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.
Many current cancer vaccine strategies suffer from the inability to mount a CD8 T cell response that is strong enough to overcome the low immunogenicity of tumors. Viruses naturally possess the ...sizes, geometries, and physical properties for which the immune system has evolved to recognize, and mimicking those properties with nanoparticles can produce robust platforms for vaccine design. Using the nonviral E2 core of pyruvate dehydrogenase, we have engineered a viral-mimicking vaccine platform capable of encapsulating dendritic cell (DC)-activating CpG molecules in an acid-releasable manner and displaying MHC I-restricted SIINFEKL peptide epitopes. Encapsulated CpG activated bone marrow-derived DCs at a 25-fold lower concentration in vitro when delivered with the E2 nanoparticle than with unbound CpG alone. Combining CpG and SIINFEKL within a single multifunctional particle induced ∼3-fold greater SIINFEKL display on MHC I by DCs over unbound peptide. Importantly, combining CpG and SIINFEKL to the E2 nanoparticle for simultaneous temporal and spatial delivery to DCs showed increased and prolonged CD8 T cell activation, relative to free peptide or peptide-bound E2. By codelivering peptide epitopes and CpG activator in a particle of optimal DC-uptake size, we demonstrate the ability of a noninfectious protein nanoparticle to mimic viral properties and facilitate enhanced DC activation and cross-presentation.
Helium is the second-most abundant element in the Universe after hydrogen and is one of the main constituents of gas-giant planets in our Solar System. Early theoretical models predicted helium to be ...among the most readily detectable species in the atmospheres of exoplanets, especially in extended and escaping atmospheres
. Searches for helium, however, have hitherto been unsuccessful
. Here we report observations of helium on an exoplanet, at a confidence level of 4.5 standard deviations. We measured the near-infrared transmission spectrum of the warm gas giant
WASP-107b and identified the narrow absorption feature of excited metastable helium at 10,833 angstroms. The amplitude of the feature, in transit depth, is 0.049 ± 0.011 per cent in a bandpass of 98 angstroms, which is more than five times greater than what could be caused by nominal stellar chromospheric activity. This large absorption signal suggests that WASP-107b has an extended atmosphere that is eroding at a total rate of 10
to 3 × 10
grams per second (0.1-4 per cent of its total mass per billion years), and may have a comet-like tail of gas shaped by radiation pressure.
Abstract Neural oscillations with a frequency of around 10 Hz are thought to be a ubiquitous phenomenon in sensory cortices, and it has been hypothesized that the level of 10 Hz activity is related ...to local cortical excitability. During spatial attention, the visual alpha rhythm has been found to be modulated according to the direction of attention. Specifically, the alpha rhythm desynchronizes over visual cortex contralateral to the direction of attention and synchronizes over visual cortex ipsilateral to the direction of attention, and these modulations have been associated with facilitation and inhibition of sensory processing. In the somatosensory domain, the reactivity of a similar rhythm, known as the mu rhythm, during attention tasks is a current topic of inquiry and somatotopic modulation of the mu rhythm by directed attention have been reported. In this paper, we investigate how lateralized spatial attention modulates the ongoing somatosensory mu rhythm, and how such modulation impacts sensory information processing. 128 channel EEG was recorded while subjects performed a somatosensory spatial attention task. In addition to analyses on scalp recorded data, a spatial filtering method was utilized to investigate spatial attention effects in the source space. The direction of spatial attention was found to have a significant somatotopic effect on the ongoing mu rhythm occurring in primary somatosensory cortex. Concurrently, the visual alpha rhythm was significantly elevated above the baseline level during somatosensory attention, demonstrating a cross-modal effect. Lastly, an analysis was performed to investigate the correlation between the level of prestimulus mu activity and subsequent stimulus evoked activity in primary somatosensory cortex.
