By exploiting the computing power and local data of distributed clients, federated learning (FL) features ubiquitous properties such as reduction of communication overhead and preserving data ...privacy. In each communication round of FL, the clients update local models based on their own data and upload their local updates via wireless channels. However, latency caused by hundreds to thousands of communication rounds remains a bottleneck in FL. To minimize the training latency, this work provides a multi-armed bandit-based framework for online client scheduling (CS) in FL without knowing wireless channel state information and statistical characteristics of clients. Firstly, we propose a CS algorithm based on the upper confidence bound policy (CS-UCB) for ideal scenarios where local datasets of clients are independent and identically distributed (i.i.d.) and balanced. An upper bound of the expected performance regret of the proposed CS-UCB algorithm is provided, which indicates that the regret grows logarithmically over communication rounds. Then, to address non-ideal scenarios with non-i.i.d. and unbalanced properties of local datasets and varying availability of clients, we further propose a CS algorithm based on the UCB policy and virtual queue technique (CS-UCB-Q). An upper bound is also derived, which shows that the expected performance regret of the proposed CS-UCB-Q algorithm can have a sub-linear growth over communication rounds under certain conditions. Besides, the convergence performance of FL training is also analyzed. Finally, simulation results validate the efficiency of the proposed algorithms.
Victory and defeat, love and loss are the prevalent realities of Letters from the Greatest Generation, a remarkable and frank collection of World War II letters penned by American men and women ...serving overseas. Here, the hopes and dreams of the greatest generation fill each page, and their voices ring loud and clear. "It's all part of the game but it's bloody and rough," wrote one soldier to his wife. "Wearing two stripes now and as proud as an old cat with five kittens," marked another. Yet, as many countries rejoiced on V-E Day, soldiers were "too tired and sad to celebrate." While visiting a German concentration camp, one man wrote, "I don't like Army life but I'm glad we are here to stop these atrocities." True to the everyday thoughts of these fighters, this collection of letters can be as amusing as it is worrying. As one soldier noted, "I know lice don't crawl so I figured they were fleas." A fitting tribute to all veterans, this book is one every American should own and read.
Omnivores can dampen trophic cascades by feeding at multiple trophic levels, yet few studies have evaluated how intraspecific variation of omnivores influences community structure. The speckled dace ...(
Rhinichthys osculus
) is a common and omnivorous minnow that consumes algae and invertebrates. We studied effects of size and size structure on top-down control by dace and how effects scaled with density. Dace were manipulated in a mesocosm experiment and changes in invertebrate and algal communities and ecosystem function were monitored. Omnivores affected experimental communities via two distinct trophic pathways (benthic and pelagic). In the benthic pathway, dace reduced macroinvertebrate biomass, thereby causing density-mediated indirect effects that led to increased benthic algal biomass. Dace also reduced pelagic predatory macroinvertebrate biomass (hemipterans), thereby increasing the abundance of emerging insects. The effect of dace and hemipterans on emerging insects was mediated by a non-linear response to dace with peak emergence at intermediate dace density. In contrast with recent studies, omnivore size and size structure had no clear effect, indicating that small and large dace in our experiment shared similar functional roles. Our results support that the degree to which omnivores dampen trophic cascades depends on their relative effect on multiple trophic levels, such that the more omnivorous a predator is, the more likely cascades will be dampened. Availability of abundant macroinvertebrates, and the absence of top predators, may have shifted dace diets from primary to secondary consumption, strengthening density-dependent trophic cascades. Both omnivore density and dietary shifts are important factors influencing omnivore-mediated communities.
