To test the hypothesis that amantadine hydrochloride is a safe and effective treatment for behavioral disturbances--for example, hyperactivity and irritability--in children with autism.
Thirty-nine ...subjects (intent to treat; 5-19 years old; IQ > 35) had autism diagnosed according to DSM-IV and ICD-10 criteria using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic. The Aberrant Behavior Checklist-Community Version (ABC-CV) and Clinical Global Impressions (CGI) scale were used as outcome variables. After a 1-week, single-blind placebo run-in, patients received a single daily dose of amantadine (2.5 mg/kg per day) or placebo for the next week, and then bid dosing (5.0 mg/kg per day) for the subsequent 3 weeks.
When assessed on the basis of parent-rated ABC-CV ratings of irritability and hyperactivity, the mean placebo response rate was 37% versus amantadine at 47% (not significant). However, in the amantadine-treated group there were statistically significant improvements in absolute changes in clinician-rated ABC-CVs for hyperactivity (amantadine -6.4 versus placebo -2.1; p = .046) and inappropriate speech (-1.9 versus 0.4; p = .008). CGI scale ratings were higher in the amantadine group: 53% improved versus 25% (p = .076). Amantadine was well tolerated.
Parents did not report statistically significant behavioral change with amantadine. However, clinician-rated improvements in behavioral ratings following treatment with amantadine suggest that further studies with this or other drugs acting on the glutamatergic system are warranted. The design of these and similar drug trials in children with autistic disorder must take into account the possibility of a large placebo response.
BACKGROUND: Increasing access to essential respiratory medicines and influenza vaccination has been a priority for over three decades. Their use remains low in low- and middle-income countries ...(LMICs), where little is known about factors influencing use, or about the use of influenza
vaccination for preventing respiratory exacerbations.METHODS: We estimated rates of regular use of bronchodilators, inhaled corticosteroids and influenza vaccine, and predictors for use among 19 000 adults in 23 high-income countries (HICs) and LMIC sites.RESULTS: Bronchodilators,
inhaled corticosteroids and influenza vaccine were used significantly more in HICs than in LMICs, after adjusting for similar clinical needs. Although they are used more commonly by people with symptomatic or severe respiratory disease, the gap between HICs and LMICs is not explained by the
prevalence of chronic obstructive pulmonary disease or doctor-diagnosed asthma. Site-specific factors are likely to influence use differently. The gross national income per capita for the country is a strong predictor for use of these treatments, suggesting that economics influence under-treatment.CONCLUSION:
We still need a better understanding of determinants for the low use of essential respiratory medicines and influenza vaccine in low-income settings. Identifying and addressing these more systematically could improve the access and use of effective treatments.
Background. Recent studies of growth hormone supplementation in chronic heart failure have been associated with variable results. Acquired abnormalities of biochemical parameters of the growth ...hormone insulin-like growth factor I axis have been associated with severe chronic heart failure. There are suggestions of an acquired growth hormone resistance with deficient insulin-like growth factor I in some patients.
Objectives. Therefore, we set out to investigate the clinical and functional status and the degree of cytokine and neurohormonal alteration of chronic heart failure patients with deficient insulin-like growth factor I responses.
Methods. Patients with chronic heart failure were divided into two groups according to their insulin-like growth factor I levels (classified according to the manufacturer’s assay range in normal controls): low insulin-like growth factor I <104 (n = 20; 89 ± 9.6 ng/ml), and normal/high >104 ng/ml (n = 32; 169 ± 52 ng/ml). Between groups there was no difference in age (low versus high: 65.3 ± 12.1 versus 61.6 ± 9.1 years, p = 0.21), body mass index, aerobic capacity (peak oxygen consumption: low versus high: 15.5 ± 5.2 versus 17.3 ± 6.3 mL/kg/min, p = 0.23), left ventricular ejection fraction, New York Heart Association classification.
