Mushroom: An Oracular Sound Processor

Composers of digital music today have a bewildering variety of sound-processing tools and techniques at their disposal. At their best, these tools allow composers to hone a sound to perfection. However, they can also lead us into a routine which bypasses avenues of experimentation, simply because the known tools work so well and their sonic output is so attractive. An alternative strategy is oracular sound processing. An oracular sound processor creates a derived version of its input whose characteristics could not have been fully predicted, while affording the user little or no parametric control over the process.

BRCA1 - A good predictive marker of drug sensitivity in breast cancer treatment?

There are currently only two predictive markers of response to chemotherapy for breast cancer in routine clinical use, namely the Estrogen receptor-alpha and the HER2 receptor. The breast and ovarian cancer susceptibility gene BRCA1 is an important genetic factor in hereditary breast and ovarian cancer and there is increasing evidence of an important role for BRCA1 in the sporadic forms of both cancer types. Our group and numerous others have shown in both preclinical and clinical studies that BRCA1 is an important determinant of chemotherapy responses in breast cancer. In this review we will outline the current understanding of the role of BRCA1 as a determinant of response to DNA damaging and microtubule damaging chemotherapy. We will then discuss how the known functions of this multifaceted protein may provide mechanistic explanations for its role in chemotherapy responses. (c) 2006 Elsevier B.V. All rights reserved.

The effect of pesticides on Byssus formation in the common mussel, Mytilus edulis

Seed mussels (Mytilus edulis) were exposed to a range of pesticides and PCBs, several of which caused a reduction in byssal attachment at higher concentrations. In queen scallops (Chlamys opercularis) byssus formation was similarly affected although this species was more sensitive than M. edulis. The sensitivity of mussels was greater at higher temperatures and decreased with increase in size. Of the compounds tested Endosulfan (organochlorine) was the most toxic, causing a 50% reduction in byssal attachment after 24 h at 0•45 mg/l. Trichlorphon (organophosphate) was the least toxic and did not affect byssal attachment at concentrations up to 30 mg/l. The probable cause of decreased byssal attachment is a reduction in pedal activity, although it is possible that direct interference with the synthesis or combination of byssus components may be involved. It is suggested that byssogenesis tests offer a rapid and convenient technique for the routine screening of potential marine pollutants.

Robust automated tumour segmentation on histological and immunohistochemical tissue images

Tissue microarray (TMA) is a high throughput analysis tool to identify new diagnostic and prognostic markers in human cancers. However, standard automated method in tumour detection on both routine histochemical and immunohistochemistry (IHC) images is under developed. This paper presents a robust automated tumour cell segmentation model which can be applied to both routine histochemical tissue slides and IHC slides and deal with finer pixel-based segmentation in comparison with blob or area based segmentation by existing approaches. The presented technique greatly improves the process of TMA construction and plays an important role in automated IHC quantification in biomarker analysis where excluding stroma areas is critical. With the finest pixel-based evaluation (instead of area-based or object-based), the experimental results show that the proposed method is able to achieve 80% accuracy and 78% accuracy in two different types of pathological virtual slides, i.e., routine histochemical H&E and IHC images, respectively. The presented technique greatly reduces labor-intensive workloads for pathologists and highly speeds up the process of TMA construction and provides a possibility for fully automated IHC quantification.

Creating continuity out of the disruption of a diagnosis of HIV during pregnancy

AIM: To understand the uniqueness of the experience of testing HIV positive from the perspective of pregnant women.

BACKGROUND: As more people learn of their HIV diagnosis through routine screening processes, it is timely to reflect on the impact of receiving an unexpected positive result.

DESIGN: A prospective qualitative study.

METHODS: This paper draws on the case studies of four women who were participating in a larger prospective qualitative study of reproductive decision-making, pregnancy and childbirth following HIV diagnosis. Multiple interviews were conducted following diagnosis during pregnancy, and, after the birth of their babies. Thematic data analysis was undertaken.

RESULTS: Drawing on Becker's theory of disruption, we document the 'sudden disjuncture' of their antenatal diagnosis and the embodied emotional struggle the women engaged in to create continuity in their lives. A diagnosis of HIV disrupted the women's biographies in terms of their health, relationships and social identity. As pregnant women, the threat of HIV was experienced most significantly in relation to their unborn child. However, their narratives also revealed how a diagnosis of HIV in the context of pregnancy, whilst traumatic, provided a focus for regaining continuity in their lives, as the baby became a metaphor for hope and orientation toward the future.

