Fundamental analysis : portfolio management tool

The complex process of selecting a portfolio of financial instruments takes into account a particular investment objective, risk aversion of the investor, but also the impact of endogenous and exogenous factors on the evolution and return of the financial instruments. The central point of this paper is the selection of a portfolio of financial instruments based only on financial descriptors for the insurer’s financial status In the first phase, we proposed and tested a statistical model aimed at the connections between the financial statements descriptors of issuers and the market values return of stocks issued by them. Thus, we identified those descriptors, which in the period under review (2010-2013), had a direct impact on the dynamics of stock prices traded on the capital market in Europe and USA. We analyze companies that are part from the structure of Down Jones Industrial Average, WIG 20 and Euro Stoxx50. In the second stage, we calculated the return of the selected companies on the selected period by using investment signals based on fundamental analysis. The main results support the idea that an investor can have a portfolio that generates returns by using exclusively financial descriptors

Use of mefloquine in children - a review of dosage, pharmacokinetics and tolerability data

Currently available data provide a scientific basis for the use of mefloquine in small children in the chemoprophylaxis setting and as a part of treatment regimens for children living in endemic areas

Pregnancy and Fetal Outcomes After Exposure to Mefloquine in the Pre- and Periconception Period and During Pregnancy

Pregnant women who travel to malarious areas and their clinicians need data on the safety of malaria chemoprophylaxis. The drug safety database analysis of mefloquine exposure in pregnancy showed that the birth defect prevalence and fetal loss in maternal, prospectively-monitored cases were comparable to background rate

Final analysis of the international observational S-Collate study of peginterferon alfa-2a in patients with chronic hepatitis B

Background and aims Sustained off-treatment immune control is achievable in a proportion of patients with chronic hepatitis B treated with peginterferon alfa-2a. We evaluated on-treatment predictors of hepatitis B surface antigen (HBsAg) clearance 3 years after peginterferon alfa-2a treatment and determined the incidence of hepatocellular carcinoma. Methods A prospective, international, multicenter, observational study in patients with chronic hepatitis B who have been prescribed peginterferon alfa-2a (40KD) in a real-world setting. The primary endpoint was HBsAg clearance after 3 years' follow-up. Results The modified intention-to-treat population comprised 844 hepatitis B e antigen (HBeAg)positive patients (540 [64%] completed 3 years' follow-up), and 872 HBeAg-negative patients (614 [70%] completed 3 years' follow-up). At 3 years' follow-up, HBsAg clearance rates in HBeAg-positive and HBeAg-negative populations, respectively, were 2% (16/844) and 5% (41/872) in the modified intention-to-treat population and 5% [16/328] and 10% [41/ 394] in those with available data. In HBeAg-positive patients with data, Week 12 HBsAg levels <1500, 1500-20,000, and >20,000 IU/mL were associated with HBsAg clearance rates at 3 years' follow-up of 11%, 1%, and 5%, respectively (Week 24 predictability was similar). In HBeAg-negative patients with available data, a 6510% decline vs a <10% decline in HBsAg at Week 12 was associated with HBsAg clearance rates of 16% vs 4%. Hepatocellular carcinoma incidence was lower than REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B) model predictions. Conclusions Sustained off-treatment immune control is achieved with peginterferon alfa-2a in a real-world setting. HBsAg clearance 3 years after completion of peginterferon alfa-2a can be predicted on the basis of on-treatment HBsAg kinetics

Pregnancy and Fetal Outcomes After Exposure to Mefloquine in the Pre- and Periconception Period and During Pregnancy

Pregnant women who travel to malarious areas and their clinicians need data on the safety of malaria chemoprophylaxis. The drug safety database analysis of mefloquine exposure in pregnancy showed that the birth defect prevalence and fetal loss in maternal, prospectively-monitored cases were comparable to background rates

