Infectious agents and colorectal cancer: a review of Helicobacter pylori, Streptococcus bovis, JC virus, and human papillomavirus.

Based on the high volume of bacteria and viruses that the intestine is exposed to and the importance of infectious agents in some gastrointestinal and anogenital cancers, it is not surprising the many studies have evaluated the association between colorectal cancer and infectious agents. This review highlights investigations of four agents in relation to colorectal cancer. Helicobacter pylori, Streptococcus bovis, JC virus, and human papillomavirus have all been evaluated as possible etiologic agents for colorectal cancer. For each of these agents, a review of possible mechanisms for carcinogenesis and epidemiologic evidence is discussed, and future directions for research are proposed

Gamma Ray Large Area Space Telescope (GLAST) Balloon Flight Data Handling Overview

The GLAST Balloon Flight Engineering Model (BFEM) represents one of 16 towers that constitute the Large Area Telescope (LAT), a high-energy (>20 MeV) gamma-ray pair-production telescope being built by an international partnership of astrophysicists and particle physicists for a satellite launch in 2006. The prototype tower consists of a Pb/Si pair-conversion tracker (TKR), a CsI hodoscopic calorimeter (CAL), an anti-coincidence detector (ACD) and an autonomous data acquisition system (DAQ). The self-triggering capabilities and performance of the detector elements have been previously characterized using positron, photon and hadron beams. External target scintillators were placed above the instrument to act as sources of hadronic showers. This paper provides a comprehensive description of the BFEM data-reduction process, from receipt of the flight data from telemetry through event reconstruction and background rejection cuts. The goals of the ground analysis presented here are to verify the functioning of the instrument and to validate the reconstruction software and the background-rejection scheme.Comment: 5 pages, 4 figures, to be published in IEEE Transacations on Nuclear Science, August 200

Evaluation of Population-Level Changes Associated With the 2021 US Preventive Services Task Force Lung Cancer Screening Recommendations in Community-Based Health Care Systems

Importance: The US Preventive Services Task Force (USPSTF) released updated lung cancer screening recommendations in 2021, lowering the screening age from 55 to 50 years and smoking history from 30 to 20 pack-years. These changes are expected to expand screening access to women and racial and ethnic minority groups. Objective: To estimate the population-level changes associated with the 2021 USPSTF expansion of lung cancer screening eligibility by sex, race and ethnicity, sociodemographic factors, and comorbidities in 5 community-based health care systems. Design, Setting, and Participants: This cohort study analyzed data of patients who received care from any of 5 community-based health care systems (which are members of the Population-based Research to Optimize the Screening Process Lung Consortium, a collaboration that conducts research to better understand how to improve the cancer screening processes in community health care settings) from January 1, 2010, through September 30, 2019. Individuals who had complete smoking history and were engaged with the health care system for 12 or more continuous months were included. Those who had never smoked or who had unknown smoking history were excluded. Exposures: Electronic health record-derived age, sex, race and ethnicity, socioeconomic status (SES), comorbidities, and smoking history. Main Outcomes and Measures: Differences in the proportion of the newly eligible population by age, sex, race and ethnicity, Charlson Comorbidity Index, chronic obstructive pulmonary disease diagnosis, and SES as well as lung cancer diagnoses under the 2013 recommendations vs the expected cases under the 2021 recommendations were evaluated using χ2 tests. Results: As of September 2019, there were 341 163 individuals aged 50 to 80 years who currently or previously smoked. Among these, 34 528 had electronic health record data that captured pack-year and quit-date information and were eligible for lung cancer screening according to the 2013 USPSTF recommendations. The 2021 USPSTF recommendations expanded screening eligibility to 18 533 individuals, representing a 53.7% increase. Compared with the 2013 cohort, the newly eligible 2021 population included 5833 individuals (31.5%) aged 50 to 54 years, a larger proportion of women (52.0% [n = 9631]), and more racial or ethnic minority groups. The relative increases in the proportion of newly eligible individuals were 60.6% for Asian, Native Hawaiian, or Pacific Islander; 67.4% for Hispanic; 69.7% for non-Hispanic Black; and 49.0% for non-Hispanic White groups. The relative increase for women was 13.8% higher than for men (61.2% vs 47.4%), and those with a lower comorbidity burden and lower SES had higher relative increases (eg, 68.7% for a Charlson Comorbidity Index score of 0; 61.1% for lowest SES). The 2021 recommendations were associated with an estimated 30% increase in incident lung cancer diagnoses compared with the 2013 recommendations. Conclusions and Relevance: This cohort study suggests that, in diverse health care systems, adopting the 2021 USPSTF recommendations will increase the number of women, racial and ethnic minority groups, and individuals with lower SES who are eligible for lung cancer screening, thus helping to minimize the barriers to screening access for individuals with high risk for lung cancer