CONCLUSIONS: As HIV testing becomes more 'routine', the findings of this study serve to remind health professionals that a positive diagnosis continues to constitute a major trauma to individuals and families.

RELEVANCE TO CLINICAL PRACTICE: We propose that appropriately educated nursing and midwifery staff could facilitate the 'meaning making' process that is required for newly diagnosed HIV positive persons to find a subjective sense of well-being in their lives.

“That’s not Ironic, that’s just Stupid!": Towards an Eclectic Account of the Discourse of Irony

This article draws on a range of models from language studies, particularly from linguistic pragmatics, in order to elucidate patterns in the production and reception of irony in its social and cultural context. An expanded view of the concept of irony, it is suggested, allows for better modelling of the creative mechanisms which underpin it, and in doing so can open the way for a fuller understanding of humour production and reception. A consequence of this broader (five-fold) typology of irony is that it can help shed light on the cultural dynamic of irony. The article uses a range of examples from different media and the lay definitions and interpretations that ordinary (non-academic) users of the language use in the comprehension of irony. Insofar as it seeks to develop an overarching model of irony, this paper draws on a variety of textual examples from a variety of sources, ranging from corpus evidence, through a stand-up comedy routine, to political wall murals and their discursive re-conformation as humour in present-day Northern Ireland. Although the central discussion is supported by insights from other linguistic, cognitive and socio-cultural approaches, the theoretical framework which emerges, with its focus on language and communication in context, is situated squarely within contemporary linguistic pragmatics.

A lower mass for the exoplanet WASP-21b

We present high-precision transit observations of the exoplanet WASP-21b, obtained with the Rapid Imager to Search for Exoplanets instrument mounted on the 2.0-m Liverpool Telescope. A transit model is fitted, coupled with a Markov chain Monte Carlo routine, to derive accurate system parameters. The two new high-precision transits allow us to estimate the stellar density directly from the light curve. Our analysis suggests that WASP-21 is evolving off the main sequence which led to a previous overestimation of the stellar density. Using isochrone interpolation, we find a stellar mass of 0.86 ± 0.04 Msun, which is significantly lower than previously reported (1.01 ± 0.03 Msun). Consequently, we find a lower planetary mass of 0.27 ± 0.01 MJup. A lower inclination (87?4 ± 0?3) is also found for the system than previously reported, resulting in a slightly larger stellar (R*= 1.10 ± 0.03 Rsun) and planetary radius (Rp= 1.14 ± 0.04 RJup). The planet radius suggests a hydrogen/helium composition with no core which strengthens the correlation between planetary density and host star metallicity. A new ephemeris is determined for the system, i.e. T0= 245 5084.519 74 ± 0.000 20 (HJD) and P= 4.322 5060 ± 0.000 0031 d. We found no transit timing variations in WASP-21b.

High-precision transit observations of the exoplanet WASP-13b with the RISE instrument

WASP-13b is a sub-Jupiter mass exoplanet orbiting a G1V type star with a period of 4.35 d.The current uncertainty in its impact parameter (0 < b < 0.46) results in poorly definedstellar and planetary radii. To better constrain the impact parameter, we have obtained highprecisiontransit observations with the rapid imager to search for exoplanets (RISE) instrumentmounted on 2.0-m Liverpool Telescope. We present four new transits which are fitted witha Markov chain Monte Carlo routine to derive accurate system parameters. We found anorbital inclination of 85. ◦ 2 ± 0. ◦ 3 resulting in stellar and planetary radii of 1.56 ± 0.04 Rand 1.39 ± 0.05RJup, respectively. This suggests that the host star has evolved off the mainsequence and is in the hydrogen-shell-burning phase.We also discuss how the limb darkeningaffects the derived system parameters.With a density of 0.17ρJ,WASP-13b joins the group oflow-density planets whose radii are too large to be explained by standard irradiation models.We derive a new ephemeris for the system, T0 = 245 5575.5136 ± 0.0016 (HJD) and P =4.353 011 ± 0.000 013 d. The planet equilibrium temperature (Tequ = 1500 K) and the brighthost star (V = 10.4mag) make it a good candidate for follow-up atmospheric studies.

