Nearly perfect near-infrared luminescence efficiency of Si nanocrystals: A comprehensive quantum yield study employing the Purcell effect.

Thin layers of silicon nanocrystals (SiNC) in oxide matrix with optimized parameters are fabricated by the plasma-enhanced chemical vapor deposition. These materials with SiNC sizes of about 4.5 nm and the SiO2 barrier thickness of 3 nm reveal external quantum yield (QY) close to 50% which is near to the best chemically synthetized colloidal SiNC. Internal QY is determined using the Purcell effect, i.e. modifying radiative decay rate by the proximity of a high index medium in a special wedge-shape sample. For the first time we performed these experiments at variable temperatures. The complete optical characterization and knowledge of both internal and external QY allow to estimate the spectral distribution of the dark and bright NC populations within the SiNC ensemble. We show that SiNCs emitting at around 1.2-1.3 eV are mostly bright with internal QY reaching 80% at room temperature and being reduced by thermally activated non-radiative processes (below 100 K internal QY approaches 100%). The mechanisms of non-radiative decay are discussed based on their temperature dependence.

Interplay of bimolecular and Auger recombination in photoexcited carrier dynamics in silicon nanocrystal/silicon dioxide superlattices.

We report results of investigating carrier recombination in silicon nanocrystal/silicon dioxide superlattices. The superlattices prepared by nitrogen-free plasma enhanced chemical vapour deposition contained layers of silicon nanocrystals. Femtosecond transient transmission optical spectroscopy was used to monitor carrier mechanisms in the samples. The three-particle Auger recombination was observed in accord with previous reports. However, under high pump intensities (high photoexcited carrier densities) the bimolecular process dominated the recombination. Detailed analysis of measured data and fitting procedure made it possible to follow and quantify the interplay between the two recombination processes. The bimolecular recombination was interpreted in terms of the trap-assisted Auger recombination.

Structural parameters effect on the electrical and electroluminescence properties of silicon nanocrystals/SiO2 superlattices.

The effect of the oxide barrier thickness (tSiO2) reduction and the Si excess ([Si]exc) increase on the electrical and electroluminescence (EL) properties of Si-rich oxynitride (SRON)/SiO2 superlattices (SLs) is investigated. The active layers of the metal-oxide-semiconductor devices were fabricated by alternated deposition of SRON and SiO2 layers on top of a Si substrate. The precipitation of the Si excess and thus formation of Si nanocrystals (NCs) within the SRON layers was achieved after an annealing treatment at 1150 °C. A structural characterization revealed a high crystalline quality of the SLs for all devices, and the evaluated NC crystalline size is in agreement with a good deposition and annealing control. We found a dramatic conductivity enhancement when the Si content is increased or the SiO2 barrier thickness is decreased, due to a larger interaction of the carrier wavefunctions from adjacent layers. EL recombination dynamics were studied, revealing radiative recombination decay times of the order of tens of microseconds. Lower lifetimes were found at higher [Si]exc, attributed to exciton confinement delocalization, whereas intermediate barrier thicknesses present the slowest decay. The electrical-to-light conversion efficiency increases monotonously at thicker barriers and smaller Si contents. We ascribe these effects mainly to free carriers, which enhance carrier transport through the SLs while strongly quenching light emission. Finally, the combination of the different results led us to conclude that tSiO2 âˆ¼ 2 nm and [Si]exc from 12 to 15 at% are the ideal structure parameters for a balanced electro-optical response of Si NC-based SLs.

Pten and p53 converge on c-Myc to control differentiation, self-renewal, and transformation of normal and neoplastic stem cells in glioblastoma.

