Predictors of the Indefinite Duration Anticoagulation Treatment Strategy In Patients with Cancer Associated Thrombosis

Background: In patients with cancer and acute venous thromboembolism (VTE), current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved.Methods and results: Among 1'247 patients with acute VTE enrolled in the Swiss Venous Thromboembolism Registry (SWIVTER) from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, and 83 (26%) tumor surgery within 6 months. Patients with cancer were older (66±14 vs. 60±19 years, p<0.001), more often hospitalized at the time of VTE diagnosis (46% vs. 36%, p=0.001), immobile for >3 days (25% vs. 16%, p<0.001), and more often had thrombocytopenia (6% vs. 1%, p<0.001) than patients without cancer. The 30-day rate of VTE-related death or recurrent VTE was 9% in cancer patients vs. 4% in patients without cancer (p<0.001), and the rates of bleeding requiring medical attention were 5% in both groups (p=0.57). Cancer patients received indefinite-duration anticoagulation treatment more often than patients without cancer (47% vs. 19%, p<0.001), and LMWH mono-therapy during the initial 3 months was prescribed to 45% vs. 8%, p<0.001, respectively. Among patients with cancer, prior VTE (OR 4.0, 95%CI 2.0-8.0), metastatic disease (OR 3.0, 95%CI 1.7-5.2), outpatient status at the time of VTE diagnosis (OR 3.8, 95%CI 1.9-7.6), and inpatient treatment (OR 4.4, 95%CI 2.1-9.2) were independently associated with the prescription of indefinite-duration anticoagulation treatment.Conclusions: Less than half of the cancer patients with acute VTE received a prescription for indefinite-duration anticoagulation treatment. Recurrent VTE, metastatic cancer, outpatient VTE diagnosis, and VTE requiring hospitalization were associated with an increased use of this strategy.

Immunogenicity and safety of an intradermal boosting strategy for vaccination against influenza in lung transplant recipients.

The immunogenicity of influenza vaccine is suboptimal in lung transplant recipients. Use of a booster dose and vaccine delivery by the intradermal rather than intramuscular route may improve response. We prospectively evaluated the immunogenicity and safety of a 2-dose boosting strategy of influenza vaccine. Sixty lung transplant recipients received a standard intramuscular injection of the 2006-2007 inactivated influenza vaccine, followed 4 weeks later by an intradermal booster of the same vaccine. Immunogenicity was assessed by measurement of geometric mean titer of antibodies after both the intramuscular injection and the intradermal booster. Vaccine response was defined as 4-fold or higher increase of antibody titers to at least one vaccine antigen. Thirty-eight out of 60 patients (63%) had a response after intramuscular vaccination. Geometric mean titers increased for all three vaccine antigens following the first dose (p &lt; 0.001). However, no significant increases in titer were observed after the booster dose for all three antigens. Among nonresponders, 3/22 (13.6%) additional patients responded after the intradermal booster (p = 0.14). The use of basiliximab was associated with a positive response (p = 0.024). After a single standard dose of influenza vaccine, a booster dose given by intradermal injection did not significantly improve vaccine immunogenicity in lung transplant recipients.

Iowa Drug Control Strategy, 2013

The Governor’s Office of Drug Policy Control offers the 2013 Drug Control Strategy pursuant to Iowa Code §80E.1. The purpose of the strategy is to describe the activities of the office and other state departments related to drug enforcement, substance abuse treatment and prevention. This report also highlights trends in respect to substance abuse within the state and sets out innovative approaches to reduce drug abuse and its associated damage to society. Finally, the Strategy shows the state funding levels for the various agencies working in this area, as divided among the three areas of emphasis: prevention, treatment and enforcement.

