A survey of a population-based sample of U.S adults was conducted to measure their attitudes about, and inform the design of the Precision Medicine Initiative's planned national cohort study.
An ...online survey was conducted by GfK between May and June of 2015. The influence of different consent models on willingness to share data was examined by randomizing participants to one of eight consent scenarios.
Of 4,777 people invited to take the survey, 2,706 responded and 2,601 (54% response rate) provided valid responses. Most respondents (79%) supported the proposed study, and 54% said they would definitely or probably participate if asked. Support for and willingness to participate in the study varied little among demographic groups; younger respondents, LGBT respondents, and those with more years of education were significantly more likely to take part if asked. The most important study incentive that the survey asked about was learning about one's own health information. Willingness to share data and samples under broad, study-by-study, menu and dynamic consent models was similar when a statement about transparency was included in the consent scenarios. Respondents were generally interested in taking part in several governance functions of the cohort study.
A large majority of the U.S. adults who responded to the survey supported a large national cohort study. Levels of support for the study and willingness to participate were both consistent across most demographic groups. The opportunity to learn health information about one's self from the study appears to be a strong motivation to participate.
IMPORTANCE: While air pollutants at historical levels have been associated with cardiovascular and respiratory diseases, it is not known whether exposure to contemporary air pollutant concentrations ...is associated with progression of emphysema. OBJECTIVE: To assess the longitudinal association of ambient ozone (O3), fine particulate matter (PM2.5), oxides of nitrogen (NOx), and black carbon exposure with change in percent emphysema assessed via computed tomographic (CT) imaging and lung function. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included participants from the Multi-Ethnic Study of Atherosclerosis (MESA) Air and Lung Studies conducted in 6 metropolitan regions of the United States, which included 6814 adults aged 45 to 84 years recruited between July 2000 and August 2002, and an additional 257 participants recruited from February 2005 to May 2007, with follow-up through November 2018. EXPOSURES: Residence-specific air pollutant concentrations (O3, PM2.5, NOx, and black carbon) were estimated by validated spatiotemporal models incorporating cohort-specific monitoring, determined from 1999 through the end of follow-up. MAIN OUTCOMES AND MEASURES: Percent emphysema, defined as the percent of lung pixels less than −950 Hounsfield units, was assessed up to 5 times per participant via cardiac CT scan (2000-2007) and equivalent regions on lung CT scans (2010-2018). Spirometry was performed up to 3 times per participant (2004-2018). RESULTS: Among 7071 study participants (mean range age at recruitment, 60 45-84 years; 3330 47.1% were men), 5780 were assigned outdoor residential air pollution concentrations in the year of their baseline examination and during the follow-up period and had at least 1 follow-up CT scan, and 2772 had at least 1 follow-up spirometric assessment, over a median of 10 years. Median percent emphysema was 3% at baseline and increased a mean of 0.58 percentage points per 10 years. Mean ambient concentrations of PM2.5 and NOx, but not O3, decreased substantially during follow-up. Ambient concentrations of O3, PM2.5, NOx, and black carbon at study baseline were significantly associated with greater increases in percent emphysema per 10 years (O3: 0.13 per 3 parts per billion 95% CI, 0.03-0.24; PM2.5: 0.11 per 2 μg/m3 95% CI, 0.03-0.19; NOx: 0.06 per 10 parts per billion 95% CI, 0.01-0.12; black carbon: 0.10 per 0.2 μg/m3 95% CI, 0.01-0.18). Ambient O3 and NOx concentrations, but not PM2.5 concentrations, during follow-up were also significantly associated with greater increases in percent emphysema. Ambient O3 concentrations, but not other pollutants, at baseline and during follow-up were significantly associated with a greater decline in forced expiratory volume in 1 second per 10 years (baseline: 13.41 mL per 3 parts per billion 95% CI, 0.7-26.1; follow-up: 18.15 mL per 3 parts per billion 95% CI, 1.59-34.71). CONCLUSIONS AND RELEVANCE: In this cohort study conducted between 2000 and 2018 in 6 US metropolitan regions, long-term exposure to ambient air pollutants was significantly associated with increasing emphysema assessed quantitatively using CT imaging and lung function.