Glioblastoma (GBM) is a highly lethal primary brain cancer with hallmark features of diffuse invasion, intense apoptosis resistance and florid necrosis, robust angiogenesis, and an immature profile with developmental plasticity. In the course of assessing the developmental consequences of central nervous system (CNS)-specific deletion of p53 and Pten, we observed a penetrant acute-onset malignant glioma phenotype with striking clinical, pathological, and molecular resemblance to primary GBM in humans. This primary, as opposed to secondary, GBM presentation in the mouse prompted genetic analysis of human primary GBM samples that revealed combined p53 and Pten mutations as the most common tumor suppressor defects in primary GBM. On the mechanistic level, the "multiforme" histopathological presentation and immature differentiation marker profile of the murine tumors motivated transcriptomic promoter-binding element and functional studies of neural stem cells (NSCs), which revealed that dual, but not singular, inactivation of p53 and Pten promotes cellular c-Myc activation. This increased c-Myc activity is associated not only with impaired differentiation, enhanced self-renewal capacity of NSCs, and tumor-initiating cells (TICs), but also with maintenance of TIC tumorigenic potential. Together, these murine studies have provided a highly faithful model of primary GBM, revealed a common tumor suppressor mutational pattern in human disease, and established c-Myc as a key component of p53 and Pten cooperative actions in the regulation of normal and malignant stem/progenitor cell differentiation, self-renewal, and tumorigenic potential.

Effect of atorvastatin 15 mg/week on serum lipids in patients with hypercholesterolemia.

Atorvastatin 15 mg/week was administered to 21 patients with hypercholesterolemia for 2 months. The mean low-density lipoprotein concentration decreased by 20% after treatment.

Application of a non-indexed dual sprayer pneumatically assisted electrospray source to the high throughput quantitation of target compounds in biological fluids.

The need for increased throughput in the quantitation of target compounds in biological fluids by high performance liquid chromatography/mass spectrometry continues to drive research in this area. This report describes the application of a prototype dual sprayer electrospray source for the quantitative analysis of biological samples. Quantitative performance for 180 compounds in a microsomal stability assay was found to be adequate when compared with a conventional single sprayer measurement. Issues with use of dual sprayers in a routine production environment are discussed.

Issues and outcomes in integrated treatment programs for dual disorders.

In an integrated, dual disorder treatment program delivered at two sites, the authors address numerous barriers to delivering services to dually diagnosed consumers and employ a set of multidimensional indicators to assess outcome. Consumers who received services through the well-implemented, integrated services program for 12 months were functioning better in the community. There was a cost shifting from mental health to drug and alcohol services, as well as a one-third increase in the total costs of care by the end of the first year of treatment. Program implementation issues are described and the clinical management implications for more effectively serving dually diagnosed consumers through integrated treatment programs are discussed.

Randomized, controlled trial of glucosamine for treating osteoarthritis of the knee.

OBJECTIVE: To determine the effectiveness of glucosamine in reducing pain from osteoarthritis of the knee. DESIGN: Randomized, double-blind parallel trial of glucosamine 500 mg three times daily or a placebo for 2 months. SETTING: Veterans Affairs Medical Center, Prescott, AZ. PARTICIPANTS: Ninety-eight patients aged 34 to 81 being treated for osteoarthritis of the knee. MAIN OUTCOME MEASURES: Pain intensity both at rest and while walking as assessed by a visual analog scale at baseline and after 30 and 60 days of treatment. RESULTS: Forty-nine patients were randomly allocated to each group. There was no statistical difference between the two groups in scores on the visual analog scale at 30 days for resting (mean [SD] score placebo group 3.5 [2.7] vs 3.3 [2.4] glucosamine group, P = 0.66) or walking (5.1 [2.6] vs 5.3 [2.4], P = 0.69); there was also no difference at 60 days for resting (3.4 [2.5] vs 3.2 [2.5], P = 0.81) or walking (4.9 [2.2] vs 4.9 [2.8], P = 0.90). There was also no statistical difference between groups in the mean change from baseline in scores on the visual analog scale (mean [SD] change for walking at 60 days placebo group -1.5 [2.5] vs glucosamine group -1.4 [3.0], P = 0.77). Two participants taking glucosamine and 4 taking placebo withdrew from the study due to adverse side effects (P = 0.67). CONCLUSION: Glucosamine was no better than placebo in reducing pain from osteoarthritis of the knee in this group of patients.

High-speed HPLC/MS/MS analysis of biological fluids: a practical review.

