Background.
A better assessment of individualized prostate cancer (PrCa) risk is needed to improve screening. The use of the prostate‐specific antigen (PSA) level for screening in the general ...population has limitations and is not currently advocated. Approximately 100 common single nucleotide polymorphisms (SNPs) have been identified that are associated with the risk of developing PrCa. The PROFILE pilot study explored the feasibility of using SNP profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The primary aim of this pilot study was to determine the safety and feasibility of PrCa screening using transrectal ultrasound‐guided PB with or without diffusion‐weighted magnetic resonance imaging (DW‐MRI) in men with a FH. A secondary aim was to evaluate the potential use of SNP profiling as a screening tool in this population.
Patients and Methods.
A total of 100 men aged 40–69 years with a FH of PrCa underwent PB, regardless of their baseline PSA level. Polygenic risk scores (PRSs) were calculated for each participant using 71 common PrCa susceptibility alleles. We treated the disease outcome at PB as the outcome variable and evaluated its associations with the PRS, PSA level, and DW‐MRI findings using univariate logistic regression.
Results.
Of the 100 men, 25 were diagnosed with PrCa, of whom 12 (48%) had clinically significant disease. Four adverse events occurred and no deaths. The PSA level and age at study entry were associated with PrCa at PB (p = .00037 and p = .00004, respectively).
Conclusion.
The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH, with a high proportion of PrCa identified requiring radical treatment. It is feasible to collect data on PrCa‐risk SNPs to evaluate their combined effect as a potential screening tool. A larger prospective study powered to detect statistical associations is in progress.
Implications for Practice:
Prostate biopsy is a feasible and safe approach to prostate cancer screening in men with a family history and detects a high proportion of prostate cancer that needs radical treatment. Calculating a polygenic risk score using prostate cancer risk single nucleotide polymorphisms could be a potential future screening tool for prostate cancer.
A better assessment of prostate cancer (PrCa) risk is needed to improve screening. The PROFILE pilot study explored the feasibility of single nucleotide polymorphism profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH.
Fungi play major roles in ecosystem processes, but the determinants of fungal diversity and biogeographic patterns remain poorly understood. Using DNA metabarcoding data from hundreds of globally ...distributed soil samples, we demonstrate that fungal richness is decoupled from plant diversity. The plant-to-fungus richness ratio declines exponentially toward the poles. Climatic factors, followed by edaphic and spatial variables, constitute the best predictors of fungal richness and community composition at the global scale. Fungi show similar latitudinal diversity gradients to other organisms, with several notable exceptions. These findings advance our understanding of global fungal diversity patterns and permit integration of fungi into a general macroecological framework.
Results from large randomised controlled trials have shown that adding docetaxel to the standard of care (SOC) for men initiating hormone therapy for prostate cancer (PC) prolongs survival for those ...with metastatic disease and prolongs failure-free survival for those without. To date there has been no formal assessment of whether funding docetaxel in this setting represents an appropriate use of UK National Health Service (NHS) resources.
To assess whether administering docetaxel to men with PC starting long-term hormone therapy is cost-effective in a UK setting.
We modelled health outcomes and costs in the UK NHS using data collected within the STAMPEDE trial, which enrolled men with high-risk, locally advanced metastatic or recurrent PC starting first-line hormone therapy.
SOC was hormone therapy for ≥2 yr and radiotherapy in some patients. Docetaxel (75mg/m2) was administered alongside SOC for six three-weekly cycles.
The model generated lifetime predictions of costs, changes in survival duration, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs).
The model predicted that docetaxel would extend survival (discounted quality-adjusted survival) by 0.89 yr (0.51) for metastatic PC and 0.78 yr (0.39) for nonmetastatic PC, and would be cost-effective in metastatic PC (ICER £5514/QALY vs SOC) and nonmetastatic PC (higher QALYs, lower costs vs SOC). Docetaxel remained cost-effective in nonmetastatic PC when the assumption of no survival advantage was modelled.
Docetaxel is cost-effective among patients with nonmetastatic and metastatic PC in a UK setting. Clinicians should consider whether the evidence is now sufficiently compelling to support docetaxel use in patients with nonmetastatic PC, as the opportunity to offer docetaxel at hormone therapy initiation will be missed for some patients by the time more mature survival data are available.
Starting docetaxel chemotherapy alongside hormone therapy represents a good use of UK National Health Service resources for patients with prostate cancer that is high risk or has spread to other parts of the body.
Docetaxel is a cost-effective intervention in patients with metastatic and nonmetastatic prostate cancer starting hormone therapy. Clinicians and National Health Service funding bodies should consider whether the evidence is now sufficiently compelling to support initiating docetaxel in patients with nonmetastatic disease.
A
bstract
Using inelastic proton-proton interactions at
GeV and 7 TeV, recorded by the ATLAS detector at the LHC, measurements have been made of the correlations between forward and backward ...charged-particle multiplicities and, for the first time, between forward and backward charged-particle summed transverse momentum. In addition, jet-like structure in the events is studied by means of azimuthal distributions of charged particles relative to the charged particle with highest transverse momentum in a selected kinematic region of the event. The results are compared with predictions from tunes of the pythia and herwig++ Monte Carlo generators, which in most cases are found to provide a reasonable description of the data.
The clinic attendance of 100 consecutive referrals to child psychiatry is described. Only 47 cases ended in agreed discharge. Different factors were found to be associated with attrition at different ...stages in the treatment-uptake process. Of referrals offered an appointment, 16% failed to attend at all; this was significantly associated with parents being against referral. Of cases offered a subsequent appointment, 40% dropped out. Continued attendance was associated with a presenting problem of general anxiety and with consultation to the referrer. Dropping out was associated with parents who were separated.
Measurements are presented of the properties of high transverse momentum jets, produced in proton-proton collisions at a center-of-mass energy of radicals = 7 TeV. The data correspond to an ...integrated luminosity of 35 pb super(-1) and were collected with the ATLAS detector in 2010. Jet mass, width, eccentricity, planar flow and angularity are measured for jets reconstructed using the anti-kt algorithm with distance parameters R = 0.6 and 1.0, with transverse momentum pT > 300 GeV and pseudorapidity eta < 2. The measurements are compared to the expectations of Monte Carlo generators that match leading-logarithmic parten showers to leading-order, or next-to-leading-order, matrix elements. The generators describe the general features of the jets, although discrepancies are observed in some distributions.
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