Miracle-dz/UniFAR-FTUs huggingface dataset:
Disease activity guided dose reduction and withdrawal of adalimumab or etanercept compared with usual care in rheumatoid arthritis: open label, randomised controlled, non-inferiority trial

Objective To evaluate whether a disease activity guided strategy of dose reduction of two tumour necrosis factor (TNF) inhibitors, adalimumab or etanercept, is non-inferior in maintaining disease control in patients with rheumatoid arthritis compared with usual care. Design Randomised controlled, open label, non-inferiority strategy trial. Setting Two rheumatology outpatient clinics in the Netherlands, from December 2011 to May 2014. Participants 180 patients with rheumatoid arthritis and low disease activity using adalimumab or etanercept; 121 allocated to the dose reduction strategy, 59 to usual care. Interventions Disease activity guided dose reduction (advice to stepwise increase the injection interval every three months, until flare of disease activity or discontinuation) or usual care (no dose reduction advice). Flare was defined as increase in DAS28-CRP (a composite score measuring disease activity) greater than 1.2, or increase greater than 0.6 and current score of at least 3.2. In the case of flare, TNF inhibitor use was restarted or escalated. Main outcome measures Difference in proportions of patients with major flare (DAS28-CRP based flare longer than three months) between the two groups at 18 months, compared against a non-inferiority margin of 20%. Secondary outcomes included TNF inhibitor use at study end, functioning, quality of life, radiographic progression, and adverse events. Results Dose reduction of adalimumab or etanercept was non-inferior to usual care (proportion of patients with major flare at 18 months, 12% v 10%; difference 2%, 95% confidence interval −12% to 12%). In the dose reduction group, TNF inhibitor use could successfully be stopped in 20% (95% confidence interval 13% to 28%), the injection interval successfully increased in 43% (34% to 53%), but no dose reduction was possible in 37% (28% to 46%). Functional status, quality of life, relevant radiographic progression, and adverse events did not differ between the groups, although short lived flares (73% v 27%) and minimal radiographic progression (32% v 15%) were more frequent in dose reduction than usual care. Conclusions A disease activity guided, dose reduction strategy of adalimumab or etanercept to treat rheumatoid arthritis is non-inferior to usual care with regard to major flaring, while resulting in the successful dose reduction or stopping in two thirds of patients. Trial registration Dutch trial register (www.trialregister.nl), NTR 3216.
Community health insurance as a viable means of increasing access to health care for rural households in Uganda

-------------------------------------------------------------------------------------ii DECLARATION -------------------------------------------------------------------------------------iii DEDICATION -------------------------------------------------------------------------------------iv ACKNOWLEDGEMENTS -----------------------------------------------------------------------------v TABLE OF CONTENTS --------------------------------------------------------------------------------vi LIST OF TABLES -------------------------------------------------------------------------------------xi LIST OF FIGURES AND MAPS ---------------------------------------------------------------------xii LIST OF ACRONYMS --------------------------------------------------------------------------------xiii GLOSSARY OF TERMS ---------------------------------------------------------------------------------xv CHAPTER ONE: INTRODUCTION 1.1 General Background ------------------------------------------------------------------------------------1 1.2 The Research Context ---------------------------------------------------------------------------2 1.2. 1 Uganda: General Overview -------------------------------------------------------------------2 1.2. 2 Uganda’s Health Indicators -------------------------------------------------------------------5 1.2. 3 Uganda’s Social Security Framework ------------------------------------------------------6 1.2. 4 Uganda’s National Health Policy ------------------------------------------------------------9 1.3 The Case for Community Health Insurance -------------------------------------------------17 1.4. The Research Problem --------------------------------------------------------------------------------20 1.5 Purpose of the Study ----------------------------------------------------------------------------------21 1.5. 1 Main Research Questions --------------------------------------------------------------------21 1.5. 2 Objectives of the Study -----------------------------------------------------------------------22 1.6 Significance of the Study ----------------------------------------------------------------------------22 1.7. Scope of the Study -------------------------------------------------------------------------------------23 1.8 Organisation of the Thesis --------------------------------------------------------------------------24 CHAPTER TWO: MAPPING THE CONCEPTUAL FRAMEWORK 2.
Personality and Obsessional Neurosis

