Measuring the solubility of solids in non-solvents: case of polystyrene in alkanes.

We introduce a simple and sensitive technique for measuring extremely low solubilities with a small sample size and small solvent volume. This technique involves measuring the decrease in the thickness of a supported thin film after exposure to a drop of known volume of solvent and removal of the solution. The feasibility of measuring very small changes in film thickness directly translates to the ability to measure extremely low solubility while at the same time using only µL of solvent. We apply the technique to the case of polystyrene with Mw values in the range 2500 g/mol to 22200 g/mol in alkane solvents and show that we can easily measure a solubility of 0.1 g/L using only 1[Formula: see text] g of material and 3[Formula: see text] L of solvent for each sample.

What can we learn about a dynamical length scale in glasses from measurements of surface mobility?

We consider the ability of recent measurements on the size of a liquid-like mobile surface region in glasses to provide direct information on the length scale of enhanced surface mobility. While these quantities are strongly related there are important distinctions that limit the ability of measurements to quantify the actual length over which the surface properties change from surface to bulk-like. In particular, we show that for temperatures near the bulk glass transition, measurements of a liquid-like mobile layer may have very limited predictive power when it comes to determining the temperature dependent length scale of enhanced surface mobility near the glass transition temperature. This places important limitations on the ability of measurements of such enhanced surface dynamics to contribute to discussion on the length scale for dynamical correlation in glassy materials.

Reduced glass transition temperatures in thin polymer films: surface effect or artifact?

We have examined the direct effect of manipulating the number of free surfaces on the measured glass transition temperature T(g) of thin polystyrene films. Thin films in the range 35 nm < h < 114 nm with molecular weights of 592 kg/mol and 1144 kg/mol were studied. Ellipsometry was used to determine the temperature dependence of the thickness and refractive index of freestanding films. By noting the change in slope in each of these quantities, a T(g) value can be assigned in quantitative agreement with previously reported results. For thin freestanding films this value is reduced from that of the bulk. The exact same films are then transferred to a Si substrate and the T(g) of the resulting supported film was determined. The T(g) values of the now supported films are the same as the bulk value and the same as previous reports of similar supported films. These experiments unambiguously show that free interfaces are the dominant cause of the T(g) reductions for the film thicknesses studied.

Measuring surface and bulk relaxation in glassy polymers.

We present a comprehensive study of gold nanoparticle embedding into polystyrene (PS) surfaces at temperatures ranging from T ( g ) + 8 K to T ( g ) - 83 K and times as long as 10(5) minutes. This range in times and temperatures allows the first concurrent observation of and differentiation between surface and bulk behavior in the 20 nm region nearest the free surface of the polymer film. Of particular importance is the temperature region near the bulk glass transition temperature where both surface and bulk processes can be measured. The results indicate that for the case of PS, enhanced surface mobility only exists at temperatures near or below the bulk T ( g ) value. The surface relaxation times are only weakly temperature dependent and near T ( g ), the enhanced mobility extends less than 10nm into the bulk of the film. The results suggest that both the concept of a "surface glass transition" and the use of glass transition temperatures to measure local mobility near interfaces may not universally apply to all polymers. The results can also be used to make a quantitative connection to molecular dynamics simulations of polymer films and surfaces.

Influence of nanoparticle size on the pH-dependent structure of adsorbed proteins studied with quantitative localized surface plasmon spectroscopy.

We have studied pH-dependent conformational transitions of Bovine Serum Albumin adsorbed onto different sizes of gold nanospheres. For larger spheres (D > 10 nm) there is evidence for a path-dependent extended state near pH 4, over a very small pH range. For smaller nanospheres (5 nm and 10 nm) the evidence for such a transition is either much weaker or completely suppressed. We suggest that the absence of the transition on small spheres is due to the fact that the protein adsorbed on such small spheres has already lost at least some of its tertiary structure. The results have important implications for the functionality of proteins adsorbed onto nanospheres or surfaces with nm scale roughness.

Effect of atmosphere on reductions in the glass transition of thin polystyrene films.

We have used nulling ellipsometry to measure the glass transition temperature, T (g) , of thin films of polystyrene in ambient, dry nitrogen, and vacuum environments. For all environments, the measured T (g) values decrease with decreasing film thickness in a way that is quantitatively similar to previously reported studies in ambient conditions. These results provide strong reinforcement of previous conclusions that such reduced T (g) values are an intrinsic property of the confined material. Furthermore, the results are in contrast to recent reports which suggest that the T (g) reductions measured by many researchers are the results of artifacts (i.e. degradation of the polymer due to annealing in ambient conditions, or moisture content).

Clinical pharmacokinetics of paracetamol.

