Nasopharyngeal Microbiota Profiles in Rural Venezuelan Children Are Associated With Respiratory and Gastrointestinal Infections

BACKGROUND: Recent research suggests that the microbiota affects susceptibility to both respiratory tract infections (RTIs) and gastrointestinal infections (GIIs). In order to optimize global treatment options, it is important to characterize microbiota profiles across different niches and geographic/socioeconomic areas where RTI and GII prevalences are high. METHODS: We performed 16S sequencing of nasopharyngeal swabs from 209 Venezuelan Amerindian children aged 6 weeks-59 months who were participating in a 13-valent pneumococcal conjugate vaccine (PCV13) study. Using random forest models, differential abundance testing, and regression analysis, we determined whether specific bacteria were associated with RTIs or GIIs and variation in PCV13 response. RESULTS: Microbiota compositions differed between children with or without RTIs (P = .018) or GIIs (P = .001). Several species were associated with the absence of infections. Some of these health-associated bacteria are also observed in developed regions, such as Corynebacterium (log2(fold change [FC]) = 3.30 for RTIs and log2(FC) = 1.71 for GIIs), while others are not commonly observed in developed regions, such as Acinetobacter (log2(FC) = 2.82 and log2(FC) = 5.06, respectively). Klebsiella spp. presence was associated with both RTIs (log2(FC) = 5.48) and GIIs (log2(FC) = 7.20). CONCLUSIONS: The nasopharyngeal microbiota of rural Venezuelan children included several bacteria that thrive in tropical humid climates. Interestingly, nasopharyngeal microbiota composition not only differed in children with an RTI but also in those with a GII, which suggests a reciprocal interplay between the 2 environments. Knowledge of region-specific microbiota patterns enables tailoring of preventive and therapeutic approaches

Impairment in work and activities of daily life in patients with psoriasis:results of the prospective BioCAPTURE registry

Background: Little is known about the extent of impairments in work and activities of daily life (ADL) in patients with psoriasis, and the influence of contextual factors such as disease-related characteristics and treatment. Therefore, this study aimed to assess these impairments in patients with psoriasis who started using biologicals/small molecule inhibitors. Methods: Using data from the prospective BioCAPTURE registry, we collected patient, disease, and treatment parameters, as well as work/ADL impairments at baseline, 6 and 12 months. Changes in impairment parameters and correlations between impairment and patient/disease characteristics were assessed using generalized estimating equations. Results: We included 194 patients in our analysis. After biological initiation, disease activity decreased significantly (PASI 11.2 at baseline versus 3.9 at 12 months, p &lt; 0.001). Work-for-pay in this cohort was lower than in the Dutch general population (53% versus 67%, p = 0.01). In patients who had work-for-pay, presenteeism improved over time (5% at baseline versus 0% at 12 months, p = 0.04). Up to half of the patients reported impairments in ADL, which did not change over time. Associations between impairments and contextual factors varied, but all impairments were associated with worse mental/physical general functioning. Conclusion: Patients with psoriasis using biologicals are less likely to have work-for-pay. Treatment improves the work productivity of employed patients, but we were unable to detect changes in ADL performance.</p

Natural and flexible error recovery for generated parsers

Parser generators are an indispensable tool for rapid language devel- opment. However, they often fall short of the finesse of a hand-crafted parser, built with the language semantics in mind. One area where generated parsers have pro- vided unsatisfactory results is that of error recovery. Good error recovery is both natural, giving recovery suggestions in line with the intention of the programmer; and flexible, allowing it to be adapted according to language insights and lan- guage changes. This paper describes a novel approach to error recovery, taking into account not only the context-free grammar, but also indentation usage. We base our approach on an extension of the SGLR parser that supports fine-grained error recovery rules and can be used to parse complex, composed languages. We take a divide-and-conquer approach to error recovery: using indentation, erro- neous regions of code are identified. These regions constrain the search space for applying recovery rules, improving performance and ensuring recovery sug- gestions local to the error. As a last resort, erroneous regions can be discarded. Our approach also integrates bridge parsing to provide more accurate suggestions for indentation-sensitive language constructs such as scopes. We evaluate our ap- proach by comparison with the JDT Java parser used in Eclipse

Providing rapid feedback in generated modular language environments adding error recovery to scannerless generalized-LR parsing

Integrated development environments (IDEs) increase programmer productivity, providing rapid, interactive feedback based on the syntax and semantics of a language. A heavy burden lies on developers of new languages to provide adequate IDE support. Code generation techniques provide a viable, efficient approach to semi-automatically produce IDE plugins. Key components for the realization of plugins are the language's grammar and parser. For embedded languages and language extensions, constituent IDE plugin modules and their grammars can be combined. Unlike conventional parsing algorithms, scannerless generalized-LR parsing supports the full set of context-free grammars, which is closed under composition, and hence can parse language embeddings and extensions composed from separate grammar modules. To apply this algorithm in an interactive environment, this paper introduces a novel error recovery mechanism, which allows it to be used with files with syntax errors -- common in interactive editing. Error recovery is vital for providing rapid feedback in case of syntax errors, as most IDE services depend on the parser -- from syntax highlighting to semantic analysis and cross-referencing. We base our approach on the principles of island grammars, and automatically generate new productions for existing grammars, making them more permissive of their inputs. To cope with the added complexity of these grammars, we adapt the parser to support backtracking. We evaluate the recovery quality and performance of our approach using a set of composed languages, based on Java and Stratego

