact, the estimated effect is near zero and statistically insignificant in the expanded specifications that control for very low birth weight and include hospital and physician fixed effects.

Mechanistic links between physiology and spectral reflectance enable previsual detection of oak wilt and drought stress.

Tree mortality due to global change-including range expansion of invasive pests and pathogens-is a paramount threat to forest ecosystems. Oak forests are among the most prevalent and valuable ecosystems both ecologically and economically in the United States. There is increasing interest in monitoring oak decline and death due to both drought and the oak wilt pathogen (Bretziella fagacearum). We combined anatomical and ecophysiological measurements with spectroscopy at leaf, canopy, and airborne levels to enable differentiation of oak wilt and drought, and detection prior to visible symptom appearance. We performed an outdoor potted experiment with Quercus rubra saplings subjected to drought stress and/or artificially inoculated with the pathogen. Models developed from spectral reflectance accurately predicted ecophysiological indicators of oak wilt and drought decline in both potted and field experiments with naturally grown saplings. Both oak wilt and drought resulted in blocked water transport through xylem conduits. However, oak wilt impaired conduits in localized regions of the xylem due to formation of tyloses instead of emboli. The localized tylose formation resulted in more variable canopy photosynthesis and water content in diseased trees than drought-stressed ones. Reflectance signatures of plant photosynthesis, water content, and cellular damage detected oak wilt and drought 12 d before visual symptoms appeared. Our results show that leaf spectral reflectance models predict ecophysiological processes relevant to detection and differentiation of disease and drought. Coupling spectral models that detect physiological change with spatial information enhances capacity to differentiate plant stress types such as oak wilt and drought.

No birth-associated maternal mortality in Japanese macaques (Macaca fuscata) despite giving birth to large-headed neonates.

Human fetuses at term are large relative to the dimensions of the maternal birth canal, implying that their birth can be associated with difficulties. The tight passage through the human birth canal can lead to devastating outcomes if birth becomes obstructed, including maternal and fetal death. Although macaques have to accommodate similarly large fetuses, relative to their maternal birth canals, it was not known whether macaque mothers face birth difficulties similar to humans. Based on 27 y of demographic data from a semi-free-ranging, closely monitored population of Japanese macaques (Macaca fuscata), we found no birth-associated mortality in macaques. This differs from the situation in many human populations. We suggest three nonmutually exclusive hypotheses to explain these observations. i) The macaque fetal skull is similarly flexible as the human fetal skull. ii) The macaque pelvis and connective tissue show greater flexibility during birth. iii) The interplay between macaque pelvic shape and birth dynamics is smoother and incurs fewer complications than in humans.

Long-term exposure to wildland fire smoke PM2.5 and mortality in the contiguous United States.

Despite the substantial evidence on the health effects of short-term exposure to ambient fine particles (PM2.5), including increasing studies focusing on those from wildland fire smoke, the impacts of long-term wildland fire smoke PM2.5 exposure remain unclear. We investigated the association between long-term exposure to wildland fire smoke PM2.5 and nonaccidental mortality and mortality from a wide range of specific causes in all 3,108 counties in the contiguous United States, 2007 to 2020. Controlling for nonsmoke PM2.5, air temperature, and unmeasured spatial and temporal confounders, we found a nonlinear association between 12-mo moving average concentration of smoke PM2.5 and monthly nonaccidental mortality rate. Relative to a month with the long-term smoke PM2.5 exposure below 0.1 µg/m3, nonaccidental mortality increased by 0.16 to 0.63 and 2.11 deaths per 100,000 people per month when the 12-mo moving average of PM2.5 concentration was of 0.1 to 5 and 5+ µg/m3, respectively. Cardiovascular, ischemic heart disease, digestive, endocrine, diabetes, mental, and chronic kidney disease mortality were all found to be associated with long-term wildland fire smoke PM2.5 exposure. Smoke PM2.5 contributed to approximately 11,415 nonaccidental deaths/y (95% CI: 6,754, 16,075) in the contiguous United States. Higher smoke PM2.5-related increases in mortality rates were found for people aged 65 and above. Positive interaction effects with extreme heat were also observed. Our study identified the detrimental effects of long-term exposure to wildland fire smoke PM2.5 on a wide range of mortality outcomes, underscoring the need for public health actions and communications that span the health risks of both short- and long-term exposure.

Estimates of actual and potential lives saved in the United States from the use of COVID-19 convalescent plasma.

In the Spring of 2020, the United States of America (USA) deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Over 500,000 patients were treated with CCP during the first year of the pandemic. In this study, we estimated the number of actual inpatient lives saved by CCP treatment in the United States of America based on CCP weekly use, weekly national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimate the potential number of lives saved if CCP had been deployed for 100% of hospitalized patients or used in 15 to 75% of outpatients. Depending on the assumptions modeled in stratified analyses, we estimated that CCP saved between 16,476 and 66,296 lives. The CCP ideal use might have saved as many as 234,869 lives and prevented 1,136,133 hospitalizations. CCP deployment was a successful strategy for ameliorating the impact of the COVID-19 pandemic in the USA. This experience has important implications for convalescent plasma use in future infectious disease emergencies.

Demographic drivers of reproductive failure in a threatened bird: Insights from a decade of data.

Hatching failure affects up to 77% of eggs laid by threatened bird species, yet the true prevalence and drivers of egg fertilization failure versus embryo mortality as underlying mechanisms of hatching failure are unknown. Here, using ten years of data comprising 4,371 eggs laid by a population of a threatened bird, the hihi (Notiomystis cincta), we investigate the relative importance of infertility and embryo death as drivers of hatching failure and explore population-level factors associated with them. We show that of the 1,438 eggs that failed to hatch (33% of laid eggs) between 2010 and 2020, 83% failed due to embryo mortality, with the majority failing in the early stages of embryonic development. In the most comprehensive estimates of infertility rates in a wild bird population to date, we find that fertilization failure accounts for around 17% of hatching failure overall and is more prevalent in years where the population is smaller and more male biased. Male embryos are more likely to die during early development than females, but we find no overall effect of sex on the successful development of embryos. Offspring fathered by within-pair males have significantly higher inbreeding levels than extra-pair offspring; however, we find no effect of inbreeding nor extra-pair paternity on embryo mortality. Accurately distinguishing between infertility and embryo mortality in this study provides unique insight into the underlying causes of reproductive failure over a long-term scale and reveals the complex risks of small population sizes to the reproduction of threatened species.