Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib

UNLABELLED Early assessment of response at 3 months of tyrosine kinase inhibitor treatment has become an important tool to predict favorable outcome. We sought to investigate the impact of relative changes of BCR-ABL transcript levels within the initial 3 months of therapy. In order to achieve accurate data for high BCR-ABL levels at diagnosis, beta glucuronidase (GUS) was used as a reference gene. Within the German CML-Study IV, samples of 408 imatinib-treated patients were available in a single laboratory for both times, diagnosis and 3 months on treatment. In total, 301 of these were treatment-naïve at sample collection. RESULTS (i) with regard to absolute transcript levels at diagnosis, no predictive cutoff could be identified; (ii) at 3 months, an individual reduction of BCR-ABL transcripts to the 0.35-fold of baseline level (0.46-log reduction, that is, roughly half-log) separated best (high risk: 16% of patients, 5-year overall survival (OS) 83% vs 98%, hazard ratio (HR) 6.3, P=0.001); (iii) at 3 months, a 6% BCR-ABL(IS) cutoff derived from BCR-ABL/GUS yielded a good and sensitive discrimination (high risk: 22% of patients, 5-year OS 85% vs 98%, HR 6.1, P=0.002). Patients at risk of disease progression can be identified precisely by the lack of a half-log reduction of BCR-ABL transcripts at 3 months.

Muscle velocity recovery cycles: Comparison between surface and needle recordings.

INTRODUCTION Recording of muscle velocity recovery cycles (MVRCs) has been developed as a technique to investigate the pathophysiology of muscle diseases. MVRCs have been measured by direct muscle stimulation and concentric electromyographic needle recording. This study was undertaken to determine whether recordings can be made with surface electrodes. METHODS MVRCs with 1 and 2 conditioning stimuli were recorded simultaneously with concentric needle and surface electrodes from the brachioradialis muscle in 12 healthy volunteers. Muscle relative refractory period, early and late supernormality, and extra-late supernormality were compared between the recording techniques. RESULTS Surface recordings were possible in all subjects. The multifiber action potentials recorded with surface electrodes were smaller than those recorded with needles, but there was no significant difference between any of their MVRC properties. CONCLUSIONS MVRCs can be recorded with surface electrodes in healthy subjects. The use of surface electrodes may facilitate the technique of recording MVRCs. Muscle Nerve 53: 205-208, 2016.

Interstellar neutral helium in the heliosphere from Interstellar Boundary Explorer observations. III. Mach number of the flow, velocity vector, and temperature from the first six years of measurements

We analyzed observations of interstellar neutral helium (ISN He) obtained from the Interstellar Boundary Explorer (IBEX) satellite during its first six years of operation. We used a refined version of the ISN He simulation model, presented in the companion paper by Sokol et al. (2015b), along with a sophisticated data correlation and uncertainty system and parameter fitting method, described in the companion paper by Swaczyna et al. We analyzed the entire data set together and the yearly subsets, and found the temperature and velocity vector of ISN He in front of the heliosphere. As seen in the previous studies, the allowable parameters are highly correlated and form a four-dimensional tube in the parameter space. The inflow longitudes obtained from the yearly data subsets show a spread of similar to 6 degrees, with the other parameters varying accordingly along the parameter tube, and the minimum chi(2) value is larger than expected. We found, however, that the Mach number of the ISN He flow shows very little scatter and is thus very tightly constrained. It is in excellent agreement with the original analysis of ISN He observations from IBEX and recent reanalyses of observations from Ulysses. We identify a possible inaccuracy in the Warm Breeze parameters as the likely cause of the scatter in the ISN He parameters obtained from the yearly subsets, and we suppose that another component may exist in the signal or a process that is not accounted for in the current physical model of ISN He in front of the heliosphere. From our analysis, the inflow velocity vector, temperature, and Mach number of the flow are equal to lambda(ISNHe) = 255 degrees.8 +/- 0 degrees.5, beta(ISNHe) = 5 degrees.16 +/- 0 degrees.10, T-ISNHe = 7440 +/- 260 K, nu(SNHe) = 25.8 +/- 0.4 km s(-1), and M-ISNHe = 5.079 +/- 0.028, with uncertainties strongly correlated along the parameter tube.

