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The Richtmyer–Meshkov instability (RMI) is experimentally investigated in a vertical shock tube using a broadband initial condition imposed on an interface between a helium–acetone mixture and argon (Atwood number
). In the present work, a shear layer is introduced at the interface to serve as a statistically repeatable, broadband initial condition to the RMI, and the density interface is accelerated by either an
planar shock wave. The development of the ensuing mixing layer is investigated using simultaneous planar laser-induced fluorescence (PLIF) and particle image velocimetry (PIV). PLIF images are processed to reveal the light-gas mole fraction, while PIV particle image pairs yield corresponding two-component planar velocity results. Field structure and distribution are explored through probability density functions (PDFs), and a decomposition is performed on concentration and velocity results to obtain a mean flow field and define fluctuations. Simultaneous concentration and velocity field measurements allow – for the first time in this regime – experimentally determined turbulence quantities such as Reynolds stresses, turbulent mass-flux velocities and turbulent kinetic energy to be obtained. We show that by the latest times the mixing layer has passed the turbulent threshold, and there is evidence of turbulent mixing occurring sooner for the higher Mach number case. Interface measurements show nonlinear growth with a power-law fit to the thickness data, and that integral measurements of mixing layer thickness are proportional to threshold measurements. Spectral analysis demonstrates the emergence of an inertial range with a slope
when considering both density and velocity effects in planar turbulent kinetic energy (TKE) measurements.
Background: A major concern of patients undergoing Gamma Knife radiosurgery (GKS) for benign tumors and other conditions is the risk of a separate secondary malignancy or malignant -transformation. The incidence of radiosurgery-associated malignancy based on long-term follow-up remains unknown. Methods: We conducted a population-based cohort study to estimate the incidence rate of both malignant transformation and a separate radiation-associated malignancy in patients undergoing GKS from 1987 to 2016 at 5 centers. Results: 11 527 patients underwent radiosurgery for meningioma (n=3261), arteriovenous malformation (n=2868), trigeminal neuralgia (n=1982), vestibular schwannoma (n=1957), pituitary adenoma (n=1193), other (n=266). The follow-up time ranged from 0.3 to 23.8 years. Four cases of malignant transformation and 3 new malignant brain tumors were reported, two of which were not within the irradiated field. The incidence of malignant transformation was 6.6 per 100 000 patient-years and of new malignancy, either locally or distant, was 5 in 100 000 patient-years. These risks are not higher than the Central Brain Tumor Registry of the United States derived annual incidence rate of all primary malignant CNS tumors of 7.15 per 100 000. Conclusions: Physicians can safely counsel patients that the risk of malignancy after stereotactic radiosurgery remains extremely low, even at long-term follow-up of greater than 10 years.
BACKGROUND: Metabolomics technology has the potential to revolutionize how we screen, diagnose, and treat cancer, as well as improve upon existing cancer molecular tests that may not sufficiently capture the complexity of most malignancies. In this study, we explore the clinical potential of metabolomics analysis in the diagnosis and risk-stratification of brain tumors. METHODS: To test the hypothesis that brain tumor type and survival could be predicted with metabolomics, we analyzed the pre-operative serum and urine samples of patients with glioblastoma (GBM), oligoastrocytoma (OA2), meningioma (M1) and compared them to healthy controls. (HC). Sera from immune-deficient NOD-SCID mice xenografted with human GBM brain tumor initiating cells were also studied. RESULTS: Metabolomics analysis of patient samples was able to accurately differentiate GBM, OA2, M1 and HC (p = 2.3 x 10-26). Subsequently, a prediction model developed and validated internally was able to diagnose GBM with a sensitivity of 86.7% and specificity of 93.8%, and distinguish whether a GBM patient possess O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation (p = 7.4 x 10-10). Within the MGMT methylated group, the model was able to predict longevity (p = 3.25 x 10-4). The model was also able to predict survival irrespective of MGMT methylation status (p = 2.9 x 10-6). CONCLUSIONS: In this study, we demonstrate that metabolomic analysis of patient biofluids can identify brain tumors, distinguish brain tumor subtypes, and independently predict MGMT status as well as longevity among GBM patients. Metabolomics analysis may facilitate non-invasive diagnosis of aggressive brain tumours.