The mid-Holocene (6000 years ago) is a standard time period for the evaluation of the simulated response of global climate models using palaeoclimate reconstructions. The latest mid-Holocene ...simulations are a palaeoclimate entry card for the Palaeoclimate Model Intercomparison Project (PMIP4) component of the current phase of the Coupled Model Intercomparison Project (CMIP6) – hereafter referred to as PMIP4-CMIP6. Here we provide an initial analysis and evaluation of the results of the experiment for the mid-Holocene. We show that state-of-the-art models produce climate changes that are broadly consistent with theory and observations, including increased summer warming of the Northern Hemisphere and associated shifts in tropical rainfall. Many features of the PMIP4-CMIP6 simulations were present in the previous generation (PMIP3-CMIP5) of simulations. The PMIP4-CMIP6 ensemble for the mid-Holocene has a global mean temperature change of −0.3 K, which is −0.2 K cooler than the PMIP3-CMIP5 simulations predominantly as a result of the prescription of realistic greenhouse gas concentrations in PMIP4-CMIP6. Biases in the magnitude and the sign of regional responses identified in PMIP3-CMIP5, such as the amplification of the northern African monsoon, precipitation changes over Europe, and simulated aridity in mid-Eurasia, are still present in the PMIP4-CMIP6 simulations. Despite these issues, PMIP4-CMIP6 and the mid-Holocene provide an opportunity both for quantitative evaluation and derivation of emergent constraints on the hydrological cycle, feedback strength, and potentially climate sensitivity.
Concerns about privacy may deter people from participating in genetic research. Recruitment and retention of biobank participants requires understanding the nature and magnitude of these concerns. ...Potential participants in a proposed biobank were asked about their willingness to participate, their privacy concerns, informed consent, and data sharing. A representative survey of 4659 U.S. adults was conducted. Ninety percent of respondents would be concerned about privacy, 56% would be concerned about researchers having their information, and 37% would worry that study data could be used against them. However, 60% would participate in the biobank if asked. Nearly half (48%) would prefer to provide consent once for all research approved by an oversight panel, whereas 42% would prefer to provide consent for each project separately. Although 92% would allow academic researchers to use study data, 80% and 75%, respectively, would grant access to government and industry researchers. Concern about privacy was related to lower willingness to participate only when respondents were told that they would receive $50 for participation and would not receive individual research results back. Among respondents who were told that they would receive $200 or individual research results, privacy concerns were not related to willingness. Survey respondents valued both privacy and participation in biomedical research. Despite pervasive privacy concerns, 60% would participate in a biobank. Assuring research participants that their privacy will be protected to the best of researchers' abilities may increase participants' acceptance of consent for broad research uses of biobank data by a wide range of researchers.
Starting with the launch of the Human Genome Project three decades ago, and continuing after its completion in 2003, genomics has progressively come to have a central and catalytic role in basic and ...translational research. In addition, studies increasingly demonstrate how genomic information can be effectively used in clinical care. In the future, the anticipated advances in technology development, biological insights, and clinical applications (among others) will lead to more widespread integration of genomics into almost all areas of biomedical research, the adoption of genomics into mainstream medical and public-health practices, and an increasing relevance of genomics for everyday life. On behalf of the research community, the National Human Genome Research Institute recently completed a multi-year process of strategic engagement to identify future research priorities and opportunities in human genomics, with an emphasis on health applications. Here we describe the highest-priority elements envisioned for the cutting-edge of human genomics going forward-that is, at 'The Forefront of Genomics'.
