| Clinical metagenomic next-generation sequencing (mNGS), the comprehensive analysis of microbial and host genetic material (DNA and RNA) in samples from patients, is rapidly moving from research to clinical laboratories. This emerging approach is changing how physicians diagnose and treat infectious disease, with applications spanning a wide range of areas, including antimicrobial resistance, the microbiome, human host gene expression (transcriptomics) and oncology. Here, we focus on the challenges of implementing mNGS in the clinical laboratory and address potential solutions for maximizing its impact on patient care and public health.

Agnostic metagenomic next-generation sequencing (mNGS) has emerged as a promising single, universal pathogen detection method for infectious disease diagnostics. This methodology allows for identification and genomic characterization of bacteria, fungi, parasites, and viruses without the need for a priori knowledge of a specific pathogen directly from clinical specimens. Although there are increasing reports of mNGS successes, several hurdles need to be addressed, such as differentiation of colonization from infection, extraneous sources of nucleic acid, method standardization, and data storage, protection, analysis, and interpretation. As more commercial and clinical microbiology laboratories develop mNGS assays, it is important for treating practitioners to understand both the power and limitations of this method as a diagnostic tool for infectious diseases.

We report, to the best of our knowledge, the first demonstration of thermally controlled soliton mode-locked frequency comb generation in microresonators. By controlling the electric current through heaters integrated with silicon nitride microresonators, we demonstrate a systematic and repeatable pathway to single- and multi-soliton mode-locked states without adjusting the pump laser wavelength. Such an approach could greatly simplify the generation of mode-locked frequency combs and facilitate applications such as chip-based dual-comb spectroscopy.

Key Points• In patients with previously diagnosed IPS, more than half (57%) had pathogens detected by currently available diagnostic methods.• Detection of a pathogen was significantly associated with high mortality regardless of significance of pathogenicity in lung. HHV-6 and HRV were rarely detected in controls, whereas CMV and Aspergillus were occasionally detected with low pathogen load. Patients with pathogens had worse day-100 survival than those without (hazard ratio, 1.88; P 5 .03). Mortality in patients with only pathogens of "uncertain" significance in lung was similar to that in patients with pathogens of "established" significance. Metagenomic next-generation sequencing did not reveal additional significant pathogens. Our study demonstrated that approximately half of patients with IPS had pathogens detected in BAL, and pathogen detection was associated with increased mortality. Thus, an expanded infection detection panel can significantly increase the diagnostic precision for idiopathic pneumonia. (Blood. 2015;125(24):3789-3797)

The generation of temporal cavity solitons in microresonators results in coherent low-noise optical frequency combs that are critical for applications in spectroscopy, astronomy, navigation or telecommunications. Breather solitons also form an important part of many different classes of nonlinear wave systems, manifesting themselves as a localized temporal structure that exhibits oscillatory behaviour. To date, the dynamics of breather solitons in microresonators remains largely unexplored, and its experimental characterization is challenging. Here we demonstrate the excitation of breather solitons in two different microresonator platforms based on silicon nitride and on silicon. We investigate the dependence of the breathing frequency on pump detuning and observe the transition from period-1 to period-2 oscillation. Our study constitutes a significant contribution to understanding the soliton dynamics within the larger context of nonlinear science.