A first step towards a global nomogram to predict disease progression for men on active surveillance

Background: Signs of disease progression (28%) and conversion to active treatment without evidence of disease progression (13%) are the main reasons for discontinuation of active surveillance (AS) in men with localised prostate cancer (PCa). We aimed to develop a nomogram to predict disease progression in these patients. Methods: As a first step in the development of a nomogram, using data from Movembers' GAP3 Consortium (n=14,380), we assessed heterogeneity between centres in terms of risk of disease progression. We started with assessment of baseline hazards for disease progression based on grouping of centres according to follow-up protocols [high: yearly; intermediate: similar to 2 yearly; and low: at year 1, 4 & 7 (i.e., PRIAS)]. We conducted cause-specific random effect Cox proportional hazards regression to estimate risk of disease progression by centre in each group. Results: Disease progression rates varied substantially between centres [median hazard ratio (MHR): 2.5]. After adjustment for various clinical factors (age, year of diagnosis, Gleason grade group, number of positive cores and PSA), substantial heterogeneity in disease progression remained between centres. Conclusions: When combining worldwide data on AS, we noted unexplained differences of disease progression rate even after adjustment for various clinical factors. This suggests that when developing a global nomogram, local adjustments for differences in risk of disease progression and competing outcomes such as conversion to active treatment need to be considered.Peer reviewe

Testing of a Tool for Prostate Cancer Screening Discussions in Primary Care

BackgroundAs prostate cancer (PCa) screening decisions often occur in outpatient primary care, a brief tool to help the PCa screening conversation in busy clinic settings is needed.MethodsA previously created 9-item tool to aid PCa screening discussions was tested in five diverse primary care clinics. Fifteen providers were recruited to use the tool for 4 weeks, and the tool was revised based upon feedback. The providers then used the tool with a convenience sample of patients during routine clinic visits. Pre- and post-visit surveys were administered to assess patients’ knowledge of the option to be screened for PCa and of specific factors to consider in the decision. McNemar’s and Stuart–Maxwell tests were used to compare pre-and post-survey responses.Results14 of 15 providers completed feedback surveys and had positive responses to the tool. All 15 providers then tested the tool on 95 men aged 40–69 at the five clinics with 2–10 patients each. The proportion of patients who strongly agreed that they had the option to choose to screen for PCa increased from 57 to 72% (p = 0.018) from the pre- to post-survey, that there are factors in the personal or family history that may affect PCa risk from 34 to 47% (p = 0.012), and that their opinions about possible side effects of treatment for PCa should be considered in the decision from 47 to 61% (p = 0.009).ConclusionA brief conversation tool for the PCa screening discussion was well received in busy primary-care settings and improved patients’ knowledge about the screening decision

Molecular epidemiology of measles viruses in China, 1995–2003

This report describes the genetic characterization of 297 wild-type measles viruses that were isolated in 24 provinces of China between 1995 and 2003. Phylogenetic analysis of the N gene sequences showed that all of the isolates belonged to genotype H1 except 3 isolates, which were genotype A. The nucleotide sequence and predicted amino acid homologies of the 294-genotype H1 strains were 94.7%–100% and 93.3%–100%, respectively. The genotype H1 isolates were divided into 2 clusters, which differed by approximately 2.9% at the nucleotide level. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Even though other measles genotypes have been detected in countries that border China, this report shows that genotype H1 is widely distributed throughout the country and that China has a single, endemic genotype. This important baseline data will help to monitor the progress of measles control in China

Reasons for Discontinuing Active Surveillance : Assessment of 21 Centres in 12 Countries in the Movember GAP3 Consortium

Background: Careful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa). Objective: Using Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation. Design, setting, and participants: We compared data from 10 296 men on AS from 21 centres across 12 countries. Outcome measurements and statistical analysis: Cumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation. Results and limitations: During 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4-28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0-13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5-2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4-2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5 yr, 4561 had follow-up for Conclusions: Our descriptive analyses of current AS practices worldwide showed that 43.6% of men drop out of AS during 5-yr follow-up, mainly due to signs of disease progression. Improvements in selection tools for AS are thus needed to correctly allocate men with PCa to AS, which will also reduce discontinuation due to conversion to active treatment without evidence of disease progression. Patient summary: Our assessment of a worldwide database of men with prostate cancer (PCa) on active surveillance (AS) shows that 43.6% drop out of AS within 5 yr, mainly due to signs of disease progression. Better tools are needed to select and monitor men with PCa as part of AS. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewe

Numerical Simulation Analysis of Dual-Beam Laser Welding of Tailored Blanks with Different Thicknesses

