Association of Baseline Patient-reported Health-related Quality of Life Metrics with Outcome in Localised Prostate Cancer.

AIMS: Although health-related quality of life (HR-QoL) outcomes are pivotal in oncology, the prognostic significance of patient-reported HR-QoL metrics is largely undefined in localised prostate cancer. We report the association of baseline HR-QoL metrics with overall survival and toxicity in localised prostate cancer. MATERIALS AND METHODS: This was a secondary analysis of a phase III randomised controlled study conducted in a single-payer health system. Patients with Gleason score ≤7, clinical stage T1b-T3a and prostate-specific antigen <30 ng/ml were randomised to neoadjuvant and concurrent androgen deprivation therapy (ADT) for 6 months starting 4 months before prostate radiotherapy or concurrent and adjuvant ADT for 6 months starting simultaneously with prostate radiotherapy. HR-QoL scores were estimated using the European Organisation for Research and Treatment of Cancer QoL questionnaire. A multistate Markov model was used to determine the association of baseline HR-QoL metrics with overall survival and a multilevel multivariable Cox regression was used to determine the association with the incidence of delayed-onset grade ≥3 radiotherapy-related toxicities. To adjust for multiple analyses, P < 0.025 was considered as statistically significant. RESULTS: Overall, 393 patients with baseline HR-QoL data were included in this analysis: 194 in the neoadjuvant arm and 199 in the adjuvant arm. Baseline financial difficulty (hazard ratio 1.020, 95% confidence interval 1.010-1.030, P = 0.02) and dyspnoea (hazard ratio 1.020, 95% confidence interval 1.003-1.030, P = 0.01) were associated with inferior overall survival. Baseline dyspnoea was associated with a higher incidence of grade ≥3 toxicity (hazard ratio 1.020, 95% confidence interval 1.010-1.030, P = 0.023). CONCLUSION: In a cohort of localised prostate cancer patients treated with radiotherapy and short-term ADT, a 10-point higher baseline financial difficulty or dyspnoea was associated with a 20% increased risk of death. With each 10-point increase in baseline dyspnoea, we noted a 20% increase in the associated risk of grade ≥3 delayed-onset radiotherapy-related toxicity.

Impact of Concomitant Medications on Biochemical Outcome in Localised Prostate Cancer Treated with Radiotherapy and Androgen Deprivation Therapy.

AIMS: Several classes of concomitant medications have been shown to affect oncological outcomes in patients with prostate cancer (PCa). We assessed the association between the use of commonly prescribed concomitant medications and biochemical relapse-free survival (bRFS) in patients with localised PCa treated with radiotherapy and androgen deprivation therapy (ADT). MATERIALS AND METHODS: A secondary pooled analysis of two phase III randomised trials was carried out. In the first trial, patients with localised PCa with clinical stage T1b-T3, prostate-specific antigen <30 ng/ml and Gleason score ≤7 were treated with radical radiotherapy and 6 months of ADT starting 4 months before or concomitantly with radiotherapy. In the second trial, patients with high-risk PCa were treated with radical radiotherapy and 36 months of ADT with randomisation to three-dimensional conformal or intensity-modulated radiotherapy. Information on concomitant medications was collected from the medical record. Univariable and multivariable Cox regression was used to identify factors associated with bRFS. RESULTS: Overall, 486 patients were evaluable. The median follow-up was 125 months; 10-year bRFS was 83.7%. On univariable analysis, receipt of metformin was significantly associated with worse bRFS. Ten-year bRFS was 73% and 85% for patients with and without concomitant metformin (adjusted hazard ratio 2.11, 95% confidence interval 1.03-4.33). Similar evidence of an association was observed with sulfonamide-based α1-receptor blockers (adjusted hazard ratio 2.72, 95% confidence interval 1.31-5.66). However, no such association was seen with receipt of quinazoline-based α1-receptor blockers (adjusted hazard ratio 1.09, 95% confidence interval 0.42-2.82). There was no significant association between bRFS and receipt of all other medication classes considered. CONCLUSIONS: In this population of patients with localised PCa treated with radiotherapy and ADT, receipt of concomitant metformin and sulfonamide-based α1-receptor blockers was associated with inferior biochemical outcome. Randomised trials are required to assess the true effect of these medications on oncological outcomes in localised PCa.

