Occupational Asthma: New Low-Molecular-Weight Causal Agents, 2000–2010

Background. More than 400 agents have been documented as causing occupational asthma (OA). The list of low-molecular-weight (LMW) agents that have been identified as potential causes of OA is constantly expanding, emphasizing the need to continually update our knowledge by reviewing the literature. Objective. The objective of this paper was to identify all new LMW agents causing occupational asthma reported during the period 2000–2010. Methods. A Medline search was performed using the keywords occupational asthma, new allergens, new causes, and low-molecular-weight agents. Results. We found 39 publications describing 41 new LMW causal agents, which belonged to the following categories: drugs (n = 12), wood dust (n = 11), chemicals (n = 8), metals (n = 4), biocides (n = 3), and miscellaneous (n = 3). The diagnosis of OA was confirmed through SIC for 35 of 41 agents, peak expiratory flow monitoring for three (3) agents, and the clinical history alone for three (3) agents. Immunological tests provided evidence supporting an IgE-mediated mechanism for eight (8) (20%) of the newly described agents. Conclusion. This paper highlights the importance of being alert to the occurrence of new LMW sensitizers, which can elicit OA. The immunological mechanism is explained by a type I hypersensitivity reaction in 20% of all newly described LMW agents

New methodology for specific inhalation challenges with occupational agents

<p>Abstract</p> <p>Background</p> <p>Inhalation challenges are used for diagnosing occupational asthma (OA). The initial methodology consisted of a "realistic" exposure without monitoring nor controlling exposure. Our aim was to design an equipment, called the GenaSIC, that allows the generation of various agents regardless of the formulation and to assess the feasibility of its use in patients investigated for OA.</p> <p>Results</p> <p>GenaSIC can generate lactose, flour, malt, isocyanates, formaldehyde and N-butyl acetate with precise and fairly stable concentrations. Using N-butyl-acetate as a control agent and real time measurement, we show that normal breathing has a negligible effect on the concentration. We exposed forty-four different subjects to a control agent and/or to a suspected occupational agent. Nineteen of the subjects were only exposed to N-butyl acetate as a control agent without experiencing any significant irritant effect (no significant changes in spirometry thereafter). Eight subjects who were exposed to both N-butyl acetate and formaldehyde did not show significant reactions. Seven subjects were exposed to dry particles (flour in six instances, malt in the other) and five showed immediate asthmatic reactions which changes in FEV1 from 20% to a maximum of 28%. Finally, ten subjects were exposed to isocyanates, four of whom showed a positive reaction, including one subject with immediate maximum changes in FEV1 of 22%.</p> <p>Conclusion</p> <p>GenaSIC offers the possibility of reliable and safe exposures to dry particles, formaldehyde and isocyanates in the investigation of OA.</p

An ECMS-based powertrain control of a parallel hybrid electric forklift

n this paper we focus on the supervisory control problem of a parallel hybrid electric vehicle (HEV): minimize fuel consumption while ensuring self-sustaining State-of-Charge (SoC). We reapply the state of the art methodology by comparing optimal results of Dynamic Programming (DP) against a real-time control candidate. After careful selection, we opted for an Equivalent Consumption Minimization Strategy (ECMS) based approach for the following reasons: (i) results are quite remarkable with less than 5% fuel usage increase when compared to DP; (ii) simple and intuitive tuning of control parameters; (iii) readily usable for code generation (prototyping). Topics that distinguish this article from others in the literature include: (i) the usage of trapezoidal rule of integration implementing DP and ECMS; consequently, the offline simulation results are intended to be more precise and representative when compared against the more common, often used rectangular rule; (ii) a particular post-processing procedure of the recorded driving cycle data based on physical interpretation; it allows consistent offline simulations with quite high sampling period (in the order of seconds); (iii) tuning of control parameters in such a way that control system is robust towards new, unknown, unpredictable but closely resembling driving cycles. In particular, we focus on the supervisory control of a forklift truck. The real-time control is able to compute: (i) the power split (i.e. a balanced usage between an internal combustion engine and a supercapacitor); (ii) the drivetrain control (i.e. automatic gear shifting and clutching). Numerous numerical implementation issues are discussed along our presentation

