Abstract
A stable-frequency transmitter with relative radial acceleration to a receiver will show a change in received frequency over time, known as a “drift rate.” For a transmission from an ...exoplanet, we must account for multiple components of drift rate: the exoplanet’s orbit and rotation, the Earth’s orbit and rotation, and other contributions. Understanding the drift rate distribution produced by exoplanets relative to Earth, can (a) help us constrain the range of drift rates to check in a Search for Extraterrestrial Intelligence project to detect radio technosignatures, and (b) help us decide validity of signals-of-interest, as we can compare drifting signals with expected drift rates from the target star. In this paper, we modeled the drift rate distribution for ∼5300 confirmed exoplanets, using parameters from the NASA Exoplanet Archive (NEA). We find that confirmed exoplanets have drift rates such that 99% of them fall within the ±53 nHz range. This implies a distribution-informed maximum drift rate ∼4 times lower than previous work. To mitigate the observational biases inherent in the NEA, we also simulated an exoplanet population built to reduce these biases. The results suggest that, for a Kepler-like target star without known exoplanets, ±0.44 nHz would be sufficient to account for 99% of signals. This reduction in recommended maximum drift rate is partially due to inclination effects and bias toward short orbital periods in the NEA. These narrowed drift rate maxima will increase the efficiency of searches and save significant computational effort in future radio technosignature searches.
Uncomplicated type 1 diabetes (T1DM) displays all features of subclinical cardiovascular disease (CVD) as is associated with inflammation, endothelial dysfunction and low endothelial progenitor ...cells. MiR-200c-3p has been shown in animal tissues to be pro-atherogenic. We aimed to explore the role of miR-200c-3p in T1DM, a model of subclinical CVD. 19 samples from T1DM patients and 20 from matched controls (HC) were analyzed. MiR-200c in plasma and peripheral blood mononuclear cells (PBMCs) was measured by real-time quantitative polymerase chain reaction. The results were compared with the following indices of vascular health: circulating endothelial progenitor cells, (CD45dimCD34+VEGFR-2+ or CD45dimCD34+CD133+) and proangiogenic cells (PACs). MiR-200c-3p was significantly downregulated in PBMCs but not in plasma in T1DM. There was a significant negative correlation between the expression of miR-200c-3p and HbA1c, interleukin-7 (IL-7), vascular endothelial growth factor-C (VEGF-C), and soluble vascular cell adhesion molecule-1, and a positive correlation with CD45dimCD34+VEGFR-2+, CD45dimCD34+CD133+ and PACs. Receiver operating curve analyses showed miR-200c-3p as a biomarker for T1DM with significant downregulation of miR-200c-3p, possibly defining subclinical CVD at HbA1c > 44.8 mmol/mol (6.2%). In conclusion, downregulated miR-200c-3p in T1DM correlated with diabetic control, VEGF signaling, inflammation, vascular health and targeting VEGF signaling, and may define subclinical CVD. Further prospective studies are necessary to validate our findings in a larger group of patients.
Cardiovascular disease (CVD) correlates with inflammation and a reduction in circulating endothelial progenitor cells (cEPCs). Recently, CVD was shown to be the main cause of mortality in individuals ...with type 1 diabetes (T1DM). In animals, miR-342 was shown to exert an anti-inflammatory effect in CVD. Hypothesis: miR-342-3p/-5p are downregulated in subclinical CVD (T1DM), whereas inflammatory cytokines are upregulated. We studied miR -342 -3p/5p in plasma/peripheral blood mononuclear cells (PBMCs) in 29 T1DM and 20 controls (HC). Vascular health was measured by fibronectin adhesion assay (FAA), cEPCs (CD45
CD34
133
cells) and by assessing inflammation and tissue inhibition of metalloproteases (TIMP-1). In T1DM IL-7, IL-8, TNFα and VEGF-C were increased in plasma. MiR-342-3p/-5p were downregulated in PBMCs in T1DM, but not in plasma.
, chemokine receptors
mRNAs, were increased in PBMCs in T1DM. MiR-342-3p was negatively correlated with TIMP-1, IL-6, IL-8, TNF-α, HbA
and
, whilst miR-342-5p was negatively correlated with TIMP-1, IL-6, IL-8 and HbA
. There was a positive correlation among miR-342-3p, FAA and cEPCs, and between miR-342-5p and cEPCs. ROC curve analyses showed significant downregulation of miR-342-3p/-5p at HbA
> 46.45 mmol/mol, indicating their potential as biomarkers for subclinical CVD. Our findings validated animal studies and confirmed the proangiogenic properties of miR-342-3p/-5p. MiR-342-3p/-5p-based intervention or monitoring may prove to be beneficial in managing CVD.
The objective of this review was to summarise published studies reporting Six Minute Walk Test (6MWT) values for adults with and without long-term conditions, to compare these with the Walk Score
®
, ...and make recommendations for healthcare professionals, policy makers and urban planners.
Scoping review.
Key databases - MEDLINE, CINAHL and EMBASE - were searched from January 2008 through March 2019 using combinations of MeSH terms and keywords for English language, peer reviewed, intervention or observational studies. Articles were included if the research included more than 10 participants, described or referenced the protocol and setting used for the 6MWT, and reported on 6MWT values. Mean shortest and longest distances walked in six minutes by people with and without long-term conditions were extracted, and differences compared between each value and the Walk Score
®
value.
