Automatic Segmentation of the Paediatric Femoral Head.

Developmental dysplasia of the hip (DDH) is a developmental deformity occurring in 0.1-3.4% of infants. Timely surgical intervention can ameliorate the condition in stable hips and reduce future cases of osteoarthritis and total hip replacement. However, current definitions of DDH are subjective, and thus would benefit from a more objective and reliable assessment metric. Since the shape of the femoral head and its congruence with the acetabulum are disrupted by DDH, analysis of the femoral head could potentially play a role in the development of novel objective morphological metric for stable DDH. Therefore, this paper aimed to segment the paediatric femoral head in stable hips from radiographs, which has not been attempted before in the chosen focus age group (1-16 years) where the pelvis and hip joint undergo significant development. Two techniques were compared against a baseline U-Net: data augmentation and region-of-interest (ROI) networks. Four models were developed either without, with just one, or with both techniques. Evaluated using tenfold cross-validation, the U-Net trained with both techniques achieved the best results, with a Dice Similarity Coefficient (DSC) of 0.951±0.037 (mean ± standard deviation, calculated with 720 images). Future work will use this segmentation algorithm to accurately characterise hip joint morphology and estimate the benefit of early surgical intervention in DDH.

Replacing mechanical protection with colorful faces-twice: parallel evolution of the non-operculate marine worm-snail genera Thylacodes (Guettard, 1770) and Cayo n. gen. (Gastropoda: Vermetidae).

Vermetid worm-snails are sessile and irregularly coiled marine mollusks common in warmer nearshore and coral reef environments that are subject to high predation pressures by fish. Often cryptic, some have evolved sturdy shells or long columellar muscles allowing quick withdrawal into better protected parts of the shell tube, and most have variously developed opercula that protect and seal the shell aperture trapdoor-like. Members of Thylacodes (previously: Serpulorbis) lack such opercular protection. Its species often show polychromatic head-foot coloration, and some have aposematic coloration likely directed at fish predators. A new polychromatic species, Thylacodes bermudensis n. sp., is described from Bermuda and compared morphologically and by DNA barcode markers to the likewise polychromatic western Atlantic species T. decussatus (Gmelin, 1791). Operculum loss, previously assumed to be an autapomorphy of Thylacodes, is shown to have occurred convergently in a second clade of the family, for which a new genus Cayo n. gen. and four new western Atlantic species are introduced: C. margarita n. sp. (type species; with type locality in the Florida Keys), C. galbinus n. sp., C. refulgens n. sp., and C. brunneimaculatus n. sp. (the last three with type locality in the Belizean reef) (all new taxa authored by Bieler, Collins, Golding & Rawlings). Cayo n. gen. differs from Thylacodes in morphology (e.g., a protoconch that is wider than tall), behavior (including deep shell entrenchment into the substratum), reproductive biology (fewer egg capsules and eggs per female; an obliquely attached egg capsule stalk), and in some species, a luminous, "neon-like", head-foot coloration. Comparative investigation of the eusperm and parasperm ultrastructure also revealed differences, with a laterally flattened eusperm acrosome observed in two species of Cayo n. gen. and a spiral keel on the eusperm nucleus in one, the latter feature currently unique within the family. A molecular phylogenetic analysis based on mitochondrial and nuclear rRNA gene sequences (12SrRNA, trnV, 16SrRNA, 28SrRNA) strongly supports the independent evolution of the two non-operculate lineages of vermetids. Thylacodes forms a sister grouping to a clade comprising Petaloconchus, Eualetes, and Cupolaconcha, whereas Cayo n. gen is strongly allied with the small-operculate species Vermetus triquetrus and V. bieleri. COI barcode markers provide support for the species-level status of the new taxa. Aspects of predator avoidance/deterrence are discussed for these non-operculate vermetids, which appear to involve warning coloration, aggressive behavior when approached by fish, and deployment of mucous feeding nets that have been shown, for one vermetid in a prior study, to contain bioactive metabolites avoided by fish. As such, non-operculate vermetids show characteristics similar to nudibranch slugs for which the evolution of warning coloration and chemical defenses has been explored previously.

Advanced IoT Pressure Monitoring System for Real-Time Landfill Gas Management.

