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Data from neurocognitive assessments may not be accurate in the context of factors impacting validity, such as disengagement, unmotivated responding, or intentional underperformance. Performance validity tests (PVTs) were developed to address these phenomena and assess underperformance on neurocognitive tests. However, PVTs can be burdensome, rely on cutoff scores that reduce information, do not examine potential variations in task engagement across a battery, and are typically not well-suited to acquisition of large cognitive datasets. Here we describe the development of novel performance validity measures that could address some of these limitations by leveraging psychometric concepts using data embedded within the Penn Computerized Neurocognitive Battery (PennCNB).
Methods:
We first developed these validity measures using simulations of invalid response patterns with parameters drawn from real data. Next, we examined their application in two large, independent samples: 1) children and adolescents from the Philadelphia Neurodevelopmental Cohort (n = 9498); and 2) adult servicemembers from the Marine Resiliency Study-II (n = 1444).
Results:
Our performance validity metrics detected patterns of invalid responding in simulated data, even at subtle levels. Furthermore, a combination of these metrics significantly predicted previously established validity rules for these tests in both developmental and adult datasets. Moreover, most clinical diagnostic groups did not show reduced validity estimates.
Conclusions:
These results provide proof-of-concept evidence for multivariate, data-driven performance validity metrics. These metrics offer a novel method for determining the performance validity for individual neurocognitive tests that is scalable, applicable across different tests, less burdensome, and dimensional. However, more research is needed into their application.
Assessment of risks of illnesses has been an important part of medicine for decades. We now have hundreds of ‘risk calculators’ for illnesses, including brain disorders, and these calculators are continually improving as more diverse measures are collected on larger samples.
Methods
We first replicated an existing psychosis risk calculator and then used our own sample to develop a similar calculator for use in recruiting ‘psychosis risk’ enriched community samples. We assessed 632 participants age 8–21 (52% female; 48% Black) from a community sample with longitudinal data on neurocognitive, clinical, medical, and environmental variables. We used this information to predict psychosis spectrum (PS) status in the future. We selected variables based on lasso, random forest, and statistical inference relief; and predicted future PS using ridge regression, random forest, and support vector machines.
Results
Cross-validated prediction diagnostics were obtained by building and testing models in randomly selected sub-samples of the data, resulting in a distribution of the diagnostics; we report the mean. The strongest predictors of later PS status were the Children's Global Assessment Scale; delusions of predicting the future or having one's thoughts/actions controlled; and the percent married in one's neighborhood. Random forest followed by ridge regression was most accurate, with a cross-validated area under the curve (AUC) of 0.67. Adjustment of the model including only six variables reached an AUC of 0.70.
Conclusions
Results support the potential application of risk calculators for screening and identification of at-risk community youth in prospective investigations of developmental trajectories of the PS.
Enterococcus causes clinically significant bloodstream infections (BSIs). In centers with a higher prevalence of vancomycin resistant enterococcus (VRE) colonization, a common clinical question is whether empiric treatment directed against VRE should be initiated in the setting of a suspected enterococcal BSI. Unfortunately, VRE treatment options are limited, and relatively expensive, and subject patients to the risk of adverse reactions. We hypothesized that the results of VRE colonization screening could predict vancomycin resistance in enterococcal BSI.
Methods:
We reviewed 370 consecutive cases of enterococcal BSI over a 7-year period at 2 tertiary-care hospitals to determine whether vancomycin-resistant BSIs could be predicted based on known colonization status (ie, patients with swabs performed within 30 days, more remotely, or never tested). We calculated sensitivity and specificity, and we plotted negative predictives values (NPVs) and positive predictive values (PPVs) as a function of prevalence.
Results:
A negative screening swab within 30 days of infection yielded NPVs of 90% and 95% in settings where <27.0% and 15.0% of enterococcal BSI are resistant to vancomycin, respectively. In patients with known VRE colonization, the PPV for VRE in enterococcal BSI was >50% at any prevalence exceeding 25%.
Conclusions:
The results of a negative VRE screening test result performed within 30 days can help eliminate unnecessary empiric therapy in patients with suspected enterococcal BSI. Conversely, patients with positive VRE screening swabs require careful consideration of empiric VRE-directed therapy when enterococcal BSI appears likely.
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.
Filamentary structures can form within the beam of protons accelerated during the interaction of an intense laser pulse with an ultrathin foil target. Such behaviour is shown to be dependent upon the formation time of quasi-static magnetic field structures throughout the target volume and the extent of the rear surface proton expansion over the same period. This is observed via both numerical and experimental investigations. By controlling the intensity profile of the laser drive, via the use of two temporally separated pulses, both the initial rear surface proton expansion and magnetic field formation time can be varied, resulting in modification to the degree of filamentary structure present within the laser-driven proton beam.