An improved immunoassay for detection of saxitoxin by surface plasmon resonance biosensors

Saxitoxin and its analogs, the causative agents of paralytic shellfish poisoning (PSP), are a worldwide threat to seafood safety. Effective monitoring of potentially contaminated fishing areas as well as screening of seafood samples is necessary to adequately protect the public. While many analytical methods exist for detecting paralytic shellfish toxins (PSTs), each technique has challenges associated with routine use. One recently developed method [1] that overcomes ethical or performance-related issues of other techniques is the surface plasmon resonance (SPR) bioassay. Notwithstanding the advantages of this method, much research remains in optimizing the sensor substrate and assay conditions to create a robust technique for rapid and sensitive measurement of PSTs. This manuscript describes a more rigorous and stable SPR inhibition immunoassay through optimization of the surface chemistry as well as determination of optimum mixture ratios and mixing times. The final system provides rapid substrate formation (18 h saxitoxin conjugation with low reagent consumption), contains a reference channel for each assay, and is capable of triplicate measurements in a single run with detection limits well below the regulatory action level. Published by Elsevier B.V.

The preparation, solubilisation and binding characteristics of a beta 2-adrenoceptor isolated from transfected Chinese hamster cells

beta2-Adrenoceptor agonists (beta -agonists) are well known for their growth promoting and repartitioning effects in many species. Although the use of these compounds to increase muscle mass in stockfarming is prohibited within the EU, under directive 96/22/EC, significant illegal use still occurs. With legal and illegal synthesis of new structurally related compounds, the detection of traditional beta -agonists and new derivatives becomes increasingly problematical. This method describes the isolation and solubilisation of a beta2-adrenoceptor from a transfected Chinese hamster ovary cell line, using the detergent digitonin. The solubilised receptor retained its activity and was isolated from the cell membrane at a concentration of 550 +/- 100 fmol mg(-1) of solubilised protein. Competition analysis using the tritiated antagonist dihydroalprenolol revealed receptor affinity for five structurally different beta -agonists, with IC50 values ranging from 2.1 +/- 0.76 X 10(-7) M for salmeterol to 1.1 +/- 0.62 x 10(-5) M for ractopamine. This study has demonstrated that transfected cell lines with a high expression of beta2-adrenoceptors are a convenient source of active receptor material. Solubilised beta (2)-adrenoceptors could form the basis of a multi-analyte screening assay for use in routine screening.

The preparation, solubilisation and binding characteristics of a beta 2-adrenoceptor isolated from transfected Chinese hamster cells

beta2-Adrenoceptor agonists (beta -agonists) are well known for their growth promoting and repartitioning effects in many species. Although the use of these compounds to increase muscle mass in stockfarming is prohibited within the EU, under directive 96/22/EC, significant illegal use still occurs. With legal and illegal synthesis of new structurally related compounds, the detection of traditional beta -agonists and new derivatives becomes increasingly problematical. This method describes the isolation and solubilisation of a beta2-adrenoceptor from a transfected Chinese hamster ovary cell line, using the detergent digitonin. The solubilised receptor retained its activity and was isolated from the cell membrane at a concentration of 550 +/- 100 fmol mg(-1) of solubilised protein. Competition analysis using the tritiated antagonist dihydroalprenolol revealed receptor affinity for five structurally different beta -agonists, with IC50 values ranging from 2.1 +/- 0.76 X 10(-7) M for salmeterol to 1.1 +/- 0.62 x 10(-5) M for ractopamine. This study has demonstrated that transfected cell lines with a high expression of beta2-adrenoceptors are a convenient source of active receptor material. Solubilised beta (2)-adrenoceptors could form the basis of a multi-analyte screening assay for use in routine screening.

Production of a monoclonal antibody and its application in an optical biosensor based assay for the quantitative measurement of Pantothenic Acid (Vitamin B5) in foodstuffs

Pantothenicacid (PA), vitamin B5, is an essential B vitamin that may be fortified in food and as such requires robust and accurate methods of detection to meet compliance legislation. This study reports the production and characterisation of the first monoclonalantibody (MAb) specific for PA and the subsequent development of a surface plasmon resonance (SPR) biosensorassay for the quantification of PA. The developed assay was compared with an SPR based commercial kit which utilised a polyclonal antibody (PAb). Foodstuffs, including cereals (n = 43), infant formulas and baby food (n = 10) and fruit juices (n = 48) were analysed by both the MAb and PAb biosensorassays and comparison plots showed good correlation (R2 0.77–0.99). The results indicate that the MAb basedbiosensorassay is suitable for the measurement of PA in foodstuffs and has the added advantage of facilitating a constant, long term supply of identical antibody. Preliminary matrix studies suggest the MAb basedassay is an excellent candidate for further validation studies and routine quality assurance based analysis.