It is generally accepted that the obsessional personality (obsessoid, anal-erotic character) is the premorbid personality most frequently associated with obsessional neurosis. Freud (1908) described the triad of traits of orderliness, parsimoniousness and obstinacy which characterizes this personality. He considered that these traits were due to reaction formation against and sublimation of anal-erotic activities and aggressive impulses into socially acceptable forms of behaviour. According to this view the anal-erotic character and obsessional neurosis share a common developmental basis—the neurosis represents a failure of repression, the regression to the anal-sadistic level of libidinal organization and the use of defences against excessive hostility.
Bring your own device organizational information security and privacy

BYOD is a growing trend in corporate environments, where employees bring their own devices to work. Factors that have led to the growing popularity of BYOD include the benefits of work flexibility, increased productivity, and efficiency of employees. Despite these benefits, there are concerns over information security and privacy. Since BYOD allows employees to access organizational data anytime anywhere, it is necessary to ensure the confidentiality and integrity of organizational information resources and assets. This paper will review BYOD, and information security and privacy in BYOD environments. Three different cases study organisational practices for BYOD security and privacy. Finally, advice on how to handle security and privacy in BYOD environments, using explicit policies, is presented. The paper will assist organisations, information technology and information security/privacy professionals to understand risks associated with BYOD, and policy development to mitigate them.
Hedge Fund Style Allocation : A Risk Adjusted Fund of Hedge Fund Perspective

The purpose of the thesis has been to explore the use of hedge fund styles when constructing portfolios of hedge funds (i.e. funds of hedge funds). The central question is if the use of hedge fund styles can significantly explain and improve risk adjusted returns (characterized by Sharpe ratios). The study has been done in collaboration with Optimized Portfolio Management AB who desire further knowledge and evaluation of hedge fund styles for their fund of hedge funds.To be able to create successful ex ante portfolios we have explored various prediction models for both risk and return. Our findings indicate that return prediction is problematic using simple models such as regression since the risk exposure of the indices appear to change significantly over time. One can however using exponentially weighted moving averages (EWMA) achieve relatively promising estimations of future returns. Covariance matrix estimation seems to be more straightforward. We have achieved promising results using both traditional EWMA models as well as improved estimators using principal component analysis.Covariance prediction models were evaluated separately using a minimum-variance portfolio optimization technique and provided a significant risk reduction compared to the aggregated hedge fund universe (represented by a naively diversified portfolio). Combinations of risk and return prediction models were evaluated using traditional mean-variance portfolio construction methods, which were optimized for Sharpe ratios. These provided a significant increase in risk adjusted returns relative to the aggregated hedge fund universe. The allocation is however discouraging due to serious instability over time.Our findings indicate that there indeed is an advantage of taking hedge fund styles into consideration when constructing funds of hedge funds in a risk adjusted perspective. However, further research into return prediction needs to be done in order to stabilize portfolio allocation. An alternative seems to be tactical style allocation on a more fundamental analysis basis.
WdCHS 3 , a Gene That Encodes a Class III Chitin Synthase in Wangiella ( Exophiala ) dermatitidis , Is Expressed Differentially under Stress Conditions

Class III chitin synthases are important for hyphal growth in some filamentous fungi but are not found in yeasts. Using a specific PCR product that encodes a portion of the class III chitin synthase of W. dermatitidis as a probe, we isolated the chitin synthase gene, WdCHS3, from this polymorphic melanized pathogen of humans. Northern blotting showed that WdCHS3 was highly expressed under stress conditions, such as the shift of cells to temperatures commensurate with infection, or to conditions that induce cellular morphogenesis in this fungus. Analysis of the 5* upstream sequence of WdCHS3 provided evidence for a negative regulatory element at between 2780 and 21600 bp. Western blotting indicated that the production of the WdChs3p was temperature dependent and temporally regulated. Disruption of WdCHS3 in a wild-type strain and in two temperature-sensitive morphological mutants resulted in significantly reduced chitin synthase activities but did not obviously affect their morphologies, growth rates, chitin contents, or virulence. This paradox suggested that the contributions of the high levels of WdCHS3 gene expression and WdChs3p production in strains subjected to stress reside in unknown or unexamined parts of the life cycle of this ecologically poorly known member of the Fungi Imperfecti. Nonetheless, this report presents the first evidence that transcription of a chitin synthase gene is regulated by a negative regulatory element in its 5* upstream sequence.
How is the relationship significance brought about? A critical realist approach

