Magnetic Resonance Imaging-Guided Focused Ultrasound Treatment of Symptomatic Uterine Fibroids Impact of Technology Advancement on Ablation Volumes in 115 Patients

Objectives: The aim of this study was to assess the impact of the advanced technology of the new ExAblate 2100 system (Insightec Ltd, Haifa, Israel) for magnetic resonance imaging (MRI)-guided focused ultrasound surgery on treatment outcomes in patients with symptomatic uterine fibroids, as measured by the nonperfused volume ratio. Materials and Methods: This is a retrospective analysis of 115 women (mean age, 42 years; range, 27-54 years) with symptomatic fibroids who consecutively underwent MRI-guided focused ultrasound treatment in a single center with the new generation ExAblate 2100 system from November 2010 to June 2011. Mean +/- SD total volume and number of treated fibroids (per patient) were 89 +/- 94 cm(3) and 2.2 +/- 1.7, respectively. Patient baseline characteristics were analyzed regarding their impact on the resulting nonperfused volume ratio. Results: Magnetic resonance imaging-guided focused ultrasound treatment was technically successful in 115 of 123 patients (93.5%). In 8 patients, treatment was not possible because of bowel loops in the beam pathway that could not be mitigated (n = 6), patient movement (n = 1), and system malfunction (n = 1). Mean nonperfused volume ratio was 88% +/- 15% (range, 38%-100%). Mean applied energy level was 5400 +/- 1200 J, and mean number of sonications was 74 +/- 27. No major complications occurred. Two cases of first-degree skin burn resolved within 1 week after the intervention. Of the baseline characteristics analyzed, only the planned treatment volume had a statistically significant impact on nonperfused volume ratio. Conclusions: With technological advancement, the outcome of MRI-guided focused ultrasound treatment in terms of the nonperfused volume ratio can be enhanced with a high safety profile, markedly exceeding results reported in previous clinical trials

Die Wiedervereinigung - eine ökonomische Erfolgsgeschichte

Die Erwartungen der Menschen nach dem Mauerfall vor 25 Jahren und der Wiedervereinigung 1990 waren enorm. Die Regierung versprach, innerhalb weniger Jahre ,,blühende Landschaften" zu schaffen. Die Euphorie der Wiedervereinigung kam nicht nur durch den Wunsch zustande, endlich wieder ein Land und eine Nation zu sein, sondern hatte auch handfeste wirtschaftliche Gründe: Die Menschen in Ostdeutschland wollten eine bessere wirtschaftliche Perspektive, mehr Chancen, ihre Möglichkeiten zu verwirklichen und letztlich mehr Wohlstand für sich und künftige Generationen zu schaffen. Die Westdeutschen erhofften sich einen Boom. Das Versprechen erwies sich sehr schnell als eine Illusion. Und es wurden - aus rein ökonomischer Sicht - wirtschaftspolitische Fehler gemacht, wie etwa die Währungsunion zu einem Wechselkurs, der wirtschaftlich die Wettbewerbsfähigkeit Ostdeutschlands schnell sinken ließ und zumindest anfänglich zu einem starken Anstieg der Arbeitslosigkeit beitrug. Und die Privatisierung durch die Treuhandanstalt war wahrscheinlich übereilt. Ist jedoch die Wiedervereinigung deshalb aus wirtschaftspolitischer Perspektive gescheitert? Es wäre falsch, das politische Versprechen vom schnellen Wohlstand als Maß für den Erfolg der Wiedervereinigung zu nehmen. Die Frage nach einem realistischen Ziel und Kriterium für eine systematische wirtschaftspolitische Bewertung der Wiedervereinigung ist schwer zu beantworten. Die Annäherung, oder Konvergenz, der Lebensbedingungen in Ost- und Westdeutschland ist ein Maß, das diesem Ziel der Bewertung nahe kommt. Es wäre jedoch irreführend, unter Konvergenz eine völlige Gleichheit aller wirtschaftlichen Indikatoren zu verstehen. Eine Gleichheit in Einkommen, Produktivität oder Vermögen wird es innerhalb einer Volkswirtschaft und eines Landes nie geben können. Jedes noch so kleine und stark integrierte Land wird immer Unterschiede zwischen Regionen und selbst innerhalb von Regionen aufweisen. Auch die verschiedenen Regionen in Westdeutschland haben seit 1945 keinen Konvergenzprozess durchgemacht, der zu einer vollständigen wirtschaftlichen Angleichung geführt hätte. Ganz im Gegenteil: Häufig gibt es zeitweise Divergenzen, also auseinanderlaufende Lebensverhältnisse und wirtschaftliche Bedingungen, manchmal wandeln sich relativ arme Regionen zu den leistungsstärksten. Das Beispiel Bayerns ist nur eines, das zeigt, dass auch Westdeutschland einen solchen Prozess erfahren hat. Aber Länder wie Italien und Spanien haben sehr große und anhaltende Unterschiede über Regionen hinweg, die sich seit Jahrhunderten nicht ausgeglichen haben, sondern durch die Globalisierung eher noch größer geworden sind. Der vorliegende Wochenbericht des DIW Berlin will zunächst einen Beitrag zur wirtschaftspolitischen Bewertung der Wiedervereinigung leisten. Wie haben sich Einkommen, Produktivität und Löhne in Westdeutschland und in Ostdeutschland angeglichen? Wie sind verschiedene Bevölkerungsgruppen von der Wiedervereinigung beeinflusst worden? Wie haben sich Vermögen und Wohlstand im Vergleich der beiden Teile Deutschlands entwickelt? Dies sind die zentralen Fragen, die in den Aufsätzen des ersten Teils dieses Wochenberichts analysiert werden

