To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
This study investigated the latent factor structure of the NIH Toolbox Cognition Battery (NIHTB-CB) and its measurement invariance across clinical diagnosis and key demographic variables including sex, race/ethnicity, age, and education for a typical Alzheimer’s disease (AD) research sample.
The NIHTB-CB iPad English version, consisting of 7 tests, was administered to 411 participants aged 45–94 with clinical diagnosis of cognitively unimpaired, dementia, mild cognitive impairment (MCI), or impaired not MCI. The factor structure of the whole sample was first examined with exploratory factor analysis (EFA) and further refined using confirmatory factor analysis (CFA). Two groups were classified for each variable (diagnosis or demographic factors). The confirmed factor model was next tested for each group with CFA. If the factor structure was the same between the groups, measurement invariance was then tested using a hierarchical series of nested two-group CFA models.
A two-factor model capturing fluid cognition (executive function, processing speed, and memory) versus crystalized cognition (language) fit well for the whole sample and each group except for those with age < 65. This model generally had measurement invariance across sex, race/ethnicity, and education, and partial invariance across diagnosis. For individuals with age < 65, the language factor remained intact while the fluid cognition was separated into two factors: (1) executive function/processing speed and (2) memory.
The findings mostly supported the utility of the battery in AD research, yet revealed challenges in measuring memory for AD participants and longitudinal change in fluid cognition.
Cognitive impairments in childhood are associated with increased risk of schizophrenia in later life, but the extent to which poor academic achievement is associated with the disorder is unclear.
Major databases were searched for articles published in English up to 31 December 2019. We conducted random-effects meta-analyses to: (1) compare general academic and mathematics achievement in youth who later developed schizophrenia and those who did not; (2) to examine the association between education level achieved and adult-onset schizophrenia; and, (3) compare general academic achievement in youth at-risk for schizophrenia and typically developing peers. Meta-regression models examined the effects of type of academic assessment, educational system, age at assessment, measurement of educational level attained, school leaving age, and study quality on academic achievement and education level among individuals with schizophrenia.
Meta-analyses, comprising data of over four million individuals, found that: (1) by age 16 years, those who later developed schizophrenia had poorer general academic (Cohen's d = −0.29, p ⩽ 0.0001) and mathematics achievement (d = −0.23, p = 0.01) than those who did not; (2) individuals with schizophrenia were less likely to enter higher education (odds ratio = 0.49, p ⩽ 0.0001); and, (3) youth reporting psychotic-like experiences and youth with a family history of schizophrenia had lower general academic achievement (d = −0.54, p ⩽ 0.0001; d = −0.39, p ⩽ 0.0001, respectively). Meta-regression analyses determined no effect modifiers.
Despite significant heterogeneity across studies, various routinely collected indices of academic achievement can identify premorbid cognitive dysfunction among individuals who are vulnerable for schizophrenia, potentially aiding the early identification of risk in the population.
In the American continent, the sugarcane borer Diatraea saccharalis (F.) is the main pest in sugarcane producing areas. The objective of this study was to assess the effect of crop residue management on damage by D. saccharalis, its egg parasitoids and the ants associated with sugarcane. The study was carried out during 2011–2012, 2012–2013 and 2013–2014 crop cycles, in three commercial fields located in different regions of Tucumán state, Argentina. Two types of crop residue management (= treatments) were compared: conservation of trash at the soil surface (CT) and trash burning (TB). In ‘trash conservation’ treatment, crop residue was allowed to remain over the soil surface during the whole sugarcane growing season, while the second treatment consisted of complete burning of trash blanket approximately 2 weeks after harvest. The injury level was measured by recording the number of stalks bored and internodes bored. Parasitism was estimated by counting the total number of eggs and number of black eggs (which indicates the occurrence of egg parasitoids). Ants (Formicidae) richness was calculated by two estimators; abundance-based coverage estimator and incidence-based coverage estimator, using the non-parametric richness estimators: Chao 2 and Jackknife. Finally, the indicator value was estimated through the measurement of specificity and fidelity. In all the parameters studied no significant difference was found between TB and CT treatments.
Antibiotics are commonly used in intensive care units (ICUs), yet differences in antibiotic use across ICUs are unknown. Herein, we studied antibiotic use across ICUs and examined factors that contributed to variation.
We conducted a retrospective cohort study using data from Ontario’s Critical Care Information System (CCIS), which included 201 adult ICUs and 2,013,397 patient days from January 2012 to June 2016. Antibiotic use was measured in days of therapy (DOT) per 1,000 patient days. ICU factors included ability to provide ventilator support (level 3) or not (level 2), ICU type (medical-surgical or other), and academic status. Patient factors included severity of illness using multiple-organ dysfunction score (MODS), ventilatory support, and central venous catheter (CVC) use. We analyzed the effect of these factors on variation in antibiotic use.
Overall, 269,351 patients (56%) received antibiotics during their ICU stay. The mean antibiotic use was 624 (range 3–1460) DOT per 1,000 patient days. Antibiotic use was significantly higher in medical-surgical ICUs compared to other ICUs (697 vs 410 DOT per 1,000 patient days; P < .0001) and in level 3 ICUs compared to level 2 ICUs (751 vs 513 DOT per 1,000 patient days; P < .0001). Higher antibiotic use was associated with higher severity of illness and intensity of treatment. ICU and patient factors explained 47% of the variation in antibiotic use across ICUs.
Antibiotic use varies widely across ICUs, which is partially associated with ICUs and patient characteristics. These differences highlight the importance of antimicrobial stewardship to ensure appropriate use of antibiotics in ICU patients.
Non-typhoidal Salmonella (NTS) serovars, sequences types and antimicrobial susceptibility profiles have specific associations with animal and human infections in Vietnam. Antimicrobial resistance may have an effect on the manifestation of human NTS infections, with isolates from asymptomatic individuals being more susceptible to antimicrobials than those associated with animals and human diarrhoea.
Raw milk cheeses are commonly consumed in France and are also a common source of foodborne outbreaks (FBOs). Both an FBO surveillance system and a laboratory-based surveillance system aim to detect Salmonella outbreaks. In early August 2018, five familial FBOs due to Salmonella spp. were reported to a regional health authority. Investigation identified common exposure to a raw goats' milk cheese, from which Salmonella spp. were also isolated, leading to an international product recall. Three weeks later, on 22 August, a national increase in Salmonella Newport ST118 was detected through laboratory surveillance. Concomitantly isolates from the earlier familial clusters were confirmed as S. Newport ST118. Interviews with a selection of the laboratory-identified cases revealed exposure to the same cheese, including exposure to batches not included in the previous recall, leading to an expansion of the recall. The outbreak affected 153 cases, including six cases in Scotland. S. Newport was detected in the cheese and in the milk of one of the producer's goats. The difference in the two alerts generated by this outbreak highlight the timeliness of the FBO system and the precision of the laboratory-based surveillance system. It is also a reminder of the risks associated with raw milk cheeses.
This report is on the synthesis by electrospinning of multiferroic core-shell nanofibers of strontium hexaferrite and lead zirconate titanate or barium titanate and studies on magneto-electric (ME) coupling. Fibers with well-defined core–shell structures showed the order parameters in agreement with values for nanostructures. The strength of ME coupling measured by the magnetic field-induced polarization showed the fractional change in the remnant polarization as high as 21%. The ME voltage coefficient in H-assembled films showed the strong ME response for the zero magnetic bias field. Follow-up studies and potential avenues for enhancing the strength of ME coupling in the core–shell nanofibers are discussed.
Metabolic resistances to atrazine (atz-R) and mesotrione (meso-R) occur in several waterhemp [Amaranthus tuberculatus (Moq.) Sauer] populations in the United States. Interestingly, although metabolic atz-R but mesotrione-sensitive A. tuberculatus populations have been reported, an Amaranthus population has not been confirmed as meso-R but atrazine-sensitive, implying an association between these traits. Experiments were designed to investigate whether the single gene conferring metabolic atz-R plays a role in meso-R. An F2 population was generated from a multiple herbicide–resistant A. tuberculatus population from McLean County, IL (MCR). A cross was made between a known meso-R male clone (MCR-6) and a herbicide-sensitive female clone from Wayne County, IL (WCS-2) to develop an F1 population. Survival of MCR-6 plants following atrazine POST treatment (14.4 kg ha−1) indicated the male parent was homozygous atz-R. F1 plants were intermated to obtain a segregating pseudo-F2 population. Dose–response and metabolic studies conducted with mesotrione using F1 plants indicated intermediate biomass reductions and metabolic rates compared with MCR-6 and WCS. F2 plants were initially treated with either mesotrione (260 g ha−1) or atrazine (2 kg ha−1) POST, and after 21 d of recovery, vegetative clones from surviving resistant plants were subsequently treated with the other herbicide. When mesotrione was applied first, the meso-R frequency was 8.2%, and when atrazine was applied first, the atz-R frequency was 75%. However, the meso-R frequency increased to 16.5% following preselection for atz-R, and 100% of surviving meso-R plants were atz-R. Our findings indicate that the gene conferring metabolic atz-R is also involved with the meso-R trait within the population tested.
