Investigation of mediastinitis due to coagulase-negative staphylococci after cardiothoracic surgery.

Six cases of coagulase-negative staphylococcal mediastinitis were identified in the latter half of 1999. A new preoperative cleansing solution was suspected by hospital staff to be a factor in the outbreak. We evaluated this possible risk factor along with other known and suspected surgical site infection risk factors in this case-control study

A Typology of Responsibility for Coastal Flood Risk Adaptation

The management of coastal flood risk is adapting to meet the challenges and increased risks posed by population change as well as by climate change, especially sea level rise. Protection is being targeted to areas where the benefits are highest, while elsewhere there is a shift towards more localized “living with floods” and “resilience” approaches. Such decentralized approaches to flood risk management (FRM) require a diverse range of stakeholder groups to be engaged as “flood risk citizens”. Engagement of households in FRM is central to this process. Despite significant research on stakeholder engagement in coastal and flood risk management, there is less focus on the nature of responsibility in coastal adaptation. There is no framework by which to assess the different types of responsibility in hazard management and adaptation, and little research on the implications of expecting these responsibilities of stakeholder groups. In this paper, we identify five types of responsibility that are embedded throughout the disaster risk reduction cycle of managing coastal flooding. We build this ”typology of responsibility” on existing work on the evolution of stakeholder engagement and stakeholder responsibility relationships in risk management processes, and a dataset of institutional stakeholder interviews and households surveys conducted across three case studies in England, the United Kingdom, in 2018 and 2019. We analyze the interviews using thematic analysis to explore institutional stakeholder perceptions of responsibility in coastal FRM, and analyze the household survey through descriptive and inferential statistics. By developing the first disaster risk reduction focused typology of responsibility for coastal flooding, we provide researchers and decision-makers with a tool to guide their planning and allocation of responsibilities in risk management for floods and other climate-driven hazards

Warehouse design and planning: A mathematical programming approach

The dynamic nature of today's competitive markets compels organizations to an incessant reassessment in an effort to respond to continuous challenges. Therefore, warehouses as an important link in most supply chains, must be continually re-evaluated to ensure that they are consistent with both market's demands and management's strategies. A number of warehouse decision support models have been proposed in the literature but considerable difficulties in applying these models still remain, due to the large amount of information to be processed and to the large number of possible alternatives. In this paper we discuss a mathematical programming model aiming to support some warehouse management and inventory decisions. In particular a large mixed-integer nonlinear programming model (MINLP) is presented to capture the trade-offs among the different inventory and warehouse costs in order to achieve global optimal design satisfying throughput requirements.(undefined)info:eu-repo/semantics/publishedVersio

Piperlongumine inhibits LMP1/MYC-dependent mouse B-lymphoma cells

AbstractPiperlongumine (PL), isolated from the fruit of Long pepper, Piper longum, is a cancer-inhibiting compound that selectively kills tumor cells while sparing their normal counterparts. Here we evaluated the efficacy with which PL suppresses malignant B cells derived from a newly developed, double-transgenic mouse model of human endemic Burkitt lymphoma (BL), designated mCD40-LMP1/iMycEμ. PL inhibited tumor cell proliferation in a concentration-dependent manner and induced apoptosis of neoplastic but not normal B cells. Treatment with PL resulted in downregulation of EBV-encoded LMP1, cellular Myc, constitutive NF-κB activity, and a host of LMP1-Myc-NF-κB-regulated target genes including Aurka, Bcat1, Bub1b, Ccnb1, Chek1, Fancd2, Tfrc and Xrcc6. Of note, p21Cip1-encoding Cdkn1a was suppressed independent of changes in Trp53 mRNA levels and p53 DNA-binding activity. Considering the central role of the LMP1–NF-κB–Myc axis in B-lineage neoplasia, these findings further our understanding of the mechanisms by which PL inhibits B-lymphoma and provide a preclinical rationale for the inclusion of PL in new interventions in blood cancers