In therapeutic doses paracetamol is a safe analgesic, but in overdosage it can cause severe hepatic necrosis. Following oral administration it is rapidly absorbed from the gastrointestinal tract, its systemic bioavailability being dose-dependent and ranging from 70 to 90%. Its rate of oral absorption is predominantly dependent on the rate of gastric emptying, being delayed by food, propantheline, pethidine and diamorphine and enhanced by metoclopramide. Paracetamol is also well absorbed from the rectum. It distributes rapidly and evenly throughout most tissues and fluids and has a volume of distribution of approximately 0.9L/kg. 10 to 20% of the drug is bound to red blood cells. Paracetamol is extensively metabolised (predominantly in the liver), the major metabolites being the sulphate and glucuronide conjugates. A minor fraction of drug is converted to a highly reactive alkylating metabolite which is inactivated with reduced glutathione and excreted in the urine as cysteine and mercapturic acid conjugates. Large doses of paracetamol (overdoses) cause acute hepatic necrosis as a result of depletion of glutathione and of binding of the excess reactive metabolite to vital cell constituents. This damage can be prevented by the early administration of sulfhydryl compounds such as methionine and N-acetylcysteine. In healthy subjects 85 to 95% of a therapeutic dose is excreted in the urine within 24 hours with about 4, 55, 30, 4 and 4% appearing as unchanged paracetamol and its glucuronide, sulphate, mercapturic acid and cysteine conjugates, respectively. The plasma half-life in such subjects ranges from 1.9 to 2.5 hours and the total body clearance from 4.5 to 5.5 ml/kg/min. Age has little effect on the plasma half-life, which is shortened in patients taking anticonvulsants. The plasma half-life is usually normal in patients with mild chronic liver disease, but its prolonged in those with decompensated liver disease.

The anti-secretory effect and pharmacokinetics of omeprazole in chronic liver disease.

The anti-secretory effects and pharmacokinetics of omeprazole were investigated in ten patients with chronic liver disease. Plasma omeprazole concentrations were measured after a 10-mg intravenous dose of omeprazole and on the first and seventh days of a 7-day course of 10 mg oral omeprazole daily. Pentagastrin tests were performed on the day before oral omeprazole was commenced and 24 h after the last oral dose. The pre-treatment basal and peak gastric acid outputs were low (mean rates of 1.44 mmol/h and 9.26 mmol/h, respectively) and following 7 days of oral 10 mg omeprazole daily, were lowered by 95% and 90% respectively. Following 10 mg intravenous omeprazole, plasma clearance was reduced, and plasma half-life and area under the concentration curve were increased, in comparison with previous studies in healthy subjects. The plasma concentration curves for oral and intravenous doses were very similar. After both the first and seventh oral doses, maximum plasma concentration and area under the curve were higher than in healthy subjects. No accumulation of omeprazole was demonstrated. The pharmacokinetics of omeprazole in chronic liver disease could be influenced by low gastric acidity, poor liver function and/or portasystemic shunting. A dose of 10 mg omeprazole daily has been shown to be an effective anti-secretory agent in chronic liver disease.

Surreptitious abuse of magnesium laxatives as a cause of chronic diarrhoea.

Surreptitious laxative abuse is increasingly considered as a possible cause of unexplained chronic diarrhoea. Laboratory services for detection of colonic stimulant laxatives are widely available; however, laboratory facilities for identifying patients with magnesium-induced diarrhoea are not commonly provided, making diagnosis difficult. We describe three patients who surreptitiously abused magnesium laxatives, and whose diagnoses were delayed, leading in each case to extensive investigations and lengthy in-patient stays. In all three cases, the diagnosis was eventually made by the simple measurement of magnesium in a random faecal sample. We would like to increase the awareness of surreptitious magnesium laxative abuse as a cause of chronic diarrhoea so that costly and unnecessary investigations may be minimized.

Thickness dependence of the dynamics in thin films of isotactic poly (methylmethacrylate).

The film thickness dependence of both the glass transition temperature (T(g)) and the 1 kHz alpha relaxation were studied for thin films of isotactic Poly (methylmethacrylate) (i-PMMA) supported on aluminium substrates. Films in the thickness range 7-200 nm were studied. The ellipsometrically determined T(g) was found to show reductions for films thinner than 60 nm, with the largest observed reduction being 12 K for a 7 nm thick film. Measurements of the T(g) were also performed on i-PMMA films supported on silicon substrates. Dielectric studies of the temperature dependent 1 kHz alpha relaxation peak, showed that the position (T(alpha)) and shape of the peak have no film thickness dependence. This was shown to hold for films with one free surface and films with a 30 nm thermally evaporated capping layer. Capping the films was shown to have no effect on the thickness dependence of either T(g) or T(alpha). The implications of these results are discussed further and the different film thickness dependencies of T(g) and T(alpha) are discussed. This is done within the framework of the Vogel-Fulcher-Tamann (VFT) theory of glass forming materials and also in the context of the existence of a dynamic correlation length xi.