Adult schistosomes live in the blood vessels and cannot easily be sampled from humans, so archived miracidia larvae hatched from eggs expelled in feces or urine are commonly used for population genetic studies. Large collections of archived miracidia on FTA cards are now available through the Schistosomiasis Collection at the Natural History Museum (SCAN). Here we describe protocols for whole genome amplification of Schistosoma mansoni and Schistosome haematobium miracidia from these cards, as well as real time PCR quantification of amplified schistosome DNA. We used microgram quantities of DNA obtained for exome capture and sequencing of single miracidia, generating dense polymorphism data across the exome. These methods will facilitate the transition from population genetics, using limited numbers of markers to population genomics using genome-wide marker information, maximising the value of collections such as SCAN.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent a disease continuum with common genetic causes and molecular pathology. We recently identified mutations in the T-cell restricted intracellular antigen-1 (TIA1) protein as a cause of ALS +/− FTD. TIA1 is an RNA-binding protein containing a low complexity domain (LCD) that promotes the assembly of membrane-less organelles, such as stress granules (SG). Whole exome sequencing of two family members with fALS/FTD revealed a novel missense mutation in the TIA1 LCD (P362L). Subsequent screening identified five more TIA1 mutations in six additional ALS patients, but none in controls. All mutation carriers presented with weakness, behavioral abnormalities or language impairments and had a final diagnosis of ALS +/− FTD. Autopsy on five TIA1 mutation carriers showed widespread neurodegeneration with TDP-43 pathology. Round eosinophilic inclusions in lower motor neurons were a consistent feature. Cellular assays revealed abnormal SG dynamics in the presence of TIA1 mutations. In summary, missense mutations in the LCD of TIA1 are a newly recognized cause of ALS/FTD with TDP-43 pathology and strengthen the role of RNA metabolism in the pathogenesis in this disease.
The Farmers’ Market Fresh Fund Incentive Program is a policy, systems and environmental intervention to improve access to fresh produce for participants on governmental assistance in the USA. The current study examined factors associated with ongoing participation in this matched monetary incentive programme.
Relationship of baseline factors with number of Fresh Fund visits was assessed using Poisson regression. Mixed-effects modelling was used to explore changes in consumption of fruits and vegetables and diet quality.
San Diego, California.
Recipients of Supplemental Nutrition Assistance Program (SNAP), Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) and Supplemental Security Income (SSI) who attended participating farmers’ markets from 2010 to 2012 (n 7298).
Among those with participation for ≤6 months, factors associated with increased visits included reporting more daily servings of fruits and vegetables (F&V) at baseline, being Vietnamese or Asian/Pacific Islander, and eligibility because of SNAP/CalFresh or SSI (v. WIC). Among those who came for 6–12 months, being Asian/Pacific Islander, eligibility because of SNAP/CalFresh and enrolling in the autumn, winter or spring were associated with a greater number of Fresh Fund visits. Among those who came for >12 months, being male and eligibility because of SSI were associated with a greater number of visits. Overall, the odds of increasing number of servings of F&V consumed increased by 2 % per month, and the odds of improved perception of diet quality increased by 10 % per month.
Sustaining and increasing Fresh Fund-type programme operations should be a top priority for future policy decisions concerning farmers’ market use in low-income neighbourhoods.