The Klebsiella pneumoniae carbapenem (KPC) β-lactamase occurs in Enterobacteriaceae and can confer resistance to all β-lactam agents including carbapenems. The enzyme may confer low-level carbapenem ...resistance, and the failure of susceptibility methods to identify this resistance has been reported. Automated and nonautomated methods for carbapenem susceptibility were evaluated for identification of KPC-mediated resistance. Ertapenem was a more sensitive indicator of KPC resistance than meropenem and imipenem independently of the method used. Carbapenemase production could be confirmed with the modified Hodge test.
How climate and ecology affect key cultural transformations remains debated in the context of long-term socio-cultural development because of spatially and temporally disjunct climate and ...archaeological records. The introduction of agriculture triggered a major population increase across Europe. However, in Southern Scandinavia it was preceded by ~500 years of sustained population growth. Here we show that this growth was driven by long-term enhanced marine production conditioned by the Holocene Thermal Maximum, a time of elevated temperature, sea level and salinity across coastal waters. We identify two periods of increased marine production across trophic levels (P1 7600-7100 and P2 6400-5900 cal. yr BP) that coincide with markedly increased mollusc collection and accumulation of shell middens, indicating greater marine resource availability. Between ~7600-5900 BP, intense exploitation of a warmer, more productive marine environment by Mesolithic hunter-gatherers drove cultural development, including maritime technological innovation, and from ca. 6400-5900 BP, underpinned a ~four-fold human population growth.
We present a search for anisotropic cosmic birefringence in 500 deg2 of southern sky observed at 150 GHz with the SPTpol camera on the South Pole Telescope. We reconstruct a map of cosmic ...polarization rotation anisotropies using higher-order correlations between the observed cosmic microwave background (CMB) E and B fields. We then measure the angular power spectrum of this map, which is found to be consistent with zero. The nondetection is translated into an upper limit on the amplitude of the scale-invariant cosmic rotation power spectrum, L(L + 1) CααL/2π < 0.10 × 10−4 rad2 (0.033 deg2, 95% C.L.). This upper limit can be used to place constraints on the strength of primordial magnetic fields, B1 Mpc < 17 nG (95% C.L.), and on the coupling constant of the Chern-Simons electromagnetic term gaγ < 4.0 × 10−2/HI (95% C.L.), where HI is the inflationary Hubble scale. For the first time, we also cross-correlate the CMB temperature fluctuations with the reconstructed rotation angle map, a signal expected to be nonvanishing in certain theoretical scenarios, and find no detectable signal. We perform a suite of systematics and consistency checks and find no evidence for contamination.
Ovarian cancer is a complex and deadly disease that remains difficult to detect at an early curable stage. Furthermore, although some oncogenic (Kras, Pten/PI3K and Trp53) pathways that are ...frequently mutated, deleted or amplified in ovarian cancer are known, how these pathways initiate and drive specific morphological phenotypes and tumor outcomes remain unclear. We recently generated Pten(fl/fl); Kras(G12D); Amhr2-Cre mice to disrupt the Pten gene and express a stable mutant form of Kras(G12D) in ovarian surface epithelial (OSE) cells. On the basis of histopathologic criteria, the mutant mice developed low-grade ovarian serous papillary adenocarcinomas at an early age and with 100% penetrance. This highly reproducible phenotype provides the first mouse model in which to study this ovarian cancer subtype. OSE cells isolated from ovaries of mutant mice at 5 and 10 weeks of age exhibit temporal changes in the expression of specific Mullerian epithelial marker genes, grow in soft agar and develop ectopic invasive tumors in recipient mice, indicating that the cells are transformed. Gene profiling identified specific mRNAs and microRNAs differentially expressed in purified OSE cells derived from tumors of the mutant mice compared with wild-type OSE cells. Mapping of transcripts or genes between the mouse OSE mutant data sets, the Kras signature from human cancer cell lines and the human ovarian tumor array data sets, documented significant overlap, indicating that KRAS is a key driver of OSE transformation in this context. Two key hallmarks of the mutant OSE cells in these mice are the elevated expression of the tumor-suppressor Trp53 (p53) and its microRNA target, miR-34a-c. We propose that elevated TRP53 and miR-34a-c may exert negatively regulatory effects that reduce the proliferative potential of OSE cells leading to the low-grade serous adenocarcinoma phenotype.
