Vibrational mismatch of metal leads controls thermal conductance of self-assembled monolayer junctions.

We present measurements of the thermal conductance of self-assembled monolayer (SAM) junctions formed between metal leads (Au, Ag, Pt, and Pd) with mismatched phonon spectra. The thermal conductance obtained from frequency domain thermoreflectance experiments is 65 ± 7 MW/m(2) K for matched Au-alkanedithiol-Au junctions, while the mismatched Au-alkanedithiol-Pd junctions yield a thermal conductance of 36 ± 3 MW/m(2) K. The experimental observation that junction thermal conductance (per molecule) decreases as the mismatch between the lead vibrational spectra increases, paired with results from molecular dynamics (MD) simulations, suggest that phonons scatter elastically at the metal-SAM interfaces. Furthermore, we resolve a known discrepancy between measurements and MD predictions of SAM thermal conductance by using a contact mechanics model to predict 54 ± 15% areal contact in the Au-alkanedithiol-Au experimental junction. This incomplete contact obscures the actual junction thermal conductance of 115 ± 22 MW/m(2) K, which is comparable to that of metal-dielectric interfaces.

Flash-within-flash synthesis of gram-scale solid-state materials.

Sustainable manufacturing that prioritizes energy efficiency, minimal water use, scalability and the ability to generate diverse materials is essential to advance inorganic materials production while maintaining environmental consciousness. However, current manufacturing practices are not yet equipped to fully meet these requirements. Here we describe a flash-within-flash Joule heating (FWF) technique-a non-equilibrium, ultrafast heat conduction method-to prepare ten transition metal dichalcogenides, three group XIV dichalcogenides and nine non-transition metal dichalcogenide materials, each in under 5 s while in ambient conditions. FWF achieves enormous advantages in facile gram scalability and in sustainable manufacturing criteria when compared with other synthesis methods. Also, FWF allows the production of phase-selective and single-crystalline bulk powders, a phenomenon rarely observed by any other synthesis method. Furthermore, FWF MoSe2 outperformed commercially available MoSe2 in tribology, showcasing the quality of FWF materials. The capability for atom substitution and doping further highlights the versatility of FWF as a general bulk inorganic materials synthesis protocol.

The diabetes community exercise programme plus usual care versus usual care in patients with type 2 diabetes: A randomised, two-arm, parallel, open-label trial.

Background: Exercise is important in type 2 diabetes (T2D) management. Focussing on Maori and Pacific people and those from deprived circumstances, the Diabetes Community Exercise Programme (DCEP) was developed to engage people with T2D in exercise. We report the evaluation of whether being offered DCEP (plus usual care) was more effective than usual care in improving glycaemic control at 1-year. Methods: A randomised, two-arm, parallel, open-label trial with blinding of outcome assessor and data analyst. Adults (age ≥35 years) with T2D recruited from two New Zealand (NZ) communities were randomised, using opaque sealed envelopes and stratified by centre with random block lengths, to DCEP or usual care. DCEP comprises twice-weekly, two-hour sessions of exercise and education over 12-weeks, followed by a twice-weekly maintenance exercise class. The primary outcome was between-group differences in mean changes of glycated haemoglobin (HbA1c) from baseline to 1-year follow-up with intention-to treat analysis. This trial is registered with the Australian NZ Clinical Trials Registry (ANZCTR): ACTRN12617001624370p and is closed to new participants. Findings: From 2018 - 2019, of 294 people screened, 165 (mean age 63·8, SD16·2 years, 56% female, 78·5% European, 14% Maori, 6% Pacific, 27% most deprived) were baseline evaluated, randomised, and analysed at study end (DCEP = 83, control = 82). Multimorbidity (≥2) and polypharmacy (>5 medications) were high (82%, 69%). We found no statistically significant between-groups differences in HbA1c (mmol/mol) change at 15 months (mean 3% higher in DCEP, 95% CI 2% lower to 8% higher, p = 0·23). Twelve-week intervention adherence was good (41% attended >80% available sessions). No adverse events were reported. Interpretation: DCEP was not effective in improving glycaemic control, possibly due to insufficient exercise intensity. Our attendance demonstrated DCEP's cultural accessibility. DCEP might be good to engage in exercise marginalised people with high Hb1Ac levels, multimorbidity, and high polypharmacy. Funding: Health Research Council of New Zealand.

