An exploration into the client at the heart of therapy : a qualitative perspective

Over 50 years ago Eysenck challenged the existing base of research into psychotherapy. Since that time, a large number of investigations have been conducted to verify the efficacy of therapy. Recently however, an increasing number of studies have cast new doubts on this research base. Instead of therapy being a function of the therapist, it is now becoming ever more apparent that the client plays a prime role in the therapeutic process. The qualitative studies presented in this paper provide some examples of research that demonstrates that clients are actively involved in their therapy, even making counselling work despite their counsellor. These studies suggest that clients may not experience therapy as beneficially as traditional outcome studies indicate. This raises a new challenge to researchers to more fully explore the client's experience of therapy, a challenge to which qualitative methods of inquiry would appear well suited

Tamoxifen, 17beta-oestradiol and the calmodulin antagonist J8 inhibit human melanoma cell invasion through fibronectin.

Invasion through stromal extracellular matrix (ECM) is part of the complex, multistep process of tumour cell invasion and metastasis. Our group has previously demonstrated that calcium and calmodulin are important in another step in the metastatic cascade - that of attachment of cells to ECM. Interestingly, the non-steroidal anti-oestrogen tamoxifen (which also has calmodulin antagonist activity), used in the treatment of breast cancer and now in metastatic cutaneous melanoma, can inhibit the attachment of normal and neoplastic cells to ECM. In this study, we investigated whether such drugs, known to inhibit cell attachment, could also subsequently reduce their invasion through a layer of human fibronectin. We examined the ability of the specific calmodulin antagonist J8, tamoxifen and its two major metabolites, N-desmethyltamoxifen (N-des) and 4-hydroxytamoxifen (4-OH), as well as the pure anti-oestrogen ICI 182,780 and 17beta-oestradiol to inhibit invasion of the human cutaneous melanoma cell line, A375-SM, uveal melanoma cells and uveal melanocytes. A375-SM cells and uveal melanoma cells showed a high level of invasion (15.2% and 33.7% respectively) compared with melanocytes (around 5%) under the experimental conditions used. Submicromolar concentrations of N-des, tamoxifen, J8 and 17beta-oestradiol significantly reduced the invasiveness of the A375-SM cell line. The uveal melanoma cells also showed similar inhibition, although at higher concentrations of these agents. 4-OH and ICI 182, 780 had little or no effect on invasion of A375-SM cells (these were not tested on uveal melanoma cells). All cells used in this study were found to be negative for type I nuclear oestrogen receptors, reinforcing the possibility that tamoxifen and 17beta-oestradiol can act via mechanisms unrelated to binding to classical oestrogen receptors to inhibit tumour cell invasion

Resistance of uveal melanoma to the interstrand cross-linking agent mitomycin C is associated with reduced expression of CYP450R

background: Uveal melanoma (UM) is the most common primary intraocular tumour of adults, frequently metastasising to the liver. Hepatic metastases are difficult to treat and are mainly unresponsive to chemotherapy. To investigate why UM are so chemo-resistant we explored the effect of interstrand cross-linking agents mitomycin C (MMC) and cisplatin in comparison with hydroxyurea (HU). methods: Sensitivity to MMC, cisplatin and HU was tested in established UM cell lines using clonogenic assays. The response of UM to MMC was confirmed in MTT assays using short-term cultures of primary UM. The expression of cytochrome P450 reductase (CYP450R) was analysed by western blotting, and DNA cross-linking was assessed using COMET analysis supported by γ-H2AX foci formation. results: Both established cell lines and primary cultures of UM were resistant to the cross-linking agent MMC (in each case P<0.001 in Student's t-test compared with controls). In two established UM cell lines, DNA cross-link damage was not induced by MMC (in both cases P<0.05 in Students's t-test compared with damage induced in controls). In all, 6 out of 6 UMs tested displayed reduced expression of the metabolising enzyme CYP450R and transient expression of CYP450R increased MMC sensitivity of UM. conclusion: We suggest that reduced expression of CYP450R is responsible for MMC resistance of UM, through a lack of bioactivation, which can be reversed by complementing UM cell lines with CYP450R

Association of specific chromosome alterations with tumour phenotype in posterior uveal melanoma

Posterior uveal melanomas have recurrent alterations of chromosomes 1, 3, 6 and 8. In particular, changes of chromosomes 3 and 8 occur in association, appear to characterize those tumours with a ciliary body component, and have been shown to be of prognostic significance. The relevance of other chromosome alterations is less certain. We have performed cytogenetic analysis on 42 previously untreated primary posterior uveal melanomas. Of interest was the observation that as tumour size increased the involvement of specific chromosome changes, and the amount of chromosome abnormalities likewise increased. Loss, or partial deletions, of the short arm of chromosome 1 were found to associate with larger ciliary body melanomas; typically, loss of the short arm resulted from unbalanced translocations, the partners of which varied. Trisomy of chromosome 21 occurred more often in ciliary body melanomas, whilst rearrangements of chromosomes 6 and 11 were primarily related to choroidal melanomas. Our results imply that alterations of chromosome 1 are important in the progression of some uveal melanomas, and that other chromosome abnormalities, besides those of chromosomes 3 and 8, are associated with ocular tumours of particular locations. © 2000 Cancer Research Campaig

On Spectral Triples in Quantum Gravity II

A semifinite spectral triple for an algebra canonically associated to canonical quantum gravity is constructed. The algebra is generated by based loops in a triangulation and its barycentric subdivisions. The underlying space can be seen as a gauge fixing of the unconstrained state space of Loop Quantum Gravity. This paper is the second of two papers on the subject.Comment: 43 pages, 1 figur