This study was designed to verify whether fluoxetine (FL), a serotonin (5-HT) re-uptake inhibitor, would interfere with nortriptyline (NT), a biphasic U-shaped curvilinear dose-response relationship recently described in our laboratory. We associated 10 mg/kg NT or vehicle to 0, 5, 10, 20 and 40 mg/kg FL, in one group, and 10 mg FL or vehicle to 0, 5, 10, 20 and 40 mg/kg NT, in another group, 30 min before the tail suspension test (TST) in mice. Although we were not able to confirm a synergistic effect between FL and NT, FL-NT association seems to require higher doses of NT to block its own anti-immobility effect at high doses, thus widening NT effective antidepressant-like dose range in mice submitted to TST.
Electroconvulsive therapy (ECT) is the most effective and fast acting therapy for treatment-resistant depression (TRD). Animal research has consistently pointed to neuroplasticity as a central mechanism of ECT action (1), however evidence in humans remains scarce (2; 3).
We assessed two independent samples of TRD patients referred for ECT. The Barcelona-sample included 13 subjects treated with bitemporal ECT and 10 healthy volunteers (HV). Four successive 3T structural MRIs were acquired: baseline, 24-48 hours after the 1st ECT session, 24-48 hours after the 9th ECT, and two weeks after ECT course completion. HV were scanned twice five weeks apart. Within the framework of the Barcelona-Sydney Clinical Imaging Collaboration, we also scanned 10 patients treated mainly with right unilateral ECT (Sydney-sample). Whole-brain longitudinal grey matter (GM) changes were measured using intra-subject diffeomorphic registration, within SPM12b.
In the Barcelona-sample, over the course of treatment bitemporal ECT produced a linear increase of GM volume in the limbic system (involving bilateral hippocampi and amygdalae). Additionally, volumetric increase within the right subgenual cortex was detected from baseline to the 9th ECT session. Such volume changes were not observed in HV. Furthermore, GM volume expansion correlated positively with depressive symptom improvement and neurocognitive performance (memory and executive function). Hippocampal and amygdalar volume increases were replicated in the Sydney-sample, although limited to the stimulated hemisphere.
ECT effects described here could be accounted for by the induction of regionally specific structural plasticity. Nevertheless, other mechanisms such as neurovascular changes should not be discarded.
Research integrating neuroimaging and molecular genetics has yielded important insights into how variability in brain chemistry predicts brain function and structure, behaviour and risk for psychopathology. Disrupted neurotransmission of glutamate within corticalstriatal-thalamocortical circuitry has been hypothesized to play a role in the pathogenesis of Obsessive-Compulsive Disorder (OCD). Candidate gene studies have identified associations between variants in glutamate system genes and OCD, particularly for SLC1A1, although these results remain controversial after GWAS and meta-analytical approaches.
To examine the effects of multiple polymorphisms of the glutamatergic pathway on frontostriatal connectivity, measured by resting state functional magnetic resonance imaging (fMRI), in OCD.
Individual multilocus genetic profile scores (MGPS) reflecting the additive effects of multiple alleles of the glutamatergic pathway, analysed by the Affymetrix GeneticChip® SNP array, were compiled for 134 OCD patients and 63 healthy controls. Association between these genetic scores and brain functional connectivity patterns between the dorsal and ventral striatal regions and limbic cortical areas including the orbitofrontal cortex and surrounding areas, such as the anterior prefrontal and perigenual anterior cingulate cortex, were investigated.
In the entire group, glutamatergic MGPS were significantly associated with connectivity patterns involving the ventral striatum and orbitofrontal cortex. Distinct relationships between MGPS and functional connectivity between the ventral striatum, amygdala, ventromedial frontal cortex and insula between OCD and healthy subjects emerged.
Glutamatergic genetic risk variants are related to normal frontostriatal connectivity; a fact that might explain the role of glutamatergic pathway disruptions in the susceptibility to develop OCD.
