Cross-reactive LTP sensitization in food-dependent exercise-induced urticaria/anaphylaxis: a pilot study of a component-resolved and in vitro depletion approach

Background: Challenge tests for food-dependent exercise-induced anaphylaxis (FDEIA) carry some risk and have a high rate of false negatives. Our aim was to explore the usefulness of an in vitro immunodepletion assay and an allergen microarray test in the identification of IgE-mediated cross-reactive food allergens in patients with suspected FDEIA or food-dependent exercise-induced urticaria and panallergen sensitization. Methods: Three patients with a history of food dependent exercise induced urticaria/anaphylaxis and food panallergen sensitization in whom a food-exercise challenge was not feasible were selected: a 25-year-old man with cholinergic urticaria who experienced generalized urticaria and angioedema during a soccer match after drinking a peach-based soft drink; a 19-year-old woman with allergic rhinitis and controlled asthma who experienced anaphylactic shock while playing soccer, having eaten walnuts in the previous 90 min; and a 57-year-old man with baker’s asthma who experienced four episodes of anaphylaxis during exercise after ingesting wheat-containing food. All individuals underwent a diagnostic work-up with skin prick tests, specific IgE (sIgE) and ImmunoCAP ISAC test. For the in vitro immunodepletion procedure, patients’ serum was pre-incubated with the suspected native allergen (peach, walnut, or wheat) in solid phase (ImmunoCAP). The eluted serum, containing unbound IgE, was collected and samples were re-tested using Immunocap ISAC 112 and compared with baseline results. Results: All individuals were sensitized to lipid transfer proteins. The first patient was sensitized to Pru p 3, Cor a 8, Jug r 3, and Ara h 9; after pre-incubation with peach there was 100% depletion of sIgE to all components. The second patient was sensitized to Pru p 3, Cor a 8, Jug r 3, and Ara h 9; immunodepletion with walnut depleted sIgE to Ara h 9 by 67%, Pru p 3 and Pla a 3 (60%), Art v 3 (75%), Jug r 3 (88%), and Cor a 8 (100%). The third patient was sensitized to Pru p 3, Jug r 3, Ara h 9, and Tri a 14; immunodepletion with wheat depleted Tri a 14 only (100%). Conclusions: In vitro immunodepletion might be a useful diagnostic tool in food dependent exercise induced urticaria/anaphylaxis with panallergen sensitization, particularly for identifying the culprit allergen and guiding dietary elimination recommendations

An assessment of functioning and non-functioning distractors in multiple-choice questions: a descriptive analysis

<p>Abstract</p> <p>Background</p> <p>Four- or five-option multiple choice questions (MCQs) are the standard in health-science disciplines, both on certification-level examinations and on in-house developed tests. Previous research has shown, however, that few MCQs have three or four functioning distractors. The purpose of this study was to investigate non-functioning distractors in teacher-developed tests in one nursing program in an English-language university in Hong Kong.</p> <p>Methods</p> <p>Using item-analysis data, we assessed the proportion of non-functioning distractors on a sample of seven test papers administered to undergraduate nursing students. A total of 514 items were reviewed, including 2056 options (1542 distractors and 514 correct responses). Non-functioning options were defined as ones that were chosen by fewer than 5% of examinees and those with a positive option discrimination statistic.</p> <p>Results</p> <p>The proportion of items containing 0, 1, 2, and 3 functioning distractors was 12.3%, 34.8%, 39.1%, and 13.8% respectively. Overall, items contained an average of 1.54 (SD = 0.88) functioning distractors. Only 52.2% (n = 805) of all distractors were functioning effectively and 10.2% (n = 158) had a choice frequency of 0. Items with more functioning distractors were more difficult and more discriminating.</p> <p>Conclusion</p> <p>The low frequency of items with three functioning distractors in the four-option items in this study suggests that teachers have difficulty developing plausible distractors for most MCQs. Test items should consist of as many options as is feasible given the item content and the number of plausible distractors; in most cases this would be three. Item analysis results can be used to identify and remove non-functioning distractors from MCQs that have been used in previous tests.</p

Information inequalities and Generalized Graph Entropies

In this article, we discuss the problem of establishing relations between information measures assessed for network structures. Two types of entropy based measures namely, the Shannon entropy and its generalization, the R\'{e}nyi entropy have been considered for this study. Our main results involve establishing formal relationship, in the form of implicit inequalities, between these two kinds of measures when defined for graphs. Further, we also state and prove inequalities connecting the classical partition-based graph entropies and the functional-based entropy measures. In addition, several explicit inequalities are derived for special classes of graphs.Comment: A preliminary version. To be submitted to a journa

Variable order Mittag-Leffler fractional operators on isolated time scales and application to the calculus of variations

We introduce new fractional operators of variable order on isolated time scales with Mittag-Leffler kernels. This allows a general formulation of a class of fractional variational problems involving variable-order difference operators. Main results give fractional integration by parts formulas and necessary optimality conditions of Euler-Lagrange type.Comment: This is a preprint of a paper whose final and definite form is with Springe