Background: Web 2.0 technologies (e.g. blogs, social networks, and wikis) are increasingly being utilized by medical schools and postgraduate training programs as tools for information dissemination. These technologies offer the unique opportunity to track metrics of user engagement and interaction. Here, we employ Web 2.0 technologies to assess academic behaviors among neurosurgery residents. Methods: We performed a retrospective review of all educational lectures, part of the core Neurosurgery Residency curriculum at the University of Toronto, posted on our teaching blog (www.TheBrainSchool.net) from Sept 2013 - Nov 2016. We looked for associations with lecturer’s academic position, timing of examinations, and lecture/subspecialty topic. Results: The overall number of clicks on 123 lectures was 1079. Most of these clicks were occurring during the in-training exam month (43%). Click numbers were significantly higher on lectures presented by faculty (mean 18.6, SD ± 4.1) compared to residents-delivered lectures (mean 8.4, SD ± 2.1) (P= 0.031). Functional neurosurgery lectures were the most downloaded (47%), followed by pediatric neurosurgery (22%). Conclusions: The current study demonstrates the value of Web 2.0 analytic tools in examining residents study behavior. Residents tend to ‘cram’ downloading lectures in the same month of training exams and display a preference for faculty-delivered lectures.
Measurement error in self-reported total sugars intake may obscure associations between sugars consumption and health outcomes, and the sum of 24 h urinary sucrose and fructose may serve as a predictive biomarker of total sugars intake.
The Study of Latinos: Nutrition & Physical Activity Assessment Study (SOLNAS) was an ancillary study to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) cohort. Doubly labelled water and 24 h urinary sucrose and fructose were used as biomarkers of energy and sugars intake, respectively. Participants’ diets were assessed by up to three 24 h recalls (88 % had two or more recalls). Procedures were repeated approximately 6 months after the initial visit among a subset of ninety-six participants.
Four centres (Bronx, NY; Chicago, IL; Miami, FL; San Diego, CA) across the USA.
Men and women (n 477) aged 18–74 years.
The geometric mean of total sugars was 167·5 (95 % CI 154·4, 181·7) g/d for the biomarker-predicted and 90·6 (95 % CI 87·6, 93·6) g/d for the self-reported total sugars intake. Self-reported total sugars intake was not correlated with biomarker-predicted sugars intake (r=−0·06, P=0·20, n 450). Among the reliability sample (n 90), the reproducibility coefficient was 0·59 for biomarker-predicted and 0·20 for self-reported total sugars intake.
Possible explanations for the lack of association between biomarker-predicted and self-reported sugars intake include measurement error in self-reported diet, high intra-individual variability in sugars intake, and/or urinary sucrose and fructose may not be a suitable proxy for total sugars intake in this study population.
Background: Lumbar fusion for degenerative indications is associated with a great degree of practice variation. We summarize the current evidence on the comparative safety and efficacy of lumbar fusion, decompression alone, or non-operative care for degenerative indications. Methods: Literature search of electronic bibliographic databases was conducted. Comparative studies reporting validated measures of safety or efficacy were included. Treatments effects were calculated through DerSimonian and Laird random effects models. Results: We retrieved 62 studies (17 randomized controlled, 15 prospective, 15 retrospective, and 15 registries), enrolling a total 302,347 adult patients. Disability, pain, and patient satisfaction following fusion, decompression alone, or non-operative care were dependent on surgical indications and study methodology. Relative to decompression alone, the risk of reoperation following fusion was increased for spinal stenosis (relative risk [RR] 1.17, 95% CI 1.06 to 1.30, p<0.004) and decreased for spondylolisthesis (RR 0.71, 95% CI 0.59 to 0.84, p<0.001). In all indications, complications were more frequent following fusion (RR 1.88, 95% CI 1.37 to 2.58, p<0.001). Mortality and treatment modality were not associated. Conclusions: Improvements were greatest in patients undergoing fusion for spondylolisthesis while complications limited the role of fusion for spinal stenosis. The relative safety and efficacy of fusion for chronic low back pain suggested careful patient selection is required.