To investigate the incidence of and risk factors for cognitive impairment in a large, well-defined clinical trial cohort of patients with early Parkinson disease (PD).
The Mini-Mental State ...Examination (MMSE) was administered periodically over a median follow-up period of 6.5 years to participants in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial and its extension studies. Cognitive impairment was defined as scoring 2 standard deviations below age- and education-adjusted MMSE norms.
Cumulative incidence of cognitive impairment in the 740 participants with clinically confirmed PD (baseline age 61.0 +/- 9.6 years, Hoehn-Yahr stage 1-2.5) was 2.4% (95% confidence interval: 1.2%-3.5%) at 2 years and 5.8% (3.7%-7.7%) at 5 years. Subjects who developed cognitive impairment (n = 46) showed significant progressive decline on neuropsychological tests measuring verbal learning and memory, visuospatial working memory, visuomotor speed, and attention, while the performance of the nonimpaired subjects (n = 694) stayed stable. Cognitive impairment was associated with older age, hallucinations, male gender, increased symmetry of parkinsonism, increased severity of motor impairment (except for tremor), speech and swallowing impairments, dexterity loss, and presence of gastroenterologic/urologic disorders at baseline.
The relatively low incidence of cognitive impairment in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism study may reflect recruitment bias inherent to clinical trial volunteers (e.g., younger age) or limitations of the Mini-Mental State Examination-based criterion. Besides confirming known risk factors for cognitive impairment, we identified potentially novel predictors such as bulbar dysfunction and gastroenterologic/urologic disorders (suggestive of autonomic dysfunction) early in the course of the disease.
Here, we present a sample-variance-limited measurement of the temperature power spectrum (TT) of the cosmic microwave background using observations of a ~1500 deg2 field made by the SPT-3G in 2018. ...We report multifrequency power spectrum measurements at 95, 150, and 220 GHz covering the angular multipole range 750 ≤ ℓ < 3000. We combine this TT measurement with the published polarization power spectrum measurements from the 2018 observing season and update their associated covariance matrix to complete the SPT-3G 2018 TT/TE/EE dataset. This is the first analysis to present cosmological constraints from SPT TT, TE, and EE power spectrum measurements jointly. We blind the cosmological results and subject the dataset to a series of consistency tests at the power spectrum and parameter level. We find excellent agreement between frequencies and spectrum types and our results are robust to the modeling of astrophysical foregrounds. We report results for Λ CDM and a series of extensions, drawing on the following parameters: the amplitude of the gravitational lensing effect on primary power spectra AL, the effective number of neutrino species Neff, the primordial helium abundance YP, and the baryon clumping factor due to primordial magnetic fields b. We find that the SPT-3G 2018 TT/TE/EE data are well fit by Λ CDM with a probability to exceed of 15%. For Λ CDM, we constrain the expansion rate today to H0 = 68.3 ± 1.5 km s–1 Mpc–1 and the combined structure growth parameter to S8 = 0.797 ± 0.042. The SPT-based results are effectively independent of Planck, and the cosmological parameter constraints from either dataset are within <1σ of each other. The addition of temperature data to the SPT-3G TE/EE power spectra improves constraints by 8–27% for each of the Λ CDM cosmological parameters. When additionally fitting AL, Neff, or Neff + YP, the posteriors of these parameters tighten by 5–24%. In the case of primordial magnetic fields, complete TT/TE/EE power spectrum measurements are necessary to break the degeneracy between b and ns, the spectral index of primordial density perturbations. We report a 95% confidence upper limit from SPT-3G data of b<1.0. The cosmological constraints in this work are the tightest from SPT primary power spectrum measurements to date and the analysis forms a new framework for future SPT analyses.
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