High-Dose Chemotherapy With Hematopoietic Stem Cell Transplant in Patients With High-Risk Breast Cancer and 4 or More Involved Axillary Lymph Nodes 20-Year Follow-up of a Phase 3 Randomized Clinical Trial:20-Year Follow-up of a Phase 3 Randomized Clinical Trial

Importance: Trials of adjuvant high-dose chemotherapy (HDCT) have failed to show a survival benefit in unselected patients with breast cancer, but long-term follow-up is lacking. Objective: To determine 20-year efficacy and safety outcomes of a large trial of adjuvant HDCT vs conventional-dose chemotherapy (CDCT) for patients with stage III breast cancer. Design, Setting, and Participants: This secondary analysis used data from a randomized phase 3 multicenter clinical trial of 885 women younger than 56 years with breast cancer and 4 or more involved axillary lymph nodes conducted from August 1, 1993, to July 31, 1999. Additional follow-up data were collected between June 1, 2016, and December 31, 2017, from medical records, general practitioners, the Dutch national statistical office, and nationwide cancer registries. Analysis was performed on an intention-to-treat basis. Statistical analysis was performed from February 1, 2018, to October 14, 2019. Interventions: Participants were randomized 1:1 to receive 5 cycles of CDCT consisting of fluorouracil, 500 mg/m 2, epirubicin, 90 mg/m 2, and cyclophosphamide, 500 mg/m 2, or HDCT in which the first 4 cycles were identical to CDCT and the fifth cycle was replaced by cyclophosphamide, 6000 mg/m 2, thiotepa, 480 mg/m 2, and carboplatin, 1600 mg/m 2, followed by hematopoietic stem cell transplant. Main Outcomes and Measures: Main end points were overall survival and safety and cumulative incidence risk of a second malignant neoplasm or cardiovascular events. Results: Of the 885 women in the study (mean [SD] age, 44.5 [6.6] years), 442 were randomized to receive HDCT, and 443 were randomized to receive CDCT. With 20.4 years median follow-up (interquartile range, 19.2-22.0 years), the 20-year overall survival was 45.3% with HDCT and 41.5% with CDCT (hazard ratio, 0.89; 95% CI, 0.75-1.06). The absolute improvement in 20-year overall survival was 14.6% (hazard ratio, 0.72; 95% CI, 0.54-0.95) for patients with 10 or more invoved axillary lymph nodes and 15.4% (hazard ratio, 0.67; 95% CI, 0.42-1.05) for patients with triple-negative breast cancer. The cumulative incidence risk of a second malignant neoplasm at 20 years or major cardiovascular events was similar in both treatment groups (20-year cumulative incidence risk for second malignant neoplasm was 12.1% in the HDCT group vs 16.2% in the CDCT group, P =.10), although patients in the HDCT group more often had hypertension (21.7% vs 14.3%, P =.02), hypercholesterolemia (15.7% vs 10.6%, P =.04), and dysrhythmias (8.6% vs 4.6%, P =.005). Conclusions and Relevance: High-dose chemotherapy provided no long-term survival benefit in unselected patients with stage III breast cancer but did provide improved overall survival in very high-risk patients (ie, with ≥10 involved axillary lymph nodes). High-dose chemotherapy did not affect long-term risk of a second malignant neoplasm or major cardiovascular events. Trial Registration: ClinicalTrials.gov Identifier: NCT03087409

Planetary Defense Ground Zero: MASCOT's View on the Rocks - an Update between First Images and Sample Return

At 01:57:20 UTC on October 3rd, 2018, after 3½ years of cruise aboard the JAXA spacecraft HAYABUSA2 and about 3 months in the vicinity of its target, the MASCOT lander was separated successfully by from an altitude of 41 m. After a free-fall of only ~5m51s MASCOT made first contact with C-type near-Earth and potentially hazardous asteroid (162173) Ryugu, by hitting a big boulder. MASCOT then bounced for ~11m3s, in the process already gathering valuable information on mechanical properties of the surface before it came to rest. It was able to perform science measurements at 3 different locations on the surface of Ryugu and took many images of its spectacular pitch-black landscape. MASCOT’s payload suite was designed to investigate the fine-scale structure, multispectral reflectance, thermal characteristics and magnetic properties of the surface. Somewhat unexpectedly, MASCOT encountered very rugged terrain littered with large surface boulders. Observing in-situ, it confirmed the absence of fine particles and dust as already implied by the remote sensing instruments aboard the HAYABUSA2 spacecraft. After some 17h of operations, MASCOT‘s mission ended with the last communication contact as it followed Ryugu’s rotation beyond the horizon as seen from HAYABUSA2. Soon after, its primary battery was depleted. We present a broad overview of the recent scientific results of the MASCOT mission from separation through descent, landing and in-situ investigations on Ryugu until the end of its operation and relate them to the needs of planetary defense interactions with asteroids. We also recall the agile, responsive and sometimes serendipitous creation of MASCOT, the two-year rush of building and delivering it to JAXA’s HAYABUSA2 spacecraft in time for launch, and the four years of in-flight operations and on-ground testing to make the most of the brief on-surface mission

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

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

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV