Tumor treating fields (TTFields) is a noninvasive, regional antimitotic treatment modality that has been approved for the treatment of recurrent glioblastoma by the U.S. FDA and has a CE mark in ...Europe. TTFields therapy delivers low‐intensity (1–3 V/cm), intermediate‐frequency (100–300 kHz), alternating electric fields to the tumor using transducer arrays placed on the skin around the region of the body containing the tumor. TTFields therapy affects metaphase, by disrupting mitotic spindle formation, and anaphase, by dielectrophoretic dislocation of intracellular constituents, resulting in apoptosis. TTFields therapy is frequency tuned to specific cancer cell types. The antimitotic effect of TTFields therapy has been demonstrated in multiple cell lines when the appropriate frequency was utilized. A phase III trial of TTFields monotherapy compared to active chemotherapy in recurrent glioblastoma patients established that TTFields therapy is associated with minimal toxicity, better quality of life, and comparable efficacy to chemotherapy. Ongoing and future trials will evaluate TTFields in newly diagnosed glioblastoma, solid tumor brain metastases, nonsmall cell lung cancer, and ovarian and pancreatic cancers.
We have now reached the genomics era within medicine; genomics is being used to personalise treatment, make diagnoses, prognoses, and predict adverse outcomes resulting from treatment with certain ...drugs. Genomic data is now abundant in healthcare, and the newly created profession of clinical bioinformaticians are responsible for its analysis. In the United Kingdom, clinical bioinformaticians are trained within a 3-year programme, integrating a work-based placement with a part-time Master's degree. As this profession is still developing, trainees can feel isolated from their peers whom are located in other hospitals and can find it difficult to gain the mentorship that they require to complete their training. Building strong networks or communities of practice (CoPs) and allowing sharing of knowledge and experiences is one solution to addressing this isolation. Within the Master's delivered at the University of Manchester, we have integrated group-centred problem-based learning (PBL) using real clinical case studies worked on during each course unit. This approach is combined with a flipped style of teaching providing access to online content in our Virtual Learning Environment before the course. The face-to-face teaching is used to focus on the application of the students' knowledge to clinical case studies. In this study, we conducted semistructured interviews with 8 students, spanning 3 cohorts of students. We evaluated the effectiveness of this style of teaching and whether it had contributed to the formation of CoPs between our students. Our findings demonstrated that this style of teaching was preferred by our students to a more traditional lecture-based format and that the problem-based learning approach enabled the formation of CoPs within these cohorts. These CoPs are valuable in the development of this new profession and assist with the production of new guidelines and policies that are helping to professionalise this new group of healthcare scientists.
Being able to characterize the process signatures of powder bed based additive manufacturing process is key to improving the product quality. This paper demonstrates the implementation of a digital ...fringe projection technique to measure surface topography of the powder bed layers during the fabrication. We focus on developing the metrology tool and observing the types of information that can be extracted from such topographical data. The performance of the system is demonstrated with selected in situ measurements. Experimental results show this system is capable of measuring powder bed signatures including the powder layer flatness, surface texture, the average height drop of the fused regions, characteristic length scales on the surface, and splatter drop location and dimension.
Amphibians are globally threatened by anthropogenic habitat loss, the wildlife trade and emerging diseases. Previous authors have hypothesized that the spread of the amphibian disease ...chytridiomycosis (
Batrachochytrium dendrobatidis) and amphibian ranaviruses are associated with the international trade in live amphibians
. The North American bullfrog (
Rana catesbeiana) is thought to be a carrier of these pathogens, is globally traded as a live commodity, and is sold live in US markets. We obtained importation data for all live amphibians, and parts thereof, into three major US ports of entry (Los Angeles, San Francisco and New York) from 2000 to 2005. Importation of live amphibians into these ports totaled almost 28 million individuals over this 6-year period. We collected samples from freshly-imported market frogs and found infection with both pathogens in all three cities and all seasons, with an overall infection prevalence of 62% (306/493) and 8.5% (50/588) for
B. dendrobatidis and ranaviruses, respectively, by PCR. This study definitively identifies these two important pathogens in recently imported live market frogs and suggests that the amphibian trade can contribute to introductions of these pathogens into new regions. It provides support for the recent listing of
B. dendrobatidis and ranaviral diseases by the OIE, and provides evidence for measures to be taken to eradicate these pathogens from the trade.
Two-step floating catchment area (2SFCA) methods that account for multiple transportation modes provide more realistic accessibility representation than single-mode methods. However, the use of the ...impedance coefficient in an impedance function (e.g., Gaussian function) introduces uncertainty to 2SFCA results. This paper proposes an enhancement to the multi-modal 2SFCA methods through incorporating the concept of a spatial access ratio (SPAR) for spatial access measurement. SPAR is the ratio of a given place's access score to the mean of all access scores in the study area. An empirical study on spatial access to primary care physicians (PCPs) in the city of Albuquerque, NM, USA was conducted to evaluate the effectiveness of SPAR in addressing uncertainty introduced by the choice of the impedance coefficient in the classic Gaussian impedance function. We used ESRI StreetMap Premium and General Transit Specification Feed (GTFS) data to calculate the travel time to PCPs by car and bus. We first generated two spatial access scores-using different catchment sizes for car and bus, respectively-for each demanding population location: an accessibility score for car drivers and an accessibility score for bus riders. We then computed three corresponding spatial access ratios of the above scores for each population location. Sensitivity analysis results suggest that the spatial access scores vary significantly when using different impedance coefficients (p < 0.05); while SPAR remains stable (p = 1). Results from this paper suggest that a spatial access ratio can significantly reduce impedance coefficient-related uncertainties in multi-modal 2SFCA methods.