The position of mefloquine as a 21st century malaria chemoprophylaxis

BACKGROUND: Malaria chemoprophylaxis prevents the occurrence of the symptoms of malaria. Travellers to high-risk Plasmodium falciparum endemic areas need an effective chemoprophylaxis. METHODS: A literature search to update the status of mefloquine as a malaria chemoprophylaxis. RESULTS: Except for clearly defined regions with multi-drug resistance, mefloquine is effective against the blood stages of all human malaria species, including the recently recognized fifth species, Plasmodium knowlesi. New data were found in the literature on the tolerarability of mefloquine and the use of this medication by groups at high risk of malaria. DISCUSSION: Use of mefloquine for pregnant women in the second and third trimester is sanctioned by the WHO and some authorities (CDC) allow the use of mefloquine even in the first trimester. Inadvertent pregnancy while using mefloquine is not considered grounds for pregnancy termination. Mefloquine chemoprophylaxis is allowed during breast-feeding. Studies show that mefloquine is a good option for other high-risk groups, such as long-term travellers, VFR travellers and families with small children. Despite a negative media perception, large pharmaco-epidemiological studies have shown that serious adverse events are rare. A recent US evaluation of serious events (hospitalization data) found no association between mefloquine prescriptions and serious adverse events across a wide range of outcomes including mental disorders and diseases of the nervous system. As part of an in-depth analysis of mefloquine tolerability, a potential trend for increased propensity for neuropsychiatric adverse events in women was identified in a number of published clinical studies. This trend is corroborated by several cohort studies that identified female sex and low body weight as risk factors. CONCLUSION: The choice of anti-malarial drug should be an evidence-based decision that considers the profile of the individual traveller and the risk of malaria. Mefloquine is an important, first-line anti-malarial drug but it is crucial for prescribers to screen medical histories and inform mefloquine users of potential adverse events. Careful prescribing and observance of contraindications are essential. For some indications, there is currently no replacement for mefloquine available or in the pipeline

Using structural fragments to design antibody binding sites

Antibodies are an essential part of the immune system. They are able to attain high specificity and affinity to almost any antigen, and through their modularity make a robust framework for protein engineering. As a result, development of therapeutic antibodies has grown rapidly and they now account for the majority of revenue in the sales of new bio-therapeutics. The established design methods are heavily based on experimental simulation of the antibody maturation process outside of the human organism, and make little use of rational computational design methods. In this thesis we analysed the applicability and issues surrounding an existing modelling paradigm and developed a novel approach towards de novo antibody design. The majority of the affinity and specificity of antibodies is modulated by a set of six binding loops called the Complementarity Determining Region (CDR). We analysed the proportion of antibody CDRs that can be modelled in a set of 15 million antibody sequences. Out of all the CDRs H3 is the only one where we observed a large number of sequences that can not be modelled accurately. We then further explored why CDR H3 is so hard to model and found that the reason is not method dependent, but is a result of a lack of suitable structures. The H3 CDR shows unique structural characteristics at full loop, four residue and single residue levels of granularity. On the topic of de-novo antibody design we developed SAbDesigner, an automated computational pipeline for designing antibodies by mimicking the binding interface of a receptor of the target protein on the CDR. SAbDesigner automatically identifies important loops for binding on the receptor and then identifies an antibody framework that is able to accommodate it through loop grafting. The designs are then computationally validated, further refined using both point mutations, and optimisations of other CDRs. Through this pipeline we proposed a set of 15 novel antibodies that target Interleukin-5, an important therapeutic target, and also performed an applicability study across other major important therapeutic targets.</p

Using structural fragments to design antibody binding sites

Antibodies are an essential part of the immune system. They are able to attain high specificity and affinity to almost any antigen, and through their modularity make a robust framework for protein engineering. As a result, development of therapeutic antibodies has grown rapidly and they now account for the majority of revenue in the sales of new bio-therapeutics. The established design methods are heavily based on experimental simulation of the antibody maturation process outside of the human organism, and make little use of rational computational design methods. In this thesis we analysed the applicability and issues surrounding an existing modelling paradigm and developed a novel approach towards de novo antibody design. The majority of the affinity and specificity of antibodies is modulated by a set of six binding loops called the Complementarity Determining Region (CDR). We analysed the proportion of antibody CDRs that can be modelled in a set of 15 million antibody sequences. Out of all the CDRs H3 is the only one where we observed a large number of sequences that can not be modelled accurately. We then further explored why CDR H3 is so hard to model and found that the reason is not method dependent, but is a result of a lack of suitable structures. The H3 CDR shows unique structural characteristics at full loop, four residue and single residue levels of granularity. On the topic of de-novo antibody design we developed SAbDesigner, an automated computational pipeline for designing antibodies by mimicking the binding interface of a receptor of the target protein on the CDR. SAbDesigner automatically identifies important loops for binding on the receptor and then identifies an antibody framework that is able to accommodate it through loop grafting. The designs are then computationally validated, further refined using both point mutations, and optimisations of other CDRs. Through this pipeline we proposed a set of 15 novel antibodies that target Interleukin-5, an important therapeutic target, and also performed an applicability study across other major important therapeutic targets.</p