Robust Superhydrophobic Surfaces via the Sand-In Method.

Superhydrophobic surfaces have gained sustained attention because of their extensive applications in the fields of self-cleaning, anti-icing, and drag reduction systems. Water droplets must have large apparent contact angle (CA) (>150°) and small CA hysteresis (<10°) on these surfaces. However, previous research usually involves complex fabrication strategies to modify the surface wettability. It is also challenging to maintain the temporal and mechanical stability of the delicate surface textures. Here, we develop a one-step solvent-free sand-in method to fabricate robust superhydrophobic surfaces directly atop various substrates with an apparent CA up to ∼163.8° and hysteresis less than 5°. The water repellency can withstand 100 Scotch tape peeling tests and remain stable after being stored under ambient humid conditions in Houston, Texas, for 18 months or being heated at 130 °C in air for 24 h. The superhydrophobic surfaces have excellent anti-icing ability, including a ∼2.6× longer water freezing time and ∼40% smaller ice adhesion strength with the temperature as low as -35 °C. Since the surface layers are fabricated by sanding the substrates with the powder additives, the surface damage can be repaired by a direct re-sanding treatment with the same powder additives. Further sand-in condition screenings broaden surface wettability from hydrophilic to superhydrophobic. The sand-in method induces the surface modification and the formation of the tribofilm. Surface and materials characterizations reveal that both microstructures and nanoscale asperities of the tribofilms contribute to the robust superhydrophobic features of sanded surfaces.

Experimental study of granular flows in a rough annular shear cell.

The study of granular flows in physics has always been important because of their recurring presence in nature and industry. However, the nonlinear and multiphase behavior exhibited by these particulate systems makes them hard to model and predict. Several experiments were conducted in the past to gain insight into granular flows. The current experimental work furthers this insight and specifically attempts to understand the effect of rough surfaces on granular flows, namely, their local flow behavior. Understanding this interaction can have implications on industrial-scale granular problems. In this work, a granular shear cell, a two-dimensional annular shear cell, was developed to conduct shear experiments where roughness is imposed on the driving surface and experimentally quantified. A digital particle tracking velocimetry data retrieval scheme was developed to extract solid fraction, velocity, and granular temperature data from the experiments as a function of the roughness factor and wheel rotation rate. In general, the steady-state results show the two distinct regions as expected-a high-velocity and dilute-gas-like kinetic region near the moving wall and a high-solid-fraction liquid-like frictional flow regime away from the moving wall. Parametric studies conducted show that the normalized slip near the moving wall decreases with increasing wall roughness and decreasing wall rotation rate. Slip is an important parameter which can be easily interpreted as momentum transfer or traction performance in granular systems related to wheel-terrain interaction, agricultural processing, and most notably granular lubrication.

Early spectra of the gravitational wave source GW170817: Evolution of a neutron star merger.

On 17 August 2017, Swope Supernova Survey 2017a (SSS17a) was discovered as the optical counterpart of the binary neutron star gravitational wave event GW170817. We report time-series spectroscopy of SSS17a from 11.75 hours until 8.5 days after the merger. Over the first hour of observations, the ejecta rapidly expanded and cooled. Applying blackbody fits to the spectra, we measured the photosphere cooling from [Formula: see text] to [Formula: see text] kelvin, and determined a photospheric velocity of roughly 30% of the speed of light. The spectra of SSS17a began displaying broad features after 1.46 days and evolved qualitatively over each subsequent day, with distinct blue (early-time) and red (late-time) components. The late-time component is consistent with theoretical models of r-process-enriched neutron star ejecta, whereas the blue component requires high-velocity, lanthanide-free material.