Case Report: Control of intestinal nematodes in captive Chlorocebus sabaeus

There are limited data on the efficacy of antiparasitic treatments and husbandry methods to control nematode infections in captive populations of African green monkeys (AGMs), Chlorocebus sabaeus. In faecal egg count (FEC) tests, 10 of the 11 (91%) adult male AGMs captured from the large feral population on the island of St Kitts had evidence of nematode infections, mostly Capillaria (8/11, 73%), Trichuris trichiura (7/11, 64%) and strongylid species (7/11, 64%) specifically (hookworm and Trichostrongylus, 50/50), but also Strongyloides fuelleborni (1/11, 9%). When kept in individual cages with cleaning and feeding regimens to prevent reinfections and treated concurrently with ivermectin (300 µg/kg, given subcutaneously) and albendazole (10 mg/kg, given orally) daily for 3 days, 60% (6/10) of the AGMs were negative at a follow-up FEC at 3 months and by FEC and necropsy at the end of the study 5-8 months later. One monkey appeared to have been reinfected with T. trichiura after being negative by FEC at 3 months post-treatment. Four AGMs were positive for T. trichiura at the 3 month FEC follow-up but were negative at the end of the study after one further treatment regimen. Although initially being cleared of Capillaria following treatment, three AGMs were found to be infected at the end of the study. The ivermectin and albendazole treatment regimen coupled with good husbandry practices to prevent reinfections effectively controlled nematode infections in captive AGMs

Efficient and accurate computation of base generation allele frequencies

Allele frequencies are used for several aspects of genomic prediction, with the assumption that these are equal to the allele frequency in the base generation of the pedigree. The current standard method, however, calculates allele frequencies from the current genotyped population. We compared the current standard method with BLUP and general least squares (GLS) methods explicitly targeting the base population to determine whether there is a more accurate and still efficient method of calculating allele frequencies that better represents the base generation. A data set based on a typical dairy population was simulated for 325,266 animals; the last 100,078 animals in generations 9 to 12 of the population were genotyped, with 1,670 SNP markers. For the BLUP method, several SNP genotypes were analyzed with a multitrait model by assuming a heritability of 0.99 and no genetic correlation among them. This method was limited by the time required for each BLUP to converge (approximately 6 min per BLUP run of 15 SNP). The GLS method had 2 implementations. The first implementation, using imputation on the fly and multiplication of sparse matrices, was very efficient and required just 49 s and 1.3 GB of random access memory. The second implementation, using a dense fullA22 −1 matrix, was very inefficient and required more than 1 d of wall clock time and more than 118.2 GB of random access memory. When no selection was considered in the simulations, all methods predicted equally well. When selection was introduced, higher correlations between the estimated allele frequency and known base generation allele frequency were observed for BLUP (0.96 ± 0.01) and GLS (0.97 ± 0.01) compared with the current standard method (0.87 ± 0.01). The GLS method decreased in accuracy when introducing incomplete pedigree, with 25% of sires in the first 5 generations randomly replaced as unknown to erroneously identify founder animals (0.93 ± 0.01) and a further decrease for 8 generations (0.91 ± 0.01). There was no change in accuracy when introducing 5% genotyping errors (0.97 ± 0.01), 5% missing genotypes (0.97 ± 0.01), or both 5% genotyping errors and missing genotypes (0.97 ± 0.01). The GLS method provided the most accurate estimates of base generation allele frequency and was only slightly slower compared with the current method. The efficient implementation of the GLS method, therefore, is very well suited for practical application and is recommended for implementation.</p

National single-step genomic method that integrates multi-national genomic information

