SPECIFIC TRANSPLANTATION ANTIGENS OF MOUSE SARCOMAS INDUCED BY ADENOVIRUS TYPE 12

A specific isograft resistance against three different mouse adeno 12 sarcomas was demonstrated in mice treated with four to eight doses of viable or X-ray-killed adeno 12 mouse tumors. Whole-body X-ray irradiation with 350 R 24 hr previous to the test challenge did not abolish the resistance, indicating that it was due to a true anamnestic immune reaction. This was further proven by the finding that similar treatment with tumors of other origin did not induce any immunity, nor did the treatment with adeno 12 tumor material induce any immunity against two neoplasms of Schmidt-Ruppin-Rous viral origin. The previous report by Trentin et al. (17) that adeno 12 infection leads to a specific transplantation immunity was fully confirmed. When the specificity of this virus-induced immunity was studied it was discovered that besides adeno virus type 12, type 7 and probably type 18 also gave the same type of resistance while adenovirus type 5 did not. A contamination of the adeno 7-infected mice with adeno type 12 was excluded by testing pooled sera from these animals for anti-adeno 12 CF or HI antibodies

The role of adjuvant chemotherapy for patients with resected pancreatic cancer: Systematic review of randomized controlled trials and meta-analysis

Background: In patients undergoing surgery for resectable pancreatic cancer prognosis still remains poor. The role of adjuvant treatment strategies (including chemotherapy and chemoradiotherapy) following resection of pancreatic cancer remains controversial. Methods: A Medline-based literature search was undertaken to identify randomized controlled trials that evaluated adjuvant chemotherapy after complete macroscopic resection for cancer of the exocrine pancreas. Five trials of adjuvant chemotherapy were eligible and critically reviewed for this article. A meta-analysis (based on published data) was performed with survival (median survival time and 5-year survival rate) being the primary endpoint. Results: For the meta-analysis, 482 patients were allocated to the chemotherapy group and 469 patients to the control group. The meta-analysis estimate for prolongation of median survival time for patients in the chemotherapy group was 3 months (95% CI 0.3-5.7 months, p = 0.03). The difference in 5-year survival rate was estimated with 3.1% between the chemotherapy and the control group (95% CI -4.6 to 10.8%, p > 10.05). Conclusion: Currently available data from randomized trials indicate that adjuvant chemotherapy after resection of pancreatic cancer may substantially prolong disease-free survival and cause a moderate increase in overall survival. In the current meta-analysis, a significant survival benefit was only seen with regard to median survival, but not for the 5-year survival rate. The optimal chemotherapy regimen in the adjuvant setting as well as individualized treatment strategies (also including modern chemoradiotherapy regimens) still remain to be defined. Copyright (C) 2008 S. Karger AG, Basel

Changes in received quality of care for knee osteoarthritis after a multicomponent intervention in a general practice in Denmark.

Objective: First-line treatment for patients with knee osteoarthritis should ideally prescribe patient education, exercise, and if needed, weight loss. In practice, however, adjunctive treatments, including painkillers and referrals to specialists, are typically introduced before these measures. This study evaluated interventions to sustainably improve general practitioner delivered care for patients with knee osteoarthritis. Design: Comparison of impacts of knee osteoarthritis care during four half-year periods: before, 6, 12, and 18 months after primary intervention based on electronic medical records (EMR) and patient questionnaires. Setting: Danish general practitioners (GPs) treating 6240 patients. Participants: Four GPs, two GP trainees, and six staff members. Interventions: Six pre-planned primary interventions: patient leaflet, GP and staff educational session, knee osteoarthritis consultation, two functional tests monitoring patient function, EMR phrase aiding consultation, and waiting room advertisement and three supportive follow-up interventions. Main outcome measures: Usage of first-line and adjunctive treatment elements, the functional tests, and the EMR phrase. Results: Approximately 50 knee osteoarthritis cases participated in each of the four half-year periods. Primary interventions had only transient effects lasting <12 months on the knee osteoarthritis care. Functional tests and EMR phrases were used predominantly during the first 6 months, where a transient drop in the referral rate to orthopedics was observed. Use of educational elements was moderate and without significant change during follow-up. Conclusion: More routine use of the primary or inclusion of novel increased-adherence interventions is needed to sustainably improve care for knee osteoarthritis patients in Danish general practice

Accommodating heterogeneous missing data patterns for prostate cancer risk prediction

Objective: We compared six commonly used logistic regression methods for accommodating missing risk factor data from multiple heterogeneous cohorts, in which some cohorts do not collect some risk factors at all, and developed an online risk prediction tool that accommodates missing risk factors from the end-user. Study Design and Setting: Ten North American and European cohorts from the Prostate Biopsy Collaborative Group (PBCG) were used for fitting a risk prediction tool for clinically significant prostate cancer, defined as Gleason grade group greater or equal 2 on standard TRUS prostate biopsy. One large European PBCG cohort was withheld for external validation, where calibration-in-the-large (CIL), calibration curves, and area-underneath-the-receiver-operating characteristic curve (AUC) were evaluated. Ten-fold leave-one-cohort-internal validation further validated the optimal missing data approach. Results: Among 12,703 biopsies from 10 training cohorts, 3,597 (28%) had clinically significant prostate cancer, compared to 1,757 of 5,540 (32%) in the external validation cohort. In external validation, the available cases method that pooled individual patient data containing all risk factors input by an end-user had best CIL, under-predicting risks as percentages by 2.9% on average, and obtained an AUC of 75.7%. Imputation had the worst CIL (-13.3%). The available cases method was further validated as optimal in internal cross-validation and thus used for development of an online risk tool. For end-users of the risk tool, two risk factors were mandatory: serum prostate-specific antigen (PSA) and age, and ten were optional: digital rectal exam, prostate volume, prior negative biopsy, 5-alpha-reductase-inhibitor use, prior PSA screen, African ancestry, Hispanic ethnicity, first-degree prostate-, breast-, and second-degree prostate-cancer family history