The Long-Run Relationship between Money, Nominal GDP, and the Price Level in Venezuela: 1950 to 1996

This paper explores whether a significant long-run relationship exists between money and nominal GDP and between money and the price level in the Venezuelan economy. We apply time-series econometric techniques to annual data for the Venezuelan economy for 1950 to 1996. An important feature of our analysis is the use of tests for unit roots and cointegration with structural breaks. Certain characteristics of the Venezuelan experience suggest that structural breaks may be important. Since the economy depends heavily on oil revenue, oil price shocks have had important influences on most macroeconomic variables. Also since the economy possesses large foreign debt, the world debt crisis that exploded in 1982 had pervasive effects on the Venezuelan economy. Radical changes in economic policy and political instability may have also significantly affected the movement of the macroeconomy. We find that a long-run relationship exists between narrow money (M1) and nominal GDP, the GDP deflator, and the CPI when one makes allowances for one or two structural breaks. We do not find such long-run relationships when broad money (M2) is used.

Endogenous Financing and the Long Run Impact of Money Growth on Output and Prices

Most monetary models make use of the quantity theory of money along with a Phillips curve. This implies a strong correlation between money growth and output in the short run (with little or no correlation between money and prices) and a strong long run correlation between money growth and inflation and inflation (with little or no correlation between money growth and output). The empirical evidence between money and inflation is very robust, but the long run money/output relationship is ambiguous at best. This paper attempts to explain this by looking at the impact of money growth on firm financing.

Equity Markets, the Money Market, and Long-Run Monetary Neutrality

This paper outlines a process for teaching long-run neutrality of money, drawing an analogy between equity markets and the money market. The key points in the discussion include the following: (1) What is the price of money? (2) Why does the long-run demand for money trace out a rectangular hyperbola? (3) Why does the slow adjustment of goods and service prices to changes in the stock of money lead to a different short-run demand for money? and (4) Why does a successful currency reform generate similar short-run movements in the price of money as movements in equity share prices after a change in the supply of shares? I have used this approach successfully for over 30 years at all levels, wherever I need to discuss the money market in a macroeconomic model.

All Alone, Without Money, No Language--Just Yiddish": An Immigrant's Letters from Missouri to Galicia

In June 1891, Shimshon Gerye, a Jewish immigrant from Galicia (a region that now falls across the border of Ukraine and Poland) living in Sedalia, Missouri, received a letter from a cousin back home. The content of the letter was probably rather mundane (a request to send money, inquiries about health), but its timing was somewhat unusual: in the thirty-five years that Shimshon had been living in America, this was apparently the first he had heard from his family in Europe. What survives of the ensuing correspondence, written in Yiddish and spanning a one-year period, provides an interesting view of the situation of the immigrant and the pressures of assimilation, as well as the Yiddish language in America at the end of the nineteenth century.

International Money and Finance

We discuss the effectiveness of pegged exchange rate regimes from an historical perspective, drawing conclusions for their effectiveness today. Starting with the classical gold standard period, we point out that a succession of pegged regimes have ended in failure; except for the first, which was ended by the outbreak of World War I, all of the others we discuss have been ended by adverse economic developments for which the regimes themselves were partly responsible. Prior to World War II the main problem was a shortage of monetary gold that we argue is implicated as a cause of the Great Depression. After World War II, more particularly from the late-1960s, the main problem has been a surfeit of the main international reserve asset, the US dollar. This has led to generalized inflation in the 1970s and into the 1980s. Today, excessive dollar international base money creation is again a problem that could have serious consequences for world economic stability.

History of Jewish coinage, and of money in the Old and New Testament

by Frederic W. Madden

SOCIAL AND BIOLOGICAL DETERMINANTS OF SHORT-TERM GROWTH VELOCITY AMONG PRESCHOOLERS OF RURAL GUATEMALA: A PATH ANALYSIS APPROACH (WEIGHT-GAIN, IRON DEFICIENCY, GASTROINTESTINAL SYMPTOMS)

This dissertation develops and tests through path analysis a theoretical model to explain how socioeconomic, socioenvironmental, and biologic risk factors simultaneously influence each other to further produce short-term, depressed growth in preschoolers. Three areas of risk factors were identified: child's proximal environment, maturational stage, and biological vulnerability. The theoretical model represented both the conceptual framework and the nature and direction of the hypotheses. Original research completed in 1978-80 and in 1982 provided the background data. It was analyzed first by nested-analysis of variance, followed by path analysis. The study provided evidence of mild iron deficiency and gastrointestinal symptomatology in the etiology of depressed, short-term weight gain. Also, there was evidence suggesting that family resources for material and social survival significantly contribute to the variability of short-term, age-adjusted growth velocity. These results challenge current views of unifocal intervention, whether for prevention or control. For policy formulations, though, the mechanisms underlying any set of interlaced relationships must be decoded. Theoretical formulations here proposed should be reassessed under a more extensive research design. It is suggested that studies should be undertaken where social changes are actually in progress; otherwise, nutritional epidemiology in developing countries operates somewhere between social reality and research concepts, with little grasp of its real potential. The study stresses that there is a connection between substantive theory, empirical observation, and policy issues. ^