Abstract
We present the star cluster catalogues for 17 dwarf and irregular galaxies in the HST Treasury Program ‘Legacy ExtraGalactic UV Survey’ (LEGUS). Cluster identification and photometry in this ...sub-sample are similar to that of the entire LEGUS sample, but special methods were developed to provide robust catalogues with accurate fluxes due to low cluster statistics. The colours and ages are largely consistent for two widely used aperture corrections, but a significant fraction of the clusters are more compact than the average training cluster. However, the ensemble luminosity, mass, and age distributions are consistent suggesting that the systematics between the two methods are less than the random errors. When compared with the clusters from previous dwarf galaxy samples, we find that the LEGUS catalogues are more complete and provide more accurate total fluxes. Combining all clusters into a composite dwarf galaxy, we find that the luminosity and mass functions can be described by a power law with the canonical index of −2 independent of age and global SFR binning. The age distribution declines as a power law, with an index of ≈− 0.80 ± 0.15, independent of cluster mass and global SFR binning. This decline of clusters is dominated by cluster disruption since the combined star formation histories and integrated-light SFRs are both approximately constant over the last few hundred Myr. Finally, we find little evidence for an upper-mass cut-off (<2σ) in the composite cluster mass function, and can rule out a truncation mass below ≈104.5M⊙ but cannot rule out the existence of a truncation at higher masses.
Ninety per cent of marine organic matter burial occurs in continental margin sediments, where a substantial fraction of organic carbon escapes oxidation and enters long-term geologic storage within ...sedimentary rocks. In such environments, microbial metabolism is limited by the diffusive supply of electron acceptors. One strategy to optimize energy yields in a resource-limited habitat is symbiotic metabolite exchange among microbial associations. Thermodynamic and geochemical considerations indicate that microbial co-metabolisms are likely to play a critical part in sedimentary organic carbon cycling. Yet only one association, between methanotrophic archaea and sulphate-reducing bacteria, has been demonstrated in marine sediments in situ, and little is known of the role of microbial symbiotic interactions in other sedimentary biogeochemical cycles. Here we report in situ molecular and incubation-based evidence for a novel symbiotic consortium between two chemolithotrophic bacteria--anaerobic ammonium-oxidizing (anammox) bacteria and the nitrate-sequestering sulphur-oxidizing Thioploca species--in anoxic sediments of the Soledad basin at the Mexican Pacific margin. A mass balance of benthic solute fluxes and the corresponding nitrogen isotope composition of nitrate and ammonium fluxes indicate that anammox bacteria rely on Thioploca species for the supply of metabolic substrates and account for about 57 ± 21 per cent of the total benthic N2 production. We show that Thioploca-anammox symbiosis intensifies benthic fixed nitrogen losses in anoxic sediments, bypassing diffusion-imposed limitations by efficiently coupling the carbon, nitrogen and sulphur cycles.
Patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA alterations have poor outcomes. MAGNITUDE found patients with homologous recombination repair gene alterations (HRR+), ...particularly BRCA1/2, benefit from first-line therapy with niraparib plus abiraterone acetate and prednisone (AAP). Here we report longer follow-up from the second prespecified interim analysis (IA2).
Patients with mCRPC were prospectively identified as HRR+ with/without BRCA1/2 alterations and randomized 1 : 1 to niraparib (200 mg orally) plus AAP (1000 mg/10 mg orally) or placebo plus AAP. At IA2, secondary endpoints time to symptomatic progression, time to initiation of cytotoxic chemotherapy, overall survival (OS) were assessed.