Association between molecular subtypes of colorectal cancer and patient survival

BACKGROUND and AIMS: Colorectal cancer (CRC) is a heterogeneous disease that can develop via several pathways. Different CRC subtypes, identified based on tumor markers, have been proposed to reflect these pathways. We evaluated the significance of these previously proposed classifications to survival. METHODS: Participants in the population-based Seattle Colon Cancer Family Registry were diagnosed with invasive CRC from 1998 through 2007 in western Washington State (N = 2706), and followed for survival through 2012. Tumor samples were collected from 2050 participants and classified into 5 subtypes based on combinations of tumor markers: type 1 (microsatellite instability [MSI]-high, CpG island methylator phenotype [CIMP] -positive, positive for BRAF mutation, negative for KRAS mutation); type 2 (microsatellite stable [MSS] or MSI-low, CIMP-positive, positive for BRAF mutation, negative for KRAS mutation); type 3 (MSS or MSI low, non-CIMP, negative for BRAF mutation, positive for KRAS mutation); type 4 (MSS or MSI-low, non-CIMP, negative for mutations in BRAF and KRAS); and type 5 (MSI-high, non-CIMP, negative for mutations in BRAF and KRAS). Multiple imputation was used to impute tumor markers for those missing data on 1-3 markers. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of subtypes with disease-specific and overall mortality, adjusting for age, sex, body mass, diagnosis year, and smoking history. RESULTS: Compared with participants with type 4 tumors (the most predominant), participants with type 2 tumors had the highest disease-specific mortality (HR = 2.20, 95% CI: 1.47-3.31); subjects with type 3 tumors also had higher disease-specific mortality (HR = 1.32, 95% CI: 1.07-1.63). Subjects with type 5 tumors had the lowest disease-specific mortality (HR = 0.30, 95% CI: 0.14-0.66). Associations with overall mortality were similar to those with disease-specific mortality. CONCLUSIONS: Based on a large, population-based study, CRC subtypes, defined by proposed etiologic pathways, are associated with marked differences in survival. These findings indicate the clinical importance of studies into the molecular heterogeneity of CRC

Eight gamma-ray pulsars discovered in blind frequency searches of Fermi LAT data

We report the discovery of eight gamma-ray pulsars in blind frequency searches using the LAT, onboard the Fermi Gamma-ray Space Telescope. Five of the eight pulsars are young (tau_c10^36 erg/s), and located within the Galactic plane (|b|<3 deg). The remaining three are older, less energetic, and located off the plane. Five pulsars are associated with sources included in the LAT bright gamma-ray source list, but only one, PSR J1413-6205, is clearly associated with an EGRET source. PSR J1023-5746 has the smallest characteristic age (tau_c=4.6 kyr) and is the most energetic (Edot=1.1E37 erg/s) of all gamma-ray pulsars discovered so far in blind searches. PSRs J1957+5033 and J2055+25 have the largest characteristic ages (tau_c~1 Myr) and are the least energetic (Edot~5E33 erg/s) of the newly-discovered pulsars. We present the timing models, light curves, and detailed spectral parameters of the new pulsars. We used recent XMM observations to identify the counterpart of PSR J2055+25 as XMMU J205549.4+253959. In addition, publicly available archival Chandra X-ray data allowed us to identify the likely counterpart of PSR J1023-5746 as a faint, highly absorbed source, CXOU J102302.8-574606. The large X-ray absorption indicates that this could be among the most distant gamma-ray pulsars detected so far. PSR J1023-5746 is positionally coincident with the TeV source HESS J1023-575, located near the young stellar cluster Westerlund 2, while PSR J1954+2836 is coincident with a 4.3 sigma excess reported by Milagro at a median energy of 35 TeV. Deep radio follow-up observations of the eight pulsars resulted in no detections of pulsations and upper limits comparable to the faintest known radio pulsars, indicating that these can be included among the growing population of radio-quiet pulsars in our Galaxy being uncovered by the LAT, and currently numbering more than 20.Comment: Submitted to Ap

Fermi Discovery of Gamma-Ray Emission from NGC 1275

We report the discovery of high-energy (E>100 MeV) gamma-ray emission from NGC 1275, a giant elliptical galaxy lying at the center of the Perseus cluster of galaxies, based on observations made with the Large Area Telescope (LAT) of the Fermi Gamma ray Space Telescope. The positional center of the gamma-ray source is only ~3' away from the NGC 1275 nucleus, well within the 95% LAT error circle of ~5'.The spatial distribution of gamma-ray photons is consistent with a point source. The average flux and power-law photon index measured with the LAT from 2008 August 4 to 2008 December 5 are F_gamma = (2.10+-0.23)x 10^{-7} ph (>100 MeV) cm^{-2} s^{-1} and Gamma = 2.17+-0.05, respectively. The measurements are statistically consistent with constant flux during the four-month LAT observing period.Previous EGRET observations gave an upper limit of F_gamma 100 MeV) cm^{-2} s^{-1} to the gamma-ray flux from NGC 1275. This indicates that the source is variable on timescales of years to decades, and therefore restricts the fraction of emission that can be produced in extended regions of the galaxy cluster. Contemporaneous and historical radio observations are also reported. The broadband spectrum of NGC 1275 is modeled with a simple one-zone synchrotron/synchrotron self-Compton model and a model with a decelerating jet flow.Comment: 27 pages, 7 figures, Accepted for publication in the Astrophysical Journa

