Traditional sociodemographic disparities in adolescent vaccination initiation for the HPV, Tdap, and MenACWY vaccines have declined in the United States of America. This decline raises the question ...of whether inequities in access have been successfully addressed. This paper synthesizes research on the resource barriers that inhibit vaccination alongside research on vaccine hesitancy where parents actively refuse vaccination. To do so, I classify the primary reason why teens are unvaccinated in the National Immunization Survey-Teen 2012-2022 into three categories: resource failure, agentic refusal, and other reasons. I use three non-exclusive subsamples of teens who are unvaccinated against the HPV (N = 87,163), MenACWY (N = 54,726), and Tdap (N = 10,947) vaccines to examine the relative importance of resource failure reasons and agentic refusal reasons for non-vaccination across time and teens' sociodemographic characteristics. Results indicate that resource failure reasons continue to explain a substantial portion of the reasons why teens are unvaccinated and disproportionately affect racially/ethnically and economically marginalized teens. Thus, even as sociodemographic inequalities in rates of vaccination have declined, inequities in access remain consequential.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure ...prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART.
Colorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF), plasma, and very large numbers of peripheral blood mononuclear cells (PBMCs) were obtained longitudinally from both participants and were studied for HIV persistence in several laboratories using molecular and culture-based detection methods, including a murine viral outgrowth assay (mVOA). Both participants initiated PrEP with tenofovir/emtricitabine during very early Fiebig stage I (detectable plasma HIV-1 RNA, antibody negative) followed by 4-drug ART intensification. Following peak viral loads, both participants experienced full suppression of HIV-1 plasma viremia. Over the following 2 years, no further HIV could be detected in blood or tissue from PrEP Participant A despite extensive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, circulating CD4+ T cell subsets, and plasma. No HIV was detected from tissues obtained from PrEP Participant B, but low-level HIV RNA or DNA was intermittently detected from various CD4+ T cell subsets. Over 500 million CD4+ T cells were assayed from both participants in a humanized mouse outgrowth assay. Three of 8 mice infused with CD4+ T cells from PrEP Participant B developed viremia (50 million input cells/surviving mouse), but only 1 of 10 mice infused with CD4+ T cells from PrEP Participant A (53 million input cells/mouse) experienced very low level viremia (201 copies/mL); sequence confirmation was unsuccessful. PrEP Participant A stopped ART and remained aviremic for 7.4 months, rebounding with HIV RNA of 36 copies/mL that rose to 59,805 copies/mL 6 days later. ART was restarted promptly. Rebound plasma HIV sequences were identical to those obtained during acute infection by single-genome sequencing. Mathematical modeling predicted that the latent reservoir size was approximately 200 cells prior to ATI and that only around 1% of individuals with a similar HIV burden may achieve lifelong ART-free remission. Furthermore, we observed that lymphocytes expressing the tumor marker CD30 increased in frequency weeks to months prior to detectable HIV-1 RNA in plasma. This study was limited by the small sample size, which was a result of the rarity of individuals presenting during hyperacute infection.
We report HIV relapse despite initiation of ART at one of the earliest stages of acute HIV infection possible. Near complete or complete loss of detectable HIV in blood and tissues did not lead to indefinite ART-free HIV remission. However, the small numbers of latently infected cells in individuals treated during hyperacute infection may be associated with prolonged ART-free remission.
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A better understanding of changes in HIV-1 population genetics with combination antiretroviral therapy (cART) is critical for designing eradication strategies. We therefore analyzed HIV-1 genetic ...variation and divergence in patients' plasma before cART, during suppression on cART, and after viral rebound. Single-genome sequences of plasma HIV-1 RNA were obtained from HIV-1 infected patients prior to cART (N = 14), during suppression on cART (N = 14) and/or after viral rebound following interruption of cART (N = 5). Intra-patient population diversity was measured by average pairwise difference (APD). Population structure was assessed by phylogenetic analyses and a test for panmixia. Measurements of intra-population diversity revealed no significant loss of overall genetic variation in patients treated for up to 15 years with cART. A test for panmixia, however, showed significant changes in population structure in 2/10 patients after short-term cART (<1 year) and in 7/10 patients after long-term cART (1-15 years). The changes consisted of diverse sets of viral variants prior to cART shifting to populations containing one or more genetically uniform subpopulations during cART. Despite these significant changes in population structure, rebound virus after long-term cART had little divergence from pretherapy virus, implicating long-lived cells infected before cART as the source for rebound virus. The appearance of genetically uniform virus populations and the lack of divergence after prolonged cART and cART interruption provide strong evidence that HIV-1 persists in long-lived cells infected before cART was initiated, that some of these infected cells may be capable of proliferation, and that on-going cycles of viral replication are not evident.