Overall, 212 HRR+ patients received niraparib plus AAP (BRCA1/2 subgroup, n = 113). At IA2 with 24.8 months of median follow-up in the BRCA1/2 subgroup, niraparib plus AAP significantly prolonged radiographic progression-free survival {rPFS; blinded independent central review; median rPFS 19.5 versus 10.9 months; hazard ratio (HR) = 0.55 95% confidence interval (CI) 0.39-0.78; nominal P = 0.0007} consistent with the first prespecified interim analysis. rPFS was also prolonged in the total HRR+ population HR = 0.76 (95% CI 0.60-0.97); nominal P = 0.0280; median follow-up 26.8 months. Improvements in time to symptomatic progression and time to initiation of cytotoxic chemotherapy were observed with niraparib plus AAP. In the BRCA1/2 subgroup, the analysis of OS with niraparib plus AAP demonstrated an HR of 0.88 (95% CI 0.58-1.34; nominal P = 0.5505); the prespecified inverse probability censoring weighting analysis of OS, accounting for imbalances in subsequent use of poly adenosine diphosphate-ribose polymerase inhibitors and other life-prolonging therapies, demonstrated an HR of 0.54 (95% CI 0.33-0.90; nominal P = 0.0181). No new safety signals were observed.
MAGNITUDE, enrolling the largest BRCA1/2 cohort in first-line mCRPC to date, demonstrated improved rPFS and other clinically relevant outcomes with niraparib plus AAP in patients with BRCA1/2-altered mCRPC, emphasizing the importance of identifying this molecular subset of patients.
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•Niraparib + AAP reduced risk of radiographic progression/death by 45% in BRCA1/2-altered mCRPC (median follow-up 24.8 mo).•Niraparib + AAP improved secondary endpoints and patient-reported outcomes in the BRCA1/2 subgroup.•Adverse events of niraparib + AAP were tolerable, manageable, and consistent with previous reports; no new safety signals.•MAGNITUDE second interim analysis continues to support niraparib + AAP for mCRPC and HRR alterations, especially BRCA1/2.•MAGNITUDE supports genomic testing for BRCA1/2 alterations in mCRPC due to poor outcomes and emerging treatment options.
The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced ...prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged.
Viral diseases (such as TSV) in shrimp (top left), diseases of juvenile crustaceans (top right), syndromic conditions such as Epizootic Shell Disease of lobsters (bottom left) and protistan pathogen ...outbreaks in aquaculture of new species (bottom right) pose significant barriers to food production from the crustacean sector. Display omitted
► Disease is a major limiting factor on food production from crustacean fisheries and aquaculture. ► Global population increases place further pressure on creating sustainability in the sector. ► Control strategies are limited to efficient biosecurity and good management practices. ► Research focus on disease mitigation, best practice and improved supply chains required.
Seafood is a highly traded food commodity. Farmed and captured crustaceans contribute a significant proportion with annual production exceeding 10M metric tonnes with first sale value of $40bn. The sector is dominated by farmed tropical marine shrimp, the fastest growing sector of the global aquaculture industry. It is significant in supporting rural livelihoods and alleviating poverty in producing nations within Asia and Latin America while forming an increasing contribution to aquatic food supply in more developed countries. Nations with marine borders often also support important marine fisheries for crustaceans that are regionally traded as live animals and commodity products. A general separation of net producing and net consuming nations for crustacean seafood has created a truly globalised food industry. Projections for increasing global demand for seafood in the face of level or declining fisheries requires continued expansion and intensification of aquaculture while ensuring best utilisation of captured stocks. Furthermore, continued pressure from consuming nations to ensure safe products for human consumption are being augmented by additional legislative requirements for animals (and their products) to be of low disease status. As a consequence, increasing emphasis is being placed on enforcement of regulations and better governance of the sector; currently this is a challenge in light of a fragmented industry and less stringent regulations associated with animal disease within producer nations. Current estimates predict that up to 40% of tropical shrimp production (>$3bn) is lost annually, mainly due to viral pathogens for which standard preventative measures (e.g. such as vaccination) are not feasible. In light of this problem, new approaches are urgently required to enhance yield by improving broodstock and larval sourcing, promoting best management practices by farmer outreach and supporting cutting-edge research that aims to harness the natural abilities of invertebrates to mitigate assault from pathogens (e.g. the use of RNA interference therapeutics). In terms of fisheries losses associated with disease, key issues are centred on mortality and quality degradation in the post-capture phase, largely due to poor grading and handling by fishers and the industry chain. Occurrence of disease in wild crustaceans is also widely reported, with some indications that climatic changes may be increasing susceptibility to important pathogens (e.g. the parasite Hematodinium). However, despite improvements in field and laboratory diagnostics, defining population-level effects of disease in these fisheries remains elusive. Coordination of disease specialists with fisheries scientists will be required to understand current and future impacts of existing and emergent diseases on wild stocks. Overall, the increasing demand for crustacean seafood in light of these issues signals a clear warning for the future sustainability of this global industry. The linking together of global experts in the culture, capture and trading of crustaceans with pathologists, epidemiologists, ecologists, therapeutics specialists and policy makers in the field of food security will allow these issues to be better identified and addressed.