Over the course of the last three or four years, the need for increased throughput analytical methods in support of drug discovery operations has dramatically increased. Once a nicety, methods which can provide reliable quantitation of target analytes in biological fluids are now necessary to keep pace with biological screening. To date, the only successful approaches to direct high-speed quantitation of large numbers of diverse compounds are based on high-performance liquid chromatography/mass spectrometric (HPLC/MS/MS) techniques. Key challenges to this task include sample preparation, the automated development of methods and the rapid analysis of many samples. Accomplishing these tasks requires the use of generic methods, which can be applied across many structurally diverse compounds. In this review, the state-of-the-art in high-speed HPLC/MS/MS is reviewed with the aim of describing the most practical and effective approaches currently in use.

A comparison of fluvastatin 40 mg every other day versus 20 mg every day in patients with hypercholesterolemia.

STUDY OBJECTIVE: To assess the efficacy of fluvastatin administered every other day versus an equivalent dose given daily in patients with hypercholesterolemia. DESIGN: Randomized, nonblinded, crossover study. SETTING: Veterans Affairs Medical Center. PATIENTS: Twenty-three patients with low-density lipoprotein (LDL) levels above 160 mg/dl despite diet therapy INTERVENTION: Patients received fluvastatin 40 mg every other day or 20 mg/day, all doses taken at bedtime. Each treatment arm was 6 weeks in duration. MEASUREMENTS AND MAIN RESULTS: A lipid profile was determined at baseline and after each regimen. Both regimens significantly lowered total cholesterol and LDL versus baseline. The LDL levels were lowered by 24% and 21% by fluvastatin 20 mg/day and 40 mg every other day, respectively. There was no statistically significant difference in lipid components between regimens. CONCLUSION: Fluvastatin 40 mg every other day is effective in lowering total cholesterol and LDL in patients with hypercholesterolemia.

Changes in serum lipids when fluvastatin is substituted for lovastatin in the same doses.

This study evaluated changes in serum lipids when fluvastatin was substituted for lovastatin using equivalent doses. Results showed that serum lipids, especially low-density lipoprotein cholesterol, significantly increase with this substitution.

Respiratory-dependent laser-Doppler flux motion in different skin areas and its meaning to autonomic nervous control of the vessels of the skin.

The aim of this study is to evaluate and quantify the respiratory dependency of cutaneous laser-Doppler flux motion in two variable innervated sites of the upper extremity (the proximal volar forearm and the fingertip) by using a computer-supported system. Various spontaneous (6-17/ min) and externally triggered (12 or 6/min) respiratory frequencies were used for comparative frequency analysis of the laser-Doppler flux signal. Further, an index (MIRSF) was determined as an indicator of the correlation between flux motion and respiration. The MIRSF is defined as the ratio of the power spectrum of the LDF signal at the specific respiratory frequency divided by the time-averaged LDF for that time period. The MIRSF enables a comparison of different intra- and interindividual flux values. A very high correlation was seen between the respiratory frequency and the MIRSF during spontaneous respiration in the skin of the proximal volar forearm; the lower the spontaneous respiratory frequency, the higher the MIRSF. However, this correlation could not be found in the results of the fingertip. The presence of a constant and therefore externally triggered respiratory frequency increased the modulations of the LDF at both measurement locations. While triggered respiration produced a decline in the taLDF of the fingertip, the taLDF of the forearm was unaffected. Considering the different innervation and hydrostatic effects the results lead to the following conclusion: the finger vessels are richly innervated with adrenoceptors which causes alpha 1-mediated vasoconstriction. In contrast to the vessels of the fingers those of the forearm seem to be under andrenergic as well as cholinergic control. Hydrostatic components appear to be more prevalent in the volar forearm site.

[Dynamic function tests for detection of physiologic and pathophysiologic reactions in cutaneous microcirculation]. / Dynamische Funktionstests zur Erfassung physiologischer und pathophysiologischer Reaktionsmuster kutaner Mikrozirkulation.