Association Between Molecular Subtypes of Colorectal Cancer and Patient Survival

Colorectal cancer (CRC) is a heterogeneous disease that can develop via several pathways. Different CRC subtypes, identified based on tumor markers, have been proposed to reflect these pathways. We evaluated the significance of these previously proposed classifications to survival

Bright AGN Source List from the First Three Months of the Fermi Large Area Telescope All-Sky Survey

The first three months of sky-survey operation with the Fermi Gamma Ray Space Telescope (Fermi) Large Area Telescope (LAT) reveals 132 bright sources at |b|>10 deg with test statistic greater than 100 (corresponding to about 10 sigma). Two methods, based on the CGRaBS, CRATES and BZCat catalogs, indicate high-confidence associations of 106 of these sources with known AGNs. This sample is referred to as the LAT Bright AGN Sample (LBAS). It contains two radio galaxies, namely Centaurus A and NGC 1275, and 104 blazars consisting of 57 flat spectrum radio quasars (FSRQs), 42 BL Lac objects, and 5 blazars with uncertain classification. Four new blazars were discovered on the basis of the LAT detections. Remarkably, the LBAS includes 10 high-energy peaked BL Lacs (HBLs), sources which were so far hard to detect in the GeV range. Another 10 lower-confidence associations are found. Only thirty three of the sources, plus two at |b|>10 deg, were previously detected with EGRET, probably due to the variable nature of these sources. The analysis of the gamma-ray properties of the LBAS sources reveals that the average GeV spectra of BL Lac objects are significantly harder than the spectra of FSRQs. No significant correlation between radio and peak gamma-ray fluxes is observed. Blazar log N - log S and luminosity functions are constructed to investigate the evolution of the different blazar classes, with positive evolution indicated for FSRQs but none for BLLacs. The contribution of LAT-blazars to the total extragalactic gamma-ray intensity is estimated.Comment: Submitted to ApJ. Not yet refereed. 61 pages, 26 figure

PKS 1502+106: a new and distant gamma-ray blazar in outburst discovered by the Fermi Large Area Telescope

The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope discovered a rapid (about 5 days duration), high-energy (E >100 MeV) gamma-ray outburst from a source identified with the blazar PKS 1502+106 (OR 103, S3 1502+10, z=1.839) starting on August 05, 2008 and followed by bright and variable flux over the next few months. Results on the gamma-ray localization and identification, as well as spectral and temporal behavior during the first months of the Fermi all-sky survey are reported here in conjunction with a multi-waveband characterization as a result of one of the first Fermi multi-frequency campaigns. The campaign included a Swift ToO (followed up by 16-day observations on August 07-22, MJD 54685-54700), VLBA (within the MOJAVE program), Owens Valley (OVRO) 40m, Effelsberg-100m, Metsahovi-14m, RATAN-600 and Kanata-Hiroshima radio/optical observations. Results from the analysis of archival observations by INTEGRAL, XMM-Newton and Spitzer space telescopes are reported for a more complete picture of this new gamma-ray blazar.Comment: 17 pages, 11 figures, accepted for The Astrophysical Journa

Early Fermi Gamma-ray Space Telescope Observations of the Quasar 3C 454.3

This is the first report of Fermi Gamma-ray Space Telescope observations of the quasar 3C 454.3, which has been undergoing pronounced long-term outbursts since 2000. The data from the Large Area Telescope (LAT), covering 2008 July 7 - October 6, indicate strong, highly variable gamma-ray emission with an average flux of ~3 x 10^{-6} photons cm^{-2} s^{-1}, for energies above 100 MeV. The gamma-ray flux is variable, with strong, distinct, symmetrically-shaped flares for which the flux increases by a factor of several on a time scale of about three days. This variability indicates a compact emission region, and the requirement that the source is optically thin to pair-production implies relativistic beaming with Doppler factor delta > 8, consistent with the values inferred from VLBI observations of superluminal expansion (delta ~ 25). The observed gamma-ray spectrum is not consistent with a simple power-law, but instead steepens strongly above ~2 GeV, and is well described by a broken power-law with photon indices of ~2.3 and ~3.5 below and above the break, respectively. This is the first direct observation of a break in the spectrum of a high luminosity blazar above 100 MeV, and it is likely direct evidence for an intrinsic break in the energy distribution of the radiating particles. Alternatively, the spectral softening above 2 GeV could be due to gamma-ray absorption via photon-photon pair production on the soft X-ray photon field of the host AGN, but such an interpretation would require the dissipation region to be located very close (less than 100 gravitational radii) to the black hole, which would be inconsistent with the X-ray spectrum of the source.Comment: Accepted by the Astrophysical Journal; corresponding authors: Greg Madejski ([email protected]) and Benoit Lott ([email protected]