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Circular features made from mammoth bone are known from across Upper Palaeolithic Eastern Europe, and are widely identified as dwellings. The first systematic flotation programme of samples from a recently discovered feature at Kostenki 11 in Russia has yielded assemblages of charcoal, burnt bone and microlithic debitage. New radiocarbon dates provide the first coherent chronology for the site, revealing it to be one of the oldest such features on the Russian Plain. The authors discuss the implications for understanding the function of circular mammoth-bone features during the onset of the Last Glacial Maximum.
High-resolution Chirp sub-bottom data were obtained offshore from the Northern Channel Islands (NCI), California, to image submerged paleoshorelines and assess local uplift rates. Although modern bathymetry is often used for modeling paleoshorelines, Chirp data image paleoshorelines buried beneath sediment that obscures their seafloor expression. The NCI were a unified landmass during the last glacial maximum (LGM; ~20 ka), when eustatic sea level was ~120 m lower than present. We identified seven paleoshorelines, ranging from ~28 to 104 m in depth, across this now-submerged LGM platform. Paleoshoreline depths were compared to local sea-level curves to estimate ages, which suggest that some were reoccupied over multiple sea-level cycles. Additionally, previous studies determined conflicting uplift rates for the NCI, ranging from 0.16 to 1.5 m/ka. Our results suggest that a rate on the lower end of this range better fits the observed submerged paleoshorelines. Using the uplift rate of ~0.16 m/ka, we estimate that paleoshorelines formed during Marine Oxygen Isotope Stage 3, the LGM, and the Younger Dryas stade are preserved on the NCI platform. These results help clarify uplift rates for the NCI and illustrate the importance of sub-bottom data for mapping submerged paleoshorelines.
OBJECTIVES/SPECIFIC AIMS: Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and an increasingly common infection in children in both hospital and community settings. Between 20% and 30% of pediatric patients will have a recurrence of symptoms in the days to weeks following an initial infection. Multiple recurrences have been successfully treated with fecal microbiota transplantation (FMT), though the body of evidence in pediatric patients is limited primarily to case reports and case series. The goal of our study was to better understand practices, success, and safety of FMT in children as well as identify risk factors associated with a failed FMT in our pediatric patients. METHODS/STUDY POPULATION: This multicenter retrospective analysis included 373 patients who underwent FMT for CDI between January 1, 2006 and January 1, 2017 from 18 pediatric centers. Demographics, baseline characteristics, FMT practices, C. difficile outcomes, and post-FMT complications were collected through chart abstraction. Successful FMT was defined as no recurrence of CDI within 60 days after FMT. Of the 373 patients in the cohort, 342 had known outcome data at two months post-FMT and were included in the primary analysis evaluating risk factors for recurrence post-FMT. An additional six patients who underwent FMT for refractory CDI were excluded from the primary analysis. Unadjusted analysis was performed using Wilcoxon rank-sum test, Pearson χ2 test, or Fisher exact test where appropriate. Stepwise logistic regression was utilized to determine independent predictors of success. RESULTS/ANTICIPATED RESULTS: The median age of included patients was 10 years (IQR; 3.0, 15.0) and 50% of patients were female. The majority of the cohort was White (89.0%). Comorbidities included 120 patients with inflammatory bowel disease (IBD) and 14 patients who had undergone a solid organ or stem cell transplantation. Of the 336 patients with known outcomes at two months, 272 (81%) had a successful outcome. In the 64 (19%) patients that did have a recurrence, 35 underwent repeat FMT which was successful in 20 of the 35 (57%). The overall success rate of FMT in preventing further episodes of CDI in the cohort with known outcome data was 87%. Unadjusted predictors of a primary FMT response are summarized. Based on stepwise logistic regression modeling, the use of fresh stool, FMT delivery via colonoscopy, the lack of a feeding tube, and a lower number of CDI episodes before undergoing FMT were independently associated with a successful outcome. There were 20 adverse events in the cohort assessed to be related to FMT, 6 of which were felt to be severe. There were no deaths assessed to be related to FMT in the cohort. DISCUSSION/SIGNIFICANCE OF IMPACT: The overall success of FMT in pediatric patients with recurrent or severe CDI is 81% after a single FMT. Children without a feeding tube, who receive an early FMT, FMT with fresh stool, or FMT via colonoscopy are less likely to have a recurrence of CDI in the 2 months following FMT. This is the first large study of FMT for CDI in a pediatric cohort. These findings, if confirmed by additional prospective studies, will support alterations in the practice of FMT in children.
