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Artificial intelligence (AI) and variant prioritization tools for genomic variant analysis are being rapidly developed for use in clinical diagnostic testing. However, their clinical utility and reliability are currently limited. Therefore, we performed a validation of a commercial AI tool (Moon) and a comprehensive reanalysis of previously collected clinical exome sequencing cases using an open-source variant prioritization tool (Exomiser) and the now-validated AI tool to test their feasibility in clinical diagnostics.

The discovery of a two-dimensional electron gas (2DEG) at the LaAlO3/SrTiO3interface1has resulted in the observation of many properties2–5not present in conventional semiconductor heterostructures, and so become a focal point for device applications6–8. Its counterpart, the two-dimensional hole gas (2DHG), is expected to complement the 2DEG. However, although the 2DEG has been widely observed9, the 2DHG has proved elusive. Herein we demonstrate a highly mobile 2DHG in epitaxially grown SrTiO3/LaAlO3/SrTiO3heterostructures. Using electrical transport measurements and in-line electron holography, we provide direct evidence of a 2DHG that coexists with a 2DEG at complementary heterointerfaces in the same structure. First-principles calculations, coherent Bragg rod analysis and depth-resolved cathodoluminescence spectroscopy consistently support our finding that to eliminate ionic point defects is key to realizing a 2DHG. The coexistence of a 2DEG and a 2DHG in a single oxide heterostructure provides a platform for the exciting physics of confined electron–hole systems and for developing applications.

Ab initiocalculations are used to identify the structural conditions under which a polar state in metals might be stabilized; this information is used to guide the experimental realization of new room-temperature polar metals.

Biserrula is an annual pasture legume endemic to the Mediterranean basin and has been recently domesticated for use in Mediterranean environments in southern Australia. Over the past 10 years the species has been associated with isolated cases of what appears to be a primary photosensitisation in sheep that graze green pastures in winter and spring. Whole-top samples of biserrula pasture were taken from a range of farmers’ paddocks over 2 years (including paddocks where photosensitisation had been observed) and methanolic extracts were screened by high-performance liquid chromatography and liquid chromatography coupled to mass spectrometry for known primary photosensitising compounds belonging to the classes furanocoumarins and dianthrones. None of these were detected. Pyrrolizidine alkaloids were also not detected and this supports the view that a secondary photosensitisation is not involved. Chlorophyll profiles were relatively unchanged between samples and this suggested that chlorophyll metabolites are unlikely to be responsible for a primary photosensitisation. A series of luteolin and apigenin mono- and diglycosides were identified in the extracts, but these are not regarded as photosensitising compounds. Further work is required to establish the photosensitising agent(s) in biserrula.

Here we report a product evaluation for a non-adherent, povidone–iodine (PVP–I) dressing, determining the clinical need for the product, performing a literature review, clinical evaluation and cost-analysis, and developing a recommendation. This evaluation included 20 patients who experienced dressing pain with the previous antimicrobial dressing. Two patients discontinued the evaluation and four ulcers were non-healing; the remaining wounds closed with the PVP–I dressing. Patients indicated a preference for the PVP–I dressing, primarily due to lack of dressing pain. The PVP–I dressing was also the most cost-efficient.

We have now demonstrated and characterized gas-filled hollow-core fiber lasers based on population inversion from acetylene (12C2H2) and HCN gas contained within the core of a kagome-structured hollow-core photonic crystal fiber. The gases are optically pumped via first order rotational-vibrational overtones near 1.5 m using 1-ns pulses from an optical parametric amplifier. Transitions from the pumped overtone modes to fundamental C-H stretching modes in both molecules create narrow-band laser emissions near 3 m. High gain resulting from tight confinement of the pump and laser light together with the active gas permits us to operate these lasers in a single pass configuration, without the use of any external resonator structure. A delay between the emitted laser pulse and the incident pump pulse has been observed and is shown to vary with pump pulse energy and gas pressure. Furthermore, we have demonstrated lasing beyond 4 m from CO and CO2using silver-coated glass capillaries, since fused silica based fibers do not transmit in this spectral region and chalcogenide fibers are not yet readily available. Studies of the laser pulse energy as functions of the pump pulse energy and gas pressure were performed. Efficiencies reaching ~ 20% are observed for both acetylene and CO2.