Light curves of the neutron star merger GW170817/SSS17a: Implications for r-process nucleosynthesis.

On 17 August 2017, gravitational waves (GWs) were detected from a binary neutron star merger, GW170817, along with a coincident short gamma-ray burst, GRB 170817A. An optical transient source, Swope Supernova Survey 17a (SSS17a), was subsequently identified as the counterpart of this event. We present ultraviolet, optical, and infrared light curves of SSS17a extending from 10.9 hours to 18 days postmerger. We constrain the radioactively powered transient resulting from the ejection of neutron-rich material. The fast rise of the light curves, subsequent decay, and rapid color evolution are consistent with multiple ejecta components of differing lanthanide abundance. The late-time light curve indicates that SSS17a produced at least ~0.05 solar masses of heavy elements, demonstrating that neutron star mergers play a role in rapid neutron capture (r-process) nucleosynthesis in the universe.

Geometric effects in microfluidics on heterogeneous cell stress using an Eulerian-Lagrangian approach.

The response of individual cells at the micro-scale in cell mechanics is important in understanding how they are affected by changing environments. To control cell stresses, microfluidics can be implemented since there is tremendous control over the geometry of the devices. Designing microfluidic devices to induce and manipulate stress levels on biological cells can be aided by computational modeling approaches. Such approaches serve as an efficient precursor to fabricating various microfluidic geometries that induce predictable levels of stress on biological cells, based on their mechanical properties. Here, a three-dimensional, multiphase computational fluid dynamics (CFD) modeling approach was implemented for soft biological materials. The computational model incorporates the physics of the particle dynamics, fluid dynamics and solid mechanics, which allows us to study how stresses affect the cells. By using an Eulerian-Lagrangian approach to treat the fluid domain as a continuum in the microfluidics, we are conducting studies of the cells' movement and the stresses applied to the cell. As a result of our studies, we were able to determine that a channel with periodically alternating columns of obstacles was capable of stressing cells at the highest rate, and that microfluidic systems can be engineered to impose heterogenous cell stresses through geometric configuring. We found that when using controlled geometries of the microfluidics channels with staggered obstructions, we could increase the maximum cell stress by nearly 200 times over cells flowing through microfluidic channels with no obstructions. Incorporating computational modeling in the design of microfluidic configurations for controllable cell stressing could help in the design of microfludic devices for stressing cells such as cell homogenizers.

In vivo markers of inflammatory response in recent-onset schizophrenia: a combined study using [(11)C]DPA-713 PET and analysis of CSF and plasma.

Several lines of evidence suggest aberrant immune response in schizophrenia, including elevated levels of cytokines. These cytokines are thought to be produced by activated microglia, the innate immune cells of the central nervous system. However, increase in translocator protein 18 kDa (TSPO), a marker of activated glia, has not been found in patients with chronic schizophrenia using second-generation radiotracers and positron emission tomography (PET)-based neuroimaging. In this study we focused on patients with recent onset of schizophrenia (within 5 years of diagnosis). Quantified levels of TSPO in the cortical and subcortical brain regions using the PET-based radiotracer [(11)C]DPA-713 were compared between the patients and healthy controls. Markers of inflammation, including interleukin 6 (IL-6), were assessed in the plasma and cerebrospinal fluid (CSF) in these participants. We observed no significant change in the binding of [(11)C]DPA-713 to TSPO in 12 patients with recent onset of schizophrenia compared with 14 controls. Nevertheless, the patients with recent onset of schizophrenia showed a significant increase in IL-6 in both plasma (P<0.001) and CSF (P=0.02). The CSF levels of IL-6 were significantly correlated with the levels of IL-6 in plasma within the total study population (P<0.001) and in patients with recent onset of schizophrenia alone (P=0.03). Our results suggest that increased levels of IL-6 may occur in the absence of changed TSPO PET signal in the brains of medicated patients with recent onset of schizophrenia. Future development of PET-based radiotracers targeting alternative markers of glial activation and immune response may be needed to capture the inflammatory signature present in the brains of patients with early-stage disease.

