479 research outputs found
Automated In-Process Cure Monitoring of Composite Laminates Using a Guided Wave-Based System with High-Temperature Piezoelectric Transducers
An in-process cure monitoring technique based on guided wave concept for carbon fiber reinforced polymer (CFRP) composites was developed. Key parameters including physical properties (viscosity and degree of cure) and state transitions (gelation and vitrification) during the cure cycle were clearly identified experimentally from the amplitude and group velocity of guided waves, validated via the semi-empirical cure process modeling software RAVEN. Using the newly developed cure monitoring system, an array of high-temperature piezoelectric transducers acting as an actuator and sensors were employed to excite and sense guided wave signals, in terms of voltage, through unidirectional composite panels fabricated from Hexcel IM7/8552 prepreg during cure in an oven. Average normalized peak voltage, which pertains to the wave amplitude, was selected as a metric to describe the guided waves phenomena throughout the entire cure cycle. During the transition from rubbery to glassy state, the group velocity of the guided waves was investigated for connection with degree of cure, Tg, and mechanical properties. This work demonstrated the feasibility of in-process cure monitoring and continued progress toward a closed-loop process control to maximize composite part quality and consistency
Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial.
BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions.
METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (≥ 200 cm/s) but no severe vasculopathy. After screening, eligible participants were randomly assigned 1:1 to continue standard transfusions (standard group) or hydroxycarbamide (alternative group). Randomisation was done at a central site, stratified by site with a block size of four, and an adaptive randomisation scheme was used to balance the covariates of baseline age and TCD velocity. The study was open-label, but TCD examinations were read centrally by observers masked to treatment assignment and previous TCD results. Participants assigned to standard treatment continued to receive monthly transfusions to maintain 30% sickle haemoglobin or lower, while those assigned to the alternative treatment started oral hydroxycarbamide at 20 mg/kg per day, which was escalated to each participant\u27s maximum tolerated dose. The treatment period lasted 24 months from randomisation. The primary study endpoint was the 24 month TCD velocity calculated from a general linear mixed model, with the non-inferiority margin set at 15 cm/s. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01425307.
FINDINGS: Between Sept 20, 2011, and April 17, 2013, 159 patients consented and enrolled in TWiTCH. 121 participants passed screening and were then randomly assigned to treatment (61 to transfusions and 60 to hydroxycarbamide). At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. Final model-based TCD velocities were 143 cm/s (95% CI 140-146) in children who received standard transfusions and 138 cm/s (135-142) in those who received hydroxycarbamide, with a difference of 4·54 (0·10-8·98). Non-inferiority (p=8·82 × 10(-16)) and post-hoc superiority (p=0·023) were met. Of 29 new neurological events adjudicated centrally by masked reviewers, no strokes were identified, but three transient ischaemic attacks occurred in each group. Magnetic resonance brain imaging and angiography (MRI and MRA) at exit showed no new cerebral infarcts in either treatment group, but worsened vasculopathy in one participant who received standard transfusions. 23 severe adverse events in nine (15%) patients were reported for hydroxycarbamide and ten serious adverse events in six (10%) patients were reported for standard transfusions. The most common serious adverse event in both groups was vaso-occlusive pain (11 events in five [8%] patients with hydroxycarbamide and three events in one [2%] patient for transfusions).
INTERPRETATION: For high-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocities and help to prevent primary stroke.
