Plasma Volume Hematocrit (PVH): “Big Data” Applied to Physiology Enabled by a New Algorithm

This work describes the ongoing analysis of blood noninvasively in vivo along with the in vitro validation of the algorithm. The blood is taken as two components, red blood cells and plasma, both of which cause elastic emission (from Mie and Rayleigh scattering) and inelastic emission (from fluorescence and Raman emission). The algorithm describes the linear dependence of the volume fractions of both red blood cells and plasma with both the elastic and inelastic emissions where the two equations are independent. These equations are used to calculate the Hematocrit which is defined as the volume fraction of red blood cells in the total volume of blood. We believe that monitoring changes in the Hematocrit with sufficient sensitivity could give information about many physiological parameters including an early indication for internal hemorrhaging. The stability of the baseline was analyzed in 10 test subjects across 29 experiments including over 8 million frames of data to give the smallest physiological increment of ±0.033 Hematocrit units. Compared to the medical standard blood draw method, with a standard deviation of ±2.0 Hematocrit units, our device is 60 times more sensitive to changes in the Hematocrit. Repeating patterns in the Hematocrit can be analyzed by a Fourier transform to give respiration rate and pulse rate earning the title of “big data.” Changes in the Hematocrit were also observed in dialysis patients (where the blood is manually cleaned due to kidney failure) and in a rat model where large portions of the blood can be removed and reintroduced. Blood loss and addition of fluid reveal changes in the Hematocrit that are distinguishable from the baseline. The algorithm was validated by a well-defined in vitro system modeling the blood components. The model demonstrates that an optically thin sample in the linear range produces a good fit by the algorithm. Finally, the blood was analyzed in vitro to demonstrate that the red blood cells and plasma show linearity within the physiological ranges observed in vivo. At 830 nm excitation, the same wavelength used in vivo, volume fractions of red blood cells and plasma at the physiological range demonstrate linearity. All of the experiments and analysis appear to give evidence supporting the measuring of changes in the Hematocrit noninvasively in vivo on a medically useful timescale

Gender differences in coping strategies of undergraduate students and their impact on self-esteem and attainment

This study sought to investigate differences in the coping strategies adopted by male and female first year students in a higher education environment and the extent to which such strategies had an impact on self-esteem and attainment. Results revealed significant differences between males and females in terms of engagement in coping strategies and academic attainment. Specifically, males exhibited greater ability to detach themselves from the emotions of a situation, were more inclined to demonstrate emotional inhibition or ‘bottling up’ of emotions and reported higher self-esteem. In addition, it was observed that females attained at a significantly higher level than males. Practical implications and recommendations for future research are identified

New sub-millimeter limits on dust in the 55 Cancri planetary system

We present new, high-sensitivity sub-millimeter observations towards 55 Cancri, a nearby G8 star with one, or possibly two, known planetary companion(s). Our 850 $\mu$m map, obtained with the SCUBA instrument on the James Clerk Maxwell Telescope, shows three peaks of emission at the 2.5 mJy level in the vicinity of the star's position. However, the observed peaks are 25\arcsec--40\arcsec away from the star and a deep $R$-band optical image reveals faint point sources that coincide with two of the sub-millimeter peaks. Thus, we do not find evidence for dust emission spatially associated with 55 Cancri. The excess 60 $\mu$m emission detected with ISO may originate from one or more of the 850 $\mu$m peaks that we attribute to background sources. Our new results, together with the HST/NICMOS coronographic images in the near-infrared, place stringent limits on the amount of dust in this planetary system, and argue against the existence of a detectable circumstellar dust disk around 55 Cnc.Comment: 11 pages, 2 PostScript figures, to appear in The Astrophysical Journal Letter

Blip glitches in Advanced LIGO data

Blip glitches are short noise transients present in data from ground-based gravitational-wave observatories. These glitches resemble the gravitational-wave signature of massive binary black hole mergers. Hence, the sensitivity of transient gravitational-wave searches to such high-mass systems and other potential short duration sources is degraded by the presence of blip glitches. The origin and rate of occurrence of this type of glitch have been largely unknown. In this paper we explore the population of blip glitches in Advanced LIGO during its first and second observing runs. On average, we find that Advanced LIGO data contains approximately two blip glitches per hour of data. We identify four subsets of blip glitches correlated with detector auxiliary or environmental sensor channels, however the physical causes of the majority of blips remain unclear

Inflammatory (B) symptoms are independent predictors of myelosuppression from chemotherapy in Non-Hodgkin Lymphoma (NHL) patients – analysis of data from a British National Lymphoma Investigation phase III trial comparing CHOP to PMitCEBO

