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Episodic memory impairment and hippocampal pathology are hallmark features of both temporal lobe epilepsy (TLE) and amnestic mild cognitive impairment (aMCI). Pattern separation (PS), which enables the distinction between similar but unique experiences, is thought to contribute to successful encoding and retrieval of episodic memories. Impaired PS has been proposed as a potential mechanism underling episodic memory impairment in aMCI, but this association is less established in TLE. In this study, we examined behavioral PS in patients with TLE and explored whether profiles of performance in TLE are similar to aMCI.
Patients with TLE, aMCI, and age-matched, healthy controls (HCs) completed a modified recognition task that relies on PS for the discrimination of highly similar lure items, the Mnemonic Similarity Task (MST). Group differences were evaluated and relationships between clinical characteristics, California Verbal Learning Test—Second Edition scores, and MST performance were tested in the TLE group.
Patients with TLE and aMCI demonstrated poorer PS performance relative to the HCs, but performance did not differ between the two patient groups. Neither the side of seizure focus nor having hippocampal sclerosis affected performance in TLE. However, TLE patients with clinically defined memory impairment showed the poorest performance.
Memory performance on a task that relies on PS was disrupted to a similar extent in TLE and aMCI. The MST could provide a clinically useful tool for measuring hippocampus-dependent memory impairments in TLE and other neurological disorders associated with hippocampal damage.
Background: A penicillin allergy guidance document containing an algorithm for challenging penicillin allergic patients with β-lactams was developed by the antimicrobial stewardship program (ASP). As part of this algorithm, a “graded challenge” order set was created containing antimicrobial orders and safety medications along with monitoring instructions. The process is designed to challenge patients at low risk of reaction with infusions of 1% of the target dose, then 10%, and finally the full dose, each 30 minutes apart. We evaluated outcomes from the order set. Methods: Orders of the graded challenge over 17 months (March 2018 through July 2019) were reviewed retrospectively. Data were collected on ordering and outcomes of the challenges and allergy documentation. Use was evaluated based on ASP-recommended indications: history of IgE-mediated or unknown reaction plus (1) no previous β-lactam tolerance and the reaction occurred >10 years ago, or (2) previous β-lactam tolerance, now requiring a different β-lactam for treatment. Only administered challenges were included and descriptive statistics were utilized. Results: Of 67 orders, 57 graded challenges were administered to 56 patients. The most common allergies were penicillins (87.7%) and cephalosporins (38.6%), with the most common reactions being unknown (41.7%) or hives (22%). The most common antibiotics challenged were ceftriaxone (43.9%), cefepime (21.1%), and cefazolin (5.3%). Antibiotics given prior to challenge included vancomycin (48.2%), fluoroquinolones (35.7%), carbapenems (21.4%), aztreonam (19.6%), and clindamycin (12.5%). The median duration of challenged antibiotic was 6 days. The infectious diseases service was consulted on 59.6% of challenges and 75.4% of challenges were administered in non-ICU settings. There was 1 reaction (1.8%) involving a rash with the second infusion, which was treated with oral diphenhydramine and had no lasting effects. Based on indications, 80.7% of challenges were aligned with ASP guidance criteria. The most common use outside of these criteria was in patients without IgE-mediated reactions (10.5%). Most of these had minor rashes and could have received a full dose of a cephalosporin. Allergy information was updated in the electronic health record after 91.2% of challenges. Conclusions: We demonstrated the utility of a graded challenge process at our academic medical center. It was well tolerated, ordered frequently by noninfectious diseases clinicians, administered primarily in non-ICU settings, and regularly resulted in updated allergy information in the medical record. With many patients initially receiving broad-spectrum antibiotics with high costs or increased rates of adverse effects, graded challenges can potentially prevent the use of suboptimal therapies with minimal time and resource investment.
Disclosures: Scott Bergman reports a research grant from Merck.
