The Prevalence and Patterns of Menopausal Symptoms in Women Living with HIV.

Increasing numbers of women with HIV are experiencing menopause. We use data from a large, representative sample of women with HIV to describe the prevalence and clustering of menopausal symptoms amongst pre-, peri- and post-menopausal women using hierarchical agglomerative cluster analysis. Of the 709 women included, 21.6%, 44.9% and 33.6% were pre-, peri- and post-menopausal, respectively. Joint pain (66.4%) was the most commonly reported symptom, followed by hot flashes (63.0%), exhaustion (61.6%) and sleep problems (61.4%). All symptoms were reported more commonly by peri- and post-menopausal women compared to pre-menopausal women. Psychological symptoms and sleep problems clustered together at all menopausal stages. Somatic and urogenital symptom clusters emerged more distinctly at peri- and post-menopause. We recommend regular and proactive assessment of menopausal symptoms in midlife women with HIV, with an awareness of how particular patterns of symptoms may evolve over the menopausal transition.

Dynamics of picosecond laser ablation for surgical treatment of colorectal cancer.

Endoluminal surgery for the treatment of colorectal neoplasia is typically carried out using electrocautery tools which imply limited precision and the risk of harm through collateral thermal damage to the adjacent healthy tissue. As a potential alternative, we present the successful colonic epithelial laser ablation by means of picosecond laser pulses. Laser ablation studies performed in ex-vivo colon tissue result in cavities with comparable thickness to early stage colorectal cancers. The corresponding histology sections exhibit only minimal collateral damage to the surrounding tissue and the depth of the ablation can be controlled precisely by means of the pulse energy. High-speed imaging has been used for the first time to visualize picosecond laser ablation of cancerous tissue in a clinically relevant model. This information was correlated with histopathology and optical surface profilometry revealing the dynamic nature of the laser tissue interaction and the need for temporal or spatial separation of pulses for optimum efficacy with regards to tissue removal. Overall, the application of picosecond laser pulses to ablate endoluminal bowel lesions demonstrates significantly improved precision and reduced thermal damage to the adjacent tissue in comparison to conventional procedures and hence will enable more precise surgical treatment of cancers.

Microstructures of negative and positive azeotropes.

Azeotropes famously impose fundamental restrictions on distillation processes, yet their special thermodynamic properties make them highly desirable for a diverse range of industrial and technological applications. Using neutron diffraction, we investigate the structures of two prototypical azeotropes, the negative acetone-chloroform and the positive benzene-methanol azeotrope. C-HO hydrogen bonding is the dominating interaction in the negative azeotrope but C-ClO halogen bonding contributes as well. Hydrogen-bonded chains of methanol molecules, which are on average longer than in pure methanol, are the defining structural feature of the positive azeotrope illustrating the fundamentally different local mixing in the two kinds of azeotropes. The emerging trend for both azeotropes is that the more volatile components experience the more pronounced structural changes in their local environments as the azeotropes form. The mixing of the acetone-chloroform azeotrope is essentially random above 20 Å, where the running Kirkwood-Buff integrals of our structural model converge closely to the ones expected from thermodynamic data. The benzene-methanol azeotrope on the other hand displays extended methanol-rich regions and consequently the running Kirkwood-Buff integrals oscillate up to at least 60 Å. Our study provides the first experimental insights into the microstructures of azeotropes and a direct link with their thermodynamic properties. Ultimately, this will provide a route for creating tailored molecular environments in azeotropes to improve and fine-tune their performances.

Molecular Reorientation Dynamics Govern the Glass Transitions of the Amorphous Ices.

The glass transitions of low-density amorphous ice (LDA) and high-density amorphous ice (HDA) are the topic of controversial discussions. Understanding their exact nature may be the key to explaining the anomalies of liquid water but has also got implications in the general context of polyamorphism, the occurrence of multiple amorphous forms of the same material. We first show that the glass transition of hydrogen-disordered ice VI is associated with the kinetic unfreezing of molecular reorientation dynamics by measuring the calorimetric responses of the corresponding H2O, H2(18)O, and D2O materials in combination with X-ray diffraction. Well-relaxed LDA and HDA show identical isotopic-response patterns in calorimetry as ice VI, and we conclude that the glass transitions of the amorphous ices are also governed by molecular reorientation processes. This "reorientation scenario" seems to resolve the previously conflicting viewpoints and is consistent with the fragile-to-strong transition from water to the amorphous ices.

