Characterization of oral and gut microbiome temporal variability in hospitalized cancer patients.

BACKGROUND: Understanding longitudinal variability of the microbiome in ill patients is critical to moving microbiome-based measurements and therapeutics into clinical practice. However, the vast majority of data regarding microbiome stability are derived from healthy subjects. Herein, we sought to determine intra-patient temporal microbiota variability, the factors driving such variability, and its clinical impact in an extensive longitudinal cohort of hospitalized cancer patients during chemotherapy. METHODS: The stool (n = 365) and oral (n = 483) samples of 59 patients with acute myeloid leukemia (AML) undergoing induction chemotherapy (IC) were sampled from initiation of chemotherapy until neutrophil recovery. Microbiome characterization was performed via analysis of 16S rRNA gene sequencing. Temporal variability was determined using coefficients of variation (CV) of the Shannon diversity index (SDI) and unweighted and weighted UniFrac distances per patient, per site. Measurements of intra-patient temporal variability and patient stability categories were analyzed for their correlations with genera abundances. Groups of patients were analyzed to determine if patients with adverse outcomes had significantly different levels of microbiome temporal variability. Potential clinical drivers of microbiome temporal instability were determined using multivariable regression analyses. RESULTS: Our cohort evidenced a high degree of intra-patient temporal instability of stool and oral microbial diversity based on SDI CV. We identified statistically significant differences in the relative abundance of multiple taxa amongst individuals with different levels of microbiota temporal stability. Increased intra-patient temporal variability of the oral SDI was correlated with increased risk of infection during IC (P = 0.02), and higher stool SDI CVs were correlated with increased risk of infection 90 days post-IC (P = 0.04). Total days on antibiotics was significantly associated with increased temporal variability of both oral microbial diversity (P = 0.03) and community structure (P = 0.002). CONCLUSIONS: These data quantify the longitudinal variability of the oral and gut microbiota in AML patients, show that increased variability was correlated with adverse clinical outcomes, and offer the possibility of using stabilizing taxa as a method of focused microbiome repletion. Furthermore, these results support the importance of longitudinal microbiome sampling and analyses, rather than one time measurements, in research and future clinical practice.

An integrative Bayesian Dirichlet-multinomial regression model for the analysis of taxonomic abundances in microbiome data.

BACKGROUND: The Human Microbiome has been variously associated with the immune-regulatory mechanisms involved in the prevention or development of many non-infectious human diseases such as autoimmunity, allergy and cancer. Integrative approaches which aim at associating the composition of the human microbiome with other available information, such as clinical covariates and environmental predictors, are paramount to develop a more complete understanding of the role of microbiome in disease development. RESULTS: In this manuscript, we propose a Bayesian Dirichlet-Multinomial regression model which uses spike-and-slab priors for the selection of significant associations between a set of available covariates and taxa from a microbiome abundance table. The approach allows straightforward incorporation of the covariates through a log-linear regression parametrization of the parameters of the Dirichlet-Multinomial likelihood. Inference is conducted through a Markov Chain Monte Carlo algorithm, and selection of the significant covariates is based upon the assessment of posterior probabilities of inclusions and the thresholding of the Bayesian false discovery rate. We design a simulation study to evaluate the performance of the proposed method, and then apply our model on a publicly available dataset obtained from the Human Microbiome Project which associates taxa abundances with KEGG orthology pathways. The method is implemented in specifically developed R code, which has been made publicly available. CONCLUSIONS: Our method compares favorably in simulations to several recently proposed approaches for similarly structured data, in terms of increased accuracy and reduced false positive as well as false negative rates. In the application to the data from the Human Microbiome Project, a close evaluation of the biological significance of our findings confirms existing associations in the literature.

The role of the gastrointestinal microbiome in infectious complications during induction chemotherapy for acute myeloid leukemia.