Decoupling of N-acetyl-aspartate and glutamate within the dorsolateral prefrontal cortex in schizophrenia.

Aberrant function of glutamatergic pathways is likely to underlie the pathology of schizophrenia. Evidence of oxidative stress in the disease pathology has also been reported. N-Acetylaspartate (NAA) is metabolically linked to both cascades and may be a key marker in exploring the interconnection of glutamatergic pathways and oxidative stress. Several studies have reported positive correlation between the levels of NAA and Glx (the sum of glutamate and glutamine) in several brain regions in healthy subjects, by using proton magnetic resonance spectroscopy ([(1)H]MRS). Interestingly, one research group recently reported decoupling of the relationship between NAA and Glx in the hippocampus of patients with schizophrenia. Here we report levels of NAA and Glx measured using [(1)H]MRS, relative to the level of creatine (Cr) as an internal control. The dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in 25 patients with schizophrenia and 17 matched healthy controls were studied. In DLPFC, NAA/Cr and Glx/Cr were significantly positively correlated in healthy controls after correction for the effect of age and smoking status and after correction for multiple comparisons (r= 0.627, P= 0.017). However, in patients with schizophrenia, the positive correlation between NAA/Cr and Glx/Cr was not observed even after correcting for these two variables (r= -0.330, P= 0.124). Positive correlation between NAA/Cr and Glx/Cr was not observed in the ACC in both groups. Decoupling of NAA and Glx in the DLPFC may reflect the interconnection of glutamatergic pathways and oxidative stress in the pathology of schizophrenia, and may possibly be a biomarker of the disease.

Dimerization and domain swapping in G-protein-coupled receptors: a computational study.

In recent years there has been an increasing number of reports describing G protein-coupled receptor (GPCR) dimerization and heterodimerization. However, the evidence on the nature of the dimers and their role in GPCR activation is inconclusive. Consequently, we present here a review of our computational studies on G protein-coupled receptor dimerization and domain swapping. The studies described include molecular dynamics simulations on receptor monomers and dimers in the absence of ligand, in the presence of an agonist, and in the presence of an antagonist (or more precisely an inverse agonist). Two distinct sequence-based approaches to studying protein interfaces are also described, namely correlated mutation analysis and evolutionary trace analysis. All three approaches concur in supporting the proposal that the dimerization interface includes transmembrane helices 5 and 6. These studies cannot distinguish between domain swapped dimers and contact dimers as the models used were restricted to the helical part of the receptor. However, it is proposed that for the purpose of signalling, the domain swapped dimer and the corresponding contact dimer are equivalent. The evolutionary trace analysis suggests that every GPCR family and subfamily (for which sufficient sequence data is available) has the potential to dimerize through this common functional site on helices 5 and 6. The evolutionary trace results on the G protein are briefly described and these are consistent with GPCR dimerization. In addition to the functional site on helices 5 and 6, the evolutionary trace analysis identified a second functional site on helices 2 and 3. Possible roles for this site are suggested, including oligomerization.

Dimerization of G-protein-coupled receptors.

The evolutionary trace (ET) method, a data mining approach for determining significant levels of amino acid conservation, has been applied to over 700 aligned G-protein-coupled receptor (GPCR) sequences. The method predicted the occurrence of functionally important clusters of residues on the external faces of helices 5 and 6 for each family or subfamily of receptors; similar clusters were observed on helices 2 and 3. The probability that these clusters are not random was determined using Monte Carlo techniques. The cluster on helices 5 and 6 is consistent with both 5,6-contact and 5,6-domain swapped dimer formation; the possible equivalence of these two types of dimer is discussed because this relates to activation by homo- and heterodimers. The observation of a functionally important cluster of residues on helices 2 and 3 is novel, and some possible interpretations are given, including heterodimerization and oligomerization. The application of the evolutionary trace method to 113 aligned G-protein sequences resulted in the identification of two functional sites. One large, well-defined site is clearly identified with adenyl cyclase, beta/gamma and regulator of G-protein signaling (RGS) binding. The other G-protein functional site, which extends from the ras-like domain onto the helical domain, has the correct size and electrostatic properties for GPCR dimer binding. The implications of these results are discussed in terms of the conformational changes required in the G-protein for activation by a receptor dimer. Further, the implications of GPCR dimerization for medicinal chemistry are discussed in the context of these ET results.