NF-κB/STAT3/PI3K signaling crosstalk in iMycEμ B lymphoma

<p>Abstract</p> <p>Background</p> <p>Myc is a well known driver of lymphomagenesis, and Myc-activating chromosomal translocation is the recognized hallmark of Burkitt lymphoma, an aggressive form of non-Hodgkin's lymphoma. We developed a model that mimics this translocation event by inserting a mouse <it>Myc </it>cDNA gene into the immunoglobulin heavy chain locus, just upstream of the intronic Eμ enhancer. These mice, designated iMyc^Eμ, readily develop B-cell lymphoma. To study the mechanism of Myc-induced lymphoma, we analyzed signaling pathways in lymphoblastic B-cell lymphomas (LBLs) from iMyc^Eμmice, and an LBL-derived cell line, iMyc^Eμ-1.</p> <p>Results</p> <p>Nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) were constitutively activated in iMyc^Eμmice, not only in LBLs but also in the splenic B-lymphocytes of young animals months before tumors developed. Moreover, inhibition of either transcription factor in iMyc^Eμ-1 cells suppressed growth and caused apoptosis, and the abrogation of NF-κB activity reduced DNA binding by both STAT3 and Myc, as well as Myc expression. Inhibition of STAT3 signaling eliminated the activity of both NF-κB and Myc, and resulted in a corresponding decrease in the level of Myc. Thus, in iMyc^Eμ-1 cells NF-κB and STAT3 are co-dependent and can both regulate Myc. Consistent with this, NF-κB and phosphorylated STAT3 were physically associated with one another. In addition, LBLs and iMyc^Eμ-1 cells also showed constitutive AKT phosphorylation. Blocking AKT activation by inhibiting PI3K reduced iMyc^Eμ-1 cell proliferation and caused apoptosis, via downregulation of NF-κB and STAT3 activity and a reduction of Myc levels. Co-treatment with NF-κB, STAT3 or/and PI3K inhibitors led to additive inhibition of iMyc^Eμ-1 cell proliferation, suggesting that these signaling pathways converge.</p> <p>Conclusions</p> <p>Our findings support the notion that constitutive activation of NF-κB and STAT3 depends on upstream signaling through PI3K, and that this activation is important for cell survival and proliferation, as well as for maintaining the level of Myc. Together, these data implicate crosstalk among NF-κB, STAT3 and PI3K in the development of iMyc^EμB-cell lymphomas.</p

Trimodal cloudiness and tropical stable layers in simulations of radiative convective equilibrium

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95176/1/grl24304.pd

Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial

Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. Methods Open label randomised controlled trial in NHS Primary Care (General Practices), Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. Results Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35–0.96, p = 0.065). A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33–3.21, p = 0.028). People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96–2.52) and six months post detoxification (7 vs 3, RR 1.45 CI 0.84–2.49). Conclusion Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens

Intercomparison of methods of coupling between convection and large-scale circulation: 1. Comparison over uniform surface conditions

As part of an international intercomparison project, a set of single column models (SCMs) and cloud-resolving models (CRMs) are run under the weak temperature gradient (WTG) method and the damped gravity wave (DGW) method. For each model, the implementation of the WTG or DGW method involves a simulated column which is coupled to a reference state defined with profiles obtained from the same model in radiative-convective equilibrium. The simulated column has the same surface conditions as the reference state and is initialized with profiles from the reference state. We performed systematic comparison of the behavior of different models under a consistent implementation of the WTG method and the DGW method and systematic comparison of the WTG and DGW methods in models with different physics and numerics. CRMs and SCMs produce a variety of behaviors under both WTG and DGW methods. Some of the models reproduce the reference state while others sustain a large-scale circulation which results in either substantially lower or higher precipitation compared to the value of the reference state. CRMs show a fairly linear relationship between precipitation and circulation strength. SCMs display a wider range of behaviors than CRMs. Some SCMs under the WTG method produce zero precipitation. Within an individual SCM, a DGW simulation and a corresponding WTG simulation can produce different signed circulation. When initialized with a dry troposphere, DGW simulations always result in a precipitating equilibrium state. The greatest sensitivities to the initial moisture conditions occur for multiple stable equilibria in some WTG simulations, corresponding to either a dry equilibrium state when initialized as dry or a precipitating equilibrium state when initialized as moist. Multiple equilibria are seen in more WTG simulations for higher SST. In some models, the existence of multiple equilibria is sensitive to some parameters in the WTG calculations