BACKGROUND: Despite increasing data on the impact of the microbiome on cancer, the dynamics and role of the microbiome in infection during therapy for acute myelogenous leukemia (AML) are unknown. Therefore, the authors sought to determine correlations between microbiome composition and infectious outcomes in patients with AML who were receiving induction chemotherapy (IC). METHODS: Buccal and fecal specimens (478 samples) were collected twice weekly from 34 patients with AML who were undergoing IC. Oral and stool microbiomes were characterized by 16S ribosomal RNA V4 sequencing using an Illumina MiSeq system. Microbial diversity and genera composition were associated with clinical outcomes. RESULTS: Baseline stool α-diversity was significantly lower in patients who developed infections during IC compared with those who did not (P = .047). Significant decreases in both oral and stool microbial α-diversity were observed over the course of IC, with a linear correlation between α-diversity change at the 2 sites (P = .02). Loss of both oral and stool α-diversity was associated significantly with the receipt of a carbapenem P < 0.001. Domination events by the majority of genera were transient (median duration, 1 sample), whereas the number of domination events by pathogenic genera increased significantly over the course of IC (P = .002). Moreover, patients who lost microbial diversity over the course of IC were significantly more likely to contract a microbiologically documented infection within the 90 days after IC neutrophil recovery (P = .04). CONCLUSIONS: The current data present the largest longitudinal analyses to date of oral and stool microbiomes in patients with AML and suggest that microbiome measurements could assist with the mitigation of infectious complications of AML therapy. Cancer 2016;122:2186-96. © 2016 American Cancer Society.

Characterization of the human gut microbiome during travelers' diarrhea.

Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the ß-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different ß-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel.

Experimental demonstration of graph-state quantum secret sharing.

Quantum communication and computing offer many new opportunities for information processing in a connected world. Networks using quantum resources with tailor-made entanglement structures have been proposed for a variety of tasks, including distributing, sharing and processing information. Recently, a class of states known as graph states has emerged, providing versatile quantum resources for such networking tasks. Here we report an experimental demonstration of graph state-based quantum secret sharing--an important primitive for a quantum network with applications ranging from secure money transfer to multiparty quantum computation. We use an all-optical setup, encoding quantum information into photons representing a five-qubit graph state. We find that one can reliably encode, distribute and share quantum information amongst four parties, with various access structures based on the complex connectivity of the graph. Our results show that graph states are a promising approach for realising sophisticated multi-layered communication protocols in quantum networks.

Experimental realization of a one-way quantum computer algorithm solving Simon's problem.

We report an experimental demonstration of a one-way implementation of a quantum algorithm solving Simon's problem-a black-box period-finding problem that has an exponential gap between the classical and quantum runtime. Using an all-optical setup and modifying the bases of single-qubit measurements on a five-qubit cluster state, key representative functions of the logical two-qubit version's black box can be queried and solved. To the best of our knowledge, this work represents the first experimental realization of the quantum algorithm solving Simon's problem. The experimental results are in excellent agreement with the theoretical model, demonstrating the successful performance of the algorithm. With a view to scaling up to larger numbers of qubits, we analyze the resource requirements for an n-qubit version. This work helps highlight how one-way quantum computing provides a practical route to experimentally investigating the quantum-classical gap in the query complexity model.

Experimental demonstration of a graph state quantum error-correction code.

Scalable quantum computing and communication requires the protection of quantum information from the detrimental effects of decoherence and noise. Previous work tackling this problem has relied on the original circuit model for quantum computing. However, recently a family of entangled resources known as graph states has emerged as a versatile alternative for protecting quantum information. Depending on the graph's structure, errors can be detected and corrected in an efficient way using measurement-based techniques. Here we report an experimental demonstration of error correction using a graph state code. We use an all-optical setup to encode quantum information into photons representing a four-qubit graph state. We are able to reliably detect errors and correct against qubit loss. The graph we realize is setup independent, thus it could be employed in other physical settings. Our results show that graph state codes are a promising approach for achieving scalable quantum information processing.

Ultraviolet four-wave mixing in the LP(02) fiber mode.

