Category label and response location shifts in category learning

The category shift literature suggests that rule-based classification, an important form of explicit learning, is mediated by two separate learned associations: a stimulus-to-label association that associates stimuli and category labels, and a label-to-response association that associates category labels and responses. Three experiments investigate whether information–integration classification, an important form of implicit learning, is also mediated by two separate learned associations. Participants were trained on a rule-based or an information–integration categorization task and then the association between stimulus and category label, or between category label and response location was altered. For rule-based categories, and in line with previous research, breaking the association between stimulus and category label caused more interference than breaking the association between category label and response location. However, no differences in recovery rate emerged. For information–integration categories, breaking the association between stimulus and category label caused more interference and led to greater recovery than breaking the association between category label and response location. These results provide evidence that information–integration category learning is mediated by separate stimulus-to-label and label-to-response associations. Implications for the neurobiological basis of these two learned associations are discussed

Relative contributions to vergence eye movements of two binocular cues for motion-in-depth

When we track an object moving in depth, our eyes rotate in opposite directions. This type of "disjunctive" eye movement is called horizontal vergence. The sensory control signals for vergence arise from multiple visual cues, two of which, changing binocular disparity (CD) and inter-ocular velocity differences (IOVD), are specifically binocular. While it is well known that the CD cue triggers horizontal vergence eye movements, the role of the IOVD cue has only recently been explored. To better understand the relative contribution of CD and IOVD cues in driving horizontal vergence, we recorded vergence eye movements from ten observers in response to four types of stimuli that isolated or combined the two cues to motion-in-depth, using stimulus conditions and CD/IOVD stimuli typical of behavioural motion-in-depth experiments. An analysis of the slopes of the vergence traces and the consistency of the directions of vergence and stimulus movements showed that under our conditions IOVD cues provided very little input to vergence mechanisms. The eye movements that did occur coinciding with the presentation of IOVD stimuli were likely not a response to stimulus motion, but a phoria initiated by the absence of a disparity signal

Human Prion Diseases in the United States

BACKGROUND: Prion diseases are a family of rare, progressive, neurodegenerative disorders that affect humans and animals. The most common form of human prion disease, Creutzfeldt-Jakob disease (CJD), occurs worldwide. Variant CJD (vCJD), a recently emerged human prion disease, is a zoonotic foodborne disorder that occurs almost exclusively in countries with outbreaks of bovine spongiform encephalopathy. This study describes the occurrence and epidemiology of CJD and vCJD in the United States. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of CJD and vCJD deaths using death certificates of US residents for 1979-2006, and those identified through other surveillance mechanisms during 1996-2008. Since CJD is invariably fatal and illness duration is usually less than one year, the CJD incidence is estimated as the death rate. During 1979 through 2006, an estimated 6,917 deaths with CJD as a cause of death were reported in the United States, an annual average of approximately 247 deaths (range 172-304 deaths). The average annual age-adjusted incidence for CJD was 0.97 per 1,000,000 persons. Most (61.8%) of the CJD deaths occurred among persons >or=65 years of age for an average annual incidence of 4.8 per 1,000,000 persons in this population. Most deaths were among whites (94.6%); the age-adjusted incidence for whites was 2.7 times higher than that for blacks (1.04 and 0.40, respectively). Three patients who died since 2004 were reported with vCJD; epidemiologic evidence indicated that their infection was acquired outside of the United States. CONCLUSION/SIGNIFICANCE: Surveillance continues to show an annual CJD incidence rate of about 1 case per 1,000,000 persons and marked differences in CJD rates by age and race in the United States. Ongoing surveillance remains important for monitoring the stability of the CJD incidence rates, and detecting occurrences of vCJD and possibly other novel prion diseases in the United States

Value of hospital antimicrobial stewardship programs [ASPs]:a systematic review

Abstract Background Hospital antimicrobial stewardship programs (ASPs) aim to promote judicious use of antimicrobials to combat antimicrobial resistance. For ASPs to be developed, adopted, and implemented, an economic value assessment is essential. Few studies demonstrate the cost-effectiveness of ASPs. This systematic review aimed to evaluate the economic and clinical impact of ASPs. Methods An update to the Dik et al. systematic review (2000–2014) was conducted on EMBASE and Medline using PRISMA guidelines. The updated search was limited to primary research studies in English (30 September 2014–31 December 2017) that evaluated patient and/or economic outcomes after implementation of hospital ASPs including length of stay (LOS), antimicrobial use, and total (including operational and implementation) costs. Results One hundred forty-six studies meeting inclusion criteria were included. The majority of these studies were conducted within the last 5 years in North America (49%), Europe (25%), and Asia (14%), with few studies conducted in Africa (3%), South America (3%), and Australia (3%). Most studies were conducted in hospitals with 500–1000 beds and evaluated LOS and change in antibiotic expenditure, the majority of which showed a decrease in LOS (85%) and antibiotic expenditure (92%). The mean cost-savings varied by hospital size and region after implementation of ASPs. Average cost savings in US studies were $732 per patient (range:$2.50 to $2640), with similar trends exhibited in European studies. The key driver of cost savings was from reduction in LOS. Savings were higher among hospitals with comprehensive ASPs which included therapy review and antibiotic restrictions. Conclusions Our data indicates that hospital ASPs have significant value with beneficial clinical and economic impacts. More robust published data is required in terms of implementation, LOS, and overall costs so that decision-makers can make a stronger case for investing in ASPs, considering competing priorities. Such data on ASPs in lower- and middle-income countries is limited and requires urgent attention

Universal DNA methylation age across mammalian tissues.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals