Relationship Between Baseline Prostate-specific Antigen on Cancer Detection and Prostate Cancer Death:Long-term Follow-up from the European Randomized Study of Screening for Prostate Cancer

Background: The European Association of Urology guidelines recommend a risk-based strategy for prostate cancer screening based on the first prostate-specific antigen (PSA) level and age. Objective: To analyze the impact of the first PSA level on prostate cancer (PCa) detection and PCa-specific mortality (PCSM) in a population-based screening trial (repeat screening every 2–4 yr). Design, setting, and participants: We evaluated 25 589 men aged 55–59 yr, 16 898 men aged 60–64 yr, and 12 936 men aged 65–69 yr who attended at least one screening visit in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial (screening arm: repeat PSA testing every 2–4 yr and biopsy in cases with elevated PSA; control arm: no active screening offered) during 16-yr follow-up (FU). Outcome measurements and statistical analysis: We assessed the actuarial probability for any PCa and for clinically significant (cs)PCa (Gleason ≥7). Cox proportional-hazards regression was performed to assess whether the association between baseline PSA and PCSM was comparable for all age groups. A Lorenz curve was computed to assess the association between baseline PSA and PCSM for men aged 60–61 yr. Results and limitations: The overall actuarial probability at 16 yr ranged from 12% to 16% for any PCa and from 3.7% to 5.7% for csPCa across the age groups. The actuarial probability of csPCa at 16 yr ranged from 1.2–1.5% for men with PSA &lt;1.0 ng/ml to 13.3–13.8% for men with PSA ≥3.0 ng/ml. The association between baseline PSA and PCSM differed marginally among the three age groups. A Lorenz curve for men aged 60–61 yr showed that 92% of lethal PCa cases occurred among those with PSA above the median (1.21 ng/ml). In addition, for men initially screened at age 60–61 yr with baseline PSA &lt;2 ng/ml, further continuation of screening is unlikely to be beneficial after the age of 68–70 yr if PSA is still &lt;2 ng/ml. No case of PCSM emerged in the subsequent 8 yr (up to age 76–78 yr). A limitation is that these results may not be generalizable to an opportunistic screening setting or to contemporary clinical practice. Conclusions: In all age groups, baseline PSA can guide decisions on the repeat screening interval. Baseline PSA of &lt;1.0 ng/ml for men aged 55–69 yr is a strong indicator to delay or stop further screening. Patient summary: In prostate cancer screening, the patient's baseline PSA (prostate-specific antigen) level can be used to guide decisions on when to repeat screening. The PSA test when used according to current knowledge is valuable in helping to reduce the burden of prostate cancer.</p

The coupled boundary layers and air-sea transfer experiment in low winds

Author Posting. © American Meteorological Society, 2007. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Bulletin of the American Meteorological Society 88 (2007): 341-356, doi:10.1175/bams-88-3-341.The Office of Naval Research's Coupled Boundary Layers and Air–Sea Transfer (CBLAST) program is being conducted to investigate the processes that couple the marine boundary layers and govern the exchange of heat, mass, and momentum across the air–sea interface. CBLAST-LOW was designed to investigate these processes at the low-wind extreme where the processes are often driven or strongly modulated by buoyant forcing. The focus was on conditions ranging from negligible wind stress, where buoyant forcing dominates, up to wind speeds where wave breaking and Langmuir circulations play a significant role in the exchange processes. The field program provided observations from a suite of platforms deployed in the coastal ocean south of Martha's Vineyard. Highlights from the measurement campaigns include direct measurement of the momentum and heat fluxes on both sides of the air–sea interface using a specially constructed Air–Sea Interaction Tower (ASIT), and quantification of regional oceanic variability over scales of O (1–104 mm) using a mesoscale mooring array, aircraft-borne remote sensors, drifters, and ship surveys. To our knowledge, the former represents the first successful attempt to directly and simultaneously measure the heat and momentum exchange on both sides of the air–sea interface. The latter provided a 3D picture of the oceanic boundary layer during the month-long main experiment. These observations have been combined with numerical models and direct numerical and large-eddy simulations to investigate the processes that couple the atmosphere and ocean under these conditions. For example, the oceanic measurements have been used in the Regional Ocean Modeling System (ROMS) to investigate the 3D evolution of regional ocean thermal stratification. The ultimate goal of these investigations is to incorporate improved parameterizations of these processes in coupled models such as the Coupled Ocean–Atmosphere Mesoscale Prediction System (COAMPS) to improve marine forecasts of wind, waves, and currents.This work was supported by the Office of Naval Research

Genome-Wide Functional Profiling Reveals Genes Required for Tolerance to Benzene Metabolites in Yeast

Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to benzene causes a number of serious health problems, including blood disorders and leukemia. Benzene undergoes complex metabolism in humans, making mechanistic determination of benzene toxicity difficult. We used a functional genomics approach to identify the genes that modulate the cellular toxicity of three of the phenolic metabolites of benzene, hydroquinone (HQ), catechol (CAT) and 1,2,4-benzenetriol (BT), in the model eukaryote Saccharomyces cerevisiae. Benzene metabolites generate oxidative and cytoskeletal stress, and tolerance requires correct regulation of iron homeostasis and the vacuolar ATPase. We have identified a conserved bZIP transcription factor, Yap3p, as important for a HQ-specific response pathway, as well as two genes that encode putative NAD(P)H:quinone oxidoreductases, PST2 and YCP4. Many of the yeast genes identified have human orthologs that may modulate human benzene toxicity in a similar manner and could play a role in benzene exposure-related disease