The markets-as-networks theorists contend, at least tacitly, the significance of business relationships for the focal firm – that is, business relationships contribute somewhat to the focal firm’s survival and growth. We do not deny the existence of significant business relationships but sustain, in contrast to the consensus within the Markets-as-Networks Theory, that relationship significance should not be a self-evident assumption. Significance cannot be a taken-for-granted property of each and every one of the focal firm’s business relationships. We adopt explicitly a critical realist position in this conceptual paper and claim that the relationship significance is an event of the business world, whose causes remain yet largely unidentified. Where the powers and liabilities of business relationships (i.e., their functions and dysfunctions) are put to work, inevitably under certain contingencies (namely the surrounding networks and markets), effects result for the focal firm (often benefits in excess of sacrifices, i.e., relationship value) and as a result the relationship significance is likely to be brought about. In addition, the relationship significance can result from the dual influence that business relationships have on a great part of the structure and powers and liabilities of the focal firm, i.e., its nature and scope respectively.
Surgical Treatment of Eyelid Tumors

Eyelid tumors constitute about 40% of all cancers located in the orbital region. Most commonly, they are basal cell carcinomas, in 90% of cases located in the lower eyelid and medial canthus. The purpose of our study was to present the management and to overview the results of surgical treatment of eyelid tumors. Materials and Methods:One hundred ninety-three patients, 89 men and 104 women, aged 16 to 87 years (mean, 63.5 years) with eyelid tumors were treated in Plastic Surgery Hospital in Polanica-Zdrój in the years 1985 to 2008. The patients were divided into 2 groups: group 1 (n = 148) was composed of patients operated on primarily in our hospital, and group 2 (n = 45) was composed of patients operated on in other hospitals, admitted for recurrence. All the patients underwent surgery involving resection of the tumor and simultaneous eyelid reconstruction. The preparations were evaluated histopathologically. Various surgical modalities were used, depending on the extent and location of the tumor. Results:Recurrence developed in 13 patients in group 1 (8.7%; 5 women and 8 men) and in 9 patients in group 2 (20%; 5 women and 4 men). Conclusions:Tumors, usually basal cell carcinoma, originate mainly in the lower eyelid and medial canthus. Surgery should be performed as soon as possible after onset of the primary tumors and should include resection and reconstructive therapy. The highest risk of recurrence is in case of squamous cell and basospinocellular tumors, and especially in melanoma. The aim of reconstructive therapy is to reconstruct aesthetically and functionally effective eyelid.
CCR Translations Trastuzumab : A Picky Partner ?

Preclinical and clinical models of HER2-positive breast cancer show that human epidermal growth factor receptor 2 (HER2)-targeted therapy with trastuzumab adds significant benefits and modest risks to conventional cytotoxic therapies. Building on this advance will likely depend on elucidation of relevant signaling pathways and mechanisms of action for effective HER2-targeted therapies. (Clin Cancer Res 2009;15(20):6311–3)
Factors influencing the biocompatibility of insertable silicon microshafts in cerebral cortex

Issues that determine the biocompatibility of insertable microelectrode arrays were investigated. Results from a limited number of tests indicated that there was minimal tissue response along the sides of the shafts when shafts were well sharpened, had sufficiently small tip angles, and were clean. Tissue was usually more reactive at the tips of the shafts. It was concluded that silicon microshafts of appropriate shaft and tip design were biocompatible along the sides of the shaft, but that relatively severe reactions could be anticipated at the tips. <<ETX>>
Targeted therapy for chronic lymphocytic leukemia: a glimpse into the future.

