Digital Medicine in Men with Advanced Prostate Cancer - A Feasibility Study of Electronic Patient-reported Outcomes in Patients on Systemic Treatment.

AIMS: Electronic patient-reported outcome (ePRO) measures have the potential to improve patient care, both at an individual level by detecting symptoms and at an organisational level to rationalise follow-up. The introduction of ePROs has many challenges, including funding, institutional rigidity and acceptability for both patients and clinicians. There are multiple examples of successful ePRO programmes but no specific feasibility studies in those who are less digitally engaged. Prostate cancer is predominantly a disease of older men and digital exclusion is associated with increased age. We assessed the feasibility of ePRO completion in older men receiving treatment for advanced prostate cancer both within the clinic and from home. MATERIALS AND METHODS: Men receiving palliative systemic treatment were asked to complete ePROs on a tablet computer in the outpatient department at 0 and 3 months. Participants were also offered optional completion from home. Feasibility was assessed via a mixed methods approach. RESULTS: On-site ePRO completion was acceptable to most patients, with 90% finding it easy or straightforward and 80% preferring electronic over paper. Remote completion was more challenging, even for those who accessed e-mail daily and owned a tablet, with only 20% of participants successfully completing ePROs. Barriers to electronic completion can be categorised as technical, attitudinal and medical. Quality of life and symptom ePRO results were comparable with published data. CONCLUSIONS: On-site completion is achievable in this population with limited staff support. However, remote completion requires further work to improve systems and acceptability for patients. Remote completion is critical to add significantly to current clinical care by detecting symptoms or stratifying follow-up.

Pervasive subduction zone devolatilization recycles CO2 into the forearc.

The fate of subducted CO2 remains the subject of widespread disagreement, with different models predicting either wholesale (up to 99%) decarbonation of the subducting slab or extremely limited carbon loss and, consequently, massive deep subduction of CO2. The fluid history of subducted rocks lies at the heart of this debate: rocks that experience significant infiltration by a water-bearing fluid may release orders of magnitude more CO2 than rocks that are metamorphosed in a closed chemical system. Numerical models make a wide range of predictions regarding water mobility, and further progress has been limited by a lack of direct observations. Here we present a comprehensive field-based study of decarbonation efficiency in a subducting slab (Cyclades, Greece), and show that ~40% to ~65% of the CO2 in subducting crust is released via metamorphic decarbonation reactions at forearc depths. This result precludes extensive deep subduction of most CO2 and suggests that the mantle has become more depleted in carbon over geologic time.

PEDOT doped with algal, mammalian and synthetic dopants: polymer properties, protein and cell interactions, and influence of electrical stimulation on neuronal cell differentiation.

Poly(3,4-ethylenedioxythiophene) (PEDOT) films were electrochemically polymerised with several synthetic (dodecylbenzosulfonic acid (DBSA)) and biological (dextran sulphate (DS), chondroitin sulphate (CS), alginic acid (ALG) and ulvan (ULV)) dopant anions, and their physical, mechanical and electrochemical properties characterised. PEDOT films incorporating the biological dopants ALG and ULV produced films of the greatest surface roughness (46 ± 5.1 and 31 ± 1.9 nm, respectively), and demonstrated significantly lower shear modulus values relative to all other PEDOT films (2.1 ± 0.1 and 1.2 ± 0.2 MPa, respectively). Quartz crystal microgravimetry was used to study the adsorption of the important extracellular matrix protein fibronectin, revealing protein adsorption to be greatest on PEDOT doped with DS, followed by DBSA, ULV, CS and ALG. Electrical stimulation experiments applying a pulsed current using a biphasic waveform (250 Hz) were undertaken using PEDOT doped with either DBSA or ULV. Electrical stimulation had a significant influence on cell morphology and cell differentiation for PEDOT films with either dopant incorporated, with the degree of branching per cell increased by 10.5× on PEDOT-DBSA and 6.5× on PEDOT-ULV relative to unstimulated cells, and mean neurite length per cell increasing 2.6× and 2.2× on stimulated vs. unstimulated PEDOT-DBSA and PEDOT-ULV, respectively. We demonstrate the cytocompatibility of synthetic and biologically doped PEDOT biomaterials, including the new algal derived polysaccharide dopant ulvan, which, along with DBSA doped PEDOT, is shown to significantly enhance the differentiation of PC12 neuronal cells under electrical stimulation.

Inhibition of smooth muscle cell adhesion and proliferation on heparin-doped polypyrrole.