Severe obstructive sleep apnea in children with syndromic craniosynostosis:analysis of pulse transit time

STUDY OBJECTIVES: We examined the association between pulse transit time (PTT) and obstructive sleep apnea (OSA) in children with syndromic craniosynostosis (SCS), where OSA is a common problem and may cause cardiorespiratory disturbance.METHODS: Retrospective study of children (age &lt;18 years) with SCS and moderate-to-severe OSA (i.e., obstructive apnea-hypopnea index [oAHI] ≥ 5), or no OSA (oAHI &lt; 1) who underwent overnight polysomnography (PSG). Children without SCS and normal PSG were included as controls. Reference intervals (RIs) for PTT were computed by non-parametric bootstrap analysis. Based on RIs of controls, the sensitivity and specificity of PTT to detect OSA were determined. In a linear mixed-model the explanatory variables assessed were sex, age, sleep stage, and time after obstructive events.RESULTS: In all 68 included children (19 SCS with OSA, 30 SCS without OSA, 19 controls), obstructive events occurred throughout all sleep stages, most prominently during rapid eye movement sleep (REM) and non-REM sleep stages N1 and N2, with evident PTT changes. Greatest reductions were observed 4 - 8 s after an event (p &lt; 0.05). In SCS with OSA, PTT RIs were lower during all sleep stages compared to SCS without OSA. The highest sensitivity was observed during N1 (55.5%), and the highest specificity during REM (76.5%). Lowest PTT values were identified during N1.CONCLUSIONS: Obstructive events occur throughout all sleep stages with transient reductions in PTT. However, PTT as a variable for OSA detection is limited by its sensitivity and specificity.</p

Severe obstructive sleep apnea in children with syndromic craniosynostosis:analysis of pulse transit time

STUDY OBJECTIVES: We examined the association between pulse transit time (PTT) and obstructive sleep apnea (OSA) in children with syndromic craniosynostosis (SCS), where OSA is a common problem and may cause cardiorespiratory disturbance.METHODS: Retrospective study of children (age &lt;18 years) with SCS and moderate-to-severe OSA (i.e., obstructive apnea-hypopnea index [oAHI] ≥ 5), or no OSA (oAHI &lt; 1) who underwent overnight polysomnography (PSG). Children without SCS and normal PSG were included as controls. Reference intervals (RIs) for PTT were computed by non-parametric bootstrap analysis. Based on RIs of controls, the sensitivity and specificity of PTT to detect OSA were determined. In a linear mixed-model the explanatory variables assessed were sex, age, sleep stage, and time after obstructive events.RESULTS: In all 68 included children (19 SCS with OSA, 30 SCS without OSA, 19 controls), obstructive events occurred throughout all sleep stages, most prominently during rapid eye movement sleep (REM) and non-REM sleep stages N1 and N2, with evident PTT changes. Greatest reductions were observed 4 - 8 s after an event (p &lt; 0.05). In SCS with OSA, PTT RIs were lower during all sleep stages compared to SCS without OSA. The highest sensitivity was observed during N1 (55.5%), and the highest specificity during REM (76.5%). Lowest PTT values were identified during N1.CONCLUSIONS: Obstructive events occur throughout all sleep stages with transient reductions in PTT. However, PTT as a variable for OSA detection is limited by its sensitivity and specificity.</p

A meta-analysis of methotrexate polyglutamates in relation to efficacy and toxicity of methotrexate in inflammatory arthritis, colitis and dermatitis

Aims: In immune-mediated inflammatory diseases (IMIDs), early symptom control is a key therapeutic goal. Methotrexate (MTX) is the first-line treatment across IMIDs. However, MTX is underutilized and suboptimally dosed, partly due to the inability of making individualized treatment decisions through therapeutic drug monitoring (TDM). To implement TDM in clinical practice, establishing a relationship between drug concentration and disease activity is paramount. In this meta-analysis, we investigated the relationship between concentrations of MTX polyglutamates (MTX-PG) in erythrocytes and efficacy as well as toxicity across IMIDs. Methods: Studies analysing MTX-PG in relation to disease activity and/or toxicity were included for inflammatory arthritis (rheumatoid [RA] and juvenile idiopathic arthritis [JIA]), inflammatory bowel disease (Crohn's and ulcerative colitis) and dermatitis (psoriasis and atopic dermatitis). Meta-analyses were performed resulting in several summary effect measures: regression coefficient (β), correlation coefficient and mean difference (of MTX-PG in responders vs. nonresponders) for IMIDs separately and collectively. Results: Twenty-five studies were included. In RA and JIA, higher MTX-PG was significantly associated with lower disease activity at 3 months (β: −0.002; 95% confidence interval [CI]: −0.004 to −0.001) and after 4 months of MTX use (β: −0.003; 95% CI: −0.005 to −0.002). Similarly, higher MTX-PG correlated with lower disease activity in psoriasis (R: −0.82; 95% CI: −0.976 to −0.102). Higher MTX-PG was observed in RA, JIA and psoriasis responders (mean difference: 5.2 nmol/L MTX-PG total; P <.01). Conclusion: We showed that higher concentrations of erythrocyte MTX-PG were associated with lower disease activity in RA, JIA and psoriasis. These findings are an important step towards implementation of TDM for MTX treatment across IMIDs