Summary Alzheimer's disease (AD) is classically defined as a dual clinicopathological entity. The recent advances in use of reliable biomarkers of AD that provide in-vivo evidence of the disease has ...stimulated the development of new research criteria that reconceptualise the diagnosis around both a specific pattern of cognitive changes and structural/biological evidence of Alzheimer's pathology. This new diagnostic framework has stimulated debate about the definition of AD and related conditions. The potential for drugs to intercede in the pathogenic cascade of the disease adds some urgency to this debate. This paper by the International Working Group for New Research Criteria for the Diagnosis of AD aims to advance the scientific discussion by providing broader diagnostic coverage of the AD clinical spectrum and by proposing a common lexicon as a point of reference for the clinical and research communities. The cornerstone of this lexicon is to consider AD solely as a clinical and symptomatic entity that encompasses both predementia and dementia phases.
Objective To compare the efficacy, safety, and cost effectiveness of direct acting oral anticoagulants (DOACs) for patients with atrial fibrillation.Design Systematic review, network meta-analysis, ...and cost effectiveness analysis. Data sources Medline, PreMedline, Embase, and The Cochrane Library.Eligibility criteria for selecting studies Published randomised trials evaluating the use of a DOAC, vitamin K antagonist, or antiplatelet drug for prevention of stroke in patients with atrial fibrillation.Results 23 randomised trials involving 94 656 patients were analysed: 13 compared a DOAC with warfarin dosed to achieve a target INR of 2.0-3.0. Apixaban 5 mg twice daily (odds ratio 0.79, 95% confidence interval 0.66 to 0.94), dabigatran 150 mg twice daily (0.65, 0.52 to 0.81), edoxaban 60 mg once daily (0.86, 0.74 to 1.01), and rivaroxaban 20 mg once daily (0.88, 0.74 to 1.03) reduced the risk of stroke or systemic embolism compared with warfarin. The risk of stroke or systemic embolism was higher with edoxaban 60 mg once daily (1.33, 1.02 to 1.75) and rivaroxaban 20 mg once daily (1.35, 1.03 to 1.78) than with dabigatran 150 mg twice daily. The risk of all-cause mortality was lower with all DOACs than with warfarin. Apixaban 5 mg twice daily (0.71, 0.61 to 0.81), dabigatran 110 mg twice daily (0.80, 0.69 to 0.93), edoxaban 30 mg once daily (0.46, 0.40 to 0.54), and edoxaban 60 mg once daily (0.78, 0.69 to 0.90) reduced the risk of major bleeding compared with warfarin. The risk of major bleeding was higher with dabigatran 150 mg twice daily than apixaban 5 mg twice daily (1.33, 1.09 to 1.62), rivaroxaban 20 mg twice daily than apixaban 5 mg twice daily (1.45, 1.19 to 1.78), and rivaroxaban 20 mg twice daily than edoxaban 60 mg once daily (1.31, 1.07 to 1.59). The risk of intracranial bleeding was substantially lower for most DOACs compared with warfarin, whereas the risk of gastrointestinal bleeding was higher with some DOACs than warfarin. Apixaban 5 mg twice daily was ranked the highest for most outcomes, and was cost effective compared with warfarin.Conclusions The network meta-analysis informs the choice of DOACs for prevention of stroke in patients with atrial fibrillation. Several DOACs are of net benefit compared with warfarin. A trial directly comparing DOACs would overcome the need for indirect comparisons to be made through network meta-analysis.Systematic review registration PROSPERO CRD 42013005324.
Although mothers influence the traits of their offspring in many ways beyond the transmission of genes, it remains unclear how important such ‘maternal effects’ are to phenotypic differences among ...individuals. Synthesizing estimates derived from detailed pedigrees, we evaluated the amount of phenotypic variation determined by maternal effects in animal populations. Maternal effects account for half as much phenotypic variation within populations as do additive genetic effects. Maternal effects most greatly affect morphology and phenology but, surprisingly, are not stronger in species with prolonged maternal care than in species without. While maternal effects influence juvenile traits more than adult traits on average, they do not decline across ontogeny for behaviour or physiology, and they do not weaken across the life cycle in species without maternal care. These findings underscore maternal effects as an important source of phenotypic variation and emphasise their potential to affect many ecological and evolutionary processes.
Pricing in the Market for Anticancer Drugs Howard, David H.; Bach, Peter B.; Berndt, Ernst R. ...