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Gold Mining in the Peruvian Amazon: Global Prices, Deforestation, and Mercury Imports

Many factors such as poverty, ineffective institutions and environmental regulations may prevent developing countries from managing how natural resources are extracted to meet a strong market demand. Extraction for some resources has reached such proportions that evidence is measurable from space. We present recent evidence of the global demand for a single commodity and the ecosystem destruction resulting from commodity extraction, recorded by satellites for one of the most biodiverse areas of the world. We find that since 2003, recent mining deforestation in Madre de Dios, Peru is increasing nonlinearly alongside a constant annual rate of increase in international gold price (∼18%/yr). We detect that the new pattern of mining deforestation (1915 ha/year, 2006–2009) is outpacing that of nearby settlement deforestation. We show that gold price is linked with exponential increases in Peruvian national mercury imports over time (R2 = 0.93, p = 0.04, 2003–2009). Given the past rates of increase we predict that mercury imports may more than double for 2011 (∼500 t/year). Virtually all of Peru's mercury imports are used in artisanal gold mining. Much of the mining increase is unregulated/artisanal in nature, lacking environmental impact analysis or miner education. As a result, large quantities of mercury are being released into the atmosphere, sediments and waterways. Other developing countries endowed with gold deposits are likely experiencing similar environmental destruction in response to recent record high gold prices. The increasing availability of satellite imagery ought to evoke further studies linking economic variables with land use and cover changes on the ground

A Randomised Controlled Trial to Assess the Efficacy of Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Falciparum Malaria in Peru

Background. Multi-drug resistant falciparum malaria is an important health problem in the Peruvian Amazon region. We carried out a randomised open label clinical trial comparing mefloquine-artesunate, the current first line treatment in this region, with dihydroartemisinin-piperaquine. Methods and Findings. Between July 2003 and July 2005, 522 patients with P. falciparum uncomplicated malaria were recruited, randomized (260 with mefloquine-artesunate and 262 with dihydroartemisinin-piperaquine), treated and followed up for 63 days. PCR-adjusted adequate clinical and parasitological response, estimated by Kaplan Meier survival and Per Protocol analysis, was extremely high for both drugs (99.6% for mefloquine-artesunate and 98.4% and for dihydroartemisinin-piperaquine) (RR: 0.99, 95%CI [0.97-1.01], Fisher Exact p=0.21). All recrudescences were late parasitological failures. Overall, gametocytes were cleared faster in the mefloquine-artesunate group (28 vs 35 days) and new gametocytes tended to appear more frequently in patients treated with dihydroartemisinin-piperaquine (day 7: 8 ( 3.6%) vs 2 (0.9%), RR: 3.84, 95%CI [0.82-17.87]). Adverse events such as anxiety and insomnia were significantly more frequent in the mefloquine-artesunate group, both in adults and children. Conclusion. Dihydroartemisinin-piperaquine is as effective as mefloquine-artesunate in treating uncomplicated P. falciparum malaria but it is better tolerated and more affordable than mefloquine-artesunate (US$1.0 versus US$18.65 on the local market). Therefore, it should be considered as a potential candidate for the first line treatment of P. falciparum malaria in Peru. Trial Registration. ClinicalTrials.gov NCT00373607 [http://www.clinicaltrials.gov/ct/show/NCT00373607]

A methodology for identifying high-need, high-cost patient personas for international comparisons.

ObjectiveTo establish a methodological approach to compare two high-need, high-cost (HNHC) patient personas internationally.Data sourcesLinked individual-level administrative data from the inpatient and outpatient sectors compiled by the International Collaborative on Costs, Outcomes, and Needs in Care (ICCONIC) across 11 countries: Australia, Canada, England, France, Germany, the Netherlands, New Zealand, Spain, Sweden, Switzerland, and the United States.Study designWe outline a methodological approach to identify HNHC patient types for international comparisons that reflect complex, priority populations defined by the National Academy of Medicine. We define two patient profiles using accessible patient-level datasets linked across different domains of care-hospital care, primary care, outpatient specialty care, post-acute rehabilitative care, long-term care, home-health care, and outpatient drugs. The personas include a frail older adult with a hip fracture with subsequent hip replacement and an older person with complex multimorbidity, including heart failure and diabetes. We demonstrate their comparability by examining the characteristics and clinical diagnoses captured across countries.Data collection/extraction methodsData collected by ICCONIC partners.Principal findingsAcross 11 countries, the identification of HNHC patient personas was feasible to examine variations in healthcare utilization, spending, and patient outcomes. The ability of countries to examine linked, individual-level data varied, with the Netherlands, Canada, and Germany able to comprehensively examine care across all seven domains, whereas other countries such as England, Switzerland, and New Zealand were more limited. All countries were able to identify a hip fracture persona and a heart failure persona. Patient characteristics were reassuringly similar across countries.ConclusionAlthough there are cross-country differences in the availability and structure of data sources, countries had the ability to effectively identify comparable HNHC personas for international study. This work serves as the methodological paper for six accompanying papers examining differences in spending, utilization, and outcomes for these personas across countries