Results. During quadriceps strength testing, patients with low insulin-like growth factor I had reduced absolute strength (−24%), and strength per unit area muscle (−14%) than patients with normal/high insulin-like growth factor I. Leg muscle cross-sectional area was lower in the low insulin-like growth factor I group (−12% and −13% for right and left legs, respectively). These alterations were accompanied by increased levels of growth hormone (+145%), tumor necrosis factor-alpha (+46%), cortisol/dehydroepiandrosterone ratio (+60%), noradrenaline (+49%) and adrenaline (+136%) (all at least p < 0.05).
Conclusions. Patients with low insulin-like growth factor I levels show signs of altered body composition, cytokine and neuroendocrine activation, to a greater extent than patients with normal/high levels.
Purpose: The aim of this study was to acquire information on the types and longevity of implant‐retained facial prostheses and the opinions of patients on several factors related to their prostheses.
...Materials and Methods: A survey of 75 maxillofacial prosthetic patients currently under treatment and review at the Maxillofacial Unit, Morriston Regional Hospital was conducted through a 23‐question postal questionnaire. These patients were selected as representative of a group of individuals receiving treatment or under review for the fabrication of maxillofacial prostheses.
Results: Of the prosthetic replacements, 83% were ear prostheses, 8% nose, 6% eye, and 2% combination prostheses. Of the 47 respondents, 8 (17%) reported that they were currently wearing their original prostheses. The remaining 39 (83%) respondents had all been provided with at least 1 replacement prosthesis. The mean lifetime of the prostheses was found to be 14 months (range: 4–36 months). The majority of replacement prostheses in this study were provided as a result of color fade or wear of the silicone material of the previous prosthesis. Individuals with no previous experience wearing a prosthesis had an unrealistic expectation of their prosthesis longevity, with a mean value of 17.8 months. In comparison, individuals with previous experience had reduced expectations, with a mean of 14.4 months. In terms of the patients' opinions of the overall quality of their prostheses, the results demonstrated that a large number of patients were satisfied. Thirty‐five patients rated their prostheses as excellent and 9 as good. At 7–12 months, 4 patients rated their prostheses as excellent and 8 as good. At 13 months, 4 patients rated their prostheses as excellent and 5 as good.
Conclusions: It is important that advice be given to patients on the expected average longevity of their prostheses, together with information on factors affecting the longevity (i.e., environmental staining, cosmetics, and cleaning regimes). In this study, 26% of the replacement prostheses were provided due to color fading of the original prosthesis. This highlights the need for continuing research in the development of materials used for the construction of facial prostheses with improved properties, and in particular, improved color stability.
Sandwich composites are of interest in marine applications due to their high strength-to-weight ratio and tailorable mechanical properties, but their resistance to air blast loading is not well ...understood. Full-scale 100 kg TNT equivalent air blast testing at a 15 m stand-off distance was performed on glass-fibre reinforced polymer (GFRP) sandwich panels with polyvinyl chloride (PVC); polymethacrylimid (PMI); and styrene acrylonitrile (SAN) foam cores, all possessing the same thickness and density. Further testing was performed to assess the blast resistance of a sandwich panel containing a stepwise graded density SAN foam core, increasing in density away from the blast facing side. Finally a sandwich panel containing compliant polypropylene (PP) fibres within the GFRP front face-sheet, was subjected to blast loading with the intention of preventing front face-sheet cracking during blast. Measurements of the sandwich panel responses were made using high-speed digital image correlation (DIC), and post-blast damage was assessed by sectioning the sandwich panels and mapping the damage observed. It was concluded that all cores are effective in improving blast tolerance and that the SAN core was the most blast tolerant out of the three foam polymer types, with the DIC results showing a lower deflection measured during blast, and post-blast visual inspections showing less damage suffered. By grading the density of the core it was found that through thickness crack propagation was mitigated, as well as damage in the higher density foam layers, thus resulting in a smoother back face-sheet deflection profile. By incorporating compliant PP fibres into the front face-sheet, cracking was prevented in the GFRP, despite damage being present in the core and the interfaces between the core and face-sheets.
