Influenza viruses are thought to be spread by droplets, but the role of aerosol dissemination is unclear and has not been assessed by previous studies. Oxygen therapy, nebulised medication and ...ventilatory support are treatments used in clinical practice to treat influenzal infection are thought to generate droplets or aerosols.
Evaluation of the characteristics of droplet/aerosol dispersion around delivery systems during non-invasive ventilation (NIV), oxygen therapy, nebuliser treatment and chest physiotherapy by measuring droplet size, geographical distribution of droplets, decay in droplets over time after the interventions were discontinued.
Three groups were studied: (1) normal controls, (2) subjects with coryzal symptoms and (3) adult patients with chronic lung disease who were admitted to hospital with an infective exacerbation. Each group received oxygen therapy, NIV using a vented mask system and a modified circuit with non-vented mask and exhalation filter, and nebulised saline. The patient group had a period of standardised chest physiotherapy treatment. Droplet counts in mean diameter size ranges from 0.3 to > 10 µm were measured with an counter placed adjacent to the face and at a 1-m distance from the subject/patient, at the height of the nose/mouth of an average health-care worker.
NIV using a vented mask produced droplets in the large size range (> 10 µm) in patients (p = 0.042) and coryzal subjects (p = 0.044) compared with baseline values, but not in normal controls (p = 0.379), but this increase in large droplets was not seen using the NIV circuit modification. Chest physiotherapy produced droplets predominantly of > 10 µm (p = 0.003), which, as with NIV droplet count in the patients, had fallen significantly by 1 m. Oxygen therapy did not increase droplet count in any size range. Nebulised saline delivered droplets in the small- and medium-size aerosol/droplet range, but did not increase large-size droplet count.
NIV and chest physiotherapy are droplet (not aerosol)-generating procedures, producing droplets of > 10 µm in size. Due to their large mass, most fall out on to local surfaces within 1 m. The only device producing an aerosol was the nebuliser and the output profile is consistent with nebuliser characteristics rather than dissemination of large droplets from patients. These findings suggest that health-care workers providing NIV and chest physiotherapy, working within 1 m of an infected patient should have a higher level of respiratory protection, but that infection control measures designed to limit aerosol spread may have less relevance for these procedures. These results may have infection control implications for other airborne infections, such as severe acute respiratory syndrome and tuberculosis, as well as for pandemic influenza infection.
NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct ...measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products.
Schizophrenia involves abnormalities in the medial frontal cortex that lead to cognitive deficits. Here we investigate a novel strategy to normalize medial frontal brain activity by stimulating ...cerebellar projections. We used an interval timing task to study elementary cognitive processing that requires both frontal and cerebellar networks that are disrupted in patients with schizophrenia. We report three novel findings. First, patients with schizophrenia had dysfunctional delta rhythms between 1-4 Hz in the medial frontal cortex. We explored cerebellar-frontal interactions in animal models and found that both frontal and cerebellar neurons were modulated during interval timing and had delta-frequency interactions. Finally, delta-frequency optogenetic stimulation of thalamic synaptic terminals of lateral cerebellar projection neurons rescued timing performance as well as medial frontal activity in a rodent model of schizophrenia-related frontal dysfunction. These data provide insight into how the cerebellum influences medial frontal networks and the role of the cerebellum in cognitive processing.
Abstract
Background and Objectives
Age-based stereotype threat (ABST) poses serious risks for the cognitive screening of older adults. This review aimed to identify and critically appraise the ...methodology and existing evidence of studies investigating the use of threat-removal (TR) strategies to overcome the effects of ABST on the cognitive performance of older adults. The types of strategies, their effectiveness in optimizing cognitive performance, and factors influencing their effectiveness were examined.
Research Design and Methods
A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PsycINFO, PubMed, Embase, Web of Science, and Scopus were searched from January 1, 1995 to November 6, 2019. Two authors independently assessed article eligibility and appraised methodological quality of eligible articles using an adaptation of the Strengthening the Reporting of Observational studies in Epidemiology guidelines. Narrative synthesis was used to summarize results.
Results
Thirty articles, reporting on 36 studies, were eligible and included. Overall, evidence for the effectiveness of TR was mixed and varied according to the explicitness of strategies and comparison conditions used. Studies examining blatant TR strategies, and those using a combination of blatant and subtle TR strategies, provided limited support for their effectiveness in overcoming ABST. However, studies evaluating subtle TR strategies provided preliminary support for their effectiveness in overcoming ABST.
Discussion and Implications
Existing studies provide limited evidence regarding the effectiveness of TR strategies in overcoming ABST due to methodological limitations. Recommendations are made for the design of future studies to differentiate the benefits of TR strategies from the detrimental effects of ABST, thus potentially informing their use in clinical practice.
