Bayesian global-local shrinkage methods for regularisation in the high dimension linear model

This paper reviews global-local prior distributions for Bayesian inference in high-dimensional regression problems including important properties of priors and efficient Markov chain Monte Carlo methods for inference. A chemometric example in drug discovery is used to compare the predictive performance of these methods with popular methods such as Ridge and LASSO regression

Input of particulate organic and dissolved inorganic carbon from the Amazon to the Atlantic Ocean

We report concentrations and isotope measurements (radiocarbon and stable carbon) of dissolved inorganic carbon (DIC) and suspended particulate organic carbon (POC) in waters collected from the mouth of the Amazon River and the North Brazil Current. Samples were collected in November 1991, when the Amazon hydrograph was at its annual minimum and the North Brazil Current had retroflected into the equatorial North Atlantic. The DIC D 14 C results revealed postbomb carbon in river and ocean waters, with slightly higher values at the river mouth. The low DIC delta(13)C signature of the river end-member (-11%) demonstrates that about half of the DIC originated from the remineralization of terrestrially derived organic matter. A linear relationship between DIC and salinity indicates that DIC was mixed nearly conservatively in the transition zone from the river mouth to the open ocean, though there was a small amount (\u3c= 10%) of organic matter remineralization in the mesohaline region. The POC Delta(14)C values in the river mouth were markedly lower than those values from the western Amazon region (Hedges et al., 1986). We conclude that the dominant source of POC near the river mouth and in the inner Amazon plume during November 1991 was aged, resuspended material of significant terrestrial character derived from shelf sediments, while the outer plume contained mainly marine-derived POC

Generation of Mycophenolate Mofetil Resistant Lymphocytes for Adoptive Immunotherapy

Background Adoptive transfer of cells targeting viral infection or tumour following allogeneic transplantation is hindered by the requirement for immunosuppression. Reports of engineered resistance to calcineurin inhibitors have highlighted the potential of conferring immunosuppressive resistance in this setting. A commonly used immunosuppressant, mycophenolate mofetil (MMF) is a non-competitive inhibitor of inosine-5’-monophosphate dehydrogenase (IMPDH). I used T cells transduced with mutated IMPDH that confers >2000-fold resistance to MMF (IMPDH2R; T333I, S351Y). Methods IMPDH2R and IMPDH2 with a catalytic site mutation (IMPDH2CS; C331A) were cloned into retroviral vectors as fusions to eGFP reporter sequences. T cells were transduced with either vector, transferred to recipient mice and evaluated in the presence or absence of MMF. Results A selective advantage for IMPDH2R was demonstrated using a 1:1 mix of CD8 T cells transduced with IMPDH2R and IMPDH2CS. These were injected into recipients distinguishable from the transferred cells using congenic markers. Transferred cells were stimulated by cognate peptide and MMF (0- 200mg/kg/day) was given daily. Selection of IMPDH2R transduced cells occurred following stimulation even without drug (Mann-Whitney Ratio IMPDH2R:IMPDH2CS p=0.0356). MMF administered significantly increased selection (Mann-Whitney MMF 0 v 200 p=0.0365). To assess function, irradiated mice were injected with EL4.OVA tumour cells subcutaneously. After 10 days, either MMF or vehicle treatment was initiated and OT1 CD8 T cells transduced with either IMPDH2CS or IMPDH2R transferred. The combination of MMF and IMPDH2R transduced cells resulted in significantly improved survival over vehicle treated mice (log rank p<0.0001) with significantly smaller tumours at day 26 (Mann-Whitney p<0.0001). This effect was due to direct synergistic effects of both MMF and transferred T cells against tumour cells. Conclusions IMPDH2R confers cells with a selective advantage. Synergy with MMF resulted in improved tumour survival. In patients requiring on-going immunosuppression during adoptive immunotherapy, this combination has great therapeutic potential

Penetration of anthropogenic carbon into organic particles of the deep ocean

] In the late 1980s, bomb C-14 was present in suspended particulate organic carbon (POC) from the North Central Pacific (NCP) and Sargasso Sea ( SS) throughout most of the water column, demonstrating that deep POC had exchanged with atmospheric CO2 in the past 30 years. Upon reoccupation of these sites in 1999 and 2000, respectively, we observed that the delta(13)C values of suspended POC were lower than those measured a decade earlier. This demonstrates that anthropogenic CO2 from fossil fuel and biomass burning has penetrated a major organic matter pool in the deep ocean. Delta(14)C measured in the suspended POC showed similar or higher values in the deep Sargasso Sea and decreased values in the deep NCP compared to those measured previously. We use a box model to show that the differences in the radiocarbon results are likely due to the presence of resuspended sediment that is laterally advected from the continental margin to the deep Sargasso Sea

