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Background: During resonance frequency (RF) hyperthermia treatment, the temperature of the tumor tissue is elevated to the range of 39–44°C. Accurate temperature monitoring is essential to guide treatments and ensure precise heat delivery and treatment quality. Magnetic resonance (MR) thermometry is currently the only clinical method to measure temperature noninvasively in a volume during treatment. However, several studies have shown that this approach is not always sufficiently accurate for thermal dosimetry in areas with motion, such as the pelvic region. Model‐based temperature estimation is a promising approach to correct and supplement 3D online temperature estimation in regions where MR thermometry is unreliable or cannot be measured. However, complete 3D temperature modeling of the pelvic region is too complex for online usage. Purpose: This study aimed to evaluate the use of proper orthogonal decomposition (POD) model reduction combined with Kalman filtering to improve temperature estimation using MR thermometry. Furthermore, we assessed the benefit of this method using data from hyperthermia treatment where there were limited and unreliable MR thermometry measurements. Methods: The performance of POD–Kalman filtering was evaluated in several heating experiments and for data from patients treated for locally advanced cervical cancer. For each method, we evaluated the mean absolute error (MAE) concerning the temperature measurements acquired by the thermal probes, and we assessed the reproducibility and consistency using the standard deviation of error (SDE). Furthermore, three patient groups were defined according to susceptibility artifacts caused by the level of intestinal gas motion to assess if the POD–Kalman filtering could compensate for missing and unreliable MR thermometry measurements. Results: First, we showed that this method is beneficial and reproducible in phantom experiments. Second, we demonstrated that the combined method improved the match between temperature prediction and temperature acquired by intraluminal thermometry for patients treated for locally advanced cervical cancer. Considering all patients, the POD–Kalman filter improved MAE by 43% (filtered MR thermometry = 1.29°C, POD–Kalman filtered temperature = 0.74°C). Moreover, the SDE was improved by 47% (filtered MR thermometry = 1.16°C, POD–Kalman filtered temperature = 0.61°C). Specifically, the POD–Kalman filter reduced the MAE by approximately 60% in patients whose MR thermometry was unreliable because of the great amount of susceptibilities caused by the high level of intestinal gas motion. Conclusions: We showed that the POD–Kalman filter significantly improved the accuracy of temperature monitoring compared to MR thermometry in heating experiments and hyperthermia treatments. The results demonstrated that POD–Kalman filtering can improve thermal dosimetry during RF hyperthermia treatment, especially when MR thermometry is inaccurate. [ABSTRACT FROM AUTHOR]

Previous studies have applied genomics and transcriptomics to identify immune and genetic markers as key indicator traits for cattle tick susceptibility/resistance; however, results differed between breeds, and there is lack of information on the use of host proteomics. Serum samples from Santa Gertrudis cattle (naïve and phenotyped over 105 days as tick‐resistant [TR] or tick‐susceptible [TS]) were used to conduct differential abundance analyses of protein profiles. Serum proteins were digested into peptides followed by identification and quantification using sequential window acquisition of all instances of theoretical fragment ion mass spectrometry. Before tick infestation, abundance of 28 proteins differed significantly (adjusted P < 10−5) between TR and TS. These differences were also observed following tick infestation (TR vs TS) with a further eight differentially abundant proteins in TR cattle, suggesting possible roles in adaptive responses. The intragroup comparisons (TS‐0 vs TS and TR‐0 vs TR) showed that tick infestation elicited quite similar responses in both groups of cattle, but with relatively stronger responses in TR cattle. Many of the significantly differentially abundant proteins in TR Santa Gertrudis cattle (before and after tick infestation) were associated with immune responses including complement factors, chemotaxis for immune cells and acute‐phase responses. [ABSTRACT FROM AUTHOR]