First inelastic neutron scattering studies on thin free standing polymer films.

Glass transition studies in free standing polymer films have revealed values of the transition temperature, T(g), which were substantially reduced below the bulk for sufficiently thin films. Here we report on the preparation of two stacks of free standing polystyrene films: 70 films with a thickness of h approximately 107 nm and 140 films with h approximately 55 nm with equivalent total sample thicknesses of approximately 7.5 microm. We have performed the first measurements on such samples using inelastic neutron scattering, and demonstrate that inelastic neutron scattering experiments, performed on the time-of-flight spectrometer IN6 and the backscattering spectrometer IN16 at the Institut Laue-Langevin, are feasible.

Dielectric and ellipsometric studies of the dynamics in thin films of isotactic poly(methylmethacrylate) with one free surface.

We have performed dielectric loss measurements at 1 kHz on thin films of isotactic poly(methyl methacrylate). A key distinction of our studies is that the samples measured were supported films with one free surface rather than films that have metallic electrodes covering both surfaces. This unique sample geometry allows us to eliminate any effects due to evaporation of metal onto the top film surface and provides a unique opportunity to make direct comparisons between dielectric loss and glass transition measurements. Film thicknesses in the range from 6 microm to 7 nm were prepared on Al coated substrates. The dielectric loss peak and ellipsometric glass transition temperature of all films were measured. The dielectric loss was found to exhibit no discernible film thickness dependence in either the temperature of the maximum loss value or the shape of the loss curve. In contrast, the measured T(g) values were found to decrease with decreasing film thickness with a maximum shift of 10 K for a 7-nm film. Dielectric measurements were also made on Al coated films and these samples also showed no shift in the temperature of the loss peak. Finally, the T(g) measurements were also made on Si substrates. These values exhibited an increasing T(g) value with film thickness with a maximum increase of approximately 15 K being measured for a 7-nm film.

Molecular weight dependence of reductions in the glass transition temperature of thin, freely standing polymer films.

We have used transmission ellipsometry to perform a comprehensive study of the glass transition temperature T(g) of freely standing polystyrene films. Six molecular weights M(w), ranging from 575 x 10(3) to 9100 x 10(3), were used in the study. For each M(w) value, large reductions in T(g) (as much as 80 degrees C below the bulk value) were observed as the film thickness h was decreased. We have studied in detail the dependence of the T(g) reductions on M(w) in a regime dominated by chain confinement effects. The empirical analysis presented is highly suggestive of the existence of a mechanism of mobility in thin freely standing films that is inhibited in the bulk and distinct from the usual cooperative motion associated with the glass transition.

Admissions of drug addicts to a general hospital: a retrospective study in the northern district of Glasgow.

Medical and surgical admissions of drug addicts to Stobhill Hospital, Glasgow in the period 1980-1984 were reviewed. Admission numbers, which totalled 123, rose markedly over the period of the study, particularly in the final year. The mean age of addicts was 21 years. Ninety-two per cent abused heroin but many abused combinations of drugs. Inadvertent narcotic overdosage was the commonest diagnosis amongst medical admissions followed by deep venous thrombosis. A small number of cases of staphylococcal endocarditis presented particular problems in diagnosis and management. The commonest reason for surgical admission was abscess formation. Whilst 85% of addicts showed markers of past infection with hepatitis B, chronic carriage of surface antigen occurred in only 10%. Few addicts had withdrawal symptoms although the practice of narcotic and/or tranquilliser prescribing varied. Many admissions were of short duration with 36% ending in patients taking their own discharge. Only 16% of addicts were notified to the Home Office.

AIDS-related cholangitis: diagnostic features and course in four patients.

Radiological features of sclerosing cholangitis are an uncommon but well recognised complication of HIV infection in homosexual males. In this report we document the clinical features and course of the disease in four patients. Four homosexual males with established AIDS were referred in 1990-92. Three of the four had intractable upper abdominal pain which was poorly responsive to opiates. Three of the patients had diarrhoea and all had weight loss. The diagnosis of AIDS related cholangitis was confirmed by endoscopic retrograde cholangiography in three cases, but in only one patient was there no evidence of biliary disease on ultrasound scanning. In the two cases with cholangiographic features of papillary stenosis, endoscopic sphincterotomy was carried out and there was subsequently a dramatic improvement in the abdominal pain. Three of the patients had evidence of gastrointestinal infection with Microsporidia (1) or Cryptosporidia (2). All the patients died within 2-9 months of the diagnosis of cholangitis, but none of the deaths resulted from hepatobiliary disease.