We have investigated the application of polypyrrole (pPy) as a material to influence neointimal cell behaviour. The physico-chemical properties of pPy doped with heparin (Hep), para-toluene sulfonate, poly(2-methoxyaniline-5-sulfonic acid) (pMAS) and nitrate ions were studied in addition to cell adhesion and proliferation studies of neointimal relevant cell lines cultured on the pPy substrates. Both smooth muscle (hSMC) and endothelial (hEC) cell types adhered and proliferated best on the smooth, hydrophilic pPy/pMAS material. Moreover, pPy/Hep is able to support the proliferation of hECs on the surface but inhibits hSMC proliferation after 4 days of culture. The inhibitory effect on hSMCs is most likely due to the well-known antiproliferative effect of heparin on hSMC growth. The results presented indicate that surface exposed heparin binds to the putative heparin receptor of hSMCs and is sufficient to inhibit proliferation. The application of galvanostatically synthesized pPy/Hep to stent surfaces presents a novel bioactive control mechanism to control neointimal cell growth.

Isolation of lipid and 2-alkylcyclobutanones from irradiated foods by supercritical fluid extraction.

The 2-alkylcyclobutanone method was adopted as a European Standard (EN1785) and MAFF Validated Method (MAFF V37) in 1996 for the detection of irradiated food containing fat. As the method requires a relatively long period (ca 2 days) of time for extraction of the 2-alkylcyclobutanones from a foodstuff, a means was sought to increase the speed at which these irradiation markers could be isolated while at the same time decreasing the amount of organic solvents required. Thus, the technique of supercritical fluid extraction (SFE) was investigated. Results showed that SFE can be used for the rapid extraction (60 min) of lipid from irradiated foods such as chicken, pork, liquid whole egg, ground beef, and from the seeds of irradiated mango and papaya with only 10 mL n-hexane being necessary for collection of the extracted sample. A method was also developed whereby the 2-alkylcyclobutanones can be selectively extracted from irradiated foods without prior extraction of the lipid. The sample extract, in 10 mL n-hexane, is purified through a Florisil SPE cartridge which is washed with 10 mL n-hexane and the 2-alkylcyclobutanones eluted with 10 mL 2% diethyl ether in n-hexane before analysis by gas chromatography/mass spectrometry. 2-Dodecylcyclobutanone and 2-tetradecylcyclobutanone were selectively extracted from irradiated chicken meat, liquid whole egg, ground beef, and mango as well as from beef burgers and baked products containing irradiated ground beef and liquid whole egg, respectively. Using this method, samples can be analyzed for irradiation treatment within 6 h as opposed to the 2-day period required for the EN1785/MAFF V37 validated method.

Molecular cloning and characterization of gut-derived cysteine proteinases associated with a host protective extract from Haemonchus contortus.

Cysteine proteinases have been implicated in the protection conferred by vaccination with detergent-soluble extracts of Haemonchus contortus. In the present study, antisera from sheep refractory to Haemonchus challenge following vaccination with a 'proteinase-enriched' Haemonchus gut membrane extract, were employed to screen a cDNA expression library of the adult parasite. This resulted in the isolation of 3 cDNAs (designated hmcp1, 4 and 6) encoding cathepsin B-like cysteine proteinases. Immunocytochemical studies specifically localized the products of these genes to the microvillar surface of the parasite's gut and RT-PCR experiments revealed that these were developmentally regulated, being expressed exclusively during the blood-feeding parasitic stages. In addition, a generic PCR approach was adopted in order to identify the predominant cysteine proteinases in a UK strain of Haemonchus. A panel of 5 cDNAs, including hmcp1 and 4, was amplified in this way. Genomic Southern blot analysis indicated that some of these enzymes were encoded by single-copy genes, whereas others were encoded by multi-copy genes. Subsequent sequence analysis revealed that the proteases identified in this study were distinct from those previously reported in USA strains of the parasite.

Cloning and characterization of glutamate dehydrogenase (GDH) from the gut of Haemonchus contortus.

Vaccination of lambs with the membrane-bound (S3) thiol-Sepharose binding protein (TSBP) fraction derived from the gut of Haemonchus contortus confers significant protection against homologous challenge. The S3 TSBP peptide profile is dominated by a major protein of ca. 60 kDa which is strongly recognized by antisera from sheep demonstrably protected following immunization with S3 TSBP. In an attempt to identify this protein, sera from protected lambs were employed to screen a lambda gt11 cDNA library of the adult parasite and resulted in the isolation of numerous clones encoding a homologue of the mitochondrial enzyme, glutamate dehydrogenase (GDH). GDH enzyme activity was readily demonstrable in S3 TSBP material and immunolocalization studies showed that the enzyme was localized to the cytoplasm of the parasite's gut. Furthermore, the enzyme appeared to be developmentally regulated, with both GDH mRNA and protein expressed almost exclusively during the blood-feeding parasitic stages.

Lipoprotein alterations in the spontaneously hypertensive rat fed diets deficient in selenium and vitamin E.

