Modular approach to select bacteriophages targeting Pseudomonas aeruginosa for their application to children suffering with cystic fibrosis

This review discusses the potential application of bacterial viruses (phage therapy) towards the eradication of antibiotic resistant Pseudomonas aeruginosa in children with cystic fibrosis (CF). In this regard, several potential relationships between bacteria and their bacteriophages are considered. The most important aspect that must be addressed with respect to phage therapy of bacterial infections in the lungs of CF patients is in ensuring the continuity of treatment in light of the continual occurrence of resistant bacteria. This depends on the ability to rapidly select phages exhibiting an enhanced spectrum of lytic activity among several well-studied phage groups of proven safety. We propose a modular based approach, utilizing both mono-species and hetero-species phage mixtures. With an approach involving the visual recognition of characteristics exhibited by phages of well studied phage groups on lawns of the standard P. aeruginosa PAO1 strain, the simple and rapid enhancement of the lytic spectrum of cocktails is permitted, allowing the development of tailored preparations for patients capable of circumventing problems associated with phage resistant bacterial mutants.

Association analysis of apolipoprotein E genotype and risk of depressive symptoms in Alzheimer's disease

OBJECTIVES: Behavioural and psychological symptoms of dementia (BPSD) are potent predictors of carer distress and admission to institutional care. In Alzheimer's disease (AD), depressive symptoms are one of the most common complaints affecting around 50% of all patients. There is speculation these symptoms result from known genetic risk factors for AD, therefore we investigated the role of apolipoprotein E epsilon4 in the aetiology of depression in AD. METHODS: In this well-characterised cohort (n = 404) from the relatively genetically homogeneous Northern Ireland population, we tested the hypothesis that genetic variants of apolipoprotein E influence the risk for depressive symptoms in AD patients using the Neuropsychiatric Inventory (NPI-D) to determine the presence of depressive symptoms during the dementing illness. RESULTS: A total of 55% of patients exhibited a history of depression/dysphoria during the course of the illness as gathered by the NPI-D questionnaire. Forty-six percent were suffering from depression/dysphoria when the analysis was restricted to the month prior to interview. No statistically significant association between genotypes or alleles of apolipoprotein E and depression/dysphoria in AD was observed, nor was any association noted between the presence of severe symptoms and genotypes/alleles of apolipoprotein E. CONCLUSIONS: These results suggest apolipoprotein E genotype creates no additional risk for depressive symptoms in AD.

Structure and bioactivity of neuropeptide F from the human parasites Schistosoma mansoni and Schistosoma japonicum

The blood flukes Schistosoma mansoni and Schistosoma japonicum inflict immense suffering as agents of human schistosomiasis. Previous investigations have found the nervous systems of these worms contain abundant immunoreactivity to antisera targeting invertebrate neuropeptide Fs (NPFs) as well as structurally similar neuropeptides of the mammalian neuropeptide Y (NPY) family. Here, cDNAs encoding NPF in these worms were identified, and the mature neuropeptides from the two species differed by only a single amino acid. Both neuropeptides feature the characteristics common among NPFs; they are 36 amino acids long with a carboxyl-terminal Gly-Arg-X-Arg-Phe-amide and Tyr residues at positions 10 and 17 from the carboxyl terminus. Synthetic S. mansoni NPF potently inhibits the forskolin-stimulated accumulation of cAMP in worm homogenates, with significant effects at 10(-11) M. This is the first demonstration of an endogenous inhibition of cAMP by an NPF, and because this is the predominant pathway associated with vertebrate NPY family peptides, it demonstrates a conservation of downstream signaling pathways used by NPFs and NPY peptides.

Investigating the cost Performance of UK Credit Unions using Radial and Non-Radial Efficiency Measures

This paper examines the relative efficiency of UK credit unions. Radial and non-radial measures of input cost efficiency plus associated scale efficiency measures are computed for a selection of input output specifications. Both measures highlighted that UK credit unions have considerable scope for efficiency gains. It was mooted that the documented high levels of inefficiency may be indicative of the fact that credit unions, based on clearly defined and non-overlapping common bonds, are not in competition with each other for market share. Credit unions were also highlighted as suffering from a considerable degree of scale inefficiency with the majority of scale inefficient credit unions subject to decreasing returns to scale. The latter aspect highlights that the UK Government's goal of larger credit unions must be accompanied by greater regulatory freedom if inefficiency is to be avoided. One of the advantages of computing non-radial measures is that an insight into potential over- or under-expenditure on specific inputs can be obtained through a comparison of the non-radial measure of efficiency with the associated radial measure. Two interesting findings emerged, the first that UK credit unions over-spend on dividend payments and the second that they under-spend on labour costs.

ATR-dependent radiation-induced gammaH2AX foci in bystander primary human astrocytes and glioma cells.