Unhealthy dietary patterns are an important contributor to obesity and related non-communicable diseases (NCDs). As with any public health challenge, as well as providing care to affected individuals, whole-population interventions are required to mitigate the environmental determinants of population dietary patterns. The World Health Organisation (WHO) has established recommendations, including a set of low-cost, high-impact ‘best buys’ for governments seeking to implement these strategies. The Irish government has stated that it wishes to make ‘the healthy choice the easy choice.’ Yet, in marked contrast to its approach to tobacco- or alcohol-related harms, the Irish government has shown reluctance in implementing those WHO-endorsed strategies or other population-level measures to address unhealthy dietary patterns. Meanwhile, commercial interests work to discredit these measures as “paternalism” or more commonly as “nanny state” violations of individual liberty.

BACKGROUND: We have previously shown that the non-selective cyclooxygenase (COX) inhibitor indomethacin retards recovery of intestinal barrier function in ischaemic injured porcine ileum. However, the relative role of COX-1 and COX-2 elaborated prostaglandins in this process is unclear. AIMS: To assess the role of COX-1 and COX-2 elaborated prostaglandins in the recovery of intestinal barrier function by evaluating the effects of selective COX-1 and COX-2 inhibitors on mucosal recovery and eicosanoid production. METHODS: Porcine ileal mucosa subjected to 45 minutes of ischaemia was mounted in Ussing chambers, and transepithelial electrical resistance was used as an indicator of mucosal recovery. Prostaglandins E1 and E2 (PGE) and 6-keto-PGF1alpha (the stable metabolite of prostaglandin I2 (PGI2)) were measured using ELISA. Thromboxane B2 (TXB2, the stable metabolite of TXA2) was measured as a likely indicator of COX-1 activity. RESULTS: Ischaemic injured tissues recovered to control levels of resistance within three hours whereas tissues treated with indomethacin (5x10(-6) M) failed to fully recover, associated with inhibition of eicosanoid production. Injured tissues treated with the selective COX-1 inhibitor SC-560 (5x10(-6) M) or the COX-2 inhibitor NS-398 (5x10(-6) M) recovered to control levels of resistance within three hours, associated with significant elevations of PGE and 6-keto-PGF1alpha compared with untreated tissues. However, SC-560 significantly inhibited TXB2 production whereas NS-398 had no effect on this eicosanoid, indicating differential actions of these inhibitors related to their COX selectivity. CONCLUSIONS: The results suggest that recovery of resistance is triggered by PGE and PGI2, which may be elaborated by either COX-1 or COX-2.

BACKGROUND: We have previously shown that the non-selective cyclooxygenase (COX) inhibitor indomethacin retards recovery of intestinal barrier function in ischaemic injured porcine ileum. However, the relative role of COX-1 and COX-2 elaborated prostaglandins in this process is unclear. AIMS: To assess the role of COX-1 and COX-2 elaborated prostaglandins in the recovery of intestinal barrier function by evaluating the effects of selective COX-1 and COX-2 inhibitors on mucosal recovery and eicosanoid production. METHODS: Porcine ileal mucosa subjected to 45 minutes of ischaemia was mounted in Ussing chambers, and transepithelial electrical resistance was used as an indicator of mucosal recovery. Prostaglandins E1 and E2 (PGE) and 6-keto-PGF1alpha (the stable metabolite of prostaglandin I2 (PGI2)) were measured using ELISA. Thromboxane B2 (TXB2, the stable metabolite of TXA2) was measured as a likely indicator of COX-1 activity. RESULTS: Ischaemic injured tissues recovered to control levels of resistance within three hours whereas tissues treated with indomethacin (5x10(-6) M) failed to fully recover, associated with inhibition of eicosanoid production. Injured tissues treated with the selective COX-1 inhibitor SC-560 (5x10(-6) M) or the COX-2 inhibitor NS-398 (5x10(-6) M) recovered to control levels of resistance within three hours, associated with significant elevations of PGE and 6-keto-PGF1alpha compared with untreated tissues. However, SC-560 significantly inhibited TXB2 production whereas NS-398 had no effect on this eicosanoid, indicating differential actions of these inhibitors related to their COX selectivity. CONCLUSIONS: The results suggest that recovery of resistance is triggered by PGE and PGI2, which may be elaborated by either COX-1 or COX-2.

