Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment of polycythemia vera with hydroxyurea and pipobroman: final results of a randomized trial initiated in 1980.

PURPOSE The overall impact of hydroxyurea (HU) or pipobroman treatments on the long-term outcome of patients with polycythemia vera (PV) has not been assessed in randomized studies. We report final analyses from the French Polycythemia Study Group (FPSG) study, which randomly assigned HU versus pipobroman as first-line therapy in 285 patients younger than age 65 years. PATIENTS AND METHODS The full methodology has been described previously. FPSG results were updated with a median follow-up of 16.3 years. Statistical analysis was performed by using competing risks on the intention-to-treat population and according to main treatment received. RESULTS Median survival was 17 years for the whole cohort, 20.3 years for the HU arm, and 15.4 years for the pipobroman arm (P = .008) and differed significantly from that in the general population. At 10, 15, and 20 years, cumulative incidence of acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) was 6.6%, 16.5%, and 24% in the HU arm and 13%, 34%, and 52% in the pipobroman arm (P = .004). Cumulative myelofibrosis incidence at 10, 15, and 20 years according to main treatment received was 15%, 24%, and 32% with HU versus 5%, 10%, and 21% with pipobroman (P = .02). CONCLUSION Data from this unique randomized trial comparing HU with another cytoreductive drug in PV showed that (1) survival of patients with PV treated with conventional agents differed from survival in the general population, (2) evolution to AML/MDS is the first cause of death, (3) pipobroman is leukemogenic and is unsuitable for first-line therapy, and (4) incidence of evolution to AML/MDS with HU is higher than previously reported, although consideration should be given to the natural evolution of PV.
Identifying and Rewarding Pharmaceutical Innovation: Application in an EU Member State

The European Pharmaceutical Forum (EPF) issued “good practice” recommendations on the need to identify and reward valuable innovation. We investigated the compliance of the Belgian reimbursement procedure with the specific EPF recommendations by analyzing all 110 submissions for added therapeutic value (ATV) in the period 2002–2007. Prior to the reimbursement decision, a relative assessment of the therapeutic value was done with a binary outcome (ATV granted or refused). Overall, ATV was granted for 61 submissions (55%) or 10 compounds per year. Because this number is similar to the number of new products with CDER priority review or with “important to major” therapeutic benefit granted by the French reimbursement authority, we expect that valuable innovation has been identified. A positive reimbursement decision was obtained in 76 cases (69%). Granting of ATV (P <.001) was the most significant factor affecting the reimbursement decision (OR and its 95% CI: 17.9 [5.5-58.3]), suggesting the Belgian reimbursement procedure also rewards value for innovative products as EPF recommends. Because more than 50% of the variance still remains unexplained, one cannot confirm or reject the impact of other factors (financial, economic, etc) possibly affecting the reimbursement decision.
The informational impact of electronic trading systems on the FTSE 100 stock index and its futures contracts

This article examines the partial adjustment factors of Financial Times Stock Exchange (FTSE) 100 stock index and stock index futures. Using high frequency data from 15 January 1997 to 17 March 2000, it aims to assess the informational impact of the electronic trading systems implemented at the London Stock Exchange and London International Financial Futures Exchange (LIFFE). The results suggest that information runs mainly from the futures market to the spot market. We find that the introduction of stock exchange trading system, in October 1997, has increased the FTSE 100 index's absolute efficiency; however, it reduced the informational feedback to the futures market. The implementation of LIFFE CONNECT at LIFFE, in May 1999, has reduced the absolute and relative efficiency of FTSE 100 futures. These findings seem to imply that during the period under scrutiny electronic trading increased the level of microstructural noise, probably due to the bid–ask bounce and order flow imbalances.
Bleeding complications to oral anticoagulant therapy: multivariate analysis of 1010 treatment years in 551 outpatients