This research presents a novel stand-alone device for the autonomous measurement of gas pressure levels on an active landfill site, which enables the real-time monitoring of gas dynamics and supports the early detection of critical events. The developed device employs advanced sensing technologies and wireless communication capabilities, enabling remote data transmission and access via the Internet. Through extensive field experiments, we demonstrate the high sampling rate of the device and its ability to detect significant events related to gas generation dynamics in landfills, such as flare shutdowns or blockages that could lead to hazardous conditions. The validation of the device's performance against a high-end analytical system provides further evidence of its reliability and accuracy. The developed technology herein offers a cost-effective and scalable solution for environmental landfill gas monitoring and management. We expect that this research will contribute to the advancement of environmental monitoring technologies and facilitate better decision-making processes for sustainable waste management.

On the independent significance of generalizations of the Wigner distribution function.

The Wigner distribution function (WDF) is a significant time-frequency analysis tool in, e.g., the theory of optical coherence and signal processing. Recently, various generalizations of the WDF associated with linear canonical transforms have been proposed to improve and broaden its applications. It is useful to identify which of these novel distributions have independent significance for further investigation. We plot these distributions for a test signal using symbolic integration to find which distributions are linear coordinate transforms of the WDF or have unique features. Five distributions are determined to be linear coordinate transforms of the WDF. Two distributions show unique characteristics. We focus on the mathematical interpretation, properties, and possible applications of those two distributions. We demonstrate how one of them can be used in the analysis of partially coherent systems.

Automated filter selection for suppression of Gibbs ringing artefacts in MRI.

Gibbs ringing creates artefacts in magnetic resonance images that can mislead clinicians. Reconstruction algorithms attempt to suppress Gibbs ringing, or an additional ringing suppression algorithm may be applied post reconstruction. Novel reconstruction algorithms are often compared with filtered Fourier reconstruction, but the choices of filters and filter parameters can be arbitrary and sub-optimal. Evaluation of different reconstruction and post-processing algorithms is difficult to automate or subjective: many metrics have been used in the literature. In this paper, we evaluate twelve of those metrics and demonstrate that none of them are fit for purpose. We propose a novel metric and demonstrate its efficacy in 1D and 2D simulations. We use our new metric to optimise and compare 17 smoothing filters for suppression of Gibbs artefacts. We examine the transfer functions of the optimised filters, with counter-intuitive results regarding the highest-performing filters. Our results will simplify and improve the comparison of novel MRI reconstruction and post-processing algorithms, and lead to the automation of ringing suppression in MRI. They also apply more generally to other applications in which data is captured in the Fourier domain.

Using an Ensemble to Identify and Classify Macroalgae Antimicrobial Peptides.

The rapid spread of multi-drug resistant microbes has lead researchers to discover natural alternative remedies such as antimicrobial peptides (AMPs). In the first line of defense, AMPs display a broad spectrum of potent activity against multi-resistant pathogenic bacteria, viruses, fungi, and even cancer. AMPs can be further characterised into families according to amino acid composition, secondary structure, and function. However, despite recent advancements in rapid computational methods for AMP prediction from various mammalian, aquatic, and terrestrial species, there is limited information regarding their presence, functional roles, and family type from marine macroalgae. In this paper, we present a promising two-tier ensemble of heterogeneous machine learning models that integrates seven well-known machine learning classifiers to predict AMPs from macroalgae. The first tier of the ensemble consists of a suite of binary classifiers that identify AMPs from protein sequence data which are then forwarded to a second-tier multi-class ensemble to characterise their functional family type. The two-tier ensemble was successfully used to identify 39 putative AMP sequences in 12 macroalgae species from three different phyla groups. The approach we describe is not limited to AMPs and can also be applied to search sequence data for other types of proteins.

Fast, sub-pixel accurate, displacement measurement method: optical and terahertz systems.

A novel (to the best of our knowledge), fast method to measure in-plane object motion in 1D with sub-pixel accuracy which complements the correlation technique is proposed. The method is verified experimentally using both visible and terahertz images. The absolute sum of grey level accumulated change is used to quantify object motion. The method requires calibration for each target, but only addition and subtraction operations. This results in a decrease of two orders of magnitude in the computation time.