Background: Executive functions have been proposed to account for individual variation in reading comprehension beyond the contributions of decoding skills and language skills. However, insight into the direct and indirect effects of multiple executive functions on fifth‐grade reading comprehension, while accounting for decoding and language skills, is limited. Aim: The present study investigated the direct and indirect effects of fourth‐grade executive functions (i.e., working memory, inhibition, and planning) on fifth‐grade reading comprehension, after accounting for decoding and language skills. Sample: The sample included 113 fourth‐grade children (including 65 boys and 48 girls; Age M = 9.89; SD =.44 years). Methods: The participants were tested on their executive functions (working memory, inhibition and planning), and their decoding skills, language skills (vocabulary and syntax knowledge) and reading comprehension, one year later. Results: Using structural equation modelling, the results indicated direct effects of working memory and planning on reading comprehension, as well as indirect effects of working memory and inhibition via decoding (χ2 = 2.46). Conclusions: The results of the present study highlight the importance of executive functions for reading comprehension after taking variance in decoding and language skills into account: Both working memory and planning uniquely contributed to reading comprehension. In addition, working memory and inhibition also supported decoding. As a practical implication, educational professionals should not only consider the decoding and language skills children bring into the classroom, but their executive functions as well. [ABSTRACT FROM AUTHOR]

Background: A 6‐week personalized integrative multidisciplinary treatment programme (PIM) was developed for children with difficult to treat AD who appeared unresponsive to treatment according to current guidelines. Objective: The aim of the present study was to identify clinical and psychosocial characteristics that predict long‐term treatment success after PIM. Methods: Treatment was considered successful when there was a 75% reduction on the Self‐Administered Eczema Area and Severity Index and/or little impact of AD on daily life, measured with the Children's Dermatology Life Quality Index (score ≤ 6), 6 months after the end of PIM. PIM is a personalized, integrative, multidisciplinary treatment programme with clearly defined goals and strategies, addressing atopic, paediatric, mental health comorbidities and general well‐being, for children and adolescents aged 8‐ to 18 years. Multivariate logistic regression models were constructed using a backward selection procedure. Questionnaires were used to assess psychosocial characteristics; clinical data was extracted from medical records. Results: In total, 79 children/adolescents with difficult to treat AD completed PIM and long‐term treatment results were available for 74 children/adolescents. The majority (77%) of children/adolescents demonstrated long‐term treatment success with PIM. Predictors of long‐term treatment success (adjusted ORs) included maternal disease acceptance OR (95% CI) 1.84 (1.15–2.94). A group (23%) of mostly females OR (95% CI) 0.10 (0.02–0.54) with multiple somatic complaints OR (95% CI) 0.88(0.80–0.97), from families where the mother has anxiety for the use of topical corticosteroids OR (95% CI) 0.62(0.40–0.94), is less likely to obtain long‐term treatment success. Conclusion: Most children and adolescents with difficult to treat AD, seemingly unresponsive to conventional treatment according to current guidelines, are able to improve with PIM. Psychosocial and family but not clinical variables, predicted long‐term treatment success after participating in PIM. [ABSTRACT FROM AUTHOR]

Background: The lexical quality hypothesis proposes that successful reading comprehension requires high quality lexical representations, which allow for efficient retrieval. These retrieval operations have however not been specified. Methods: We investigated the contribution of semantic retrieval to reading comprehension in 119 Dutch children in the upper grades of primary school, while taking decoding skills and vocabulary size into account in a longitudinal design. By using verbal fluency tasks, we measured retrieval in line with the structural organisation of the mental lexicon and additionally, a more controlled search through the mental lexicon. Results: Semantic retrieval assessed in grade 5 accounted for variance in reading comprehension in grade 6, in addition to variance accounted for by vocabulary size and reading comprehension in grade 5. Conclusions: The ability to search through the mental lexicon, along the lines of its hierarchical structure, is important for children's reading comprehension development in the upper primary grades. [ABSTRACT FROM AUTHOR]