FUNDING: National Heart, Lung, and Blood Institute, National Institutes of Health
A survey of adherence to guidelines to prevent healthcare-associated infections in Iranian intensive care units
Background: Healthcare-associated infections (HAIs) are acquired by patients while receiving care. The highest incidence of HAIs has been documented in admissions to intensive care units. Adherence to evidence-based practices is the most important step for preventing HAIs. Objectives: To determine the rate of adherence to evidence-based post-insertion recommended care practices after admission into the intensive care unit for the following devices: central line catheter, indwelling urinary catheter, and mechanical ventilator. Patients and Methods: A structured observational cross-sectional research design was used. Data were collected using a checklist and a self-report questionnaire. The minimum sample size required for this study was 276 post-insertion care episodes, and 332 episodes were observed. TheANOVA test was used to identify any significant differences among themean scores of the three devices. Results: Overall observed adherence rates were 18.3, 59.1, and 43.1 for central line catheters, indwelling urinary catheter, and mechanical ventilator, respectively. Of the observed episodes of device care, only in 9.4 of the episodes was regular oral care performed for patients on mechanical ventilators and only in 19.3 of the episodes were indwelling urinary catheters properly secure after insertion. More so, in none (0.0) of the episodes was the central line catheter hub disinfected before being accessed. Conclusions: Evidence-based post-insertion recommended care practices were not consistently and uniformly implemented in the intensive care units. Establishment of a program for the surveillance of adherence to recommended guidelines is required for improving compliance by health professionals and the quality of preventive care. © 2016, Iranian Red Crescent Medical Journal
AXL modulates extracellular matrix protein expression and is essential for invasion and metastasis in endometrial cancer
The receptor tyrosine kinase AXL promotes migration, invasion, and metastasis. Here, we evaluated the role of AXL in endometrial cancer. High immunohistochemical expression of AXL was found in 76% (63/83) of advanced-stage, and 77% (82/107) of high-grade specimens and correlated with worse survival in uterine serous cancer patients. In vitro, genetic silencing of AXL inhibited migration and invasion but had no effect on proliferation of ARK1 endometrial cancer cells. AXL-deficient cells showed significantly decreased expression of phospho-AKT as well as uPA, MMP-1, MMP-2, MMP-3, and MMP-9. In a xenograft model of human uterine serous carcinoma with AXL-deficient ARK1 cells, there was significantly less tumor burden than xenografts with control ARK1 cells. Together, these findings underscore the therapeutic potentials of AXL as a candidate target for treatment of metastatic endometrial cancer
Detection of CFRP Composite Manufacturing Defects Using a Guided Wave Approach
NASA Langley Research Center is investigating a guided-wave based defect detection technique for as-fabricated carbon fiber reinforced polymer (CFRP) composites. This technique will be extended to perform in-process cure monitoring, defect detection and size determination, and ultimately a closed-loop process control to maximize composite part quality and consistency. The overall objective of this work is to determine the capability and limitations of the proposed defect detection technique, as well as the number and types of sensors needed to identify the size, type, and location of the predominant types of manufacturing defects associated with laminate layup and cure. This includes, porosity, gaps, overlaps, through-the-thickness fiber waviness, and in-plane fiber waviness. The present study focuses on detection of the porosity formed from variations in the matrix curing process, and on local overlaps intentionally introduced during layup of the prepreg. By terminating the cycle prematurely, three 24-ply unidirectional composite panels were manufactured such that each subsequent panel had a higher final degree of cure, and lower level of porosity. It was demonstrated that the group velocity, normal to the fiber direction, of a guided wave mode increased by 5.52 percent from the first panel to the second panel and 1.26 percent from the second panel to the third panel. Therefore, group velocity was utilized as a metric for degree of cure and porosity measurements. A fully non-contact guided wave hybrid system composed of an air-coupled transducer and a laser Doppler vibrometer (LDV) was used for the detection and size determination of an overlap By transforming the plate response from the time-space domain to the frequency-wavenumber domain, the total wavefield was then separated into the incident and backscatter waves. The overlap region was accurately imaged by using a zero-lag cross-correlation (ZLCC) imaging condition, implying the incident and backscattered waves are in phase over the overlap boundaries
Cancer-associated mesothelial cells promote ovarian cancer chemoresistance through paracrine osteopontin signaling
Ovarian cancer is the leading cause of gynecological malignancy-related deaths, due to its widespread intraperitoneal metastases and acquired chemoresistance. Mesothelial cells are an important cellular component of the ovarian cancer microenvironment that promote metastasis. However, their role in chemoresistance is unclear. Here, we investigated whether cancer-associated mesothelial cells promote ovarian cancer chemoresistance and stemness in vitro and in vivo. We found that osteopontin is a key secreted factor that drives mesothelial-mediated ovarian cancer chemoresistance and stemness. Osteopontin is a secreted glycoprotein that is clinically associated with poor prognosis and chemoresistance in ovarian cancer. Mechanistically, ovarian cancer cells induced osteopontin expression and secretion by mesothelial cells through TGF-β signaling. Osteopontin facilitated ovarian cancer cell chemoresistance via the activation of the CD44 receptor, PI3K/AKT signaling, and ABC drug efflux transporter activity. Importantly, therapeutic inhibition of osteopontin markedly improved the efficacy of cisplatin in both human and mouse ovarian tumor xenografts. Collectively, our results highlight mesothelial cells as a key driver of ovarian cancer chemoresistance and suggest that therapeutic targeting of osteopontin may be an effective strategy for enhancing platinum sensitivity in ovarian cancer
Period, birth cohort and prevalence of dementia in mainland China, Hong Kong and Taiwan: a meta-analysis.