Metastasis is the major cause of death in patients with cancer; with no therapeutic cure, treatments remain largely palliative. As such, new targets and therapeutic strategies are urgently required. ...Here, we show that bone morphogenetic protein-4 (BMP4) blocks metastasis in animal models of breast cancer and predicts improved survival in patients. In preclinical models of spontaneous metastasis, BMP4 acted as an autocrine mediator to modulate a range of known metastasis-regulating genes, including
, via activation of canonical BMP-SMAD signaling. Restored BMP4 expression or therapeutically administered BMP4 protein, blocked metastasis and increased survival by sensitizing cancer cells to anoikis, thereby reducing the number of circulating tumor cells. Gene silencing of
or its downstream mediator
, reversed this phenotype. Administration of recombinant BMP4 markedly reduced spontaneous metastasis to lung and bone. Elevated levels of BMP4 and SMAD7 were prognostic for improved recurrence-free survival and overall survival in patients with breast cancer, indicating the importance of canonical BMP4 signaling in the suppression of metastasis and highlighting new avenues for therapy against metastatic disease. SIGNIFICANCE: Targeting the BMP4-SMAD7 signaling axis presents a novel therapeutic strategy to combat metastatic breast cancer, a disease that has had no reduction in patient mortality over 20 years. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/6/1304/F1.large.jpg.
Camera traps are an increasingly popular tool for monitoring medium to large mammals, but the influence of camera trap placement on the detection probabilities of different species has seldom been ...investigated. In this study we explore the influence of roads on the detection probability of medium to large mammals in three vegetation types in the Little Karoo, an arid biodiversity hotspot. We placed cameras in nine 100 m-long transects, running perpendicular from roads within a conservation area. The camera traps were spaced at ~25 m intervals, and were active for an average of 88 days each. Detection probabilities relative to distance from roads showed extensive variation between species and habitat types. There was no clear relationship between distance from the road and the detection probability of most species and guilds, although carnivore detection probability declined significantly as distance from roads increased in all vegetation types. Our results suggest that there is considerable inter-specific variation in detection probability that is significantly influenced by camera trap location relative to roads. Therefore studies that seek to maximise the detection rates of particular species or guilds (e.g. carnivores) by placing cameras on prominent roads and trails are unlikely to provide reliable estimates of the relative abundance of the broader range of sympatric species; a trend observed elsewhere but hitherto untested in arid environments. We recommend that future studies employ a mixed design of cameras located on- and off-roads to provide better estimates of biodiversity in general and predators specifically.
Wildlife population density estimates provide information on the number of individuals in an area and influence conservation management decisions. Thus, accuracy is vital. A dominant feature in many ...landscapes globally is fencing, yet the implications of fence permeability on density estimation using spatial capture-recapture modelling are seldom considered. We used camera trap data from 15 fenced reserves across South Africa to examine the density of brown hyaenas (Parahyaena brunnea). We estimated density and modelled its relationship with a suite of covariates when fenced reserve boundaries were assumed to be permeable or impermeable to hyaena movements. The best performing models were those that included only the influence of study site on both hyaena density and detection probability, regardless of assumptions of fence permeability. When fences were considered impermeable, densities ranged from 2.55 to 15.06 animals per 100 km
, but when fences were considered permeable, density estimates were on average 9.52 times lower (from 0.17 to 1.59 animals per 100 km
). Fence permeability should therefore be an essential consideration when estimating density, especially since density results can considerably influence wildlife management decisions. In the absence of strong evidence to the contrary, future studies in fenced areas should assume some degree of permeability in order to avoid overestimating population density.
Excessive STAT3 signalling via gp130, the shared receptor subunit for IL-6 and IL-11, contributes to disease progression and poor survival outcomes in patients with colorectal cancer. Here, we ...provide evidence that bazedoxifene inhibits tumour growth via direct interaction with the gp130 receptor to suppress IL-6 and IL-11-mediated STAT3 signalling. Additionally, bazedoxifene combined with chemotherapy synergistically reduced cell proliferation and induced apoptosis in patient-derived colon cancer organoids. We elucidated that the primary mechanism of anti-tumour activity conferred by bazedoxifene treatment occurs via pro-apoptotic responses in tumour cells. Co-treatment with bazedoxifene and the SMAC-mimetics, LCL161 or Birinapant, that target the IAP family of proteins, demonstrated increased apoptosis and reduced proliferation in colorectal cancer cells. Our findings provide evidence that bazedoxifene treatment could be combined with SMAC-mimetics and chemotherapy to enhance tumour cell apoptosis in colorectal cancer, where gp130 receptor signalling promotes tumour growth and progression.
To approximately compute the nonrelativistic ground state of an electrically nonneutral star, an exactly solvable model was recently introduced, and partly solved, in Krivoruchenko et al. Phys. Rev. ...D 97, 083016 (2018). The model generalizes the well-known Lane-Emden equation of a polytropic gas ball of index n = 1 to a two-fluid setting. Here its complete solution is presented in terms of simple elementary functions; it is also generalized to a more-than-two-fluid setting where it remains exactly solvable. It is shown that, given the number of nuclei, a maximal negatively charged solution and a maximal positively charged solution exist, plus a continuous family of solutions which interpolates between these extremes. Numerical comparisons show that this exactly solvable model captures the qualitative behavior of the more physical model it is supposed to approximate. Furthermore, it correctly answers the question: how nonneutral can the star be? The answer is independent of the speed of light c and the Planck quantum h . It supports Penrose's weak cosmic censorship hypothesis, in the sense that the bounds on the excess charge are compatible with the bound on the charge of a Reissner-Weyl-Nordström black hole.
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