Functional tests simulating local stresses are especially suitable for the evaluation of physiological and pathophysiological patterns in the cutaneous microcirculation, particularly if combined with non-invasive methods such as laser-Doppler fluxmetry and oxygen tension measurements. Arterial occlusion (3 min) and local heating (up to 42 degrees C) are appropriate as stimuli to simulate specific local demands on the cutaneous perfusion similar to those produced by pressure, myokinesis, heat, and inflammation. When the current microcirculatory status is described the initial values (LDF and pO2) and their time-courses during each functional test can be used to determine the so-called post-stimulatory parameters. These-- corresponding to physiological equivalents--allow statements on the vascular reactivity towards hypoxia and ischaemia. Furthermore, dynamic performance parameters can easily be derived from the poststimulatory values. They describe the capacity of cutaneous microcirculation with regard to perfusion reserves and ischaemic tolerance in local stress situations in an appropriate manner. As an example of the usefulness of functional tests for cutaneous microcirculation, the physiological and pathophysiological patterns found in systemic sclerosis are described.

[Disordered cutaneous microcirculation in diabetic neuropathic foot ulcer. Is modification by retrograde transvenous perfusion therapy possible?]. / Kutane Mikrozirkulationsstörung bei diabetischen neuropathischen Plantarulzera. Ist eine Beeinflussung durch retrograde transvenöse Perfusionstherapie möglich?

Due to the high risk of amputation they involve, diabetic neuropathic plantar ulcers (DNPU) must be regarded as a late manifestation/complication of diabetes mellitus. The suspected cause of these ulcers--disturbed cutaneous microcirculation--was studied by simultaneously measuring laser-Doppler flux (LDF) and cutaneous oxygen tension (pCUO2) in 14 patients with DNPU at three differently affected sites (dorsal forefoot, ulcer edge, lower leg). Dynamic tests (arterial occlusion, local hyperthermia) as a measure of vascular reactivity showed significantly reduced pCUO2 parameters coinciding with elevated LDF values. This reflects a shift of blood flow from the nutritive capillaries towards deeper vessels. Abolition of normal vasoconstriction in the arteriovenous shunt vessels by diabetic polyneuropathy is the assumed cause of increased AV perfusion, with a consequent rise in LDF values. In a subgroup of the above patients (n = 7) undergoing daily intravenous retrograde perfusion therapy (RVP) over 10 days several basic and dynamic microcirculatory functions were studied before and after this treatment. This subgroup showed on the forefoot and the lower leg a remarkable improvement of the microcirculatory parameters investigated, suggesting a better oxygen supply to the tissues after RVP therapy.

Short-column gradient elution high-performance liquid chromatography for the rapid determination of 7-ethoxycoumarin metabolites in liver-slice incubates.

An improved HPLC method for the analysis of 7-ethoxycoumarin and its metabolites in liver-slice incubation media is presented. The assay is based on short-column gradient elution which permits baseline resolution of the parent drug and three metabolites with a fourfold reduction in analysis time relative to existing HPLC methods. Total assay run time is 10 min. Data establishing method performance are presented which show intra- and interassay precision and accuracy to be within 13 and 7%, respectively, for separately prepared quality control samples.

Fluid and electrolyte status in athletes receiving medical care at an ultradistance triathlon.

Thirty competitors in the Hawaii Ironman Triathlon were prospectively studied to determine whether fluid and electrolyte disturbances were causes for seeking race-day medical care. Athlete weights were significantly (p < 0.0001) decreased during the race, but decreases were not different in treated (n = 11; % delta wt -2.3 +/- 2.9) versus not treated (n = 19; % delta wt - 2.0 +/- 1.9) athletes. Hyponatremia occurred in nine athletes (30%), and hypomagnesemia in six (20%), but only half of athletes were either electrolyte imbalance sought care. Although athletes receiving medical care may have fluid and electrolyte problems, these abnormalities may also occur in healthy athletes.

Disturbances of cutaneous microcirculation in patients with diabetic legs: additional parameters for a new therapeutic concept?

