Comparison of the efficacy and safety of arformoterol 15 microg twice daily and arformoterol 30 microg once daily in COPD: a single-dose, multicenter, randomized, modified-blind, two-way crossover study.

Objective: The aim of this study was to compare the efficacy and safety of nebulized arformoterol 15 microg/2 mL twice daily (ARF15 BID) and 30 microg/4 mL once daily (ARF30 QD) in subjects with moderate to severe chronic obstructive pulmonary disease (COPD).

Methods: In this single-dose, multicenter, randomized, modified-blind, 2-way crossover study, subjects aged > or =45 years with moderate to severe COPD, a forced expiratory volume in 1 second (FEV(1)) > or =0.7 L, and < or =65% predicted FEV1, and a FEV(1):forced vital capacity ratio < or =70% were randomly assigned to receive single-day treatment with ARF15 BID or ARF30 QD in random order, separated by a 5 +/- 2-day washout period.

Antiplatelet drugs and outcome in mixed admissions to an intensive care unit.

Objective: Platelet activation has been implicated in microvascular thrombosis and organ failure. We tested the hypothesis that antiplatelet drugs favorably affect outcome in patients nonelectively admitted to an intensive care unit.

Design: Retrospective cohort study.

Return of testicular function after vaccination of boars against GnRH: consequences on testes histology.

Traditionally, male pigs are surgically castrated without anaesthesia to avoid later occurrence of the sex odour of androstenone in the carcass. Active immunization against gonadotropin-releasing hormone (GnRH) is a painless alternative which inhibits LH and thus steroidogenesis in the Leydig cells. In a preceding study we clarified the return of Leydig cell function after the last dose of antigen by measuring hormones, and found a considerable variation (10 to 24 weeks) till return of their function (testosterone 0.

Efficacy of a 3-day, low-dose treatment with 5-azacytidine followed by donor lymphocyte infusions in older patients with acute myeloid leukemia or chronic myelomonocytic leukemia relapsed after allografting.

We have piloted a low-dose schedule of 5-azacytidine followed by donor lymphocyte infusions (DLIs) in patients with relapse of AML or chronic myelomonocytic leukemia (CMMoL) after allografting. Of the 26 patients (median age 62 years, range 28-75) with relapsed AML (n=24) or CMMoL (n=2), 11 (42%) had poor-risk cytogenetics. Twenty-three patients had received fludarabine-based reduced-toxicity conditioning regimens, and three had received conventional myeloablative conditioning.

Increasing program capability to provide treatment for co-occurring substance use and mental disorders: organizational characteristics.

The Dual Diagnosis Capability in Addiction Treatment and the Dual Diagnosis Capability in Mental Health Treatment indexes were used to document change in the capability of 14 substance abuse and mental health agencies to provide services to clients with co-occurring substance use and mental disorders (COD). COD capability significantly increased over 2 years, with the largest improvements seen in client assessment and staff training for COD. The role of agency structural characteristics and organizational readiness for change was also investigated.

miRNA deregulation by epigenetic silencing disrupts suppression of the oncogene PLAG1 in chronic lymphocytic leukemia.

MicroRNAs (miRNA) play a key role in cellular regulation and, if deregulated, in the development of neoplastic disorders including chronic lymphocytic leukemia (CLL). RNAs from primary cells of 50 treatment-naive CLL patients and peripheral B cells of 14 healthy donors were applied to miRNA expression profiling using bead chip technology. In CLL cells, a set of 7 up- and 19 down-regulated miRNAs was identified.

Detection of high-energy gamma-ray emission from the globular cluster 47 Tucanae with Fermi.

We report the detection of gamma-ray emissions above 200 megaelectron volts at a significance level of 17sigma from the globular cluster 47 Tucanae, using data obtained with the Large Area Telescope onboard the Fermi Gamma-ray Space Telescope. Globular clusters are expected to emit gamma rays because of the large populations of millisecond pulsars that they contain. The spectral shape of 47 Tucanae is consistent with gamma-ray emission from a population of millisecond pulsars.

Is the early postnatal rise of testosterone responsible for a later male pattern of growth hormone secretion in pigs?