We have studied similar to 2100 early-type galaxies in the SDSS DR3 which have been detected by the GALEX Medium Imaging Survey (MIS), in the redshift range 0 < z < 0.11. Combining GALEX UV ...photometry with corollary optical data from the SDSS, we find that, at a 95% confidence level, at least similar to 30% of galaxies in this sample have UV to optical colors consistent with some recent star formation within the last Gyr. In particular, galaxies with an NUV - r color less than 5.5 are very likely to have experienced such recent star formation, taking into account the possibility of a contribution to NUV flux from the UV upturn phenomenon. We find quantitative agreement between the observations and the predictions of a semianalytical Lambda CDM hierarchical merger model and deduce that early-type galaxies in the redshift range 0 < z < 0.11 have similar to 1%-3% of their stellar mass in stars less than 1 Gyr old. The average age of this recently formed population is similar to 300-500 Myr. We also find that "monolithically" evolving galaxies, where recent star formation can be driven solely by recycled gas from stellar mass loss, cannot exhibit the blue colors (NUV - r < 5.5) seen in a significant fraction ( similar to 30%) of our observed sample.
In the SPARTAN study, compared with placebo, apalutamide added to ongoing androgen deprivation therapy significantly prolonged metastasis-free survival (MFS) and time to symptomatic progression in ...patients with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC). Overall survival (OS) results at the first interim analysis (IA1) were immature, with 104 of 427 (24%) events required for planned final OS analysis. Here, we report the results of a second pre-specified interim analysis (IA2).
One thousand two hundred and seven patients with nmCRPC were randomized 2-:-1 to apalutamide (240-mg daily) or placebo. The primary end point of the study was MFS. Subsequent therapy for metastatic CRPC was permitted. When the primary end point was met, the study was unblinded. Patients receiving placebo who had not yet developed metastases were offered open-label apalutamide. At IA2, pre-specified analysis of OS was undertaken, using a group-sequential testing procedure with O’Brien–Fleming-type alpha spending function. Safety and second progression-free survival (PFS2) were assessed.
Median follow-up was 41-months. With 285 (67% of required) OS events, apalutamide was associated with an improved OS compared with placebo (HR 0.75; 95% CI 0.59–0.96; P-=-0.0197), although the P-value did not cross the pre-specified O’Brien–Fleming boundary of 0.0121. Apalutamide improved PFS2 (HR 0.55; 95% CI 0.45–0.68). At IA2, 69% of placebo-treated and 40% of apalutamide-treated patients had received subsequent life-prolonging therapy for metastatic CRPC. No new safety signals were observed.
In patients with nmCRPC, apalutamide was associated with a 25% reduction in risk of death compared with placebo. This OS benefit was observed despite crossover of placebo-treated patients and higher rates of subsequent life-prolonging therapy for the placebo group.
To investigate whether effects on food intake are seen in obese subjects receiving exogenous administration of ghrelin.
Randomised, double-blind, placebo-controlled study of intravenous ghrelin at ...doses 1 pmol/kg/min and 5 pmol/kg/min.
In all, 12 healthy lean subjects (mean body mass index (BMI) 20.5+/-0.17 kg/m(2)) and 12 healthy overweight and obese subjects (mean BMI 31.9+/-1.02 kg/m(2)).