This paper presents a formal framework for achieving multi-contact bipedal robotic walking, and realizes this methodology experimentally on two robotic platforms: AMBER2 and Assume The Robot Is A Sphere (ATRIAS). Inspired by the key feature encoded in human walking—multi-contact behavior—this approach begins with the analysis of human locomotion and uses it to motivate the construction of a hybrid system model representing a multi-contact robotic walking gait. Human-inspired outputs are extracted from reference locomotion data to characterize the human model or the spring-loaded invert pendulum (SLIP) model, and then employed to develop the human-inspired control and an optimization problem that yields stable multi-domain walking. Through a trajectory reconstruction strategy motivated by the process that generates the walking gait, the mathematical constructions are successfully translated to the two physical robots experimentally.
A recent mixed-methods study on the state of emergency medical services (EMS) research in Canada led to the generation of nineteen actionable recommendations. As part of the dissemination plan, a survey was distributed to EMS stakeholders to determine the anticipated impact and feasibility of implementing these recommendations in Canadian systems.
An online survey explored both the implementation impact and feasibility for each recommendation using a five-point scale. The sample consisted of participants from the Canadian National EMS Research Agenda study (published in 2013) and additional EMS research stakeholders identified through snowball sampling. Responses were analysed descriptively using median and plotted on a matrix. Participants reported any planned or ongoing initiatives related to the recommendations, and required or anticipated resources. Free text responses were analysed with simple content analysis, collated by recommendation.
The survey was sent to 131 people, 94 (71.8%) of whom responded: 30 EMS managers/regulators (31.9%), 22 researchers (23.4%), 15 physicians (16.0%), 13 educators (13.8%), and 5 EMS providers (5.3%). Two recommendations (11%) had a median impact score of 4 (of 5) and feasibility score of 4 (of 5). Eight recommendations (42%) had an impact score of 5, with a feasibility score of 3. Nine recommendations (47%) had an impact score of 4 and a feasibility score of 3.
For most recommendations, participants scored the anticipated impact higher than the feasibility to implement. Ongoing or planned initiatives exist pertaining to all recommendations except one. All of the recommendations will require additional resources to implement.
The objectives of the study were to analyze the association between Parkinson’s disease and restless legs syndrome, and explore the relationship between mood disorder comorbidity (anxiety and depression), pain, and restless legs syndrome. This study included 123 Parkinson’s disease patients and 123 healthy controls matched for age and gender, and evaluated for anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence. This was performed using semi-structured interviews and a neurological examination. Restless Legs Syndrome diagnostic criteria and the following inventories were used; Hospital Anxiety and Depression Scale, Brief Pain Inventory, and Pain Disability Index. Parkinson’s disease patients had significantly greater anxiety severity, depression severity, pain severity, pain interference, pain disability, and restless legs syndrome prevalence in comparison to controls. In addition, Parkinson’s disease patients’ comorbid for anxiety and depression had significantly greater pain severity, pain interference, and pain disability, but not RLS prevalence, in comparison to Parkinson’s disease only, Parkinson’s disease anxiety, and Parkinson’s disease depression patients. Pain interference, pain severity, and pain disability is greater among Parkinson’s disease patients with anxiety and depression, in comparison to Parkinson’s disease patients without anxiety and depression. On the contrary, the prevalence of restless legs syndrome was not found to be relevant.
Objective of this study was assess the prevalence of Essential of Essential Tremor in Parkinson’s disease population Essential tremor (ET) is the most common movement disorders and is much more common than Parkinson’s disease, in general population. Essential Tremor and Parkinson’s disease (PD) tremor differ in type, frequency and distribution. Despite being two separate disorders, there have been cases reported of coexistence of ET-PD. Some studies have reported an increase in the incidence of ET in relatives of patients with PD, yet the risk of developing PD in ET patients has not been thoroughly investigated. Our study set out to determine the prevalence of precedent ET in PD patients. We conducted a retrospective chart review analysis of 332 idiopathic PD patients to determine how many of them had ET prior to the diagnosis of PD and the percentage of them who were also diagnosed with ET. Our results indicated that the prevalence of precedent ET among a population of idiopathic PD patients was not any higher than the prevalence of ET in a comparable general population. Our results support the notion that ET and PD are mutually independent disorders. Further studies are needed to understand the exact relationship between these two disorders
To date evidence of the relationship between cognition and Aβ amyloid during the early stages of Alzheimer's Disease (AD) has been inconsistent. This study aimed to describe the nature and magnitude of the relationship between Aβ amyloid and cognitive performance of individuals without dementia.
