Undetectable ultrasensitive PSA after radical prostatectomy for prostate cancer predicts relapse-free survival

Radical retropubic prostatectomy is considered by many centres to be the treatment of choice for men aged less than 70 years with localized prostate cancer. A rise in serum prostate-specific antigen after radical prostatectomy occurs in 10–40% of cases. This study evaluates the usefulness of novel ultrasensitive PSA assays in the early detection of biochemical relapse. 200 patients of mean age 61.2 years underwent radical retropubic prostatectomy. Levels ≤ 0.01 ng ml–1 were considered undetectable. Mean pre-operative prostate-specific antigen was 13.3 ng ml–1. Biochemical relapse was defined as 3 consecutive rises. The 2-year biochemical disease-free survival for the 134 patients with evaluable prostate-specific antigen nadir data was 61.1% (95% CI: 51.6–70.6%). Only 2 patients with an undetectable prostate-specific antigen after radical retropubic prostatectomy biochemically relapsed (3%), compared to 47 relapses out of 61 patients (75%) who did not reach this level. Cox multivariate analysis confirms prostate-specific antigen nadir ≤ 0.01 ng ml–1 to be a superb independent variable predicting a favourable biochemical disease-free survival (P < 0.0001). Early diagnosis of biochemical relapse is feasible with sensitive prostate-specific antigen assays. These assays more accurately measure the prostate-specific antigen nadir, which is an excellent predictor of biochemical disease-free survival. Thus, sensitive prostate-specific antigen assays offer accurate prognostic information and expedite decision-making regarding the use of salvage prostate-bed radiotherapy or hormone therapy. © 2000 Cancer Research Campaign http://www.bjcancer.co

Train Positioning Using Video Odometry

Reliable Data Systems have developed a video-based odometry system that enables trains to measure velocities and distances travelled without the need for trackside infrastructure. The Study Group was asked to investigate ways of improving the accuracy of such a system, and to suggest any improvements that might be made. The work performed in the week followed along these strands: (a). Elimination of errors in video odometery induced by pitch and height; (b) Robust calculation of (i) the train velocity and (ii) the track curvature; (c). Accurate determination of the position of a train on a track by assimilating Curvature information; (d). Determining where on UK’s railway map a train journey takes place, based purely on video odometry and (e). Drawing a track map

Simulating a Community Mental Health Service During the COVID-19 Pandemic: Effects of Clinician-Clinician Encounters, Clinician-Patient-Family Encounters, Symptom-Triggered Protective Behaviour, and Household Clustering.

Objectives: Face-to-face healthcare, including psychiatric provision, must continue despite reduced interpersonal contact during the COVID-19 (SARS-CoV-2 coronavirus) pandemic. Community-based services might use domiciliary visits, consultations in healthcare settings, or remote consultations. Services might also alter direct contact between clinicians. We examined the effects of appointment types and clinician-clinician encounters upon infection rates. Design: Computer simulation. Methods: We modelled a COVID-19-like disease in a hypothetical community healthcare team, their patients, and patients' household contacts (family). In one condition, clinicians met patients and briefly met family (e.g., home visit or collateral history). In another, patients attended alone (e.g., clinic visit), segregated from each other. In another, face-to-face contact was eliminated (e.g., videoconferencing). We also varied clinician-clinician contact; baseline and ongoing "external" infection rates; whether overt symptoms reduced transmission risk behaviourally (e.g., via personal protective equipment, PPE); and household clustering. Results: Service organisation had minimal effects on whole-population infection under our assumptions but materially affected clinician infection. Appointment type and inter-clinician contact had greater effects at low external infection rates and without a behavioural symptom response. Clustering magnified the effect of appointment type. We discuss infection control and other factors affecting appointment choice and team organisation. Conclusions: Distancing between clinicians can have significant effects on team infection. Loss of clinicians to infection likely has an adverse impact on care, not modelled here. Appointments must account for clinical necessity as well as infection control. Interventions to reduce transmission risk can synergize, arguing for maximal distancing and behavioural measures (e.g., PPE) consistent with safe care

Transcriptome profiling to identify genes involved in peroxisome assembly and function

