An exploration of attributional style using the Descriptive Experience Sampling method

This study explored the association between cognitive style and depression. Phase I: 195 participants completed questionnaires that assessed cognitive style and psychological distress. Among these participants the expected relationships were found between depression, anxiety, interpersonal sensitivity, attributional style, and rumination; Phase II: Six participants selected based on their attributional style engaged in Descriptive Experience Sampling, which entails wearing a small device that will beep at random intervals, recording their awareness at the sound of the beep, and being interviewed within twenty-four hours of doing so. The inner experiences revealed by DES did not generally show the patterns suggested by current theories of depression. Two individuals who appeared to be at greatest risk for depression, one of whom was in the low risk group based on the Phase I screening data, did show signs of more negatively valenced inner experience and more thoughts consistent with Beck\u27s cognitive theory of depression

Partitioning 3-homogeneous latin bitrades

A latin bitrade $(T^{\diamond}, T^{\otimes})$ is a pair of partial latin squares which defines the difference between two arbitrary latin squares $L^{\diamond} \supseteq T^{\diamond}$ and $L^{\diamond} \supseteq T^{\otimes}$ of the same order. A 3-homogeneous bitrade $(T^{\diamond}, T^{\otimes})$ has three entries in each row, three entries in each column, and each symbol appears three times in $T^{\diamond}$. Cavenagh (2006) showed that any 3-homogeneous bitrade may be partitioned into three transversals. In this paper we provide an independent proof of Cavenagh's result using geometric methods. In doing so we provide a framework for studying bitrades as tessellations of spherical, euclidean or hyperbolic space.Comment: 13 pages, 11 figures, fixed the figures. Geometriae Dedicata, Accepted: 13 February 2008, Published online: 5 March 200

Cyclic cycle systems of the complete multipartite graph

In this paper, we study the existence problem for cyclic $\ell$-cycle decompositions of the graph $K_m[n]$, the complete multipartite graph with $m$ parts of size $n$, and give necessary and sufficient conditions for their existence in the case that $2\ell \mid (m-1)n$

Identifying flaws in the security of critical sets in latin squares via triangulations

In this paper we answer a question in theoretical cryptography by reducing it to a seemingly unrelated geometrical problem. Drápal (1991) showed that a given partition of an equilateral triangle of side n into smaller, integer-sided equilateral triangles gives rise to, under certain conditions, a latin trade within the latin square based on the addition table for the integers (mod n). We apply this result in the study of flaws within certain theoretical cryptographic schemes based on critical sets in latin squares. We classify exactly where the flaws occur for an infinite family of critical sets. Using Drápal's result, this classification is achieved via a study of the existence of triangulations of convex regions that contain prescribed triangles

Criteria for the use of omics-based predictors in clinical trials.

The US National Cancer Institute (NCI), in collaboration with scientists representing multiple areas of expertise relevant to 'omics'-based test development, has developed a checklist of criteria that can be used to determine the readiness of omics-based tests for guiding patient care in clinical trials. The checklist criteria cover issues relating to specimens, assays, mathematical modelling, clinical trial design, and ethical, legal and regulatory aspects. Funding bodies and journals are encouraged to consider the checklist, which they may find useful for assessing study quality and evidence strength. The checklist will be used to evaluate proposals for NCI-sponsored clinical trials in which omics tests will be used to guide therapy

Retinoic acid-responsive CD8 effector T-cells are selectively increased in IL-23-rich tissue in gastrointestinal GvHD.

