Airway stenting with the LT-Mold? for severe glotto-subglottic stenosis or intractable aspiration: experience in 65 cases.

The purpose of this study was to assess the safety and efficacy of stenting in upper airway reconstructions for benign laryngotracheal stenosis (LTS) with a newly designed prosthesis, the LT-Mold?. The LT-Mold and its proper use during open surgery and endoscopy are described, and the experience gathered from a prospectively collected database on 65 patients treated for complex LTS or severe aspiration is reported. This series is compared to the results of other stenting methods. All patients were available for evaluation. In all but one case, the prosthesis was removed at the end of the study. The new prosthesis did not induce any stent-related trauma to the supraglottis, glottis and subglottis. Before adding a distal round-shaped silicone cap to the LT-Mold, granulation tissue was usually seen at the stent-mucosal interface at the tracheostoma level. In 14 cases, there has been a spontaneous extrusion of the prosthesis through the mouth; this problem was solved by fixing the prosthesis through the reinforced portion of the prosthesis at the cap level and by adding one fixation stitch in the supraglottis. We have to document the loss of the silicone cap in three cases. This problem was resolved by designing a new prototype with an integrated cap, glued with a slow hardening silicone glue. Fifty-four (83 %) of 65 patients were decannulated after a mean duration of stenting of 3 months (range 1-12 months). The mean follow-up after decannulation was 23 months (range 1 month to 10 years). The experience gathered with the LT-Mold shows that long-term stenting for complex LTS is safely achieved when the prosthesis is used with its distal integrated silicone cap. The softness and smoothness of the prosthesis with a round-shaped configuration of both extremities help avoid ulceration and granulation tissue formation in the reconstructed airway. Adequate fixation is mandatory to avoid extrusion.

Uric acid and cardio-metabolic risk factors : an epidemiological approach

The role of serum uric acid (SUA) in cardio-metabolic conditions has long been contentious. It is still unclear if SUA is an independent risk factor or marker of cardio-metabolic conditions and most observed associations are not necessarily causal. This study aimed to further understand and explore the causal role of SUA in cardio-metabolic conditions using genetic and non-genetic epidemiological methods in population-based data. In the first part of this study, we found moderate to high heritability estimates for SUA and fractional excretion of urate (FEUA) suggesting the role of genetic factors in the etiology of hyperuricemia. With regards to the role of SUA on inflammatory markers (IMs), a strong positive association of SUA with C-reactive protein (CRP) and a weaker positive association with tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was observed, which was in part mediated by body mass index (BMI). These findings suggest that SUA may have a role in sterile inflammation. In view of the inconsistency surrounding the causal nature and direction of the relation between SUA and adiposity, we applied a bidirectional Mendelian randomization approach using genetic variants to decipher the association. The finding that elevated SUA is a consequence rather than a cause of adiposity was not totally unexpected and is compatible with the hypothesis that hyperinsulinemia, accompanying obesity, enhances renal proximal tubular reabsorption of uric acid. The fourth part of this study examined the relationship between SUA and blood pressure (BP) in young adults. The association between SUA and BP, significant only in females, was strongly attenuated upon adjustment for BMI. The possibility that BMI lies in the causal pathway may explain the attenuation observed in the associations of SUA with BP and IMs. Finally, a significant hockey-stick shaped association of SUA with social phobia in our data suggests a protective effect of SUA only up to a certain concentration. Although our study findings have shed some light on the uncertainty underlying the pathophysiology of SUA, more compelling evidence using longitudinal designs, randomized controlled trials and the use of robust genetic tools is warranted to increase our understanding of the clinical significance of SUA.

Cardiac raptor deletion impairs adaptive hypertrophy, alters metabolic gene expression and causes heart failure in mice

Background: Mammalian target of rapamycin (mTOR), a central regulator of cell growth, is found in two structurally and functionally distinct multiprotein complexes called mTOR complex (mTORC)1 and mTORC2. The specific roles of each of these branches of mTOR signaling have not been dissected in the adult heart. In the present study, we aimed to bring new insights into the function of cardiac mTORC1-mediated signaling in physiological as well as pathological situations.Methods: We generated mice homozygous for loxP-flanked raptor and positive for the tamoxifen-inducible Cre recombinase (MerCreMer) under control of the α- myosin heavy chain promoter. The raptor gene encodes an essential component of mTORC1. Gene ablation was induced at the age of 10-12 weeks, and two weeks later the raptor cardiac-knockout (raptor-cKO) mice started voluntary cagewheel exercise or were subjected to transverse aortic constriction (TAC) to induce pressure overload.Results: In sedentary raptor-cKO mice, ejection fractions gradually decreased, resulting in significantly reduced values at 38 days (P < 0.001). Raptor-cKO mice started to die during the fifth week after the last tamoxifen injection. At that time, the mortality rate was 36% in sedentary (n = 11) and 64% in exercising (n = 14) mice. TAC-induced pressure overload resulted in severe cardiac dysfunction already at earlier timepoints. Thus, at 7-9 days after surgery, ejection fraction and fractional shortening values were 22.3% vs 43.5% and 10.2% vs 21.5% in raptor-cKO vs wild-type mice, respectively. This was accompanied by significant reductions of ventricular wall and septal thickness as well as an increase in left ventricular internal diameter. Moreover, ventricular weight to tibial length ratios were increased in wild-type, but not in the raptor-cKO TAC mice. Together, this shows that raptor-cKO mice rapidly developed dilated cardiomyopathy without going through a phase of adaptive hypertrophy. Expression of ANP and β-MHC was induced in all raptor-cKO mice irrespective of the cardiac load conditions. Consistent with reduced mTORC1 activity, phosphorylation of ribosomal S6 kinase and 4E-BP1 was blunted, indicating reduced protein synthesis. Moreover, expression of multiple genes involved in the regulation of energy metabolism was altered, and followed by a shift from fatty acid to glucose oxidation.Conclusion: Our study suggests that mTORC1 coordinates protein and energy metabolic pathways in the heart. Moreover, we demonstrate that raptor is essential for the cardiac adaptation to increased workload and importantly, also for normal physiological cardiac function.

Evaluation of Gap-Graded Asphalt Concrete Mixtures Part II: Statistical Design and Analysis, HR-157, 1973

This report presents the results of a comparative laboratory study between well- and gap-graded aggregates used in asphalt concrete paving mixtures. A total of 424 batches of asphalt concrete mixtures and 3, 960 Marshall and Hveem specimens were examined. The main thrust of the statistical analysis conducted in this experiment was in the calibration study and in Part I of the experiment. In the former study, the compaction procedure between the Iowa State University Lab and the Iowa Highway Commission Lab was calibrated. By an analysis of the errors associated with the measurements we were able to separate the "preparation" and "determination" errors for both laboratories as well as develop the calibration curve which describes the relationship between the compaction procedures at the two labs. In Part I, the use of a fractional factorial design in a split plot experiment in measuring the effect of several factors on asphalt concrete strength and weight was exhibited. Also, the use of half normal plotting techniques for indicating significant factors and interactions and for estimating errors in experiments with only a limited number of observations was outlined,

Retrieving Cloud Characteristics from Ground-Based Daytime Color All-Sky Images

A discussion is presented of daytime sky imaging and techniques that may be applied to the analysis of full-color sky images to infer cloud macrophysical properties. Descriptions of two different types of skyimaging systems developed by the authors are presented, one of which has been developed into a commercially available instrument. Retrievals of fractional sky cover from automated processing methods are compared to human retrievals, both from direct observations and visual analyses of sky images. Although some uncertainty exists in fractional sky cover retrievals from sky images, this uncertainty is no greater than that attached to human observations for the commercially available sky-imager retrievals. Thus, the application of automatic digital image processing techniques on sky images is a useful method to complement, or even replace, traditional human observations of sky cover and, potentially, cloud type. Additionally, the possibilities for inferring other cloud parameters such as cloud brokenness and solar obstruction further enhance the usefulness of sky imagers

Investigation of High Performance Concrete Pavement, MLR-05-01, 2006

The Iowa DOT has been using blended cements in ternary mixes since 1999. Use of these supplementary cementitious materials gives concrete with higher strengths and much lower permeability. Use of these materials has been incorporated for use in High Performance Concrete (HPC) decks to achieve lower permeability and thus long term performance. Since we have been using these materials in paving, it would be informative to determine what concrete pavement properties are enhanced as related to high performance concrete. The air void system was excellent at a spacing factor of 0.0047 in (0.120 mm). AVA spacing factor results are much higher than the hardened air void analysis. Although only 3 samples were tested between the image analysis air content and the RapidAir457, there is pretty good agreement between those test methods. Air void analysis indicates that excessive vibration was not required to place the concrete. Vibration was well within the specification limits with an average of 6683 vpm’s with a standard deviation of 461. Overall ride of the project was very good. The average smoothness for the project was 2.1 in/mile (33.8 mm/km). The International Roughness Index (IRI) was 81 in/mi (1.29 m/km). The compressive strength was 6260 psi (43.2 MPa) at 28 days and 6830 (47.1 MPa) at 56 days. The modulus of rupture by third point loading (MOR-TPL) tested at 28 days was 660 psi (4.55 MPa). The AASHTO T277 rapid chloride permeability results at 28 days using the Virginia cure method correlate fairly well with the 56 and 90 day results with standard curing. The Virginia cure method 28 day results were 2475 coulombs and the standard cure 56 and 90 day test results were 2180 and 2118, respectively.