IMPORTANCE: Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD), yet much of COPD risk remains unexplained. OBJECTIVE: To determine whether dysanapsis, a mismatch of ...airway tree caliber to lung size, assessed by computed tomography (CT), is associated with incident COPD among older adults and lung function decline in COPD. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of 2 community-based samples: the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, which involved 2531 participants (6 US sites, 2010-2018) and the Canadian Cohort of Obstructive Lung Disease (CanCOLD), which involved 1272 participants (9 Canadian sites, 2010-2018), and a case-control study of COPD: the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), which involved 2726 participants (12 US sites, 2011-2016). EXPOSURES: Dysanapsis was quantified on CT as the geometric mean of airway lumen diameters measured at 19 standard anatomic locations divided by the cube root of lung volume (airway to lung ratio). MAIN OUTCOMES AND MEASURES: Primary outcome was COPD defined by postbronchodilator ratio of forced expired volume in the first second to vital capacity (FEV1:FVC) less than 0.70 with respiratory symptoms. Secondary outcome was longitudinal lung function. All analyses were adjusted for demographics and standard COPD risk factors (primary and secondhand tobacco smoke exposures, occupational and environmental pollutants, and asthma). RESULTS: In the MESA Lung sample (mean SD age, 69 years 9 years; 1334 women 52.7%), 237 of 2531 participants (9.4%) had prevalent COPD, the mean (SD) airway to lung ratio was 0.033 (0.004), and the mean (SD) FEV1 decline was −33 mL/y (31 mL/y). Of 2294 MESA Lung participants without prevalent COPD, 98 (4.3%) had incident COPD at a median of 6.2 years. Compared with participants in the highest quartile of airway to lung ratio, those in the lowest had a significantly higher COPD incidence (9.8 vs 1.2 cases per 1000 person-years; rate ratio RR, 8.12; 95% CI, 3.81 to 17.27; rate difference, 8.6 cases per 1000 person-years; 95% CI, 7.1 to 9.2; P < .001) but no significant difference in FEV1 decline (−31 vs −33 mL/y; difference, 2 mL/y; 95% CI, −2 to 5; P = .30). Among CanCOLD participants (mean SD age, 67 years 10 years; 564 women 44.3%), 113 of 752 (15.0%) had incident COPD at a median of 3.1 years and the mean (SD) FEV1 decline was −36 mL/y (75 mL/y). The COPD incidence in the lowest airway to lung quartile was significantly higher than in the highest quartile (80.6 vs 24.2 cases per 1000 person-years; RR, 3.33; 95% CI, 1.89 to 5.85; rate difference, 56.4 cases per 1000 person-years; 95% CI, 38.0 to 66.8; P<.001), but the FEV1 decline did not differ significantly (−34 vs −36 mL/y; difference, 1 mL/y; 95% CI, −15 to 16; P=.97). Among 1206 SPIROMICS participants (mean SD age, 65 years 8 years; 542 women 44.9%) with COPD who were followed up for a median 2.1 years, those in the lowest airway to lung ratio quartile had a mean FEV1 decline of −37 mL/y (15 mL/y), which did not differ significantly from the decline in MESA Lung participants (P = .98), whereas those in highest quartile had significantly faster decline than participants in MESA Lung (−55 mL/y 16 mL/y ; difference, −17 mL/y; 95% CI, −32 to −3; P = .004). CONCLUSIONS AND RELEVANCE: Among older adults, dysanapsis was significantly associated with COPD, with lower airway tree caliber relative to lung size associated with greater COPD risk. Dysanapsis appears to be a risk factor associated with COPD.
There is a lack of appropriate melanoma models that can be used to evaluate the efficacy of novel therapeutic modalities. Here, we discuss the current state of the art of melanoma models including ...genetically engineered mouse, patient-derived xenograft, zebrafish, and ex vivo and in vitro models. We also identify five major challenges that can be addressed using such models, including metastasis and tumor dormancy, drug resistance, the melanoma immune response, and the impact of aging and environmental exposures on melanoma progression and drug resistance. Additionally, we discuss the opportunity for building models for rare subtypes of melanomas, which represent an unmet critical need. Finally, we identify key recommendations for melanoma models that may improve accuracy of preclinical testing and predict efficacy in clinical trials, to help usher in the next generation of melanoma therapies.
There is a lack of appropriate melanoma models that can be used to evaluate the efficacy of novel therapeutic modalities. Here, we discuss the current state of the art of melanoma models including genetically engineered mouse, patient-derived xenograft, zebrafish, and ex vivo and in vitro models. We also identify five major challenges that can be addressed using such models, including metastasis and tumor dormancy, drug resistance, the melanoma immune response, and the impact of aging and environmental exposures on melanoma progression and drug resistance. Additionally, we discuss the opportunity for building models for rare subtypes of melanomas, which represent an unmet critical need. Finally, we identify key recommendations for melanoma models that may improve accuracy of preclinical testing and predict efficacy in clinical trials, to help usher in the next generation of melanoma therapies.
