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Wind-driven upwelling in the ocean around Antarctica helps regulate the exchange of carbon dioxide (CO2) between the deep sea and the atmosphere, as well as the supply of dissolved silicon to the euphotic zone of the Southern Ocean. Diatom productivity south of the Antarctic Polar Front and the subsequent burial of biogenic opal in underlying sediments are limited by this silicon supply. We show that opal burial rates, and thus upwelling, were enhanced during the termination of the last ice age in each sector of the Southern Ocean. In the record with the greatest temporal resolution, we find evidence for two intervals of enhanced upwelling concurrent with the two intervals of rising atmospheric CO2 during deglaciation. These results directly link increased ventilation of deep water to the deglacial rise in atmospheric CO2.

Core isotope measurements in the equatorial Pacific Ocean reveal that although atmospheric dust deposition during the last ice age was higher than today’s, the productivity of the equatorial Pacific Ocean did not increase; this may have been because iron-enabled greater nutrient consumption, mainly in the Southern Ocean, reduced the nutrients available in the equatorial Pacific Ocean, and hence also productivity there. The equatorial Pacific Ocean is one of the major high-nutrient, low-chlorophyll regions in the global ocean. In such regions, the consumption of the available macro-nutrients such as nitrate and phosphate is thought to be limited in part by the low abundance of the critical micro-nutrient iron 1 . Greater atmospheric dust deposition 2 could have fertilized the equatorial Pacific with iron during the last ice age—the Last Glacial Period (LGP)—but the effect of increased ice-age dust fluxes on primary productivity in the equatorial Pacific remains uncertain 3 , 4 , 5 , 6 . Here we present meridional transects of dust (derived from the 232 Th proxy), phytoplankton productivity (using opal, 231 Pa/ 230 Th and excess Ba), and the degree of nitrate consumption (using foraminifera-bound δ 15 N) from six cores in the central equatorial Pacific for the Holocene (0–10,000 years ago) and the LGP (17,000–27,000 years ago). We find that, although dust deposition in the central equatorial Pacific was two to three times greater in the LGP than in the Holocene, productivity was the same or lower, and the degree of nitrate consumption was the same. These biogeochemical findings suggest that the relatively greater ice-age dust fluxes were not large enough to provide substantial iron fertilization to the central equatorial Pacific. This may have been because the absolute rate of dust deposition in the LGP (although greater than the Holocene rate) was very low. The lower productivity coupled with unchanged nitrate consumption suggests that the subsurface major nutrient concentrations were lower in the central equatorial Pacific during the LGP. As these nutrients are today dominantly sourced from the Subantarctic Zone of the Southern Ocean, we propose that the central equatorial Pacific data are consistent with more nutrient consumption in the Subantarctic Zone, possibly owing to iron fertilization as a result of higher absolute dust fluxes in this region 7 , 8 . Thus, ice-age iron fertilization in the Subantarctic Zone would have ultimately worked to lower, not raise, equatorial Pacific productivity.

Deposition of continental mineral aerosols (dust) in the Eastern Tropical North Atlantic Ocean, between the coast of Africa and the Mid-Atlantic Ridge, was estimated using several strategies based on the measurement of aerosols, trace metals dissolved in seawater, particulate material filtered from the water column, particles collected by sediment traps and sediments. Most of the data used in this synthesis involve samples collected during US GEOTRACES expeditions in 2010 and 2011, although some results from the literature are also used. Dust deposition generated by a global model serves as a reference against which the results from each observational strategy are compared. Observation-based dust fluxes disagree with one another by as much as two orders of magnitude, although most of the methods produce results that are consistent with the reference model to within a factor of 5. The large range of estimates indicates that further work is needed to reduce uncertainties associated with each method before it can be applied routinely to map dust deposition to the ocean. Calculated dust deposition using observational strategies thought to have the smallest uncertainties is lower than the reference model by a factor of 2–5, suggesting that the model may overestimate dust deposition in our study area. This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’.

The emotional, social, and psychological needs of retired men are often overlooked in favor of their medical and financial needs. This book paints a picture of what successful retirement and aging can look like for any man, no matter his age, position, talents, or challenges.

This study explored the economic costs and response rate of mail and web-based surveys with practicing dentists. A random sample of 6,000 practicing dentists was randomly assigned into three groups of 2,000: choice (mail or web-based), postal mail, or web-based. The Florida Tobacco Control Survey 2009, which is composed of 28 questions (including subject demographic questions), served as the survey instrument. A total of 1,232 surveys were returned by the three different groups (21% overall response rate). Response rates were best for the mail (26%) with the worst response rate coming from the Web group (11%). However, a cost-effectiveness analysis revealed that web surveys were 2.68 times more cost effective.

A possible imprint on equatorial Pacific sediments of a deglacial reinvigoration of the Southern Ocean overturning is increased opal accumulation rate. This would arise from the transmission of silica-rich deep water to the equatorial thermocline via Subantarctic Mode Water and an associated increase in diatom productivity. In search of this imprint, sediment cores from the central (TT013-PC72) and eastern (V19-30) equatorial Pacific have been analyzed for 230Th-normalized opal accumulation rates over the past five and three glacial terminations, respectively. Equatorial opal accumulation rates sustained relatively low values over much of the records and were punctuated by large increases centered on some terminations, but not all. Furthermore, two periods of increased opal flux were observed that do not coincide with terminations. Sources other than the Southern Ocean may need to be considered in the silica budget of the equatorial Pacific, but the 13C of Neogloboquadrina dutertrei can be used to support the presence of a deepwater nutrient signal in each case. Although a common deglacial mechanism, or a common imprint thereof, for each of the late Pleistocene glaciations remains elusive, the combination of opal flux and 13C of N. dutertrei provides a diagnostic for past injection of deepwater nutrients into the Equatorial Undercurrent.