On efficient Bayesian inference for models with stochastic volatility

An efficient method for Bayesian inference in stochastic volatility models uses a linear state space representation to define a Gibbs sampler in which the volatilities are jointly updated. This method involves the choice of an offset parameter and we illustrate how its choice can have an important effect on the posterior inference. A Metropolis–Hastings algorithm is developed to robustify this approach to choice of the offset parameter. The method is illustrated on simulated data with known parameters, the daily log returns of the Eurostoxx index and a Bayesian vector autoregressive model with stochastic volatility

Compound random measures and their use in Bayesian non‐parametrics

A new class of dependent random measures which we call compound random measures is proposed and the use of normalized versions of these random measures as priors in Bayesian non‐parametric mixture models is considered. Their tractability allows the properties of both compound random measures and normalized compound random measures to be derived. In particular, we show how compound random measures can be constructed with gamma, σ‐stable and generalized gamma process marginals. We also derive several forms of the Laplace exponent and characterize dependence through both the Lévy copula and the correlation function. An augmented Pólya urn scheme sampler and a slice sampler are described for posterior inference when a normalized compound random measure is used as the mixing measure in a non‐parametric mixture model and a data example is discussed

Temporal variability of Delta C-14, delta C-13, and C/N in sinking particulate organic matter at a deep time series station in the northeast Pacific Ocean

A 6-year time series of Delta(14) C, delta(13) C, and C/N measurements in deep sinking particulate organic matter ( POM) is presented for an abyssal site, Station M in the northeast Pacific Ocean. The Delta(14)C values revealed that sinking POM at 3450 m depth ( 650 m above bottom) contained old carbon despite its presumed short transit time in the water column. The isotopic and chemical properties of the sinking POM varied with time and appear to be controlled by more than one major process. In 1993, 1994, and late 1996, isotopic signatures and C/N molar ratios indicate negligible or vertically homogeneous influence of resuspended particles from the bottom or particles laterally transported from the margin to the study site. However, during early 1995 and 1998, Delta(14)C values were lower than those during other periods and C/N values at three deep depths were not equal, indicating that the study site was influenced by resuspended sediments more severely than during other periods. During mid-1995 to mid-1996, delta(13)C values decreased abruptly while Delta(14)C values increased slightly, and C/N values were extremely high ( up to -80) at 50 and 600 m above bottom; these results suggest input of degraded, modern, terrestrial organic matter. The periods of anomalous isotopic signatures, as well as vertically heterogeneous C/N values [ Smith et al., 2001], were correlated with high discharge periods of California rivers with a time lag of 2 to 4 months. The correlation suggests that regional meteorological events are important in controlling the biogeochemical properties of particles at Station M by varying the intensity of resuspension and transport of organic matter from the continental margin

An evaluation of dexterity and cutaneous sensibility tests for use with medical gloves

© 2015 Institution of Mechanical Engineers.The ability of selected dexterity and cutaneous sensibility tests to measure the effect of medical glove properties (material, fit, and number of layers) on manual performance was analyzed. Manual performance testing of gloves to-date has focused on thicker gloves where the effects are more obvious. However, clinicians have reported dissatisfaction with some medical gloves and a perceived detriment to performance of new materials compared to latex. Three tests (Purdue Pegboard Test, Crawford Small Parts Dexterity Test, and Semmes-Weinstein Monofilaments) were performed by 18 subjects in five hand conditions (ungloved; best-fitting, loose-fitting and a double layer of latex examination gloves; best-fitting vinyl gloves). Tests were performed in the ungloved condition first, and the order of the gloved tests was randomized. Learning behavior was also measured. The Purdue test showed a significant effect of hand condition, but no differences between latex and vinyl. No significant effect of hand condition was found in the Crawford "Pins and Collars" test, but the "Screws" test showed promising discrimination between glove types. The Monofilaments test showed a significant effect of hand condition on cutaneous sensibility, particularly a reduction when "double-gloving," but no significant differences between glove types. Existing tests show some ability to measure the effect of gloves and their properties on manual performance but are not comprehensive and require further validation. In order to fully describe the effects of medical gloves on manual performance, further tests should be designed with greater resolution and that better replicate clinical manual tasks