Accuracy of LightCycler® SeptiFast for the detection and identification of pathogens in the blood of patients with suspected sepsis: a systematic review protocol

Background: There is growing interest in the potential utility of molecular diagnostics in improving the detection of life-threatening infection (sepsis). LightCycler® SeptiFast is a multipathogen probebased real-time PCR system targeting DNA sequences of bacteria and fungi present in blood samples within a few hours. We report here the protocol of the first systematic review of published clinical diagnostic accuracy studies of this technology when compared with blood culture in the setting of suspected sepsis. Methods/design: Data sources: the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA), the NHS Economic Evaluation Database (NHSEED), The Cochrane Library, MEDLINE, EMBASE, ISI Web of Science, BIOSIS Previews, MEDION and the Aggressive Research Intelligence Facility Database (ARIF). Study selection: diagnostic accuracy studies that compare the real-time PCR technology with standard culture results performed on a patient's blood sample during the management of sepsis. Data extraction: three reviewers, working independently, will determine the level of evidence, methodological quality and a standard data set relating to demographics and diagnostic accuracy metrics for each study. Statistical analysis/data synthesis: heterogeneity of studies will be investigated using a coupled forest plot of sensitivity and specificity and a scatter plot in Receiver Operator Characteristic (ROC) space. Bivariate model method will be used to estimate summary sensitivity and specificity. The authors will investigate reporting biases using funnel plots based on effective sample size and regression tests of asymmetry. Subgroup analyses are planned for adults, children and infection setting (hospital vs community) if sufficient data are uncovered. Dissemination: Recommendations will be made to the Department of Health (as part of an open-access HTA report) as to whether the real-time PCR technology has sufficient clinical diagnostic accuracy potential to move forward to efficacy testing during the provision of routine clinical care.

Effect of intravenous beta-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial

BACKGROUND:
In a previous randomised controlled phase 2 trial, intravenous infusion of salbutamol for up to 7 days in patients with acute respiratory distress syndrome (ARDS) reduced extravascular lung water and plateau airway pressure. We assessed the effects of this intervention on mortality in patients with ARDS.
METHODS:
We did a multicentre, placebo-controlled, parallel-group, randomised trial at 46 UK intensive-care units between December, 2006, and March, 2010. Intubated and mechanically ventilated patients (aged =16 years) within 72 h of ARDS onset were randomly assigned to receive either salbutamol (15 µg/kg ideal bodyweight per h) or placebo for up to 7 days. Randomisation was done by a central telephone or web-based randomisation service with minmisation by centre, pressure of arterial oxygen to fractional inspired oxygen concentration (PaO(2)/F(I)O(2)) ratio, and age. All participants, caregivers, and investigators were masked to group allocation. The primary outcome was death within 28 days of randomisation. Analysis was by intention-to-treat. This trial is registered, ISRCTN38366450 and EudraCT number 2006-002647-86.
FINDINGS:
We randomly assigned 162 patients to the salbutamol group and 164 to the placebo group. One patient in each group withdrew consent. Recruitment was stopped after the second interim analysis because of safety concerns. Salbutamol increased 28-day mortality (55 [34%] of 161 patients died in the salbutamol group vs 38 (23%) of 163 in the placebo group; risk ratio [RR] 1·47, 95% CI 1·03-2·08).
INTERPRETATION:
Treatment with intravenous salbutamol early in the course of ARDS was poorly tolerated. Treatment is unlikely to be beneficial, and could worsen outcomes. Routine use of ß-2 agonist treatment in ventilated patients with this disorder cannot be recommended.

A self-reported work sampling study in community pharmacy practice

Lack of time to implement pharmaceutical care has been cited as a barrier to the routine provision of this extended patient-care service. Using self-reported work sampling methodology, this study investigated how community pharmacists utilise their time. Pharmacists working in community pharmacies in the Greater Belfast area were found to spend approximately 49% of their time engaged in professional activities, 29% in semi-professional activities and 22% involved in non-professional activities. The activity to which pharmacists devoted the majority of their time was product assembly and labelling, this being a task which can be performed by trained technical staff. Only 9.5% of community pharmacists' time was devoted to counselling patients on their prescription medicines. Wide variation in the amount of time apportioned to each activity was observed between the participating community pharmacists (n=30). Staffing levels within the community pharmacy were found to significantly influence pharmacists' involvement in a number of activities, with pharmacists who worked in pharmacies employing multiple pharmacists devoting more time to the assembly and labelling of products and less time to administrative tasks, non-professional encounters and to miscellaneous professional activities. Pharmacists working in pharmacies with a high prescription turnover were found to devote significantly less time to counselling patients regarding OTC products and in responding to patient symptoms.