OBJECTIVE: There have been dramatic societal changes in East Asia over the last hundred years. Several of the established risk factors could have important period and cohort effects. This study explores temporal variation of dementia prevalence in mainland China, Hong Kong and Taiwan taking study methods into account. METHODS: Seventy prevalence studies of dementia in mainland China, Hong Kong and Taiwan were identified from 1980 to 2012. Five period groups (before 1990, 1990 ~ 1994, 1995 ~ 1999, 2000 ~ 2004 and 2005 ~ 2012) and five birth cohort groups (1895 ~ 1909, 1910 ~ 1919, 1920 ~ 1929, 1930 ~ 1939 and 1940 ~ 1950) were categorised using the year of investigation and 5-year age groups. Pooled prevalence by age, period and birth cohort groups was estimated through meta-regression model and meta-analysis taking diagnostic criteria and age structure into account. RESULTS: After adjusting for diagnostic criteria, the study age range and age structure, the prevalence of dementia in the older population aged 60 years and over fluctuated across periods but not reaching significance and were estimated as 1.8%, 2.5%, 2.1%, 2.4% and 3.1% for the five periods from pre-1990 to 2005 ~ 2012. A potential increasing pattern from less to more recent birth cohort groups was found in the major studies using older diagnostic criteria with wider differences in the age groups over 70 years. CONCLUSIONS: This study found no significant variation across periods but suggested a potential cohort effect. The influence of societal changes might moderate early life experiences across different generations with substantial impact on mental health in older age.There is no specific funding contributing to this study. Yu-Tzu Wu received a PhD scholarship
from the Cambridge Trust, University of Cambridge. Fiona E. Matthews and A. Matthew
Prina were supported by the Medical Research Council [grand number U105292687 and
MR/K021907/1]This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/gps.414
Normative data and discriminative properties of short form 36 (SF-36) in Turkish urban population
BACKGROUND: SF-36 has been both translated into different languages and adapted to different cultures to obtain comparable data on health status internationally. However there have been only a limited number of studies focused on the discriminative ability of SF-36 regarding social and disease status in developing countries. The aim of this study was to obtain population norms of the short form 36 (SF-36) health survey and the association of SF-36 domains with demographic and socioeconomic variables in an urban population in Turkey. METHODS: A cross-sectional study. Face to face interviews were carried out with a sample of households. The sample was systematically selected from two urban Health Districts in Izmir, Turkey. The study group consisted of 1,279 people selected from a study population of 46,290 people aged 18 and over. RESULTS: Internal consistencies of the scales were high, with the exception of mental health and vitality. Physical health scales were associated with both age and gender. On the other hand, mental health scales were less strongly associated with age and gender. Women reported poorer health compared to men in general. Social risk factors (employment status, lower education and economic strain) were associated with worse health profiles. The SF-36 was found to be capable of discriminating disease status. CONCLUSION: Our findings, cautiously generalisable to urban population, suggest that the SF-36 can be a valuable tool for studies on health outcomes in Turkish population. SF-36 may also be a promising measure for research on health inequalities in Turkey and other developing countries
Apraxia in progressive nonfluent aphasia
The clinical and neuroanatomical correlates of specific apraxias in neurodegenerative disease are not well understood. Here we addressed this issue in progressive nonfluent aphasia (PNFA), a canonical subtype of frontotemporal lobar degeneration that has been consistently associated with apraxia of speech (AOS) and in some cases orofacial apraxia, limb apraxia and/or parkinsonism. Sixteen patients with PNFA according to current consensus criteria were studied. Three patients had a corticobasal syndrome (CBS) and two a progressive supranuclear palsy (PSP) syndrome. Speech, orofacial and limb praxis functions were assessed using the Apraxia Battery for Adults-2 and a voxel-based morphometry (VBM) analysis was conducted on brain MRI scans from the patient cohort in order to identify neuroanatomical correlates. All patients had AOS based on reduced diadochokinetic rate, 69% of cases had an abnormal orofacial apraxia score and 44% of cases (including the three CBS cases and one case with PSP) had an abnormal limb apraxia score. Severity of orofacial apraxia (but not AOS or limb apraxia) correlated with estimated clinical disease duration. The VBM analysis identified distinct neuroanatomical bases for each form of apraxia: the severity of AOS correlated with left posterior inferior frontal lobe atrophy; orofacial apraxia with left middle frontal, premotor and supplementary motor cortical atrophy; and limb apraxia with left inferior parietal lobe atrophy. Our findings show that apraxia of various kinds can be a clinical issue in PNFA and demonstrate that specific apraxias are clinically and anatomically dissociable within this population of patients
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