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Objectives: Long-term neurological response to treatment after a severe traumatic brain injury (sTBI) is a dynamic process. Failure to capture individual heterogeneity in recovery may impact findings from single endpoint sTBI randomized controlled trials (RCT). The present study re-examined the efficacy of erythropoietin (Epo) and transfusion thresholds through longitudinal modeling of sTBI recovery as measured by the Disability Rating Scale (DRS). This study complements the report of primary outcomes in the Epo sTBI RCT, which failed to detect significant effects of acute treatment at 6 months post-injury. Methods: We implemented mixed effects models to characterize the recovery time-course and to examine treatment efficacy as a function of time post-injury and injury severity. Results: The inter-quartile range (25th–75th percentile) of DRS scores was 20–28 at week1; 8–24 at week 4; and 3–17 at 6 months. TBI severity group was found to significantly interact with Epo randomization group on mean DRS recovery curves. No significant differences in DRS recovery were found in transfusion threshold groups. Conclusions: This study demonstrated the value of taking a comprehensive view of recovery from sTBI in the Epo RCT as a temporally dynamic process that is shaped by both treatment and injury severity, and highlights the importance of the timing of primary outcome measurement. Effects of Epo treatment varied as a function of injury severity and time. Future studies are warranted to understand the possible moderating influence of injury severity on treatment effects pertaining to sTBI recovery. (JINS, 2019, 25, 293–301)
Background: To determine whether exosomal microRNAs (miRNAs) in CSF of patients with FTD can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic FTD Initiative (GENFI) cohort and in sporadic FTD. Methods: GENFI participants were either carriers of a pathogenic mutation or at risk of carrying a mutation because a first-degree relative was a symptomatic mutation carrier. Exosomes were isolated from CSF of 23 -pre-symptomatic and 15 symptomatic mutation carriers, and 11 healthy non-mutation carriers. Expression of miRNAs was measured using qPCR arrays. MiRNAs differentially expressed in symptomatic compared to pre-symptomatic mutation carriers were evaluated in 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer’s disease (AD), and 10 healthy controls (HCs). Results: In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared to pre-symptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 [90% CI: 0.79-0.98] and 0.81 [90% CI: 0.68-0.93], and when combined an area of 0.93 [90% CI: 0.87-0.99]. In sporadic FTD, only miR-632 was significantly decreased compared to sporadic AD and HCs. Decrease of miR-632 revealed an area of 0.89 [90% CI: 0.80-0.98]. Conclusions: Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.
The Dicyemida and Orthonectida are two groups of tiny, simple, vermiform parasites that have historically been united in a group named the Mesozoa. Both Dicyemida and Orthonectida have just two cell layers and appear to lack any defined tissues. They were initially thought to be evolutionary intermediates between protozoans and metazoans but more recent analyses indicate that they are protostomian metazoans that have undergone secondary simplification from a complex ancestor. Here we describe the first almost complete mitochondrial genome sequence from an orthonectid, Intoshia linei, and describe nine and eight mitochondrial protein-coding genes from Dicyema sp. and Dicyema japonicum, respectively. The 14 247 base pair long I. linei sequence has typical metazoan gene content, but is exceptionally AT-rich, and has a unique gene order. The data we have analysed from the Dicyemida provide very limited support for the suggestion that dicyemid mitochondrial genes are found on discrete mini-circles, as opposed to the large circular mitochondrial genomes that are typical of the Metazoa. The cox1 gene from dicyemid species has a series of conserved, in-frame deletions that is unique to this lineage. Using cox1 genes from across the genus Dicyema, we report the first internal phylogeny of this group.
Cognitive remediation (CR) training has emerged as a promising approach to improving cognitive deficits in schizophrenia and related psychosis. The limited availability of psychological services for psychosis is a major barrier to accessing this intervention however. This study investigated the effectiveness of a low support, remotely accessible, computerised working memory (WM) training programme in patients with psychosis.
