False positive bronchoalveolar lavage galactomannan: Effect of host and cut-off value.

OBJECTIVES: Bronchoalveolar lavage galactomannan (BAL-GM) is a mycological criterion for diagnosis of probable invasive aspergillosis (IA) per European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORT-MSG) consensus criteria, but its real-world positive predictive value (PPV) has not been well-studied. Our aim was to estimate the PPV of BAL-GM in a contemporary cohort of patients with positive BAL-GM. METHODS: We identified consecutive patients with ≥1 positive BAL-GM value (index ≥ 0.5) at Brigham and Women's Hospital from 11/2009 to 3/2016. We classified patients as having no, possible, probable, or proven IA, excluding BAL-GM as mycological criterion. RESULTS: We studied 134 patients: 54% had hematologic malignancy (HM), and 10% were solid organ transplant (SOT) recipients. A total of 42% of positive (≥0.5) BAL-GM results were falsely positive (PPV 58%). The number of probable IA cases was increased by 23% using positive BAL-GM as mycologic criterion alone. PPV was higher in patients with HM or SOT (P < 0.001) and with use of higher thresholds for positivity (BAL-GM ≥ 1 vs 1-0.8 vs 0.8-0.5: P = 0.002). CONCLUSIONS: 42% of positive BAL-GM values were falsely positive. We propose a critical reassessment of BAL-GM cutoff values in different patient populations. Accurate noninvasive tests for diagnosis of IA are urgently needed.

Integrative in vivo analysis of the ethanolamine utilization bacterial microcompartment in Escherichia coli.

Bacterial microcompartments (BMCs) are self-assembling protein megacomplexes that encapsulate metabolic pathways. Although approximately 20% of sequenced bacterial genomes contain operons encoding putative BMCs, few have been thoroughly characterized, nor any in the most studied Escherichia coli strains. We used an interdisciplinary approach to gain deep molecular and functional insights into the ethanolamine utilization (Eut) BMC system encoded by the eut operon in E. coli K-12. The eut genotype was linked with the ethanolamine utilization phenotype using deletion and overexpression mutants. The subcellular dynamics and morphology of the E. coli Eut BMCs were characterized in cellula by fluorescence microscopy and electron (cryo)microscopy. The minimal proteome reorganization required for ethanolamine utilization and the in vivo stoichiometric composition of the Eut BMC were determined by quantitative proteomics. Finally, the first flux map connecting the Eut BMC with central metabolism in cellula was obtained by genome-scale modeling and 13C-fluxomics. Our results reveal that contrary to previous suggestions, ethanolamine serves both as a nitrogen and a carbon source in E. coli K-12, while also contributing to significant metabolic overflow. Overall, this study provides a quantitative molecular and functional understanding of the BMCs involved in ethanolamine assimilation by E. coli.IMPORTANCEThe properties of bacterial microcompartments make them an ideal tool for building orthogonal network structures with minimal interactions with native metabolic and regulatory networks. However, this requires an understanding of how BMCs work natively. In this study, we combined genetic manipulation, multi-omics, modeling, and microscopy to address this issue for Eut BMCs. We show that the Eut BMC in Escherichia coli turns ethanolamine into usable carbon and nitrogen substrates to sustain growth. These results improve our understanding of compartmentalization in a widely used bacterial chassis.

