33 research outputs found
The influence of year-end bonuses on colorectal cancer screening
The objective of the paper is to estimate the effect of physician bonus eligibility on CRC screening while controlling for patient and primary care physician characteristics. The study is retrospective, using a managed care plan’s claims data on fifty-year-old commercially insured patients in the years 2000 and 2001. The data also include links to enrollment and provider files. Multivariate logistic regression models are used to assess the association between CRC screening receipt and physician bonus eligibility. The results indicate that the probability that a patient received a CRC screening was approximately 3 percentage points higher in the year physicians were eligible for a bonus. There were also significant differences according to the gender of both the patient and physician, income, and race.
Overestimate of Committed Warming
Palaeoclimate variations are an essential component in constraining future projections of climate change as a function of increasing anthropogenic greenhouse gases. The Earth System Sensitivity (ESS) describes the multi-millennial response of Earth (in terms of global mean temperature) to a doubling of CO2 concentrations. A recent study used a correlation of inferred temperatures and radiative forcing from greenhouse gases over the past 800,000 years to estimate the ESS from present day CO2 is about 9 degrees C, and to imply a long-term commitment of 3-7 degrees C even if greenhouse gas levels remain at present-day concentrations. However, we demonstrate that the methodology of ref. 2 does not reliably estimate the ESS in the presence of orbital forcing of ice age cycles and therefore conclude that the inferred present-day committed warming is considerably overestimated
Impact of model physics on estimating the surface mass balance of the Greenland ice sheet
Long-term predictions of sea level rise from increased Greenland ice sheet melting have been derived using Positive Degree Day models only. It is, however, unknown precisely what uncertainties are associated with applying this simple surface melt parameterization for future climate. We compare the behavior of a Positive Degree Day and Energy Balance/ Snowpack model for estimating the surface mass balance of the Greenland ice sheet under a warming climate. Both models were first tuned to give similar values for present-day mass balance using 10 years of ERA-40 climatology and were then run for 300 years, forced with the output of a GCM in which atmospheric CO2 increased to 4 times preindustrial levels. Results indicate that the Positive Degree Day model is more sensitive to climate warming than the Energy Balance model, generating annual runoff rates almost twice as large for a fixed ice sheet geometry. Roughly half of this difference was due to differences in the volume of melt generated and half was due to differences in refreezing rates in the snowpack. Our results indicate that the modeled snowpack properties evolve on a multidecadal timescale to changing climate, with a potentially large impact on the mass balance of the ice sheet; an evolution that was absent from the Positive Degree Day model. Copyright 2007 by the American Geophysical Union
Climate Science Special Report: Fourth National Climate Assessment (NCA4), Volume I
New observations and new research have increased our understanding of past, current, and future climate change since the Third U.S. National Climate Assessment (NCA3) was published in May 2014. This Climate Science Special Report (CSSR) is designed to capture that new information and build on the existing body of science in order to summarize the current state of knowledge and provide the scientific foundation for the Fourth National Climate Assessment (NCA4)
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Validation of the Pneumonia Severity Index Among Patients Treated at Home or in the Hospital
Objective: To assess the predictive validity of the pneumonia severity-of-illness index (PSI), a mortality prediction rule, and extend the work of others by including data on outpatients treated for pneumonia. Methods: Prospective study of 675 consecutive patients with community-acquired pneumonia (CAP) [501 inpatients and 174 outpatients] treated at primary care practice clinics or emergency departments at nine medical centers (five community healthcare systems, three university-affiliated hospital systems, and one Veterans Affairs Medical Center) in Georgia and Virginia in the US between November 1996 and March 1998. Data, including demographic characteristics, co-morbid conditions, laboratory and chest x-ray results, were collected from surveys administered to patients at inception, 2, 15, and 30 days and from retrospective medical chart review. We computed the PSI for each patient using demographic and prognostic factors including age, gender, co-existing illnesses, vital signs, laboratory test results and the corresponding logistic regression parameters from previous research. In addition, the Pneumonia Outcomes Research Team (PORT) prediction rule was used to risk adjust patients for mortality severity by disposition. Results: The PSI performed well in its ability to predict mortality for our sample of patients with an area under the Receiver Operating Curve (ROC) of 0.757, significantly different than chance (pCommunity-acquired-pneumonia, Pneumonia, Risk-factors
Racial Differences in Cardiac Catheterization as a Function of Patients’ Beliefs
Objectives. We examined racial differences in cardiac catheterization rates and reviewed whether patients’ beliefs or other variables were associated with observed disparities. Methods. We did a prospective observational cohort study of 1045 White and African American patients at 5 Veterans Affairs (VA) medical centers whose nuclear imaging studies indicated reversible cardiac ischemia. Results. There were few demographic differences between White and African American patients in our sample. African Americans were less likely than Whites to undergo cardiac catheterization. African Americans were more likely than Whites to indicate a strong reliance on religion and to report racial and social class discrimination and were less likely to indicate a generalized trust in people but did not differ from White patients on numerous other attitudes about health and health care. Neither sociodemographic or clinical characteristics nor patients’ beliefs explained the observed disparities, but physicians’ assessments of the procedure’s importance and patients’ likelihood of coronary disease seemed to account for differences not otherwise explained. Conclusions. Patients’ preferences are not the likely source of racial disparities in the use of cardiac catheterization among veterans using VA care, but physicians’ assessments warrant further attention