Tuberculosis (TB) is generally considered a disease that principally afflicts the low-income segments of a population. In the Nanshan District of Shenzhen, China, with the economic transformation and a new Headquarters Economy (HE) emerging, there are now more cases in office workers than in manufacturing workers. To illustrate this trend, we describe a small TB outbreak in an office building located in the centre of the rapidly growing HE district. Two active pulmonary tuberculosis cases were found in workers who shared an office, and whole genome sequencing showed that the genetic distance between the strains of the two cases was just one single nucleotide polymorphism, consistent with intra-office transmission. Investigation of 30 other workers in the same or adjacent offices with interviews, interferon-gamma release assays (IGRAs) and chest X-rays, identified one new TB case and latent tuberculosis infection (LTBI) in 40.0% (12/30) of the contacts. The offices were under-ventilated. None of the IGRA positive, asymptomatic contacts agreed to receive treatment for LTBI, presumably due to TB stigma, and over the next 2 years 69.0% (20/29) of the contacts were lost to follow-up. Treatment for LTBI and stigma of TB remain challenges here. Office workers in the HE of rapidly economic developing areas should be targeted with increased vigilance by TB control programmes.
Due to the growing interest in the role of dietary patterns (DPs) on chronic diseases, we assessed the association between a posteriori identified DPs in the Seguimiento Universidad de Navarra (SUN) Project – a prospective cohort study in a Mediterranean country – and breast cancer (BC) risk.
DPs were ascertained through a principal component analysis based on 31 predefined food groups. BC cases were initially identified through self-report or, if deceased, from death certificates or by notification by the next kin. Women reporting BC were asked to provide a copy of their medical report and diagnoses for confirmation purposes. We fitted Cox regression models to assess the association between adherence to the identified DPs and BC risk.
Spanish university graduates.
We included 10 713 young and middle-aged – mainly premenopausal – women.
After a median follow-up of 10·3 years, we identified 100 confirmed and 168 probable incident BC cases. We described two major DPs: ‘Western dietary pattern’ (WDP) and ‘Mediterranean dietary pattern’ (MDP). A higher adherence to a WDP was associated with an increased risk of overall BC (multivariable-adjusted HR for confirmed BC Q4 v. Q1 1·70; 95 % CI 0·93, 3·12; P for trend = 0·045). Contrarily, adherence to a MDP was inversely associated with premenopausal BC (multivariable-adjusted HR Q4 v. Q1 0·33; 95 % CI 0·12, 0·91). No significant associations were observed for postmenopausal BC.
Whereas a higher adherence to the WDP may increase the risk of BC, a higher adherence to the MDP may decrease the risk of premenopausal BC.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
Fascioliasis is a zoonotic disease caused by liver flukes transmitted by freshwater lymnaeid snails. Donkey and horse reservoir roles have been highlighted in human endemic areas. Liver fluke infection in mules has received very limited research. Their role in disease transmission, epidemiological importance and Fasciola hepatica pathogenicity are studied for the first time. Prevalence was 39.5% in 81 mules from Aconcagua, and 24.4% in 127 from Uspallata, in high-altitude areas of Mendoza province, Argentina. A mean amount of 101,242 eggs/mule/day is estimated. Lymnaeids from Uspallata proved to belong to ribosomal DNA internal transcribed spacer (ITS) markers ITS-1 and ITS-2 combined haplotype 3C of Galba truncatula. These lymnaeids were experimentally susceptible to infection by egg miracidia from mules. Infectivity, number of cercariae/snail and shedding period fit the enhanced F. hepatica/G. truncatula transmission pattern at very high altitude. This indicates that the mule is able to maintain the F. hepatica cycle independently. Individual burdens of 20 and 97 flukes were found. Mule infection susceptibility is intermediate between donkey and horse, although closer to the latter. Anatomo-pathology and histopathology indicate that massive infection may cause mule death. Haematological value decreases of red blood cells, haemoglobin, leucocytes and lymphocytes indicate anaemia and strong immunosuppression. Strongly increased biochemical marker values indicate liver function alterations. The mule probably played a role in the past exchanges with Chile and Bolivia through Mendoza province. Evidence suggests that mules could contribute to the spread of both F. hepatica and G. truncatula to human fascioliasis-endemic areas in these countries.
The Composite Index of Anthropometric Failure (CIAF) can only be applied to children under 5 years of age and does not contemplate obesity. The aim of this study was to propose an Extended CIAF (ECIAF) that combines the characterization of malnutrition due to undernutrition and excess weight, and apply it in six Argentine provinces.
ECIAF excludes children not in anthropometric failure (group A) and was calculated from a percentage of children included in malnutrition categories B: wasting only; C: wasting and underweight; D: wasting, stunting and underweight; E: stunting and underweight; F: stunting only; Y: underweight only; G: only weight excess; and H: stunting and weight excess.
Cross-sectional study conducted in Buenos Aires, Catamarca, Chubut, Jujuy, Mendoza and Misiones (Argentina).
10 879 children of both sexes aged between 3 and 13·99.