Abstract. One thousand and ten patient years of oral anticoagulant therapy with vitamin‐K‐antagonists were reviewed with regard to major bleeding complications. The incidence of bleeding that necessitated hospital admission was 2.7% per year (95% confidence limits, 1.7–3.7%). The major source of bleeding was the alimentary tract, whereas no cases of intracranial bleeding were found. Various factors with potential effects on the bleeding risk were evaluated by multivariate statistical analysis, and the following independent risk factors were identified: age > 75 years and hypertension increased the bleeding risk by 10.5% and 4.5%, respectively. Each recorded prothrombin value significantly below the therapeutic range increased the bleeding risk by 3.9%, and each year of treatment increased the risk by 2.0%. These figures may be used to estimate the risk of major bleeding in an individual patient. Current treatment with thiazide diuretics was found to increase the bleeding risk by 5.2%. However, this observation requires further documentation and analysis. Although no lethal episodes of bleeding occurred, the developing field of indications for oral anticoagulant therapy should be considered on the basis of a continuous substantial risk of major bleeding.
Cranial Capacity of Zinjanthropus and other Australopithecines

assemblage is of a short powerful hand with strong, curved digits, surmounted by broad, flat nails and held in marked flexion. The thumb is strong and opposable, though possibly rather short. At a recent conference at Burg Wartenstein, Austria, organized by the Wenner-Gren Foundation for Anthropological Research, an attempt was made to produce a diagnosis for the genus Homo. It was agreed that such a diagnosis could not be made unless certain characters and character complexes were present in combination. Included in these characters, which are referable to the skull, the brain and the post-cranial skeleton, was the criterion that 'the hand is capable of making tools of a recognizable culture. ' If one assumes that the artefacts of an early Oldowan culture found on the living floor were the work of the species the remains of which are found there, then this criterion is fulfilled and, in addition, an interesting conclusion is possible: that toolmaking was established in the human lineage long before the hand had assumed its modern human form. If, on the other hand, one bears the possibility in mind that some other, more advanced form was the toolmaker and the known incumbents of the floor were its victims, then it is in the functional morphology of the hand itself that one must look for evidence of toolmaking. On anatomical grounds there is no doubt that theOlduvai' hand was sufficiently advanced in terms of the basic power and precision grips to have used naturally occurring objects as tools to good advantage. There is less certainty about toolmaking, which involves not only a peripheral but also a central intellectual factor as Oakley (1949) has long insisted. The report on the Bed I juvenile skull fragments, soon to be published, may throw some light on this question by indicating the approximate cranial capacity of the juvenile skull. Given the intellectual ability, the construction of the crude, rather small pebble-tools of the type found on the living floor, is well within the physical capacity of the Olduvai hand. Precision grip, which is imperfectly evolved in the fossil hand, is not an essential requisite at this level of craftsmanship as personal experiments in the construction of '01dowan' pebble-tools and 'Chellean' hand-axes have shown (Fig. 2).
Collaborative remembering of emotional events: The case of Rabin's assassination

Individual and collaborative remembering of the assassination of Israel's Prime Minister, Itzhak Rabin, were compared. In line with previous laboratory findings on memory of neutral stimuli, it was hypothesised that collaborative remembering (three individuals reaching a common response) and nominal remembering (three individual responses pooled together) of the assassination would be more accurate than individual remembering. A total of 146 participants responded (115 individually and 120 in groups of three) to open-ended and multiple-choice questionnaires (among them, 89 responded twice with a week of intertest interval) about Rabin's assassination and the events that preceded and followed it. Data analysis showed that the collaborative responses to the open-ended questionnaire contained more details (both accurate and inaccurate) than the individual responses, and that the responses to the multiple-choice questionnaire were more accurate than the individual responses. However, the collaborative responses contained fewer details (both accurate and inaccurate) than the nominal responses. Responses to the two questionnaires were more accurate on the retest when they followed collaborative rather than individual responses on the original test. The inferiority of the collaborative relative to the nominal remembering was attributed to collaborative inhibition, whereas the positive effect of collaborative remembering on performance on the retest was attributed to the contribution of contextual cues.
A survey of short sea shipping and its prospects in the USA

