The use of colonic stents as a bridge to surgery in malignant colonic obstruction - A dual trust experience over 10 years.

Introduction: Worldwide colonic cancer is the third most common cancer with up to 30% of cases presenting with large bowel obstruction. Self-expanding metal stents (SEMS) have been used as a bridge to surgery (BTS) in the treatment of this malignant obstruction. We review the outcomes of SEMS as a BTS across two high volume colorectal units. Methodology: A retrospective analysis of patients undergoing colonic stenting as a bridge to surgery was performed; outcomes were compared to previously published figures on emergency colonic resections. Inclusion criteria were adults (>18 years of age) undergoing colonic stenting for colonic obstruction with a view to elective resection. Patients undergoing stenting for palliation of symptoms were excluded. Results: 39 patients were identified across both trusts over a ten-year period. 90 day mortality following BTS was found to be 3.6% and there was an 82.1% (32/39) technical success rate. 46.4% proceeded to an elective resection which was started laparoscopically. Permanent stoma rate was observed at 14.3% for elective surgery. Conclusion: Stenting for relief of acute malignant obstruction as a bridge to surgery is a viable option in select patients. Further research is required to determine oncological safety and rate of local recurrences.

Straight to test reduces time to investigation and treatment.

Straight to test (STT) is a recognised pathway for improving the waiting time for red flag referrals. Electronic patient care records (ECR) provide clinicians with a greater volume of clinical information allowing virtual triage and STT. We aimed to assess if using ECR and STT can reduce delays in diagnosis and treatment. A review of 300 colorectal referrals between 2018-2019 was performed. Patients awaiting an appointment were reviewed electronically, by a single colorectal surgeon and re-triaged STT if appropriate. The delay in time from referral to initial review was removed, creating a second group for statistical comparison to demonstrate time saved if the strategy was adopted at the point of original triage. 91.3% (n= 274) were red flag referrals. 94% (n=282) were sent STT. Patients processed via traditional referral and clinic had a median time to scope of 36 days compared with 22.5 days, p < 0.001 if triaged STT via virtual clinic. Median time to management was 59 days for traditional and 35 days for STT, p < 0.001.

Hamiltonian Engineering with Multicolor Drives for Fast Entangling Gates and Quantum Crosstalk Cancellation.

Quantum computers built with superconducting artificial atoms already stretch the limits of their classical counterparts. While the lowest energy states of these artificial atoms serve as the qubit basis, the higher levels are responsible for both a host of attractive gate schemes as well as generating undesired interactions. In particular, when coupling these atoms to generate entanglement, the higher levels cause shifts in the computational levels that lead to unwanted ZZ quantum crosstalk. Here, we present a novel technique to manipulate the energy levels and mitigate this crosstalk with simultaneous off-resonant drives on coupled qubits. This breaks a fundamental deadlock between qubit-qubit coupling and crosstalk. In a fixed-frequency transmon architecture with strong coupling and crosstalk cancellation, additional cross-resonance drives enable a 90 ns CNOT with a gate error of (0.19±0.02)%, while a second set of off-resonant drives enables a novel CZ gate. Furthermore, we show a definitive improvement in circuit performance with crosstalk cancellation over seven qubits, demonstrating the scalability of the technique. This Letter paves the way for superconducting hardware with faster gates and greatly improved multiqubit circuit fidelities.

Accounting for Viscoelasticity When Interpreting Nano-Composite High-Deflection Strain Gauges.