Dynamically controlled deposition of colloidal nanoparticle suspension in evaporating drops using laser radiation.

Dynamic control of the distribution of polystyrene suspended nanoparticles in evaporating droplets is investigated using a 2.9 µm high power laser. Under laser radiation a droplet is locally heated and fluid flows are induced that overcome the capillary flow, and thus a reversal of the coffee-stain effect is observed. Suspension particles are accumulated in a localised area, one order of magnitude smaller than the original droplet size. By scanning the laser beam over the droplet, particles can be deposited in an arbitrary pattern. This finding raises the possibility for direct laser writing of suspended particles through a liquid layer. Furthermore, a highly uniform coating is possible by manipulating the laser beam diameter and exposure time. The effect is expected to be universally applicable to aqueous solutions independent of solutes (either particles or molecules) and deposited substrates.

Evolution of Hydrogen Dynamics in Amorphous Ice with Density.

The single-particle dynamics of hydrogen atoms in several of the amorphous ices are reported using a combination of deep inelastic neutron scattering (DINS) and inelastic neutron scattering (INS). The mean kinetic energies of the hydrogen nuclei are found to increase with increasing density, indicating the weakening of hydrogen bonds as well as a trend toward steeper and more harmonic hydrogen vibrational potential energy surfaces. DINS shows much more pronounced changes in the O-H stretching component of the mean kinetic energy going from low- to high-density amorphous ices than indicated by INS and Raman spectroscopy. This highlights the power of the DINS technique to retrieve accurate ground-state kinetic energies beyond the harmonic approximation. In a novel approach, we use information from DINS and INS to determine the anharmonicity constants of the O-H stretching modes. Furthermore, our experimental kinetic energies will serve as important benchmark values for path-integral Monte Carlo simulations.

Polar stacking of molecules in liquid chloroform.

Using neutron diffraction and the isotopic substitution technique we have investigated the local structure of liquid chloroform. A strong tendency for polar stacking of molecules with collinear alignment of dipole moments is found. We speculate that these polar stacks contribute to the performance of chloroform as a solvent.

Flexible delivery of Er:YAG radiation at 2.94 µm with negative curvature silica glass fibers: a new solution for minimally invasive surgical procedures.

We present the delivery of high energy microsecond pulses through a hollow-core negative-curvature fiber at 2.94 µm. The energy densities delivered far exceed those required for biological tissue manipulation and are of the order of 2300 J/cm(2). Tissue ablation was demonstrated on hard and soft tissue in dry and aqueous conditions with no detrimental effects to the fiber or catastrophic damage to the end facets. The energy is guided in a well confined single mode allowing for a small and controllable focused spot delivered flexibly to the point of operation. Hence, a mechanically and chemically robust alternative to the existing Er:YAG delivery systems is proposed which paves the way for new routes for minimally invasive surgical laser procedures.

Delivery of high energy Er:YAG pulsed laser light at 2.94 µm through a silica hollow core photonic crystal fibre.

In this paper the delivery of high power Er:YAG laser pulses through a silica hollow core photonic crystal fibre is demonstrated. The Er:YAG wavelength of 2.94 µm is well beyond the normal transmittance of bulk silica but the unique hollow core guidance allows silica to guide in this regime. We have demonstrated for the first time the ability to deliver high energy pulses through an all-silica fibre at 2.94 µm. These silica fibres are mechanically and chemically robust, biocompatible and have low sensitivity to bending. A maximum pulse energy of 14 mJ at 2.94 µm was delivered through the fibre. This, to our knowledge, is the first time a silica hollow core photonic crystal fibre has been shown to transmit 2.94 µm laser light at a fluence exceeding the thresholds required for modification (e.g. cutting and drilling) of hard biological tissue. Consequently, laser delivery systems based on these fibres have the potential for the realization of novel, minimally-invasive surgical procedures.

Mechanisms of Cation Exchange by Pseudomonas aeruginosa PAO1 and PAO1 wbpL, a Strain with a Truncated Lipopolysaccharide.