We surveyed the empirical literature to determine how well six diversity hypotheses account for spatial patterns in species richness across varying scales of grain and extent. Worldwide. We ...identified 393 analyses ('cases') in 297 publications meeting our criteria. These criteria included the requirement that more than one diversity hypothesis was tested for its relationship with species richness. We grouped variables representing the hypotheses into the following 'correlate types': climate/productivity, environmental heterogeneity, edaphics/nutrients, area, biotic interactions and dispersal/history (colonization limitation or other historical or evolutionary effect). For each case we determined the 'primary' variable: the one most strongly correlated with taxon richness. We defined 'primacy' as the proportion of cases in which each correlate type was represented by the primary variable, relative to the number of times it was studied. We tested for differences in both primacy and mean coefficient of determination of the primary variable between the hypotheses and between categories of five grouping variables: grain, extent, taxon (animal vs. plant), habitat medium (land vs. water) and insularity (insular vs. connected). Climate/productivity had the highest overall primacy, and environmental heterogeneity and dispersal/history had the lowest. Primacy of climate/productivity was much higher in large-grain and large-extent studies than at smaller scales. It was also higher on land than in water, and much higher in connected systems than in insular ones. For other hypotheses, differences were less pronounced. Throughout, studies on plants and animals showed similar patterns. Coefficients of determination of the primary variables differed little between hypotheses and across the grouping variables, the strongest effects being low means in the smallest grain class and for edaphics/nutrients variables, and a higher mean for water than for land in connected systems but vice versa in insular systems. We highlight areas of data deficiency. Our results support the notion that climate and productivity play an important role in determining species richness at large scales, particularly for non-insular, terrestrial habitats. At smaller extents and grain sizes, the primacy of the different types of correlates appears to differ little from null expectation. In our analysis, dispersal/history is rarely the best correlate of species richness, but this may reflect the difficulty of incorporating historical factors into regression models, and the collinearity between past and current climates. Our findings are consistent with the view that climate determines the capacity for species richness. However, its influence is less evident at smaller spatial scales, probably because (1) studies small in extent tend to sample little climatic range, and (2) at large grains some other influences on richness tend to vary mainly within the sampling unit.
Broad‐scale variation in taxonomic richness is strongly correlated with climate. Many mechanisms have been hypothesized to explain these patterns; however, testable predictions that would distinguish ...among them have rarely been derived. Here, we examine several prominent hypotheses for climate–richness relationships, deriving and testing predictions based on their hypothesized mechanisms. The ‘energy–richness hypothesis’ (also called the ‘more individuals hypothesis’) postulates that more productive areas have more individuals and therefore more species. More productive areas do often have more species, but extant data are not consistent with the expected causal relationship from energy to numbers of individuals to numbers of species. We reject the energy–richness hypothesis in its standard form and consider some proposed modifications. The ‘physiological tolerance hypothesis’ postulates that richness varies according to the tolerances of individual species for different sets of climatic conditions. This hypothesis predicts that more combinations of physiological parameters can survive under warm and wet than cold or dry conditions. Data are qualitatively consistent with this prediction, but are inconsistent with the prediction that species should fill climatically suitable areas. Finally, the ‘speciation rate hypothesis’ postulates that speciation rates should vary with climate, due either to faster evolutionary rates or stronger biotic interactions increasing the opportunity for evolutionary diversification in some regions. The biotic interactions mechanism also has the potential to amplify shallower, underlying gradients in richness. Tests of speciation rate hypotheses are few (to date), and their results are mixed.
An ASCO provisional clinical opinion offers timely clinical direction to ASCO's membership after publication or presentation of potentially practice-changing data from major studies. This provisional ...clinical opinion addresses the role of treatment deintensification in the management of p16+ oropharyngeal cancer (OPC).
For patients with p16+ OPC, current treatment approaches are well established. In the good-prognosis subset of nonsmoking p16+ patients with early-stage disease, these treatments have been highly successful, albeit with significant associated acute and late toxicity. Deintensification of surgical, radiation, and medical treatment in an effort to reduce toxicity while preserving high survival rates is an appropriate therapeutic objective currently being explored in patients who are experiencing the best treatment results. However, careful delineation of this good-risk subset is essential. While the current eighth edition of the American Joint Committee on Cancer staging system is prognostically robust, it should not be interpreted as reason to alter therapeutic decisions or justify treatment deintensification. The development of transoral surgical techniques and the adoption of intensity-modulated radiation therapy planning have been transformative in disease management and suggest potentially beneficial approaches. Recent advances in systemic treatments have been notable. The optimal integration and modification of these modalities to ameliorate toxicity has not been defined and remains an important focus of current investigation.
The hypothesis that de-escalation of treatment intensity for patients with p16+ OPC can reduce long-term toxicity without compromising survival is compelling and necessitates careful study and the analysis of well-designed clinical trials before changing current treatment standards. Treatment deintensification for these patients should only be undertaken in a clinical trial. Additional information is available at www.asco.org/head-neck-cancer-guidelines .
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