Response shift due to diagnosis and primary treatment of localized prostate cancer: a then-test and a vignette study

Aim Whether a prostate cancer diagnosis induces response shift has not been established so far. Therefore, we assessed response shift in men who were diagnosed with localized prostate cancer. Patients and methods Out of 3,892 men who completed a questionnaire before screening, 82 were subsequently diagnosed with prostate cancer. Response shift was assessed in 52 (response 63%) by the then-test (EuroQol self-rating of health, Short-Form 36 mental health and vitality) and a novel method: rating of vignettes relating to side effects of prostate cancer treatment (urinary, bowel and erectile dysfunction). Three then-tests were conducted: two referencing pre-diagnosis (measured pre

Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD

Different perceptions of the burden of upper GI endoscopy: an empirical study in three patient groups

Background: Few studies have evaluated patients' perceived burden of cancer surveillance tests. Cancer screening and surveillance, however, require a large number of patients to undergo potentially burdensome tests with only some experiencing health gains from it. We investigated the determinants of patients' reported burden of upper gastrointestinal (GI) endoscopy by comparing data from three patient groups. Patients and methods: A total of 476 patients were included: 180 patients under regular surveillance for Barrett esophagus (BE), a premalignant disorder; 214 patients with non-specific upper GI symptoms (NS), and 82 patients recently diagnosed with upper GI cancer (CA). We assessed pain, discomfort and overall burden experienced during endoscopy, symptoms in the week afterwards and psychological distress over time (Hospital Anxiety and Depression scale and Impact of Event Scale). Results: Two-thirds (66%) of patients reported discomfort and overall burden of upper GI endoscopy. Only 23% reported any pain. BE patients reported significantly less discomfort, pain and overall burden than the other patients: those with NS reported more discomfort, CA patients more pain, and both more overall burden. These differences could be statistically explained by the number of previous endoscopies and whether sedation was provided or not, but not by patient characteristics. Conclusion: The perception of upper GI endoscopy varies by patient group, due to potential adaptation after multiple endoscopies and aspects of th

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

Active submarine eruption of boninite in the northeastern Lau Basin

Subduction of oceanic crust and the formation of volcanic arcs above the subduction zone are important components in Earth’s geological and geochemical cycles. Subduction consumes and recycles material from the oceanic plates, releasing fluids and gases that enhance magmatic activity, feed hydrothermal systems, generate ore deposits and nurture chemosynthetic biological communities. Among the first lavas to erupt at the surface from a nascent subduction zone are a type classified as boninites. These lavas contain information about the early stages of subduction, yet because most subduction systems on Earth are old and well-established, boninite lavas have previously only been observed in the ancient geological record. Here we observe and sample an active boninite eruption occurring at 1,200 m depth at the West Mata submarine volcano in the northeast Lau Basin, southwest Pacific Ocean. We find that large volumes of H2O, CO2 and sulphur are emitted, which we suggest are derived from the subducting slab. These volatiles drive explosive eruptions that fragment rocks and generate abundant incandescent magma-skinned bubbles and pillow lavas. The eruption has been ongoing for at least 2.5 years and we conclude that this boninite eruption is a multi-year, low-mass-transfer-rate eruption. Thus the Lau Basin may provide an important site for the long-term study of submarine volcanic eruptions related to the early stages of subduction

Survival of Desulfotomaculum spores from estuarine sediments after serial autoclaving and high-temperature exposure

International audienceBacterial spores are widespread in marine sediments, including those of thermophilic, sulphate-reducing bacteria, which have a high minimum growth temperature making it unlikely that they grow in situ. These Desulfotomaculum spp. are thought to be from hot environments and are distributed by ocean currents. Their cells and spores upper temperature limit for survival is unknown, as is whether they can survive repeated high-temperature exposure that might occur in hydrothermal systems. This was investigated by incubating estuarine sediments significantly above (40–80 1C) maximum in situ temperatures (B23 1C), and with and without prior triple autoclaving. Sulphate reduction occurred at 40–60 1C and at 60 1C was unaffected by autoclaving. Desulfotomaculum sp. C1A60 was isolated and was most closely related to the thermophilic D. kuznetsovii T (B96% 16S rRNA gene sequence identity). Cultures of Desulfotomaculum sp. C1A60, D. kuznetsovii T and D. geothermicum B2T survived triple autoclaving while other related Desulfotomaculum spp. did not, although they did survive pasteurisation. Desulfotomaculum sp. C1A60 and D. kuznetsovii cultures also survived more extreme autoclaving (C1A60, 130 1C for 15 min; D. kuznetsovii, 135 1C for 15 min, maximum of 154 1C reached) and high-temperature conditions in an oil bath (C1A60, 1301 for 30 min, D. kuznetsovii 140 1C for 15 min). Desulfotomaculum sp. C1A60 with either spores or predominantly vegetative cells demonstrated that surviving triple autoclaving was due to spores. Spores also had very high culturability compared with vegetative cells (B30 Â higher). Combined extreme temperature survival and high culturability of some thermophilic Desulfotomaculum spp. make them very effective colonisers of hot environments, which is consistent with their presence in subsurface geothermal waters and petroleum reservoirs