We report UV four-wave mixing in the LP(02) mode of a photonic crystal fiber when pumped by a frequency-doubled 532 nm microchip laser in the normal dispersion regime. A pure LP(02) mode was generated for the pump light by a broadband all-fiber mode converter. Ultraviolet signal wavelengths as short as 342 nm were generated.

1064 nm laser-induced defects in pure SiO2 fibers.

We investigate evidence of the formation of nonbridging oxygen hole centers in pure silica photonic crystal fibers from 5 ps 1064 nm pulses. The formation of the defects is attributed to the breaking of stressed silicon-oxygen bonds in the glass matrix through a many-photon process. We compare the photodarkening induced by the 1064 nm pump with photodarkening induced by short wavelength light in a 1064 nm pumped supercontinuum extending to 400 nm. It is shown that the higher peak power at the pump wavelength makes it a more significant cause of photodarkening when compared to the shorter wavelength light generated in the fiber.

Nonlinear optics in the LP(02) higher-order mode of a fiber.

The distinct disperion properties of higher-order modes in optical fibers permit the nonlinear generation of radiation deeper into the ultraviolet than is possible with the fundamental mode. This is exploited using adiabatic, broadband mode convertors to couple light efficiently from an input fundamental mode and also to return the generated light to an output fundamental mode over a broad spectral range. For example, we generate visible and UV supercontinuum light in the LP(02) mode of a photonic crystal fiber from sub-ns pulses with a wavelength of 532 nm.

Reduced transpiration response to precipitation pulses precedes mortality in a piñon-juniper woodland subject to prolonged drought.

Global climate change is predicted to alter the intensity and duration of droughts, but the effects of changing precipitation patterns on vegetation mortality are difficult to predict. Our objective was to determine whether prolonged drought or above-average precipitation altered the capacity to respond to the individual precipitation pulses that drive productivity and survival. We analyzed 5 yr of data from a rainfall manipulation experiment in piñon-juniper (Pinus edulis-Juniperus monosperma) woodland using mixed effects models of transpiration response to event size, antecedent soil moisture, and post-event vapor pressure deficit. Replicated treatments included irrigation, drought, ambient control and infrastructure control. Mortality was highest under drought, and the reduced post-pulse transpiration in the droughted trees that died was attributable to treatment effects beyond drier antecedent conditions and reduced event size. In particular, trees that died were nearly unresponsive to antecedent shallow soil moisture, suggesting reduced shallow absorbing root area. Irrigated trees showed an enhanced response to precipitation pulses. Prolonged drought initiates a downward spiral whereby trees are increasingly unable to utilize pulsed soil moisture. Thus, the additive effects of future, more frequent droughts may increase drought-related mortality.

Two-photon interference between disparate sources for quantum networking.

Quantum networks involve entanglement sharing between multiple users. Ideally, any two users would be able to connect regardless of the type of photon source they employ, provided they fulfill the requirements for two-photon interference. From a theoretical perspective, photons coming from different origins can interfere with a perfect visibility, provided they are made indistinguishable in all degrees of freedom. Previous experimental demonstrations of such a scenario have been limited to photon wavelengths below 900 nm, unsuitable for long distance communication, and suffered from low interference visibility. We report two-photon interference using two disparate heralded single photon sources, which involve different nonlinear effects, operating in the telecom wavelength range. The measured visibility of the two-photon interference is 80 ± 4%, which paves the way to hybrid universal quantum networks.

Modulational instability in a silicon-on-insulator directional coupler: role of the coupling-induced group velocity dispersion.

We report frequency conversion experiments in silicon-on-insulator (SOI) directional couplers. We demonstrate that the evanescent coupling between two subwavelength SOI waveguides is strongly dispersive and significantly modifies modulational instability (MI) spectra through the coupling induced group velocity dispersion (GVD). As the separation between two 380-nm-wide silicon photonic wires decreases, the increasing dispersion of the coupling makes the GVD in the symmetric supermode more normal and suppresses the bandwidth of the MI gain observed for larger separations.

