Philadelphia-Negative Classical Myeloproliferative Neoplasms: Critical Concepts and Management Recommendations From European LeukemiaNet

We present a review of critical concepts and produce recommendations on the management of Philadelphia-negative classical myeloproliferative neoplasms, including monitoring, response definition, first-and second-line therapy, and therapy for special issues. Key questions were selected according the criterion of clinical relevance. Statements were produced using a Delphi process, and two consensus conferences involving a panel of 21 experts appointed by the European LeukemiaNet (ELN) were convened. Patients with polycythemia vera (PV) and essential thrombocythemia (ET) should be defined as high risk if age is greater than 60 years or there is a history of previous thrombosis. Risk stratification in primary myelofibrosis (PMF) should start with the International Prognostic Scoring System (IPSS) for newly diagnosed patients and dynamic IPSS for patients being seen during their disease course, with the addition of cytogenetics evaluation and transfusion status. High-risk patients with PV should be managed with phlebotomy, low-dose aspirin, and cytoreduction, with either hydroxyurea or interferon at any age. High-risk patients with ET should be managed with cytoreduction, using hydroxyurea at any age. Monitoring response in PV and ET should use the ELN clinicohematologic criteria. Corticosteroids, androgens, erythropoiesis-stimulating agents, and immunomodulators are recommended to treat anemia of PMF, whereas hydroxyurea is the first-line treatment of PMF-associated splenomegaly. Indications for splenectomy include symptomatic portal hypertension, drug-refractory painful splenomegaly, and frequent RBC transfusions. The risk of allogeneic stem-cell transplantation-related complications is justified in transplantation-eligible patients whose median survival time is expected to be less than 5 years.

Non Classical Design in MOSFETs for Improving OTA gain-bandwidth trade off

In this paper, gain-bandwidth (GB) trade-off associated with analog device/circuit design due to conflicting requirements for enhancing gain and cutoff frequency is examined. It is demonstrated that the use of a nonclassical source/drain (S/D) profile (also known as underlap channel) can alleviate the GB trade-off associated with analog design. Operational transconductance amplifier (OTA) with 60 nm underlap S/D MOSFETs achieve 15 dB higher open loop voltage gain along with three times higher cutoff frequency as compared to OTA with classical nonunderlap S/D regions. Underlap design provides a methodology for scaling analog devices into the sub-100 nm regime and is advantageous for high temperature applications with OTA, preserving functionality up to 540 K. Advantages of underlap architecture over graded channel (GC) or laterally asymmetric channel (LAC) design in terms of GB behavior are demonstrated. Impact of transistor structural parameters on the performance of OTA is also analyzed. Results show that underlap OTAs designed with spacer-to-straggle ratio of 3.2 and operated below a bias current of 80 microamps demonstrate optimum performance. The present work provides new opportunities for realizing future ultra wide band OTA design with underlap DG MOSFETs in silicon-on-insulator (SOI) technology. Index Terms—Analog/RF, double gate, gain-bandwidth product, .

Berry phase for a spin 1/2 particle in a classical fluctuating field

The effect of fluctuations in the classical control parameters on the Berry phase of a spin 1/2 interacting with an adiabatically cyclically varying magnetic field is analyzed. It is explicitly shown that in the adiabatic limit dephasing is due to fluctuations of the dynamical phase.

Connections between Classical and Parametric Network Entropies

This paper explores relationships between classical and parametric measures of graph (or network) complexity. Classical measures are based on vertex decompositions induced by equivalence relations. Parametric measures, on the other hand, are constructed by using information functions to assign probabilities to the vertices. The inequalities established in this paper relating classical and parametric measures lay a foundation for systematic classification of entropy-based measures of graph complexity.

Rift Valley Fever Epidemiology, Surveillance, and Control: What Have Models Contributed?

Background: Rift Valley fever (RVF) is an emerging vector-borne zoonotic disease that represents a threat to human health, animal health, and livestock production, particularly in Africa. The epidemiology of RVF is not well understood, so that forecasting RVF outbreaks and carrying out efficient and timely control measures remains a challenge. Various epidemiological modeling tools have been used to increase knowledge on RVF epidemiology and to inform disease management policies.

Interlaboratory comparison of real-time polymerase chain reaction methods to detect Coxiella burnetii, the causative agent of Q fever

The bacterium Coxiella burnetii, which has a wide host range, causes Q fever. Infection with C burnetii can cause abortions, stillbirth, and the delivery of weak offspring in ruminants. Coxiella burnetii infection is zoonotic, and in human beings it can cause chronic, potentially fatal disease. Real-time polymerase chain reaction (PCR) is increasingly being used to detect the organism and to aid in diagnosis both in human and animal cases. Many different real-time PCR methods, which target different genes, have been described. To assess the comparability of the C. burnetii real-time PCR assays in use in different European laboratories, a panel of nucleic acid extracts was dispatched to 7 separate testing centers. The testing centers included laboratories from both human and animal health agencies. Each laboratory tested the samples using their in-house real-time PCR methods. The results of this comparison show that the most common target gene for real-time PCR assays is the IS1111 repeat element that is present in multiple copies in the C. burnetii genome. Many laboratories also use additional real-time PCR tests that target single-copy genes. The results of the current study demonstrate that the assays in use in the different laboratories are comparable, with general agreement of results for the panel of samples.

Coxiella burnetii (Q fever) seroprevalence in cattle

Human cases of Q fever appear to be common in Northern Ireland compared to the rest of the British Isles. The purpose of this study was to describe the seroepidemiology of Coxiella burnetii infection in cattle in Northern Ireland in terms of seroprevalence and determinants of infection. A total of 5182 animals (from a stratified systematic random sample of 273 herds) were tested with a commercial C. burnetii phase 2 IgG ELISA. A total of 6.2% of animals and 48.4% of herds tested positively. Results from a multilevel logistic regression model indicated that the odds of cattle being infected with Q fever increased with age, Friesian breed, being from large herds and from dairy herds. Large dairy herd animal prevalence was 12.5% compared to 2.1% for small beef herds. Preliminary seroprevalence in sheep (12.3%), goats (9.3%), pigs (0%) rats (9.7%) and mice (3.2%) using indirect immunofluorescence is reported.

Human seroprevalence to Coxiella bumetii (Q fever) in Northern Ireland

Despite the widespread prevalence of infection with Coxiella burnetii, there have been few large population-based studies examining the epidemiology of this infection. The aim of this study was to examine the distribution and determinants of C. burnetii past infection in Northern Ireland (NI). Coxiella burnetii phase II specific IgG antibodies were measured by enzyme-linked immunosorbent assay in stored serum from 2394 randomly selected subjects, aged 12-64, who had participated in population-based surveys of cardiovascular risk factors performed in 1986 and 1987. The overall prevalence of C. burnetii antibody positivity was 12.8%. The prevalence of sero-positivity was slightly higher in males than that in females (14.3% versus 11.2%, P = 0.02). Sero-positivity was low in children (