Reunification: An economic success story

People's expectations after the fall of the Berlin Wall 25 years ago and of reunification in 1990 were huge. The government promised to create "flourishing landscapes" within a few years. The euphoria of reunification came not only through the desire to finally become one country and one nation again but also had tangible economic reasons: the people from East Germany wanted better economic prospects, more opportunities to realize their potential, and ultimately to create more well-being for themselves and future generations. West Germans were hoping for a boom. This promise very quickly proved to be an illusion. And, solely from an economic perspective, economic policy errors were made, such as monetary union at an exchange rate that caused East Germany's economic competitiveness to fall rapidly and, at least initially, contributed to a sharp rise in unemployment. In addition, privatization through the Treuhandanstalt was probably premature. Nevertheless, did reunification fail from an economic policy perspective? It would be misguided to take the political promises of whirlwind prosperity as a measure of the success of reunification. It is difficult to answer the question as to what are realistic objectives and criteria for a systematic economic policy evaluation of reunification. The convergence of living conditions in eastern and western Germany is a measure that comes close to assessing this objective. It would be misleading, however, to equate convergence with complete equality of all economic indicators. Equality of income, productivity, or assets will never be achieved in any economy or country. There will always be differences between regions, and even within regions, in any small or highly integrated country. The different regions in western Germany have not undergone this process since 1945, which would have led to full economic convergence, had the country not been divided. Quite the contrary: there are often temporary divergences, i.e., diverging living and economic conditions, sometimes relatively poor regions transform into the most productive. Bavaria is just one example of western Germany experiencing such a process. Countries such as Italy and Spain have very large and persistent differences across regions that have not evened out for centuries but have actually become even greater through globalization. This present DIW Economic Bulletin is intended as an initial contribution to the economic policy evaluation of reunification. To what extent have income, productivity, and wages converged in western and eastern Germany? How has reunification influenced different population groups? How have assets and well-being developed in both parts of Germany? These are the key questions analyzed in the first part of this DIW Economic Bulletin. [...

Modulation of RNA splicing enhances response to BCL2 inhibition in leukemia.

Therapy resistance is a major challenge in the treatment of cancer. Here, we performed CRISPR-Cas9 screens across a broad range of therapies used in acute myeloid leukemia to identify genomic determinants of drug response. Our screens uncover a selective dependency on RNA splicing factors whose loss preferentially enhances response to the BCL2 inhibitor venetoclax. Loss of the splicing factor RBM10 augments response to venetoclax in leukemia yet is completely dispensable for normal hematopoiesis. Combined RBM10 and BCL2 inhibition leads to mis-splicing and inactivation of the inhibitor of apoptosis XIAP and downregulation of BCL2A1, an anti-apoptotic protein implicated in venetoclax resistance. Inhibition of splicing kinase families CLKs (CDC-like kinases) and DYRKs (dual-specificity tyrosine-regulated kinases) leads to aberrant splicing of key splicing and apoptotic factors that synergize with venetoclax, and overcomes resistance to BCL2 inhibition. Our findings underscore the importance of splicing in modulating response to therapies and provide a strategy to improve venetoclax-based treatments

Molecular Predictors of Immunophenotypic Measurable Residual Disease Clearance in Acute Myeloid Leukemia

