Getting your life back on track after stroke : a phase II multi-centered, single-blind, randomized, controlled trial of the Stroke Self-Management Program vs. the Stanford Chronic Condition Self-Management Program or standard care in stroke survivors

Background Self-management is seen as a primary mechanism to support the optimization of care for people with chronic diseases such as symptomatic vascular disease. There are no established and evidence-based stroke-specific chronic disease self-management programs. Our aim is to evaluate whether a stroke-specific program is safe and feasible as part of a Phase II randomized-controlled clinical trial.
Methods Stroke survivors are recruited from a variety of sources including: hospital stroke services, local paper advertisements, Stroke South Australia newsletter (volunteer peer support organization), Divisions of General Practice, and community service providers across Adelaide, South Australia. Subjects are invited to participate in a multi-center, single-blind, randomized, controlled trial. Eligible participants are randomized to either;
• standard care,
• standard care plus a six week generic chronic condition self-management group education program, or,
• standard care plus an eight week stroke specific self-management education group program.
Interventions are conducted after discharge from hospital. Participants are assessed at baseline, immediate post intervention and six months.
Study Outcomes The primary outcome measures determine study feasibility and safety, measuring, recruitment, participation, compliance and adverse events.
Secondary outcomes include:
• positive and active engagement in life measured by the Health Education Impact Questionnaire,
• improvements in quality of life measured by the Assessment of Quality of Life instrument,
• improvements in mood measured by the Irritability, Depression and Anxiety Scale,
• health resource utilization measured by a participant held diary and safety.

Conclusion The results of this study will determine whether a definitive Phase III efficacy trial is justified.

Lesbian and gay experiences of primary care in one borough in North London, UK

This paper reports the findings of a research study which explored the experiences of lesbians and gay men in relation to primary care services in general practice in a multiracial borough in North London, UK. The research took a qualitative approach and used several methods including a literature review, interviews with stakeholders (n = 6), focus group discussions (n = 27) and completion (n = 42) of a survey distributed to lesbians and gay men locally. The process facilitated the development of a grounded theory. The important themes to emerge were finding a GP and coming out, sexual health issues, mental health issues and communication with the GP. Given the high level of mobility among this population, there were problems in maintaining continuity of care, and a lack of protocols to facilitate the sharing of knowledge between patients and practitioners while reducing reliance on heterosexual assumptions. There were clear differences between the treatment of women and men in relation to sexual health, and neither approach could be said to be patient centred or inclusive of diversity of need. The fact that many informants accessed alternative sources of healthcare indicated that they were concerned to promote and maintain their health and wellbeing in a holistic manner. The lack of transparent protocols within general practice inhibited some informants from being as open and honest about their sexuality with their GPs as they were with their families or their employers. The findings highlight (1) the need for organisational development within primary care to improve sensitivity to the needs of lesbians and gay men; (2) the value of research to engage with the social experiences of lesbians and gay men; (3) the importance of engaging with the differing experiences of lesbians and gay men in relation to sexual health concerns.

Clustering of Th cell epitopes on exposed regions of HIV envelope despite defects in antibody activity

A long-standing question in the field of immunology concerns the factors that contribute to Th cell epitope immunodominance. For a number of viral membrane proteins, Th cell epitopes are localized to exposed protein surfaces, often overlapping with Ab binding sites. It has therefore been proposed that Abs on B cell surfaces selectively bind and protect exposed protein fragments during Ag processing, and that this interaction helps to shape the Th cell repertoire. While attractive in concept, this hypothesis has not been thoroughly tested. To test this hypothesis, we have compared Th cell peptide immunodominance in normal C57BL/6 mice with that in C57BL/6MT/MT mice (lacking normal B cell activity). Animals were first vaccinated with DNA constructs expressing one of three different HIV envelope proteins, after which the CD4 T cell response profiles were characterized toward overlapping peptides using an IFN- ELISPOT assay. We found a striking similarity between the peptide response profiles in the two mouse strains. Profiles also matched those of previous experiments in which different envelope vaccination regimens were used. Our results clearly demonstrate that normal Ab activity is not required for the establishment or maintenance of Th peptide immunodominance in the HIV envelope response. To explain the clustering of Th cell epitopes, we propose that localization of peptide on exposed envelope surfaces facilitates proteolytic activity and preferential peptide shuttling through the Ag processing pathway.

Consequences of immunodominant epitope deletion for minor influenza virus-specific CD8+-T-cell responses

The extent to which CD8+ T cells specific for other antigens expand to compensate for the mutational loss of the prominent DbNP366 and DbPA224 epitopes has been investigated using H1N1 and H3N2 influenza A viruses modified by reverse genetics. Significantly increased numbers of CD8+ KbPB1703+ , CD8+ KbNS2114+, and CD8+ DbPB1-F262+ T cells were found in the spleen and in the inflammatory population recovered by bronchoalveolar lavage from mice that were first given the -NP-PA H1N1 virus intraperitoneally and then challenged intranasally with the homologous H3N2 virus. The effect was less consistent when this prime-boost protocol was reversed. Also, though the quality of the response measured by cytokine staining showed some evidence of modification when these minor CD8+-T-cell populations were forced to play a more prominent part, the effects were relatively small and no consistent pattern emerged. The magnitude of the enhanced clonal expansion following secondary challenge suggested that the prime-boost with the -NP-PA viruses gave a response overall that was little different in magnitude from that following comparable exposure to the unmanipulated viruses. This was indeed shown to be the case when the total response was measured by ELISPOT analysis with virus-infected cells as stimulators. More surprisingly, the same effect was seen following primary challenge, though individual analysis of the CD8+ KbPB1703+ , CD8+ KbNS2114+, and CD8+ DbPB1-F262+ sets gave no indication of compensatory expansion. A possible explanation is that novel, as yet undetected epitopes emerge following primary exposure to the -NP-PA deletion viruses. These findings have implications for both natural infections and vaccines.

Differential tumor necrosis factor receptor 2-mediated editing of virus-specific CD8+ effector T cells

Much of the CD8+ T cell response in H2b mice with influenza pneumonia is directed at the nucleoprotein366-374 (NP366) and acid polymerase224-233 (PA224) peptides presented by the H2Db MHC class I glycoprotein. These DbNP366- and DbPA224-specific T cell populations are readily analyzed by staining with tetrameric complexes of MHC+ peptide (tetramers) or by cytokine production subsequent to in vitro stimulation with the cognate peptides. The DbPA224-specific CD8+ effector T cells make more tumor necrosis factor (TNF) α than the comparable CD8+DbNP366+ set, a difference reflected in the greater sensitivity of the CD8+DbPA224+ population to TNF receptor (TNFR) 2-mediated apoptosis under conditions of in vitro culture. Freshly isolated CD8+DbNP366+ and CD8+DbPA224+ T cells from influenza-infected TNFR2-/- mice produce higher levels of IFN-γ and TNF-α after in vitro stimulation with peptide, although the avidity of the T cell receptor-epitope interaction does not change. Increased numbers of both CD8+DbPA224+ and CD8+DbNP366+ T cells were recovered from the lungs (but not the spleens) of secondarily challenged TNFR2-/- mice, a pattern that correlates with the profiles of TNFR expression in the TNFR2+/+ controls. Thus, it seems that TNFR2-mediated editing of influenza-specific CD8+ T cells functions to limit the numbers of effectors that have localized to the site of pathology in the lung but does not modify the size of the less activated responder T cell populations in the spleen. Therefore, the massive difference in magnitude for the secondary, although not the primary, response to these DbNP366 and DbPA224 epitopes cannot be considered to reflect differential TNFR2-mediated T cell editing.

You can spend your life dying or you can spend your life living : identity transition in people who are HIV-positive

This article examines, through the lenses of HIV-positive people, the unique phenomenon of identity transition. This research proposes that life-changing illnesses, such as HIV, are an undesired 'possession' that people accept to varying degrees, which we refer to as 'ownership'. While illnesses, such as HIV compel individuals to undergo a transformation process that usually begins with a deep feeling of detachment, and then proceeds to acceptance of their illness, and to feeling empowered and in control of their HIV status and lives, this process is very complex and non-linear as it involves many iterative progressions in identity transition. These transitions are highly individualistic; however, the underlying theme is that the more positive trajectories were those of people who focus on their new lives, living with HIV (i.e. taking ownership of their illness), rather than focusing on what they have lost when they became HIV-positive. The findings demonstrate that identity transition is a result of the ways that individuals rework, negotiate and transform their roles, actions and behaviours through their active engagement with support mechanisms. This study suggests that it is vital to promote positive interactions with support mechanisms to ensure that those with HIV view themselves positively.

A novel romance : conceptualising emotional attachment as a barrier to adoption

The Technology Acceptance Model (TAM) aims to understand consumers’ adoption of new technologies. Some 30 years after TAM was first proposed, it is still widely used today. This paper proposes an extended version of the TAM, with the primary addition to it being the construct of consumers’ emotional attachment to an existing product. The expanded TAM, Technology Acceptance Model with Emotional Attachment (TAME), is applied to the understudied area of e-book reader technology and its adoption by consumers who read for pleasure versus for academic purposes, as has been the focus of past research on e-book readers. The extended model considers consumers’ emotional attachment to paper books (pbooks) as a likely barrier to the take up of e-book reader technology.