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The American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and North American Association of Central Cancer Registries collaborate to provide annual updates ...on cancer incidence and mortality and trends by cancer type, sex, age group, and racial/ethnic group in the United States. In this report, we also examine trends in stage-specific survival for melanoma of the skin (melanoma).
Incidence data for all cancers from 2001 through 2017 and survival data for melanoma cases diagnosed during 2001-2014 and followed-up through 2016 were obtained from the Centers for Disease Control and Prevention- and National Cancer Institute-funded population-based cancer registry programs compiled by the North American Association of Central Cancer Registries. Data on cancer deaths from 2001 to 2018 were obtained from the National Center for Health Statistics' National Vital Statistics System. Trends in age-standardized incidence and death rates and 2-year relative survival were estimated by joinpoint analysis, and trends in incidence and mortality were expressed as average annual percent change (AAPC) during the most recent 5 years (2013-2017 for incidence and 2014-2018 for mortality).
Overall cancer incidence rates (per 100 000 population) for all ages during 2013-2017 were 487.4 among males and 422.4 among females. During this period, incidence rates remained stable among males but slightly increased in females (AAPC = 0.2%, 95% confidence interval CI = 0.1% to 0.2%). Overall cancer death rates (per 100 000 population) during 2014-2018 were 185.5 among males and 133.5 among females. During this period, overall death rates decreased in both males (AAPC = -2.2%, 95% CI = -2.5% to -1.9%) and females (AAPC = -1.7%, 95% CI = -2.1% to -1.4%); death rates decreased for 11 of the 19 most common cancers among males and for 14 of the 20 most common cancers among females, but increased for 5 cancers in each sex. During 2014-2018, the declines in death rates accelerated for lung cancer and melanoma, slowed down for colorectal and female breast cancers, and leveled off for prostate cancer. Among children younger than age 15 years and adolescents and young adults aged 15-39 years, cancer death rates continued to decrease in contrast to the increasing incidence rates. Two-year relative survival for distant-stage skin melanoma was stable for those diagnosed during 2001-2009 but increased by 3.1% (95% CI = 2.8% to 3.5%) per year for those diagnosed during 2009-2014, with comparable trends among males and females.
Cancer death rates in the United States continue to decline overall and for many cancer types, with the decline accelerated for lung cancer and melanoma. For several other major cancers, however, death rates continue to increase or previous declines in rates have slowed or ceased. Moreover, overall incidence rates continue to increase among females, children, and adolescents and young adults. These findings inform efforts related to prevention, early detection, and treatment and for broad and equitable implementation of effective interventions, especially among under resourced populations.
Background
The American Cancer Society, the Centers for Disease Control and Prevention, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate to ...provide annual updates on cancer occurrence and trends in the United States.
Methods
Data on new cancer diagnoses during 2001 through 2016 were obtained from the Centers for Disease Control and Prevention‐funded and National Cancer Institute‐funded population‐based cancer registry programs and compiled by the North American Association of Central Cancer Registries. Data on cancer deaths during 2001 through 2017 were obtained from the National Center for Health Statistics' National Vital Statistics System. Trends in incidence and death rates for all cancers combined and for the leading cancer types by sex, racial/ethnic group, and age were estimated by joinpoint analysis and characterized by the average annual percent change during the most recent 5 years (2012‐2016 for incidence and 2013‐2017 for mortality).
Results
Overall, cancer incidence rates decreased 0.6% on average per year during 2012 through 2016, but trends differed by sex, racial/ethnic group, and cancer type. Among males, cancer incidence rates were stable overall and among non‐Hispanic white males but decreased in other racial/ethnic groups; rates increased for 5 of the 17 most common cancers, were stable for 7 cancers (including prostate), and decreased for 5 cancers (including lung and bronchus lung and colorectal). Among females, cancer incidence rates increased during 2012 to 2016 in all racial/ethnic groups, increasing on average 0.2% per year; rates increased for 8 of the 18 most common cancers (including breast), were stable for 6 cancers (including colorectal), and decreased for 4 cancers (including lung). Overall, cancer death rates decreased 1.5% on average per year during 2013 to 2017, decreasing 1.8% per year among males and 1.4% per year among females. During 2013 to 2017, cancer death rates decreased for all cancers combined among both males and females in each racial/ethnic group, for 11 of the 19 most common cancers among males (including lung and colorectal), and for 14 of the 20 most common cancers among females (including lung, colorectal, and breast). The largest declines in death rates were observed for melanoma of the skin (decreasing 6.1% per year among males and 6.3% among females) and lung (decreasing 4.8% per year among males and 3.7% among females). Among children younger than 15 years, cancer incidence rates increased an average of 0.8% per year during 2012 to 2016, and cancer death rates decreased an average of 1.4% per year during 2013 to 2017. Among adolescents and young adults aged 15 to 39 years, cancer incidence rates increased an average of 0.9% per year during 2012 to 2016, and cancer death rates decreased an average of 1.0% per year during 2013 to 2017.
