Trends in viable microbial bioburden on surfaces within a paediatric bone marrow transplant unit.

BACKGROUND: Despite their role being historically overlooked, environmental surfaces have been shown to play a key role in the transmission of pathogens causative of healthcare-associated infection. To guide infection prevention and control (IPC) interventions and inform clinical risk assessments, more needs to be known about microbial surface bioburdens. AIM: To identify the trends in culturable bacterial contamination across communal touch sites over time in a hospital setting. METHODS: Swab samples were collected over nine weeks from 22 communal touch sites in a paediatric bone marrow transplant unit. Samples were cultured on Columbia blood agar and aerobic colony counts (ACC) per 100 cm2 were established for each site. Individual colony morphologies were grouped and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or 16s rDNA sequencing. FINDINGS: Highest mean counts were observed for sites associated with ward management activity and computer devices (3.29 and 2.97 ACC/100 cm2 respectively). A nurses' station keyboard had high mean ACC/100 cm2 counts (10.67) and diversity, while laundry controls had high mean ACC/100 cm2 counts (4.70) and low diversity. Micrococcus luteus was identified in all sampling groups. Clinical staff usage sites were contaminated with similar proportions of skin and environmental flora (52.19-46.59% respectively), but sites associated with parental activities were predominantly contaminated by environmental microflora (86.53%). CONCLUSION: The trends observed suggest patterns in microbial loading based on site activities, surface types and user groups. Improved understanding of environmental surface contamination could help support results interpretation and IPC interventions, improving patient safety.

Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy.

The identification of patient-derived, tumor-reactive T cell receptors (TCRs) as a basis for personalized transgenic T cell therapies remains a time- and cost-intensive endeavor. Current approaches to identify tumor-reactive TCRs analyze tumor mutations to predict T cell activating (neo)antigens and use these to either enrich tumor infiltrating lymphocyte (TIL) cultures or validate individual TCRs for transgenic autologous therapies. Here we combined high-throughput TCR cloning and reactivity validation to train predicTCR, a machine learning classifier that identifies individual tumor-reactive TILs in an antigen-agnostic manner based on single-TIL RNA sequencing. PredicTCR identifies tumor-reactive TCRs in TILs from diverse cancers better than previous gene set enrichment-based approaches, increasing specificity and sensitivity (geometric mean) from 0.38 to 0.74. By predicting tumor-reactive TCRs in a matter of days, TCR clonotypes can be prioritized to accelerate the manufacture of personalized T cell therapies.

Compositionality in visual perception.

Quilty-Dunn et al.'s wide-ranging defense of the Language of Thought Hypothesis (LoTH) argues that vision traffics in abstract, structured representational formats. We agree: Vision, like language, is compositional - just as words compose into phrases, many visual representations contain discrete constituents that combine in systematic ways. Here, we amass evidence extending this proposal, and explore its implications for how vision interfaces with the rest of the mind.

The Newport Quinsy Simulator.

BACKGROUND: The junior otolaryngologist is responsible for recognition and drainage of the peritonsillar abscess. Although other simulators have been proposed, there is still a need for an accessible, educationally useful, low-cost peritonsillar abscess simulator to build skills and confidence in the novice. METHODS: The peritonsillar abscess simulator was constructed from basic disposable healthcare equipment and a party balloon. Evaluation of this Newport Quinsy Simulator was performed by expert and novice clinicians, who provided feedback in the form of Likert scales and free-text qualitative responses. RESULTS: Overall, 24 clinicians evaluated the simulator. All felt the simulator was useful for the novice otolaryngologist, and represented the key anatomy and motor skills needed to drain a peritonsillar abscess. Qualitative evaluation highlighted the educational usefulness of the simulator as a peritonsillar abscess training device. CONCLUSION: The Newport Quinsy Simulator is affordable, accessible, easy to use and educationally valuable to the novice otolaryngologist.

Problems and Mysteries of the Many Languages of Thought.

"What is the structure of thought?" is as central a question as any in cognitive science. A classic answer to this question has appealed to a Language of Thought (LoT). We point to emerging research from disparate branches of the field that supports the LoT hypothesis, but also uncovers diversity in LoTs across cognitive systems, stages of development, and species. Our letter formulates open research questions for cognitive science concerning the varieties of rules and representations that underwrite various LoT-based systems and how these variations can help researchers taxonomize cognitive systems.

Right coronary artery to left ventricle coronary cameral fistula in a cat.

A six-month-old female intact domestic shorthair cat was presented for evaluation of a loud heart murmur. Transthoracic echocardiography revealed dilation of the left ventricle secondary to an abnormal vessel shunting blood into the left ventricular outflow tract at a high velocity during diastole. Multidetector computed tomography angiography revealed a coronary cameral fistula that originated at the right coronary artery, encircled the heart, and then terminated into the left ventricular outflow tract. This case report documents the first known case of a coronary cameral fistula in a cat. Multimodal imaging was an essential aspect to diagnosing the congenital lesion in this case.

Do water and soil nutrient scarcities differentially impact the performance of diploid and tetraploid Solidago gigantea (Giant Goldenrod, Asteraceae)?

Plants require water and nutrients for survival, although the effects of their availabilities on plant fitness differ amongst species. Genome size variation, within and across species, is suspected to influence plant water and nutrient requirements, but little is known about how variations in these resources concurrently affect plant fitness based on genome size. We examined how genome size variation between autopolyploid cytotypes influences plant morphological and physiological traits, and whether cytotype-specific trait responses differ based on water and/or nutrient availability. Diploid and autotetraploid Solidago gigantea (Giant Goldenrod) were grown in a greenhouse under four soil water:N+P treatments (L:L, L:H, H:L, H:H), and stomata characteristics (size, density), growth (above- and belowground biomass, R/S), and physiological (Anet , E, WUE) responses were measured. Resource availabilities and cytotype identity influenced some plant responses but their effects were independent of each other. Plants grown in high-water and nutrient treatments were larger, plants grown in low-water or high-nutrient treatments had higher WUE but lower E, and Anet and E rates decreased as plants aged. Autotetraploids also had larger and fewer stomata, higher biomass and larger Anet than diploids. Nutrient and water availability could influence intra- and interspecific competitive outcomes. Although S. gigantea cytotypes were not differentially affected by resource treatments, genome size may influence cytogeographic range patterning and population establishment likelihood. For instance, the larger size of autotetraploid S. gigantea might render them more competitive for resources and niche space than diploids.

Biophotonic tools for probing extracellular matrix mechanics.

The complex, hierarchical and heterogeneous biomechanics of the extracellular matrix (ECM) are central to the health of multicellular organisms. Characterising the distribution, dynamics and above all else origins of ECM biomechanics are challenges that have captivated researchers for decades. Recently, a suite of biophotonics techniques have emerged as powerful new tools to investigate ECM biomechanics. In this mini-review, we discuss how the non-destructive, sub-micron resolution imaging capabilities of Raman spectroscopy and nonlinear microscopy are being used to interrogate the biomechanics of thick, living tissues. These high speed, label-free techniques are implemented during mechanical testing, providing unprecedented insight into the compositional and structural response of the ECM to changes in the mechanical environment.

Thymic B Cells as a New Player in the Type 1 Diabetes Response.

Type 1 diabetes (T1d) results from a sustained autoreactive T and B cell response towards insulin-producing ß cells in the islets of Langerhans. The autoreactive nature of the condition has led to many investigations addressing the genetic or cellular changes in primary lymphoid tissues that impairs central tolerance- a key process in the deletion of autoreactive T and B cells during their development. For T cells, these studies have largely focused on medullary thymic epithelial cells (mTECs) critical for the effective negative selection of autoreactive T cells in the thymus. Recently, a new cellular player that impacts positively or negatively on the deletion of autoreactive T cells during their development has come to light, thymic B cells. Normally a small population within the thymus of mouse and man, thymic B cells expand in T1d as well as other autoimmune conditions, reside in thymic ectopic germinal centres and secrete autoantibodies that bind selective mTECs precipitating mTEC death. In this review we will discuss the ontogeny, characteristics and functionality of thymic B cells in healthy and autoimmune settings. Furthermore, we explore how in silico approaches may help decipher the complex cellular interplay of thymic B cells with other cells within the thymic microenvironment leading to new avenues for therapeutic intervention.

Risk of torsion in superior rectus transposition surgery augmented with posterior scleral fixation sutures.

It has been reported that superior rectus transposition combined with medial rectus recession can provide as good results as transposition of both vertical rectus muscles, with no adverse effects on torsion or postoperative vertical misalignment. Further augmentation of transposition surgery can be achieved through the use of posterior fixation sutures, myopexy and botulinum toxin into the medial rectus. We report a patient with complete bilateral traumatic sixth cranial nerve palsies who underwent sequential superior rectus transposition surgery combined with medial rectus recession. The surgery was augmented with a myopexy (posterior suture joining superior and lateral recti with no scleral fixation) in the first eye and with a posterior fixation suture (with scleral fixation) in the second eye. After the second procedure, despite a significant improvement in horizontal alignment, the patient developed 15 degrees of incyclotorsion which was attributed to the scleral fixation suture. The patient underwent removal of the scleral suture and 3 months postoperatively had a significant reduction in incyclotorsion to 8 degrees; however this continued to be a barrier to fusion. Vertical rectus transposition of superior and inferior recti augmented with posterior scleral fixation sutures is one type of conventional surgery for complete lateral rectus palsy. In more recent times, it has become common to transpose the superior rectus alone along with recession of the contracted medial rectus. This procedure can also be augmented with a posterior fixation suture which may or may not be attached to the sclera. Whilst this surgery has gained popularity it is not without risk as demonstrated by our case in which transposition of the superior rectus was associated with postoperative incyclotorsion. In this case a possible explanation may be the use of a the posterior scleral fixation suture as it did not occur when no scleral fixation was used. Furthermore, removal of the posterior scleral fixation suture did reduce the torsion significantly although it did not eliminate it.

Evaluation of DISORDER: Retrospective Image Motion Correction for Volumetric Brain MRI in a Pediatric Setting.

BACKGROUND AND PURPOSE: Head motion causes image degradation in brain MR imaging examinations, negatively impacting image quality, especially in pediatric populations. Here, we used a retrospective motion correction technique in children and assessed image quality improvement for 3D MR imaging acquisitions. MATERIALS AND METHODS: We prospectively acquired brain MR imaging at 3T using 3D sequences, T1-weighted MPRAGE, T2-weighted TSE, and FLAIR in 32 unsedated children, including 7 with epilepsy (age range, 2-18 years). We implemented a novel motion correction technique through a modification of k-space data acquisition: Distributed and Incoherent Sample Orders for Reconstruction Deblurring by using Encoding Redundancy (DISORDER). For each participant and technique, we obtained 3 reconstructions as acquired (Aq), after DISORDER motion correction (Di), and Di with additional outlier rejection (DiOut). We analyzed 288 images quantitatively, measuring 2 objective no-reference image quality metrics: gradient entropy (GE) and MPRAGE white matter (WM) homogeneity. As a qualitative metric, we presented blinded and randomized images to 2 expert neuroradiologists who scored them for clinical readability. RESULTS: Both image quality metrics improved after motion correction for all modalities, and improvement correlated with the amount of intrascan motion. Neuroradiologists also considered the motion corrected images as of higher quality (Wilcoxon z = -3.164 for MPRAGE; z = -2.066 for TSE; z = -2.645 for FLAIR; all P < .05). CONCLUSIONS: Retrospective image motion correction with DISORDER increased image quality both from an objective and qualitative perspective. In 75% of sessions, at least 1 sequence was improved by this approach, indicating the benefit of this technique in unsedated children for both clinical and research environments.

Caregiver self-efficacy to talk about sex predicts conversations about HIV transmission risk with perinatally infected young people in Zimbabwe.

Given advances in care and treatment for HIV, perinatally infected young people are surviving into adolescence. These young people are making decisions about engaging in sexual relationships and it is critical to ensure they have the information they need to engage responsibly in sexual activity, particularly in an era where adherence to treatment could make their virus undetectable. The main objective of this analysis was to examine whether an HIV-positive young person's knowledge about forward transmission is associated with caregiver self-efficacy to talk about sex and general caregiver communication. Using data from a 12-month prospective cohort of caregivers of HIV-positive children aged 9-15 on ART and pre-ART in rural Zimbabwe, we found that caregiver self-efficacy to talk about sex predicted whether conversations about HIV transmission would occur between caregiver and the young person. However, by the end of 12-months, nearly two-thirds of caregivers of HIV-positive teenagers in our sample had still not explained how their adolescents could spread the virus to others despite these caregivers saying their adolescent should know this information at baseline. We discuss the implications for designing sexual and reproductive health (SRH) programs among populations of young people perinatally infected with HIV to ensure that this breakthrough generation receives the SRH support they need.

Synergistic Antibacterial Effects of Metallic Nanoparticle Combinations.

Metallic nanoparticles have unique antimicrobial properties that make them suitable for use within medical and pharmaceutical devices to prevent the spread of infection in healthcare. The use of nanoparticles in healthcare is on the increase with silver being used in many devices. However, not all metallic nanoparticles can target and kill all disease-causing bacteria. To overcome this, a combination of several different metallic nanoparticles were used in this study to compare effects of multiple metallic nanoparticles when in combination than when used singly, as single elemental nanoparticles (SENPs), against two common hospital acquired pathogens (Staphylococcus aureus and Pseudomonas. aeruginosa). Flow cytometry LIVE/DEAD assay was used to determine rates of cell death within a bacterial population when exposed to the nanoparticles. Results were analysed using linear models to compare effectiveness of three different metallic nanoparticles, tungsten carbide (WC), silver (Ag) and copper (Cu), in combination and separately. Results show that when the nanoparticles are placed in combination (NPCs), antimicrobial effects significantly increase than when compared with SENPs (P < 0.01). This study demonstrates that certain metallic nanoparticles can be used in combination to improve the antimicrobial efficiency in destroying morphologically distinct pathogens within the healthcare and pharmaceutical industry.

Precision Health: Bringing Oral Health into the Context of Overall Health.

Unprecedented advances in genomics, data science, and biotechnology have ushered in a new era of health care in which interventions are increasingly tailored to individual patients. Precision-based approaches extend to oral health, which is essential to overall health. Harnessing the full potential of precision oral health will depend on research to more fully understand the factors that underlie health and contribute to disease-including the human genome, microbiome, epigenome, proteome, and others.

How to carry out microbiological sampling of healthcare environment surfaces? A review of current evidence.

There is increasing evidence that the hospital surface environment contributes to the spread of pathogens. However, evidence on how best to sample these surfaces is inconsistent and there is no guidance or legislation in place on how to do this. The aim of this review was to assess current literature on surface sampling methodologies, including the devices used, processing methods, and the environmental and biological factors that might influence results. Studies published prior to March 2019 were selected using relevant keywords from ScienceDirect, Web of Science, and PubMed. Abstracts were reviewed and all data-based studies in peer-reviewed journals in the English language were included. Microbiological air and water sampling in the hospital environment were not included. Although the numbers of cells or virions recovered from hospital surface environments were generally low, the majority of surfaces sampled were microbiologically contaminated. Of the organisms detected, multidrug-resistant organisms and clinically significant pathogens were frequently isolated and could, therefore, present a risk to vulnerable patients. Great variation was found between methods and the available data were incomplete and incomparable. Available literature on sampling methods demonstrated deficits with potential improvements for future research. Many of the studies included in the review were laboratory-based and not undertaken in the real hospital environment where sampling recoveries could be affected by the many variables present in a clinical environment. It was therefore difficult to draw overall conclusions; however, some recommendations for the design of routine protocols for surface sampling of healthcare environments can be made.

Research priorities for the pan-Canadian Oncology Symptom Triage and Remote Support practice guides: a modified nominal group consensus.

Introduction: The pan-Canadian Oncology Symptom Triage and Remote Support (costars) team is studying how to improve the quality and consistency of cancer symptom management. Methods: A 1-day invitational meeting was held 24 October 2017 in Ottawa, Ontario, to review the current evidence from costars projects and to establish research priorities for a future largescale implementation study. The meeting included 36 participants who were clinicians from adult oncology, pediatric oncology, and homecare; policymakers from national, provincial, and regional organizations; researchers; and a patient. Half the day involved summarizing evidence from four costars studies and experiences with implementing the costars symptom practice guides. The second half of the day used a modified nominal group technique to generate research questions within small groups, presentation of research questions to all participants, and two rounds of voting to reach consensus on research priorities. Results: Participants proposed 4 research categories:■ User-centred augmentation to enhance usability (for example, designing a mobile costars solution)■ Outcome measurement (for example, determining key competencies for clinicians)■ Regular renewal of costars to keep pace with evolving evidence (for example, updates for novel therapies)■ Integration into clinical practice (for example, meaningful engagement of patients and caregivers in study design). Conclusions: Across categories, the top 3 priorities were effect on health services use, competency development, and a mobile costars solution. Future research will address identified priorities, reflecting the needs and perspectives of diverse stakeholders. Stakeholder collaboration will continue to guide our approach to operationalizing this priority research agenda.

U.S. prevalence of endocrine therapy-naïve locally advanced or metastatic breast cancer.

Background: Variations in treatment choice, or late stage at first diagnosis, mean that, despite guideline recommendations, not all patients with hormone receptor (hr)-positive locally advanced or metastatic breast cancer (la/mbca) will have received endocrine therapy before disease progression. In the present study, we aimed to estimate the proportion of women with postmenopausal hr-positive la/mbca in the United States who are endocrine therapy-naïve. Methods: Women in the Optum Electronic Health Record (ehr) database with a breast cancer (bca) diagnosis (January 2008-March 2015) were included. Patient and malignancy characteristics were identified using structured data fields and natural-language processing of free-text clinical notes. The proportion of women with postmenopausal hr-positive, human epidermal growth factor 2 (her2)-negative (or unknown) la/mbca who had not received prior endocrine therapy was determined. Results were extrapolated to the entire U.S. population using the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results database. Results are presented descriptively. Results: In the ehr database, 11,831 women with bca had discernible information on postmenopausal status, hr status, and disease stage. Of those women, 1923 (16.3%) had postmenopausal hr-positive, her2-negative (or unknown) la/mbca, and 70.7% of those 1923 patients (n = 1360) had not received prior endocrine therapy, accounting for 11.5% of the overall population. Extrapolating those estimates nationally suggests an annual incidence of 14,784 cases, and a 5-year limited duration prevalence of 50,638 cases. Conclusions: A substantial proportion of women with postmenopausal hr-positive la/mbca in the United States could be endocrine therapy-naïve.