Photonic integrated Mach-Zehnder interferometer with an on-chip reference arm for optical coherence tomography

Optical coherence tomography (OCT) is a noninvasive, three-dimensional imaging modality with several medical and industrial applications. Integrated photonics has the potential to enable mass production of OCT devices to significantly reduce size and cost, which can increase its use in established fields as well as enable new applications. Using silicon nitride (Si(3)N(4)) and silicon dioxide (SiO(2)) waveguides, we fabricated an integrated interferometer for spectrometer-based OCT. The integrated photonic circuit consists of four splitters and a 190 mm long reference arm with a foot-print of only 10 × 33 mm(2). It is used as the core of a spectral domain OCT system consisting of a superluminescent diode centered at 1320 nm with 100 nm bandwidth, a spectrometer with 1024 channels, and an x-y scanner. The sensitivity of the system was measured at 0.25 mm depth to be 65 dB with 0.1 mW on the sample. Using the system, we imaged human skin in vivo. With further optimization in design and fabrication technology, Si(3)N(4)/SiO(2) waveguides have a potential to serve as a platform for passive photonic integrated circuits for OCT

Multispectral three-dimensional optical coherence tomography

A spectral-domain OCT system operating at 1300 nm wavelength region, capable of acquiring 47,000 A-lines/s, was designed and developed. Its axial and transverse resolutions were 6 micro and 15 &micro respectively. OCT images of human skin were obtained in vivo using three OCT systems, in order to find the optimal wavelength region for dermal imaging. 800 nm OCT system provided better image contrast over other two wavelength regions. Meanwhile, 1300 nm wavelength region was needed to obtain information from deeper dermal layers. To determine the effect of melanin pigmentation on OCT, images were taken from subjects with different ethnic origins. Interestingly, melanin pigmentation was found to have little effect on penetration depth in OCT. In vitro tumour samples, comprising samples with different degrees of dysplasia, were imaged at 800 nm, 1060 nm and 1300 nm wavelength regions to find the capability of OCT to diagnose microstructural changes occurring during tumour progression. 800 nm OCT system was capable to detect the malignant changes with higher contrast than other wavelength regions. However, higher wavelength regions were required to penetrate deeper in densely scattering tumour samples at advanced stages. OCT system operating at 1060 nm was combined with a photoacoustic imaging (PAT) system to obtain complementary information from biological tissues. This multimodal OCT/PAT system demonstrated its potential to deliver microstructural information based on optical scattering and vascular information based on optical absorption in living mice and human skin. The results indicate OCT as a promising imaging modality that can have profound applications in several areas of clinical diagnostic imaging

Structural manipulations of a shelter resource reveal underlying preference functions in a shell-dwelling cichlid fish

Many animals can modify the environments in which they live, thereby changing the selection pressures they experience. A common example of such niche construction is the use, creation or modification of environmental resources for use as nests or shelters. Because these resources often have correlated structural elements, it can be difficult to disentangle the relative contribution of these elements to resource choice, and the preference functions underlying niche-construction behaviour remain hidden. Here, we present an experimental paradigm that uses 3D scanning, modelling and printing to create replicas of structures that differ with respect to key structural attributes. We show that a niche-constructing, shell-dwelling cichlid fish,; Neolamprologus multifasciatus; , has strong open-ended preference functions for exaggerated shell replicas. Fish preferred shells that were fully intact and either enlarged, lengthened or had widened apertures. Shell intactness was the most important structural attribute, followed by shell length, then aperture width. We disentangle the relative roles of different shell attributes, which are tightly correlated in the wild, but nevertheless differentially influence shelter choice and therefore niche construction in this species. We highlight the broad utility of our approach when compared with more traditional methods (e.g. two-choice tasks) for studying animal decision-making in a range of contexts

Aggression and spatial positioning of kin and non-kin fish in social groups

Group-living animals must share space and resources with group mates, who can be either kin or non-kin, and it is often unclear how competitive or cooperative group members should be. In a group-living cichlid, we show that co-habiting females are less aggressive to their female kin (relative to non-kin) despite living at equivalent distances to one another. This pattern was not detected among co-habiting males, revealing that kin-directed social behavior can differ between the sexes.Group-living animals are faced with the challenge of sharing space and local resources amongst group members who may be either relatives or non-relatives. Individuals may reduce the inclusive fitness costs they incur from competing with relatives by either reducing their levels of aggression toward kin, or by maintaining physical separation between kin. In this field study, we used the group-living cichlid Neolamprologus multifasciatus to examine whether within-group aggression is reduced among group members that are kin, and whether kin occupy different regions of their group's territory to reduce kin competition over space and local resources. We determined the kinship relationships among cohabiting adults via microsatellite genotyping and then combined these with spatial and behavioral analyses of groups in the wild. We found that aggressive contests between group members declined in frequency with spatial separation between their shelters. Female kin did not engage in aggressive contests with one another, whereas non-kin females did, despite the fact these females lived at similar distances from one another on their groups' territories. Contests within male-male and male-female dyads did not clearly correlate with kinship. Non-kin male-male and male-female dyads lived at more variable distances from one another on their territories than their corresponding kin dyads. Together, our study indicates that contests among group members can be mediated by relatedness in a sex-dependent manner. We also suggest that spatial relationships can play an important role in determining the extent to which group members compete with one another