Conclusions
Although overall cancer death rates continue to decline, incidence rates are leveling off among males and are increasing slightly among females. These trends reflect population changes in cancer risk factors, screening test use, diagnostic practices, and treatment advances. Many cancers can be prevented or treated effectively if they are found early. Population‐based cancer incidence and mortality data can be used to inform efforts to decrease the cancer burden in the United States and regularly monitor progress toward goals.
The Centers for Disease Control and Prevention, the American Cancer Society, the National Cancer Institute, and the North American Association of Central Cancer Registries collaborate to provide annual updates on cancer occurrence and trends in the United States and to address a special topic of interest. Part I of this report focuses on national cancer statistics, and part II characterizes progress in achieving select Healthy People 2020 objectives related to 4 common cancers.
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Integration of viral DNA into the host genome is a central event in the replication cycle and the pathogenesis of retroviruses, including HIV. Although most cells infected with HIV are rapidly ...eliminated in vivo, HIV also infects long-lived cells that persist during combination antiretroviral therapy (cART). Cells with replication competent HIV proviruses form a reservoir that persists despite cART and such reservoirs are at the center of efforts to eradicate or control infection without cART. The mechanisms of persistence of these chronically infected long-lived cells is uncertain, but recent research has demonstrated that the presence of the HIV provirus has enduring effects on infected cells. Cells with integrated proviruses may persist for many years, undergo clonal expansion, and produce replication competent HIV. Even proviruses with defective genomes can produce HIV RNA and may contribute to ongoing HIV pathogenesis. New analyses of HIV infected cells suggest that over time on cART, there is a shift in the composition of the population of HIV infected cells, with the infected cells that persist over prolonged periods having proviruses integrated in genes associated with regulation of cell growth. In several cases, strong evidence indicates the presence of the provirus in specific genes may determine persistence, proliferation, or both. These data have raised the intriguing possibility that after cART is introduced, a selection process enriches for cells with proviruses integrated in genes associated with cell growth regulation. The dynamic nature of populations of cells infected with HIV during cART is not well understood, but is likely to have a profound influence on the composition of the HIV reservoir with critical consequences for HIV eradication and control strategies. As such, integration studies will shed light on understanding viral persistence and inform eradication and control strategies. Here we review the process of HIV integration, the role that integration plays in persistence, clonal expansion of the HIV reservoir, and highlight current challenges and outstanding questions for future research.
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The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) ...collaborate to provide annual updates on cancer occurrence and trends in the United States. This Annual Report highlights survival rates. Data were from the CDC- and NCI-funded population-based cancer registry programs and compiled by NAACCR. Trends in age-standardized incidence and death rates for all cancers combined and for the leading cancer types by sex were estimated by joinpoint analysis and expressed as annual percent change. We used relative survival ratios and adjusted relative risk of death after a diagnosis of cancer (hazard ratios HRs) using Cox regression model to examine changes or differences in survival over time and by sociodemographic factors.
Overall cancer death rates from 2010 to 2014 decreased by 1.8% (95% confidence interval CI = -1.8 to -1.8) per year in men, by 1.4% (95% CI = -1.4 to -1.3) per year in women, and by 1.6% (95% CI = -2.0 to -1.3) per year in children. Death rates decreased for 11 of the 16 most common cancer types in men and for 13 of the 18 most common cancer types in women, including lung, colorectal, female breast, and prostate, whereas death rates increased for liver (men and women), pancreas (men), brain (men), and uterine cancers. In contrast, overall incidence rates from 2009 to 2013 decreased by 2.3% (95% CI = -3.1 to -1.4) per year in men but stabilized in women. For several but not all cancer types, survival statistically significantly improved over time for both early and late-stage diseases. Between 1975 and 1977, and 2006 and 2012, for example, five-year relative survival for distant-stage disease statistically significantly increased from 18.7% (95% CI = 16.9% to 20.6%) to 33.6% (95% CI = 32.2% to 35.0%) for female breast cancer but not for liver cancer (from 1.1%, 95% CI = 0.3% to 2.9%, to 2.3%, 95% CI = 1.6% to 3.2%). Survival varied by race/ethnicity and state. For example, the adjusted relative risk of death for all cancers combined was 33% (HR = 1.33, 95% CI = 1.32 to 1.34) higher in non-Hispanic blacks and 51% (HR = 1.51, 95% CI = 1.46 to 1.56) higher in non-Hispanic American Indian/Alaska Native compared with non-Hispanic whites.