Summary: Background: Alpine climate treatment has historically been used in Europe to treat atopic dermatitis (AD), but no randomized trials have been conducted to provide evidence for its effectiveness. Objective: To investigate the long‐term effectiveness of alpine climate treatment for children with difficult to treat AD. Materials & Methods: A pragmatic, open, randomized controlled trial was conducted. Children diagnosed with AD that was considered difficult to treat, aged between 8 and 18 years and willing to be treated in Switzerland were randomized to a six‐week personalized integrative multidisciplinary treatment period in a clinical setting in the alpine climate (Switzerland) or an outpatient setting in moderate maritime climate (Netherlands). Study assessments were conducted at the Wilhelmina Children's Hospital; an electronic portal was used for the collection of questionnaire data. Primary outcomes were disease activity (SAEASI), quality of life (CDLQI) and catastrophizing thoughts (JUCKKI/JU) 6 months after intervention. Other assessments were immediately and 6 weeks after intervention. Subgroup analyses concerned asthma‐related outcomes. Children were randomly assigned to either the intervention or control group using a covariate adaptive randomization method, taking age and asthma diagnosis into account. Children, parents and healthcare professionals involved in treatment were not blinded to group assignment. Data were analysed according to intention‐to‐treat with linear mixed‐effects models for continuous outcomes. The trial is registered at Current Controlled Trials ISCRTN88136485. Results: Between 14 September 2010 and 30 September 2014, 88 children were enrolled in the trial, 84 children were randomized (41 assigned to intervention, 43 to control) of whom 77 completed the intervention (38 of 41 (93%) intervention, 39 of 43 (91%) control) and 74 completed follow‐up (38 of 41 (93%) intervention, 36 of 43 (84%) control). Six months after intervention there were no significant differences between the groups on disease activity (SAEASI mean difference −3.4 (95%CI −8.5 to 1.7)), quality of life (CDLQI mean difference ‐0.3 (95%CI −2.0 to 1.4)) and catastrophizing thoughts (JUCCKI/JU subscale mean difference −0.7 (95%CI −1.4 to −0.0)). Immediately and 6 weeks after intervention, disease activity and quality of life were significantly different in favour of alpine climate treatment. Mean differences on SAEASI were −10.1 (95%CI −14.5 to −5.8) and −8.4 (95%CI −12.2 to −4.6) and on CDLQI −1.9 (95%CI −3.3 to −0.5) and −1.5 (95%CI −2.8 to −0.3) immediately and 6 weeks after the intervention, respectively. There were no long‐term differences on asthma‐related outcomes. Five serious adverse events occurred during the study period, which were not thought to be related to the treatment. Conclusions & Clinical relevance: For children with difficult to treat AD, there was no additional long‐term benefit of alpine climate treatment, in contrast to the short‐term, compared to an outpatient treatment programme in moderate maritime climate, using a personalized integrative multidisciplinary treatment approach. [ABSTRACT FROM AUTHOR]

We examine convergence properties of errors in a class of adaptive systems that correspond to adaptive control of linear time-invariant plants with state variables accessible. We demonstrate the existence of a sticking region in the error space where the state errors move with a finite velocity independent of their magnitude. We show that these properties are exhibited by adaptive systems with closed-loop reference models, which have been demonstrated to exhibit improved transient performance. A simulation study is included to illustrate the size of this sticking region and its dependence on various system parameters. With the existence of sticking regions shown for inner-loop adaptive controllers, its impact on outer-loop control is demonstrated for systems that implement inner-loop adaptation. A flight control example is presented to illustrate this impact of sticking in a practical application. [ABSTRACT FROM AUTHOR]

Background Among persons with a mild intellectual disability or borderline intellectual functioning, differences in their characteristics imply that a differentiated approach is required to meet their needs. This retrospective study examined whether the history of support/treatment programs and the type of healthcare providers involved matched the specific support needs of persons with a mild intellectual disability or borderline intellectual functioning. Method Five (previously identified) profiles of persons with a mild intellectual disability or borderline intellectual functioning were used to investigate to what extent the support needs of this group had been met. For the 250 persons with mild intellectual disability or borderline intellectual functioning who matched these five profiles, data were collected retrospectively from their case files. Results Persons with mild intellectual disability or borderline intellectual functioning received a very similar amount and type of support/treatment programs. Differences between the profiles were found for non-verbal therapy, residential treatment and contacts with social work. Regarding the type of healthcare providers involved, differences between the profiles emerged for specialised intellectual disability services, youth services and specialised addiction services. Conclusions The support programs for a heterogeneous population of persons with mild intellectual disability or borderline intellectual functioning seem to be suboptimal, indicating that more differentiation is required in the services offered to these individuals. [ABSTRACT FROM AUTHOR]

The article offers a study on less requirement for an oral steroid burst and sustained asthma control 12 months after high altitude climate treatment (HACT) for severe asthma consisting of questionnaires planned for each patient at 0, 3, 6, and 12 months after HACT; and study showed that HACT results in less exacerbations and sustained long‐term asthma control in patients with uncontrolled severe asthma as HACT could be an adequate treatment option for uncontrolled severe asthmatic patients.