An agent-based approach to value theory and wealth distribution in economics

Any attempt to model an economy requires foundational assumptions about the relations between prices, values and the distribution of wealth. These assumptions exert a profound influence over the results of any model. Unfortunately, there are few areas in economics as vexed as the theory of value. I argue in this paper that the fundamental problem with past theories of value is that it is simply not possible to model the determination of value, the formation of prices and the distribution of income in a real economy with analytic mathematical models. All such attempts leave out crucial processes or make unrealistic assumptions which significantly affect the results. There have been two primary approaches to the theory of value. The first, associated with classical economists such as Ricardo and Marx were substance theories of value, which view value as a substance inherent in an object and which is conserved in exchange. For Marxists, the value of a commodity derives solely from the value of the labour power used to produce it - and therefore any profit is due to the exploitation of the workers. The labour theory of value has been discredited because of its assumption that labour was the only ‘factor’ that contributed to the creation of value, and because of its fundamentally circular argument. Neoclassical theorists argued that price was identical with value and was determined purely by the interaction of supply and demand. Value then, was completely subjective. Returns to labour (wages) and capital (profits) were determined solely by their marginal contribution to production, so that each factor received its just reward by definition. Problems with the neoclassical approach include assumptions concerning representative agents, perfect competition, perfect and costless information and contract enforcement, complete markets for credit and risk, aggregate production functions and infinite, smooth substitution between factors, distribution according to marginal products, firms always on the production possibility frontier and firms’ pricing decisions, ignoring money and credit, and perfectly rational agents with infinite computational capacity. Two critical areas include firstly, the underappreciated Sonnenschein-Mantel- Debreu results which showed that the foundational assumptions of the Walrasian general-equilibrium model imply arbitrary excess demand functions and therefore arbitrary equilibrium price sets. Secondly, in real economies, there is no equilibrium, only continuous change. Equilibrium is never reached because of constant changes in preferences and tastes; technological and organisational innovations; discoveries of new resources and new markets; inaccurate and evolving expectations of businesses, consumers, governments and speculators; changing demand for credit; the entry and exit of firms; the birth, learning, and death of citizens; changes in laws and government policies; imperfect information; generalized increasing returns to scale; random acts of impulse; weather and climate events; changes in disease patterns, and so on. The problem is not the use of mathematical modelling, but the kind of mathematical modelling used. Agent-based models (ABMs), objectoriented programming and greatly increased computer power however, are opening up a new frontier. Here a dynamic bargaining ABM is outlined as a basis for an alternative theory of value. A large but finite number of heterogeneous commodities and agents with differing degrees of market power are set in a spatial network. Returns to buyers and sellers are decided at each step in the value chain, and in each factor market, through the process of bargaining. Market power and its potential abuse against the poor and vulnerable are fundamental to how the bargaining dynamics play out. Ethics therefore lie at the very heart of economic analysis, the determination of prices and the distribution of wealth. The neoclassicals are right then that price is the enumeration of value at a particular time and place, but wrong to downplay the critical roles of bargaining, power and ethics in determining those same prices.

N-acetyl cysteine for depressive symptoms in bipolar disorder - a double blind, randomized, placebo-controlled trial

Background: Treatment-resistant subthreshold depression is a major problem in bipolar disorder. Both depression and bipolar disorderare complicated by glutathione depletion. We hypothesized that treatment with N-acetyl cysteine (NAC), a safe, orally bioavailable precursor of glutathione, may improve the depressive component of bipolar disorder.

Methods: A randomized, double-blind, multicenter, placebo-controlled study of individuals (n 75) with bipolar disorder in the maintenance phase treated with NAC (1 g twice daily) adjunctive to usual medication over 24 weeks, with a 4-week washout. The two primary outcomes were the Montgomery Asberg Depression Rating Scale (MADRS) and time to a mood episode. Secondary outcomes included the Bipolar Depression Rating Scale and 11 other ratings of clinical status, quality of life, and functioning.

Results: NAC treatment caused a significant improvement on the MADRS (least squares mean difference [95% confidence interval]: 8.05 [13.16, 2.95], p .002) a n d most secondary scales at end point. Benefit was evident by 8 weeks on the Global Assessment of Functioning Scale and Social and Occupational Functioning Assessment Scale and at 20 weeks on the MADRS. Improvements were lost after washout. There was no effect of NAC on time to a mood episode (log-rank test: p .968) and no significant between-group differences inadverse events. Effect sizes at end point were medium to high for improvements in MADRS and 9 of the 12 secondary readouts.