Composite cognitive measures were developed from the Australian Imaging Biomarkers and Lifestyle study neuropsychological test battery using data from 768 healthy older adults and 133 adults with mild cognitive impairment (MCI). A subgroup of this sample (174 healthy, 53 MCI) underwent neuroimaging for Aβ amyloid.
Within the MCI group individuals with high Aβ amyloid showed selective impairment for memory compared with those with low Aβ amyloid; however, this difference was not evident in the healthy group.
The current findings provide further evidence of the relationship between Aβ amyloid and cognition, with memory impairment being the primary symptom of the underlying disease during the prodromal phases of AD.
The prognostic value of subjective memory complaints (SMCs) in the diagnosis of dementia of the Alzheimer's type is unclear. While some studies have found an association between SMCs and cognitive decline, many have found a stronger association with depression, which raises questions about their diagnostic utility.
We examined the cross-sectional association between SMC severity (as measured using the MAC-Q, a brief SMC questionnaire) and affect, memory, and Alzheimer's disease (AD) biomarkers (β-amyloid deposition and the apolipoprotein E ε4 (APOEε4) allele) in healthy elderly controls (HC; M = 78.74 years, SD = 6.7) and individuals with mild cognitive impairment (MCI; M = 72.74 years, SD = 8.8). We analyzed a subset of individuals drawn from the Australian Imaging Biomarkers and Lifestyle (AIBL) Study of Aging.
SMCs were more severe in MCI patients than in HCs. SMC severity was related to affective variables and the interaction between age and group membership (HC/MCI). Within the HC group, SMC severity was related to affective variables only, while severity correlated only with age in the MCI group. SMCs were not related to cognitive variables or AD biomarkers.
SMCs were related to solely by poorer mood (greater depressive and anxious symptomatology) in the cognitively healthy elderly however mean levels were subclinical. This finding argues for the assessment of affective symptomatology in conjunction with cognitive assessment in elderly memory complainers. Future AIBL research will focus on assessing other AD biomarkers, such as brain atrophy and Aβ plasma markers, in relation to complaint severity. Once our 36-month follow-up data are collected, we propose to assess whether SMCs can predict future cognitive decline.
The Th3P4-type lanthanum sulfides are n-type semiconductors and a continuous series of solid solutions is found between the compositions of La3S4 and La2S3. These materials are attractive for use in high temperature thermoelectric applications because of their high melting points, low thermal conductivities and their inherent ability to vary the electron concentration from a maximum of 6.02 × 1021 cm−3 for La3S4 to zero for La2S3 (i.e., self-doping). In this study, La3S4 compounds in which trivalent La has been partially substituted by divalent Sm, Eu or Yb (La3−xMxS4 , x = 0.1 to 0.9) have been prepared by the pressure assisted reaction sintering method and were found to have the Th3P4 structure. The thermoelectric properties (Seebeck coefficient and electrical resistivity) were measured as a function of temperature and the optimum composition was found for x between 0.2 and 0.3 in which the electrical power factor was a maximum at 1000°C.
The phase relationships and the important structural, electrical and thermal properties of the R3X4-R2X3 (where R = lanthanides and X = S, Se and Te) phases having the Th3P4 -type structure are reviewed. The room temperature electrical resistivity and Seebeck coefficient of these materials are independent of R and only slightly dependent on X, but critically dependent on the X:R ratio. The long term stability of these phases is also reviewed. Although these materials have good thermoelectric properties there are some problems which need to be solved before these phases can be utilized in thermoelectric devices. These problems include long term stability, higher than desirable thermal conductivities, and low electron mobilities.