The potential role of community pharmacy staff in reducing patient delay in consulting with symptoms of rheumatoid arthritis: a qualitative study.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis which can cause joint damage and reduced quality of life. Early treatment of RA within 3 months of symptom onset is associated with improved clinical outcomes. However, this window of opportunity is often missed. One important contributing factor is patients with symptoms of RA delaying consulting their general practitioner (GP). Previous research indicates that patients with inflammatory arthritis are likely to visit pharmacies for advice before consulting their GP. Therefore, pharmacists are well positioned to identify patients with symptoms of early inflammatory arthritis and signpost them appropriately. This research examines community pharmacy staff's knowledge, perceptions, and approaches to management of patients presenting with symptoms of RA in order to identify training needs and other opportunities for intervention to enhance the role of pharmacy staff in the pathway to care. METHODS: Semi-structured interviews were conducted with 19 community pharmacy staff in the West Midlands (UK), during a 12-month period (2017-2018). The interviews were audio-recorded, transcribed, and analyzed using thematic analysis facilitated by NVivo 12. RESULTS: There was considerable variation in knowledge and perceptions of RA and the need for early treatment amongst pharmacists and other pharmacy staff. The potential role of pharmacists and other pharmacy staff in reducing delay in help-seeking was also discussed. Four themes emerged from thematic analysis: (1) Variations in perceptions and knowledge about RA. (2) The role of the pharmacy in increasing public awareness about RA. (3) The role of the pharmacy staff in facilitating access to the GP. (4) Practical considerations for pharmacy-based interventions. CONCLUSION: Variability in knowledge and perceptions of RA amongst pharmacists, and amongst other pharmacy staff will affect effective signposting of suspected RA cases. This study identifies opportunities for enhanced training of community pharmacists and other pharmacy staff in relation to inflammatory arthritis as well as other pharmacy-based interventions, such as public awareness campaigns about RA and other musculoskeletal conditions. Together with existing referral services and other pharmacy-based initiatives this could result in enhanced signposting to GP consultation or other appropriate NHS services for inflammatory symptoms and reduced treatment delay.

Efficient focusing of microwave hyperthermia for small deep-seated breast tumors treatment using particle swarm optimization.

Focused microwave hyperthermia is a technique with advantage of high accuracy and low side effects for breast tumor treatments. In this study, an efficient focusing technique for noninvasive microwave hyperthermia treatment for breast tumors is presented. Particle Swarm Optimization (PSO) is used to find the optimum excitations (phases and amplitudes) of a three dimension (3D) Micro-Strip Patch (MSP) antenna array operating at 2.45 GHz. The antenna excitations are optimized to maximize the power loss density and the Specific Absorption Rate (SAR) at the tumor location, to reach the required hyperthermia temperature (above 42 °C) at the tumor location without causing hot spots in healthy tissues. The technique is tested on a challenging scenario of a 3D realistic breast model having a tumor less than 1 cm3 volume and embedded in different locations deep in the glandular tissue of a very dense breast. The results confirmed the capability of the focusing technique.

Breath-Based Diagnosis of Infectious Diseases: A Review of the Current Landscape.

Various analytical methods can be applied to concentrate, separate, and examine trace volatile organic metabolites in the breath, with the potential for noninvasive, rapid, real-time identification of various disease processes, including an array of microbial infections. Although biomarker discovery and validation in microbial infections can be technically challenging, it is an approach that has shown great promise, especially for infections that are particularly difficult to identify with standard culture and molecular amplification-based approaches. This article discusses the current state of breath analysis for the diagnosis of infectious diseases.

A Mixed Integer Linear Programming Approach to Electrical Stimulation Optimization Problems.

Electrical stimulation optimization is a challenging problem. Even when a single region is targeted for excitation, the problem remains a constrained multi-objective optimization problem. The constrained nature of the problem results from safety concerns while its multi-objectives originate from the requirement that non-targeted regions should remain unaffected. In this paper, we propose a mixed integer linear programming formulation that can successfully address the challenges facing this problem. Moreover, the proposed framework can conclusively check the feasibility of the stimulation goals. This helps researchers to avoid wasting time trying to achieve goals that are impossible under a chosen stimulation setup. The superiority of the proposed framework over alternative methods is demonstrated through simulation examples.

Breath-based diagnosis of fungal infections.

Invasive aspergillosis and other invasive fungal infections are associated with significant morbidity and mortality in immunocompromised patients, in large part due to limitations of existing diagnostic methods for these infections. Detection of species-specific volatile sesquiterpene metabolites of fungal origin in the breath of patients with invasive fungal infections allows the diagnosis and monitoring of these infections in vivo, non-invasively and more rapidly than possible with current diagnostic methods. While detection of exogenous microbial volatile metabolites in the breath has opened up a new and exciting dimension of diagnostic research and development in infectious diseases, we discuss the daunting challenges to volatile diagnostic biomarker discovery and clinical development.