Guidelines for the safe practice of total intravenous anaesthesia (TIVA): Joint Guidelines from the Association of Anaesthetists and the Society for Intravenous Anaesthesia.

Guidelines are presented for safe practice in the use of intravenous drug infusions for general anaesthesia. When maintenance of general anaesthesia is by intravenous infusion, this is referred to as total intravenous anaesthesia. Although total intravenous anaesthesia has advantages for some patients, the commonest technique used for maintenance of anaesthesia in the UK and Ireland remains the administration of an inhaled volatile anaesthetic. However, the use of an inhalational technique is sometimes not possible, and in some situations, inhalational anaesthesia is contraindicated. Therefore, all anaesthetists should be able to deliver total intravenous anaesthesia competently and safely. For the purposes of simplicity, these guidelines will use the term total intravenous anaesthesia but also encompass techniques involving a combination of intravenous infusion and inhalational anaesthesia. This document is intended as a guideline for safe practice when total intravenous anaesthesia is being used, and not as a review of the pros and cons of total intravenous anaesthesia vs. inhalational anaesthesia in situations where both techniques are possible.

Benthic ecological status of Algerian harbours.

This work is an overview of all available benthic data collected in the Algerian harbours between 1983 and 2001. So, total of 571 stations were reported in the 10 major Algerian harbours along the Algerian coast (1200km). Two main categories of harbours were distinguished according to their hydrodynamic regime and volume of water exchange between inner harbour basins and the entrance of the harbours. Univariate, multivariate, benthic indices and Biological Traits of Life approaches were applied on stations sampled in the late 1990s and long-term observations in six out of these ten harbours. These approaches assessed the main characteristics and ecological statuses from these south Mediterranean harbours. One of the main characteristics of the Algerian harbours was the very high species diversity (847 species). Although all the fauna was dominated by pollution-tolerant species; some harbours such as Bethioua and Djendjen hosted normal benthic communities as found in the open sea, but also included some pollution indicator species typical of a slight polluted system. On the contrary, the newly constructed port of Skikda showed perturbed benthic communities in relation to hydrocarbon pollution. Biological Traits of Life analysis reinforced the separation of benthic species along a gradient reflecting their sensitivity or tolerance to pollution. This response was related to an increase in organic matter content, probably associated with a general organic and metal contamination, from the entrance of the harbour to the innermost basins in areas with weak circulation, high sedimentation rate and concentrations of pollutants. Except for Oran harbour, where the poor to moderate ecological status remained unchanged with time, the other harbours showed an improvement or a slight degradation. A strategy of long-term monitoring should be promoted, based on a restricted and selected number of stations characteristic of the different basins and water masses occupying the harbours.

Production of pyroxene ceramics from the fine fraction of incinerator bottom ash.

Incinerator bottom ash (IBA) is normally processed to extract metals and the coarse mineral fraction is used as secondary aggregate. This leaves significant quantities of fine material, typically less than 4mm, that is problematic as reuse options are limited. This work demonstrates that fine IBA can be mixed with glass and transformed by milling, calcining, pressing and sintering into high density ceramics. The addition of glass aids liquid phase sintering, milling increases sintering reactivity and calcining reduces volatile loss during firing. Calcining also changes the crystalline phases present from quartz (SiO2), calcite (CaCO3), gehlenite (Ca2Al2SiO7) and hematite (Fe2O3) to diopside (CaMgSi2O6), clinoenstatite (MgSiO3) and andradite (Ca3Fe2Si3O12). Calcined powders fired at 1080°C have high green density, low shrinkage (<7%) and produce dense (2.78 g/cm(3)) ceramics that have negligible water absorption. The transformation of the problematic fraction of IBA into a raw material suitable for the manufacture of ceramic tiles for use in urban paving and other applications is demonstrated.

Use of lean principals to improve flow of patients with fractured neck of femur--the HOPE study.

We describe the implementation of a care pathway for patients with fractured neck of femur (NOF) using Lean and Six Sigma principles. After introduction of the Lean pathway, 32 patients out a total of 86 (37%) with fractured NOF were admitted to the Trauma Ward within 4 hours of presentation to the hospital; prior to implementation this was 16 patients out of a total of 59 (27%). Post-Lean an earlier mean theatre start time of 8.40am was achieved, resulting in a 38 minute increase in daily theatre time. An additional 52 patients (12%) received surgery within 24 hours of admission, resulting in 1 night length of stay reduction. Lean methodology proved an effective method to guide change resulting in an improved journey for the patient and significant workflow gains.