State Transition Graphs for Semantic Analysis of Movement Behaviours

A behaviour can be defined as a sequence of states or activities occurring one after another. A behaviour consisting of a finite number of reoccurring states/activities may be represented by a directed weighted graph with nodes and edges corresponding, respectively, to the possible states and transitions between them, while the weights represent the probabilities or frequencies of the state and transition occurrences. The same applies to multiple behaviours sharing the same set of possible states. In analysis of movement data, state transition graphs can be used to represent semantic abstractions of mobility behaviours, where states correspond to semantic categories of visited places (such as ‘home’, ‘work’, ‘shop’), activities of moving objects (‘driving’, ‘walking’, ‘exercising’, etc.) or characteristics of the movement (‘straight movement’, ‘sharp turn’, ‘acceleration’, ‘stop’, etc.). Such a representation supports the exploration and analysis of the semantic aspect (i.e. the meaning or purposes) of movement. For comprehensive analysis of movement data, state transition graphs need to be combined with representations reflecting the spatial and temporal aspects of the movement. This requires appropriate coordination between different visual displays (graphs, maps and temporal views) and appropriate reaction to analytical operations applied to any of the representations of the same data. We define in an abstract way the reactions of a graph display to analytical operations of querying, partitioning and direct selection. We also propose visual and interactive display features supporting comparisons between data subsets and between results of different operations. We demonstrate the use of the display features by examples of real-world and synthetic data sets

Budesonide/formoterol and formoterol provide similar rapid relief in patients with acute asthma showing refractoriness to salbutamol

BACKGROUND: To compare the efficacy and safety of budesonide/formoterol (Symbicort(®)) with formoterol (Oxis(®)) in the treatment of patients with acute asthma who showed evidence of refractoriness to short-acting β(2)-agonist therapy. METHODS: In a 3 hour, randomized, double-blind study, a total of 115 patients with acute asthma (mean FEV(1 )40% of predicted normal) and a refractory response to salbutamol (mean reversibility 2% of predicted normal after inhalation of 400 μg), were randomized to receive either budesonide/formoterol (320/9 μg, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 1280/36 μg]) or formoterol (9 μg, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 36 μg]). The primary efficacy variable was the average FEV(1 )from the first intake of study medication to the measurement at 90 minutes. Secondary endpoints included changes in FEV(1 )at other timepoints and change in respiratory rate at 180 minutes. Treatment success, treatment failure and patient assessment of the effectiveness of the study medication were also measured. RESULTS: FEV(1 )increased after administration of the study medication in both treatment groups. No statistically significant difference between the treatment groups was apparent for the primary outcome variable, or for any of the other efficacy endpoints. There were no statistically significant between-group differences for treatment success, treatment failure or patient assessment of medication effectiveness. Both treatments were well tolerated. CONCLUSION: Budesonide/formoterol and formoterol provided similarly rapid relief of acute bronchoconstriction in patients with asthma who showed evidence of refractoriness to a short-acting β(2)-agonist

A panel of kallikrein markers can predict outcome of prostate biopsy following clinical work-up: an independent validation study from the European Randomized Study of Prostate Cancer screening, France

<p>Abstract</p> <p>Background</p> <p>We have previously shown that a panel of kallikrein markers - total prostate-specific antigen (PSA), free PSA, intact PSA and human kallikrein-related peptidase 2 (hK2) - can predict the outcome of prostate biopsy in men with elevated PSA. Here we investigate the properties of our panel in men subject to clinical work-up before biopsy.</p> <p>Methods</p> <p>We applied a previously published predictive model based on the kallikrein panel to 262 men undergoing prostate biopsy following an elevated PSA (≥ 3 ng/ml) and further clinical work-up during the European Randomized Study of Prostate Cancer screening, France. The predictive accuracy of the model was compared to a "base" model of PSA, age and digital rectal exam (DRE).</p> <p>Results</p> <p>83 (32%) men had prostate cancer on biopsy of whom 45 (54%) had high grade disease (Gleason score 7 or higher). Our model had significantly higher accuracy than the base model in predicting cancer (area-under-the-curve [AUC] improved from 0.63 to 0.78) or high-grade cancer (AUC increased from 0.77 to 0.87). Using a decision rule to biopsy those with a 20% or higher risk of cancer from the model would reduce the number of biopsies by nearly half. For every 1000 men with elevated PSA and clinical indication for biopsy, the model would recommend against biopsy in 61 men with cancer, the majority (≈80%) of whom would have low stage <it>and </it>low grade disease at diagnosis.</p> <p>Conclusions</p> <p>In this independent validation study, the model was highly predictive of prostate cancer in men for whom the decision to biopsy is based on both elevated PSA and clinical work-up. Use of this model would reduce a large number of biopsies while missing few cancers.</p