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The aggregation of neurocognitive deficits among the non-psychotic first-degree relatives of adult- and childhood-onset schizophrenia patients suggests that there may be a common etiology for these deficits in childhood- and adult-onset illness. However, there is considerable heterogeneity in the presentation of neurobiological abnormalities, and whether there are differences in the extent of familial transmission for specific domains of cognitive function has not been systematically addressed.
We employed variance components analysis, as implemented in SOLAR-Eclipse, to evaluate the evidence of familial transmission for empirically derived composite scores representing attention, working memory, verbal learning, verbal retention, and memory for faces. We contrast estimates for adult- and childhood-onset schizophrenia families and matched community control pedigrees, and compare our findings to previous reports based on analogous neurocognitive assessments.
We observed varying degrees of familial transmission; attention and working memory yielded comparable, significant estimates for adult-onset and community control pedigrees; verbal learning was significant for childhood-onset and community control pedigrees; and facial memory demonstrated significant familial transmission only for childhood-onset schizophrenia. Model-fitting analyses indicated significant differences in familiality between adult- and childhood-onset schizophrenia for attention, working memory, and verbal learning.
By comprehensively assessing a wide range of neurocognitive domains in adult- and childhood-onset schizophrenia families, we provide additional support for specific neurocognitive domains as schizophrenia endophenotypes. Whereas comparable estimates of familial transmission for certain dimensions of cognitive functioning support a shared etiology of adult- and childhood-onset neurocognitive function, observed differences may be taken as preliminary evidence of partially divergent multifactorial architectures.
Despite its numerous side effects, clozapine is still the most effective antipsychotics making it an ideal reference substance to validate the efficacy of novel compounds for the treatment of schizophrenia. However, blood–brain barrier permeability for most new molecular entities is unknown, requiring central delivery. Thus, we performed a dose-finding study for chronic intracerebroventricular (icv) delivery of clozapine in mice.
Specifically, we implanted wild-type C57BL/6J mice with osmotic minipumps (Alzet) delivering clozapine at a rate of 0.15 µl/h at different concentrations (0, 3.5, 7 and 14 mg/ml, i.e. 0, 12.5, 25 and 50 µg/day). Mice were tested weekly in a modified SHIRPA paradigm, for locomotor activity in the open field and for prepulse inhibition (PPI) of the acoustic startle response (ASR) for a period of 3 weeks.
None of the clozapine concentrations caused neurological deficits or evident gross behavioural alterations in the SHIRPA paradigm. In male mice, clozapine had no significant effect on locomotor activity or PPI of the ASR. In female mice, the 7 and 14 mg/ml dose of clozapine significantly affected both open field activity and PPI, while 3.5 mg/ml of clozapine increased PPI but had no effects on locomotor activity.
Our findings indicate that 7 mg/ml may be the optimal dose for chronic icv delivery of clozapine in mice, allowing comparison to screen for novel antipsychotic compounds.
Public support is usually a precondition for the adoption and successful implementation of costly policies. We argue that such support is easier to achieve with policy-packages that incorporate primary and ancillary measures. We specifically distinguish command-and-control and market-based measures as primary measures and argue that the former will usually garner more public support than the latter given the low-visibility tendency of costs associated with command-and-control measures. Nevertheless, if included in a policy-package, ancillary measures are likely to increase public support by reducing negative effects of primary measures. Based on a choice experiment with a representative sample of 2,034 Swiss citizens, we assessed these arguments with respect to political efforts to reduce vehicle emissions. The empirical analysis supported the argument that policy-packaging affects public support positively, particularly generating more support when ancillary measures are added. Lastly, we ultimately observe that command-and-control measures obtain more public support than market-based instruments.