ning of a revolution in the treatment of CLL, with a series of small molecules in various stages of clinical development that target novel aspects of CLL biology. This progress results from a better understanding of the biology of CLL, including a realization that it is often a quite proliferative disease, depends on the tissue microenvironment, and upregulates antiapoptotic pathways to avoid programmed cell death. In addition, the mechanisms by which CLL develops resistance to conventional chemotherapy are becomingbetterdefined.Theseinsightsarenowleadingtothedevelopmentofagentsthatspecificallytargetthepathophysiologyofthe disease. The logical combination of these agents promises to dramatically alter the treatment of CLL and may eventually lead to therapy that is both more effective and less toxic. The strategy of targeting Bcl-2 through navitoclax is an important first step in changing our therapeutic approach in CLL.
10 k.y. depositional cyclicity in the early Eocene: Stratigraphic and 40Ar/39Ar evidence from the lacustrine Green River Formation

Ar/ 39 Ar dating of sanidine from two interbedded tuffs reveals that the maximum average duration of depositional cycles in the Wilkins Peak Member, Green River For- mation, was ;10 k.y. , marking the first time that subprecessional cycles have been rec- ognized in lacustrine strata. The origin of these cycles is uncertain, but may relate to a nonlinear climatic response to orbital forcing of insolation. Alternatively, regional tectonic and geomorphic controls on drainage stability may have promoted autocyclic delivery of sediment to the lake. Owing to an interaction between basin-floor relief and varying am- plitudes of lake expansion, only one-third of the cycles identified near the basin center are present near the basin margin. This spatial variability in the temporal completeness of the stratigraphic record is not apparent from examination of individual localities, indi- cating that studies based on time-series analysis from other lacustrine systems may need reevaluation.
A Regulatory Approach to Derivative Markets: The Benefits of Private Sector Oversight

Beginning in the 1980’s over-the-counter (OTC) derivatives began trading in large amounts. Their trading volume grew rapidly, to a total notional value of $88.2tn by the end of 1999; their gross market value was about $2.8tn. However, since such large amounts of money are at stake in the OTC derivatives market, gaps in the regulatory framework and standards have the potential to cause large financial losses, which have that ability to undermine confidence in the financial system. As a result, there has been an ongoing debate in the United States about the proper role for regulation in the market for derivatives. In order to properly asses a regulatory approach, legislators and market participants must have thorough knowledge in derivatives and understand the market effectively. The derivatives market is vast with different derivative instruments that are traded on exchanges and over OTC markets. The large amounts of derivatives trading, and their potential threat to the stability of the global financial system, needs to be monitored by an effective regulatory framework that promotes growth and innovation and prevents risks and market failures. The successful role of the private sector in creating standardization and stability within the OTC derivatives market suggests that this type of framework could be successful in monitoring the market. 1 John O. Matthews and Cathy A. Rusinko, “Regulation in the US OTC derivatives market: Towards a more collaborative framework,” Derivatives Use, Trading & Regulation 7.4 (2002): 337.
A Trimeric Anti-HER2/neu ScFv and Tumor Necrosis Factor-α Fusion Protein Induces HER2/neu Signaling and Facilitates Repair of Injured Epithelia

Tumor necrosis factor (TNF)-α genetically fused to the carboxyl terminus of a single-chain Fv (ScFv) antibody specific for the human HER2/neu (anti-HER2/neu ScFv-TNF-α) forms a homotrimeric structure that retains both TNF-α activity and the ability to bind HER2/neu. In contrast to anti-HER2/neu IgG3, anti-HER2/neu ScFv-TNF-α induces potent HER2/neu signaling, activating the downstream mitogen-activated protein kinase (MAPK) and Akt pathways in SKBR3 cells. Activation of MAPK and Akt by anti-HER2/neu ScFv-TNF-α inhibited the apoptosis of SKBR3 cells induced by actinomycin D. Remarkably, anti-HER2/neu ScFv-TNF-α facilitated the repair of injured epithelia. Accelerated wound healing required binding to HER2/neu but not TNF-α activity since anti-HER2/neu ScFv-TNF-α (S147Y), containing a mutant TNF-α with significantly decreased biological activity, demonstrated equivalent ability to facilitate wound healing and soluble HER2/neu inhibited the effect. These results suggest that trimeric anti-HER2/neu ScFv has the potential to facilitate wound healing. In addition, fusion with TNF-α provides a novel approach to producing polymeric antibodies.
Vernalization-induced flowering in cereals is associated with changes in histone methylation at the VERNALIZATION1 gene