Cancer death rates continue to decrease in the United States. However, progress in reducing death rates and improving survival is limited for several cancer types, underscoring the need for intensified efforts to discover new strategies for prevention, early detection, and treatment and to apply proven preventive measures broadly and equitably.
Abstract
Background
The American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and North American Association of Central Cancer Registries provide annual ...updates on cancer occurrence and trends by cancer type, sex, race, ethnicity, and age in the United States. This year’s report highlights the cancer burden among men and women age 20–49 years.
Methods
Incidence data for the years 1999 to 2015 from the Centers for Disease Control and Prevention- and National Cancer Institute–funded population-based cancer registry programs compiled by the North American Association of Central Cancer Registries and death data for the years 1999 to 2016 from the National Vital Statistics System were used. Trends in age-standardized incidence and death rates, estimated by joinpoint, were expressed as average annual percent change.
Results
Overall cancer incidence rates (per 100 000) for all ages during 2011–2015 were 494.3 among male patients and 420.5 among female patients; during the same time period, incidence rates decreased 2.1% (95% confidence interval CI = −2.6% to −1.6%) per year in men and were stable in females. Overall cancer death rates (per 100 000) for all ages during 2012–2016 were 193.1 among male patients and 137.7 among female patients. During 2012–2016, overall cancer death rates for all ages decreased 1.8% (95% CI = −1.8% to −1.8%) per year in male patients and 1.4% (95% CI = −1.4% to −1.4%) per year in females. Important changes in trends were stabilization of thyroid cancer incidence rates in women and rapid declines in death rates for melanoma of the skin (both sexes). Among adults age 20–49 years, overall cancer incidence rates were substantially lower among men (115.3 per 100 000) than among women (203.3 per 100 000); cancers with the highest incidence rates (per 100 000) among men were colon and rectum (13.1), testis (10.7), and melanoma of the skin (9.8), and among women were breast (73.2), thyroid (28.4), and melanoma of the skin (14.1). During 2011 to 2015, the incidence of all invasive cancers combined among adults age 20–49 years decreased −0.7% (95% CI = −1.0% to −0.4%) among men and increased among women (1.3%, 95% CI = 0.7% to 1.9%). The death rate for (per 100 000) adults age 20–49 years for all cancer sites combined during 2012 to 2016 was 22.8 among men and 27.1 among women; during the same time period, death rates decreased 2.3% (95% CI = −2.4% to −2.2%) per year among men and 1.7% (95% CI = −1.8% to −1.6%) per year among women.
Conclusions
Among people of all ages and ages 20–49 years, favorable as well as unfavorable trends in site-specific cancer incidence were observed, whereas trends in death rates were generally favorable. Characterizing the cancer burden may inform research and cancer-control efforts.
Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4⁺T cells. Some of ...these CD4⁺T cells are clonally expanded; most of the proviruses are defective. It is not known if any of the clonally expanded cells carry replication-competent proviruses. We report that a highly expanded CD4⁺ T-cell clone contains an intact provirus. The highly expanded clone produced infectious virus that was detected as persistent plasma viremia during cART in an HIV-1–infected patient who had squamous cell cancer. Cells containing the intact provirus were widely distributed and significantly enriched in cancer metastases. These results show that clonally expanded CD4⁺T cells can be a reservoir of infectious HIV-1.
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Changes in bioavailable dust-borne iron (Fe) supply to the iron-limited Southern Ocean may influence climate by modulating phytoplankton growth and CO₂ fixation into organic matter that is exported ...to the deep ocean. The chemical form (speciation) of Fe impacts its bioavailability, and glacial weathering produces highly labile and bioavailable Fe minerals in modern dust sources. However, the speciation of dust-borne Fe reaching the iron-limited Southern Ocean on glacial−interglacial timescales is unknown, and its impact on the bioavailable iron supply over geologic time has not been quantified. Here we use X-ray absorption spectroscopy on subantarctic South Atlantic and South Pacific marine sediments to reconstruct dust-borne Fe speciation over the last glacial cycle, and determine the impact of glacial activity and glaciogenic dust sources on bioavailable Fe supply. We show that the Fe(II) content, as a percentage of total dust-borne Fe, increases from ∼5 to 10% in interglacial periods to ∼25 to 45% in glacial periods. Consequently, the highly bioavailable Fe(II) flux increases by a factor of ∼15 to 20 in glacial periods compared with the current interglacial, whereas the total Fe flux increases only by a factor of ∼3 to 5. The change in Fe speciation is dominated by primary Fe(II) silicates characteristic of glaciogenic dust. Our results suggest that glacial physical weathering increases the proportion of highly bioavailable Fe(II) in dust that reaches the subantarctic Southern Ocean in glacial periods, which represents a positive feedback between glacial activity and cold glacial temperatures.
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