<p>Abstract</p> <p>Background</p> <p>Toxicity from chemotherapy is highly variable, unpredictable and results in substantial morbidity and increased healthcare costs. New predictors of toxicity are required to improve the safety and efficacy of chemotherapy. Inflammatory or B symptoms in lymphoma are associated with elevated plasma inflammatory markers and predict worse treatment response and survival. Recent data suggest that systemic inflammation results in reduced hepatic drug metabolism and increased toxicity from chemotherapy. We investigated whether B symptoms were associated with greater toxicity in patients treated for non-Hodgkin lymphoma (NHL).</p> <p>Methods</p> <p>The British National Lymphoma Investigation compared two chemotherapy regimens in older patients with aggressive NHL. Approximately 50% of patients had B symptoms. Demographic and toxicity data on 664 patients were analysed to identify predictors of toxicity by multivariate analysis, with particular reference to B symptoms.</p> <p>Results</p> <p>Using univariate analyses, severe (grades 3–4) leucopenia, anaemia, thrombocytopenia, nausea and vomiting and diarrhoea occurred more frequently in patients with B symptoms. The associations between B symptoms and severe leucopenia (OR 1.7, p = 0.005) and anaemia (OR 2.3, p = 0.025) persisted after adjustment for other prognostic factors in multivariate analyses. The use of granulocyte colony stimulating factor reduced neutropenia in patients with both A and B symptoms.</p> <p>Conclusion</p> <p>For the first time and in a large NHL cohort we have shown that inflammatory symptoms are independent predictors for myelosuppression from chemotherapy. These data will enable improved prognostication for toxicity and provide individualisation of therapy in NHL and other tumours. These findings also create the potential for strategies used prior to chemotherapy aimed at reducing systemic inflammation in order to improve drug metabolism and reduce treatment-related toxicity.</p> <p>Trial registration number</p> <p>ISRCTN98741793</p

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) promotes mitochondrial dysfunction and apoptosis induced by 7hydroxystaurosporine and mitogen-activated protein kinase kinase inhibitors in human leukemia cells that ectopically express Bcl-2

ABSTRACT Previous studies have demonstrated that cotreatment with mitogen activated-protein kinase kinase (MEK) 1/2 inhibitors (e.g., PD184352) and the checkpoint abrogator 7-hydroxystaurosporine (UCN-01) dramatically induces apoptosis in a variety of human leukemia and multiple myeloma cell types. The purpose of this study was to evaluate the roles of Bcl-2 family members and the relative contribution of the intrinsic mitochondrial versus the extrinsic receptor-related apoptotic pathways to MEK inhibitors/UCN-01-induced leukemic cell death. Cotreatment of U937 cells with PD184352 and UCN-01 resulted in the activation of procaspase-3, -9, and -8 as well as Bid cleavage

α-Adrenergic inhibition of proliferation in HepG2 cells stably transfected with the α1B-adrenergic receptor through a p42MAP kinase/p21Cip1/WAF1-dependent pathway

AbstractActivation of α1B adrenergic receptors (α1BAR) promotes DNA synthesis in primary cultures of hepatocytes, yet expression of α1BAR in hepatocytes rapidly declines during proliferative events. HepG2 human hepatoma cells, which do not express α1BAR, were stably transfected with a rat α1BAR cDNA (TFG2 cells), in order to study the effects of maintained α1BAR expression on hepatoma cell proliferation. TFG2 cells had a decreased rate of growth compared to mock transfected HepG2 cells as revealed by a decrease in [3H]thymidine incorporation into DNA. Stimulation of α1BAR with phenylephrine caused a further large reduction in TFG2 cell growth, whereas no effect on growth was observed in mock transfected cells. Reduced cell growth correlated with increased percentages of cells found in G0/G1 and G2/M phases of the cell cycle. In TFG2 cells, phenylephrine increased p42MAP kinase activity by 1.5- to 2.0-fold for up to 24 h and increased expression of the cyclin dependent kinase inhibitor protein p21Cip1/WAF1. Treatment of TFG2 cells with the specific MEK1 inhibitor PD98059, or infection with a −/− MEK1 recombinant adenovirus permitted phenylephrine to increase rather than decrease [3H]thymidine incorporation. In addition, inhibition of MAP kinase signaling by PD98059 or MEK1 −/− blunted the ability of phenylephrine to increase p21Cip1/WAF1 expression. In agreement with a role for increased p21Cip1/WAF1 expression in causing growth arrest, infection of TFG2 cells with a recombinant adenovirus to express antisense p21Cip1/WAF1 mRNA blocked the ability of phenylephrine to increase p21Cip1/WAF1 expression and to inhibit DNA synthesis. Antisense p21Cip1/WAF1 permitted phenylephrine to stimulate DNA synthesis in TFG2 cells, and abrogated growth arrest. These results suggest that transformed hepatocytes may turn off the expression of α1BARs in order to prevent the activation of a growth inhibitory pathway. Activation of this inhibitory pathway via α1BAR appears to be p42MAP kinase and p21Cip1/WAF1 dependent

