Weekly paclitaxel, gemcitabine, and external irradiation followed by randomized farnesyl transferase inhibitor R115777 for locally advanced pancreatic cancer.

PURPOSE: The Radiation Therapy Oncology Group (RTOG) multi-institutional Phase II study 98-12, evaluating paclitaxel and concurrent radiation (RT) for locally advanced pancreatic cancer, demonstrated a median survival of 11.3 months and a 1-year survival of 43%. The purpose of the randomized Phase II study by RTOG 0020 was to evaluate the addition of weekly low- dose gemcitabine with concurrent paclitaxel/RT and to evaluate the efficacy and safety of the farnesyl transferase inhibitor R115777 following chemoradiation. PATIENTS AND METHODS: Patients with unresectable, nonmetastatic adenocarcinoma of the pancreas were eligible. Patients in Arm 1 received gemcitabine, 75 mg/m(2)/week, and paclitaxel, 40 mg/m(2)/week, for 6 weeks, with 50.4 Gy radiation (CXRT). Patients in Arm 2 received an identical chemoradiation regimen but then received maintenance R115777, 300 mg twice a day for 21 days every 28 days (CXRT+R115777), until disease progression or unacceptable toxicity. RESULTS: One hundred ninety-five patients were entered into this study, and 184 were analyzable. Grade 4 nonhematologic toxicities occurred in less than 5% of CXRT patients. The most common grade 3/4 toxicity from R115777 was myelosuppression; however, grade 3/4 hepatic, metabolic, musculoskeletal, and neurologic toxicities were also reported. The median survival time was 11.5 months and 8.9 months for the CXRT and CXRT+R115777 arms, respectively. CONCLUSIONS: The CXRT arm achieved a median survival of almost 1-year, supporting chemoradiation as an important therapeutic modality for locally advanced pancreatic cancer. Maintenance R115777 is not effective and is associated with a broad range of toxicities. These findings provide clinical evidence that inhibition of farnesylation affects many metabolic pathways, underscoring the challenge of developing an effective K-ras inhibitor

Positron Emission Tomography-Computed Tomography Compared with Invasive Mediastinal Staging in Non-small Cell Lung Cancer: Results of Mediastinal Staging in the Early Lung Positron Emission Tomography Trial

IntroductionPatients with non-small cell lung cancer (NSCLC) require careful preoperative staging to define resectability for potential cure. 18Fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG PET-CT) is widely used to stage NSCLC. If the mediastinum is positive on PET-CT examination, some practitioners conclude that the patient is inoperable and refer the patient for nonsurgical treatment.MethodsIn this analysis of a previously reported trial comparing PET-CT with conventional imaging in the diagnostic work-up of patients with clinical stage I, II, or IIIA NSCLC, we determined the accuracy of PET-CT in mediastinal staging compared with invasive mediastinal staging either by mediastinoscopy alone or by mediastinoscopy combined with thoracotomy.ResultsAll 149 patients had mediastinal nodal staging at mediastinoscopy alone (14), thoracotomy alone (64), or both (71). The sensitivity of PET-CT was 70% (95% confidence interval [CI], 48–85%), and specificity was 94% (95% CI, 88–97%). Of 22 patients with a PET-CT interpreted as positive for mediastinal nodes, 8 did not have tumor. The positive predictive value and negative predictive value were 64% (95% CI, 43–80%) and 95% (95% CI, 90–98%), respectively. Based on PET-CT alone, eight patients would have been denied potentially curative surgery if the mediastinal abnormalities detected by PET-CT had not been evaluated with an invasive mediastinal procedure.ConclusionsPET-CT assessment of the mediastinum is associated with a clinically relevant false-positive result. Our study confirms the need for pathologic confirmation of mediastinal lymph node abnormalities detected by PET-CT