Ninety patients were enrolled into a single blind randomised controlled trial of CR. Effectiveness of the intervention was assessed in terms of neuropsychological performance, social and occupational function, and functional MRI 2 weeks post-intervention, with neuropsychological and social function again assessed 3–6 months post-treatment.
Patients who completed the intervention showed significant gains in both neuropsychological function (measured using both untrained WM and episodic task performance, and a measure of performance IQ), and social function at both 2-week follow-up and 3–6-month follow-up timepoints. Furthermore, patients who completed MRI scanning showed improved resting state functional connectivity relative to patients in the placebo condition.
CR training has already been shown to improve cognitive and social function in patient with psychosis. This study demonstrates that, at least for some chronic but stable outpatients, a low support treatment was associated with gains that were comparable with those reported for CR delivered entirely on a 1:1 basis. We conclude that CR has potential to be delivered even in services in which psychological supports for patients with psychosis are limited.
In precision agriculture, the selection and use of appropriate sensors determine the type and quality of information that will feed decision-support models. A wide variety of sensors, spectral ranges, data collection and processing approaches are used, sometimes leading to confusion. Whether in transmission or reflectance mode, multispectral or hyperspectral, laboratory or field-based or even satellite-borne, in order to achieve meaningful and accurate measurements it is essential to have a clear understanding of which part of the electromagnetic spectrum the sensors relate to and how the corresponding radiation interacts with the substrate (e.g. soils, crops, livestock products). Sensors in the visible range (390-700 nm) use colour to identify certain properties of the substrate (e.g. chlorophyll and pigments in crops, organic matter contents in soil) and can be used to detect and quantify colour changes that could, in turn, be correlated with changes in those properties. Alternatively, radiation in the near (NIR, 750-2500 nm) and mid infrared (MIR, 2500-25 000 nm) interacts with the molecular bonds that constitute organic and inorganic matter and, therefore, sensors with detectors in these ranges provide different but interrelated information on the chemical composition of the substrate. Shorter wavelength radiation in the form of X-Rays (0.1-10 nm) induces fluorescence in the substrate and XRF sensors provide elemental atomic information that is highly applicable to the study of soils, sediments and fluids. At the James Hutton Institute, we have expertise in the use of all these types of sensors and are developing practical applications based on a thorough understanding of the processes involved. In this paper we provide an overview of the capabilities and applications of the different sensors used in precision agriculture, not only with a theoretical understanding, but also with an awareness of the practicalities involved.
Changes in seroprevalence of cysticercosis diagnosed in Chandigarh, India between 1998 and 2014 were investigated by extraction and analysis of data from records held at the Postgraduate Institute of Medical Education and Research in Chandigarh. Among the total number of samples for which cysticercosis had been suspected during this period (N = 9650), 1716 (17·8%) were seropositive. Adults were more likely to be seropositive than children, and women were more likely to be seropositive than men. In addition to there being fewer patients with suspicion of cysticercosis over the data analysis period, the proportion of patients seropositive also reduced significantly. Despite these reductions, which are probably associated with improved infrastructure and sanitation within Chandigarh, and despite meat consumption being relatively rare in this area, the extent of cysticercosis in this population remains problematic. Further efforts should be made to reduce transmission of this infection, with particular emphasis on women. Such efforts should follow the One Health concept, and involve medical efforts (including diagnosis and treatment of T. solium tapeworm carriers), veterinary efforts directed towards meat inspection and prevention of infection of pigs, and environmental health and sanitation engineers (to minimize environmental contamination with human waste).
Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset.
Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA.
Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) < 0.01]. The structure of EPDS responses significantly differed between Europe and the USA (∆*CFI > 0.01), but not between European countries (∆*CFI < 0.01).
Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.
Epidemiology formed the basis of ‘the Barker hypothesis’, the concept of ‘developmental programming’ and today’s discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.