Sensorimotor Plasticity after Music-Supported Therapy in Chronic Stroke Patients Revealed by Transcranial Magnetic Stimulation

BACKGROUND: Several recently developed therapies targeting motor disabilities in stroke sufferers have shown to be more effective than standard neurorehabilitation approaches. In this context, several basic studies demonstrated that music training produces rapid neuroplastic changes in motor-related brain areas. Music-supported therapy has been recently developed as a new motor rehabilitation intervention. METHODS AND RESULTS: In order to explore the plasticity effects of music-supported therapy, this therapeutic intervention was applied to twenty chronic stroke patients. Before and after the music-supported therapy, transcranial magnetic stimulation was applied for the assessment of excitability changes in the motor cortex and a 3D movement analyzer was used for the assessment of motor performance parameters such as velocity, acceleration and smoothness in a set of diadochokinetic movement tasks. Our results suggest that the music-supported therapy produces changes in cortical plasticity leading the improvement of the subjects' motor performance. CONCLUSION: Our findings represent the first evidence of the neurophysiological changes induced by this therapy in chronic stroke patients, and their link with the amelioration of motor performance. Further studies are needed to confirm our observations.

Cost evaluation and comparison of three decision strategies to revascularize : results of the suspected CAD protocol of the european CMR registry

Background: Cardiac magnetic resonance (CMR) is accepted as a method to assess suspected coronary artery disease (CAD). Nonetheless, invasive coronary angiography (CXA) combined or not with fractional flow reserve (FFR) remains the main diagnostic test to evaluate CAD. Little data exist on the economic impact of the use of these procedures in a population with a low to intermediate pre-test probability. Objective: To compare the costs of 3 decision strategies to revascularize a patient with suspected CAD: 1) strategy guided by CMR 2) hypothetical strategy guided by CXA-FFR, 3) hypothetical strategy guided by CXA alone.

Structural abnormalities in the thalamus of migraineurs with aura: a multiparametric study at 3 T.

BACKGROUND AND OBJECTIVES: The thalamus exerts a pivotal role in pain processing and cortical excitability control, and migraine is characterized by repeated pain attacks and abnormal cortical habituation to excitatory stimuli. This work aimed at studying the microstructure of the thalamus in migraine patients using an innovative multiparametric approach at high-field magnetic resonance imaging (MRI). DESIGN: We examined 37 migraineurs (22 without aura, MWoA, and 15 with aura, MWA) as well as 20 healthy controls (HC) in a 3-T MRI equipped with a 32-channel coil. We acquired whole-brain T1 relaxation maps and computed magnetization transfer ratio (MTR), generalized fractional anisotropy, and T2* maps to probe microstructural and connectivity integrity and to assess iron deposition. We also correlated the obtained parametric values with the average monthly frequency of migraine attacks and disease duration. RESULTS: T1 relaxation time was significantly shorter in the thalamus of MWA patients compared with MWoA (P < 0.001) and HC (P ≤ 0.01); in addition, MTR was higher and T2* relaxation time was shorter in MWA than in MWoA patients (P < 0.05, respectively). These data reveal broad microstructural alterations in the thalamus of MWA patients compared with MWoA and HC, suggesting increased iron deposition and myelin content/cellularity. However, MWA and MWoA patients did not show any differences in the thalamic nucleus involved in pain processing in migraine. CONCLUSIONS: There are broad microstructural alterations in the thalamus of MWA patients that may underlie abnormal cortical excitability control leading to cortical spreading depression and visual aura.

Association of biomarkers of lipid modification with functional and morphological indices of coronary stenosis severity in stable coronary artery disease.