Both vitamin E and selenium (Se) are antioxidant nutrients that play important roles in preventing in vivo lipid peroxidation. In this investigation, Se and vitamin E were found to influence lipoprotein levels in the spontaneously hypertensive rat (SHR). Four-week-old inbred SHRs were fed a basal (B) diet with 1% cholesterol deficient in both selenium and vitamin E (B+cho diet) or identical diets to which either vitamin E (B+E+cho) or selenium (B+Se+cho) or both micronutrients were added (B+Se+E+cho). Plasma-cho and lipoprotein-cho levels were measured after 6, 12, 16, and 18 weeks of feeding the experimental diets. Rats fed the B+cho diet for at least 12 weeks had plasma-cho levels about twice that observed for rats fed the B+E+Se+cho diet. Plasma-cho levels for rats in the two Se deficient groups (B+cho and B+E+cho) were, however, similar at any time point. Se deficiency was associated with increased plasma-cho, very low density lipoprotein-cho (VLDL-cho) and low-density lipoprotein-cho (LDL-cho). Vitamin E supplementation interacted with Se deficiency to increase plasma VLDL-cho levels. Neither vitamin E alone nor the interaction between vitamin E and Se consistently influenced LDL-cho levels. The percent cholesteryl ester in LDL from rats fed the Se-deficient diets (B+cho or B+E+cho) was at least twice that observed for rats fed the B+E+Se+cho diet. Plasma lipid peroxidation products were highly elevated in rats fed the B+cho diet compared with values for the B+E+cho or the B+E+Se+cho fed rats (which were not significantly different). These results suggest that dietary Se deficiency increases plasma-cho, VLDL-cho, and LDL-cho levels by a mechanism that may be unrelated to its role as an antioxidant nutrient.

The effect of irradiation dose and storage time on the ESR signal in the cuticle of different components of the exoskeleton of Norway lobster (Nephrops norvegicus).

This paper examines the potential of ESR spectroscopy to determine if Norway lobsters have been irradiated. Ninety samples, each containing 3 whole Norway lobsters, were prepared, thirty were used as controls while the remaining sixty were given irradiation doses of approximately either 1 or 3 kGy. Following irradiation the samples were stored at 1 degree C for 0, 7, 14, 21 or 28 d. After each storage period the cuticle of the tail, carapace, claws and walking legs was removed, freeze-dried and ground prior to analysis using ESR spectroscopy. The control spectra were subtracted from their respective irradiated spectra thereby leaving the radiation-induced signal. Peak heights of the signals were measured. The ESR signals derived from the different components of the exoskeleton were similar in shape and varied only in their intensities. The claw samples gave the most intense signal while that from the walking legs was the weakest. There was a significant decay in the signal intensity over the storage period with the signal derived from cuticle of the claws showing the greatest diminution (44%) and that of the tail the least (17%). The signal intensities of the walking legs and carapace decreased by 22% and 30% respectively. In conclusion ESR spectroscopy is a useful technique for the qualitative detection of irradiated Norway lobster and shows considerable potential for quantification of dose received.

Colonization of dental plaque by respiratory pathogens in medical intensive care patients.

OBJECTIVE: To assess the prevalence of oral colonization by respiratory pathogens in a group of ICU patients, with specific attention to dental plaque and the oral mucosa. DESIGN: Prospective, nonrandomized study with age-matched controls. SETTINGS: Medical ICU in a tertiary-care Veterans Affairs Medical Center and a dental school outpatient preventive dentistry clinic. PATIENTS: Nonconsecutive, unselected patients admitted to the medical ICU during a 2-month period; controls were age-matched patients seen for the first time in the preventive dentistry clinic. INTERVENTIONS: None. MEASUREMENTS: Oral hygienic status was assessed in both groups using a semiquantitative system. Quantitative cultures of dental plaque and buccal mucosa were done within 12 hrs of medical ICU admission and every third day thereafter until discharge/death from the medical ICU. In controls, cultures of plaque and buccal mucosa were done on the initial visit only. Severity of illness of medical ICU patients was quantitated using the Acute Physiology and Chronic Health Evaluation (APACHE II) system and McCabe-Jackson criteria. MAIN RESULTS: Oral hygiene of medical ICU patients was poor. These patients had a mean plaque score (1.9 +/- 0.2) that was significantly greater than that same score seen in outpatients of the preventive dentistry clinic (1.4 +/- 0.1; p less than .005). Plaque and/or oral mucosa of 22 (65%) of 34 medical ICU patients were colonized by respiratory pathogens, in contrast to only four (16%) of 25 preventive dentistry clinic patients (p less than .005). The potential respiratory pathogens cultured from medical ICU patients included methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and ten genera of Gram-negative bacilli. Colonization by respiratory pathogens was statistically associated with concomitant antibiotic therapy within the medical ICU group of patients, but not with severity of illness. Although medical ICU patients tended to have more dental plaque than preventive dentistry clinic patients, there was no statistically significant association noted between the presence of dental plaque and respiratory pathogen colonization. CONCLUSIONS: These findings suggest that bacteria commonly causing nosocomial pneumonia colonize the dental plaque and oral mucosa of intensive care patients. In many cases, this colonization occurs by large numbers of bacteria. Dental plaque may be an important reservoir of these pathogens in medical ICU patients. Efforts to improve oral hygiene in medical ICU patients could reduce plaque load and possibly reduce oropharyngeal colonization.