At the QEII Health Sciences Centre Emergency Department (ED) in Halifax, Nova Scotia, advanced care paramedics (ACPs) perform procedural sedation and analgesia (PSA) for many indications, including orthopedic procedures. We have begun using ACPs as sedationists for emergent upper gastrointestinal (UGI) endoscopy. This study compares ACP-performed ED PSA for UGI endoscopy and orthopedic procedures in terms of adverse events, airway intervention, vasopressor requirement, and PSA medication use.
Methods
A data set was built from an ED PSA quality control database matching 61 UGI endoscopy PSAs to 183 orthopedic PSAs by propensity scores calculated using age, gender, and the American Society of Anesthesiologists (ASA) classification. Outcomes assessed were hypotension (systolic BP<100 mm Hg or a 15% decrease from baseline), hypoxia (SaO2<90%), apnea (>30 sec), vomiting, arrhythmias, death, airway intervention, vasopressor requirement, and PSA medication use.
Results
UGI endoscopy patients experienced hypotension more frequently than orthopedic patients (OR=4.11, CI: 2.05-8.22) and required airway repositioning less often (OR=0.24, CI: 0.10-0.59). They received ketamine more frequently (OR=15.7, CI: 4.75-67.7) and fentanyl less often (OR=0.30, CI: 0.15-0.63) than orthopedic patients. Four endoscopy patients received phenylephrine, and one required intubation. No patient died in either group.
Conclusions
In ACP-led sedation for UGI endoscopy and orthopedic procedures, adverse events were rare with the notable exception of hypotension, which was more frequent in the endoscopy group. Only endoscopy patients required vasopressor treatment and intubation. We provide preliminary evidence that ACPs can manage ED PSA for emergent UGI endoscopy, although priorities must shift from pain control to hemodynamic optimization.
Phased VLA observations of the Galactic center magnetar J1745-2900 over 8-12 GHz reveal rich single pulse behavior. The average profile is comprised of several distinct components and is fairly stable over day timescales and GHz frequencies. The average profile is dominated by the jitter of relatively narrow pulses. The pulses in each of the four profile components are uncorrelated in phase and amplitude, although the occurrence of pulse components 1 and 2 appear to be correlated. Using a collection of the brightest individual pulses, we verify that the index of the dispersion law is consistent with the expected cold plasma value of 2. The scattering time is weakly constrained, but consistent with previous measurements, while the dispersion measure DM = 1763+3−10 pc cm−3 is lower than previous measurements, which could be a result of time variability in the line-of-sight column density or changing pulse profile shape over time or frequency.
The collective response of electrons in an ultrathin foil target irradiated by an ultraintense (${\sim}6\times 10^{20}~\text{W}~\text{cm}^{-2}$) laser pulse is investigated experimentally and via 3D particle-in-cell simulations. It is shown that if the target is sufficiently thin that the laser induces significant radiation pressure, but not thin enough to become relativistically transparent to the laser light, the resulting relativistic electron beam is elliptical, with the major axis of the ellipse directed along the laser polarization axis. When the target thickness is decreased such that it becomes relativistically transparent early in the interaction with the laser pulse, diffraction of the transmitted laser light occurs through a so called ‘relativistic plasma aperture’, inducing structure in the spatial-intensity profile of the beam of energetic electrons. It is shown that the electron beam profile can be modified by variation of the target thickness and degree of ellipticity in the laser polarization.
Introduction: Acute upper gastrointestinal (UGI) bleeding is a relatively common emergency resulting in death in 6 to 8% of cases. UGI endoscopy is the intervention of choice which requires procedural sedation and analgesia (PSA). The Halifax Infirmary emergency department (ED) performs 1000 PSAs annually, performed by advanced care paramedics (ACPs). This has been shown safe for other indications for PSA, such as orthopedic procedures. Considering that UGI endoscopy involves upper airway manipulation, and patients are at an increased risk of massive bleeding, this procedure would be expected to be more complex and have an increased risk of adverse events (AEs). This study aims to compare PSA for UGI endoscopy performed by ACPs to that for orthopedic procedures for AEs, airway intervention and medication use. Methods: This study is a retrospective review of an ACP-performed ED PSA quality control database. A dataset was built matching 64 UGI endoscopy PSAs to 192 orthopedic PSAs by propensity scores calculated using age, gender and ASA classification. Outcomes assessed were hypotension (SBP < 100, or 15% decrease from baseline), hypoxia (SaO2 < 90), apnea (> 30sec), vomiting, arrhythmias and death in the ED. The need for airway intervention and medication use was assessed. Results: The UGI endoscopy group was 4.60 times more likely to suffer hypotension than the orthopedic group (OR=4.6, CI:2.2-9.6), and a fifth as likely to require airway repositioning (OR=0.2, CI:0.1-0.5). One endoscopy patient required endotracheal intubation. No patient died in either group. Compared to the orthopedic group, the UGI endoscopy group was one-third as likely to receive fentanyl (OR=0.3, CI:0.2-0.6). When fentanyl was administered, endoscopy patients received an average 26.7 mcg less than orthopedic patients. The endoscopy group was 15.4 times more likely to receive ketamine (OR=15.4, CI:4.7-66.5), and received 34.4 mg less on average. Four endoscopy patients received phenylephrine compared to none in the orthopedic group. There were no other differences. Conclusion: ED PSA for UGI endoscopy appears to differ significantly from that performed for orthopedic procedures. It was associated with more frequent hypotension and increased use of ketamine as a sedative. Patients undergoing UGI endoscopy were less likely to receive fentanyl and require airway repositioning. Only patients in the endoscopy group required intubation or a vasopressor agent.