To study disturbed microcirculation involved in the pathogenesis of diabetic neuropathic plantar ulcers (DNPU), we recorded dynamic changes in laser-Doppler flux (LDF) and cutaneous oxygen tension (pcuO2) caused by short-time arterial occlusion and local heating at three different sites (forefoot, ulcer edge, lower leg) in patients (n = 14) with DNPU and healthy controls (n = 18). Significantly reduced dynamic pcuO2 parameters coincided with a significant increase of flux in the patient group. This post-stimulatory "hypoxic hyperemia" indicates a shifting of blood flux, reducing circulation of the nutritive capillaries comparable to an internal "steal effect". This may predispose to the development of DNPU when additional stresses influence the initial borderline balance, characterized by similar pcuO2 and increased flux values compared to controls. Abolishment of normal vasoconstriction in the shunt vessels by diabetic polyneuropathy is the assumed cause of increased arteriovenous perfusion and therefore raised flux values. Non-invasive testing of microcirculatory functions demonstrates characteristic disturbances in DNPU patients and could be used as additional parameters for new therapeutic concepts as the intravenous retrograde perfusion (RVP). After RVP therapy, applied to a subgroup (n = 7) of the patients, some dynamic microcirculatory parameters improved, allowing a preliminary quantitative evaluation of a therapeutic regimen.

[Respiration-dependence of cutaneous laser Doppler flow motion]. / Atemabhängigkeit kutaner Laser-Doppler-Fluxmotion.

The aim of this study was to show and to quantify the breath-dependency of cutaneous fluxmotion in the volar proximal forearm using a new computer-aided system. A meanflux-related index (MI) representing the intensity of the influence of respiration on fluxmotion was calculated. There was a good correlation between MI and the rate of respiration under spontaneous breathing: the lower the rate of respiration, the higher the value of MI. Prescribing a constant breathing rhythm amplifies this frequency-dependent effect. According to occurrence of low rates of respiration (< 12/min) also under physiological conditions the respiration should be simultaneously recorded while assessing fluxmotion.

Extensive linear epidermal nevus associated with hemangiomas of bones and vitamin-D-resistant rickets.

The association of connate, left-sided, extensive epidermal verrucous nevus, multiple isolated bone tumors and vitamin-D-resistant rickets since childhood seen in a 20-year-old male patient corresponded to an epidermal nevus syndrome (ENS). However, other organ involvement occasionally associated with ENS could not be found in this patient, and his intraosseous tumors represented histologically benign hemangiomas. Serum analysis revealed hypophosphatemia (together with phosphaturia), decreased levels of 1,25-dihydroxycholecalciferol and elevated levels of alkaline phosphatase indicating hypophosphatemic osteomalacia. Therefore we suppose that vitamin-D-resistant rickets combined with skeletal tumors represents a peculiar type of osteomalacia caused by unilateral mesenchymomas.

[Cutaneous microcirculation in pretibial necrobiosis lipoidica. Comparative laser Doppler flowmetry and oxygen partial pressure determinations in patients and healthy probands]. / Kutane Mikrozirkulation bei prätibialer Nekrobiosis lipoidica. Vergleichende Laser-Doppler-Fluxmetrie und Sauerstoffpartialdruckmessungen bei Patienten und Hautgesunden.

Necrobiosis lipoidica (NL) is a chronic, skin disease usually localized pretibially and often associated with diabetes mellitus. Primary vascular disturbances are considered pathogenetic for NL. In order to determine microcirculatory alterations in "idiopathic" NL linked with neither arterial hypertension nor diabetes mellitus, we performed simultaneous measurements of laser-Doppler flux (LDF) and oxygen tension (pcuO2) in 10 non-diabetic patients with NL and in 10 age- and sex-matched healthy volunteers. We examined the centre of the pretibial NL plaque, its border and the non-affected skin of the proximal lower leg at probe temperatures of 36 degrees C (flux) and 37 degrees C (pcuO2). Corresponding sites and temperatures were chosen for the controls. In addition, the degrees of hyperaemia caused by arterial occlusion (3 min) and during local heating (42 degrees C) were continuously measured. The initial pcuO2 values were found to be lowered, in contrast to increased fluxes within and around the NL lesions. In addition, responses of both flux and pcuO2 to the hyperaemic stimuli were weaker than in the corresponding skin of the healthy controls. Only minor differences from controls or none at all were found in clinically unaffected lower leg skin of the patients. Our results indicate a local alteration of microcirculation in patients with "idiopathic" NL that occurs independently of diabetes.