Deep and abyssal ocean warming from 35 years of repeat hydrography

Global and regional ocean warming deeper than 2000 m is investigated using 35 years of sustained repeat hydrographic survey data starting in 1981. The global long-term temperature trend below 2000 m, representing the time period 1991–2010, is equivalent to a mean heat flux of 0.065 ± 0.040 W m?2 applied over the Earth's surface area. The strongest warming rates are found in the abyssal layer (4000–6000 m), which contributes to one third of the total heat uptake with the largest contribution from the Southern and Pacific Oceans. A similar regional pattern is found in the deep layer (2000–4000 m), which explains the remaining two thirds of the total heat uptake yet with larger uncertainties. The global average warming rate did not change within uncertainties pre-2000 versus post-2000, whereas ocean average warming rates decreased in the Pacific and Indian Oceans and increased in the Atlantic and Southern Oceans

Impact of febrile neutropenia on R-CHOP chemotherapy delivery and hospitalizations among patients with diffuse large B-cell lymphoma

PURPOSE: This analysis from an observational study of clinical practice describes the impact of febrile neutropenia (FN) on chemotherapy delivery and hospitalizations. METHODS: Adults with diffuse large B-cell lymphoma (DLBCL) scheduled to receive ≥3 cycles of 2- or 3-weekly CHOP with rituximab (R-CHOP-14/21) were eligible. Primary outcome was incidence of FN. RESULTS:FN data were available for 409 patients receiving R-CHOP-14 and 702 patients receiving R-CHOP-21. FN incidence was R-CHOP-14, 20% (81/409) and R-CHOP-21, 19% (133/702). Rates of primary prophylaxis with granulocyte-colony stimulating factor were R-CHOP-14, 84% (345/409) and R-CHOP-21, 36% (252/702). A large number of patients experienced their first FN episode in cycle 1 (R-CHOP-14, 24/81 [30%]; R-CHOP-21, 63/133 [47%]). Multiple risk factors (≥2) for FN were more frequent in patients experiencing FN than in patients not experiencing FN (R-CHOP-14, 60/81 [74%] versus 179/328 [55%]; R-CHOP-21, 98/133 [74%] versus 339/569 [60%]). A similar trend was observed for unplanned hospitalizations (R-CHOP-14, 63/81 [78%] versus 68/328 [21%]; R-CHOP-21, 105/133 [79%] versus 100/569 [18%]). Achievement of chemotherapy relative dose intensity ≥90% was lower among patients experiencing FN than in patients not experiencing FN (R-CHOP-14, 30/81 [37%] versus 234/328 [71%]; R-CHOP-21, 83/133 [62%] versus 434/569 [76%]). CONCLUSIONS:In patients with DLBCL treated with R-CHOP-14 or R-CHOP-21, patients with an event of FN were more likely to experience suboptimal chemotherapy delivery and increased incidence of unplanned hospitalizations than those without FN. FN-related hospitalizations are likely to impact chemotherapy delivery and to incur substantial costs

New exactly solvable systems with Fock symmetry

New superintegrable systems are presented which, like the Hydrogen atom, possess a dynamical symmetry w.r.t. algebra o(4). One of them simulates a neutral fermion with non-trivial dipole moment, interacting with the external e.m. field. This system is presented in both non-relativistic and relativistic formulations. Another recently discovered system (see arXiv:1208.2886v1) is non-relativistic and includes the minimal and spin-orbit interaction with the external electric field. It is shown that all the considered systems are shape invariant. Applying this quality, these systems are integrated using the tools of SUSY quantum mechanics.Comment: Section 6 and some new references are adde

Full-depth temperature trends in the Northeastern Atlantic through the early 21st century

The vertical structure of temperature trends in the northeastern Atlantic (NEA) is investigated from a blend of Argo and hydrography data. The representativeness of sparse hydrography sampling in the basin-mean is assessed using a numerical model. Between 2003 and 2013, the NEA underwent a strong surface cooling (0-450?m) and a significant warming at intermediate and deep levels (1000?m-3000?m) that followed a strong cooling trend observed between 1988 and 2003. During 2003-2013, gyre-specific changes are found in the upper 1000?m (warming and cooling of the subtropical and subpolar gyres, respectively) whilst the intermediate and deep warming primarily occurred in the subpolar gyre, with important contributions from isopycnal heave and water mass property changes. The full-depth temperature change requires a local downward heat flux of 0.53?±?0.06?W?m?2 through the sea-surface, and its vertical distribution highlights the likely important role of the NEA in the recent global warming hiatus

A review of global ocean temperature observations: Implications for ocean heat content estimates and climate change