The ability of bacterial cells to sequester cations is well recognized, despite the fact that the specific binding sites and mechanistic details of the process are not well understood. To address these questions, the cation-exchange behavior of Pseudomonas aeruginosa PAO1 cells with a truncated lipopolysaccharide (LPS) (PAO1 wbpL) and cells further modified by growth in a magnesium-deficient medium (PAO1 wbpL - Mg(2+)) were compared with that of wild-type P. aeruginosa PAO1 cells. P. aeruginosa PAO1 cells had a negative surface charge (zeta potential) between pH 11 and 2.2, due to carboxylate groups present in the B-band LPS. The net charge on PAO1 wbpL cells was increasingly positive below pH 3.5, due to the influence of NH(3)(+) groups in the core LPS. The zeta potentials of these cells were also measured in Na(+), Ca(2+), and La(3+) electrolytes. Cells in the La(3+) electrolyte had a positive zeta potential at all pH values tested. Growing P. aeruginosa PAO1 wbpL in magnesium-deficient medium (PAO1 wbpL - Mg(2+)) resulted in an increase in its zeta potential in the pH range from 3.0 to 6.5. In cation-exchange experiments carried out at neutral pH with either P. aeruginosa PAO1 or PAO1 wbpL, the concentration of bound Ca(2+) was found to decrease as the pH was reduced from 7.0 to 3.5. At pH 3.5, the bound Mg(2+) concentration decreased sharply, revealing the activity of surface sites for cation exchange and their pH dependence. Infrared spectroscopy of attached biofilms suggested that carboxylate and phosphomonoester functional groups within the core LPS are involved in cation exchange.

Analysis of optical damage mechanisms in hollow-core waveguides delivering nanosecond pulses from a Q-switched Nd:YAG laser.

Hollow-core waveguides consisting of a glass capillary tube with an internal reflective coating are capable of delivering pulse energies of tens of millijoules with improved focusability compared to step index fibers of similar core diameter. We demonstrate the capability of these fibers to deliver high-power Q-switched pulses at the fundamental (1064 nm), second (532 nm), and third (355 nm) harmonics of a Nd:YAG laser, both in terms of peak power and beam quality delivered. In terms of peak power delivery, the primary limitation is the occurrence of bend-induced optical damage to the reflective coating. The damage mechanism and the influential factors are analyzed, in particular, the dependence upon the number of guided modes, core diameter, coating thicknesses, and input polarization alignment.

MiniCog: a method for administering psychological tests and experiments on a handheld personal digital assistant.

Because of their minimal cost, size, and weight, handheld personal digital assistants (PDAs) are appealing as a means for administering response time tasks "in the field" or to participants in longitudinal studies who need repeated access to the testing equipment. We have developed a software package that allows investigators to author simple scripts on their desktop computers and administer the compiled tasks on PDAs. MiniCog presents instructions, practice trials with auditory feedback, and visual stimuli in random or fixed sequential orders with fixed or variable durations and intertrial intervals and records single-button responses and response times. Data from each trial are stored with a user ID, user-entered demographics and notes, and a time-and-date stamp, for later upload to a desktop computer. MiniCog performs automatic calculations of mean response time and error rate, available to users with a password and stored with the other data for upload.

Single-mode mid-IR guidance in a hollow-core photonic crystal fiber.

We report, for the first time, bandgap guidance above 3 mum in a silica based air-core photonic crystal fiber. The peak of the bandgap is at 3.14mum with a typical attenuation of ~ 2.6 dB m-1. By further optimization of the structure, modeling suggests that a loss below 1 dB m-1 should be achievable, greatly extending the useful operating range of silica-based single-mode fibers. Such fibers have many potential applications in the mid-IR, offering an alternative to fluoride, tellurite or chalcogenide glass based optical fibers for chemical and biological sensing applications.

Combining platinum, paclitaxel and anthracycline in patients with advanced gynaecological malignancy.

