Bending and precipitate formation mechanisms in epitaxial Ge-core/GeSn-shell nanowires.

Core-shell Ge/GeSn nanowires provide a route to dislocation-free single crystal germanium-tin alloys with desirable light emission properties because the Ge core acts as an elastically compliant substrate during misfitting GeSn shell growth. However, the uniformity of tin incorporation during reduced pressure chemical vapor deposition may be limited by the kinetics of mass transfer to the shell during GeSn growth. The balance between Sn precursor flux and available surfaces for GeSn nucleation and growth determines whether defects are formed and their type. On the one hand, when the Sn precursor delivery is insufficient, local variations in Sn arrival rate at the nanowire surfaces during GeSn growth produce asymmetries in shell growth that induce wire bending. This inhomogeneous elastic dilatation due to the varying composition occurs via deposition of Sn-poor regions on some of the {112} sidewall facets of the nanowires. On the other hand, when the available nanowire surface area is insufficient to accommodate the arriving Sn precursor flux, Sn-rich precipitate formation results. Between these two extremes, there exists a regime of growth conditions and nanowire densities that permits defect-free GeSn shell growth.

Orlistat in responding obese type 2 diabetic patients: meta-analysis findings and cost-effectiveness as rationales for reimbursement in Sweden and Switzerland.

OBJECTIVE: The aim of this study is to review the clinical and economic rationale for the reimbursement of orlistat in responding obese patients with type 2 diabetes. METHODS: Data from seven randomized controlled clinical trials of orlistat in overweight and obese patients with type 2 diabetes were pooled. A subgroup analysis involving patients who achieved a response (defined as a weight loss of >/=5% after 12 weeks of treatment) was conducted. The outcomes of the pooled analysis were then used to construct a Markov health economic model covering an 11-y period. The incidences of diabetes-related micro- and macrovascular complications were derived from the United Kingdom Prospective Diabetes Study. The effects of changes in body mass index, and the impact of micro- and macrovascular complications on utilities were derived from published sources. Publicly available cost data were used and are presented here in 2001 Euros. Discounting of 3% was applied. A probabilistic sensitivity analysis was conducted to examine the robustness of results. RESULTS: A total of 1249 patients treated with orlistat and 1230 given placebo were eligible for the intent-to-treat analysis. At the end of the study period, 23% of orlistat patients achieved a weight reduction of >/=5%. These patients showed a mean decrease in HbA1C of 1.16%, a weight reduction of 8.6 kg, a reduction in total cholesterol of 5.3% and a reduction in systolic blood pressure of 5.2 mmHg. The base-case economic analysis revealed costs per quality-adjusted life year gained of euro14 000 in Sweden and euro13 600 in Switzerland. CONCLUSION: The data presented here support the utilization and reimbursement of orlistat in overweight and obese diabetic patients who respond to the treatment.

Gene expression in gastric biopsies from patients infected with Helicobacter pylori.

BACKGROUND: Helicobacter pylori infection has protean effects on gene expression in the host gastric mucosa, which have been investigated by gene chip analysis in vitro. In this study the effects of H. pylori infection on host gene expression in the gastric antral mucosa in patients were examined. METHODS: One gastric antral biopsy was obtained from a total of 18 untreated patients undergoing routine endoscopic evaluation of chronic abdominal complaints. Nine patients had histologic evidence of H. pylori infection and 9 age- and sex-matched patients had no histologic evidence of H. pylori infection. A microarray analysis was performed using a gene chip containing 35,000 human expressed sequence tags on RNA extracted from endoscopic, gastric antral biopsies, and average gene expression among infected and uninfected patients was compared. RESULTS: Underexpressed genes in infected patients' mucosa included gastric intrinsic factor and several metallothionein isoforms. Overexpressed genes in infected patients' mucosa comprised MHC Class II molecules, immunoglobulin and B-cell activation genes, as well as genes known to induce apoptosis. Changes in expression were confirmed for a subset of genes by SYBR green real-time PCR. CONCLUSIONS: Microarray analysis of antral biopsies from patients with and without H. pylori infection revealed differential expression of metal regulatory, immunity and inflammation-related genes.

Cascades of popping bubbles along air/foam interfaces.

We report image analysis of popping bubbles during the collapsing of two-dimensional (2D) and 3D aqueous foams. Although temporal and spatial correlations between successive popping bubbles within avalanches are emphasized, the breaking of a soap film at the air/foam interface seems to be independent of (i) the topology, (ii) the local curvature, and (iii) the size of the popping bubble. Possible mechanisms for cascades of pops are proposed and discussed.

Avalanches of popping bubbles in collapsing foams.