Biomarkers of blood lipid modification and oxidative stress have been associated with increased cardiovascular morbidity. We sought to determine whether these biomarkers were related to functional indices of stenosis severity among patients with stable coronary artery disease. We studied 197 consecutive patients with stable coronary artery disease due to single vessel disease. Fractional flow reserve (FFR) ≤ 0.80 was assessed as index of a functionally significant lesion. Serum levels of secretory phospholipase A2 (sPLA2) activity, secretory phospholipase A2 type IIA (sPLA2-IIA), myeloperoxydase (MPO), lipoprotein-associated phospholipase A2 (Lp-PLA2), and oxidized low-density lipoprotein (OxLDL) were assessed using commercially available assays. Patients with FFR > 0.8 had higher sPLA2 activity, sPLA2 IIA, and OxLDL levels than patients with FFR ≤ 0.8 (21.25 [16.03-27.28] vs 25.85 [20.58-34.63] U/mL, p < 0.001, 2.0 [1.5-3.4] vs 2.6 [2.0-3.4] ng/mL, p < 0.01; and 53.0 [36.0-71.0] vs 64.5 [50-89.25], p < 0.001 respectively). Patients with FFR > 0.80 had similar Lp-PLA2 and MPO levels versus those with FFR ≤ 0.8. sPLA2 activity, sPLA2 IIA significantly increased area under the curve over baseline characteristics to predict FFR ≤ 0.8 (0.67 to 0.77 (95 % confidence interval [CI]: 0.69-0.85) p < 0.01 and 0.67 to 0.77 (95 % CI: 0.69-0.84) p < 0.01, respectively). Serum sPLA2 activity as well as sPLA2-IIA level is related to functional characteristics of coronary stenoses in patients with stable coronary artery disease.

Melt/peridotite interaction in the Southern Lanzo peridotite: Field, textural and geochemical evidence

This paper presents field, petrographic-structural and geochemical data on spinet and plagioclase peridotites from the southern domain of the Lanzo ophiolitic peridotite massif (Western Alps). Spinet lherzolites, harzburgites and dunites crop out at Mt. Arpone and Mt. Musine. Field evidence indicates that pristine porphyroclastic spinet lherzolites are transformed to coarse granular spinet harzburgites, which are in turn overprinted by plagioclase peridotites, while strongly depleted spinet harzburgite and dunite bands and bodies replace the plagioclase peridotites. On the northern flank of Mt. Arpone, deformed, porphyroclastic (lithospheric) lherzolites, with diffuse pyroxenite banding, represent the oldest spinel-facies rocks. They show microstructures of a composite subsolidus evolution, suggesting provenance from deeper (asthenospheric) mantle levels and accretion to the lithosphere. These protoliths are locally transformed to coarse granular (reactive) spinet harzburgites and dunites, which show textures reminiscent of melt/rock reaction and geochemical characteristics suggesting that they are products of peridotite interaction with reactively percolating melts. Geochemical data and modelling suggest that <1-5% fractional melting of spinel-facies DMM produced the injected melts. Plagioclase peridotites are hybrid rocks resulting from pre-existing spinet peridotites and variable enrichment of plagioclase and micro-gabbroic material by percolating melts. The impregnating melts attained silica-saturation, as testified by widespread orthopyroxene replacement of olivine, during open system migration in the lithosphere. At Mt. Musine, coarse granular spinet harzburgite and dunite bodies replace the plagioclase peridotites. Most of these replacive, refractory peridotites have interstitial magmatic clinopyroxene with trace element compositions in equilibrium with MORB, while some Cpx have REE-depleted patterns suggesting transient geochemical features of the migrating MORB-type melts, acquired by interaction with the ambient plagioclase peridotite. These replacive spinet harzburgite and dunite bodies are interpreted as channels exploited for focused and reactive migration of silica-undersaturated melts with aggregate MORB compositions. Such melts were unrelated to the silica-saturated melts that refertilized the pre-existing plagioclase peridotites. Finally, MORB melt migration occurred along open fractures, now recorded as gabbroic dikes. Our data document the complexity of rock-types and mantle processes in the South Lanzo peridotite massif and describe a composite tectonic and magmatic scenario that is not consistent with the ``asthenospheric scenario'' proposed by previous authors. We envisage a ``transitional scenario'' in which extending subcontinental lithospheric mantle was strongly modified (both depleted and refertilized) by early melts with MORB-affinity formed by decompression partial melting of the upwelling asthenosphere, during pre-oceanic rifting and lithospheric thinning in the Ligurian Tethys realm. (C) 2006 Elsevier B.V. All rights reserved.

Effects of pioglitazone on renal calcium excretion.