The Standard Model with gravity couplings

In this paper, we examine the coupling of matter fields to gravity within the framework of the Standard Model of particle physics. The coupling is described in terms of Weyl fermions of a definite chirality, and employs only (anti)self-dual or left-handed spin connection fields. It is known from the work of Ashtekar and others that such fields can furnish a complete description of gravity without matter. We show that conditions ensuring the cancellation of perturbative chiral gauge anomalies are not disturbed. We also explore a global anomaly associated with the theory, and argue that its removal requires that the number of fundamental fermions in the theory must be multiples of 16. In addition, we investigate the behavior of the theory under discrete transformations P, C and T; and discuss possible violations of these discrete symmetries, including CPT, in the presence of instantons and the Adler-Bell-Jackiw anomaly.Comment: Extended, and replaced with LaTex file. 25 Page

Reassessing changes in diurnal temperature range: Intercomparison and evaluation of existing global data set estimates

Changes in diurnal temperature range (DTR) over global land areas are compared from a broad range of independent data sets. All data sets agree that global-mean DTR has decreased significantly since 1950, with most of that decrease occurring over 1960–1980. The since-1979 trends are not significant, with inter-data set disagreement even over the sign of global changes. Inter-data set spread becomes greater regionally and in particular at the grid box level. Despite this, there is general agreement that DTR decreased in North America, Europe, and Australia since 1951, with this decrease being partially reversed over Australia and Europe since the early 1980s. There is substantive disagreement between data sets prior to the middle of the twentieth century, particularly over Europe, which precludes making any meaningful conclusions about DTR changes prior to 1950, either globally or regionally. Several variants that undertake a broad range of approaches to postprocessing steps of gridding and interpolation were analyzed for two of the data sets. These choices have a substantial influence in data sparse regions or periods. The potential of further insights is therefore inextricably linked with the efficacy of data rescue and digitization for maximum and minimum temperature series prior to 1950 everywhere and in data sparse regions throughout the period of record. Over North America, station selection and homogeneity assessment is the primary determinant. Over Europe, where the basic station data are similar, the postprocessing choices are dominant. We assess that globally averaged DTR has decreased since the middle twentieth century but that this decrease has not been linear

Gender differences in the association between adiposity and probable major depression: a cross-sectional study of 140,564 UK Biobank participants

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Previous studies on the association between adiposity and mood disorder have produced contradictory results, and few have used measurements other than body mass index (BMI). We examined the association between probable major depression and several measurements of adiposity: BMI, waist circumference (WC), waist-hip-ratio (WHR), and body fat percentage (BF%).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; We conducted a cross-sectional study using baseline data on the sub-group of UK Biobank participants who were assessed for mood disorder. Multivariate logistic regression models were used, adjusting for potential confounders including: demographic and life-style factors, comorbidity and psychotropic medication.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Of the 140,564 eligible participants, evidence of probable major depression was reported by 30,145 (21.5%). The fully adjusted odds ratios (OR) for obese participants were 1.16 (95% confidence interval (CI) 1.12, 1.20) using BMI, 1.15 (95% CI 1.11, 1.19) using WC, 1.09 (95% CI 1.05, 1.13) using WHR and 1.18 (95% CI 1.12, 1.25) using BF% (all p &#60;0.001). There was a significant interaction between adiposity and gender (p = 0.001). Overweight women were at increased risk of depression with a dose response relationship across the overweight (25.0-29.9 kg/m2), obese I (30.0-34.9 kg/m2), II (35.0-39.9 kg/m2) and III (≥40.0 kg/m2) categories; fully adjusted ORs 1.14, 1.20, 1.29 and 1.48, respectively (all p &#60; 0.001). In contrast, only obese III men had significantly increased risk of depression (OR 1.29, 95% CI 1.08, 1.54, p = 0.006).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Adiposity was associated with probable major depression, irrespective of the measurement used. The association was stronger in women than men. Physicians managing overweight and obese women should be alert to this increased risk

A systematic review of the effectiveness and cost-effectiveness of peer education and peer support in prisons.

BACKGROUND: Prisoners experience significantly worse health than the general population. This review examines the effectiveness and cost-effectiveness of peer interventions in prison settings. METHODS: A mixed methods systematic review of effectiveness and cost-effectiveness studies, including qualitative and quantitative synthesis was conducted. In addition to grey literature identified and searches of websites, nineteen electronic databases were searched from 1985 to 2012. Study selection criteria were: Population: Prisoners resident in adult prisons and children resident in Young Offender Institutions (YOIs). INTERVENTION: Peer-based interventions Comparators: Review questions 3 and 4 compared peer and professionally led approaches. OUTCOMES: Prisoner health or determinants of health; organisational/ process outcomes; views of prison populations. STUDY DESIGNS: Quantitative, qualitative and mixed method evaluations. RESULTS: Fifty-seven studies were included in the effectiveness review and one study in the cost-effectiveness review; most were of poor methodological quality. Evidence suggested that peer education interventions are effective at reducing risky behaviours, and that peer support services are acceptable within the prison environment and have a positive effect on recipients, practically or emotionally. Consistent evidence from many, predominantly qualitative, studies, suggested that being a peer deliverer was associated with positive effects. There was little evidence on cost-effectiveness of peer-based interventions. CONCLUSIONS: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health; peer support services are also an acceptable source of help within the prison environment and can have a positive effect on recipients. Research into cost-effectiveness is sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ref: CRD42012002349