We report acoustic measurements of popping bubbles during the collapsing of aqueous foams. The sound pattern is analyzed using classical methods of statistical physics. It is found that membrane rupture concerns a wide variety of situations: small and large membranes at the air/foam interface. Avalanches of popping bubbles are put into evidence. Time durations in between successive pops seem to be distributed on a universal power law.

Psychophysical estimates of cochlear phase response: masking by harmonic complexes.

Harmonic complexes with identical component frequencies and amplitudes but different phase spectra may be differentially effective as maskers. Such harmonic waveforms, constructed with positive or negative Schroeder phases, have similar envelopes and identical long-term power spectra, but the positive Schroeder-phase waveform is typically a less effective masker than the negative Schroeder-phase waveform. These masking differences have been attributed to an interaction between the masker phase spectrum and the phase characteristic of the basilar membrane. To explore this relationship, the gradient of stimulus phase change across masker bandwidth was varied by systematically altering the Schroeder-phase algorithm. Observers detected a signal tone added in-phase to a single component of a masker whose frequencies ranged from 200 to 5000 Hz, with a fundamental frequency of 100 Hz. For signal frequencies of 1000-4000 Hz, differences in masking across the harmonic complexes could be as large as 5-10 dB for phase gradients changing by only 10%. The phase gradient that resulted in a minimum amount of masking varied with signal frequency, with low frequencies masked least effectively by stimuli with rapidly changing component phases and high frequencies masked by stimuli with more shallow phase gradients. A gammachirp filter was implemented to model these results, predicting the qualitative changes in curvature of the phase-byfrequency function estimated from the empirical data: In some cases, small modifications to the gammachirp filter produced better quantitative predictions of curvature changes across frequency, but this filter, as implemented here, was unable to accurately represent all the data.

Different auditory filter bandwidth estimates based on profile analysis, notched noise, and hybrid tasks.

Auditory filter bandwidths were estimated in three experiments. The first experiment was a profile-analysis experiment. The stimuli were composed of sinusoidal components ranging in frequency from 200 to 5000 Hz. The standard stimulus was the sum of equal-amplitude tones, and the signal stimulus had a power spectrum that varied up-down ... up-down. The number of components ranged from four to 60. Interval-by-interval level randomization prevented the change in level of a single component from reliably indicating the change from standard to signal. The second experiment was a notched-noise experiment in which the 1000-Hz tone to be detected was added to a noise with a notch arithmetically centered at 1000 Hz. Detection thresholds were estimated both in the presence of and in the absence of level randomization. In the third, hybrid, experiment a 1000-Hz tone was to be detected, and the masker was composed of equal-amplitude sinusoidal components ranging in frequency from 200 to 5000 Hz. For this experiment, thresholds were estimated both in the presence and absence of level variation. For both the notched-noise and hybrid experiments, only modest effects of level randomization were obtained. A variant of Durlach et al.'s channel model ["Towards a model for discrimination of broadband signals," J. Acoust. Soc. Am. 80, 63-72 (1986)] was used to estimate auditory filter bandwidths for all three experiments. When a two-parameter roex(p,r) filter weighting function was used to fit the data, bandwidth estimates were approximately two to three times as large for the two detection tasks than for the profile-analysis task.

Donor polymorphism of tumor necrosis factor gene: relationship with variable severity of hepatitis C recurrence after liver transplantation.

BACKGROUND: Hepatitis C-related liver failure is the leading indication for liver transplantation worldwide. Although histologic recurrence is identified in the majority of patients, the spectrum of allograft injury is wide. To date, most studies have focused on the contribution of immunosuppression and viral factors. We hypothesized that the allograft plays a significant role in determining timing and severity of hepatitis C virus (HCV) recurrence. The purpose of this analysis was to determine if genetic polymorphisms of the tumor necrosis factor (TNF) locus were associated with the highly variable severity of HCV recurrence. METHODS: Thirty-one HCV-seropositive liver transplant recipients with long-term follow-up were studied. Genomic DNA was extracted from archived donor spleens which corresponded to each patient. We performed polymerase chain reaction amplification, followed by sequencing for two promoter TNF-alpha variants (at positions -238 and -308), and restriction fragment length analysis for four polymorphic loci within the TNF-beta gene (NcoI, TNFc, aa13, and aa26). RESULTS: The relative prevalence of polymorphisms corresponded to distributions previously reported in normal control populations. Twenty-two of 31 (71%) patients received a donor liver homozygous for the wild type allele (TNF1) at the -308 TNF-alpha promoter region. The interval to histologic recurrence was significantly shorter and severity of HCV allograft hepatitis was significantly greater in patients with one or two TNF308.2 alleles. At last follow-up biopsy, 5 of 9 (56%) patients with a TNF308.2 donor liver had evidence of severe histological activity index as compared to 2 of 22 (9%) of patients receiving a donor liver homozygous for the TNF1 allele (P = 0.01). There was no correlation between rejection rates and the presence of any TNF-alpha or TNF-beta alleles. TNF-beta polymorphisms within the donor liver did not correlate with severity of HCV recurrence. CONCLUSIONS: The donor TNF-alpha promoter genotype may influence the inflammatory response to HCV reinfection of the graft and contribute to accelerated graft injury. If the association between this genetic marker (TNF308.2) and disease progression is confirmed, it could improve our understanding of HCV pathogenesis and influence donor selection and patient management.