The continuing growth of international container trade has created capacity problems at major US ports, and the truck-based freight transportation has caused a deterioration of traffic congestion on important US transportation corridors. Using inland and coastal waterways, short sea shipping (SSS) can provide an improvement to these problems. Furthermore, SSS offers many additional benefits for the environment, the economy and society as a whole. Both the US Department of Transportation and the European Commission actively support SSS as an alternative, environmentally friendly mode of transportation. However, there are obstacles, administrative barriers and challenges that should be addressed. Several successful operations on both sides of the Atlantic make a strong case in favour of SSS. SSS can develop customized and technologically advanced solutions that will further integrate it into the intermodal transportation chain and will improve its image among shippers as a mode that can provide reliable door-to-door transportation. This paper reviews several studies on the subject and discusses the latest developments on SSS in the US and in Europe. It also addresses the major issues and the benefits of SSS and examines the prospects for potential short sea operations in the US. Finally, it proposes research opportunities for a multimodal transportation system that will include a short sea component.
Randomised controlled trial of transcutaneous electrical muscle stimulation of the lower extremities in patients with chronic obstructive pulmonary disease

Background: Although exercise training improves exercise tolerance in most patients with chronic obstructive pulmonary disease (COPD), some patients with severe disease may not be able to tolerate exercise training due to incapacitating breathlessness. Transcutaneous electrical muscle stimulation (TCEMS) has been shown to improve muscle strength, muscle mass, and performance in paraplegics, patients with knee ligament injury, and patients with peripheral vascular disease. We hypothesised that TCEMS of the lower extremities can improve muscle strength and exercise tolerance in patients with moderate to severe COPD. Methods: A randomised controlled trial of TCEMS of the lower extremities was performed in 18 medically stable patients of mean (SD) age 60.0 (1.5) years with a mean forced expiratory volume in 1 second (FEV1) of 1.03 (0.10) l (38% predicted) and residual volume/total lung capacity (RV/TLC) of 59 (2)%. Stimulation of the lower extremities was performed three times a week, 20 minutes each session, for six continuous weeks. Quadriceps and hamstring muscle strength, exercise capacity, and peak oxygen uptake were measured at baseline and after 6 weeks of stimulation. Results: TCEMS improved both the quadriceps strength (by 39.0 (20.4)% v 9.0 (8.1)%, p=0.046) and hamstring muscle strength (by 33.9 (13.0)% v 2.9 (4.7)%, p=0.038) in the treated (n=9) and sham treated (n=9) groups, respectively. The improvement in muscle strength carried over to better performance in the shuttle walk test in the treated group (36.1% v 1.6% in the treated and sham groups respectively, p=0.007, Mann-Whitney U test). There was no significant change in lung function, peak workload, or peak oxygen consumption in either group. Muscle stimulation was well tolerated by the patients with no dropouts and better than 95% compliance with the protocol. Conclusions: TCEMS of peripheral muscles can be a useful adjunct to the comprehensive pulmonary rehabilitation of patients with COPD.
Clinical diagnostic accuracy and magnetic resonance imaging of patients referred by physical therapists, orthopaedic surgeons, and nonorthopaedic providers.

STUDY DESIGN Nonexperimental, retrospective design. OBJECTIVES This study was designed to compare clinical diagnostic accuracy (CDA) between physical therapists (PTs), orthopaedic surgeons (OSs), and nonorthopaedic providers (NOPs) at Keller Army Community Hospital on patients with musculoskeletal injuries (MSI) referred for magnetic resonance imaging (MRI). BACKGROUND US Army PTs are frequently the first credentialed providers privileged to examine and diagnose patients with musculoskeletal injuries. Physical therapists assigned at Keller Army Community Hospital have also been credentialed with privileges to order MRI studies for several years. METHODS AND MEASURES To reduce provider bias, a retrospective analysis was performed on 560 patients referred for MRI over an 18-month period. An electronic review of each patient's radiological profile was performed to assess agreement between clinical diagnosis and MRI findings. Data analyses were performed through descriptive statistics and contingency tables. RESULTS Analysis on agreement between clinical diagnosis and MRI findings produced a CDA of 74.5% (108/145) for PTs, 80.8% (139/172) for OSs, and 35.4% (86/243) for NOPs. There was a significant difference in CDA between PTs and NOPs (P<.001), and between OSs and NOPs (P<.001). There was no difference in CDA between PTs and OSs (P>.05). CONCLUSIONS Clinical diagnostic accuracy by PTs and OSs on patients with musculoskeletal injuries was significantly greater than for NOPs, with no difference noted between PTs and OSs.
Feline spongiform encephalopathy: fibril and PrP studies