Prolonged exposure to low temperatures (vernalization) accelerates the transition to reproductive growth in many plant species, including the model plant Arabidopsis thaliana and the economically important cereal crops, wheat and barley. Vernalization-induced flowering is an epigenetic phenomenon. In Arabidopsis, stable down-regulation of FLOWERING LOCUS C (FLC) by vernalization is associated with changes in histone modifications at FLC chromatin. In cereals, the vernalization response is mediated by stable induction of the floral promoter VERNALIZATION1 (VRN1), which initiates reproductive development at the shoot apex. We show that in barley (Hordeum vulgare), repression of HvVRN1 before vernalization is associated with high levels of histone 3 lysine 27 trimethylation (H3K27me3) at HvVRN1 chromatin. Vernalization caused increased levels of histone 3 lysine 4 trimethylation (H3K4me3) and a loss of H3K27me3 at HvVRN1, suggesting that vernalization promotes an active chromatin state at VRN1. Levels of these histone modifications at 2 other flowering-time genes, VERNALIZATION2 and FLOWERING LOCUS T, were not altered by vernalization. Our study suggests that maintenance of an active chromatin state at VRN1 is likely to be the basis for epigenetic memory of vernalization in cereals. Thus, regulation of chromatin state is a feature of epigenetic memory of vernalization in Arabidopsis and the cereals; however, whereas vernalization-induced flowering in Arabidopsis is mediated by epigenetic regulation of the floral repressor FLC, this phenomenon in cereals is mediated by epigenetic regulation of the floral activator, VRN1.
Altered molecular adaptation to exercise in children with type 1 diabetes: beyond hypoglycemia

Rosa JS, Galassetti PR. Altered molecular adaptation to exercise in children with type 1 diabetes: beyond hypoglycemia. Pediatric Diabetes 2009: 10: 213–226. Jaime S Rosa and Pietro R Galassetti Department of Pediatrics, Institute for Clinical Translational Science, University of California, Irvine, Orange, CA, USA; and Department of Pharmacology, School of Medicine, University of California, Irvine, Irvine, CA, USA
On Embedding Rectangular Grids in Hypercubes

The following graph-embedding question is addressed: given a two-dimensional grid and the smallest hypercube with at least as many nodes as grid points, how can one assign grid points to hypercube nodes (with at most one grid point per node) so as to keep grid neighbors near each other in the cube? An embedding scheme for an infinite class of two-dimensional grids is given that keeps grid neighbors within a distance of two apart. >
New methodology for computer-aided modelling of biomolecular structure and dynamics. 1. Non-cyclic structures.

A general methodology is proposed for the conformational modelling of biomolecular systems. The approach allows one: (i) to describe the system under investigation by an arbitrary set of internal variables, i.e., torsion angles, bond angles, and bond lengths; it offers a possibility to pass from the free structure to a completely fixed one with the number of variables from 3N to zero, respectively, where N is the number of atoms; (ii) to consider both, a single molecule and a complex of many molecules, (e.g., proteins, water, ligands, etc.) in terms of one universal model; (iii) to study the dynamics of the system using explicit analytical Lagrangian equations of motion, thus opening up possibilities for investigations of slow concerted motions such as domain oscillations in proteins etc.; (iv) to calculate the partial derivatives of various functions of conformation, e.g., the conformational energy or external constraints imposed, using a standard efficient procedure regardless of the variables and the structure of the system. The approach is meant to be used in various investigations concerning the conformations and dynamics of biomacromolecules.