Acetohydroxyacid synthase (AHAS) inhibitors are highly successful commercial herbicides. New kinetic data show that the binding of these compounds leads to reversible accumulative inhibition of AHAS. Crystallographic data (to a resolution of 2.17 Å) for an AHAS-herbicide complex shows that closure of the active site occurs when the herbicidal inhibitor binds, thus preventing exchange with solvent. This feature combined with new kinetic data shows that molecular oxygen promotes an accumulative inhibition leading to the conclusion that the exceptional potency of these herbicides is augmented by subversion of an inherent oxygenase side reaction. The reactive oxygen species produced by this reaction are trapped in the active site, triggering oxidation reactions that ultimately lead to the alteration of the redox state of the cofactor flavin adenine dinucleotide (FAD), a feature that accounts for the observed reversible accumulative inhibition. [ABSTRACT FROM AUTHOR]

Abstract: Background: Synaptic dysfunction occurs early in Alzheimer's disease (AD) and is recognized to be a primary pathological target for treatment. Synapse degeneration or dysfunction contributes to clinical signs of dementia through altered neuronal communication; the degree of synaptic loss correlates strongly with cognitive impairment. The molecular mechanisms underlying synaptic degeneration are still unclear, and identifying abnormally expressed synaptic proteins in AD brain will help to elucidate such mechanisms and to identify therapeutic targets that might slow AD progression. Methods: Synaptosomal fractions from human autopsy brain tissue from subjects with AD (n = 6) and without AD (n = 6) were compared using two-dimensional differential in-gel electrophoresis. AD pathology is region specific; human subjects can be highly variable in age, medication, and other factors. To counter these factors, two vulnerable areas (the hippocampus and the temporal cortex) were compared with two relatively spared areas (the motor and occipital cortices) within each group. Proteins exhibiting significant changes in expression were identified (≥20% change, Newman-Keuls P value < .05) using either matrix-assisted laser desorption ionization time-of-flight or electrospray ionisation quadrupole-time of flight mass spectrometry. Results: Twenty-six different synaptic proteins exhibited more than twofold differences in expression between AD and normal subjects. These proteins are involved in regulating different cellular functions, including energy metabolism, signal transduction, vesicle transport, structure, and antioxidant activity. Conclusion: Comparative proteome analysis uncovered markers of pathogenic mechanisms involved in synaptic dysfunction. [Copyright &y& Elsevier]

Background Copper-associated hepatitis is an inherited disease in the Labrador Retriever. Apart from genetic factors, dietary intake of copper and zinc are suspected to play a role in the pathogenesis. Objectives To investigate whether dietary copper and zinc levels of commercially available dry diets are associated with hepatic copper and zinc concentrations in Labrador Retrievers. Animals Fifty-five Labrador Retrievers that were fed a single brand and type of commercial dry food for at least 1 year. Of these, 44 dogs were family members of Labrador Retrievers with copper-associated hepatitis. Methods Liver biopsies, blood samples, and diet samples were obtained. Liver specimens were scored histologically and copper and zinc concentrations were quantified. Dietary concentrations of copper and zinc were measured. The association between dietary intake of copper and zinc and hepatic copper and zinc concentrations was investigated by linear regression analysis. Results High dietary copper and low dietary zinc levels were significantly associated with high hepatic copper levels. No association between dietary intake and hepatic zinc was present. Conclusions and Clinical Relevance Dietary copper and zinc at current levels in commercially available dry dog food can influence hepatic copper and can be a risk factor for the development of copper-associated hepatitis in Labrador Retrievers with a genetic susceptibility to copper. [ABSTRACT FROM AUTHOR]