Two meta-analyses have suggested that the addition of an anthracycline to platinum-based chemotherapy may improve survival in advanced ovarian cancer, and two randomised trials have demonstrated superiority of paclitaxel over cyclophosphamide in platinum combinations. A combination of platinum, anthracycline and paclitaxel would, therefore, be a reasonable experimental arm of any future randomised trial in patients with epithelial ovarian carcinoma (EOC). Patients who required chemotherapy for EOC but were ineligible for standard trials or had other gynaecological tumours that required similar platinum-based chemotherapy were considered for this pilot. The platinum/anthracycline/paclitaxel regimen (G-CAT) was given 3-weekly and consisted of doxorubicin 50 mg/m(2) or epirubicin 60 mg/m(2) intravenously (i.v.) bolus, paclitaxel 175 mg/m(2) (i.v.) over 3 h and either cisplatin 75 mg/m(2) (i.v.) or carboplatin AUC 6, with granulocyte colony-stimulating factor (G-CSF) at the neutrophil nadir. Different combinations were used in order to determine the least toxic regimen. Toxicity and response were assessed according to CTC and WHO criteria, respectively. 26 patients entered the study, 13 with EOC and 13 with other gynaecological cancers (peritoneal, fallopian tube, mixed Mullerian). Median age was 49 years (range: 27-67). 8 patients received carboplatin/doxorubicin/paclitaxel, 8 cisplatin/doxorubicin/paclitaxel and 10 carboplatin/epirubicin/paclitaxel. A total of 135 cycles of chemotherapy were delivered, with a median of 6 cycles per patient (range: 2-6). 54 (40%) cycles required G-CSF support and 17 (65%) patients required at least one dose reduction. All patients experienced grade 4 neutropenia and 13 (50%) patients developed grade 3-4 thrombocytopenia (12 of whom had received carboplatin). There were 4 (15%) patients with grade 3/4 infections but no septic deaths. Non-haematological toxicities were manageable, lethargy occurred in 75% of cisplatin-treated patients. Grade 1/2 cardiotoxicity, as assessed pre- and post-treatment by left ventricular ejection fraction, was observed in 6/13 (46%) patients who had received doxorubicin and 2/7 (29%) epirubicin-treated patients. No clinically detectable cardiac toxicity was encountered. The response rate in 25 evaluable patients was 76% (12 CR, 7 PR). Dose intensity was highest in the carboplatin/epirubicin/paclitaxel combination. G-CAT shows high activity and can be administered safely, but only very fit patients are suitable for this regimen as it is associated with considerable toxicity. Carboplatin/epirubicin/paclitaxel was the best tolerated regimen overall.

The application of a non-imaging nuclear probe system to the critically ill: laboratory validation and a clinical trial.

Non-imaging nuclear probe systems have been available for bedside monitoring of left ventricular function since the early 1970s. The purpose of this study was to evaluate a recently developed system, the Cardioscint (Oakfield Instruments, Oxford, UK), both in the laboratory and clinically prior to its application in the critically ill on the intensive care unit. The probe system was stable at body temperature for prolonged periods and its count rate capability was adequate for those encountered clinically. An adequate period of data acquisition was shown to be important because random isotope decay produces a significant noise at these count rates. Left ventricular ejection fraction in patients with symmetrical ventricular contraction agree closely with the results obtained with radionuclide ventriculography (mean difference = 0.98%, S.D. = 2.8%, n = 30). However, in patients with asymmetrical ventricular contraction the agreement is poor (mean difference = -3.0%, S.D. = 6.2%, n = 10).

Bedside assessment of myocardial performance in the critically ill.

No measurement of myocardial performance currently available in the ICU can be regarded is ideal. Table 2 summarises the main features of the major monitoring techniques. As many of the indices of myocardial performance are interdependent, quantifying the contribution of each component to overall cardiac function is not possible currently, and the clinical utility of monitoring each individually is not therefore established. Bedside measurements of LV dimensions, volumes and ejection fraction, and the other indices of systolic and diastolic function can now be made, but the case for their routine use in influencing clinical practice remains unproven. Transoesophageal echocardiography has an important and established diagnostic role and has been used successfully for continuous monitoring during surgery, but practical considerations seriously limit its potential for routine use. Radionuclide techniques allow the measurement of many of the same parameters and have the potential for continuous use, but practical problems and the additional risk of radiation exposure may limit this application in the critical care environment. Doppler techniques are non-invasive, provide continuous data and are simple to operate, but the data provided has important limitations. Although the pulmonary artery catheter has been in use for over twenty years, questions regarding the information is provides concerning myocardial function remain and the extent to which it should influence therapeutic decisions is still controversial. However with the development of additional facilities, particularly the continuous measurement of cardiac output the pulmonary artery catheter seems likely to remain the mainstay of bedside monitoring of myocardial performance in the critically ill in the immediate future.

Comparison of end-tidal and arterial carbon dioxide measurements during anaesthesia with the laryngeal mask airway.

We have confirmed the value of measurement of end-tidal carbon dioxide concentration as an indicator of arterial carbon dioxide tension during the use of the laryngeal mask airway in healthy patients breathing spontaneously. The mean difference between arterial and end-tidal carbon dioxide tension was 0.52 kPa (range 0-1.5 kPa), which is similar to the difference which has been reported when a tracheal tube has been used.