Sequence dependent exposure of mammary carcinoma cells to Taxotere® and the MEK1/2 inhibitor U0126 causes enhanced cell killing in vitro

Taxol (paclitaxel) and Taxotere (docetaxel) are considered as two of the most important anticancer chemotherapy drugs. The cytotoxic action of these drugs has been linked to their ability to inhibit microtubule depolymerization, causing growth arrest and subsequent cell death. Studies by a number of laboratories have also linked suppression of mitogen activated protein kinase (MAPK) signaling to enhanced Taxol toxicity. The present study examined the interactions of the semi-synthetic taxane Taxotere with MEK1/2 inhibitors in epithelial tumor cells. Concurrent treatment of MDA-MB-231 mammary and DU145 prostate carcinoma cells with Taxotere and MEK1/2 inhibitor resulted in protection from the anti-proliferative effects of Taxotere in MTT assays. In contrast, in MCF-7 mammary cells, concurrent Taxotere and MEK1/2 inhibitor treatment weakly enhanced the antiproliferative effects of the taxane. Sequential treatment of MDA-MB-231 and MCF-7 cells with Taxotere followed by MEK1/2 inhibitor also enhanced the anti-proliferative effects of the taxane in MTT assays. However, no enhancement was observed in DU145 or PC-3 cells. Colony formation assays, including isobologram analyses, provided a more definitive demonstration that MCF-7 and MDA-MB-231 cells were sensitized to the toxic effects of Taxotere by U0126. Similar data were observed using Laulimalide, which binds to tubulin at a different site to Taxotere. The enhancement in Taxotere anti-proliferative effects by U0126 correlated with increased cell killing, 48-72h after treatment of cells that was blocked by inhibition of caspase 9, but not caspase 8, function. This observation was associated with prolonged suppression of ERK1/2 and AKT activity, without alteration in either p38 or JNK1/2 activity. Collectively these findings demonstrate that sequential administration of Taxotere followed by MEK1/2 inhibition can lead to increased cell death and loss of reproductive capacity in some, but not all, human tumor cells. ©2003 Landes Bioscience.Fil: Yacoub, Adly. Virginia Commonwealth University; Estados UnidosFil: Han, Song Iy. Virginia Commonwealth University; Estados UnidosFil: Caron, Ruben Walter. Virginia Commonwealth University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Gilfor, Donna. Virginia Commonwealth University; Estados UnidosFil: Mooberry, Susan. Southwest Foundation for Biomedical Research; Estados UnidosFil: Grant, Steven. Virginia Commonwealth University; Estados UnidosFil: Dent, Paul. Virginia Commonwealth University; Estados Unido

Bat use of commercial coniferous plantations at multiple spatial scales: Management and conservation implications

Commercial plantations are primarily managed for timber production, and are frequently considered poor for biodiversity, particularly for mammalian species. Bats, which constitute one fifth of mammal species worldwide, have undergone large declines throughout Europe, most likely due to widespread habitat loss and degradation. Bat use of modified landscapes such as urban or agricultural environments has been relatively well studied, however, intensively managed plantations have received less attention, particularly in Europe. We assessed three of the largest, most intensively managed plantations in the UK for the occurrence of bats, activity levels and relative abundance in response to environmental characteristics at multiple spatial scales, using an information theoretic approach. We recorded or captured nine species;Pipistrellus pipistrellusandP.pygmaeuswere the most commonly recorded species on acoustic detectors and femaleP.pygmaeuswere the most commonly captured. The influence of environmental characteristics on bat activity varied by species or genus, although all bat species avoided dense stands. Occurrence and activity of clutter and edge adapted species were associated with lower stand densities and more heterogeneous landscapes whereas open adapted bats were more likely to be recorded at felled stands and less likely in areas that were predominantly mature conifer woodland. In addition, despite morphological similarities,P.pipstrellusandP.pygmaeuswere found foraging in different parts of the plantation. This study demonstrates that with sympathetic management, non-native conifer plantations may have an important role in maintaining and supporting bat populations, particularly forPipistrellusspp