We conducted a retrospective exploratory analysis to evaluate the effects of baseline tumour immune infiltrate on disease-free survival (DFS) outcomes in patients with fully resected stage IIC–IIIC ...melanoma receiving adjuvant vemurafenib monotherapy or placebo in the BRIM8 study.
BRIM8 was a phase III, international, double-blind, randomised, placebo-controlled study. Eligible patients with BRAFV600 mutation–positive, completely resected melanoma were randomly assigned to oral vemurafenib (960 mg twice daily) or matching placebo for 52 weeks. The primary end point was DFS. The association of CD8+ T-cell infiltration and programmed death ligand 1 (PD-L1) expression with DFS, as measured by immunohistochemistry, was explored retrospectively.
Four hundred ninety-eight patients were randomly assigned to receive adjuvant vemurafenib (n = 250) or placebo (n = 248); tumour samples were available for biomarker analysis for approximately 60% of patients. In the pooled biomarker population, placebo-treated patients with <1% CD8+ T cells in the tumour centre had shorter median DFS than those with ≥1% CD8+ T cells (7.7 versus 47.8 months). DFS benefit from vemurafenib versus placebo was greater in patients with <1% CD8+ T cells hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.34–0.92) than in patients with ≥1% CD8+ T cells (HR 0.77; 95% CI 0.48–1.22). Likewise, median DFS was shorter among placebo-treated patients with <5% versus ≥5% PD-L1+ immune cells (IC) in the tumour (7.2 versus 47.8 months). A greater DFS benefit with vemurafenib versus placebo was observed in patients with <5% PD-L1+IC (HR 0.36; 95% CI 0.24–0.56) than in patients with ≥5% PD-L1+IC (HR 0.99; 95% CI 0.58–1.69).
The presence of CD8+ T cells and PD-L1+IC are favourable prognostic factors for DFS. Treatment with adjuvant vemurafenib may overcome the poor DFS prognosis associated with low CD8+ T-cell count or PD-L1 expression.
NCT01667419
•This study confirms the positive prognosis associated with immune/PD-L1+ tumour infiltrate in BRAF mutant melanoma.•The benefit of adjuvant anti–PD-1 therapy in preventing recurrence is less evident in patients with PD-L1–negative tumours.•Adjuvant vemurafenib may overcome the poor prognosis associated with reduced immune/PD-L1–positive tumour infiltrate.•This study suggests that BRAF inhibition may benefit patients with lower levels of baseline immune infiltrate.
Since the work of Ebbesen et al. Nature (London) 391, 667 (1998), there has been immense interest in the optical properties of subwavelength holes in metal layers. While the enhanced transmission ...observed is generally associated with surface plasmon polaritons (SPPs), theoretical predictions suggest a similar response with perfectly conducting materials. However, Pendry et al. Science 305, 847 (2004) proposed that, if textured on a subwavelength scale, even perfect conductors support surface modes. Here, using microwave radiation incident upon an array of metal waveguides, we observe peaks in the transmissivity below cutoff and confirm the crucial role of these SPP-like modes in the mechanism responsible.
The Rayleigh-Taylor instability in its highly nonlinear, turbulent stage causes atomic-scale mixing of the shell material with the fuel in the compressed core of inertial-confinement fusion targets. ...The density of shell material mixed into the outer core of direct-drive plastic-shell spherical-target implosions on the 60-beam, OMEGA laser system is estimated to be 3.4(+/-1.2) g/cm(3) from time-resolved x-ray spectroscopy, charged-particle spectroscopy, and core x-ray images. The estimated fuel density, 3.6(+/-1) g/cm(3), accounts for only approximately 50% of the neutron-burn-averaged electron density, n(e)=2.2(+/-0.4)x10(24) cm(-3).
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