Sexual differentiation in Placentalia consists of several consecutive steps during fetal, postnatal, and premature development. It is known from male rats that an elevation in testosterone synthesis is observable within 2 d of birth, which leads to a male pattern of growth hormone (GH) secretion with low base levels and high amplitudes compared with that in females. In the male pig, a transient rise in testosterone concentration occurs about 4 wk after birth, but it is unknown whether it results in a later male pattern of GH secretion.

A population of gamma-ray millisecond pulsars seen with the Fermi Large Area Telescope.

Pulsars are born with subsecond spin periods and slow by electromagnetic braking for several tens of millions of years, when detectable radiation ceases. A second life can occur for neutron stars in binary systems. They can acquire mass and angular momentum from their companions, to be spun up to millisecond periods and begin radiating again.

Detection of 16 gamma-ray pulsars through blind frequency searches using the Fermi LAT.

Pulsars are rapidly rotating, highly magnetized neutron stars emitting radiation across the electromagnetic spectrum. Although there are more than 1800 known radio pulsars, until recently only seven were observed to pulse in gamma rays, and these were all discovered at other wavelengths. The Fermi Large Area Telescope (LAT) makes it possible to pinpoint neutron stars through their gamma-ray pulsations.

Inhibition of sphingomyelin hydrolysis: targeting the lipid mediator ceramide as a key regulator of cellular fate.

Ceramide, an intracellular lipid mediator, is generated by transient hydrolysis of sphingomyelin in response to agonists inducing inflammation and apoptosis, ionizing radiation, chemotherapeutics or ischaemia/reperfusion. An elevated intracellular ceramide production is predominantly induced by an elevated hydrolytic activity of sphingomyelinases or by the activity of enzymes controlling de novo synthesis, such as ceramide synthase. Ceramide is implicated in various cellular responses, acting as an autonomous intracellular effector in cell cycle regulation, differentiation, senescence, and apoptosis.

Measurement of the cosmic ray e+ +e- spectrum from 20 GeV to 1 TeV with the Fermi Large Area Telescope.

Designed as a high-sensitivity gamma-ray observatory, the Fermi Large Area Telescope is also an electron detector with a large acceptance exceeding 2 m;{2} sr at 300 GeV. Building on the gamma-ray analysis, we have developed an efficient electron detection strategy which provides sufficient background rejection for measurement of the steeply falling electron spectrum up to 1 TeV. Our high precision data show that the electron spectrum falls with energy as E-3.

Non-intensive treatment with low-dose 5-aza-2'-deoxycytidine (DAC) prior to allogeneic blood SCT of older MDS/AML patients.

Novel, non-intensive treatment options in older MDS/AML patients planned for allografting, with the goal of down-staging the underlying disease and bridging time to transplantation, are presently being developed. 5-azacytidine and decitabine (DAC) are of particular interest, as they can be given repetitively, with very limited non-hematologic toxicity and result in responses both in MDS and AML even at low doses. We describe 15 consecutive patients (median age 69 years, range 60-75 years) with MDS (n=10) or AML (n=5) who all received first-line treatment with DAC and subsequent allografting (from sibling donor in four patients, unrelated donor in 11) after reduced-intensity conditioning with the FBM regimen.

Fermi observations of high-energy gamma-ray emission from GRB 080916C.

Gamma-ray bursts (GRBs) are highly energetic explosions signaling the death of massive stars in distant galaxies. The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gammaray energy. In September 2008, Fermi observed the exceptionally luminous GRB 080916C, with the largest apparent energy release yet measured.

Prospective assessment of hepatic function and mechanisms of dysfunction in the critically ill.

Liver dysfunction affects a variety of metabolic pathways in the critically ill, but mechanisms remain poorly understood. We prospectively assessed markers of hepatic injury and function in sepsis and I/R injury in vivo and molecular mechanisms in human liver tissue ex vivo. Markers of hepatocellular injury, synthesis, and excretion, including plasma disappearance rate of indocyanine green (ICG), were measured in 48 patients with severe sepsis.

The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells.

The three DNA methyltransferase (DNMT)-inhibiting cytosine nucleoside analogues, azacitidine, decitabine and zebularine, which are currently studied as nonintensive therapy for myelodysplastic syndromes and acute myeloid leukemia (AML), differ in structure and metabolism, suggesting that they may have differential molecular activity. We investigated cellular and molecular effects of the three substances relative to cytarabine in Kasumi-1 AML blasts. Under in vitro conditions mimicking those used in clinical trials, the DNMT inhibitors inhibited proliferation and triggered apoptosis but did not induce myeloid differentiation.