Coherent supercontinuum generation in photonic crystal fiber with all-normal group velocity dispersion.

We demonstrate supercontinuum generation in a photonic crystal fiber with all-normal group velocity dispersion. Pumping a short section of this fiber with compressed pulses from a compact amplified fiber laser generates a 200 nm bandwidth continuum with typical self-phase-modulation characteristics. We demonstrate that the supercontinuum is compressible to a duration of 26 fs. It therefore has a high degree of coherence between all the frequency components, and is a single pulse in the time domain. A smooth, flat spectrum spanning 800 nm is achieved using a longer piece of fiber.

Stable low-loss optical nanofibres embedded in hydrophobic aerogel.

Nanofibres, optical fibres narrower than the wavelength of light, degrade in hours on exposure to air. We show that encapsulation in hydrophobic silica aerogel (refractive index 1.05) provides protection and stability (over 2 months) without sacrificing low attenuation, strong confinement and accessible evanescent field. The measured attenuation was <0.03 dB/mm, over 10 × lower than reported with other encapsulants. This enables many nanofibre applications based on their extreme small size and strong external evanescent field, such as optical sensors, nonlinear optics, nanofibre circuits and high-Q resonators. The aerogel is more than a waterproof box, it is a completely-compatible gas-permeable material in intimate contact with the nanofibre and hydrophobic on both the macroscopic and molecular scales. Its benefits are illustrated by experiments on gas sensing (exploiting the aerogel's porosity) and supercontinuum generation (exploiting its ultra-low index).

Ultrashort pulse compression and delivery in a hollow-core photonic crystal fiber at 540 nm wavelength.

We have fabricated a bandgap-guiding hollow-core photonic crystal fiber (PCF) capable of transmitting and compressing ultrashort pulses in the green spectral region around 532 nm. When propagating subpicosecond pulses through 1 m of this fiber, we have observed soliton-effect temporal compression by up to a factor of 3 to around 100 fs. This reduces the wavelength at which soliton effects have been observed in hollow-core PCF by over 200 nm. We have used the pulses delivered at the output of the fiber to machine micrometer-scale features in copper.

More than threefold expansion of highly nonlinear photonic crystal fiber cores for low-loss fusion splicing.

We have formed low-loss fusion splices from highly nonlinear (HNL) photonic crystal fibers (PCFs) with small cores and high air-filling fractions to fibers with much larger mode field diameters (MFDs). The PCF core was locally enlarged by the controlled collapse of holes around the core while keeping other holes open. The fiber was then cleaved at the enlarged core and spliced to the large MFD fiber with a conventional electric arc fusion splicer. Splice losses as low as 0.36 dB were achieved between a PCF and a standard single-mode fiber (SMF) with MFDs of 1.8 microm and 5.9 microm, respectively.

Narrowband high-fidelity all-fibre source of heralded single photons at 1570 nm.

An all-fibre heralded single photon source operating at 1570 nm has been demonstrated. The device generates correlated photon pairs, widely spaced in frequency, through four-wave mixing in a photonic crystal fibre. Separation of the pair photons and narrowband filtering is all achieved in fibre. The output heralded single photon rate was 9.2 x 10(4) per second, with a counts-to-accidentals ratio of 10.4 and a heralding fidelity of 52 %. Furthermore, narrowband filtering ensured that the output single photon state was near time-bandwidth limited with a coherence length of 4 ps. Such a source is well suited to quantum information processing applications.

Nonclassical 2-photon interference with separate intrinsically narrowband fibre sources.

In this paper, we demonstrate a source of photon pairs based on four-wave-mixing in photonic crystal fibres. Careful engineering of the phase matching conditions in the fibres enables us to create photon pairs at 597 nm and 860 nm in an intrinsically factorable state showing no spectral correlations. This allows for heralding one photon in a pure state and hence renders narrow band filtering obsolete. The source is narrow band, bright and achieves an overall detection efficiency of up to 21% per photon. For the first time, a Hong-Ou-Mandel interference with unfiltered photons from separate fibre sources is presented.