The reflectance spectroscopic characteristics of cyanobacteria-dominated microbial mats in the McMurdo Dry Valleys (MDVs) were measured using a hyperspectral point spectrometer aboard an unmanned aerial system (remotely piloted aircraft system, unmanned aerial vehicle or drone) to determine whether mat presence, type and activity could be mapped at a spatial scale sufficient to characterize inter-annual change. Mats near Howard Glacier and Canada Glacier (ASPA 131) were mapped and mat samples were collected for DNA-based microbiome analysis. Although a broadband spectral parameter (a partial normalized difference vegetation index) identified mats, it missed mats in comparatively deep (> 10 cm) water or on bouldery surfaces where mats occupied fringing moats. A hyperspectral parameter (B6) did not have these shortcomings and recorded a larger dynamic range at both sites. When linked with colour orthomosaic data, B6 band strength is shown to be capable of characterizing the presence, type and activity of cyanobacteria-dominated mats in and around MDV streams. 16S rRNA gene polymerase chain reaction amplicon sequencing analysis of the mat samples revealed that dominant cyanobacterial taxa differed between spectrally distinguishable mats, indicating that spectral differences reflect underlying biological distinctiveness. Combined rapid-repeat hyperspectral measurements can be applied in order to monitor the distribution and activity of sentinel microbial ecosystems across the terrestrial Antarctic.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Hospice nurses frequently encounter patients and families under tremendous emotional distress, yet the communication techniques they use in emotionally charged situations have rarely been investigated. In this study, researchers sought to examine hospice nurses’ use of validation communication techniques, which have been shown in prior research to be effective in supporting individuals experiencing emotional distress.
Researchers performed a directed content analysis of audiorecordings of 65 hospice nurses’ home visits by identifying instances when nurses used validation communication techniques and rating the level of complexity of those techniques.
All nurses used validation communication techniques at least once during their home visits. Use of lower level (i.e., more basic) techniques was more common than use of higher level (i.e., more complex) techniques.
Significance of Results
Although hospice nurses appear to use basic validation techniques naturally, benefit may be found in the use of higher level techniques, which have been shown to result in improved clinical outcomes in other settings.
Due to concerns over increasing fluoroquinolone (FQ) resistance among gram-negative organisms, our stewardship program implemented a preauthorization use policy. The goal of this study was to assess the relationship between hospital FQ use and antibiotic resistance.
Large academic medical center.
We performed a retrospective analysis of FQ susceptibility of hospital isolates for 5 common gram-negative bacteria: Acinetobacter spp., Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Primary endpoint was the change of FQ susceptibility. A Poisson regression model was used to calculate the rate of change between the preintervention period (1998–2005) and the postimplementation period (2006–2016).
Large rates of decline of FQ susceptibility began in 1998, particularly among P. aeruginosa, Acinetobacter spp., and E. cloacae. Our FQ restriction policy improved FQ use from 173 days of therapy (DOT) per 1,000 patient days to <60 DOT per 1,000 patient days. Fluoroquinolone susceptibility increased for Acinetobacter spp. (rate ratio [RR], 1.038; 95% confidence interval [CI], 1.005–1.072), E. cloacae (RR, 1.028; 95% CI, 1.013–1.044), and P. aeruginosa (RR, 1.013; 95% CI, 1.006–1.020). No significant change in susceptibility was detected for K. pneumoniae (RR, 1.002; 95% CI, 0.996–1.008), and the susceptibility for E. coli continued to decline, although the decline was not as steep (RR, 0.981; 95% CI, 0.975–0.987).
A stewardship-driven FQ restriction program stopped overall declining FQ susceptibility rates for all species except E. coli. For 3 species (ie, Acinetobacter spp, E. cloacae, and P. aeruginosa), susceptibility rates improved after implementation, and this improvement has been sustained over a 10-year period.