Recently developed direct-acting antiviral (DAA) treatments for hepatitis C virus (HCV) are groundbreaking in their high efficacy across disease genotypes and lack of severe side effects. This study used a cost-of-illness (COI) approach to estimate the net value conferred by one of these novel drug combinations, sofosbuvir and velpatasir (SOF/VEL), recently licensed for generic manufacture in India.
This study considered COI from lifetime earnings lost due to disability and premature death from HCV infection. Risk of death and disability in future years was calculated using a Markov state-transition model with parameters determined from the literature. The future earnings of sampled patients were predicted using an empirical earnings model, with coefficients determined from India Human Development Survey data. Costs to both the patient and secondarily infected individuals were considered.
Preliminary results suggested that curing individuals diagnosed with chronic HCV in India would preserve INR 3.7 million (USD 55,750) in earnings per person. For non-cirrhotic (NC) and compensated cirrhotic (CC) individuals, the expected benefits associated with preventing secondary infections were worth between one and forty-one percent of the value of benefits conferred to the diagnosed individuals (depending on sex and extent of liver damage). Treating decompensated cirrhotic (DC) individuals with DAAs alone offered minimal earnings benefits because these individuals will likely remain disabled and unable to work without a liver transplant. Expected net benefits of treatment were substantial for NC and CC patients, ranging from INR 640,349 (USD 9,531) for NC women to INR 10.7 million (USD 158,968) for CC men. The cost of treatment for DC individuals exceeded the expected earnings benefits.
For average NC and CC individuals, the cost of treatment with SOF/VEL is offset by the benefits of increased future productivity. Increased earnings are not sufficient to offset the cost of treatment for DC individuals, but treatment may still be justified on the basis of the intrinsic value of health improvements and other treatment benefits.
Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently described life-threatening autoimmune disorder associated with a characteristic multi-stage neuropsychiatric syndrome. Although it is known that the majority of patients experience neuropsychological disturbance post-treatment, some aspects of the cognitive profile remain unclear. Methods: This study sought to investigate patterns of cognitive functioning in a sample of anti-NMDAR encephalitis patients. Seven (6F:1M; mean age, 26.4 years; range, 16–37 years) treated patients completed a comprehensive set of neurocognitive and social functioning measures. Performance was analyzed using normative data (where available), and comparison with matched controls (10F:4M; mean age, 25.8 years; range, 16–38 years). Results: Individual cognitive profiles ranged from within normal limits to extensive dysfunction. Relative to controls, the patient group’s performance was affected in the domains of verbal/ visual memory, working memory, attention, processing speed, executive functioning, and social cognition. The patient group also reported significantly higher levels of anxiety compared to controls. Conclusions: These results add to the accumulating evidence that neurocognitive deficits, consistent with the distribution and functions of the NMDAR system can persist during recovery from anti-NMDAR encephalitis. This is the first study to provide evidence of performance decrements on measures of social cognition, including some involving theory of mind. (JINS, 2016, 22, 828–838)
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
Among dialysis facilities participating in a bloodstream infection (BSI) prevention collaborative, access-related BSI incidence rate improvements observed immediately following implementation of a bundle of BSI prevention interventions were sustained for up to 4 years. Overall, BSI incidence remained unchanged from baseline in the current analysis.