High-altitude treatment has been applied for more than a century in the treatment of pulmonary diseases including asthma. Many uncontrolled and controlled studies have shown its beneficial effects in children and adolescents with house dust mite allergic asthma. A recent study also showed an improvement in markers of airway inflammation in adult patients with severe intrinsic asthma, suggesting that factors other than HDM avoidance may contribute to the beneficial influence of the high-altitude climate therapy on asthma. The dry mountain climate not only has decreased levels of mite allergens but also decreased levels of pollens, fungal spores and air pollution, as well as high exposure to UV light with immunomodulatory and anti-inflammatory effects. Treatments targeting environmental control have never been investigated systematically in severe asthma, which is surprising, as environmental factors have been recognized as important contributors to asthma severity for many years and more evidence has been accumulating ever since. Preliminary evidence shows the beneficial effects of high-altitude treatment in patients with severe refractory asthma on symptoms, lung function and oral corticosteroid requirement, irrespective of atopic status. In this narrative review, we will discuss why high-altitude treatment might be a promising therapeutic option for patients who suffer from this disabling disease. [ABSTRACT FROM AUTHOR]

From a number of cross-sectional and longitudinal studies, it can be concluded that there is a very close association between house dust mite (HDM) exposure and HDM sensitization. In addition, HDM exposure in already sensitized individuals can trigger an exacerbation of asthma, and prolonged exposure can lead to the persistence of symptoms. Asthma is usually more severe in sensitized patients who are exposed to higher allergen levels. There is clear biological plausibility for the role of HDM allergens, in that the proteolytic activity of their enzymes can actively damage the airway epithelium. In effectively mite allergen-free environments, as in hospitals or in high-altitude Alpine clinics, the condition of asthmatic patients improves both symptomatically and in terms of non-specific bronchial responsiveness. Even 1 month at high altitude can result in a reduction in airways inflammation, measured as adenosine monophosphate, bronchial hyper-responsiveness, blood eosinophils and eosinophilic cationic protein.

Outer membrane proteins (OMPs) of Gram-negative bacteria are key molecules that interface the cell with the environment. Traditional biochemical and genetic approaches have yielded a wealth of knowledge relating to the function of OMPs. Nonetheless, with the completion of the Escherichia coli genome sequencing project there is the opportunity to further expand our understanding of the organization, expression and function of the OMPs in this Gram-negative bacterium. In this report we describe a proteomic approach which provides a platform for parallel analysis of OMPs. We propose a rapid method for isolation of bacterial OMPs using carbonate incubation, purification and protein array by two-dimensional electrophoresis, followed by protein identification using mass spectrometry. Applying this method to examine E. coli K-12 cells grown in minimal media we identified 21 out of 26 (80%) of the predicted integral OMPs that are annotated in SWISS-PROT release 37 and predicted to separate within the range of pH 4–7 and molecular mass 10–80 kDa. Five outer membrane lipoproteins were also identified and only minor contamination by nonmembrane proteins was observed. Importantly, this research readily demonstrates that integral OMPs, commonly missing from 2D gel maps, are amenable to separation by two-dimensional electrophoresis. Two of the identified OMPs (YbiL, YeaF) were previously known only from their ORFs, and their identification confirms the cognate genes are transcribed and translated. Furthermore, we show that like the E. coli iron receptors FhuE and FhuA, the expression of YbiL is markedly increased by iron limitation, suggesting a putative role for this protein in iron transport. In an additional demonstration we show the value of parallel protein analysis to document changes in E. coli OMP expression as influenced by culture temperature. [ABSTRACT FROM AUTHOR]