In order to meet the requirements of alignment capability, gap tolerance and welding track control, dual-beam laser welding has been put forward to weld tailored blanks with different thicknesses. The arrangement mode and power ratio of dual-beam laser determine the heat transfer and temperature field distribution, and then influence the weld profile and weld quality. In this study, based on consideration of the temperature dependence of material physical properties, convection and radiation heat transfer, and material latent heat, the finite element model was developed. The model validated was conducted to compare with experimental results and it showed good agreement. The arrangement mode and power ratio of dual-beam laser welding were compared and optimized based on the consideration of the weld width on top surface and gap tolerance. Finally, the temperature field characteristics with the preferable process were analyzed in detail according to the numerical simulation. The calculated results indicated the weld width is mainly controlled by the laser irradiation on the thin plate, and dual-beam laser welding of tailored blanks has great advantages on improving heat transfer, weld profile and gap tolerance, which helps to reduce welding defects and enhance welding quality

Patterns and determinants of wood physical and mechanical properties across major tree species in China

The physical and mechanical properties of wood affect the growth and development of trees, and also act as the main criteria when determining wood usage. Our understanding on patterns and controls of wood physical and mechanical properties could provide benefits for forestry management and bases for wood application and forest tree breeding. However, current studies on wood properties mainly focus on wood density and ignore other wood physical properties. In this study, we established a comprehensive database of wood physical properties across major tree species in China. Based on this database, we explored spatial patterns and driving factors of wood properties across major tree species in China. Our results showed that (i) compared with wood density, air-dried density, tangential shrinkage coefficient and resilience provide more accuracy and higher explanation power when used as the evaluation index of wood physical properties. (ii) Among life form, climatic and edaphic variables, life form is the dominant factor shaping spatial patterns of wood physical properties, climatic factors the next, and edaphic factors have the least effects, suggesting that the effects of climatic factors on spatial variations of wood properties are indirectly induced by their effects on species distribution

Development and validation of pretreatment nomogram for disease-specific mortality in gastric cancer-A competing risk analysis

Background In several reports, gastric cancer nomograms for predicting overall or disease-specific survival have been described. The American Joint Committee on Cancer (AJCC) introduced the attractiveness of disease-specific mortality (DSM) as an endpoint of risk model. This study aimed to develop the first pretreatment gastric cancer nomogram for predicting DSM that considers competing risks (CRs). Methods The prediction model was developed using data for 5231 gastric cancer patients. Fifteen prognosticators, which were registered at diagnosis, were evaluated. The nomogram for DSM was created as visualizations of the multivariable Fine and Gray regression model. An independent cohort for external validation consisted of 389 gastric cancer patients from a different institution. The performance of the model was assessed by discrimination (Harrell's concordance (C)-index), calibration, and decision curve analysis. DSM and CRs were evaluated, paying special attention to host-related factors such as age and Eastern Cooperative Oncology Group performance status (ECOG PS), by using Gray's univariable method. Results Fourteen prognostic factors were selected to develop the nomogram. The new nomogram for DSM exhibited good discrimination. Its C-index of 0.887 surpassed that of the American Joint Committee on Cancer (AJCC) clinical staging (0.794). The C-index was 0.713 (AJCC, 0.582) for the external validation cohort. The nomogram showed good performance internally and externally, in the calibration and decision curve analysis. Host-related factors including age and ECOG PS, were strongly correlated with competing risks. Conclusions The newly developed nomogram accurately predicts DSM, which can be used for patient counseling in clinical practice

Asperuloside Prevents Peri-Implantitis via Suppression of NF-κB and ERK1/2 on Rats

Peri-implantitis is characterized by inflammatory cell infiltration and hyperactivation of the osteoclasts surrounding dental implants which can result in bone resorption and ultimately implant failure. Therefore, coordinating the activity of inflammatory response and bone-resorbing osteoclasts is crucial for the prevention of peri-implantitis. Asperuloside (ASP), an iridoid glycoside, has significant anti-inflammatory activities, suggesting the great potential in attenuating peri-implantitis bone resorption. A ligature-induced peri-implantitis model in the maxilla of rats was established, and the effects of ASP on preventing peri-implantitis were evaluated after four weeks of ligation using micro-CT and histological staining. RT-PCR, western blotting, tartrate-resistant acid phosphatase (TRAP), and immunofluorescent staining were conducted on osteoclasts to confirm the mechanisms of ASP on osteoclastogenesis. The results show that ASP could lead to attenuation of alveolar bone resorption in peri-implantitis by inhibiting osteoclast formation and decreasing pro-inflammatory cytokine levels in vivo. Furthermore, ASP could inhibit osteoclastogenesis by downregulating expression levels of transcription factors nuclear factor of activated T-cell (NFATc1) via restraining the activations of nuclear factor kappa beta (NF-κB) and the phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2). In conclusion, ASP could significantly attenuate bone resorption in peri-implantitis via inhibition of osteoclastogenesis by suppressing NF-κB and ERK1/2 signaling pathways activations