This paper presents a novel approach for the determination of True-Speed-Over-Ground for trains. Speed determination is accomplished by correlating the received signals of two side-looking radar sensors. The theoretically achievable precision is derived. Test measurements are done in two different scenarios to give a proof of concept. Thereafter a series of field measurements is performed to rate the practical suitability of the approach. The results of the measurements are thoroughly evaluated. The test and field measurements are carried out using a 24 GHz frequency modulated continuous wave radar.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
Engineering Changes (ECs) are substantial elements of the design process of technical products and are in particular relevant for companies due to enormous additional costs and time delays they can cause. In order to better understand ECs and realize efficient Engineering Change Management (ECM), different approaches exist. One aspect of ECM are change propagation analysis, which try to analyze knock-on effects of an EC on other product elements or the development process. How ECs can propagate is in particular difficult to assess for complex products realized within different engineering domains (mechanical, electrical and software engineering). To address this challenge, ECs are classified, strategies to cope with ECs are presented and change propagation approaches are analyzed in this paper. Thereby a lack of indicators for cross-domain propagation is identified. To overcome this issue, the distinction of domain-specific and cross-domain linkage types is proposed and a set of linkage types is presented. Further research is motivated to integrate these linkage types in product models while also considering processes and organizational structures as additional dimensions of ECM.
Ocular complaints prompt a significant number of emergency department (ED) visits, and they can range from benign to sight-threatening. Detailed fundoscopic examination is difficult, even for experienced providers. Point-of-care ultrasound (POCUS) is increasingly utilized in the ED for numerous applications, including ocular evaluation. We present a case in which ocular POCUS was used to diagnose a submacular hemorrhage in a patient who presented with acute painless loss of vision. Ocular POCUS can be readily employed to assess for myriad clinically significant pathologies.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Kochia is one of the most problematic weeds in the United States. Field studies were conducted in five states (Wyoming, Colorado, Kansas, Nebraska, and South Dakota) over 2 yr (2010 and 2011) to evaluate kochia control with selected herbicides registered in five common crop scenarios: winter wheat, fallow, corn, soybean, and sugar beet to provide insight for diversifying kochia management in crop rotations. Kochia control varied by experimental site such that more variation in kochia control and biomass production was explained by experimental site than herbicide choice within a crop. Kochia control with herbicides currently labeled for use in sugar beet averaged 32% across locations. Kochia control was greatest and most consistent from corn herbicide programs (99%), followed by soybean (96%) and fallow (97%) herbicide programs. Kochia control from wheat herbicide programs was 93%. With respect to the availability of effective herbicide options, glyphosate-resistant kochia control was easiest in corn, soybean, and fallow, followed by wheat; and difficult to manage with herbicides in sugar beet.
To define optimal thromboprophylaxis strategy after stent implantation in superior or total cavopulmonary connections.
Stent thrombosis is a rare complication of intravascular stenting, with a perceived higher risk in single-ventricle patients.
All patients who underwent stent implantation within superior or total cavopulmonary connections (caval vein, innominate vein, Fontan, or branch pulmonary arteries) were included. Cohort was divided into aspirin therapy alone versus advanced anticoagulation, including warfarin, enoxaparin, heparin, or clopidogrel. Primary endpoint was in-stent or downstream thrombus, and secondary endpoints included bleeding complications.
A total of 58 patients with single-ventricle circulation underwent 72 stent implantations. Of them 14 stents (19%) were implanted post-superior cavopulmonary connection and 58 (81%) post-total cavopulmonary connection. Indications for stenting included vessel/conduit stenosis (67%), external compression (18%), and thrombotic occlusion (15%). Advanced anticoagulation was prescribed for 32 (44%) patients and aspirin for 40 (56%) patients. Median follow up was 1.1 (25th–75th percentile, 0.5–2.6) years. Echocardiograms were available in 71 patients (99%), and advanced imaging in 44 patients (61%). Thrombosis was present in two patients on advanced anticoagulation (6.3%) and none noted in patients on aspirin (p = 0.187). Both patients with in-stent thrombus underwent initial stenting due to occlusive left pulmonary artery thrombus acutely post-superior cavopulmonary connection. There were seven (22%) significant bleeding complications for advanced anticoagulation and none for aspirin (p < 0.001).
Antithrombotic strategy does not appear to affect rates of in-stent thrombus in single-ventricle circulations. Aspirin alone may be sufficient for most patients undergoing stent implantation, while pre-existing thrombus may warrant advanced anticoagulation.