Pharmacokinetics and hemodynamic effects of single oral doses of thalidomide in asymptomatic human immunodeficiency virus-infected subjects.

Thalidomide (alpha-N-phthalimidoglutarimide), a potent inhibitor of tumor necrosis factor alpha (TNF-alpha), is proving to be a promising drug in the treatment of a number of inflammatory, autoimmune, and HIV-associated disorders. The pharmacokinetics and hemodynamic effects of two single oral doses of thalidomide (100 and 200 mg) were investigated, using a randomized, two-period crossover design, in a group of asymptomatic, male HIV-seropositive subjects. Thalidomide pharmacokinetics were linear at the doses studied, and were best described by a one-compartment model with first-order absorption and elimination processes. The drug was rapidly absorbed, with a mean absorption half-life of 0.95 hr (range, 0.16-2.49 hr) and 1.19 hr (range, 0.33-3.53 hr) after 100- and 200-mg doses, respectively. The corresponding mean Cmax values were 1.15+/-0.24 microg/ml (100 mg) and 1.92+/-0.47 microg/ml (200 mg; p<0.001), which were achieved (Tmax) at 2.5+/-1.5 h and 3.3+/-1.4 hr, respectively. Plasma concentrations of thalidomide declined thereafter, in a log-linear manner, with elimination half-lives of 4.6+/-1.2 hr (100 mg) and 5.3+/-2.2 hr (200 mg). The apparent volumes of distribution (Vdss/F) were 69.9+/-15.6 liters (100 mg) and 82.7+/-34.9 liters (200 mg) while total body clearances (Cl/F) were 10.4+/-2.1 and 10.8+/-1.7 liters/hr, respectively. Significant dose-dependent decreases in supine systolic and diastolic blood pressures were seen for up to 2 hr postdosing; somnolence, headache, dizziness, and confusion were also reported more frequently at the higher dose of thalidomide.

Safety, pharmacokinetics, and antiretroviral activity of the potent, specific human immunodeficiency virus protease inhibitor nelfinavir: results of a phase I/II trial and extended follow-up in patients infected with human immunodeficiency virus.

The safety, antiretroviral activity, and pharmacokinetic profile of nelfinavir, a potent and specific inhibitor of human immunodeficiency virus (HIV) protease, were assessed in a small open-label phase I/II dose-ranging study in protease inhibitor-naive HIV-positive men. A total of 22 patients with baseline plasma HIV RNA > or = 20,000 copies/mL and CD4+ counts between 200 and 500 cells/mm3 were enrolled in the study. Of the 22 patients, 20 were evaluated for activity; 10 patients assigned to 771 mg/day base equivalent (300 mg three times daily) and 10 patients assigned to 1,026 mg/day base equivalent (600 mg twice daily) given monotherapy. A capsule formulation of nelfinavir was used. The initial study period was 28 days; patients showing a virologic response of 1 log10 reduction were eligible for enrollment in an extension phase and addition of nucleoside analogues. A maximally tolerated dose of nelfinavir was not established. A dose-response relationship was observed for four (40%) patients in the 771-mg group and six (60%) patients in the 1,026-mg group experiencing a reduction from baseline in plasma HIV RNA of at lest 1 log during the 28-day study. Of these patients, five sustained the reduction in plasma HIV RNA beyond day 28 (2 patients receiving 771 mg/day and 3 patients receiving 1,026 mg/day). Median increases from baseline in CD4+ counts at day 28 were 216 cell/mm3 and 86 cell/mm3 in the 771-mg and 1,026-mg groups, respectively. After oral administration, median nelfinavir plasma concentrations on day 28 reached a maximum at 1 hour (2,966 ng/mL) in the 771-mg group and at 3 hours (3,157 ng/mL) in the 1,026-mg group. Data for 22 patients were included in the safety analysis; 12 patients (55%) reported at least one grade 2 or worse (moderate, severe, or very severe) adverse event. The most common grade 2 or worse adverse event was diarrhea, reported by two patients (20%) receiving 771 mg/day and seven patients (70%) receiving 1,026 mg/day; followed by nausea, flatulence, asthenia, and headache (each reported in 1 patient [10%] in the 771-mg group) and dizziness (reported in 1 patient [10%] receiving 1,026 mg/day). In the small subgroup (n = 6) who continued taking nelfinavir for longer periods (between 8 and 15 months), virologic responses were sustained in the majority of patients with good tolerability. Nelfinavir is an active HIV-protease inhibitor with favorable pharmacokinetics, good tolerability, and sustained antiviral effects. Results of this early phase I/II dose-ranging study provided data for the safety and antiretroviral activity of nelfinavir and led to the selection of higher doses for phase II/III trials to further optimize virologic and immunologic responses.