Oscillating Asymmetric Dark Matter

We study the dynamics of dark matter (DM) particle-antiparticle oscillations within the context of asymmetric DM. Oscillations arise due to small DM number-violating Majorana-type mass terms, and can lead to recoupling of annihilation after freeze-out and washout of the DM density. We derive the density matrix equations for DM oscillations and freeze-out from first principles using nonequilibrium field theory, and our results are qualitatively different than in previous studies. DM dynamics exhibits particle-vs-antiparticle "flavor" effects, depending on the interaction type, analogous to neutrino oscillations in a medium. "Flavor-sensitive" DM interactions include scattering or annihilation through a new vector boson, while "flavor-blind" interactions include scattering or s-channel annihilation through a new scalar boson, or annihilation to pairs of bosons. In particular, we find that flavor-sensitive annihilation does not recouple when coherent oscillations begin, and that flavor-blind scattering does not lead to decoherence.Comment: 23 pages, 4 figures, A typo fixed, References adde

Risk-taking attitudes and their association with process and outcomes of cardiac care: a cohort study

<p>Abstract</p> <p>Background</p> <p>Prior research reveals that processes and outcomes of cardiac care differ across sociodemographic strata. One potential contributing factor to such differences is the personality traits of individuals within these strata. We examined the association between risk-taking attitudes and cardiac patients' clinical and demographic characteristics, the likelihood of undergoing invasive cardiac procedures and survival.</p> <p>Methods</p> <p>We studied a large inception cohort of patients who underwent cardiac catheterization between July 1998 and December 2001. Detailed clinical and demographic data were collected at time of cardiac catheterization and through a mailed survey one year post-catheterization. The survey included three general risk attitude items from the Jackson Personality Inventory. Patients' (n = 6294) attitudes toward risk were categorized as risk-prone versus non-risk-prone and were assessed for associations with baseline clinical and demographic characteristics, treatment received (i.e., medical therapy, coronary artery bypass graft (CABG) surgery, percutaneous coronary intervention (PCI)), and survival (to December 2005).</p> <p>Results</p> <p>2827 patients (45%) were categorized as risk-prone. Having risk-prone attitudes was associated with younger age (p < .001), male sex (p < .001), current smoking (p < .001) and higher household income (p < .001). Risk-prone patients were more likely to have CABG surgery in unadjusted (Odds Ratio [OR] = 1.21; 95% CI 1.08–1.36) and adjusted (OR = 1.18; 95% CI 1.02–1.36) models, but were no more likely to have PCI or any revascularization. Having risk-prone attitudes was associated with better survival in an unadjusted survival analysis (Hazard Ratio [HR] = 0.78 (95% CI 0.66–0.93), but not in a risk-adjusted analysis (HR = 0.92, 95% CI 0.77–1.10).</p> <p>Conclusion</p> <p>These exploratory findings suggest that patient attitudes toward risk taking may <b>contribute to </b>some of the documented differences in use of invasive cardiac procedures. An awareness of these associations could help healthcare providers as they counsel patients regarding cardiac care decisions.</p

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Response of Bosc and Cold Snap™ pears to thinning with NAA, 6-BA, ACC and S-ABA

Adjusting the crop-load of European pears [Pyrus communis L.] by hand thinning is currently required to ensure marketable size of most cultivars grown in Ontario. The benefits of chemical thinning pears and their effect on fruit quality and fresh-market returns was investigated in a three-year study where a series of foliar chemical thinning sprays was applied during the 10-mm fruitlet stage to Bosc and Cold Snapâ ˘ pear trees growing in commercial orchards in the Niagara Peninsula, Ontario. Treatments included an untreated and hand-thinned control, and two concentrations each of 6-benzyladenine (6-BA; 75 mg L-1 and 150 mg L-1), naphthalene acetic acid (10 mg L-1 and 20 mg L-1), 1-aminocyclopropane carboxylic acid (150 mg L-1 and 300 mg L-1) and s-abscisic acid (s-ABA; 150 mg L-1 and 300 mg L-1). Overall, all thinning products reduced crop load at least once in the three-year study, although this varied by year and cultivar. Higher concentrations were more effective than lower concentrations. Napthalene aceditic acid (both rates), 150 mg L-1 6-BA and 300 mg L-1 s-ABA were most consistent. Since the crop load of control trees was not heavy, minimal hand thinning was required and all thinning treatments reduced crop value compared with the untreated trees. There were minimal effects on starch hydrolysis, soluble solids, fruit firmness and skin colour at harvest.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author