Since the dawn of the jet age, passengers on all jet transports, except Concorde, have traveled at about the same speed — a standard Mach 0 83-0 87 range as a practical compromise. After 27 years of supersonic commercial travel, British Airways and Air France retired their fleet of Concorde aircraft at the end of 2003 because it was considered no longer profitable. Clearly, with the retirement of Concorde, the world has lost the only aircraft offering passenger transportation at supersonic speeds. Over the past several years manufacturers have proposed new aircraft designs that promise an increase in transportation speeds. In particular, the business jet market appears to present a business case for an exclusive supersonic business jet (SSBJ). However, there is a key-hurdle which has, until now, prevented the successful launch of a SSBJ hardware program: the development cost for an all-new aircraft quickly eradicates the soughtafter business case. This paper presents the results of a parametric sizing study which aims to answer the following question: is it possible to drastically reduce the development effort of a supersonic business jet design by converting an existing Learjet airframe into a supersonic vehicle while sustaining FAA interest and approval? This paper discusses selected aircraft sizing trades and operations related constraints. The feasibility study indicates some level of technical plausibility for the case of converting an existing airframe into a certifiable lower-cost supersonic aircraft. Acknowledging the range of actual complications related to the task of economically modifying and certifying a legacy airframe towards a SSBJ, it appears that a larger size SSBJ offers significant technical and economical advantages which outweigh the ‘off-the-shelf’ Learjet case.
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.
Schizophrenia is characterized by profound and disabling deficits in the ability to recognize emotion in facial expression and tone of voice. Although these deficits are well documented in established schizophrenia using recently validated tasks, their predictive utility in at-risk populations has not been formally evaluated.
Method.
The Penn Emotion Recognition and Discrimination tasks, and recently developed measures of auditory emotion recognition, were administered to 49 clinical high-risk subjects prospectively followed for 2 years for schizophrenia outcome, and 31 healthy controls, and a developmental cohort of 43 individuals aged 7–26 years. Deficit in emotion recognition in at-risk subjects was compared with deficit in established schizophrenia, and with normal neurocognitive growth curves from childhood to early adulthood.
Results.
Deficits in emotion recognition significantly distinguished at-risk patients who transitioned to schizophrenia. By contrast, more general neurocognitive measures, such as attention vigilance or processing speed, were non-predictive. The best classification model for schizophrenia onset included both face emotion processing and negative symptoms, with accuracy of 96%, and area under the receiver-operating characteristic curve of 0.99. In a parallel developmental study, emotion recognition abilities were found to reach maturity prior to traditional age of risk for schizophrenia, suggesting they may serve as objective markers of early developmental insult.
Conclusions.
Profound deficits in emotion recognition exist in at-risk patients prior to schizophrenia onset. They may serve as an index of early developmental insult, and represent an effective target for early identification and remediation. Future studies investigating emotion recognition deficits at both mechanistic and predictive levels are strongly encouraged.
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.
The extent and severity of wheat take-all (caused by Gaeumannomyces graminis var. tritici (Ggt)) can vary considerably between growing seasons. The current study aimed to identify climatic factors associated with differing concentrations of Ggt DNA in soil and take-all disease at different stages of a sequence of wheat crops. Pre-sowing soil Ggt DNA concentrations and subsequent take-all disease in consecutive wheat crop sequences were compared across six seasons in 90 commercial cropping fields in Canterbury and Southland, New Zealand, between 2003 and 2009. Disease progress was assessed in additional fields in 2004/05 and 2005/06. While a general pattern in inoculum and disease fluctuations was evident, there were exceptions among wheat crop sequences that commenced in different years, especially for first wheat crops. In three consecutive growing seasons, there was very low inoculum increase in the first wheat crop, while increases in first wheat crops during the following three seasons was much greater. Low spring–summer rainfall was associated with low build-up of inoculum in first wheat crops. The inoculum derived from the first wheat then determined the amount of primary inoculum for the subsequent second wheat, thereby influencing the severity of take-all in that crop. Differing combinations of weather conditions during one wheat crop in a sequence and the conditions experienced by the next crop provided explanations of the severity of take-all at grain fill and the resulting post-harvest soil Ggt DNA concentrations in second wheat crops. Examples of contrasting combinations were: (a) a moderate take-all epidemic and high post-harvest inoculum that followed high rainfall during grain fill, despite low pre-sowing soil Ggt DNA concentrations; (b) severe take-all and moderate to high inoculum build-up following high pre-sowing soil Ggt DNA concentrations and non-limiting rainfall; and (c) low spring and early summer rainfall slowing epidemic development in second wheat crops, even where there were high pre-sowing soil Ggt DNA concentrations. The importance of the environmental conditions experienced during a particular growing season was also illustrated by differences between growing seasons in take-all progress in fields in the same take-all risk categories based on pre-sowing soil Ggt DNA concentrations.