The evolution of ocean temperature measurement systems is presented with a focus on the development and accuracy of two critical devices in use today (expendable bathythermographs and conductivity‐temperature‐depth instruments used on Argo floats). A detailed discussion of the accuracy of these devices and a projection of the future of ocean temperature measurements are provided. The accuracy of ocean temperature measurements is discussed in detail in the context of ocean heat content, Earth's energy imbalance, and thermosteric sea level rise. Up‐to‐date estimates are provided for these three important quantities. The total energy imbalance at the top of atmosphere is best assessed by taking an inventory of changes in energy storage. The main storage is in the ocean, the latest values of which are presented. Furthermore, despite differences in measurement methods and analysis techniques, multiple studies show that there has been a multidecadal increase in the heat content of both the upper and deep ocean regions, which reflects the impact of anthropogenic warming. With respect to sea level rise, mutually reinforcing information from tide gauges and radar altimetry shows that presently, sea level is rising at approximately 3 mm yr−1 with contributions from both thermal expansion and mass accumulation from ice melt. The latest data for thermal expansion sea level rise are included here and analyzed

Research Directions in the Clinical Implementation of Pharmacogenomics: An Overview of US Programs and Projects

Response to a drug often differs widely among individual patients. This variability is frequently observed not only with respect to effective responses but also with adverse drug reactions. Matching patients to the drugs that are most likely to be effective and least likely to cause harm is the goal of effective therapeutics. Pharmacogenomics (PGx) holds the promise of precision medicine through elucidating the genetic determinants responsible for pharmacological outcomes and using them to guide drug selection and dosing. Here we survey the US landscape of research programs in PGx implementation, review current advances and clinical applications of PGx, summarize the obstacles that have hindered PGx implementation, and identify the critical knowledge gaps and possible studies needed to help to address them

Induction of Blood Brain Barrier Tight Junction Protein Alterations by CD8 T Cells

Disruption of the blood brain barrier (BBB) is a hallmark feature of immune-mediated neurological disorders as diverse as viral hemorrhagic fevers, cerebral malaria and acute hemorrhagic leukoencephalitis. Although current models hypothesize that immune cells promote vascular permeability in human disease, the role CD8 T cells play in BBB breakdown remains poorly defined. Our laboratory has developed a novel murine model of CD8 T cell mediated central nervous system (CNS) vascular permeability using a variation of the Theiler's virus model of multiple sclerosis. In previous studies, we observed that MHC class II−/− (CD4 T cell deficient), IFN-γR−/−, TNF-α−/−, TNFR1−/−, TNFR2−/−, and TNFR1/TNFR2 double knockout mice as well as those with inhibition of IL-1 and LTβ activity were susceptible to CNS vascular permeability. Therefore, the objective of this study was to determine the extent immune effector proteins utilized by CD8 T cells, perforin and FasL, contributed to CNS vascular permeability. Using techniques such as fluorescent activated cell sorting (FACS), T1 gadolinium-enhanced magnetic resonance imaging (MRI), FITC-albumin leakage assays, microvessel isolation, western blotting and immunofluorescent microscopy, we show that in vivo stimulation of CNS infiltrating antigen-specific CD8 T cells initiates astrocyte activation, alteration of BBB tight junction proteins and increased CNS vascular permeability in a non-apoptotic manner. Using the aforementioned techniques, we found that despite having similar expansion of CD8 T cells in the brain as wildtype and Fas Ligand deficient animals, perforin deficient mice were resistant to tight junction alterations and CNS vascular permeability. To our knowledge, this study is the first to demonstrate that CNS infiltrating antigen-specific CD8 T cells have the capacity to initiate BBB tight junction disruption through a non-apoptotic perforin dependent mechanism and our model is one of few that are useful for studies in this field. These novel findings are highly relevant to the development of therapies designed to control immune mediated CNS vascular permeability

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Can Survival Prediction Be Improved By Merging Gene Expression Data Sets?

BACKGROUND:High-throughput gene expression profiling technologies generating a wealth of data, are increasingly used for characterization of tumor biopsies for clinical trials. By applying machine learning algorithms to such clinically documented data sets, one hopes to improve tumor diagnosis, prognosis, as well as prediction of treatment response. However, the limited number of patients enrolled in a single trial study limits the power of machine learning approaches due to over-fitting. One could partially overcome this limitation by merging data from different studies. Nevertheless, such data sets differ from each other with regard to technical biases, patient selection criteria and follow-up treatment. It is therefore not clear at all whether the advantage of increased sample size outweighs the disadvantage of higher heterogeneity of merged data sets. Here, we present a systematic study to answer this question specifically for breast cancer data sets. We use survival prediction based on Cox regression as an assay to measure the added value of merged data sets. RESULTS:Using time-dependent Receiver Operating Characteristic-Area Under the Curve (ROC-AUC) and hazard ratio as performance measures, we see in overall no significant improvement or deterioration of survival prediction with merged data sets as compared to individual data sets. This apparently was due to the fact that a few genes with strong prognostic power were not available on all microarray platforms and thus were not retained in the merged data sets. Surprisingly, we found that the overall best performance was achieved with a single-gene predictor consisting of CYB5D1. CONCLUSIONS:Merging did not deteriorate performance on average despite (a) The diversity of microarray platforms used. (b) The heterogeneity of patients cohorts. (c) The heterogeneity of breast cancer disease. (d) Substantial variation of time to death or relapse. (e) The reduced number of genes in the merged data sets. Predictors derived from the merged data sets were more robust, consistent and reproducible across microarray platforms. Moreover, merging data sets from different studies helps to better understand the biases of individual studies and can lead to the identification of strong survival factors like CYB5D1 expression