Policy -Strategy Option Description, January 30, 2009

Like many states, Iowa faces significant challenges on the energy front.  Energy prices have  surged in recent years to record levels before declining precipitously following the financial  crisis that broke in September 2008.  Despite this pullback, the fundamentals that contributed to  higher energy prices are expected to return once economies rebound. Oil prices have gone up  on increased demand, driven in large part by developing countries such as China and India,  whose economies have been rapidly expanding.  Natural gas prices have also fluctuated  dramatically, trading in a range from $4.50 to $13.00/MMBtu over the past year, but are unlikely  to remain at low levels over the long term.  As shown in our analysis later on in this report, the  difference in levelized cost of electricity from a gas‐fired combined cycle plant can vary  significantly depending on the fuel cost.    Dependence on others for energy supply involves significant risks and uncertainties.  Thus, if  Iowa wishes to reduce its dependence on others – or even achieve energy independence – Iowa  needs to pursue actions on a numbers of fronts.  Following the status quo is not an option.    A carbon tax would change the energy landscape in Iowa.  Since Iowa is currently 75%  dependent on coal, a carbon tax could mean that generators, and in turn ratepayers, could be on  the hook for higher electricity prices, though it remains to be seen exactly what the tax scheme  will be.  In addition to existing plants, a carbon tax would also have a significant impact on the  cost of new generation plant.  We have modeled carbon taxes ranging from $0‐50/ton in our  analysis in the Appendix.  However, if a more aggressive carbon policy came into play resulting  in market values of for example, $100/ton or even $200/ton, then that could raise the cost of coal‐  and gas‐fired generation significantly, making alternatives such as wind more economical.

Influence of magnetic field strength and image registration strategy on voxel-based morphometry in a study of Alzheimer's disease.

Multi-centre data repositories like the Alzheimer's Disease Neuroimaging Initiative (ADNI) offer a unique research platform, but pose questions concerning comparability of results when using a range of imaging protocols and data processing algorithms. The variability is mainly due to the non-quantitative character of the widely used structural T1-weighted magnetic resonance (MR) images. Although the stability of the main effect of Alzheimer's disease (AD) on brain structure across platforms and field strength has been addressed in previous studies using multi-site MR images, there are only sparse empirically-based recommendations for processing and analysis of pooled multi-centre structural MR data acquired at different magnetic field strengths (MFS). Aiming to minimise potential systematic bias when using ADNI data we investigate the specific contributions of spatial registration strategies and the impact of MFS on voxel-based morphometry in AD. We perform a whole-brain analysis within the framework of Statistical Parametric Mapping, testing for main effects of various diffeomorphic spatial registration strategies, of MFS and their interaction with disease status. Beyond the confirmation of medial temporal lobe volume loss in AD, we detect a significant impact of spatial registration strategy on estimation of AD related atrophy. Additionally, we report a significant effect of MFS on the assessment of brain anatomy (i) in the cerebellum, (ii) the precentral gyrus and (iii) the thalamus bilaterally, showing no interaction with the disease status. We provide empirical evidence in support of pooling data in multi-centre VBM studies irrespective of disease status or MFS.

NFκB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses.

Neutrophils are antigen-transporting cells that generate vaccinia virus (VACV)-specific T-cell responses, yet how VACV modulates neutrophil recruitment and its significance in the immune response are unknown. We generated an attenuated VACV strain that expresses HIV-1 clade C antigens but lacks three specific viral genes (A52R, K7R, and B15R). We found that these genes act together to inhibit the NFκB signaling pathway. Triple ablation in modified virus restored NFκB function in macrophages. After virus infection of mice, NFκB pathway activation led to expression of several cytokines/chemokines that increased the migration of neutrophil populations (Nα and Nβ) to the infection site. Nβ cells displayed features of antigen-presenting cells and activated virus-specific CD8 T cells. Enhanced neutrophil trafficking to the infection site correlated with an increased T-cell response to HIV vector-delivered antigens. These results identify a mechanism for poxvirus-induced immune response and alternatives for vaccine vector design.

Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis.