Home blood pressure recording in mild hypertension: value of distinguishing sustained from clinic hypertension and effect on diagnosis and treatment. Bath Health District Hypertension Study Group.

To identify the prevalence and magnitude of clinic changes in blood pressure and determine their effects on the diagnosis and treatment of hypertension, 268 patients with a BP greater than or equal to 160/95 mmHg on three consecutive occasions (twice in the general practitioner's surgery and once in the hospital clinic) recorded a home BP series with an electronic sphygmomanometer. Of these patients, 114 had never received antihypertensive treatment and 154 were receiving treatment. On return to the hospital clinic (second clinic visit) the BP was measured independently by the patient and doctor using electronic and mercury sphygmomanometers respectively and compared with the mean BP of the home series. In some 80% of both untreated and treated patients the second clinic BP was higher than the mean BP of the home series and in some 40% of patients a clinic rise of greater than 20/10 mmHg was recorded. Clinic falls in BP occurred in some 20% of both untreated and treated patients, but averaged only 4/4 mmHg. Treatment decisions based on a mean diastolic blood pressure of greater than or equal to 95 mmHg in the home series resulted in antihypertensive treatment not being started in 38% of untreated patients and not increased in 31% or reduced in 16% of treated patients when treatment would have been started, increased or continued unchanged on the basis of the second clinic (fourth recorded) diastolic blood pressure of greater than or equal to 95 mmHg. A patient recorded home series provides a representative sample of BP which distinguishes patients with sustained hypertension from those with clinic hypertension and may help reduce the overdiagnosis and overtreatment of mild hypertension.

Value of patient-recorded home blood pressure series in distinguishing sustained from office hypertension: effects on diagnosis and treatment of mild hypertension. Bath District Hypertension Study Group.

To identify the incidence and magnitude of office hypertension and determine its effect on diagnosis and treatment, 104 patients with a systolic blood pressure greater than or equal to 160 mmHg and a diastolic blood pressure greater than or equal to 95 mmHg on three consecutive office visits recorded a home BP series with an electronic sphygmomanometer. At the fourth office visit the blood pressure was measured independently by the patient and doctor using electronic and mercury sphygmomanometers, respectively, and compared with the mean blood pressure of the home series. In 80% of patients, the fourth office blood pressure was higher than the mean blood pressure of the home series. An office rise greater than or equal to 10/5 mmHg occurred in some 60% of patients, greater than or equal to 20/10 mmHg in 36% and 30/15 mmHg in 19% of patients. Office falls in blood pressure occurred in 20% of patients but averaged 3/2 mmHg. Treatment decisions based on the mean blood pressure of the home series resulted in treatment not being started in 25 patients (24%) who would have received treatment on their fourth office blood pressures. A patient-recorded home series provides a representative sample of blood pressure distinguishing patients with sustained hypertension from those with office hypertension and reducing the over diagnosis and over treatment of mild hypertension.