Background
Patient-facing digital technologies may reduce barriers to and alleviate the burden on genetics services. However, no work has synthesised the evidence for patient-facing digital ...interventions for genomics/genetics education and empowerment, or to facilitate service engagement more broadly. It is also unclear which groups have been engaged by digital interventions.
Aim
This systematic review explores which existing patient-facing digital technologies have been used for genomics/genetics education and empowerment, or to facilitate service engagement, and for whom and for which purposes the interventions have been developed.
Methods
The review adhered to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Eight databases were searched for literature. Information was extracted into an Excel sheet and analysed in a narrative manner. Quality assessments were conducted using the Mixed Methods Appraisal Tool.
Results
Twenty-four studies were included, of which 21 were moderate or high quality. The majority (88%) were conducted in the United States of America or within a clinical setting (79%). More than half (63%) of the interventions were web-based tools, and almost all focussed on educating users (92%). There were promising results regarding educating patients and their families and facilitating engagement with genetics services. Few of the studies focussed on empowering patients or were community-based.
Conclusion
Digital interventions may be used to deliver information about genetics concepts and conditions, and positively impact service engagement. However, there is insufficient evidence related to empowering patients and engaging underserved communities or consanguineous couples. Future work should focus on co-developing content with end users and incorporating interactive features.
Global amphibian declines are linked with the presence of specific, highly virulent genotypes of the emerging fungal disease chytridiomycosis caused by Batrachochytrium dendrobatidis (Bd) known as ...the global panzootic lineage (Bd‐GPL). The global trade in amphibians for human consumption is suspected to have facilitated emergence of the disease, but evidence to support this is largely lacking. Here, we investigated the role the Lithobates catesbeianus (North American bullfrog) trade in spreading Bd genotypes by comparing strains associated with L. catesbeianus to a global panel using 36 sequenced loci from multiple chromosomal regions. Most bullfrogs were infected with Bd‐GPL genotypes, but we also detected novel, highly divergent Bd genotypes (Bd‐Brazil) from a live bullfrog in a US market and from native Brazilian anurans in the Atlantic Forest where bullfrogs are widely farmed. Sexual reproduction was also detected for the first time in Bd in the form of a hybrid genotype between the Bd‐GPL and Bd‐Brazil lineages in the Atlantic Forest. Despite the demonstration that ribosomal RNA types in Bd fail to undergo concerted evolution (over 20 sequence types may be found in a single strain), the Bd‐GPL and Bd‐Brazil lineages form largely separate clusters of related internal transcribed spacer (ITS) RNA sequences. Using ITS sequences, we then demonstrate the presence of Bd‐Brazil in Japan, primarily on invasive L. catesbeianus. The finding that Bd is capable of sexual reproduction between panzootic and endemic genotypes emphasizes the risk of international wildlife trade as a source of additional Bd epizootics owing to hybridization.
See also the Perspective by Mckenzie and Peterson
This study aimed to investigate whether a bioinformatics application can streamline genome reanalysis and yield new diagnoses for patients with rare diseases.
We developed TierUp to identify variants ...in new disease genes for unresolved rare disease cases recruited to the 100,000 Genomes Project, all of whom underwent genome sequencing. TierUp uses the NHS Genomic Medicine Service bioinformatics infrastructure by securely accessing case details from the Clinical Interpretation Portal application programming interface and by querying the curated PanelApp database for novel gene–disease associations. We applied TierUp to 948 cases, and a subset of variants were reclassified according to the American College of Medical Genetics and Genomics/Association of Molecular Pathology guidelines.
A rare form of spondylometaphyseal dysplasia was diagnosed through TierUp reanalysis, and an additional 4 variants have been reported to date. From a total of 564,441 variants across patients, TierUp highlighted 410 variants present in novel disease genes in under 77 minutes, successfully expediting an important reanalysis strategy.
TierUp supports claims that automation can reduce the time taken to reanalyze variants and increase the diagnostic yield from molecular testing. Clinical services should leverage bioinformatics expertise to develop tools that enable routine reanalysis. In addition, services must also explore the ethical, legal, and health economic considerations raised by automation.
The goal of this study was to create and demonstrate a system to perform fast and inexpensive quality dimensional inspection for industrial assembly line applications with submillimeter uncertainty. ...Our focus is on the positional errors of the assembled pieces on a larger part as it is assembled. This is achieved by using an open-source photogrammetry architecture to gather a point cloud data of an assembled part and then comparing this to a computer-aided design (CAD) model. The point cloud comparison to the CAD model is used to quantify errors in position using the iterative closest point (ICP) algorithm. Augmented reality is utilized to view the errors in a live-video feed and effectively display said errors. The initial demonstration showed an assembled position error of 9 mm ± 0.4 mm for a 40-mm high post.
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