Portfolio-optimization models for small investors

Since 2010, the client base of online-trading service providers has grown significantly. Such companies enable small investors to access the stock market at advantageous rates. Because small investors buy and sell stocks in moderate amounts, they should consider fixed transaction costs, integral transaction units, and dividends when selecting their portfolio. In this paper, we consider the small investor’s problem of investing capital in stocks in a way that maximizes the expected portfolio return and guarantees that the portfolio risk does not exceed a prescribed risk level. Portfolio-optimization models known from the literature are in general designed for institutional investors and do not consider the specific constraints of small investors. We therefore extend four well-known portfolio-optimization models to make them applicable for small investors. We consider one nonlinear model that uses variance as a risk measure and three linear models that use the mean absolute deviation from the portfolio return, the maximum loss, and the conditional value-at-risk as risk measures. We extend all models to consider piecewise-constant transaction costs, integral transaction units, and dividends. In an out-of-sample experiment based on Swiss stock-market data and the cost structure of the online-trading service provider Swissquote, we apply both the basic models and the extended models; the former represent the perspective of an institutional investor, and the latter the perspective of a small investor. The basic models compute portfolios that yield on average a slightly higher return than the portfolios computed with the extended models. However, all generated portfolios yield on average a higher return than the Swiss performance index. There are considerable differences between the four risk measures with respect to the mean realized portfolio return and the standard deviation of the realized portfolio return.

A simple asthma prediction tool for preschool children with wheeze or cough

BACKGROUND Many preschool children have wheeze or cough, but only some have asthma later. Existing prediction tools are difficult to apply in clinical practice or exhibit methodological weaknesses. OBJECTIVE We sought to develop a simple and robust tool for predicting asthma at school age in preschool children with wheeze or cough. METHODS From a population-based cohort in Leicestershire, United Kingdom, we included 1- to 3-year-old subjects seeing a doctor for wheeze or cough and assessed the prevalence of asthma 5 years later. We considered only noninvasive predictors that are easy to assess in primary care: demographic and perinatal data, eczema, upper and lower respiratory tract symptoms, and family history of atopy. We developed a model using logistic regression, avoided overfitting with the least absolute shrinkage and selection operator penalty, and then simplified it to a practical tool. We performed internal validation and assessed its predictive performance using the scaled Brier score and the area under the receiver operating characteristic curve. RESULTS Of 1226 symptomatic children with follow-up information, 345 (28%) had asthma 5 years later. The tool consists of 10 predictors yielding a total score between 0 and 15: sex, age, wheeze without colds, wheeze frequency, activity disturbance, shortness of breath, exercise-related and aeroallergen-related wheeze/cough, eczema, and parental history of asthma/bronchitis. The scaled Brier scores for the internally validated model and tool were 0.20 and 0.16, and the areas under the receiver operating characteristic curves were 0.76 and 0.74, respectively. CONCLUSION This tool represents a simple, low-cost, and noninvasive method to predict the risk of later asthma in symptomatic preschool children, which is ready to be tested in other populations.

Risk factors associated with cast complications in horses: 398 cases (1997-2006)

OBJECTIVE To determine the frequency of and risk factors for complications associated with casts in horses. DESIGN Multicenter retrospective case series. ANIMALS 398 horses with a half-limb or full-limb cast treated at 1 of 4 hospitals. PROCEDURES Data collected from medical records included age, breed, sex, injury, limb affected, time from injury to hospital admission, surgical procedure performed, type of cast (bandage cast [BC; fiberglass tape applied over a bandage] or traditional cast [TC; fiberglass tape applied over polyurethane resin-impregnated foam]), limb position in cast (flexed, neutral, or extended), and complications. Risk factors for cast complications were identified via multiple logistic regression. RESULTS Cast complications were detected in 197 of 398 (49%) horses (18/53 [34%] horses with a BC and 179/345 [52%] horses with a TC). Of the 197 horses with complications, 152 (77%) had clinical signs of complications prior to cast removal; the most common clinical signs were increased lameness severity and visibly detectable soft tissue damage Cast sores were the most common complication (179/398 [45%] horses). Casts broke for 20 (5%) horses. Three (0.8%) horses developed a bone fracture attributable to casting Median time to detection of complications was 12 days and 8 days for horses with TCs and BCs, respectively. Complications developed in 71%, 48%, and 47% of horses with the casted limb in a flexed, neutral, and extended position, respectively. For horses with TCs, hospital, limb position in the cast, and sex were significant risk factors for development of cast complications. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that 49% of horses with a cast developed cast complications.

T cells infiltrate the liver and kill hepatocytes in HLA-B(∗)57:01-associated floxacillin-induced liver injury.

Drug-induced liver injury is a major safety issue. It can cause severe disease and is a common cause of the withdrawal of drugs from the pharmaceutical market. Recent studies have identified the HLA-B(∗)57:01 allele as a risk factor for floxacillin (FLUX)-induced liver injury and have suggested a role for cytotoxic CD8(+) T cells in the pathomechanism of liver injury caused by FLUX. This study aimed to confirm the importance of FLUX-reacting cytotoxic lymphocytes in the pathomechanism of liver injury and to dissect the involved mechanisms of cytotoxicity. IHC staining of a liver biopsy from a patient with FLUX-induced liver injury revealed periportal inflammation and the infiltration of cytotoxic CD3(+) CD8(+) lymphocytes into the liver. The infiltration of cytotoxic lymphocytes into the liver of a patient with FLUX-induced liver injury demonstrates the importance of FLUX-reacting T cells in the underlying pathomechanism. Cytotoxicity of FLUX-reacting T cells from 10 HLA-B(∗)57:01(+) healthy donors toward autologous target cells and HLA-B(∗)57:01-transduced hepatocytes was analyzed in vitro. Cytotoxicity of FLUX-reacting T cells was concentration dependent and required concentrations in the range of peak serum levels after FLUX administration. Killing of target cells was mediated by different cytotoxic mechanisms. Our findings emphasize the role of the adaptive immune system and especially of activated drug-reacting T cells in human leukocyte antigen-associated, drug-induced liver injury.

Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions.

OBJECTIVE To systematically review evidence on genetic risk factors for carbamazepine (CBZ)-induced hypersensitivity reactions (HSRs) and provide practice recommendations addressing the key questions: (1) Should genetic testing for HLA-B*15:02 and HLA-A*31:01 be performed in patients with an indication for CBZ therapy to reduce the occurrence of CBZ-induced HSRs? (2) Are there subgroups of patients who may benefit more from genetic testing for HLA-B*15:02 or HLA-A*31:01 compared to others? (3) How should patients with an indication for CBZ therapy be managed based on their genetic test results? METHODS A systematic literature search was performed for HLA-B*15:02 and HLA-A*31:01 and their association with CBZ-induced HSRs. Evidence was critically appraised and clinical practice recommendations were developed based on expert group consensus. RESULTS Patients carrying HLA-B*15:02 are at strongly increased risk for CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in populations where HLA-B*15:02 is common, but not CBZ-induced hypersensitivity syndrome (HSS) or maculopapular exanthema (MPE). HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported from Asian countries only, including China, Thailand, Malaysia, and India. HLA-B*15:02 is rare among Caucasians or Japanese; no HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported so far in these groups. HLA-A*31:01-positive patients are at increased risk for CBZ-induced HSS and MPE, and possibly SJS/TEN and acute generalized exanthematous pustulosis (AGEP). This association has been shown in Caucasian, Japanese, Korean, Chinese, and patients of mixed origin; however, HLA-A*31:01 is common in most ethnic groups. Not all patients carrying either risk variant develop an HSR, resulting in a relatively low positive predictive value of the genetic tests. SIGNIFICANCE This review provides the latest update on genetic markers for CBZ HSRs, clinical practice recommendations as a basis for informed decision making regarding the use of HLA-B*15:02 and HLA-A*31:01 genetic testing in patients with an indication for CBZ therapy, and identifies knowledge gaps to guide future research. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Oxypurinol directly and immediately activates the drug-specific T cells via the preferential use of HLA-B*58:01

Allopurinol (ALP) hypersensitivity is a major cause of severe cutaneous adverse reactions and is strongly associated with the HLA-B*58:01 allele. However, it can occur in the absence of this allele with identical clinical manifestations. The immune mechanism of ALP-induced severe cutaneous adverse reactions is poorly understood, and the T cell-reactivity pattern in patients with or without the HLA-B*58:01 allele is not known. To understand the interactions among the drug, HLA, and TCR, we generated T cell lines that react to ALP or its metabolite oxypurinol (OXP) from HLA-B*58:01(+) and HLA-B*58:01(-) donors and assessed their reactivity. ALP/OXP-specific T cells reacted immediately to the addition of the drugs and bypassed intracellular Ag processing, which is consistent with the "pharmacological interaction with immune receptors" (p-i) concept. This direct activation occurred regardless of HLA-B*58:01 status. Although most OXP-specific T cells from HLA-B*58:01(+) donors were restricted by the HLA-B*58:01 molecule for drug recognition, ALP-specific T cells also were restricted to other MHC class I molecules. This can be explained by in silico docking data that suggest that OXP binds to the peptide-binding groove of HLA-B*58:01 with higher affinity. The ensuing T cell responses elicited by ALP or OXP were not limited to particular TCR Vβ repertoires. We conclude that the drug-specific T cells are activated by OXP bound to HLA-B*58:01 through the p-i mechanism.

ESAPP Quarterly Report (April 01 - June 30, 2005)

Description and budget of secretariat and project activities Horn of Africa.

ESAPP Quarterly Report (January 01 - March 31, 2005)

Description and budget of secretariat and project activities Horn of Africa.

ESAPP Quarterly Report (January 01 - December 31, 2004)

Description and budget of secretariat and project activities Horn of Africa.

Detection efficiency of microchannel plates for e(-) and pi(-) in the momentum range from 17.5 to 345 MeV/c

High-energy e(-) and pi(-) were measured by the multichannel plate (MCP) detector at the PiM1 beam line of the High Intensity Proton Accelerator Facilities located at the Paul Scherrer Institute, Villigen, Switzerland. The measurements provide the absolute detection efficiencies for these particles: 5.8% +/- 0.5% for electrons in the beam momenta range 17.5-300 MeV/c and 6.0% +/- 1.3% for pions in the beam momenta range 172-345 MeV/c. The pulse height distribution determined from the measurements is close to an exponential function with negative exponent, indicating that the particles penetrated the MCP material before producing the signal somewhere inside the channel. Low charge extraction and nominal gains of the MCP detector observed in this study are consistent with the proposed mechanism of the signal formation by penetrating radiation. A very similar MCP ion detector will be used in the Neutral Ion Mass (NIM) spectrometer designed for the JUICE mission of European Space Agency (ESA) to the Jupiter system, to perform measurements of the chemical composition of the Galilean moon exospheres. The detection efficiency for penetrating radiation determined in the present studies is important for the optimisation of the radiation shielding of the NIM detector against the high-rate and high-energy electrons trapped in Jupiter's magnetic field. Furthermore, the current studies indicate that MCP detectors can be useful to measure high-energy particle beams at high temporal resolution. (C) 2015 AIP Publishing LLC.