Optical Trajectory Manipulations Using the Self-Written Waveguide Technique.

This study is novel for several reasons: We used a thin drop cast layer of dry photosensitive materials to study the behaviors of wet photopolymer media using microscopic distances during the Self-Written Waveguide (SWW) process; then, we examined the self-trajectories formed inside the solid material. The results provide a framework for theoretical and experimental examinations by handling the effects of manipulating the alignment of fibers. The other main advantage of these techniques is their lightweight, easy to process, highly flexible, and ultimately low-cost nature. First, the SWW process in wet photopolymer media (liquid solutions) was examined under three cases: single-, counter-, and co-fiber exposure. Then, the SWWs formed inside the solid material were examined along with the effects of manipulating the alignment of the fibers. In all cases, high precision measurements were used to position the fiber optic cables (FOCs) before exposure using a microscope. The self-writing process was indirectly monitored by observing (imaging) the light emerging from the side of the material sample during SWW formation. In this way, we examined the optical waveguide trajectories formed in Acrylamide/Polyvinyl Alcohol (AA/PVA), a photopolymer material (sensitized at 532 nm). First, the transmission of light by this material is characterized. Then, the bending and merging of the waveguides that occur are investigated. The predictions of our model are shown to qualitatively agree with the observed trajectories. The largest index changes taking place at any time during exposure, i.e., during SWW formation, are shown to take place at the positions where the largest exposure light intensity is present. Typically, such maxima exist close to the input face. The first maximum is referred to as the location of the Primary Eye. Other local maxima also appear further along the SWW and are referred to as Secondary Eyes, i.e., eyes deeper within the material.

Multi-layered full-field phase imaging using continuous-wave terahertz ptychography.

Due to the unique properties of terahertz (THz) waves, THz phase imaging has been widely investigated to retrieve the absorption and phase modulation of dielectric two-dimensional thin samples, as well as multiple stacked samples. In this Letter, we apply the three-dimensional ptychographic iterative engine algorithm for continuous-wave THz full-field multi-layered phase imaging. The complex-valued transmission function of two-layered polypropylene thin plates and the corresponding probe function are reconstructed, respectively, which are immune to crosstalk of different layers. The phenomenon of the field-of-view enlargement at the second object layer is observed. This lensless compact imaging method can be potentially used for THz three-dimensional imaging.

Precautions for Patients Taking Aromatase Inhibitors.

Aromatase inhibitors are the drug of choice for the treatment of estrogen receptor- or progesterone receptor-positive breast cancer in postmenopausal women. Aromatase is an enzyme that catalyzes the final and rate-limiting step in the biosynthesis of estrogen. Inhibitors of this enzyme are an effective therapy for breast cancer. The benefits of these agents have been clearly shown through various clinical trials, yet adherence may be challenging for some patients due to issues of drug interactions, proper first dose education, and adverse effects. Education to prevent and treat adverse effects is of the utmost importance to promote adherence.

Label-free color staining of quantitative phase images of biological cells by simulated Rheinberg illumination.

Modern microscopes are designed with functionalities that are tailored to enhance image contrast. Dark-field imaging, phase contrast, differential interference contrast, and other optical techniques enable biological cells and other phase-only objects to be visualized. Quantitative phase imaging refers to an emerging set of techniques that allow for the complex transmission function of the sample to be measured. With this quantitative phase image available, any optical technique can then be simulated; it is trivial to generate a phase contrast image or a differential interference contrast image. Rheinberg illumination, proposed almost a century ago, is an optical technique that applies color contrast to images of phase-only objects by introducing a type of optical staining via an amplitude filter placed in the illumination path that consists of two or more colors. In this paper, the complete theory of Rheinberg illumination is derived, from which an algorithm is proposed that can digitally simulate the technique. Results are shown for a number of quantitative phase images of diatom cells obtained via digital holographic microscopy. The results clearly demonstrate the potential of the technique for label-free color staining of subcellular features.

Orthographic projection images-based photon-counted integral Fourier holography.