ECIAF in preschool children (3 to 4·99 years) was 15·1 %. The highest prevalence was registered in Mendoza (16·7 %) and the lowest in Misiones (12·0 %). In school children (5 to 13·99 years) ECIAF was 28·6 %. Mendoza also recorded the highest rate (30·7 %), while Catamarca and Chubut had the lowest values (27·0 %). In the whole sample, about 25 % of the malnutrition was caused by undernutrition and 75 % by excess weight.
The ECIAF summarizes anthropometric failure by both deficiency and excess weight and it highlights that a quarter of the malnutrition in the Argentine population was caused by undernutrition, although there are differences between Provinces (P < 0·05). ECIAF estimates are higher than those of CIAF or under-nutrition.
We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.
This presentation will enable the learner to:
1.Explore the current molecular landscape of pediatric high grade gliomas
2.Recognize the value of personalized oncogenomic analysis, particularly in rare and/or aggressive tumors
3.Discuss the current status of NTRK inhibitor clinical trials
Background: SMA is a neurodegenerative disease caused by biallelic deletion/mutation of the survival motor neuron (SMN1) gene. In the phase 1 trial (NCT02122952), SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of 15 symptomatic SMA1 patients (3 at a lower dose [cohort 1] and 12 at the proposed therapeutic dose [cohort 2]). This report describes long-term follow-up study design and data from the phase 1 study. Methods: Patients in the phase 1 study could rollover into a long-term follow-up study (NCT03421977). The primary objective is to collect long-term safety data (serious adverse events, hospitalizations, and adverse events of special interest). Annual follow-up will occur for 15 years. Additionally, patient record transfers from local clinician(s) will be requested. Safety assessments include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. Efficacy assessments include physical examination to assess developmental milestones. Results: As of September 27, 2018, the oldest patients are 59.2 (cohort 1) and 52.1 (cohort 2) months old and free of permanent ventilation. Preliminary data, including survival and developmental milestones, will be presented. Conclusions: Patients treated with a one-time dose of AVXS-101 continue to gain strength, develop, and achieve new milestones, demonstrating a long-term, durable response.
Introduction: Very low concentrations of high-sensitivity cardiac troponin can rule-out myocardial infarction (MI) at ED arrival in patients with chest pain. However, this single troponin rule-out strategy works poorly in patients with renal impairment and elevated baseline troponin levels. The objective of this study was to develop and validate a troponin adjustment strategy to accurately rule-out MI with a single hs-cTnTmeasurement in patients with kidney dysfunction. Methods: We used data from three cohorts of ED chest pain patients to develop an adjustment score for a high-sensitivity troponin T (hs-cTnT) assay in patients with kidney dysfunction. The derivation cohort (n = 8846) used administrative and registry data. Two validation cohorts (n = 1187 and 1092) were prospectively-collected. The score assigned points for increasing hs-cTnT levels and subtracted points for lower estimated glomerular filtration rate (eGFR). In the derivation cohort, hs-cTnT concentrations achieving 98.5% sensitivity in of patients with eGFR ≥60, 45-59, 30-44, 15-29 and <15 were assigned ascending positive integer values. Negative integer values were assigned to eGFR values 45-59, 30-44, 15-29 and <15. The scpres for troponin and eGFR were summed for each patient, with scores ranging from −4 to +5. The proportion of patients with 7-day MI ruled out by a score ≤0, sensitivity, NPV, negative likelihood ratio (LR-) and area under the curve (AUC) were quantified in each study cohort. Results: The derivation and validation cohorts had 7-day MI rates of 5.7, 8.6 and 9.1%. In the derivation cohort, a score ≤0 ruled out MI in 35% of patients, with a sensitivity for 7-day MI of 99.5% (95% CI 98-100), NPV of 99.9% (95% CI 98.4-99.9), LR- of 0.02 (95% CI 0.01-0.05) and AUC of 0.88. In the first validation cohort, a score ≤0 ruled out MI in 45% of patients, with a sensitivity for 7-day MI of 97% (95% CI 90-100%), NPV of 99% (95% CI 98-100%), LR- 0.06 (0.02-0.18) and AUC of 0.89. In the second validation cohort, a score ≤0 ruled out MI in 20% of patients, with a sensitivity for 7-day MI of 96% (95% CI 93-99%), NPV of 98% (95% CI 96-100%), LR- of 0.16 (95% CI 0.07-0.39) and AUC of 0.78. Conclusion: We developed and validated a simple scoring system to adjust hs-cTnT concentrations for a patient's kidney function that enables MI to be ruled out in a large proportion of chest pain patients using a single measurement on ED presentation.