Evidence for the ground-state resonance of 26O.

Evidence for the ground state of the neutron-unbound nucleus (26)O was observed for the first time in the single proton-knockout reaction from a 82 MeV/u (27)F beam. Neutrons were measured in coincidence with (24)O fragments. (26)O was determined to be unbound by 150(-150)(+50) keV from the observation of low-energy neutrons. This result agrees with recent shell-model calculations based on microscopic two- and three-nucleon forces.

Testis-specific transcriptional control.

In the testis, tissue-specific transcription is essential for proper expression of the genes that are required for the reproduction of the organism. Many testis-specific genes are required for mitotic proliferation of spermatogonia, spermatocytes undergoing genetic recombination and meiotic divisions, and differentiation of haploid spermatids. In this article we describe some of the genes that are transcribed in male germinal cells and in non-germinal testis cells. Because significant progress has been made in examination of promoter elements and their cognate transcription factors that are involved in controlling transcription of the testis-specific linker histone H1t gene in primary spermatocytes, this work will be reviewed in greater detail. The gene is transcriptionally active in spermatocytes and repressed in all other germinal and non-germinal cell types and, therefore, it serves as a model for study of regulatory mechanisms involved in testis-specific transcription.

Pediatric IgA nephropathy: clinical features at presentation and outcome for African-Americans and Caucasians.

AIM: To determine the disease severity at onset and outcome for African-American and Caucasian pediatric patients with IgA nephropathy diagnosed at the Le Bonheur Children's Medical Center since 1990. DESIGN/METHODS: The study population included all patients diagnosed with IgA nephropathy at the Le Bonheur Children's Medical Center from January 1990 through February 2004. All were below age 18 at biopsy. Clinical features assessed at diagnosis were age, gender, presence of hypertension, history of macroscopic hematuria, degree of proteinuria, severity of renal histology and pattern for immunofluorescent reactants. STATISTICS: Student's t-test was used to compare age at biopsy and length of follow-up between the 2 groups. Fisher's exact test was used to compare features at presentation and patterns of immunofluorescence. Kidney survival was predicted by the Kaplan-Meier method. RESULTS: Forty-seven patients (17 African-American, 29 Caucasian) were studied. Clinical features at diagnosis and pattern for all immunofluorescent reactants did not differ significantly between the 2 groups. Mesangial deposition of C1q occurred in 4/17 African-Americans as compared to 1/27 Caucasians (p = 0.06). Four patients (2 African-Americans, 2 Caucasians) progressed to end-stage renal disease. Predicted kidney survival was 96% (94% in African-Americans and 97% in Caucasians) at 1 year and 91% (94% in African-Americans and 89% in Caucasians) at 5 years from diagnosis. Mean time from diagnosis to end-stage renal disease or last follow-up was 3.3 years (3.8 for African-Americans, 3.0 for Caucasians). Macroscopic hematuria occurred prior to diagnosis for 90% of the Caucasian as compared to 61% of the African-American patients (p = 0.03). Urinalysis was normal at last follow-up visit for 24% of African-American patients and 32% of Caucasian patients. CONCLUSION: In a relatively small sample from a single center, except for the difference in macroscopic hematuria, clinical features at diagnosis and outcome of IgA nephropathy appear similar for African-American and Caucasian pediatric patients.

Terminal protein-induced stretching of bacteriophage phi29 DNA.

Stretching of DNA molecules helps to resolve detail during the fluorescence microscopy of both single DNA molecules and single DNA-protein complexes. To make stretching occur, intricate procedures of specimen preparation and manipulation have been developed in previous studies. By contrast, the present study demonstrates that conventional procedures of specimen preparation cause DNA stretching to occur, if the specimen is the double-stranded DNA genome of bacteriophage phi29. Necessary for this stretching is a protein covalently bound at both 5' termini of phi29 DNA molecules. Some DNA molecules are attached to a cover glass only at the two ends. Others are attached at one end only with the other end free in solution. The extent of stretching varies from approximately 50% overstretched to approximately 50% understretched. The understretched DNA molecules are internally mobile to a variable extent. In addition to stretching, some phi29 DNA molecules also undergo assembly to form both linear and branched concatemers observed by single-molecule fluorescence microscopy. The assembly also requires the terminal protein. The stretched DNA molecules are potentially useful for observing DNA biochemistry at the single molecule level.