Unlike coherent imaging techniques, light field imaging uses incoherent (white light) illumination to generate a digital hologram of three-dimensional (3D) objects in real time. Multiple projections (or elemental images) of a 3D object are captured using a microlens array attached to a digital camera. Orthographic projection images (OPIs) can be synthesized from the recorded elemental images. The synthesized intensity-based OPIs are then multiplied by the corresponding phase functions and combined to form a digital hologram (also known as an integral hologram) of a 3D object under illumination. In this study, we analyze the performance of a synthesized integral hologram under low light imaging (photon-counting) conditions. The feasibility of this technique is verified experimentally by capturing the elemental images and subsequently generating orthographic projection images and by varying photon counts to reconstruct the digital holograms.

Single Core Genome Sequencing for Detection of both Borrelia burgdorferi Sensu Lato and Relapsing Fever Borrelia Species.

Lyme disease, initially described as Lyme arthritis, was reported before nucleic-acid based detection technologies were available. The most widely used diagnostic tests for Lyme disease are based on the serologic detection of antibodies produced against antigens derived from a single strain of Borrelia burgdorferi. The poor diagnostic accuracy of serological tests early in the infection process has been noted most recently in the 2018 Report to Congress issued by the U.S. Department of Health and Human Services Tick-Borne Disease Working Group. Clinical Lyme disease may be caused by a diversity of borreliae, including those classified as relapsing fever species, in the United States and in Europe. It is widely accepted that antibiotic treatment of Lyme disease is most successful during this critical early stage of infection. While genomic sequencing is recognized as an irrefutable direct detection method for laboratory diagnosis of Lyme borreliosis, development of a molecular diagnostic tool for all clinical forms of borreliosis is challenging because a "core genome" shared by all pathogenic borreliae has not yet been identified. After a diligent search of the GenBank database, we identified two highly conserved segments of DNA sequence among the borrelial 16S rRNA genes. We further developed a pair of Borrelia genus-specific PCR primers for amplification of a segment of borrelial 16S rRNA gene as a "core genome" to be used as the template for routine Sanger sequencing-based metagenomic direct detection test. This study presented examples of base-calling DNA sequencing electropherograms routinely generated in a clinical diagnostic laboratory on DNA extracts of human blood specimens and ticks collected from human skin bites and from the environment. Since some of the tick samples tested were collected in Ireland, borrelial species or strains not known to exist in the United States were also detected by analysis of this 16S rRNA "core genome". We recommend that hospital laboratories located in Lyme disease endemic areas begin to use a "core genome" sequencing test to routinely diagnose spirochetemia caused by various species of borreliae for timely management of patients at the early stage of infection.

Metagenomic 16S rRNA gene sequencing survey of Borrelia species in Irish samples of Ixodes ricinus ticks.

The spirochetal bacterium Borrelia miyamotoi is a human pathogen and has been identified in many countries throughout the world. This study reports for the first time the presence of Borrelia miyamotoi in Ireland, and confirms prior work with the detection of B. garinii and B. valaisiana infected ticks. Questing Ixodes ricinus nymph samples were taken at six localities within Ireland. DNA extraction followed by Sanger sequencing was used to identify the species and strains present in each tick. The overall rate of borrelial infection in the Irish tick population was 5%, with a range from 2% to 12% depending on the locations of tick collection. The most prevalent species detected was B. garinii (70%) followed by B. valaisiana (20%) and B. miyamotoi (10%). Knowledge of Borrelia species prevalence is important and will guide appropriate selection of antigens for serology test kit manufacture, help define the risk of infection, and allow medical authorities to formulate appropriate strategies and guidelines for diagnosis and treatment of Borrelia diseases.

Dimensionality reduction for visualizing single-cell data using UMAP.

Advances in single-cell technologies have enabled high-resolution dissection of tissue composition. Several tools for dimensionality reduction are available to analyze the large number of parameters generated in single-cell studies. Recently, a nonlinear dimensionality-reduction technique, uniform manifold approximation and projection (UMAP), was developed for the analysis of any type of high-dimensional data. Here we apply it to biological data, using three well-characterized mass cytometry and single-cell RNA sequencing datasets. Comparing the performance of UMAP with five other tools, we find that UMAP provides the fastest run times, highest reproducibility and the most meaningful organization of cell clusters. The work highlights the use of UMAP for improved visualization and interpretation of single-cell data.