Yeast cells were induced to proliferate peroxisomes, and microarray transcriptional profiling was used to identify PEX genes encoding peroxins involved in peroxisome assembly and genes involved in peroxisome function. Clustering algorithms identified 224 genes with expression profiles similar to those of genes encoding peroxisomal proteins and genes involved in peroxisome biogenesis. Several previously uncharacterized genes were identified, two of which, YPL112c and YOR084w, encode proteins of the peroxisomal membrane and matrix, respectively. Ypl112p, renamed Pex25p, is a novel peroxin required for the regulation of peroxisome size and maintenance. These studies demonstrate the utility of comparative gene profiling as an alternative to functional assays to identify genes with roles in peroxisome biogenesis

Frequency Analysis and Sheared Reconstruction for Rendering Motion Blur

International audienceMotion blur is crucial for high-quality rendering but is also very expensive. Our first contribution is a frequency analysis of motion-blurred scenes, including moving objects, specular reflections, and shadows. We show that motion induces a shear in the frequency domain, and that the spectrum of moving scenes is usually contained in a wedge. This allows us to compute adaptive space-time sampling rates, to accelerate rendering. For uniform velocities and standard axis-aligned reconstruction, we show that the product of spatial and temporal bandlimits or sampling rates is constant, independent of velocity. Our second contribution is a novel sheared reconstruction filter that tightly packs the wedge of frequencies in the Fourier domain, and enables even lower sampling rates. We present a rendering algorithm that computes a sheared reconstruction filter per pixel, without any intermediate Fourier representation. This often permits synthesis of motion-blurred images with far fewer rendering samples than standard techniques require

Quantitative mass spectrometry reveals a role for the GTPase Rho1p in actin organization on the peroxisome membrane

We have combined classical subcellular fractionation with large-scale quantitative mass spectrometry to identify proteins that enrich specifically with peroxisomes of Saccharomyces cerevisiae. In two complementary experiments, isotope-coded affinity tags and tandem mass spectrometry were used to quantify the relative enrichment of proteins during the purification of peroxisomes. Mathematical modeling of the data from 306 quantified proteins led to a prioritized list of 70 candidates whose enrichment scores indicated a high likelihood of them being peroxisomal. Among these proteins, eight novel peroxisome-associated proteins were identified. The top novel peroxisomal candidate was the small GTPase Rho1p. Although Rho1p has been shown to be tethered to membranes of the secretory pathway, we show that it is specifically recruited to peroxisomes upon their induction in a process dependent on its interaction with the peroxisome membrane protein Pex25p. Rho1p regulates the assembly state of actin on the peroxisome membrane, thereby controlling peroxisome membrane dynamics and biogenesis

Vagus nerve stimulation for depression: efficacy and safety in a European study

Background Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression. Method An open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically. Results The baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score <10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%). Conclusions VNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European stud

CRIRES+ detection of CO emissions lines and temperature inversions on the dayside of WASP-18b and WASP-76b

The dayside atmospheres of ultra-hot Jupiters (UHJs) are predicted to possess temperature inversion layers with extremely high temperatures at high altitudes. We observed the dayside thermal emission spectra of WASP-18b and WASP-76b with the new CRIRES+ high-resolution spectrograph at near-infrared wavelengths. Using the cross-correlation technique, we detected strong CO emission lines in both planets, which confirms the existence of temperature inversions on their dayside hemispheres. The two planets are the first UHJs orbiting F-type stars with CO emission lines detected; previous detections were mostly for UHJs orbiting A-type stars. Evidence of weak H2O emission signals is also found for both planets. We further applied forward-model retrievals on the detected CO lines and retrieved the temperature-pressure profiles along with the CO volume mixing ratios. The retrieved logarithmic CO mixing ratio of WASP-18b (-2.2) is slightly higher than the value predicted by the self-consistent model assuming solar abundance. For WASP-76b, the retrieved CO mixing ratio (-3.6) is broadly consistent with the value of solar abundance. In addition, we included the equatorial rotation velocity (Veq ) in the retrieval when analyzing the line profile broadening. The obtained Veq is 7.0 km/s for WASP-18b and 5.2 km/s for WASP-76b, which are consistent with the tidally locked rotational velocities.Comment: 11 pages, 12 figures; accepted for publication in A&