Many adults with autism spectrum disorder (ASD) remain undiagnosed. Specialist assessment clinics enable the detection of these cases, but such services are often overstretched. It has been proposed that unnecessary referrals to these services could be reduced by prioritizing individuals who score highly on the Autism-Spectrum Quotient (AQ), a self-report questionnaire measure of autistic traits. However, the ability of the AQ to predict who will go on to receive a diagnosis of ASD in adults is unclear.
We studied 476 adults, seen consecutively at a national ASD diagnostic referral service for suspected ASD. We tested AQ scores as predictors of ASD diagnosis made by expert clinicians according to International Classification of Diseases (ICD)-10 criteria, informed by the Autism Diagnostic Observation Schedule-Generic (ADOS-G) and Autism Diagnostic Interview-Revised (ADI-R) assessments.
Of the participants, 73% received a clinical diagnosis of ASD. Self-report AQ scores did not significantly predict receipt of a diagnosis. While AQ scores provided high sensitivity of 0.77 [95% confidence interval (CI) 0.72–0.82] and positive predictive value of 0.76 (95% CI 0.70–0.80), the specificity of 0.29 (95% CI 0.20–0.38) and negative predictive value of 0.36 (95% CI 0.22–0.40) were low. Thus, 64% of those who scored below the AQ cut-off were ‘false negatives’ who did in fact have ASD. Co-morbidity data revealed that generalized anxiety disorder may ‘mimic’ ASD and inflate AQ scores, leading to false positives.
The AQ's utility for screening referrals was limited in this sample. Recommendations supporting the AQ's role in the assessment of adult ASD, e.g. UK NICE guidelines, may need to be reconsidered.
We have successfully demonstrated optical aperture synthesis at the 4-m Anglo-Australian Telescope. By using a multi-hole mask over the (re-imaged) primary mirror and recording the resulting fringe patterns with high time resolution, diffraction-limited images of sufficiently bright objects can be reconstructed. The data processing uses closure phases to overcome the effects of atmospheric turbulence. We show an image of the double star η Oph, with component separation 0″.45.
Several outbreaks of hepatitis A in men who have sex with men (MSM) were reported in the 1980s and 1990s in Australia and other countries. An effective hepatitis A virus (HAV) vaccine has been available in Australia since 1994 and is recommended for high-risk groups including MSM. No outbreaks of hepatitis A in Australian MSM have been reported since 1996. In this study, we aimed to estimate HAV transmissibility in MSM populations in order to inform targets for vaccine coverage in such populations. We used mathematical models of HAV transmission in a MSM population to estimate the basic reproduction number (R0) and the probability of an HAV epidemic occurring as a function of the immune proportion. We estimated a plausible range for R0 of 1·71–3·67 for HAV in MSM and that sustained epidemics cannot occur once the proportion immune to HAV is greater than ~70%. To our knowledge this is the first estimate of R0 and the critical population immunity threshold for HAV transmission in MSM. As HAV is no longer endemic in Australia or in most other developed countries, vaccination is the only means of maintaining population immunity >70%. Our findings provide impetus to promote HAV vaccination in high-risk groups such as MSM.
Group III-Sb compound semiconductors are promising materials for future CMOS circuits. Especially, In1-xGaxSb is considered as a complimentary p-type channel material to n-type In1-xGaxAs MOSFET due to the superior hole transport properties and similar chemical properties in III-Sb’s to those of InGaAs. The heteroepitaxial growth of In1-xGaxSb on Si substrate has significant advantage for volume fabrication of III-V ICs. However large lattice mismatch between InGaSb and Si results in many growth-related defects (micro twins, threading dislocations and antiphase domain boundaries); these defects also act as deep acceptor levels. Accordingly, unintentional doping in InGaSb films causes additional scattering, increase junction leakages and affects the interface properties. In this paper, we studied the correlations between of defects and hole carrier densities in GaSb and strained In1-xGaxSb quantum well layers by using various designs of metamorphic superlattice buffers.