We sequenced part of the mitochondrial 12S ribosomal RNA gene of 23 specimens of Sarcoptes scabieifrom eight wombats, one dog and three humans. Twelve of the 326 nucleotide positions varied among these mites and there were nine haplotypes (sequences) that differed by 1–8 nucleotides. Phylogenetic analyses indicated that these mites were from two lineages: (1) mites from wombats from Victoria, Australia, and mites from the humans and dog from the Northern Territory, Australia (haplotypes 1–4, 9); and (2) mites from the humans and dog from the Northern Territory (haplotypes 5–8). Mites from the three different hosts (wombats, a dog and humans) had not diverged phylogenetically; rather, these mites had similar 12S sequences. Thus, we conclude that these mites from wombats, humans and a dog are closely related, and that they diverged from a common ancestor relatively recently. This conclusion is consistent with the argument that people and/or their dogs introduced to Australia the S. scabieimites that infect wombats in Australia . So, S. scabiei, which has been blamed for the extinction of populations of wombats in Australia, may be a parasitic mite that was introduced to Australia with people and/or their dogs. These data show that the mitochondrial 12S rRNA gene may be a suitable population marker of S. scabieifrom wombats, dogs and humans in Australia.

Thomas Huxley is often identified as the originator of the doctrineknown as ``epiphenomenalism,'' but there appears to be littleappreciation for the details of Huxley's theory. In particular,conflicting interpretations show that there is uncertainty about twoaspects of his position: whether mental states are completelywithout causal powers or simply have no influence on the behavior theyare typically taken to explain, and whether conscious epiphenomena arethemselves physical states of the brain or immaterial items. I clarifythese issues and show that Huxley's brand of epiphenomenalism is in factdifferent from the forms usually attributed to him.

Clinicians are exposed to numerous hypertension guidelines. However, their enthusiasm for these guidelines, and the impact of the guidelines, appears modest at best. Barriers to the successful implementation of a guideline can be identified at the level of the clinician, the patient or the practice setting; however, the shortcomings of the guidelines themselves have received little attention. In this paper, we review the hypertension guidelines that are most commonly encountered by Canadian clinicians: the "1999 Canadian Recommendations for the Management of Hypertension," "The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" in the United States and the "1999 World Health Organization-International Society of Hypertension Guidelines for the Management of Hypertension." The key points of these guidelines are compared and the shortcomings that may impede their ability to influence practice are discussed. The main implications for future guideline developers are outlined.

Current learning approaches to computer vision have mainly focussed on low-level image processing and object recognition, while tending to ignore high-level processing such as understanding. Here we propose an approach to object recognition that facilitates the transition from recognition to understanding. The proposed approach embraces the synergistic spirit of soft computing, exploiting the global search powers of genetic programming to determine fuzzy probabilistic models. It begins by segmenting the images into regions using standard image processing approaches, which are subsequently classified using a discovered fuzzy Cartesian granule feature classifier. Understanding is made possible through the transparent and succinct nature of the discovered models. The recognition of roads in images is taken as an illustrative problem in the vision domain. The discovered fuzzy models while providing high levels of accuracy (97%), also provide understanding of the problem domain through the transparency of the learnt models. The learning step in the proposed approach is compared with other techniques such as decision trees, naïve Bayes and neural networks using a variety of performance criteria such as accuracy, understandability and efficiency.

The aim of the present study was to explore the perspectives of patients receiving treatment for colorectal cancer and compare priorities and attitudes in rural and urban areas.

The appearance of chronic intestinal inflammation in IL-10 knockout mice suggests IL-10 may inhibit adverse responses to luminal antigen. Moreover, this inflammation is associated with an increase in class II MHC molecule expression on intestinal epithelial cells. Thus, the role of IL-10 regulation in epithelial cell function was investigated. Using RT-PCR, it was shown that intestinal epithelial cells express mRNA for both subunits of the IL-10 receptor-signaling complex. In addition, biotinylated IL-10 was shown to bind to both cultured and freshly isolated intestinal epithelial cells prepared from the small or large intestine. This binding appeared specific as it was blocked by neutralizing antibodies to IL-10 but not the isotype control. Moreover, an excess of native IL-10 also inhibited the binding of radiolabeled IL-10. To evaluate whether IL-10 mediated any functions through this receptor, epithelial cells were cultured with IL-10 alone or with IFN-gamma plus IL-10. IL-10 alone had no detectable effects on epithelial cell growth or their expression of class II MHC molecules but it did antagonize the effect of IFN-gamma on the viability of cultured cells. In addition, IL-10 blocked the IFN-gamma-induced expression of class II MHC molecules on cultured epithelial cells. These results suggest that IL-10 binds to a specific receptor on intestinal epithelial cells and may regulate the contribution of epithelial cells to the inflammatory and immune response in the digestive tract.