Context: Glitazones increase fracture risk in long-term users and in postmenopausal women. Studies have demonstrated deleterious effects of glitazones on bone metabolism. Glitazones also have direct renal tubular effects increasing sodium reabsorption. We hypothesized that glitazones may also regulate renal calcium excretion. Design: In this double-blind, randomized, placebo-controlled, four-way, crossover study, we examined the effects of pioglitazone (45 mg/d for 6 wk) or placebo on renal calcium and phosphate excretion and PTH levels during different sodium intakes in 16 individuals (eight with type 2 diabetes and eight with essential hypertension). Results: Pioglitazone had no effect on corrected plasma calcium and phosphate levels but decreased significantly the alkaline phosphatase and PTH levels. Pioglitazone induced on average a 45% increase in urinary calcium excretion. The fractional excretion of calcium rose to the same extent, suggesting a glomerular filtration rate-independent effect. Sodium intake did not influence the calciuric effect of pioglitazone. Changes in diurnal and nocturnal calciuria were similar. There was no effect of pioglitazone on phosphate excretion. Conclusion: Pioglitazone decreases PTH levels and increases urinary calcium excretion, independently from changes in glomerular filtration rate and from the sodium load, suggesting an inhibitory effect of pioglitazone on the tubular reabsorption of calcium. These effects may contribute to the increased fracture risk with glitazone treatment.

Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat cancer cachexia model.

Rats bearing the Yoshida AH-130 ascites hepatoma showed enhanced fractional rates of protein degradation in gastrocnemius muscle, heart, and liver, while fractional synthesis rates were similar to those in non-tumor bearing rats. This hypercatabolic pattern was associated with marked perturbations of the hormonal homeostasis and presence of tumor necrosis factor in the circulation. The daily administration of a goat anti-murine TNF IgG to tumor-bearing rats decreased protein degradation rates in skeletal muscle, heart, and liver as compared with tumor-bearing rats receiving a nonimmune goat IgG. The anti-TNF treatment was also effective in attenuating early perturbations in insulin and corticosterone homeostasis. Although these results suggest that tumor necrosis factor plays a significant role in mediating the changes in protein turnover and hormone levels elicited by tumor growth, the inability of such treatment to prevent a reduction in body weight implies that other mediators or tumor-related events were also involved.

Raman analysis of multilayer automotive paints in forensic science: measurement variability and depth profile?

The aim of this work is to study the influence of several analytical parameters on the variability of Raman spectra of paint samples. In the present study, microtome thin section and direct (no preparation) analysis are considered as sample preparation. In order to evaluate their influence on the measures, an experimental design such as 'fractional full factorial' with seven factors (including the sampling process) is applied, for a total of 32 experiments representing 160 measures. Once the influence of sample preparation highlighted, a depth profile of a paint sample is carried out by changing the focusing plane in order to measure the colored layer under a clearcoat. This is undertaken in order to avoid sample preparation such a microtome sectioning. Finally, chemometric treatments such as principal component analysis are applied to the resulting spectra. The findings of this study indicate the importance of sample preparation, or more specifically, the surface roughness, on the variability of the measurements on a same sample. Moreover, the depth profile experiment highlights the influence of the refractive index of the upper layer (clearcoat) when measuring through a transparent layer.

J-shaped association between serum glucose and functional outcome in acute ischemic stroke.

BACKGROUND AND PURPOSE: Hyperglycemia after stroke is associated with larger infarct volume and poorer functional outcome. In an animal stroke model, the association between serum glucose and infarct volume is described by a U-shaped curve with a nadir ≈7 mmol/L. However, a similar curve in human studies was never reported. The objective of the present study is to investigate the association between serum glucose levels and functional outcome in patients with acute ischemic stroke. METHODS: We analyzed 1446 consecutive patients with acute ischemic stroke. Serum glucose was measured on admission at the emergency department together with multiple other metabolic, clinical, and radiological parameters. National Institutes of Health Stroke Scale (NIHSS) score was recorded at 24 hours, and Rankin score was recorded at 3 and 12 months. The association between serum glucose and favorable outcome (Rankin score ≤2) was explored in univariate and multivariate analysis. The model was further analyzed in a robust regression model based on fractional polynomial (-2-2) functions. RESULTS: Serum glucose is independently correlated with functional outcome at 12 months (OR, 1.15; P=0.01). Other predictors of outcome include admission NIHSS score (OR, 1.18; P<0001), age (OR, 1.06; P<0.001), prestroke Rankin score (OR, 20.8; P=0.004), and leukoaraiosis (OR, 2.21; P=0.016). Using these factors in multiple logistic regression analysis, the area under the receiver-operator characteristic curve is 0.869. The association between serum glucose and Rankin score at 12 months is described by a J-shaped curve with a nadir of 5 mmol/L. Glucose values between 3.7 and 7.3 mmol/L are associated with favorable outcome. A similar curve was generated for the association of glucose and 24-hour NIHSS score, for which glucose values between 4.0 and 7.2 mmol/L are associated with a NIHSS score <7. Discussion-Both hypoglycemia and hyperglycemia are dangerous in acute ischemic stroke as shown by a J-shaped association between serum glucose and 24-hour and 12-month outcome. Initial serum glucose values between 3.7 and 7.3 mmol/L are associated with favorable outcome.