The Coupled Boundary Layers and Air–Sea Transfer Experiment in Low Winds

The Office of Naval Research's Coupled Boundary Layers and Air–Sea Transfer (CBLAST) program is being conducted to investigate the processes that couple the marine boundary layers and govern the exchange of heat, mass, and momentum across the air–sea interface. CBLAST-LOW was designed to investigate these processes at the low-wind extreme where the processes are often driven or strongly modulated by buoyant forcing. The focus was on conditions ranging from negligible wind stress, where buoyant forcing dominates, up to wind speeds where wave breaking and Langmuir circulations play a significant role in the exchange processes. The field program provided observations from a suite of platforms deployed in the coastal ocean south of Martha's Vineyard. Highlights from the measurement campaigns include direct measurement of the momentum and heat fluxes on both sides of the air–sea interface using a specially constructed Air–Sea Interaction Tower (ASIT), and quantification of regional oceanic variability over scales of O (1–104 mm) using a mesoscale mooring array, aircraft-borne remote sensors, drifters, and ship surveys. To our knowledge, the former represents the first successful attempt to directly and simultaneously measure the heat and momentum exchange on both sides of the air–sea interface. The latter provided a 3D picture of the oceanic boundary layer during the month-long main experiment. These observations have been combined with numerical models and direct numerical and large-eddy simulations to investigate the processes that couple the atmosphere and ocean under these conditions. For example, the oceanic measurements have been used in the Regional Ocean Modeling System (ROMS) to investigate the 3D evolution of regional ocean thermal stratification. The ultimate goal of these investigations is to incorporate improved parameterizations of these processes in coupled models such as the Coupled Ocean–Atmosphere Mesoscale Prediction System (COAMPS) to improve marine forecasts of wind, waves, and currents

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

The coupled boundary layers and air-sea transfer experiment in low winds (CBLAST-LOW)

Bull. American Mereorol. Soc., Vol. 88, 3, 341-356.The article of record as published may be located at http://dx.doi.org/10.1175/BAMS-88-3-341Observations from a suite of platforms deployed in the coastal ocean are being combined with numerical models and simulations to investigate the processes that couple the atmosphere and ocean

Impacts of a population-based prostate cancer screening programme on excess total mortality rates in men with prostate cancer:a randomized controlled trial

<p>Objectives To assess the effect of screening in terms of excess mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC).</p><p>Methods A total of 141,578 men aged 55-69 were randomized to systematic screening or usual care in ERSPC sections in Finland, Italy, the Netherlands and Sweden. The excess number of deaths was defined as the difference between the observed number of deaths in the prostate cancer (PC) patients and the expected number of deaths up to 31 December 2006. The expected number was derived from mortality of all study participants before a diagnosis with PC adjusted for study centre, study arm and study attendance. The excess mortality rates were compared between the two study arms.</p><p>Results The PC incidence was 9.25 per 1000 person-years in the intervention arm and 5.49 per 1000 person-years in the control arm, relative risk (RR) 1.69 (95% confidence interval [CI] 1.62-1.76). The excess mortality among men with PC was 0.29 per 1000 person-years in the intervention arm and 0.37 per 1000 person-years in the control arm; the RR for excess mortality was 0.77 (95% CI 0.55-1.08). The absolute risk reduction in the excess mortality was 0.08 per 1000 person-years. The overall mortality was not significantly different between the intervention and the control arms of the study: RR 0.99 (95% CI 0.96-1.01).</p><p>Conclusions Although the reduction in excess mortality was not statistically significant, the between-arm reduction in excess mortality rate was in line with the previously reported 20% reduction in the disease-specific mortality. This finding indicates that the reduction in PC mortality in the ERSPC trial cannot be due to a bias in cause of death adjudication.</p>

Absolute effect of prostate cancer screening: balance of benefits and harms by center within the European randomized study of prostate cancer screening

PURPOSE The balance of benefits and harms in prostate cancer screening has not been sufficiently characterized. We related indicators of mortality reduction and overdetection by center within the European Randomized Study of Prostate Cancer Screening (ERSPC). EXPERIMENTAL DESIGN We analyzed the absolute mortality reduction expressed as number needed to invite (NNI = 1/absolute risk reduction; indicating how many men had to be randomized to screening arm to avert a prostate cancer death) for screening and the absolute excess of prostate cancer detection as number needed for overdetection (NNO = 1/absolute excess incidence; indicating the number of men invited per additional prostate cancer case), and compared their relationship across the seven ERSPC centers. RESULTS Both absolute mortality reduction (NNI) and absolute overdetection (NNO) varied widely between the centers: NNI, 200-7,000 and NNO, 16-69. Extent of overdiagnosis and mortality reduction was closely associated [correlation coefficient, r = 0.76; weighted linear regression coefficient, β = 33; 95% confidence interval (CI), 5-62; R (2) = 0.72]. For an averted prostate cancer death at 13 years of follow-up, 12 to 36 excess cases had to be detected in various centers. CONCLUSIONS The differences between the ERSPC centers likely reflect variations in prostate cancer incidence and mortality, as well as in screening protocol and performance. The strong interrelation between the benefits and harms suggests that efforts to maximize the mortality effect are bound to increase overdiagnosis and might be improved by focusing on high-risk populations. The optimal balance between screening intensity and risk of overdiagnosis remains unclear. Clin Cancer Res; 1-7. ©2015 AACR