Three-dimensional calibration targets for optical coherence tomography

The recent expansion of clinical applications for optical coherence tomography (OCT) is driving the development of approaches for consistent image acquisition. There is a simultaneous need for time-stable, easy-to-use imaging targets for calibration and standardization of OCT devices. We present calibration targets consisting of three-dimensional structures etched into nanoparticle-embedded resin. Spherical iron oxide nanoparticles with a predominant particle diameter of 400 nm were homogeneously dispersed in a two part polyurethane resin and allowed to harden overnight. These samples were then etched using a precision micromachining femtosecond laser with a center wavelength of 1026 nm, 100kHz repetition rate and 450 fs pulse duration. A series of lines in depth were etched, varying the percentage of inscription energy and speed of the translation stage moving the target with respect to the laser. Samples were imaged with a dual wavelength spectral-domain OCT system and point-spread function of nanoparticles within the target was measured

Superconductivity in single crystals of a quasi-one dimensional infinite chain cuprate Srx_xCa1−x_{1-x}CuO2_2 at 90 K

Although there is no complete theory of high temperature superconductivity, the importance of CuO$_2$ planes in cuprate superconductors is confirmed from both theory and experiments. Strong Coulomb repulsion between electrons on the CuO$_2$ plane makes the resultant electron system highly correlated and a difficult problem to solve since exact solutions of many-body Hamiltonian in two dimensions do not exist. If however, superconductivity can arise in structures having chains rather than planes and having a high critical temperature, then the high temperature superconductivity problem could become more tractable since exact solutions in one dimension do exist. In this paper, we report the observation of bulk superconductivity in single crystals of a cuprate Sr$_x$Ca$_{1-x}$CuO$_2$ at very high critical temperature, T$_c$, of $\sim$ 90 K whose structure reveals the presence of infinite double chains of Cu-O-Cu-O instead of CuO$_2$ planes, thus, ensuring quasi-one dimensional superconductivity. Bulk superconducting behaviour was observed in \textit{dc} magnetisation, \textit{ac} susceptibility as well as resistance measurements. The observation of bulk superconductivity in Sr$_x$Ca$_{1-x}$CuO$_2$ having chains of Cu-O-Cu-O rather than planes of CuO$_2$ at a high T$_c$ of 90 K is expected to profoundly impact our understanding of high temperature superconductivity.Comment: 15 pages, 4 figure

Transposon libraries identify novel Mycobacterium bovis BCG genes involved in the dynamic interactions required for BCG to persist during in vivo passage in cattle

Background BCG is the most widely used vaccine of all time and remains the only licensed vaccine for use against tuberculosis in humans. BCG also protects other species such as cattle against tuberculosis, but due to its incompatibility with current tuberculin testing regimens remains unlicensed. BCG’s efficacy relates to its ability to persist in the host for weeks, months or even years after vaccination. It is unclear to what degree this ability to resist the host’s immune system is maintained by a dynamic interaction between the vaccine strain and its host as is the case for pathogenic mycobacteria. Results To investigate this question, we constructed transposon mutant libraries in both BCG Pasteur and BCG Danish strains and inoculated them into bovine lymph nodes. Cattle are well suited to such an assay, as they are naturally susceptible to tuberculosis and are one of the few animal species for which a BCG vaccination program has been proposed. After three weeks, the BCG were recovered and the input and output libraries compared to identify mutants with in vivo fitness defects. Less than 10% of the mutated genes were identified as affecting in vivo fitness, they included genes encoding known mycobacterial virulence functions such as mycobactin synthesis, sugar transport, reductive sulphate assimilation, PDIM synthesis and cholesterol metabolism. Many other attenuating genes had not previously been recognised as having a virulence phenotype. To test these genes, we generated and characterised three knockout mutants that were predicted by transposon mutagenesis to be attenuating in vivo: pyruvate carboxylase, a hypothetical protein (BCG_1063), and a putative cyclopropane-fatty-acyl-phospholipid synthase. The knockout strains survived as well as wild type during in vitro culture and in bovine macrophages, yet demonstrated marked attenuation during passage in bovine lymph nodes confirming that they were indeed involved in persistence of BCG in the host. Conclusion These data show that BCG is far from passive during its interaction with the host, rather it continues to employ its remaining virulence factors, to interact with the host’s innate immune system to allow it to persist, a property that is important for its protective efficacy.</p

Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection: a nested, case-control diagnostic accuracy study

Background We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.Methods We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew’s Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for “viral infection”, “transcriptome”, “biomarker”, and “blood”. We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive participants) during their first week of PCR positivity.Findings We identified 20 candidate blood transcriptomic signatures of viral infection from 18 studies and evaluated their accuracy among 169 blood RNA samples from 96 participants over 24 weeks. Participants were recruited between March 23 and March 31, 2020. 114 samples were from 41 participants with SARS-CoV-2 infection, and 55 samples were from 55 test-negative controls. The median age of participants was 36 years (IQR 27–47) and 69 (72%) of 96 were women. Signatures had little overlap of component genes, but were mostly correlated as components of type I interferon responses. A single blood transcript for IFI27 provided the highest accuracy for discriminating between test-negative controls and test-positive individuals at the time of their first positive SARS-CoV-2 PCR result, with AUROC of 0·95 (95% CI 0·91–0·99), sensitivity 0·84 (0·70–0·93), and specificity 0·95 (0·85–0·98) at a predefined threshold (Z score >2). The transcript performed equally well in individuals with and without symptoms. Three other candidate signatures (including two to 48 transcripts) had statistically equivalent discrimination to IFI27 (AUROCs 0·91–0·95).Interpretation Our findings support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection for screening individuals at high risk of infection, such as contacts of index cases, to facilitate early case isolation and early use of antiviral treatments as they emerge

Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529