The aim of this paper was to develop a national single-step genomic BLUP that integrates multi-national genomic estimated breeding values (EBV) and associated reliabilities without double counting dependent data contributions from the different evaluations. Simultaneous use of all data, including phenotypes, pedigree, and genotypes, is a condition to obtain unbiased EBV. However, this condition is not always fully met, mainly due to unavailability of foreign raw data for imported animals. In dairy cattle genetic evaluations, this issue is traditionally tackled through the multiple across-country evaluation (MACE) of sires, performed by Interbull Centre (Uppsala, Sweden). Multiple across-country evaluation regresses all the available national information onto a joint pedigree to obtain country-specific rankings of all sires without sharing the raw data. In the context of genomic selection, the issue is handled by exchanging sire genotypes and by using MACE information (i.e., MACE EBV and reliabilities), as a valuable source of “phenotypic” data. Although all the available data are considered, these “multi-national” genomic evaluations use multi-step methods assuming independence of various sources of information, which is not met in all situations. We developed a method that handles this by single-step genomic evaluation that jointly (1) uses national phenotypic, genomic, and pedigree data; (2) uses multi-national genomic information; and (3) avoids double counting dependent data contributions from an animal’s own records and relatives’ records. The method was demonstrated by integrating multi-national genomic EBV and reliabilities of Brown Swiss sires, included in the InterGenomics consortium at Interbull Centre, into the national evaluation in Slovenia. The results showed that the method could (1) increase reliability of a national (genomic) evaluation; (2) provide consistent ranking of all animals: bulls, cows, and young animals; and (3) increase the size of a genomic training population. These features provide more efficient and transparent selection throughout a breeding program

A synbiotic-containing amino acid-based formula improves gut microbiota in non-IgE-mediated allergic infants

BACKGROUND: Prebiotics and probiotics (synbiotics) can modify gut microbiota and have potential in allergy management when combined with amino acid-based formula (AAF) for infants with cow's milk allergy (CMA). METHODS: This multicenter, double-blind, randomized controlled trial investigated the effects of an AAF including synbiotic blend on percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group (ER/CC) in feces from infants with suspected non-IgE-mediated CMA. Feces from age matched healthy breastfed infants were used as reference (HBR) for primary outcomes. CMA subjects were randomized and received test or control formula for 8 weeks. Test formula was a hypoallergenic, nutritionally complete AAF including a prebiotic blend of fructo-oligosaccharides and the probiotic strain Bifidobacterium breve M-16V. Control formula was AAF without synbiotics. RESULTS: Thirty-five (test) and 36 (control) subjects were randomized; HBR included 51 infants. At week 8, median percentage of bifidobacteria was higher in test group vs control group (35.4 vs. 9.7%, respectively P&lt;0.001), whereas ER/CC was lower (9.5 vs. 24.2%, respectively; P&lt;0.001). HBR levels of bifidobacteria and ER/CC were 55 and 6.5%, respectively. CONCLUSION: AAF including specific synbiotics, which results in levels of bifidobacteria and ER/CC approximating levels in HBR group, improves the fecal microbiota of infants with suspected non-IgE-mediated CMA

A Practical Guide for the Diagnosis of Primary Enteric Nervous System Disorders

Objective:Primary gastrointestinal neuropathies are a heterogeneous group of enteric nervous system (ENS) disorders that continue to cause difficulties in diagnosis and histological interpretation. Recently, an international working group published guidelines for histological techniques and reporting, along with a classification of gastrointestinal neuromuscular pathology. The aim of this article was to review and summarize the key issues for pediatric gastroenterologists on the diagnostic workup of congenital ENS disorders. In addition, we provide further commentary on the continuing controversies in the field.Results:Although the diagnostic criteria for Hirschsprung disease are well established, those for other forms of dysganglionosis remain ill-defined. Appropriate tissue sampling, handling, and expert interpretation are crucial to maximize diagnostic accuracy and reduce interobserver variability. The absence of validated age-related normal values for neuronal density, along with the lack of correlation between clinical and histological findings, result in significant diagnostic uncertainties while diagnosing quantitative aberrations such as hypoganglionosis or ultrashort Hirschsprung disease. Intestinal neuronal dysplasia remains a histological description of unclear significance.Conclusions:The evaluation of cellular quantitative or qualitative abnormalities of the ENS for clinical diagnosis remains complex. Such analysis should be carried out in laboratories that have the necessary expertise and access to their own validated reference values