Acceptability of oxygen concentrators: the patient's view.

The impact of the installation of an oxygen concentrator on the lifestyle of 30 patients in two health districts has been investigated using a questionnaire. Marked improvements in general well-being (83% of respondents), breathing (82%), mobility (62%) and sleep pattern (52%) were reported. The long term nature of the aims of treatment were understood by 83% of the respondents and the mean period of time the patients used the concentrator was satisfactory. However, 34% of respondents had a concentrator with only one outlet and 70% had the concentrator situated in a commonly used room with the possibility of problems with noise. Thirty one percent of the respondents were still smoking. The recommendations given to patients for the sitting of the concentrator and the number of outlets should be improved. However, the oxygen concentrator was found to be generally well tolerated and this refutes criticism that patients may find it restricting.

Accuracy of perception of severity of asthma: patients treated in general practice.

OBJECTIVE: To determine the frequency of poor perception of severity of asthma in general practice. DESIGN: Asthmatic patients recorded their perceived severity of asthma, with a visual analogue score, and a coded measurement of their peak expiratory flow up to four times daily for 14 consecutive days. SETTINGS: 11 general practices in and around Bristol. SUBJECTS: 255 asthmatic patients (139 men and 116 women) aged 17-76 who were recruited by random selection from the general practices' disease registers or when they requested prescriptions for inhaled bronchodilators. MAIN OUTCOME MEASURES: Correlation between visual analogue scores and peak expiratory flow (as a percentage of predicted peak flow). RESULTS: 152 (60%) of the patients showed no significant correlation between visual analogue asthma scores and simultaneous peak flow measurements (p > 0.05) and were termed poor discriminators. The distribution of good and poor discriminators within each general practice was similar (chi 2 = 6.11, df = 10). The two groups were not characterised by differences in the maximum, minimum, or standard deviation of peak expiratory flow or visual analogue score; in age; or in the proportion of men and women in each group. CONCLUSIONS: In general practice a high proportion of asthmatic patients do not reliably detect changes in their lung function. This reinforces the need for careful objective assessment of lung function in the management of asthma.

Backstage, frontstage: an analysis of work and leisure roles of women recreational softball players.

American culture and attitudes are profoundly homophobic. Studies abound that describe the violence and discrimination that traditionally have been part of a homosexual's life. Growing up "queer" in the United States prompts many homosexuals to consciously or unconsciously suppress homoerotic feelings (Forstein, 1988). The traditionally male and female identities in society are strongly connected to heterosexuality. Reality and fear that constrain a homosexual result in what Schwanberg (1993) states is a "rigidly segmented life in which one works as a straight person and plays as a gay one" (p. 47). Utilizing Goffmanian terminology, this study will explore the presentation of front and backstage selves of women recreational softball players in Alaska.

A compartmental pharmacokinetic evaluation of long-acting rilpivirine in HIV-negative volunteers for pre-exposure prophylaxis.

Rilpivirine long-acting (RPV-LA) is a parenteral formulation enabling prolonged plasma exposure. We explored its multiple-compartment pharmacokinetics (PK) after a single dose, for pre-exposure prophylaxis. Sixty-six HIV-negative volunteers were enrolled: women received an intramuscular dose of 300, 600, or 1,200 mg, with plasma and genital levels measured to 84 days postdose; men receiving 600 mg had similar PK determined in plasma and rectum. Ex vivo antiviral activity of cervicovaginal lavage (CVL) was also assessed. After a single dose, RPV concentrations peaked at days 6-8 and were present in plasma and genital-tract fluid to day 84. Vaginal and male rectal tissue levels matched those in plasma. At the 1,200 mg dose, CVL showed greater antiviral activity, above baseline, at days 28 and 56. All doses were well tolerated. All doses gave prolonged plasma and genital-tract rilpivirine exposure. PK and viral inhibition of repeated doses will be important in further dose selection.