Self-written waveguides in photopolymer.

Self-written waveguide (SWW) trajectories fabricated inside a dry photopolymer bulk material, acrylamide/polyvinyl alcohol (AA/PVA), are studied. Their production using both Gaussian and Laguerre-Gauss exposing (writing) light beams, output from optical fibers, is explored. The formation of the primary and secondary eyes is also discussed. Furthermore, the interactions that take place when two counterpropagating beams pass through the photopolymer material (both Gaussian and Laguerre-Gauss) are examined. In all cases experimental and theoretical results are presented. Good agreement between the predictions of the proposed model and experimental observations are demonstrated.

Exosome-Based Detection of EGFR T790M in Plasma from Non-Small Cell Lung Cancer Patients.

Purpose: About 60% of non-small cell lung cancer (NSCLC) patients develop resistance to targeted epidermal growth factor receptor (EGFR) inhibitor therapy through the EGFR T790M mutation. Patients with this mutation respond well to third-generation tyrosine kinase inhibitors, but obtaining a tissue biopsy to confirm the mutation poses risks and is often not feasible. Liquid biopsies using circulating free tumor DNA (cfDNA) have emerged as a noninvasive option to detect the mutation; however, sensitivity is low as many patients have too few detectable copies in circulation. Here, we have developed and validated a novel test that overcomes the limited abundance of the mutation by simultaneously capturing and interrogating exosomal RNA/DNA and cfDNA (exoNA) in a single step followed by a sensitive allele-specific qPCR.Experimental Design: ExoNA was extracted from the plasma of NSCLC patients with biopsy-confirmed T790M-positive (N = 102) and T790M-negative (N = 108) samples. The T790M mutation status was determined using an analytically validated allele-specific qPCR assay in a Clinical Laboratory Improvement Amendment laboratory.Results: Detection of the T790M mutation on exoNA achieved 92% sensitivity and 89% specificity using tumor biopsy results as gold standard. We also obtained high sensitivity (88%) in patients with intrathoracic disease (M0/M1a), for whom detection by liquid biopsy has been particularly challenging.Conclusions: The combination of exoRNA/DNA and cfDNA for T790M detection has higher sensitivity and specificity compared with historical cohorts using cfDNA alone. This could further help avoid unnecessary tumor biopsies for T790M mutation testing. Clin Cancer Res; 24(12); 2944-50. ©2018 AACR.

Low photon count based digital holography for quadratic phase cryptography.

Recently, the vulnerability of the linear canonical transform-based double random phase encryption system to attack has been demonstrated. To alleviate this, we present for the first time, to the best of our knowledge, a method for securing a two-dimensional scene using a quadratic phase encoding system operating in the photon-counted imaging (PCI) regime. Position-phase-shifting digital holography is applied to record the photon-limited encrypted complex samples. The reconstruction of the complex wavefront involves four sparse (undersampled) dataset intensity measurements (interferograms) at two different positions. Computer simulations validate that the photon-limited sparse-encrypted data has adequate information to authenticate the original data set. Finally, security analysis, employing iterative phase retrieval attacks, has been performed.

A Review of Hologram Storage and Self-Written Waveguides Formation in Photopolymer Media.

Photopolymer materials have received a great deal of attention because they are inexpensive, self-processing materials that are extremely versatile, offering many advantages over more traditional materials. To achieve their full potential, there is significant value in understanding the photophysical and photochemical processes taking place within such materials. This paper includes a brief review of recent attempts to more fully understand what is needed to optimize the performance of photopolymer materials for Holographic Data Storage (HDS) and Self-Written Waveguides (SWWs) applications. Specifically, we aim to discuss the evolution of our understanding of what takes place inside these materials and what happens during photopolymerization process, with the objective of further improving the performance of such materials. Starting with a review of the photosensitizer absorptivity, a dye model combining the associated electromagnetics and photochemical kinetics is presented. Thereafter, the optimization of photopolymer materials for HDS and SWWs applications is reviewed. It is clear that many promising materials are being developed for the next generation optical applications media.