Variations in the ratio between von Willebrand factor and its cleaving protease during systemic inflammation and association with severity and prognosis of organ failure.

Von Willebrand factor (VWF) and related parameters as well as the protease activity regulating its biological activity were measured in plasma of healthy controls and patients with different cause and severity of systemic inflammation to examine the efficacy of the measures to detect highly prothrombotic states including thrombotic microangiopathy (TMA), one of the sequelae of sepsis. Plasma levels of VWF increased with increasing severity of systemic inflammation, probably due to activation of the endothelium. In parallel, the proteolytic activity of VWF inactivating protease, ADAMTS13, stepwise declined with the severity of inflammation, emphasizing the role of VWF-triggered platelet aggregation on the endothelium subsequently followed by development of TMA.

Anti-platelet drugs and outcome in severe infection: clinical impact and underlying mechanisms.

Platelet activation contributes to microvascular thrombosis and organ failure in systemic inflammation. We tested the hypothesis whether anti-platelet drugs might favourably affect outcome in patients at risk for organ failure as well as in a mouse model of endotoxin shock. Two hundred twenty-four consecutive patients who were admitted for community acquired pneumonia over a time period of 5 years to a University Hospital were enrolled; about 20% of whom received anti-platelet drugs (acetylsalicylic acid, thienopyridines) for secondary prevention of cardiovascular disease.

Effects of two levels of feed allocation on IGF-I concentrations and metabolic parameters in GnRH-immunized boars.

Immunocastration of boars leads to a maintenance of growth harmone (GH) and a loss of anabolic hormones [androgens, oestrogens, insulin-like growth factor (IGF-I)] but an increase of voluntary feed intake. The aim of the experiment was to clarify whether IGF-I is increased by increasing feed supply in immunocastrated boars leading to improved anabolism. Two groups of six boars were given 2 or 3 kg of feed (13.

An improved microtitre enzyme immunoassay to measure the boar taint steroid 5α-androst-16-en-3-one in blood plasma of pigs.

Androstenone (5α-androst-16-en-3-one) is a volatile steroid which is synthesized in boar testes and stored in high amounts in fat thus leading to an urine-like odor in pork. Whereas microtiter assays (MTA) exist for fat determination, measurement in blood with MTA was not yet possible. The system reported here is based on a specific antiserum and a horse radish peroxidase conjugate as tracer.

Open digestion under reflux for the determination of total arsenic in seafood by inductively coupled plasma atomic emission spectrometry with hydride generation.

A method for the determination of arsenic (As) in seafood by inductively coupled plasma atomic emission spectrometry with continuous hydride generation is described. Several analytical parameters have been investigated and optimised. The analytical features of the method (recovery, precision, accuracy and limit of detection) were calculated.

Endovascular histologic effects of ultrathin gold- or vitronectin-coated platinum aneurysm coils in a rodent arterial occlusion model: a preliminary investigation.

Background And Purpose: Novel stratagems to improve the efficacy of platinum coils in occluding cerebral aneurysms have primarily involved coating coils with materials thought likely to provoke more desirable histologic reactions. No investigations to date, however, have evaluated the utility of gold or vitronectin coatings, despite known endovascular histologic effects of these agents, which may be favorable for treating cerebral aneurysms. This study was conducted to evaluate the degree of endovascular histologic change associated with ultrathin gold- or vitronectin-coated platinum coils.

The Fermi Gamma-Ray Space Telescope discovers the pulsar in the young galactic supernova remnant CTA 1.

Energetic young pulsars and expanding blast waves [supernova remnants (SNRs)] are the most visible remains after massive stars, ending their lives, explode in core-collapse supernovae. The Fermi Gamma-Ray Space Telescope has unveiled a radio quiet pulsar located near the center of the compact synchrotron nebula inside the supernova remnant CTA 1. The pulsar, discovered through its gamma-ray pulsations, has a period of 316.

Study of B meson decays with excited eta and eta' mesons.

Using 383 x 10(6) BBover pairs from the BABAR data sample, we report results for branching fractions of six charged B-meson decay modes, where a charged kaon recoils against a charmless resonance decaying to KKover* or etapipi final states with mass in the range (1.2-1.8) GeV/c2.