Sensitivity to changes in level and envelope patterns across frequency.

In the first experiment, two measurements were compared--sensitivity to across-frequency changes in level and sensitivity to across-frequency changes in the modulation phase of SAM tones. For the level task, multi-tone stimuli composed of 2-80 tones ranging in frequency from 200 to 5000 Hz were used. For the phase task, the same frequency range was used, and 2-80 SAM tones were tested. For the level task, observers discriminated between a multi-tone, equal-amplitude standard and one of two signals--a one-step or an up-down signal. The one-step signal had higher levels at low frequencies and lower levels at high frequencies. The up-down signal had components with levels that varied high-low-high-low. For the phase task, the standard was the sum of SAM tones with identical modulator phases across frequency. The one-step signal had a common modulator phase at low frequencies and a different common modulator phase at high frequencies. The up-down signal had modulator phases that varied lag-lead-lag-lead. The results suggest that sensitivity to across-frequency changes in level and modulation phase reflect similar initial processing stages. In a second experiment, SAM tones were used, and psychometric functions were measured for the level task, the phase task, and a condition in which changes in level and modulator phase were both present. The standard was "flat," and an up-down signal was to be detected. For one observer, the data suggest that level and phase information are independently represented. For the other two observers, interactions between the two features of the stimuli are apparent. A multiple-looks model was moderately successful in accounting for the data.

The effects of amplitude perturbation and increasing numbers of components in profile analysis.

In a profile-analysis task, the effect of randomly perturbing the amplitudes of the components of multi-tone stimuli was studied in two experiments. In the first experiment, thresholds for a signal added in-phase to the central component of a standard were measured for different numbers of components in two conditions. In one condition thresholds were measured in blocks for six different "jagged" standards, and in another, thresholds were measured when one of the six standards was chosen randomly on a presentation-by-presentation basis. Regardless of condition, thresholds did not depend on the numbers of components and increased magnitude of perturbation increased thresholds. Moreover, the slope relating thresholds to number of components did not increase with increasing magnitude of perturbation. In the second experiment, the signal consisted of an increase in amplitude of the central components and a decrease in amplitude of the outer components of the standard (a stimulus type which has been shown to maximize the change in threshold with increasing number of components). The amplitudes of component tones were selected randomly on a presentation-by-presentation basis. Thresholds fell with increases in the number of components, but the slope relating thresholds to numbers of components did not change as the magnitude of perturbation increased. The latter result contrasts with that reported by Kidd et al. [J. Acoust. Soc. Am. 90, 1340-1354 (1991)].

Sensitivity to changes in overall level and spectral shape: an evaluation of a channel model.

Two experiments involving level and spectral shape discrimination which test an optimal channel model developed by Durlach et al. [J. Acoust. Soc Am. 80, 63-72 (1986)] are described. The model specifies how the auditory system compares and/or combines intensity information in different frequency channels. In the first experiment, psychometric functions were obtained for the discrimination of changes in level and discrimination of changes in spectral shape for an eight-tone complex sound. A variety of different base spectral shapes were tested. In some conditions, level randomization was introduced to reduce the reliability of across-interval changes in level. Increasing the amount of level variation degraded performance for the level discrimination task but had no effect on the shape discrimination task. In all conditions, sensitivity to changes in spectral shape was superior to sensitivity to changes in level. Consequently, two models of central noise are evaluated in an attempt to explain these results; one in which central noise acts prior to the formation of the likelihood ratio and one in which central noise degrades the likelihood ratio. The former model is more successful in accounting for the data. In a second experiment, the detectability of a level increment to one component of a multitone complex was measured. The frequency content of the complex was varied by systematically removing six components from a 23-component complex. Thresholds were measured for increments at three different signal frequencies. A common trend in the data was that when there was a spectral gap directly above the signal frequency, thresholds were lowest. This result differs from the predictions of a simple channel model, and contrasts with results presented by Green and Berg [Q. J. Exp. Psychol. 43A, 449-458 (1991)].

The function of sentence accents and given/new information in speech processing: different strategies for normal-hearing and hearing-impaired listeners?

