68Ga-PSMA-PET/CT-directed IGRT/SBRT for oligometastases of recurrent prostate cancer after initial surgery.

Background: We evaluated efficacy and toxicity of 68Ga-PSMA-Positron Emission Tomography/Computed Tomography (PET/CT)-directed stereotactic body radiotherapy and image-guided radiotherapy (SBRT/IGRT) for oligometastases of prostate cancer recurrences after previous surgery.Methods: Nineteen patients were analyzed within a prospective PET-registry study (064/2013BO1) and retrospectively analyzed (807/2017BO2) fulfilling the following inclusion criteria: biochemical recurrence after radical prostatectomy, ≤five 68Ga-PSMA-PET/CT positive lesions. Biochemical control was evaluated with EORTC (European Organization for Research and Treatment of Cancer)- and Phenix-definitions. Toxicity was scored according to CTCAE-criteria v. 4.03.Results: A total of 38 oligometastases (19 patients, 2 with re-treatment) were treated with SBRT/IGRT from October 2014 to July 2017. 68Ga-PSMA-PET/CT-positive lesions were detected on average 39 months (5-139) after prostatectomy (pT2b-3b pN0-1 cM0). Mean PSA (Prostate-specific antigen)-level at time of imaging reached 2.2 ng/mL (range 0.2-10.1). PET/CT-positive lesions were treated with different fractionation schedules reaching biological equivalent doses (BED) of 116.7-230.0 Gy. Concomitant androgen deprivation therapy (ADT) was given in seven patients. After a median follow-up of 17 months (4-42) all patients were alive. Estimated 1-year PSA- control (n = 19) reached 80.8% (Phenix) and 67.5% (EORTC). A PSA-decline (≥50%) was detected in 16/19 patients after radiotherapy. Higher graded G3+-acute toxicity did not occur. Temporary late G3-proctitis was detected in one patient.Conclusions: Reaching of nadir ≤0.1 or 0.2 ng/mL was associated by improved DMFS (distant metastases free survival) and could serve as a surrogate endpoint for RT of oligometastases after initial prostatectomy. Short term effects of 68Ga-PSMA-PET/CT-based ablative radiotherapy for oligometastases demonstrated an acceptable toxicity profile and favorable biochemical response.

Visual uncertainty influences the extent of an especial skill.

An especial skill in basketball emerges through highly repetitive practice at the 15 ft free throw line. The extent of the role vision plays in the emergence of an especial skill is unknown. We examined the especial skills of ten skilled basketball players in normal and blurred vision conditions where participants wore corrective lenses. As such, we selectively manipulated visual information without affecting the participants' explicit knowledge that they were shooting free throws. We found that shot efficiency was significantly lower in blurred vision conditions as expected, and that the concave shape of shot proficiency function in normal vision conditions became approximately linear in blurred vision conditions. By applying a recently proposed generalization model of especial skills, we suggest that the linearity of shot proficiency function reflects the participants' lesser dependence on especial skill in blurred vision conditions. The findings further characterize the role of visual context in the emergence of an especial skill.

IL18 and IL18R1 polymorphisms, lung CT and fibrosis: A longitudinal study in coal miners.

It has been suggested that interleukin (IL)-18 plays a role in the development of inflammatory and fibrosing lung diseases. Associations of polymorphisms in the genes coding for IL-18 (IL18 /G-656T, C-607A, G-137C, T113G, C127T) and its receptor (IL18R1 /C-69T) with coal workers' pneumoconiosis (CWP) were studied in 200 miners who were examined in 1990, 1994 and 1999. Coal-dust exposure was assessed according to job history and ambient measures. The main health outcome was lung computed tomography (CT) score in 1990. Internal coherence was assessed by studying CT score in 1994, 4-yr change in CT score and CWP incidence and prevalence. CT score in 1990 was a good predictor of radiographic grade in 1999 and, therefore, an appropriate subclinical quantitative trait. The IL18 -137C allele was associated with lower CT score in 1990 and 1994 (1.24 versus 1.69 and 1.57 versus 2.46, respectively), slower progression of CT score between 1990 and 1994 and lower pneumoconiosis prevalence in 1999 relative to the G allele (0.33 versus 0.77 and 8.2 versus 19.6%, respectively). Smoking- or dust-adjustment, and stratification on IL18R1 genotype and adjustment for haplotype effects did not change the conclusions. In conclusion, the results of the present study suggest a role for IL18 in reducing the development of this fibrosing lung disease.

GSTM1 and GSTP1 and respiratory health in asthmatic children exposed to ozone.

Acute exposure to ozone has been related to a wide spectrum of health effects in susceptible individuals. Genetic factors may influence interindividual variation in ozone response. The current authors investigated the relationships between common polymorphisms in two genes involved in response to oxidative stress, i.e. glutathione S-transferases M1 (GSTM1) and P1 (GSTP1), and both respiratory symptoms and lung function in response to ozone among childhood asthmatics. A total of 151 asthmatic children, who were participants in a randomised controlled trial of antioxidant vitamin supplementation in Mexico City, were studied. Children were genotyped using PCR methods and followed from October 1998-April 2000. Increases in reported breathing difficulty were associated with ozone exposure in children with GSTM1 null (8%, 95% confidence interval (CI) 1-15%, per 20-ppb increase in 1-h maximum daily average over 7 days) or GSTP1 Valine/Valine (Val/Val) genotypes (14%, 95% CI 5-25%). In children with both GSTM1 null and GSTP1 Val/Val genotypes, the increase in breathing difficulty associated with a 20-ppb increase in ozone exposure was even greater (21%, 95% CI 5-39%). GSTP1 genotypes were not significantly associated with ozone-related lung function changes. In conclusion, asthmatic children with glutathione S-transferase M1 null and glutathione S-transferase P1 Valine/Valine genotypes appear more susceptible to developing respiratory symptoms related to ozone exposure.