The launch and subsequent motion of a projectile provide a context for several quantities that yearn to be optimised. Most notable is the horizontal range of the projectile, a problem dating back to Galileo and still studied in modern times; see, for example , , , . In a different direction, the articles  and  provide a solution to the problem of finding the angle of launch that results in the trajectory of longest arc length.
Photoreceptors have high energy demands and densely packed mitochondria through which light passes before phototransduction. Old world primates including humans have three cone photoreceptor types mediating color vision with short (S blue), medium (M green), and long (L red) wavelength sensitivities. However, S-cones are enigmatic. They comprise <10% of the total cone population, their responses saturate early, and they are susceptible in aging and disease. Here, we show that primate S-cones actually have few mitochondria and are fueled by glycolysis, not by mitochondrial respiration. Glycolysis has a limited ability to sustain activity, potentially explaining early S-cone saturation. Mitochondria act as optical filters showing reduced light transmission at 400–450 nm where S-cones are most sensitive (420 nm). This absorbance is likely to arise in a mitochondrial porphyrin that absorbs strongly in the Soret band. Hence, reducing mitochondria will improve S-cone sensitivity but result in increased glycolysis as an alternative energy source, potentially increasing diabetic vulnerability due to restricted glucose access. Further, glycolysis carries a price resulting in premature functional decline as seen in aged S-cones. Soret band absorption may also impact on mitochondrial rich M and L cones by reducing sensitivity at the lower end of their spectral sensitivity range resulting in increased differentiation from S-cone responses. These data add to the list of unique characteristic of S-cones and may also explain aspects of their vulnerability.
In late summer, sometime between cal a.d. 340–405, a hoard of tightly packed, stacked copper-alloy vessels was deposited in the Vale of Pewsey, Wiltshire. The corrosion of the vessels allowed for the preservation of delicate plant macrofossils and pollen. Analysis of this material has provided insights into the date, season and context of this act of structured deposition. A second hoard of similar vessels was deposited in the fourth or fifth century only a few miles away at Wilcot. The hoards and their deposition relate to Romano-British lifeways, at a time when the region was on the cusp of a dramatic period of change. The distribution of late Roman coins and belt fittings offers further insights into the social and economic character of Wiltshire at their times of deposition.
Objective: To determine whether volumetric measures of the hippocampus, entorhinal cortex, and other cortical measures can differentiate between cognitively normal individuals and subjects with mild cognitive impairment (MCI). Method: Magnetic resonance imaging (MRI) data from 46 cognitively normal subjects and 50 subjects with MCI as part of the Boston University Alzheimer’s Disease Center research registry and the Alzheimer’s Disease Neuroimaging Initiative were used in this cross-sectional study. Cortical, subcortical, and hippocampal subfield volumes were generated from each subject’s MRI data using FreeSurfer v6.0. Nominal logistic regression models containing these variables were used to identify subjects as control or MCI. Results: A model containing regions of interest (superior temporal cortex, caudal anterior cingulate, pars opercularis, subiculum, precentral cortex, caudal middle frontal cortex, rostral middle frontal cortex, pars orbitalis, middle temporal cortex, insula, banks of the superior temporal sulcus, parasubiculum, paracentral lobule) fit the data best (R2 = .7310, whole model test chi-square = 97.16, p < .0001). Conclusions: MRI data correctly classified most subjects using measures of selected medial temporal lobe structures in combination with those from other cortical areas, yielding an overall classification accuracy of 93.75%. These findings support the notion that, while volumes of medial temporal lobe regions differ between cognitively normal and MCI subjects, differences that can be used to distinguish between these two populations are present elsewhere in the brain.
Governments are often punished for negative events such as economic downturns and financial shocks. However, governments can address such shocks with salient policy responses that might mitigate public punishment. We use three high-quality nationally representative surveys collected around a key event in the history of the Dutch economy, namely the outbreak of the financial crisis in 2008, to examine how voters responded to a salient government bailout. The results illustrate that governments can get substantial credit for pursuing a bailout in the midst of a financial crisis. Future research should take salient policy responses into account to fully understand the public response to the outbreak of financial and economic crises.