The continuous trend of achieving more complex microelectronics with smaller nodes yet larger wafer sizes in microelectronics manufacturing lead to aggressive development requirements for chemical mechanical planarization (CMP) process. Particularly, beyond the 14 nm technology the development needs made it a must to introduce high mobility channel materials such as Ge. CMP is an enabler for integration of these new materials into future devices. In this study, we implemented a design of experiment (DOE) methodology in order to understand the optimized CMP slurry parameters such as optimal concentration of surface active agent (sodium dodecyl sulfate-SDS), concentration of abrasive particles and pH from the viewpoint of high removal rate and selectivity while maintaining a defect free surface finish. The responses examined were particle size distribution (slurry stability), zeta potential, material removal rate (MRR) and the surface defectivity as a function of the selected design variables. The impact of fumed silica particle loadings, oxidizer (H2O2) concentration, SDS surfactant concentration and pH were analyzed on Ge/silica selectivity through material removal rate (MRR) surface roughness and defectivity analyses.
Thin films of Polyvinylidene Fluoride (PVDF) copolymers have been incorporated within ferroelectric field effect transistors, all organic thin film transistor devices (OTFTs), piezoelectric actuators, and recently proposed as the ferroelectric layer in a promising multiferroic tunnel junction configuration . The properties of most of these devices would benefit from reduced thickness and better thickness control of the ferroelectric layer during device processing.
A proven means for fabricating ultrathin films of the PVDF copolymer is the Langmuir-Blodgett (LB) technique. This technique involves dissolving the polymer in a volatile solvent which is then dispersed dropwise onto a purified water subphase, leaving an ultrathin layer of the copolymer on the water surface. The ability to control the thickness on the molecular level is the most prominent feature of this technique.
In some early studies , the minimum thickness of these films was found to be about 5 Angstroms, or roughly the same thickness as the intermolecular spacing of the all-trans β phase for the ferroelectric polymers. Later studies have led to the fabrication of films composed of thicker transfer steps: ∼ 1.8 nm per deposition . The discrepancy is likely explained by the nature of the VDF molecule: it is not an amphiphile.
In this study, we further investigate the properties of Langmuir films of ferroelectric copolymers and discuss the observation of an apparent monolayer phase transition based on abrupt changes observed in the compressibility of the films. The main goal of this project is to discover the extent to which the device properties (like transfer step thickness) of PVDF films can be modified through processing conditions.
In this paper we present a study of the switching kinetics of SrTiO3 based resistive switching memory devices. A pulse scheme is used to cycle the cells between the high resistive state (HRS) and the low resistive state (LRS) thereby monitoring the transient currents for a precise analysis of the SET and RESET transitions. By variation of the width and amplitude of the applied pulses the switching kinetics are studied between 10-8 and 104 s. Taking the pre-switching currents into account, a power dependency of the SET is found that emphasizes the importance of local Joule heating for the nonlinearity of the switching kinetics.
Two related outbreaks (in 2009 and 2012) of cryptosporidiosis in Norwegian schoolchildren during a stay at a remote holiday farm provided us with a natural experiment to investigate possible secondary transmission of Cryptosporidium parvum IIa A19G1R1. After the children had returned home, clinical data and stool samples were obtained from their household contacts. Samples were investigated for the presence of Cryptosporidium oocysts by immunofluorescence antibody test. We found both asymptomatic and symptomatic infections, which are likely to have been secondary transmission. Laboratory-confirmed transmission rate was 17% [4/23, 95% confidence interval (CI) 7·0–37·1] in the 2009 outbreak, and 0% (95% CI 0–16·8) in the 2012 outbreak. Using a clinical definition, the probable secondary transmission rate in the 2012 outbreak was 8% (7/83, 95% CI 4·1–16·4). These findings highlight the importance of hygienic and public health measures during outbreaks or individual cases of cryptosporidiosis. We discuss our findings in light of previous studies reporting varying secondary transmission rates of Cryptosporidium spp.