In Nova Scotia (NS) the arrival of COVID-19 led to immediate closures of all cardiac rehabilitation (CR) programs and redeployment of staff. Doors opened again two months later with CR teams needing to quickly develop and implement a virtual version of CR. Months following, with the reduction of COVID cases, programs were transitioned back to in-person on-site/hybrid models. Throughout transitions, the goal was to develop safe, effective and sustainable CR models of care with measured outcomes comparative to core elements of traditional on-site CR.

An S‐estimator of multivariate location and scale minimizes the determinant of the covariance matrix, subject to a constraint on the magnitudes of the corresponding Mahalanobis distances. The relationship between S‐estimators and w‐estimators of multivariate location and scale can be used to calculate robust estimates of covariance matrices. Elemental subsets of observations are generated to derive initial estimates of means and covariances, and the w‐estimator equations are then iterated until convergence to obtain the S‐estimates. An example shows that converging to a (local) minimum from the initial estimates from the elemental subsets is an effective way of determining the overall minimum. None of the estimates gained from the elemental samples is close to the final solution. © 1998 John Wiley & Sons, Ltd.

Previous studies have shown that normal intestinal epithelial cells (IECs) are able to selectively activate CD8(+) T cells with suppressor activity, inducing proliferation associated with the activation of both the CD8-associated kinase p56(lck) and the T cell receptor (TCR)-associated kinase p59(fyn). This process appears to relate in part to a 180-kDa IEC surface glycoprotein, gp180, which binds to CD8 and activates CD8-associated p56(lck). However, purified gp180 alone is unable to induce T cell proliferation and does not activate p59(fyn). Because the class Ib molecule CD1d is expressed by IECs and monoclonal antibodies (mAbs) against CD1d inhibit IEC-induced proliferation of CD8(+) T cells, co-immunoprecipitation and enzyme-linked immunosorbent assay studies were performed, which demonstrated an association of gp180 and CD1d on the IEC surface. Interestingly, the activation of p59(fyn) in IEC-T cell co-cultures was blocked by the anti-CD1d mAb D5 but not by the anti-gp180 mAb B9. Conversely, treatment of IECs with mAb B9 inhibited IEC-induced activation of p56(lck) but not p59(fyn). More directly, a human CD1d cDNA (FO-1 D5) transfectant was able to activate p59(fyn) but not p56(lck). These data suggest that the CD1d-gp180 complex on the surface of IECs can be recognized by the TCR-CD8 co-receptor, resulting in the activation of CD8(+) T cells.

Profiles Jennifer Tipton, an award-winning lighting designer for dance, theatre, and opera, who continues a twenty-five-year collaboration with the Paul Taylor Dance Company at New York's City Center Theatre.

This study was conducted to investigate the effects of sex and school level on the computer anxiety of rural middle school and secondary students when home availability and school use of computers are controlled. A total of 1,067 students in middle and secondary grades in six rural school districts participated in the study. The instrument used was the Computer Anxiety Scale with Cronbach's reliability coefficients ranging from .83 to .91, depending on the school level of the students. Sex and school level differences were found in home availability, but not in school use of computers. The findings suggest computer anxiety is not affected by sex or school level when home availability and school use of a computer is statistically controlled.

The paper describes a computational and experimental study of the application of advanced ceramic materials for thermal insulation of the swirl chamber of the passenger car IDI diesel engine. Four ceramic materials, having a wide range of physical properties, were evaluated. These were syalon 101, aluminium titanate, reaction bonded silicon nitride (RBSN) and tetragonal zirconia polycrystals (TZP). A detailed finite element study was carried out in support of component design which examined parameters such as heat flux, operating temperature, thermal and assembly stresses and evaluated the requirements for interference fits between metallic and ceramic components. Experimental work was initially carried out on a steady state dynamometer test stand and later supported by vehicle tests on a chassis dynamometer and test track.The investigation has shown that current engineering ceramic materials have the potential for application in engine combustion chambers. A total of 254 hours of engine testing with ceramic chambers was achieved without catastrophic engine failure. Engine performance was unchanged by the adoption of a thermally insulated swirl chamber, probably because the increase in swirl chamber surface temperature obtained (increased from 660 to about 850°C at full load) was insufficient to modify the thermodynamic cycle. Hydrocarbon emissions were generally increased, however; this was due in part to the difficulty of sealing the air gap behind the ceramic chamber at the fuel injector and glow plug interfaces.