There is an increasing interest in pasture-based dairy systems in Europe, mainly because of increasing production costs for intensive dairying. Milk is a matrix of compounds that influence nutritional and manufacturing properties, many dependent on husbandry linked to pasture-based systems (increase in pasture intake, forage : concentrate ratio, clover inclusion in swards/silages and use of alternative dairy breeds). The present study investigated the impact of three grazing-based dairy systems with contrasting feeding intensity or reliance on pasture intakes (conventional high-intensity, low pasture intake [CH], organic medium-intensity, medium pasture intake [OM], conventional low-intensity, high pasture intake [CL]) on milk fatty acid (FA) profiles, protein composition and α-tocopherol and antioxidants concentrations. The proportion of animals of alternative breeds (e.g. Jersey) and crossbred cows in the herd increased with decreasing production intensity (CH < OM < CL). Milk constituents known to be beneficial for human health, such as vaccenic acid, rumenic acid, monounsaturated FA, polyunsaturated FA, antioxidants and caseins, were elevated with decreasing production intensity (CH < OM < CL), while less desirable saturated FA were lower, although not all differences between OM and CL were significant. Omega-3 FA were maximized under OM practices, primarily as a result of higher clover intake. Increases in pasture intake may explain the higher concentrations of desirable FA while increased use of crossbreed cows is likely to be responsible for higher total protein and casein content of milk; a combination of these two factors may explain increased antioxidant levels. The higher concentrations of vaccenic acid, rumenic acid, omega-3 FA, lutein, zeaxanthin, protein and casein in OM and CL milk were found over most sampling months and in both years, reinforcing the higher nutritional quality and manufacturing properties associated with milk from these systems. A switch to pasture-based dairy products would increase the intake of milk's beneficial compounds and reduce consumption of less desirable saturated FA.
The present paper provides an approach for the design and analysis of variety trials that are used to obtain quality trait data. These trials are multi-phase in nature, comprising a field phase followed by one or more laboratory phases. Typically the laboratory phases are costly relative to the field phase and this imposes a limit on the number of samples that can be tested. Historically, this has been achieved by sacrificing field replication, either by testing a single replicate plot for each variety or a single composite sample, obtained by combining material from several field replicates. An efficient statistical analysis cannot be applied to such data so that valid inference and accurate prediction of genetic effects may be precluded. A solution that has appeared recently in the literature is the use of partial replication, in which some varieties are tested using multiple field replicates and the remainder as single replicates only. In the present paper, an approach is proposed in which some varieties are tested using individual field replicate samples and others as composite samples. Replication in the laboratory is achieved by splitting a relatively small number of field samples into sub-samples for separate processing. It is shown that, if necessary, some of the composite samples may be split for this purpose. It is also shown that, given a choice of field compositing and laboratory replication strategy, an efficient design for a laboratory phase may be obtained using model-based techniques. The methods are illustrated using two examples. It is demonstrated that the approach provides more accurate variety predictions compared with the partial replication approach and that the gains can be substantial if the field variation is large relative to the laboratory variation.
Although usually thought of as external environmental stressors, a significant heritable component has been reported for measures of stressful life events (SLEs) in twin studies.
Method
We examined the variance in SLEs captured by common genetic variants from a genome-wide association study (GWAS) of 2578 individuals. Genome-wide complex trait analysis (GCTA) was used to estimate the phenotypic variance tagged by single nucleotide polymorphisms (SNPs). We also performed a GWAS on the number of SLEs, and looked at correlations between siblings.
Results
A significant proportion of variance in SLEs was captured by SNPs (30%, p = 0.04). When events were divided into those considered to be dependent or independent, an equal amount of variance was explained for both. This ‘heritability’ was in part confounded by personality measures of neuroticism and psychoticism. A GWAS for the total number of SLEs revealed one SNP that reached genome-wide significance (p = 4 × 10−8), although this association was not replicated in separate samples. Using available sibling data for 744 individuals, we also found a significant positive correlation of R2 = 0.08 in SLEs (p = 0.03).
Conclusions
These results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.