Food intake, appetite and palatability of food, ghrelin and other obesity-related hormones, growth hormone.
Low-dose infusion of ghrelin increased ad libitum energy intake at a buffet meal in the obese group only (mean increase 36.6+/-9.4%, P<0.01.) High-dose ghrelin infusion increased energy intake in both groups (mean increase 20.1+/-10.6% in the lean and 70.1+/-15.5% in the obese, P<0.01 in both cases.) Ghrelin infusion increased palatability of food in the obese group.
Ghrelin increases food intake in obese as well as lean subjects. Obese people are sensitive to the appetite-stimulating effects of ghrelin and inhibition of circulating ghrelin may be a useful therapeutic target in the treatment of obesity.
Recent years have seen several advances in the treatment of locally advanced and metastatic bladder cancer. We summarize the current state of the art for advanced bladder cancer treatment.
A ...comprehensive review of published, prospective phase II/III clinical trials and retrospective analyses of patients with advanced bladder cancer was performed.
Adjuvant and neoadjuvant chemotherapeutic strategies around the time of radical cystectomy have been used to decrease the risk of subsequent metastatic disease. Although the benefit of adjuvant chemotherapy remains unproven, neoadjuvant chemotherapy is associated with a modest 5% to 6% absolute survival benefit in 2 meta-analyses of the available data. Chemoradiation is feasible and effective in some patients, allowing bladder preservation with an acceptable risk of progression. Randomized, phase III data comparing methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy to gemcitabine/cisplatin showed similar response proportions and overall survival with less toxicity in the gemcitabine/cisplatin arm. This has led to the widespread use of gemcitabine/cisplatin as first line chemotherapy for metastatic bladder cancer. The optimal agents and regimens for second line chemotherapy remain undefined. Similarly biological and targeted therapies for advanced bladder cancer remain investigational.
Combination cisplatin based neoadjuvant chemotherapy may benefit patients with locally advanced bladder cancer. Gemcitabine/cisplatin has replaced methotrexate, vinblastine, doxorubicin and cisplatin as the regimen of choice in patients with good renal function. The optimal regimens for the medically unfit patient and second line chemotherapy remain undefined. The development of targeted therapies, less toxic regimens and improved cytotoxic agents are necessary to improve outcomes.
BACKGROUND AND PURPOSEMultidetector CT has emerged as the standard of care imaging technique to evaluate cervical spine trauma. Our aim was to evaluate the performance of a convolutional neural ...network in the detection of cervical spine fractures on CT. MATERIALS AND METHODSWe evaluated C-spine, an FDA-approved convolutional neural network developed by Aidoc to detect cervical spine fractures on CT. A total of 665 examinations were included in our analysis. Ground truth was established by retrospective visualization of a fracture on CT by using all available CT, MR imaging, and convolutional neural network output information. The ĸ coefficients, sensitivity, specificity, and positive and negative predictive values were calculated with 95% CIs comparing diagnostic accuracy and agreement of the convolutional neural network and radiologist ratings, respectively, compared with ground truth. RESULTSConvolutional neural network accuracy in cervical spine fracture detection was 92% (95% CI, 90%-94%), with 76% (95% CI, 68%-83%) sensitivity and 97% (95% CI, 95%-98%) specificity. The radiologist accuracy was 95% (95% CI, 94%-97%), with 93% (95% CI, 88%-97%) sensitivity and 96% (95% CI, 94%-98%) specificity. Fractures missed by the convolutional neural network and by radiologists were similar by level and location and included fractured anterior osteophytes, transverse processes, and spinous processes, as well as lower cervical spine fractures that are often obscured by CT beam attenuation. CONCLUSIONSThe convolutional neural network holds promise at both worklist prioritization and assisting radiologists in cervical spine fracture detection on CT. Understanding the strengths and weaknesses of the convolutional neural network is essential before its successful incorporation into clinical practice. Further refinements in sensitivity will improve convolutional neural network diagnostic utility.
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