Two experiments were carried out to investigate how the correspondence between sentence accentuation and distribution of information is used in human word processing. A forced-choice task with target words embedded in sentences was employed for this purpose. Target words provided either 'given' or 'new' information, and were either accented or unaccented. The subjects had to choose between two words that differed in the last consonant by one phonetic feature (e.g., mouth/mouse). The first experiment involved both normal-hearing and hearing-impaired listeners. A fixed amount of noise was used to reduce the quality of speech for normal-hearing listeners, in order to enable a comparison between the two listener groups. The results of the first experiment showed different processing patterns for normal-hearing and hearing-impaired listeners. The hearing-impaired listeners were more accurate with words that were properly accented for their information value, whereas the normal-hearing subjects were more accurate with accented than unaccented words regardless of their information value. A new group of normal-hearing subjects was tested in a second experiment with speech of more severely reduced quality. The results indicated that, under these circumstances, the normal-hearing listeners changed their strategy and also showed an interaction between information value and accent. It seems that, as speech becomes less intelligible, listeners depend increasingly on linguistic expectations stemming from the correlation between information value and accentuation.

On the mechanism of energy transfer to Tb3+ ions in proteins. A time-resolved luminescence study of the Tb-elastase complex.

Intraprotein energy transfer to terbium ions is widely used for probing distances of calcium sites in proteins. In this work we have performed a time-resolved study of the sensitized luminescence in elastase using a pulsed laser excitation at 265 nm. Terbium-sensitized luminescence was found to build-up within about 150 microseconds, which indicates that the protein transfers energy at a rate several orders of magnitude slower than expected for a singlet state donor. From the rise time of the signal and from its variation with the oxygen concentration, it can be deduced that 80% of the transfer originates from the first triplet excited state of one unique aromatic residue. From the comparison of protein fluorescence and sensitized terbium luminescence excitation spectra the sensitizer was identified as a tryptophan, presumably Trp141, which is situated only 0.7-0.9 nm away from the Tb site. The results are at variance with the usual assumption that energy is transferred from the first excited singlet state of aromatic residues according to a long-range dipole-dipole interaction and are more consistent with a short-distance exchange mechanism.

Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors.

Steatohepatitis (fatty liver hepatitis), histologically identical to alcoholic disease, occurs in some obese patients after jejunoileal bypass. A similar lesion occurs rarely in obese patients without bypass surgery, but the risk factors are poorly understood. Hepatic steatosis, steatohepatitis and fibrosis were sought in 351 apparently nonalcoholic patients at autopsy and various risk factors were evaluated. Incidence of steatosis and steatohepatitis correlated with the degree of obesity. Steatohepatitis was found in 18.5% of markedly obese patients and 2.7% of lean patients. Additional risk factors for steatohepatitis were type II diabetes, weight loss in the preterminal period shortly before death and intravenous glucose therapy in the last week of life. Severe fibrosis was found in 13.8% of markedly obese patients and in 6.6% of lean patients; this difference was largely explained by the higher prevalence of diabetes in obese groups. The risk factors defined in this study are known to be associated with abnormalities of free fatty acid metabolism. Obesity, type II diabetes and intravenous glucose therapy are associated with hyperinsulinemia, which may inhibit fatty acid oxidation. Obesity and weight loss increase the presentation of fatty acids to the liver. Similar metabolic changes may occur in obese patients after jejunoileal bypass surgery. Thus this study supports the hypothesis that fatty acids have a role in the hepatocellular necrosis found in some obese individuals.

Eosinophilic gastroenteritis presenting in an adolescent with isolated colonic involvement.

Eosinophilic gastroenteritis most commonly involves the stomach and proximal small intestine with eosinophilic inflammation of either the mucosa, submucosa or serosa. The patient reported here had isolated eosinophilic colitis. The initial presentation with iron deficiency anaemia owing to occult gastrointestinal blood loss emphasises the need to evaluate the entire gastrointestinal tract in patients with eosinophilic gastroenteritis.

Partial nodular transformation of liver in an adult with persistent ductus venosus. Review with hypothesis on pathogenesis.

Partial nodular transformation of the liver (PNT) is a rare condition of unknown pathogenesis in which nodules composed of hepatocytes replace portions of the parenchyma. There is usually evidence of portal hypertension and portal vein thrombosis. We present a case of PNT in a man with persistent ductus venosus and hypoplasia of the major intrahepatic portal veins but without evidence of portal hypertension or portal vein thrombosis. Portal venules were largely absent between nodules, as documented by morphometry. We suggest the pathogenesis of PNT is similar to that previously proposed for nodular regenerative hyperplasia, that is, atrophy occurs in parenchyma with insufficient blood supply and nodules arise by hyperplasia in areas with adequate supply. Partial nodular transformation and nodular regenerative hyperplasia differ mainly in the cause and distribution of the portal vein obliteration.