Effect of histamine H2-receptor blockade on gastric emptying and serum gastrin in man.

The effect of orally administered metiamide, a Histamine H2-receptor antagonist, on the rate of gastric emptying was assessed in 24 uncomplicated duodenal ulcer patients given a standard meal containing indium 113m D.T.P.A. chelate. Metiamide produced significant slowing of gastric emptying when compared with control studies performed on the same patients following oral administration of a placebo. In a further study the effect of metiamide on the serum gastrin response to a protein meal was assessed in seven healthy male volunteers. Paired experiments demonstrated that a significantly greater elevation of serum gastrin occurred after metiamide than after placebo. The delay in gastric emptying produced by metiamide may be mediated by an elevation of the serum gastrin concentration.

When Does a Glass Transition Temperature Not Signify a Glass Transition?

We present a simple model that links enhanced mobility at the free surface to the dilatometric glass transition temperature, Tg in thin films. The model shows that what is typically measured as a dilatometric Tg, characterized by the hallmark "kink" in the plot of film thickness versus temperature, only represents the dynamics of an infinitesimally thin layer of the sample. In other words, the measured dilatometric Tg value in thin films is no longer a good reporter of the dynamics. Calculations based on the model are found to agree with a vast body of thin film Tg measurements. While mathematically simple, the model contains all the necessary physics of a near surface layer with enhanced dynamics and a length scale over which the surface dynamics monotonically varies from surface enhanced to bulk-like. The model demonstrates that the typical dilatometric measurement of the glass transition is not necessarily a real glass transition.

A direct quantitative measure of surface mobility in a glassy polymer.

Thin polymer films have striking dynamical properties that differ from their bulk counterparts. With the simple geometry of a stepped polymer film on a substrate, we probe mobility above and below the glass transition temperature Tg. Above Tg the entire film flows, whereas below Tg only the near-surface region responds to the excess interfacial energy. An analytical thin-film model for flow limited to the free surface region shows excellent agreement with sub-Tg data. The system transitions from whole-film flow to surface localized flow over a narrow temperature region near the bulk Tg. The experiments and model provide a measure of surface mobility in a simple geometry where confinement and substrate effects are negligible. This fine control of the glassy rheology is of key interest to nanolithography among numerous other applications.

Measuring the kinetics and activity of adsorbed proteins: in vitro lysozyme deposited onto hydrogel contact lenses over short time periods.

A new process has been developed to determine the biological activity of an intact layer of lysozyme deposited onto a biomaterial surface. This process is applied to a number of common hydrogel contact lenses. The activity of the surface-adsorbed protein is measured using a standard micrococcal activity assay, with extra steps to distinguish between protein on the surface and protein in solution. This is in contrast to protein extraction work in which the activity of all adsorbed protein is measured. For ionic materials, which are known to deposit large amounts of protein, particularly positively charged proteins such as lysozyme, there is evidence for loosely bound protein re-entering the solution, thus making it impossible to truly separate out the surface-adsorbed protein. This optimized process provides the first quantification of the biological activity of an intact layer of surface-adsorbed protein at a hydrogel interface.

Simultaneous monitoring of electroformation of phospholipid vesicles by quartz crystal microbalance and optical microscopy.

The electroformation of giant vesicles from 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC) was monitored using quartz crystal microbalance with dissipation monitoring (QCM-D) and optical microscopy, simultaneously using a novel sample cell design. A gold-coated QCM crystal was used as one of the electrodes and an Indium-tin-oxide (ITO)-coated glass slide was used as the second electrode for electroformation. Increases in the frequency and decreases in the dissipation were observed immediately upon voltage application between the two electrodes, indicating the loss of lipid from the QCM surface. Concurrently, we observed vesicles on the QCM electrode surface by differential interference contrast (DIC)-optical microscopy. The lipid-coated substrates were measured with AFM at various stages in the electroformation, and a significant change in the morphology of the lipid film was observed. Ellipsometry was used to find the average thickness of lipid film. The QCM data were fitted to a viscoelastic model to determine the viscoelastic properties and time dependence of the film thickness. All methods used to determine film thickness give values in reasonable quantitative agreement. Differences between the methods are consistent with what one might expect due to what is actually measured in the individual techniques. The comparison between mass loss and observed vesicles suggest that the vesicles formed are first localized to the substrate and then slowly released into the solution. By comparing the mass lost from the lipid film, to the total surface area of lipid vesicles observed, it is apparent that only a relatively small fraction of the lipid goes into the production of unilamellar vesicles with sizes detectable with optical microscopy.