High-deflection strain gauges show potential as economical and user-friendly sensors for capturing large deformations. The interpretation of these sensors is much more complex than that of conventional strain gauges due to the viscoelastic nature of strain gauges. This research endeavor developed and tested a model for interpreting sensor outputs that includes the time-dependent nature of strain gauges. A model that captures the effect of quasi-static strains was determined by using a conventional approach of fitting an equation to observed data. The dynamic relationship between the strain and the resistance was incorporated by superimposing dynamic components onto the quasi-static model to account for spikes in resistances that accompany each change in sensor strain and subsequent exponential decays. It was shown that the model can be calibrated for a given sensor by taking two data points at known strains. The resulting sensor-specific model was able to interpret strain-gauge electrical signals during a cyclical load to predict strain with an average mean absolute error (MAE) of 1.4% strain, and to determine the strain rate with an average MAE of 0.036 mm/s. The resulting model and tuning procedure may be used in a wide range of applications, such as biomechanical monitoring and analysis.

Demonstration of a High-Fidelity cnot Gate for Fixed-Frequency Transmons with Engineered ZZ Suppression.

Improving two-qubit gate performance and suppressing cross talk are major, but often competing, challenges to achieving scalable quantum computation. In particular, increasing the coupling to realize faster gates has been intrinsically linked to enhanced cross talk due to unwanted two-qubit terms in the Hamiltonian. Here, we demonstrate a novel coupling architecture for transmon qubits that circumvents the standard relationship between desired and undesired interaction rates. Using two fixed frequency coupling elements to tune the dressed level spacings, we demonstrate an intrinsic suppression of the static ZZ while maintaining large effective coupling rates. Our architecture reveals no observable degradation of qubit coherence (T_{1},T_{2}>100 µs) and, over a factor of 6 improvement in the ratio of desired to undesired coupling. Using the cross-resonance interaction, we demonstrate a 180 ns single-pulse controlled not (cnot) gate, and measure a cnot fidelity of 99.77(2)% from interleaved randomized benchmarking.

Adapting an emergency general surgery service in response to the COVID-19 pandemic.

INTRODUCTION: In response to the COVID-19 pandemic, our emergency general surgery (EGS) service underwent significant restructuring, including establishing an enhanced ambulatory service and undertaking nonoperative management of selected pathologies. The aim of this study was to compare the activity of our EGS service before and after these changes. METHODS: Patients referred by the emergency department were identified prospectively over a 4-week period beginning from the date our EGS service was reconfigured (COVID) and compared with patients identified retrospectively from the same period the previous year (Pre-COVID), and followed up for 30 days. Data were extracted from handover documents and electronic care records. The primary outcomes were the rate of admission, ambulation and discharge. RESULTS: There were 281 and 283 patients during the Pre-COVID and COVID periods respectively. Admission rate decreased from 78.7% to 41.7%, while there were increased rates of ambulation from 7.1% to 17.3% and discharge from 6% to 22.6% (all p<0.001). For inpatients, mean duration of admission decreased (6.9 to 4.8 days), and there were fewer operative or endoscopic interventions (78 to 40). There were increased ambulatory investigations (11 to 39) and telephone reviews (0 to 39), while early computed tomography scan was increasingly used to facilitate discharge (5% vs 34.7%). There were no differences in 30-day readmission or mortality. CONCLUSIONS: Restructuring of our EGS service in response to COVID-19 facilitated an increased use of ambulatory services and imaging, achieving a decrease of 952 inpatient bed days in this critical period, while maintaining patient safety.

Asymmetric Bilateral Lichen Striatus: A Rare Presentation following Multiple Blaschko's Lines.

Lichen striatus (LS) is an uncommon, acquired, self-limited, and benign linear dermatosis of unknown etiology that most often occurs unilaterally and is confined to the lines of Blaschko. A healthy 7-year-old girl presented to our clinic with bilateral asymmetric LS occurring on the right arm and left leg of 1-year duration. Very few cases of bilateral LS have been previously reported in the literature, with none from clinics within the United States. The etiology of LS is currently unknown; however its confinement to Blaschko's lines, which represent embryologic migration of skin cell clones, does provide insight into a possible pathogenesis. It seems most likely that an individual's development of LS is linked to their genetic predisposition and a subsequent triggering event. Our case serves as a strong example of a rare presentation of LS and facilitates discussion of the clinical diagnostic process and possible pathogenesis of this dermatosis.