MDV3100 is an androgen-receptor antagonist that blocks androgens from binding to the androgen receptor and prevents nuclear translocation and co-activator recruitment of the ligand-receptor complex. It also induces tumour cell apoptosis, and has no agonist activity. Because growth of castration-resistant prostate cancer is dependent on continued androgen-receptor signalling, we assessed the antitumour activity and safety of MDV3100 in men with this disease. This phase 1–2 study was undertaken in five US centres in 140 patients. Patients with progressive, metastatic, castration-resistant prostate cancer were enrolled in dose-escalation cohorts of three to six patients and given an oral daily starting dose of MDV3100 30 mg. The final daily doses studied were 30 mg (n=3), 60 mg (27), 150 mg (28), 240 mg (29), 360 mg (28), 480 mg (22), and 600 mg (3). The primary objective was to identify the safety and tolerability profile of MDV3100 and to establish the maximum tolerated dose. The trial is registered with ClinicalTrials.gov, number NCT00510718. We noted antitumour effects at all doses, including decreases in serum prostate-specific antigen of 50% or more in 78 (56%) patients, responses in soft tissue in 13 (22%) of 59 patients, stabilised bone disease in 61 (56%) of 109 patients, and conversion from unfavourable to favourable circulating tumour cell counts in 25 (49%) of the 51 patients. PET imaging of 22 patients to assess androgen-receptor blockade showed decreased 18F-fluoro-5α-dihydrotestosterone binding at doses from 60 mg to 480 mg per day (range 20–100%). The median time to progression was 47 weeks (95% CI 34–not reached) for radiological progression. The maximum tolerated dose for sustained treatment (>28 days) was 240 mg. The most common grade 3–4 adverse event was dose-dependent fatigue (16 [11%] patients), which generally resolved after dose reduction. We recorded encouraging antitumour activity with MDV3100 in patients with castration-resistant prostate cancer. The results of this phase 1–2 trial validate in man preclinical studies implicating sustained androgen-receptor signalling as a driver in this disease. Medivation, the Prostate Cancer Foundation, National Cancer Institute, the Howard Hughes Medical Institute, Doris Duke Charitable Foundation, and Department of Defense Prostate Cancer Clinical Trials Consortium.

Summary The health effects of bathing in coastal waters is an area of scientific controversy. We conducted the first ever randomised \"trial\" of an environmental exposure to measure the health effects of this activity. The trial was spread over four summers in four UK resorts and 1216 adults took part. Detailed interviews were used to collect data on potential confounding factors and intensive water quality monitoring was used to provide more precise indices of exposure. 548 people were randomised to bathing, and the exposure included total immersion of the head. Crude rates of gastroenteritis were significantly higher in the exposed group (14·8 per 100) than the unexposed group (9·7 per 100; p=0·01). Linear trend and multiple logistic regression techniques were used to establish relations between gastroenteritis and microbiological water quality. Of a range of microbiological indicators assayed only faecal streptococci concentration, measured at chest depth, showed a significant dose-response relation with gastroenteritis. Adverse health effects were identified when faecal streptococci concentrations exceeded 32 per 100 mL. This relation was independent of non-water-related predictors of gastroenteritis. We do not suggest that faecal streptococci caused the excess of gastrointestinal symptoms in sea bathers but these microorganisms do seem to be a better indicator of water quality than the traditional coliform counts. Bathing water standards should be revised with these findings in mind.

We propose a new methodology to estimate empirically the input price-induced technical change and total factor productivity (TFP) growth in China. Our primary goal is to test Hicks’ induced innovation hypothesis by examining whether technical change in China has been induced by sharp increase in input prices that have accompanied its rapid economic growth. Utilizing the idea of a firm’s two-stage optimization problem, we develop a new parametric form of the variable profit function wherein the derived input demand and output supply functions can be easily constrained to be regular, and the functional structure is parsimonious in the number of parameters. Applying this methodology to Chinese time series data for 1986–2017, we find that not only is wage-induced innovation significant and quantitatively important, but also that it substantially buffered a decline in TFP growth before 2006 that would otherwise be substantial. Overall, we conclude that China’s economic growth is predominantly driven by wage-induced innovation along with massive injection of heavily subsidized physical inputs in public works and huge investment in industrial sectors.

OBJECTIVES: This study identified possible dose-response relationships among bathers exposed to marine waters contaminated with domestic sewage and subsequent risk of nonenteric illness. METHODS: Four intervention follow-up studies were conducted within the United Kingdom. Healthy volunteers (n = 1273) were randomized into bather and nonbather groups. Intensive water-quality monitoring was used to assign five bacteriological indices of water quality to individual bathers. Illnesses studied were acute febrile respiratory illness, and eye, ear, and skin ailments. RESULTS: Fecal streptococci exposure was predictive of acute febrile respiratory illness, while fecal coliform exposure was predictive of ear ailments. Estimated thresholds of effect occurred at bather exposures above 60 fecal streptococci and 100 fecal coliform per 100 ml of water, respectively. Although no relationship was found between eye ailments and indicator organism exposure, compared with nonbathers, bathers were at higher risk for eye ailments. CONCLUSIONS: Nonenteric illness can be transmitted via recreational contact with marine waters contaminated with sewage. These results argue against the use of a single indicator to establish water quality standards.