Invasive aspergillosis (IA) is a life-threatening infection due to Aspergillus fumigatus and other Aspergillus spp. Drugs targeting the fungal cell membrane (triazoles, amphotericin B) or cell wall (echinocandins) are currently the sole therapeutic options against IA. Their limited efficacy and the emergence of resistance warrant the identification of new antifungal targets. Histone deacetylases (HDACs) are enzymes responsible of the deacetylation of lysine residues of core histones, thus controlling chromatin remodeling and transcriptional activation. HDACs also control the acetylation and activation status of multiple non-histone proteins, including the heat shock protein 90 (Hsp90), an essential molecular chaperone for fungal virulence and antifungal resistance. This review provides an overview of the different HDACs in Aspergillus spp. as well as their respective contribution to total HDAC activity, fungal growth, stress responses, and virulence. The potential of HDAC inhibitors, currently under development for cancer therapy, as novel alternative antifungal agents against IA is discussed.

Generation of biological association networks: A novel strategy to detect new targets in cancer therapy

The aim of this work was to design a novel strategy to detect new targets for anticancer treatments. The rationale was to build Biological Association Networks from differentially expressed genes in drug-resistant cells to identify important nodes within the Networks. These nodes may represent putative targets to attack in cancer therapy, as a way to destabilize the gene network developed by the resistant cells to escape from the drug pressure. As a model we used cells resistant to methotrexate (MTX), an inhibitor of DHFR. Selected node-genes were analyzed at the transcriptional level and from a genotypic point of view. In colon cancer cells, DHFR, the AKR1 family, PKC¿, S100A4, DKK1, and CAV1 were overexpressed while E-cadherin was lost. In breast cancer cells, the UGT1A family was overexpressed, whereas EEF1A1 was overexpressed in pancreatic cells. Interference RNAs directed against these targets sensitized cells towards MTX.

Iowa Strategy for Homeland Security and Emergency Management 2009-2014, August 31, 2009

Address sustainability in all efforts. Sustainability should be at the core of all levels of homeland security and emergency management effort in Iowa. Capabilities need to be built for the long term, and without a sustainability plan in place, projects can quickly deplete uncertain levels of funding. Utilize an all-hazards methodology. Developing capabilities that are effective during a variety of disaster and emergency scenarios represents sound planning and resource management. Enhance capabilities through joint planning, training and exercise. Effective capabilities developed through coordinated planning efforts and an ongoing joint training and exercising program to ensure sustainment of prepared response. Utilize a collaborative approach to build capability. We will utilize whatever partnerships are necessary to build capability in the most effective manner possible. Regional partnerships have been, and will continue to be, in the forefront of the State of Iowa’s efforts to build and enhance capability. Enhance statewide capabilities. Whenever possible, we will identify and augment existing resources to provide statewide capability during a disaster or terrorist attack. Awareness, outreach and education. Open communication is critical to the success of any initiative. All projects implemented will have awareness, education and outreach components to ensure that all stakeholders are informed as to their responsibilities, capabilities and access. Information sharing and a common operating picture. The timely exchange of critical/actionable information is imperative to the success of every operation. The identification of a common operating picture allows decision makers to make informed decisions based on a unified understanding of the events around them.

Harvesting strategy and N fertilization influence ¹³⁴Cs uptake by forage plants

Selostus: Korjuuaika ja typpilannoitus vaikuttavat rehukasvien radiocesiumpitoisuuteen

Changes in the foraging strategy of female South American sea lions (Carnivora: Pinnipedia) after parturition.

This study tests the hypothesis that female South American sea lions shift from off-shore, pelagic prey to coastal, benthic prey after parturition in order to reduce the foraging trip duration and hence the time pups remain unattended on the beach during early lactation. The δ13C and δ15N values of the serum and blood cells of 26 South American sea lion suckling pups from northern Patagonia were used to track the dietary changes of their mothers from late pregnancy to early lactation, after correction for differential isotopic fractionation between tissues. Primary producers and potential prey species were also analysed to establish a baseline for interpreting the stable isotope concentration of serum and blood cells. Isotopic ratios revealed a generalized increase in the consumption of coastal-benthic prey after parturition. Such a generalized post-partum shift will allow females to spend more time on land and look after their pups. The effects of this foraging strategy on the nutritional quality of the female"s diet are discussed.