The brains from 18 cats were examined for the presence of the fibrils and modified PrP protein which are molecular diagnostic markers for scrapie-like diseases. Thirteen cats were referred with clinical neurological signs potentially indicative of feline spongiform encephalopathy (FSE). Of these, five had histopathological changes of FSE, five had other lesions of the central nervous system, and in three the brain was normal. The remaining five cats had no clinical neurological signs and were selected as controls. Fibrils and modified PrP protein were found in the brains of the five cats with FSE and in one of the cats with neurological signs but no histopathological changes in the central nervous system. Fibrils were present in the absence of modified PrP in the brains of two cats, one with neurological signs and a histologically confirmed meningioma, and one with no neurological signs and a histologically normal brain.
Blood flow and metabolism in locally advanced breast cancer: relationship to response to therapy.

UNLABELLED Locally advanced breast cancer (LABC) is commonly treated with neoadjuvant chemotherapy followed by definitive surgery. The factors influencing the response of LABC to presurgical chemotherapy are incompletely understood. To characterize in vivo tumor biology in patients with LABC, we measured pretherapy blood flow and glucose metabolism in LABC, compared measurements with clinical and pathologic parameters, and examined blood flow and response to subsequent neoadjuvant chemotherapy. METHODS Thirty-seven patients with newly diagnosed LABC underwent (18)F-FDG and (15)O-water PET imaging. Thirty-one of these patients underwent neoadjuvant chemotherapy, and response was evaluated by serial measurements of tumor size and pathologic examination after definitive surgery after chemotherapy. Tumor metabolism was estimated from graphic analysis of dynamic (18)F-FDG studies and was expressed as the metabolic rate of (18)F-FDG (MRFDG). Blood flow was estimated from dynamic images after bolus (15)O-water injection using a 1-compartment model. Tumor blood flow and metabolism were compared with clinical and pathologic parameters and with response to chemotherapy. RESULTS Both blood flow and metabolism were significantly higher in tumor than in normal breast. Tumor blood flow and metabolism were correlated but highly variable. There were weak associations of metabolism with patient age and tumor grade and of blood flow with estrogen receptor status. There was a statistically significant trend for patients with a high MRFDG to have a poorer response to therapy (P = 0.001). Response was not significantly correlated with any other parameters. A low ratio of MRFDG to blood flow was the best predictor of macroscopic complete response (CR) (P = 0.02 vs. non-CR). Preliminary analysis of patient follow-up showed the ratio of MRFDG to blood flow to also be predictive of disease-free survival. CONCLUSION Despite uniformly large tumor size, blood flow and metabolism in LABC are highly variable. High glucose metabolism predicts a poor response to neoadjuvant chemotherapy, and low MRFDG relative to blood flow is a predictor of CR. Further work is needed to elucidate the biologic mechanisms underlying these findings.
I Trust my Zombies: A Trust-enabled Botnet