Conclusions: NAC appears a safe and effective augmentation strategy for depressive symptoms in bipolar  disorder.

The place of information and communication technology-mediated consultations in primary care : GPs' perspectives

Background: New information and communication technologies such as email and text messaging have been shown to be useful in some aspects of primary care service delivery. Little is known about Scottish GPs’ attitudes towards the adoption of these technologies as routine consultation tools.

Objectives: To explore GPs’ perceptions of the potential place of new non-face-to-face consultation technologies in the routine delivery of primary care; to explore GPs’ perceived barriers to the introduction of these technologies and to identify the processes by which GPs feel that new consultation technologies could be incorporated into routine primary care.

Methods: Qualitative interview study: 20 in-depth semi-structured interviews carried out with maximum variation sample of GPs across Scotland.

Results: Whilst the face-to-face consultation was seen as central to much of the clinical and diagnostic work of primary care, many GPs were conditionally willing to consider using new technologies in the future, particularly to carry out administrative or less complex tasks and therefore maximize practice efficiency and patient convenience. Key considerations were access to appropriate training, IT support and medico-legal guidance.

Conclusions: GPs are conditionally willing to use new consultation media if clinically appropriate and if medico-legal and technical support is available.

Multicentre phase I/II study of PI-88, a heparanase inhibitor in combination with docetaxel in patients with metastatic castrate-resistant prostate cancer

Background: Docetaxel (Taxotere) improve survival and prostate-specific antigen (PSA) response rates in patients with metastatic castrate-resistant prostate cancer (CRPC). We studied the combination of PI-88, an inhibitor of angiogenesis and heparanase activity, and docetaxel in chemotherapy-naive CRPC.

Patients and methods: We conducted a multicentre open-label phase I/II trial of PI-88 in combination with docetaxel. The primary end point was PSA response. Secondary end points included toxicity, radiologic response and overall survival. Doses of PI-88 were escalated to the maximum tolerated dose; whereas docetaxel was given at a fixed 75 mg/m2 dose every three weeks

Results: Twenty-one patients were enrolled in the dose-escalation component. A further 35 patients were randomly allocated to the study to evaluate the two schedules in phase II trial. The trial was stopped early by the Safety Data Review Board due to a higher-than-expected febrile neutropenia of 27%. In the pooled population, the PSA response (50% reduction) was 70%, median survival was 61 weeks (6–99 weeks) and 1-year survival was 71%.

Conclusions: The regimen of docetaxel and PI-88 is active in CRPC but associated with significant haematologic toxicity. Further evaluation of different scheduling and dosing of PI-88 and docetaxel may be warranted to optimise efficacy with a more manageable safety profile.

Effect of insulin-like growth factor I on HIV type 1 long terminal repeat-driven chloramphenicol acetyltransferase expression

In this study, we have investigated the ability of insulin-like growth factor I (IGF-I) to inhibit HIV long terminal repeat (LTR)-driven gene expression. Using COS 7 cells cotransfected with tat and an HIV LTR linked to a chloramphenicol acetyltransferase (CAT) reporter, we observed that physiological levels of IGF-I (10-9 M) significantly inhibited CAT expression in a concentration- and time-dependent manner. IGF-I did not inhibit C AT expression in COS 7 cells transfected with pSVCAT, and did not affect CAT expression in the absence of cotransfection with tat . Transfection of HIV-1 proviral DNA into COS 7 cells +/- IGF-I resulted in a significant decrease ( p 0.05) in infectious virion production. Both IGF-I and Ro24-7429 inhibited LTR-driven C AT expression, while TNF- alpha -enhanced CAT expression was not affected by IGF-I. On the other hand, a plasmid encoding parathyroid hormone-related peptide exhibited dramatic additivity of inhibition of CAT expression in COS 7 cells. Finally, we show that in Jurkat or U937 cells cotransfected with HIVLTRCAT/tat, IGF-I significantly inhibited CAT expression. Further, interleukin 4 showed in U937 cells inhibition of CAT expression that was not additive to IGF-I induced inhibition. Our data demonstrate that IGF-I can specifically inhibit HIVLTRCAT expression. This inhibition may occur at the level of the tat /TAR interaction. Finally, this IGF-I effect is seen in target cell lines and similar paths of inhibition may be involved in the various cell types employed.

Spectroscopic study of the effects of pressure media on high-pressure phase transitions in natrolite

Structural phase transitions in natrolite have been investigated as a function of pressure and different hydrostatic media using micro-Raman scattering and synchrotron infrared (IR) spectroscopy. Natrolite undergoes two reversible phase transitions at 0.86 and 1.53 GPa under pure water pressure medium. These phase transitions are characterized by the changes in the vibrational frequencies of four- and eight-membered rings related to the variations in the bridging T−O−T angles and the geometry of the elliptical eight-ring channels under pressure. Concomitant to the changes in the framework vibrational modes, the number of the O−H stretching vibrational modes of natrolite changes as a result of the rearrangements of the hydrogen bonds in the channels caused by a successive increase in the hydration level under hydrostatic pressure. Similar phase transitions were also observed at relatively higher pressures (1.13 and 1.59 GPa) under alcohol−water pressure medium. Furthermore, no phase transition was found up to 2.52 GPa if a lower volume ratio of the alcohol−water to natrolite was employed. This indicates that the water content in the pressure media plays a crucial role in triggering the pressure-induced phase transitions in natrolite. In addition, the average of the mode Grüneisen parameters is calculated to be about 0.6, while the thermodynamic Grüneisen parameter is found to be 1.33. This might be attributed to the contrast in the rigidity between the TO4 tetrahedral primary building units and other flexible secondary building units in the natrolite framework upon compression and subsequent water insertion.

The politics of the pharmaceutical industry and access to medicines : world pharmacy and India

The Pharmaceutical Industry presents one of India’s most successful stories of economic expansion and improvements in public health. Indian firms have made access to quality medicines possible and affordable in many developing countries. Indian pharmaceuticals are also exported on a large scale to the United States and other highly regulated markets. A wave of mergers, acquisitions and tie-ups point to growing integration between Indian firms and global pharma multinationals.

The Politics of the Pharmaceutical Industry and Access to Medicines: World Pharmacy and India examines this important industry from different economic, social and political perspectives. Topics covered include the implications of TRIPS-compliant intellectual property rights, the role of flexibilities under TRIPS, the market regulation system, the role of Indian firms in exporting HIV/AIDS medications to Africa, the issue of free trade agreements, the power and reach of foreign pharmaceutical multinationals in India’s domestic market, and the sustainability of India as a major generics supplier.

Adolescents' perception of the relationship between movement skills, physical activity and sport

Movement skill competence is important to organised youth physical activity participation, but it is unclear how adolescents view this relationship. The primary aim of this study was to explore adolescents’ perception of the relationship between movement skills, physical activity and sport, and whether their perceptions differed according to extent of participation in organised physical activities. We recruited 33 (17 male) Grade 11 and 12 students (aged 16 to 18) from two secondary schools in Australia. Focus groups were allocated according to whether or not students participated in organised physical activity, where ‘organised activity’ was defined as activity which involved regular classes, training or competition, was reasonably structured or formal, or had a teacher, instructor or coach. There were three all-male ‘organised’ groups, one mixed-gender ‘organised’ group and one all-female ‘not-organised’ group. Students were asked about their attitudes towards physical activity and sport, the relationship between childhood skill proficiency and later physical activity and their perceptions of the appropriate time taken to learn movement skills. Group discussions lasted for approximately 50 minutes, were recorded and were then transcribed verbatim. Transcripts were read using a constant comparison method, in which quotes were continually compared to other quotes. A thematic analysis was conducted in which the transcripts were analysed inductively. Participation in organised sport had no bearing on opinions regarding whether lack of childhood skill development would negatively impact latter participation. It did, however, subtly influence opinions regarding whether skill could be successfully acquired later in life. When asked whether not having well-developed skills as a child would negatively impact on participation in sport/physical activity later in life, the response was mixed, but this was not related to their involvement in organised sport or activities. Students who believed early skill proficiency related to subsequent activity thought this was due to skill ability and motivation. An alternate view was that subsequent activity did not need to be based on skill proficiency; also, one’s environment might change, resulting in differing opportunities/constraints. Students felt skills could be learnt at any time in life (dependent on motivation), but that learning skills at a younger age would be easier and that skills learnt later would not be as developed. Fear of failure was identified as a barrier to learning when older. We conclude that motivation towards participation in sport and physical activity is affected by adolescents’ perception of their own movement skill ability. Therefore, developing children’s actual and perceived movement skills may help to increase adolescent physical activity. Since those with intrinsic achievement orientations were not as inclined towards organised activity, we may also need to provide physical activity options that resonate with intrinsic achievement motivations.