Radiotherapy is an important treatment for patients suffering from high-grade malignant gliomas. Non-targeted (bystander) effects may influence these cells' response to radiation and the investigation of these effects may therefore provide new insights into mechanisms of radiosensitivity and responses to radiotherapy as well as define new targets for therapeutic approaches. Normal primary human astrocytes (NHA) and T98G glioma cells were irradiated with helium ions using the Gray Cancer Institute microbeam facility targeting individual cells. Irradiated NHA and T98G glioma cells generated signals that induced gammaH2AX foci in neighbouring non-targeted bystander cells up to 48 h after irradiation. gammaH2AX bystander foci were also observed in co-cultures targeting either NHA or T98G cells and in medium transfer experiments. Dimethyl sulphoxide, Filipin and anti-transforming growth factor (TGF)-beta 1 could suppress gammaH2AX foci in bystander cells, confirming that reactive oxygen species (ROS) and membrane-mediated signals are involved in the bystander signalling pathways. Also, TGF-beta 1 induced gammaH2AX in an ROS-dependent manner similar to bystander foci. ROS and membrane signalling-dependent differences in bystander foci induction between T98G glioma cells and normal human astrocytes have been observed. Inhibition of ataxia telangiectasia mutated (ATM) protein and DNA-PK could not suppress the induction of bystander gammaH2AX foci whereas the mutation of ATM- and rad3-related (ATR) abrogated bystander foci induction. Furthermore, ATR-dependent bystander foci induction was restricted to S-phase cells. These observations may provide additional therapeutic targets for the exploitation of the bystander effect.

Influence of prolonged hospitalization on overall bed occupancy: a five-year single-centre study

Background: Effective bed use is crucial to an efficient NHS. Current targets suggest a decrease in mean occupancy as the most appropriate method of improving overall efficiency. The elderly and those suffering from complex medical problems are thought to account for a high proportion of overall bed occupancy.

Aim: To assess the effect of prolonged hospital stay (>100 days) on overall bed occupancy in a modern teaching hospital.

Design: Retrospective analysis.

Methods: Analysis of all admission episodes (n = 117 178) over a five-year period in a large teaching hospital in a single UK region, serving a population of approximately 200 000. A logistic regression multi-factorial model was used to assess the effect of demographic and diagnostic variables on duration of stay.

Results: A prolonged stay (>100 days) was seen in 648 admission episodes (0.6%). These accounted for 11% of the overall bed occupancy over the 5-year period. Excluding all prolonged admission episodes from our analysis made no difference to the overall median length of stay.

Discussion: Prolonged hospitalizations have a significant impact on bed occupancy. Targeting these very long (>100 days) hospital stays may better improve overall efficiency, compared to targeting mean or median length of stay.

Public awareness and views on unlicensed use of medicines in children.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT center dot There is increasing concern about the use of those medicines in children which have not been fully studied and licensed for childhood use. Such use is not uncommon, due in large part to a lack of availability of fully licensed products and formulations that are suitable for children. center dot There is little published information on the views of the public on this important area of paediatric care. WHAT THIS STUDY ADDS center dot A survey of 1000 members of the public in Northern Ireland indicated that such use of medicines in children is not well known. center dot However, when informed about this practice, the majority believed that it would compromise safety and increase the likelihood of adverse effects. They also believed that parents/guardians should be told if their child was prescribed a medicine that had not been fully tested in children. center dot Participants in the survey indicated that they would be reluctant to involve their child in a clinical trial to help with the licensing process unless the child was suffering from a life-threatening illness. To explore awareness and views of the general public on unlicensed use of medicines in children and on the participation of children in clinical trials. Members of the public completed a questionnaire survey administered by face-to-face interview in public areas in N. Ireland. The main outcome measures were the views on unlicensed use of medicines in children and on clinical trials in children. One thousand participants (59.2% female) took part; 610 were parents. Most participants (86%) had no previous knowledge about unlicensed use of medicines in children. Being a parent did not influence this nor did being a parent of a child who suffered from a health problem (P > 0.05). Most participants (92%) felt that parents should be told about unlicensed use of medicines, with the doctor most frequently selected as the person who should inform parents. At the outset, only 1.8% of participants felt that the use of medicines in children was unsafe. However, having been informed about unlicensed use of medicines, this proportion increased dramatically (62.4%; P <0.001). Views on whether participants would enter a child of their own into a clinical trial varied according to the health status of the child (P <0.05) i.e. a child in good health (3.9%) vs a child with a life-threatening condition (41.9%). There is limited public knowledge of unlicensed use of medicines in children and a general reluctance to involve children in clinical trials unless the child to be involved has a life-threatening condition.

Bimanual co-ordination in Huntington's disease

The ability of Huntington's disease patients to co-ordinate their two hands with and without external cueing was investigated. Twelve Huntington's disease patients and sex- and age-matched controls performed a bimanual cranking task at two speeds (0.5 Hz, 1.5 Hz) and phase relationships (in-phase, anti-phase), with and without an external metronome cue. Data were sampled at 200 Hz, and raw displacement data for each hand, mean and standard deviation measures of the relative positions of the two hands and their velocities were then calculated. All participants could perform the in-phase movement, at both speeds; however, the Huntington's disease patients were more variable and less accurate than the control participants, particularly at the fast speed. While controls could perform the anti-phase movement, in which rotation of the cranks differed by 180 degrees at both speeds, Huntington's disease patients were unable to do so at either speed, reverting to the in-phase movement at the slow speed. An external metronome cue did not improve the performance of the Huntington's disease patients, which differentiated this group from patients suffering from Parkinson's disease. The Huntington's disease patients' inability to perform the anti-phase movement may be due to damage to the basal ganglia and its output regions.

The Impact of Engagement Processes on the First Appointment Attendance Rate at a Regional Outpatient Psychological Trauma Service.

The effectiveness of simple measures to increase attendance at first appointments is briefly reviewed. The Family Trauma Centre’s remit and pre-study engagement process are described. The perceived idiosyncratic aspects of inviting people suffering from psychological trauma to attend a clinical service are noted as contributory factors in initially tolerating a high first appointment DNA rate. Three new initial engagement processes are then described and results of their application to 30 referrals in total are presented. The overwhelming finding is that paying close attention to any of the three initial engagement processes significantly increases first appointment attendance. Based on these findings the Centre developed a new initial engagement protocol.. The principle that services should pay more attention to their engagement processes than on the characteristics of their client groups when seeking to reduce first appointment DNA rates is supported.

Creating Safety for Trauma Survivors: What can Therapists do?

This paper serves as a reminder to those working clinically in the field of trauma of the necessity for therapists to adequately include issues of safety within the therapeutic process. Addressing these issues is an integral part of the therapy and not simply a practical prerequisite or a parallel process. Validation of this thesis is drawn from trauma literature and an account of safety issues relating to the therapeutic setting and processes is given. Case examples illustrate the type of issues that might usefully be addressed within the therapeutic context to increase individual and family safety for clients as they continue to live within their local communities. This paper draws on recent work undertaken at the Family Trauma Centre. This Centre, based in South Belfast, is in its second year of operation. The Family Trauma Centre has a primary remit to provide clinical treatment for children and their families suffering from the traumatic effects of the ‘Troubles’ in Northern Ireland. The community context for this work has been one of continuous low-grade conflict in the midst of a ‘Peace’ process.

A New Restricted Full-Rank Single-Symbol Decodable Design for Four Transmit Antennas

Recently, a single-symbol decodable transmit strategy based on preprocessing at the transmitter has been introduced to decouple the quasi-orthogonal space-time block codes (QOSTBC) with reduced complexity at the receiver [9]. Unfortunately, it does not achieve full diversity, thus suffering from significant performance loss. To tackle this problem, we propose a full diversity scheme with four transmit antennas in this letter. The proposed code is based on a class of restricted full-rank single-symbol decodable design (RFSDD) and has many similar characteristics as the coordinate interleaved orthogonal designs (CIODs), but with a lower peak-to-average ratio (PAR).

The politics of ethical foreign policy::A responsibility to protect whom?

Ethical foreign policy persists as a problem of international relations, especially regarding humanitarian intervention. However, despite apparent international upheavals, the debate about the ethics of humanitarian intervention has remained fundamentally unchanged. To escape the limits of this debate, this article deconstructs British claims to ethical foreign policy since 1997, reading these claims against themselves and against contemporary humanitarian intervention literature. It finds that Britain’s ethical framework, the ‘doctrine of international community’, which justifies interventions in Kosovo, Sierra Leone and Afghanistan, is undone by the anomalous, yet exemplary, invasion of Iraq. This demonstrates the politics of ethical foreign policy: first, that any intervention, no matter how ‘ethical’ or ‘right’, produces suffering and death; and, second, that we cannot know for sure whether we are doing the right thing by intervening. Embracing, rather than effacing, the political nature of ethical foreign policy opens up a more intellectually honest and positive potential future for relating to the foreign in a responsible manner.

`No dream is ever just a dream': Stanley Kubrick's Eyes Wide Shut as monofilm

This article examines Stanley Kubrick's final film, Eyes Wide Shut (1999), in relation to its source text, J.M.Q. Davies's 1999 translation of Arthur Schnitzler's Traumnovelle/Dream Story, originally published in 1926. Both the film and the novel are viewed through the lens of monodrama, a dramatic genre characterized by the attempt to convey the subjective psychical experience of a strong central protagonist. Monodramatic traits may also be found in the novel and film, and the article explores how this adaptation typifies certain aspects of the monodrama form and how those traits are portrayed through the specific conventions and limitations of the differing media.