Background: Alterations in gastrointestinal motility and hormone secretion, especially activation of the ileal brake, have been documented in malabsorption. Aim: To investigate whether artificially-induced accelerated small intestinal transit activates the ileal brake mechanism. Methods: Eight healthy volunteers (four female, four male; age 21 ± 3 years) participated in four experiments: (a) meal with either oral magnesium sulphate (MgSO4) or placebo; and (b) fasting with either oral MgSO4 or placebo. Antroduodenal motility was recorded by perfusion manometry. Duodenocaecal transit time was determined by the lactulose H2 breath test. Gall-bladder volume was measured by ultrasound at regular intervals, and blood samples were drawn for determination of cholecystokinin and peptide YY (RIA). Twenty-four hour faecal weight and fat excretion were determined. Results: MgS04 significantly accelerated duodenocaecal transit time and increased faecal fat and weight in all subjects. MgSO4 significantly delayed the reoccurrence of phase III and affected antroduodenal motility during fasting but not after meal ingestion. Postprandial gall-bladder relaxation and postprandial peptide YY release were significantly increased during the MgSO4 experiment compared to placebo. Conclusions: The osmotic laxative MgS04 accelerates intestinal transit both in the fasting and fed state. MgS04 activates the ileal brake mechanism only in the fed state, with peptide YY release and inhibition of gall-bladder emptying. [ABSTRACT FROM AUTHOR]

Cellobiohydrolase I is an industrially important exocellulase secreted in high yields by the filamentous fungus Trichoderma reesei. The nature and effect of glycosylation of CBHI and other cellulolytic enzymes is largely unknown, although many other structural and mechanistic aspects of cellulolytic enzymes are well characterised. Using a combination of liquid chromatography, electrospray mass spectrometry, solid-phase Edman degradation, and monosaccharide analysis we have identified every site of glycosylation of CBHI from a high cellulase-producing mutant strain of T. reesei, ALKO2877, and characterised each site in terms of its modifying carbohydrate and site-specific heterogeneity. The catalytic core domain comprises three N-linked glycans which each consist of a single N-acetylglucosamine residue. Within the glycopeptide linker domain, all eight threonines are variably glycosylated with between at least one, and up to three, mannose residues per site. All serines in this domain are at least partially glycosylated with a single mannose residue. This linker region has also been shown to be sulfated by a combination of ion chromatography and collision-induced dissociation electrospray mass spectrometry. The sulfate is probably mannose-linked. The biological significance of N-linked single N-acetylglucosamine in the catalytic core, and mannose sulfation in the linker region, is not known. [ABSTRACT FROM AUTHOR]

In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen- induced changes in AR. The effect of allergen challenge on AR was investigated in 21 atopic asthmatic patients. Allergen challenge resulted in a significant decrease in PC20 histamine after 24 h. When the group was divided into three subgroups according to baseline PC20 histamine, a significant decrease in PC20 histamine was found only in patients with relatively high baseline PC20 histamine (groups 1 and 2). A significant inverse correlation was found between baseline PC20 and allergen-induced PC20 histamine. The effect of repeated allergen challenge on AR was studied in eight patients. The first allergen challenge resulted in a significant decrease in PC20 histamine; no further decrease in mean PC20 histamine was seen after the second allergen challenge. These results suggest that allergen-induced changes in AR occur mainly in patients with relatively high baseline PC20 values. Once an increase in AR is induced, further allergen challenge does not always result in further increase in AR. [ABSTRACT FROM AUTHOR]

Background Anti-allergic mattress encasing may provide clinical benefit in asthmatic patients. However, the effect of mattress encasings on allergen-specific parameters, such as bronchial reactions to house dust mite (HDM) challenge, is not clear. Objective To investigate the effect of anti-allergic mattress encasings on allergen sensitivity in patients with moderate to severe asthma. Methods Twenty-seven patients with asthma and HDM allergy were studied in a double-blind, placebo-controlled study. Concentrations of Dermatophagoides pteronyssinus (Der p 1) were measured in mattress dust before and after 1 year of treatment; bronchial histamine challenge, bronchial challenge with HDM and intradermal skin challenges with HDM were performed. The number of eosinophils in peripheral blood was assessed. Results In the active group, but not in the placebo group, there was a significant reduction in Der p 1 concentration in the dust collected from the mattresses after 1 year of treatment compared to before. There was a significant difference between the groups with respect to HDM-induced early-reaction (ER) in the airways and the number of blood eosinophils, which reflected an increase in ER and eosinophils in the placebo group without significant change in the active group. No significant improvement in PC20 histamine, late-reaction (LR) and skin tests was found in either groups. Conclusion Our data suggest that encasings protect against a further increase in allergen sensitivity in asthmatic patients, so their use should be recommended. [ABSTRACT FROM AUTHOR]