Gastrointestinal (GI) graft-versus-host disease (GvHD) is a major barrier in allogeneic hematopoietic stem-cell transplantation (AHST). The metabolite retinoic acid (RA) potentiates GI-GvHD in mice via alloreactive T-cells expressing the RA-receptor-alpha (RARα), but the role of RA-responsive cells in human GI-GvHD remains undefined. We therefore used conventional and novel sequential immunostaining and flow cytometry to scrutinize RA-responsive T-cells in tissues and blood of AHST patients and characterize the impact of RA on human T-cell alloresponses. Expression of RARα by human mononuclear cells was increased after RA exposure. RARαhi mononuclear cells were increased in GI-GvHD tissue, contained more cellular RA-binding proteins, localized with tissue damage and correlated with GvHD severity and mortality. Using a targeted candidate protein approach we predicted the phenotype of RA-responsive T-cells in the context of increased microenvironmental IL-23. Sequential immunostaining confirmed the presence of a population of RARahi CD8 T-cells with the predicted phenotype, co-expressing the effector T-cell transcription factor T-bet and the IL-23-specific receptor. These cells were increased in GI- but not skin-GvHD tissues and were also selectively expanded in GI-GvHD patient blood. Finally, functional approaches demonstrated RA predominantly increased alloreactive GI-tropic RARahi CD8 effector T-cells, including cells with the phenotype identified in vivo. IL-23-rich conditions potentiated this effect by selectively increasing b7 integrin expression on CD8 effector T-cells and reducing CD4 T-cells with a regulatory cell phenotype. In conclusion we have identified a population of RA-responsive effector T-cells with a distinctive phenotype which are selectively expanded in human GI-GvHD and represent a potential new therapeutic target

Bortezomib, thalidomide, dexamethasone, and panobinostat for patients with relapsed multiple myeloma (MUK-six): a multicentre, open-label, phase 1/2 trial

Background Panobinostat (a pan histone deacetylase inhibitor) is approved in combination with bortezomib and dexamethasone for patients with relapsed multiple myeloma who have received two or more previous lines of therapy. We aimed to improve the safety of this combination and investigate efficacy by incorporating low-dose thalidomide, using sub-cutaneous weekly bortezomib, and determining the maximum tolerated dose of panobinostat in this regimen. Methods We did a phase 1/2, multicentre, open-label trial (MUK six) at four hospitals in the UK, enrolling patients with relapsed, or relapsed and refractory, multiple myeloma aged at least 18 years, with an Eastern Cooperative Oncology Group performance status of 2 or less who had previously received 1–4 lines of therapy. Exclusion criteria included any antimyeloma treatment within 28 days of study drugs (except dexamethasone 160 mg >48 h before treatment). We used a rolling six escalation design to determine the maximum tolerated dose of panobinostat, and allocated patients to receive subcutaneous bortezomib 1·3 mg/m2, and oral thalidomide 100 mg, dexamethasone 20 mg, and panobinostat 10, 15, or 20 mg (escalated to 20 mg according to the escalation schedule). Treatment was given during a 21-day cycle (bortezomib on days 1 and 8; thalidomide every day; dexamethasone on days 1, 2, 8, and 9; and panobinostat on days 1, 3, 5, 8, 10, and 12) for 16 cycles in the absence of disease progression or unacceptable toxicity. Patients were permitted to come off study for autologous stem cell transplantation. The primary objective was to determine the maximum tolerated dose and recommended dose of panobinostat, and to estimate the proportion of patients with an overall response that was equal to a partial response or greater within 16 cycles of treatment at the recommended panobinostat dose in the modified intention-to-treat population. We assessed safety in all patients who received a trial drug (ie, bortezomib, thalidomide, dexamethasone, or panobinostat). This trial is registered at ClinicalTrials.gov, number NCT02145715, and with the ISRCTN registry, number ISRCTN59395590 and is closed to recruitment. Findings Between Jan 31, 2013, and Oct 30, 2014, we enrolled 57 eligible patients who received at least one dose of trial medication or any drug. One dose-limiting toxicity was reported (grade 3 hyponatremia at the 20 mg dose), therefore the maximum tolerated dose was not reached, and 20 mg was deemed to be the recommended dose. 46 patients were treated with panobinostat 20 mg (the intention-to-treat population). 42 patients (91%, 80% CI 83·4–96·2) of 46 achieved the primary endpoint of an overall response that was equal to a partial response or greater. Most adverse events were grade 1–2 with few occurrences of grade 3–4 diarrhoea or fatigue. The most common adverse events of grade 3 or worse in the safety population (n=57) were reduced neutrophil count (15 [26%]), hypophosphatemia (11 [19%]), and decreased platelet count (8 [14%]). 46 serious adverse events were reported in 27 patients; of 14 suspected to be related to the trial medication, seven (50%) were gastrointestinal disorders. Interpretation Panobinostat 20 mg in combination with bortezomib, thalidomide, and dexamethasone is an efficacious and well tolerated regimen for patients with relapsed multiple myeloma