The Journal of economic perspectives,
2015, Letnik:
29, Številka:
1
Journal Article
Recenzirano
Odprti dostop
In 2011, Bristol-Myers Squibb set the price of its newly approved melanoma drug ipilimumab—brand name Yervoy—at $120,000 for a course of therapy. The drug was associated with an incremental increase ...in life expectancy of four months. Drugs like ipilimumab have fueled the perception that the launch prices of new anticancer drugs and other drugs in the so-called “specialty” pharmaceutical market have been increasing over time and that increases are unrelated to the magnitude of the expected health benefits. In this paper, we discuss the unique features of the market for anticancer drugs and assess trends in the launch prices for 58 anticancer drugs approved between 1995 and 2013 in the United States. We restrict attention to anticancer drugs because the use of median survival time as a primary outcome measure provides a common, objective scale for quantifying the incremental benefit of new products. We find that the average launch price of anticancer drugs, adjusted for inflation and health benefits, increased by 10 percent annually—or an average of $8,500 per year—from 1995 to 2013. We argue that the institutional features of the market for anticancer drugs enable manufacturers to set the prices of new products at or slightly above the prices of existing therapies, giving rise to an upward trend in launch prices. Government-mandated price discounts for certain classes of buyers may have also contributed to launch price increases as firms sought to offset the growth in the discount segment by setting higher prices for the remainder of the market.
Summary In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging–Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's ...disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD.
Despite significant advances in treatment, stigma and discrimination toward persons with mental illness and drug addiction have remained constant in past decades. Prior work suggests that portraying ...other stigmatized health conditions (i.e., HIV/AIDS) as treatable can improve public attitudes toward those affected. Our study compared the effects of vignettes portraying persons with untreated and symptomatic versus successfully treated and asymptomatic mental illness and drug addiction on several dimensions of public attitudes about these conditions. We conducted a survey-embedded randomized experiment using a national sample (N = 3940) from an online panel. Respondents were randomly assigned to read one of ten vignettes. Vignette one was a control vignette, vignettes 2–5 portrayed individuals with untreated schizophrenia, depression, prescription pain medication addiction and heroin addiction, and vignettes 6–10 portrayed successfully treated individuals with the same conditions. After reading the randomly assigned vignette, respondents answered questions about their attitudes related to mental illness or drug addiction. Portrayals of untreated and symptomatic schizophrenia, depression, and heroin addiction heightened negative public attitudes toward persons with mental illness and drug addiction. In contrast, portrayals of successfully treated schizophrenia, prescription painkiller addiction, and heroin addiction led to less desire for social distance, greater belief in the effectiveness of treatment, and less willingness to discriminate against persons with these conditions. Portrayal of persons with successfully treated mental illness and drug addiction is a promising strategy for reducing stigma and discrimination toward persons with these conditions and improving public perceptions of treatment effectiveness.
•Depictions of untreated mental illness and addiction increase social stigma.•Depictions of persons with treated drug addiction decrease social stigma.•Depictions of treated schizophrenia improve attitudes about recovery.•Depictions of treated addiction improve attitudes about treatment effectiveness.
The schizophrenia spectrum disorders are neurodevelopmental illnesses with a lifetime prevalence near 1%, producing extensive functional impairment and low expectations for recovery. Until recently, ...treatment in the United States has largely attempted to stabilize individuals with chronic schizophrenia. The identification and promotion of evidence-based practices for schizophrenia via the Patient Outcomes Research Team, combined with international studies supporting the value of early intervention, provided the foundation for the Recovery After an Initial Schizophrenia Episode (RAISE) project. The RAISE studies further supported the value of reducing the duration of untreated psychosis and providing a multi-element treatment called coordinated specialty care (CSC) to improve outcomes for patients in usual treatment settings. Although CSC programs have proliferated rapidly in the United States, many challenges remain in the treatment and recovery of individuals with schizophrenia in the aftermath of RAISE.
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