Intermediate wheatgrass (Thinopyrum intermedium; IWG) is a perennial cereal crop undergoing development for grain production; however, grain yield declines of >75% are often observed after year 2 of the perennial stand and may be linked to soil nutrient depletion. Intercropping IWG with a perennial legume such as alfalfa (Medicago sativa) could benefit nutrient cycling while increasing agroecological diversity. Intermediate wheatgrass was established at five environmentally diverse sites in Minnesota, USA in (1) bi-culture with alfalfa, (2) non-fertilized monoculture and (3) monoculture fertilized annually in the spring with 80 kg N/ha. At northern sites where alfalfa growth was favoured, IWG grain yields were reduced in year 2 by growing IWG in bi-culture with alfalfa, relative to the monoculture systems. Across all sites IWG grain yield decreased by 90% in the non-fertilized monoculture, 80% in the fertilized monoculture and 65% in the bi-culture from year 2 to 4 and plant macronutrient concentrations decreased by 25–70%. In year 4, IWG grain yield was similar or greater in the bi-culture than the fertilized monoculture at three of the five sites and alfalfa biomass was correlated positively with grain yield, harvest index and nutrient uptake in the year 4 bi-culture. Chemical-nitrogen fertilization increased grain yields in year 2 but did not mitigate the decline in yields as stands aged. Intermediate wheatgrass in the bi-culture had similar yields and nutrient uptake and lower yield declines than the chemically fertilized stand at sites where alfalfa growth was maintained throughout the life of the stand.
The Drygalski Ice Tongue presents an ~80 km long floating obstacle to alongshore flows in the Victoria Land coastal ocean region of the Western Ross Sea. Here we use oceanographic data from near to the tongue to explore the interplay between the floating glacier and the local currents and stratification. A vessel-based circuit of the glacier, recording ocean temperature and salinity profiles, reveals the southwest corner to be the coldest and most complex in terms of vertical structure. The southwest corner structure beneath the surface warm, salty layer sustains a block of very cold water extending to 200 m depth. In this same location there was a distinct layer at 370 m not seen anywhere else of water at ~−1.93°C. The new observations broadly, but not directly, support the presence of a coherent Victoria Land Coastal Current. The data suggest the northward moving coastal current turns against the Coriolis force and works its way anticlockwise around the glacier, but with leakage beneath the glacier through the highly ‘rippled’ underside, resulting in a spatially heterogeneous supply to the Terra Nova Bay Polynya region – an important location for the formation of high-salinity shelf water.
Ice patches and the alpine are important elements of the sociocultural landscape of the Greater Yellowstone Area, and they transcend the jurisdictional boundaries that divide the lands on which they occur. The ice patch record complements traditional sources of archaeological knowledge through the addition of well-dated organic artifacts, such as shafts from hunting tools, recovered in a readily recognizable context. This paper examines the types of wood used in the manufacture of hunting implements recovered at Greater Yellowstone Area ice patches through the analysis of nine unique wooden shafts and shaft fragments from five sites. Five shafts are birch (Betula spp.), two are willow (Salix spp.), one is fir (Abies sp.), and one is pine (Pinus sp.). The shafts included in this analysis range in age from 9230 ± 25 B.P. to 215 ± 20 B.P. Diagnostic Oxbow and Pelican Lake chipped stone projectile points recovered in association with ice patches provide additional temporal resolution regarding use of these features. One of the four sites that yielded wooden shafts contains a record of bighorn sheep (Ovis canadensis) hunting between 3885 ± 25 B.P. and 879 ± 23 B.P.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
Emerging evidence from epidemiological studies supports the notion that maternal folate status regulated by dietary and genetic factors early in pregnancy may influence the risk of autism spectrum disorders (ASD). In this review, we provide an overview of what is known about the role of folate in the aetiology of neurodevelopmental disorders; summarise relevant biological, genetic and epigenetic mechanisms; and synthesise the evidence from human observational studies and randomised controlled trials that have examined the relationship between maternal folate and ASD or related traits. Much of the existing literature on this topic is subject to limitations such as potential confounding by healthy behaviours and other dietary factors, and exposure assessed within limited exposure windows. As the existing evidence is inconclusive, further research remains to be conducted in order to verify this hypothesis. Complete assessment of maternal functional folate status through the pre- and peri-conceptional periods requires biological measurement of folate, vitamin B12 and homocysteine and genetic variants involved in one-carbon metabolism and epigenetic mechanisms. In addition to more complete assessment of maternal functional folate status, careful consideration of potential confounding is warranted.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.