Defending against botnets has always been a cat and mouse game. Cyber-security researchers and government agencies attempt to detect and take down botnets by playing the role of the cat. In this context, a lot of work has been done towards reverse engineering certain variants of malware families as well as understanding the network protocols of botnets to identify their weaknesses (if any) and exploit them. While this is necessary, such an approach offers the botmasters the ability to quickly counteract the defenders by simply performing small changes in their arsenals. We attempt a different approach by actually taking the role of the Botmaster, to eventually anticipate his behavior. That said, in this presentation, we present a novel computational trust mechanism for fully distributed botnets that allows for a resilient and stealthy management of the infected machines (zombies). We exploit the highly researched area of computational trust to create an autonomous mechanism that ensures the avoidance of common botnet tracking mechanisms such as sensors and crawlers. In our futuristic botnet, zombies are both smart and cautious. They are cautious in the sense that they are careful with whom they communicate with. Moreover, they are smart enough to learn from their experiences and infer whether their fellow zombies are indeed who they claim to be and not government agencies' spies. We study different computational trust models, mainly based on Bayesian inference, to evaluate their advantages and disadvantages in the context of a distributed botnet. Furthermore, we show, via our experimental results, that our approach is significantly stronger than any technique that has been seen in botnets to date. Finally, we step out of the adversarial perspective and touch the topic of countermeasures against our own approach.
Lasting Impacts of Indonesia’s Financial Crisis

We study the poverty impacts over time and space of Indonesia’s severe economy‐wide crisis of 1998, using 10 large national surveys spanning 1993–2002. On allowing for shifts in relative prices stemming from the crisis, we find a sharp but geographically uneven increase in the poverty rate in 1998, reflecting both the unevenness in the extent of the economic contraction and the differing initial conditions at the local level. Our counterfactual analyses indicate geographically diverse recovery rates 4 years later. Proportionate impacts on the poverty rate in both 1998 and 2002 were greater in initially better‐off and less unequal districts. In the aggregate, a large share—possibly half—of the poverty count in 2002 is attributed to the 1998 crisis.
THE RELATIONSHIP OF IN VITRO LYMPHOCYTE COMPATIBILITY TO HOMOGRAFT SENSITIVITY IN MAN *

In another paper’ in this monograph, we have presented evidence that cultured human peripheral blood lymphocytes are immunologically capable and show immunological specificity. As outlined in that paper, their degree of response to specific and nonspecific stimuli can be quantitated by counting the number of cells which have enlarged in culture and those cells undergoing mitosis. Wilson2 has shown that if a n animal is immunized with a skin graft from an unrelated animal, thoracic duct lymphocytes from the recipient kill cultured renal cells derived from an animal of the donor’s strain. These lymphocytes will not attack renal cells from other strains known to have markedly different histocompatibility antigens, demonstrating the specificity of this cytotoxic effect. Many investigators have used lymphocytes to sensitize individuals, producing accelerated rejection of the skin graft from the donor of the lymphocytes to the immunized individual. This shows that the lymphocyte contains histocompatibility antigens and is capable of producing an immune reaction to these. Therefore, the lymphocyte appears to be representative of both the donor’s and the recipient’s contribution in transplantation. Brent and Medawar? have used lymphocytes injected subcutaneously to test for genetically determined histocompatibility differences between various animals. They have found no reaction to injected lymphocytes transferred within an inbred strain. This correlates with the finding by numerous investigators that transplants from one identical twin to the other are not rejected. These observations provide a basis for the assumption that differences in histocompatibility antigens are genetically determined. Bain et al.* have shown that if peripheral blood lymphocytes from two unrelated individuals are mixed in vitro, there is an increase in the incorporation of radioactive thymidine into DNA. Monozygous twins showed no such response, while among a series of dizygous twins, two pairs were found who also did not react with each other. We have done similar studies on lymphocyte mixtures. However, our method of quantitation depends on counting the percentage of cells which have become enlarged in culture, and adding to these the percentage of cells in mitosis, since these latter derive from enlarged cells. The details of the culture methods are described e l ~ e w h e r e . ~ A time curve of this response (FIGURE 1) demonstrates that the peak of observable reaction occurs between seven and eight days. The degree of this reaction varies from no increase over the spontaneous rate of enlargement and mitosis (approximately five per cent) in identical twins, to a response of 85 per cent observed in two individuals from widely divergent ethnic backgrounds. As a rule, blood relatives show less of a response. than unrelated