Medical device security.

Medical device security represents a growing problem within the healthcare industry. An increasing number of medical devices and systems contain critical health related information for which integrity, availability, and confidentiality must be maintained. HIPAA's Security Rule requires that US healthcare providers have a security program addressing this problem in place by April 21, 2005. Through a collaborative effort, ACCE and ECRI have developed the first comprehensive guideline for implementing the security management and risk analysis process for medical technology.

Clinical and pathologic features of West Nile virus infection in native North American owls (Family strigidae).

Since the initial report of West Nile virus in the northeastern United States in 1999, the virus has spread rapidly westward and southward across the country. In the summer of 2002, several midwestern states reported increased cases of neurologic disease and mortality associated with West Nile virus infection in various native North American owl species. This report summarizes the clinical and pathologic findings for 13 captive and free-ranging owls. Affected species were all in the family Strigidae and included seven snowy owls (Nyctea scandiaca), four great-horned owls (Bubo virginianus), a barred owl (Strix varia), and a short-eared owl (Asio flammeus). Neurologic signs identified included head tilt, uncoordinated flight, paralysis, tremors, and seizures. Owls that died were screened for flaviviral proteins by immunohistochemical staining of formalin-fixed tissues, followed by specific polymerase chain reaction assay to confirm West Nile virus with fresh tissues when available. Microscopic lesions were widespread, involving brain, heart, liver, kidney, and spleen, and were typically nonsuppurative with infiltration by predominantly lymphocytes and plasma cells. Lesions in owls were much more severe than those previously reported in corvids such as crows, which are considered highly susceptible to infection and are routinely used as sentinel species for monitoring for the presence and spread of West Nile virus. This report is the first detailed description of the pathology of West Nile virus infection in Strigiformes and indicates that this bird family is susceptible to natural infection with West Nile virus.

Transcriptional control of the testis-specific histone H1t gene.

The mammalian testis-specific linker histone H1t is synthesized only in pachytene primary spermatocytes during spermatogenesis. In this review we summarize some of the progress made in our laboratory and in other laboratories in understanding transcriptional regulation of this gene. The gene is transcriptionally active in pachytene primary spermatocytes and is repressed in all other germinal and non-germinal cell types. To place the transcriptional control of the testis-specific histone H1t gene in the proper context, we briefly review recent literature concerning mammalian linker histone genes in general and we compare and contrast these with the testis-specific histone H1t gene.

The bacteriophage straight phi29 portal motor can package DNA against a large internal force.

As part of the viral infection cycle, viruses must package their newly replicated genomes for delivery to other host cells. Bacteriophage straight phi29 packages its 6.6-microm long, double-stranded DNA into a 42 x 54 nm capsid by means of a portal complex that hydrolyses ATP. This process is remarkable because entropic, electrostatic and bending energies of the DNA must be overcome to package the DNA to near-crystalline density. Here we use optical tweezers to pull on single DNA molecules as they are packaged, thus demonstrating that the portal complex is a force-generating motor. This motor can work against loads of up to 57 pN on average, making it one of the strongest molecular motors reported to date. Movements of over 5 microm are observed, indicating high processivity. Pauses and slips also occur, particularly at higher forces. We establish the force-velocity relationship of the motor and find that the rate-limiting step of the motor's cycle is force dependent even at low loads. Notably, the packaging rate decreases as the prohead is filled, indicating that an internal force builds up to approximately 50 pN owing to DNA confinement. Our data suggest that this force may be available for initiating the ejection of the DNA from the capsid during infection.

Cryoelectron-microscopy image reconstruction of symmetry mismatches in bacteriophage phi29.

A method has been developed for three-dimensional image reconstruction of symmetry-mismatched components in tailed phages. Although the method described here addresses the specific case where differing symmetry axes are coincident, the method is more generally applicable, for instance, to the reconstruction of images of viral particles that deviate from icosahedral symmetry. Particles are initially oriented according to their dominant symmetry, thus reducing the search space for determining the orientation of the less dominant, symmetry-mismatched component. This procedure produced an improved reconstruction of the sixfold-symmetric tail assembly that is attached to the fivefold-symmetric prolate head of phi29, demonstrating that this method is capable of detecting and reconstructing an object that included a symmetry mismatch. A reconstruction of phi29 prohead particles using the methods described here establishes that the pRNA molecule has fivefold symmetry when attached to the prohead, consistent with its proposed role as a component of the stator in the phi29 DNA packaging motor.

Simultaneous recovery of copper and degradation of 2,4-dichlorophenoxyacetic acid in aqueous systems by a combination of electrolytic and photolytic processes.

In mixed industrial effluent the presence of metal ions can retard the destruction of organic contaminants and the efficiency of recovery of the metal is reduced by the presence of the organic species. Results are presented for copper-2,4-dichlorophenoxyacetic acid (2,4-D) system in which both effects occur. An electrochemical cell alone can be used to recover copper in the pH range 1.5-4.5 but it is not capable of achieving complete disappearance of 2,4-D by anodic oxidation. A photolytic cell alone can achieve the destruction of 2,4-D at pH 3.5 but leaves copper in solution. A combined photolytic-electrochemical system using an activated carbon concentrator cathode achieves the rapid simultaneous destruction of 2,4-D and recovery of copper. Results are presented for the recovery of more than 90% copper from, and >99.9%, destruction of the organochlorine compound 2,4-D in, a solution containing 100 mg dm(-3) copper and 50 mg dm(-3) 2.4-D. The photolytic degradation of 2,4-D depends on the intensity of the UV-probe. Only 19% degradation is achieved after 8 h with the 150 W UV-probe but the corresponding value with the 400 W UV-probe is 100%. In the case of 150 W UV-probe the degradation of 2,4-D proceeds through the formation of 2,4-dichlorophenol and phenol. The concentration of these intermediates are very low in the case of 400 W UV-probe because the speed of the degradation of 2,4-D is very fast. The addition of TiO2 (1 g dm(-3)), as a semiconductor material, and H202 (1.5 g dm(-3)) as an oxidant, increases the photolytic degradation of 2,4-D.

Effect of gastrin and anti-gastrin antibodies on proliferation of hepatocyte cell lines.

Gastrin (G-17) and its precursor glycine-extended gastrin (G-17-gly) have been shown to be trophic to some gastrointestinal tumors. This in vitro study assessed the effect of G-17, G-17-gly, anti-gastrin antibodies (anti-G-17), and the CCK-B receptor antagonist PD135,158 on three hepatoma cell lines (PLC/PRF/5, HepG2 and MCA-RH7777) and an embryonic liver cell line (WRL68). The pancreatic adenocarcinoma cell line AR42J was used as a positive control. G-17 and G-17-gly caused significant proliferation of AR42J and WRL68 cell lines. G-17-gly but not G-17 induced significant proliferation of the PLC/PRF/5 cell line. Anti-G-17 and PD135,158 significantly inhibited unstimulated AR42J and WRL68 cell lines. Anti-G-17 also inhibited the proliferative effects of G-17 and G-17-gly on AR42J, WRL68, and PLC/PRF/5 cell lines, whereas PD135,158 inhibited the proliferative effect of G-17 only. G-17 and G-17-gly as well as anti-G-17 and PD135,158 had no effect on HepG2 and MCA-RH77777 cell lines. It is concluded that G-17-stimulated proliferation is mediated via the CCK-B receptor and G-17-gly via a separate, as yet uncharacterized, receptor. There may therefore be a role for gastrin in embryonic hepatocellular proliferation and perhaps also in the proliferation of some hepatocellular tumors.

Photocatalytic degradation of trans-cinnamic, dihydrocinnamic, trans-caffeic, and dihydrocaffeic acids and characterization of the products.

Catalysed degradation of aqueous solutions of cinnamic 1, dihydrocinnamic 2, dihydrocaffeic 3 and trans-caffeic 4 acids in the presence of (TiO2) and UV radiation and the products identified by HPLC, and after treatment with diazomethane by GC-MS have been studied. A pH range of 3 to 11 was used. The four acids, in the presence of TiO2 in the dark, underwent little degradation. Extended irradiation of all the acids in the presence of TiO2 produced complete degradation as shown by TOC measurements. Initially the volume of carbon dioxide produced rose steadily to a constant value.