Measurable residual disease (MRD) is a powerful prognostic factor in acute myeloid leukemia (AML). However, pre-treatment molecular predictors of immunophenotypic MRD clearance remain unclear. We analyzed a dataset of 211 patients with pre-treatment next-generation sequencing who received induction chemotherapy and had MRD assessed by serial immunophenotypic monitoring after induction, subsequent therapy, and allogeneic stem cell transplant (allo-SCT). Induction chemotherapy led to MRD- remission, MRD+ remission, and persistent disease in 35%, 27%, and 38% of patients, respectively. With subsequent therapy, 34% of patients with MRD+ and 26% of patients with persistent disease converted to MRD-. Mutations in CEBPA, NRAS, KRAS, and NPM1 predicted high rates of MRD- remission, while mutations in TP53, SF3B1, ASXL1, and RUNX1 and karyotypic abnormalities including inv (3), monosomy 5 or 7 predicted low rates of MRD- remission. Patients with fewer individual clones were more likely to achieve MRD- remission. Among 132 patients who underwent allo-SCT, outcomes were favorable whether patients achieved early MRD- after induction or later MRD- after subsequent therapy prior to allo-SCT. As MRD conversion with chemotherapy prior to allo-SCT is rarely achieved in patients with specific baseline mutational patterns and high clone numbers, upfront inclusion of these patients into clinical trials should be considered

Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global public health crisis. Multiple observations indicate poorer post-infection outcomes for patients with cancer than for the general population. Herein, we highlight the challenges in caring for patients with acute leukaemias and myeloid neoplasms amid the COVID-19 pandemic. We summarise key changes related to service allocation, clinical and supportive care, clinical trial participation, and ethical considerations regarding the use of lifesaving measures for these patients. We recognise that these recommendations might be more applicable to high-income countries and might not be generalisable because of regional differences in health-care infrastructure, individual circumstances, and a complex and highly fluid health-care environment. Despite these limitations, we aim to provide a general framework for the care of patients with acute leukaemias and myeloid neoplasms during the COVID-19 pandemic on the basis of recommendations from international experts

ALCAM (CD166) Expression and Serum Levels in Pancreatic Cancer

BACKGROUND: This study was conducted to evaluate the expression of the activated leukocyte cell adhesion molecule (ALCAM) in pancreatic cancer (PAC) and to determine whether or not the ectodomain shedding of ALCAM (s-ALCAM) could serve as a biomarker in the peripheral blood of PAC patients. MATERIAL AND METHODS: Tissue specimens and blood sera of patients with PAC (n = 264 and n = 116, respectively) and the sera of 115 patients with chronic pancreatitis (CP) were analyzed via ALCAM immunohistochemistry and s-ALCAM ELISA tests. Results were correlated with clinical, histopathological, and patient survival data (Chi-square test, Kaplan-Meier analysis, log-rank test, respectively). RESULTS: ALCAM was expressed in the majority of PAC lesions. Immunohistochemistry and serum ELISA tests revealed no association between ALCAM expression in primary tumors or s-ALCAM and clinical or histopathological data. Neither ALCAM nor s-ALCAM showed a significant impact regarding overall survival (p = 0.261 and p = 0.660, respectively). S-ALCAM serum levels were significantly elevated compared to the sera of CP patients (p<0.001). The sensitivity of s-ALCAM in detecting PAC was 58.6% at a specificity of 73.9% (AUC = 0.69). CONCLUSIONS: ALCAM is expressed in the majority of PAC lesions, but statistical analysis revealed no association with clinical or pathological data. Although significantly elevated in patients with PAC, the sensitivity and specificity of the s-ALCAM serum quantification test was low. Therefore, its potential as a novel diagnostic marker for PAC remains elusive and further investigations are required

Identification of heavy-flavour jets with the CMS detector in pp collisions at 13 TeV

Many measurements and searches for physics beyond the standard model at the LHC rely on the efficient identification of heavy-flavour jets, i.e. jets originating from bottom or charm quarks. In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented. Heavy-flavour jet identification algorithms have been improved compared to those used previously at centre-of-mass energies of 7 and 8 TeV. For jets with transverse momenta in the range expected in simulated $\mathrm{t}\overline{\mathrm{t}}$ events, these new developments result in an efficiency of 68% for the correct identification of a b jet for a probability of 1% of misidentifying a light-flavour jet. The improvement in relative efficiency at this misidentification probability is about 15%, compared to previous CMS algorithms. In addition, for the first time algorithms have been developed to identify jets containing two b hadrons in Lorentz-boosted event topologies, as well as to tag c jets. The large data sample recorded in 2016 at a centre-of-mass energy of 13 TeV has also allowed the development of new methods to measure the efficiency and misidentification probability of heavy-flavour jet identification algorithms. The heavy-flavour jet identification efficiency is measured with a precision of a few per cent at moderate jet transverse momenta (between 30 and 300 GeV) and about 5% at the highest jet transverse momenta (between 500 and 1000 GeV)

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis