The outcome of peripheral T-cell lymphoma patients failing first-line therapy: A report from the prospective international T-cell project

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Predictors of remote practice location in the first seven cohorts of James Cook University MBBS graduates

Introduction: This article describes factors predicting James Cook University (JCU) medical graduates undertaking at least 1 year of remote practice. The cross-sectional design involved point-in-time (2015) analysis of the JCU medical school's ongoing longitudinal graduate tracking database. Participants were the first seven cohorts of graduates from the JCU medical school who had completed at least their postgraduate year (PGY) 4 in Australia (n=529); that is, PGY 4 to PGY 10 graduates. Methods: Multiple logistic regression and Classification and Regression Tree (CART) analysis of medical graduate application data (age, gender, hometown, interview score, ethnicity), undergraduate data (scholarships awarded, clinical school location) and postgraduation data (internship location, specialty training) was performed. Analysis identified independent predictors of having practised for at least 1 year in a 'remote' Australian town (Australian Standard Geographic Classification Remoteness Area 4-5). Results: Forty-seven (9%) of JCU Bachelor of Medicine and Bachelor of Surgery graduates in the first seven cohorts had practised for at least 1 year in a remote location between PGY 4 and 10. Practice in a 'remote' town was predicted by undertaking rural generalist training (p<0.001; prevalence odds ratio (POR)=17.0), being awarded an 'above average' interview score at medical school selection (p=0.006; POR=5.1), attending the Darwin clinical school in years 5-6 (p=0.005; POR=4.7), being female (p=0.016, POR=3.6) and undertaking an outer-regional or remotely based internship (p=0.006; POR=3.5). CART analysis identified Indigenous graduates as another key subgroup of remote practice graduates. Conclusions: This study provides the first Australian evidence that likelihood of remote medical practice is enhanced by investment in a 'remote pipeline' - medical education via clinical schools and internships in rural/remote locations, with a later option of a rural generalist pathway. The proportion of medical graduates working in remote practice may also be increased by preferentially selecting Indigenous Australian applicants and applicants who score highly for communication, teamwork, self-reliance and motivation for rural and remote practice

Fast-ignition design transport studies: realistic electron source, integrated PIC-hydrodynamics, imposed magnetic fields

Transport modeling of idealized, cone-guided fast ignition targets indicates the severe challenge posed by fast-electron source divergence. The hybrid particle-in-cell [PIC] code Zuma is run in tandem with the radiation-hydrodynamics code Hydra to model fast-electron propagation, fuel heating, and thermonuclear burn. The fast electron source is based on a 3D explicit-PIC laser-plasma simulation with the PSC code. This shows a quasi two-temperature energy spectrum, and a divergent angle spectrum (average velocity-space polar angle of 52 degrees). Transport simulations with the PIC-based divergence do not ignite for > 1 MJ of fast-electron energy, for a modest 70 micron standoff distance from fast-electron injection to the dense fuel. However, artificially collimating the source gives an ignition energy of 132 kJ. To mitigate the divergence, we consider imposed axial magnetic fields. Uniform fields ~50 MG are sufficient to recover the artificially collimated ignition energy. Experiments at the Omega laser facility have generated fields of this magnitude by imploding a capsule in seed fields of 50-100 kG. Such imploded fields are however more compressed in the transport region than in the laser absorption region. When fast electrons encounter increasing field strength, magnetic mirroring can reflect a substantial fraction of them and reduce coupling to the fuel. A hollow magnetic pipe, which peaks at a finite radius, is presented as one field configuration which circumvents mirroring.Comment: 16 pages, 17 figures, submitted to Phys. Plasma

Essential (Mg, fe, zn and cu) and non-essential (cd and pb) elements in predatory insects (vespa crabro and vespa velutina): A molecular perspective

The recent introduction of the Asian yellow-legged hornet, Vespa velutina, into Europe has raised concern regarding the threat to honeybees and the competition with the European hornet, Vespa crabro. The aim of this study was to investigated essential (Mg, Fe, Zn, Cu) and non-essential (Cd and Pb) elements in these two species. Element concentrations were determined in the whole body and separately in the head, thorax and abdomen using atomic absorption spectrometry (AAS). The changes in essential element concentration and speciation during metamorphosis were also studied using size exclusion chromatography followed by AAS and proteomic analysis. In both species, the essential elements were more concentrated in the abdomen due to the presence of fat bodies. Magnesium, Fe and Zn concentrations were significantly higher in V. crabro than in V. velutina and could have been related to the higher aerobic energy demand of the former species required to sustain foraging flight. Low concentrations of Cd and Pb were indicative of low environmental exposure. The concentration and speciation of essential elements, particularly Fe, varied among the developmental stages, indicating a modification of ligand preferences during metamorphosis. Overall, the results in the present study provide a better understanding of the hornet metal metabolism and a foundation for additional studies

Dynamic Control of Laser Produced Proton Beams

The emission characteristics of intense laser driven protons are controlled using ultra-strong (of the order of 10^9 V/m) electrostatic fields varying on a few ps timescale. The field structures are achieved by exploiting the high potential of the target (reaching multi-MV during the laser interaction). Suitably shaped targets result in a reduction in the proton beam divergence, and hence an increase in proton flux while preserving the high beam quality. The peak focusing power and its temporal variation are shown to depend on the target characteristics, allowing for the collimation of the inherently highly divergent beam and the design of achromatic electrostatic lenses.Comment: 9 Pages, 5 figure

Cone-Guided Fast Ignition with no Imposed Magnetic Fields

Simulations of ignition-scale fast ignition targets have been performed with the new integrated Zuma-Hydra PIC-hydrodynamic capability. We consider an idealized spherical DT fuel assembly with a carbon cone, and an artificially-collimated fast electron source. We study the role of E and B fields and the fast electron energy spectrum. For mono-energetic 1.5 MeV fast electrons, without E and B fields, the energy needed for ignition is E_f^{ig} = 30 kJ. This is about 3.5x the minimal deposited ignition energy of 8.7 kJ for our fuel density of 450 g/cm^3. Including E and B fields with the resistive Ohm's law E = \eta J_b gives E_f^{ig} = 20 kJ, while using the full Ohm's law gives E_f^{ig} > 40 kJ. This is due to magnetic self-guiding in the former case, and \nabla n \times \nabla T magnetic fields in the latter. Using a realistic, quasi two-temperature energy spectrum derived from PIC laser-plasma simulations increases E_f^{ig} to (102, 81, 162) kJ for (no E/B, E = \eta J_b, full Ohm's law). This stems from the electrons being too energetic to fully stop in the optimal hot spot depth.Comment: Minor revisions in response to referee comment

Individuación y mercado educacional en chile

Este artículo sistematiza hallazgos de distintas investigaciones sobre la educación chilena para comprender los mercados educativos. A sus reportados déficits de equidad y calidad, se discute su efecto profundizador de la individualización. Prácticas antes emplazadas en el mundo de la vida o en la política ahora son colonizadas mercantilmente, articulando la experiencia de vida como continuo individual de elección de mercado y rendimiento alienado. Se experimenta el mercado educativo como constricción de libertad, lo que se suma a la inequidad y la baja calidad promedio documentada

Inhibition of Melanogenesis by the Pyridinyl Imidazole Class of Compounds: Possible Involvement of the Wnt/β-Catenin Signaling Pathway

While investigating the role of p38 MAPK in regulating melanogenesis, we found that pyridinyl imidazole inhibitors class compounds as well as the analog compound SB202474, which does not inhibit p38 MAPK, suppressed both α-MSH-induced melanogenesis and spontaneous melanin synthesis. In this study, we demonstrated that the inhibitory activity of the pyridinyl imidazoles correlates with inhibition of the canonical Wnt/β-catenin pathway activity. Imidazole-treated cells showed a reduction in the level of Tcf/Lef target genes involved in the β-catenin signaling network, including ubiquitous genes such as Axin2, Lef1, and Wisp1 as well as cell lineage-restricted genes such as microphthalmia-associated transcription factor and dopachrome tautomerase. Although over-expression of the Wnt signaling pathway effector β-catenin slightly restored the melanogenic program, the lack of complete reversion suggested that the imidazoles interfered with β-catenin-dependent transcriptional activity rather than with β-catenin expression. Accordingly, we did not observe any significant change in β-catenin protein expression. The independence of p38 MAPK activity from the repression of Wnt/β-catenin signaling pathway was confirmed by small interfering RNA knockdown of p38 MAPK expression, which by contrast, stimulated β-catenin-driven gene expression. Our data demonstrate that the small molecule pyridinyl imidazoles possess two distinct and opposite mechanisms that modulate β-catenin dependent transcription: a p38 inhibition-dependent effect that stimulates the Wnt pathway by increasing β-catenin protein expression and an off-target mechanism that inhibits the pathway by repressing β-catenin protein functionality. The p38-independent effect seems to be dominant and, at least in B16-F0 cells, results in a strong block of the Wnt/β-catenin signaling pathway

T-cell project: an international, longitudinal, observational study of patients with aggressive peripheral T-cell lymphoma

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of neoplasms that are derived from post-thymic lymphoid cells at different stages of differentiation and with different morphological patterns, phenotypes, and clinical presentations. PTCLs are highly diverse, reflecting the diverse cells from which they can originate and are currently sub-classified using World Health Organization (WHO) 2008 criteria. Peripheral T-Cell Lymphomas account for 5%-10% of all lymphoproliferative disorders in the Western hemisphere, with an overall incidence of 0.5-2 per 100,000 individuals per year, and have a striking epidemiological distribution, with higher incidence in Asia. The clinical features of PTCL are extremely heterogeneous. PTCLs express even more clinical diversity than B-cell non-Hodgkin's lymphomas, and there is a close, though not absolute, relationship between some unusual clinical features and certain histological subtypes

Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study

To assess the prognosis of peripheral T-cell lymphoma unspecified, we retrospectively analyzed 385 cases fulfilling the criteria defined by the World Health Organization classification. Factors associated with a worse overall survival (OS) in a univariate analysis were age older than 60 years (P=.0002), equal to or more than 2 extranodal sites (P=.0002), lactic dehydrogenase (LDH) value at normal levels or above (P<.0001), performance status (PS) equal to or more than 2 (Pless than or equal to.0001), stage III or higher (P=.0001), and bone marrow involvement (P=.0001). Multivariate analysis showed that age (relative risk, 1.732; 95% CI, 1.300-2.309; P<.0001), PS (relative risk, 1.719; 95% CI, 1.269-2.327, P<.0001), LDH level (relative risk, 1.905; 95% CI, 1.415-2.564; P<.0001), and bone marrow involvement (relative risk, 1.454; 95% CI, 1.045-2.023; P=.026) were factors independently predictive for survival. Using these 4 variables we constructed a new prognostic model that singled out 4 groups at different risk: group 1, no adverse factors, with 5-year and 10-year OS of 62.3% and 54.9%, respectively; group 2, one factor, with a 5-year and 10-year OS of 52.9% and 38.8%, respectively; group 3, 2 factors, with 5-year and 10-year OS of 32.9% and 18.0%, respectively; group 4,3 or 4 factors, with a 5-year and 10-year OS of 18.3 and 12.6%, respectively (Pless than or equal to.0001; log-rank, 66.79)