Publisher Correction: Random access quantum information processors using multimode circuit quantum electrodynamics.

In the original version of this Article, the affiliation details for Peter Groszkowski and Jens Koch were incorrectly given as 'Department of Physics, University of Chicago, Chicago, IL, 60637, USA', instead of the correct 'Department of Physics and Astronomy, Northwestern University, Evanston, Illinois 60208, USA'. This has now been corrected in both the PDF and HTML versions of the Article.

Random access quantum information processors using multimode circuit quantum electrodynamics.

Qubit connectivity is an important property of a quantum processor, with an ideal processor having random access-the ability of arbitrary qubit pairs to interact directly. This a challenge with superconducting circuits, as state-of-the-art architectures rely on only nearest-neighbor coupling. Here, we implement a random access superconducting quantum information processor, demonstrating universal operations on a nine-qubit memory, with a Josephson junction transmon circuit serving as the central processor. The quantum memory uses the eigenmodes of a linear array of coupled superconducting resonators. We selectively stimulate vacuum Rabi oscillations between the transmon and individual eigenmodes through parametric flux modulation of the transmon frequency. Utilizing these oscillations, we perform a universal set of quantum gates on 38 arbitrary pairs of modes and prepare multimode entangled states, all using only two control lines. We thus achieve hardware-efficient random access multi-qubit control in an architecture compatible with long-lived microwave cavity-based quantum memories.

Mental health services use by melanoma patients receiving adjuvant interferon: association of pre-treatment mental health care with early discontinuation.

BACKGROUND: Although high-dose interferon (hd-ifn) is the sole approved adjuvant systemic treatment for melanoma in many jurisdictions, it is toxic. We sought to assess the population-level effects of hd-ifn toxicity, particularly neuropsychiatric toxicity, hypothesizing that such toxicity would have the greatest effect on mental health services use in advanced resected melanoma. METHODS: This retrospective population-based registry study considered all melanoma patients receiving adjuvant hd-ifn in Ontario during 2008-2012. Toxicity was investigated through health services use compatible with hd-ifn toxicity (for example, mental health physician billings). Using stage data reported from cancer centres about a subset of patients (stages iib-iiic), a propensity-matched analysis compared such service use in patients who did and did not receive hd-ifn. Associations between early hd-ifn discontinuation and health services use were examined. RESULTS: Of 718 melanoma patients who received hd-ifn, 12% were 65 years of age and older, and 83% had few or no comorbidities. One third of the patients experienced 1 or more toxicity-associated health care utilization events within 1 year of starting hd-ifn. Of 420 utilization events, 364 (87%) were mental health-related, with 54% being family practitioner visits, and 39% being psychiatrist visits. In the propensity-matched analysis, patients receiving hd-ifn were more likely than untreated matched controls to use a mental health service (p = 0.01), with 42% of the control group and 51% of the hd-ifn group using a mental health service in the period spanning the 12 months before to the 24 months after diagnosis. In the multivariable analysis, early drug discontinuation was more likely in the presence of pre-existing mental health issues (odds ratio: 2.0; 95% confidence limits: 1.1, 3.4). CONCLUSIONS: Stage iib-iiic melanoma patients carry a substantial burden of mental health services use whether or not receiving hd-ifn, highlighting an important survivorship issue for these patients. High-dose interferon is associated with more use of mental health services, and pre-treatment use of mental health services is associated with treatment discontinuation. That association should be kept in mind when hd-ifn is being considered.

Triggering immunological memory against the tapeworm Hymenolepis diminuta to protect against colitis.

Infection with parasitic helminths can ameliorate the severity of concomitant inflammatory disease. To use the tapeworm, Hymenolepis diminuta, and to extend this concept by assessing whether triggering a memory response against the worm inhibits dinitrobenzene sulphonic acid (DNBS)-induced colitis in Balb/c mice. Initial studies revealed that oral infection with 1, 3 or 5 H. diminuta cysticercoids 8 days before intrarectal administration of DNBS (3 mg) resulted in less severe inflammation and that infected mice displayed an increased propensity for T helper-2 immunity. A 1 mg dose of a PBS-soluble extract of the worm (HdAg) delivered intraperitoneally concomitant with DNBS was anticolitic as determined by macroscopic and histological disease scores 72 hour post-DNBS. Mice infected 28 days previously had a memory response as determined by HdAg-evoked increases in interleukin (IL)-4 and IL-10 from in vitro stimulated splenocytes and serum anti-H. diminuta IgG. Moreover, mice infected with 5 H. diminuta 28 days previously were protected from DNBS-induced colitis by secondary infection or 100 µg HdAg (ip.) at the time of DNBS treatment. An additional approach to managing inflammatory disease could be infection with H. diminuta followed by eliciting antiworm recall responses.

Suppression of colitis by adoptive transfer of helminth antigen-treated dendritic cells requires interleukin-4 receptor-α signaling.

Infection with helminth parasites has been explored as a treatment for autoimmune and inflammatory diseases. As helminth antigens have potent immunomodulation properties capable of inducing regulatory programs in a variety of cell types, transferring cells treated with helminth antigens represents a novel extension to helminth therapy. Previous work determined that transfer of bone marrow-derived dendritic cells (DC) pulsed with a crude extract of the tapeworm Hymenolepis diminuta (HD) can suppress colitis in recipient mice. The present study explored the mechanism of disease suppression and the importance of interleukin (IL)-4 signaling. Transfer of HD-DCs suppressed dinitrobenzene sulfonic acid (DNBS)-induced colitis through activation of recipient IL-4 receptor-α. The transferred HD-DCs required IL-4Rα and the capacity to secrete IL-10 to drive IL-4 and IL-10 production and to suppress colitis in recipient mice. Treatment of DCs with IL-4 evokes an alternatively activated phenotype, but adoptive transfer of these cells did not affect the outcome of colitis. Collectively, these studies demonstrate the complexity between IL-4 and IL-10 in donor cells and recipient, and the requirement for parasite- and host-derived factors in this novel form of cell therapy. Thus IL-4Rα signaling is revealed as a pathway that could be exploited for helminth antigen cell-based therapy.

Progressive Bidirectional Age-Related Changes in Default Mode Network Effective Connectivity across Six Decades.

The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20-29 to 70-79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging.

A comprehensive tractography study of patients with bipolar disorder and their unaffected siblings.

BACKGROUND: Diffusion tensor imaging studies show reductions in fractional anisotropy (FA) in individuals with bipolar disorder and their unaffected siblings. However, the use of various analysis methods is an important source of between-study heterogeneity. Using tract-based spatial statistics, we previously demonstrated widespread FA reductions in patients and unaffected relatives. To better interpret the neuroanatomical pattern of this previous finding and to assess the influence of methodological heterogeneity, we here applied tractography to the same sample. METHODS: Diffusion-weighted images were acquired for 96 patients, 69 unaffected siblings and 56 controls. We applied TRACULA, an extension of a global probabilistic tractography algorithm, to automatically segment 18 major fiber tracts. Average FA within each tract and at each cross-section along each tract was compared between groups. RESULTS: Patients had reduced FA compared to healthy controls and their unaffected siblings in general, and in particular in the parietal part of the superior longitudinal fasciculus. In unaffected siblings, FA was nominally reduced compared to controls in the corpus callosum. Point-wise analyses indicated that similar effects were present along extended sections, but with variable effect sizes. Current symptom severity negatively correlated with FA in several fronto-limbic association tracts. CONCLUSIONS: The differential sensitivity of analysis techniques likely explains between-study heterogeneity in anatomical localization of FA reductions. The present tractography analysis confirms the presence of overall FA reductions in patients with bipolar disorder, which are most pronounced in the superior longitudinal fasciculus. Unaffected siblings may display similar, albeit more subtle and anatomically restricted FA reductions. Hum Brain Mapp 37:3474-3485, 2016. © 2016 Wiley Periodicals, Inc.

Serological diagnosis of Leptospirosis in bovine serum samples using a microsphere immunoassay.

Leptospirosis causes significant economic loss within the cattle industry worldwide. Current diagnostic methods are generally inadequate for dealing with large numbers of samples, are outdated, and provide little useful diagnostic and epidemiological information. This aim of this study was to apply a microsphere immunoassay (MIA), utilising Luminex xMap technology, to 200 bovine serum samples to determine this method's usefulness in leptospirosis diagnosis in comparison with the current gold standard, the microscopic agglutination test (MAT). Although MAT is the most widely used laboratory test for the diagnosis of leptospirosis, its reliance on live cultures, subjective interpretation of results and an inability to differentiate between antibody classes, suggest MAT is no longer the best method for the diagnosis of leptospirosis. The results presented in this paper show that MIA was able to determine reactive from non-reactive samples when compared with MAT, and was able to differentiate IgG and IgM classes of antibody. The results suggest increased sensitivity in MIA and the ability to multiplex up to 500 antigens at one time allows for significant improvements in cost-effectiveness as well as a reduced dependency on live cultures. The relatively low cost, high throughput platform and differentiation of antibody class, as shown in previous research, make this assay worthy of consideration for the diagnosis of leptospirosis in small-scale or large-scale bovine populations.

Recurrent major depression and right hippocampal volume: A bivariate linkage and association study.

Previous work has shown that the hippocampus is smaller in the brains of individuals suffering from major depressive disorder (MDD) than those of healthy controls. Moreover, right hippocampal volume specifically has been found to predict the probability of subsequent depressive episodes. This study explored the utility of right hippocampal volume as an endophenotype of recurrent MDD (rMDD). We observed a significant genetic correlation between the two traits in a large sample of Mexican American individuals from extended pedigrees (ρg = -0.34, p = 0.013). A bivariate linkage scan revealed a significant pleiotropic quantitative trait locus on chromosome 18p11.31-32 (LOD = 3.61). Bivariate association analysis conducted under the linkage peak revealed a variant (rs574972) within an intron of the gene SMCHD1 meeting the corrected significance level (χ(2) = 19.0, p = 7.4 × 10(-5)). Univariate association analyses of each phenotype separately revealed that the same variant was significant for right hippocampal volume alone, and also revealed a suggestively significant variant (rs12455524) within the gene DLGAP1 for rMDD alone. The results implicate right-hemisphere hippocampal volume as a possible endophenotype of rMDD, and in so doing highlight a potential gene of interest for rMDD risk.

Genome-wide linkage on chromosome 10q26 for a dimensional scale of major depression.

Major depressive disorder (MDD) is a common and potentially life-threatening mood disorder. Identifying genetic markers for depression might provide reliable indicators of depression risk, which would, in turn, substantially improve detection, enabling earlier and more effective treatment. The aim of this study was to identify rare variants for depression, modeled as a continuous trait, using linkage and post-hoc association analysis. The sample comprised 1221 Mexican-American individuals from extended pedigrees. A single dimensional scale of MDD was derived using confirmatory factor analysis applied to all items from the Past Major Depressive Episode section of the Mini-International Neuropsychiatric Interview. Scores on this scale of depression were subjected to linkage analysis followed by QTL region-specific association analysis. Linkage analysis revealed a single genome-wide significant QTL (LOD=3.43) on 10q26.13, QTL-specific association analysis conducted in the entire sample revealed a suggestive variant within an intron of the gene LHPP (rs11245316, p=7.8×10(-04); LD-adjusted Bonferroni-corrected p=8.6×10(-05)). This region of the genome has previously been implicated in the etiology of MDD; the present study extends our understanding of the involvement of this region by highlighting a putative gene of interest (LHPP).