Two hundred and sixty-nine studies comprising approximately 28,170 participants were included in the review. Adults with long-term conditions achieved considerably shorter 6MWT values than adults without long-term conditions, and walked less distance than indicated by the Walk Score
®
.
The premise of the Walk Score
®
is applicable for adults without long-term conditions, but for the Walk Score
®
to be useful for adults with long-term conditions, it should be used only as a guide and if personal and environmental factors are also taken into consideration. The design of neighborhoods needs to be inclusively walkable so that people can 'care for their own health' through being physically active on an everyday basis.
Bevacizumab is a vascular endothelial growth factor-A-specific angiogenesis inhibitor indicated as an adjunct to chemotherapy for the treatment of several types of cancer. Hypertension is commonly ...observed during bevacizumab treatment, and high-grade toxicity can limit therapy and lead to other cardiovascular complications. The factors that contribute to interindividual variability in blood pressure response to bevacizumab treatment are not well understood. In this review, we outline research efforts to understand the mechanisms and pathophysiology of hypertension resulting from bevacizumab treatment. Moreover, we highlight current knowledge of the pharmacogenetics of bevacizumab-induced hypertension, which may be used to develop strategies to prevent or minimize this toxicity.
The physicochemical stability of protein therapeutics is of significant pharmaceutical interest. Immunoglobulin gamma (IgG) hinge region fragmentation has recently garnered attention as an important ...degradation route of therapeutic monoclonal antibodies. In this work, the rates and relative amount of fragment species are compared for five different IgGs (IgG1–5) with widely varying solution properties. Native size-exclusion chromatography (SEC), sodium dodecyl sulfate (SDS)-based SEC, and capillary electrophoresis-SDS were used to characterize IgG1 fragmentation after storage at 30°C, 40°C, and 50°C. Two-dimensional correlation analysis of the chromatograms as a function of time was used to illustrate the relative rates of cleavage. Interestingly, the relative rate of Fab cleavage was greater than that of other species. An average apparent energy of activation for IgG1 fragmentation was also measured for all five molecules. This work suggests that IgG1 fragmentation is primarily hinge sequence dependent and other IgG1molecules should behave similarly within the limits of the solution conditions used.
Introduction
Dementia is a neurodegenerative condition characterized by cognitive decline and increased functional dependency. With most persons living with dementia (PLWDs) residing at home, ...home-based interventions provide a convenient and individualized alternative for person-centered care. Most of the evidence focused on specific interventions or exercise-based activities; there remains a gap in understanding the impacts of a broader range of non-exercise interventions on PLWDs and their caregivers. This review aimed to understand the impacts of home-based, non-exercise interventions on the behavioral, functional, cognitive, and mood outcomes of PLWDs, and their caregiver's quality of life (QoL), burden and mood.
Methods
Search for studies published up to June 2020 was conducted on CINAHL, PsycArticles, PubMed, SAGE Journals, Science Direct, and Web of Science. A search was also done manually based on the bibliographies of selected articles. The inclusion criteria for the systematic review were: (i) participants with a medical diagnosis of dementia, (ii) participants who resided at own home, (iii) intervention in the home setting, (iv) investigate interventions other than physical exercise, (v) randomized controlled trials (RCTs) or quasi-experimental studies, and (vi) full-text study published in English and in a peer-reviewed journal.
Results and discussion
Eighteen studies consisting of 14 RCTs and 4 quasi-experimental studies were included. Interventions included were occupational therapy, cognitive rehabilitation, tailored activity program, cognitive stimulation therapy, personalized reminiscence, music therapy, reality orientation, biobehavioral and multicomponent interventions. Results were mixed, but important intervention features were highlighted. Personalized activities for PLWDs that are aligned to their interest and ability appeared to contribute to intervention effectiveness especially in reducing behavioral symptoms and improving functional status. Involvement of caregivers in interventions is another feature of effective interventions for both the PLWDs and the caregivers' QoL, provided it is not deemed demanding or challenging to the caregivers. The inclusion of caregiver's education was effective in reducing caregivers' burden, particularly when the interventions improved the PLWD's functional status.
A radio-telemetry recording system is presented which is applied to stimulate specific brain areas and record neuronal activity in a free-roaming rat. The system consists of two major parts: ...stationary section and mobile section. The stationary section contains a laptop, a Micro Control Unit (MCU), an FM transmitter and a receiver. The mobile section is composed of the headstage and the backpack (which includes the mainboard, FM transmitter, and receiver), which can generate biphasic microcurrent pulses and simultaneously acquire neuronal activity. Prior to performing experiments, electrodes are implanted in the Ventral Posterolateral (VPL) thalamic nucleus, primary motor area (M1) and Medial Forebrain Bundle (MFB) of the rat. The stationary section modulates commands from the laptop for stimulation and demodulates signals for neuronal activity recording. The backpack is strapped on the back of the rat and executes commands from the stationary section, acquires neuronal activity, and transmits the neuronal activity singles of the waking rat to the stationary section. All components in the proposed system are commercially available and are fabricated from Surface Mount Devices (SMD) in order to reduce the size (25 mm × 15 mm × 2 mm) and weight (10 g with battery). During actual experiments, the backpack, which is powered by a rechargeable Lithium battery (4 g), can generate biphasic microcurrent pulse stimuli and can also record neuronal activity via the FM link with a maximum transmission rate of 1 kbps for more than one hour within a 200 m range in an open field or in a neighboring chamber. The test results show that the system is able to remotely navigate and control the rat without any prior training, and acquire neuronal activity with desirable features such as small size, low power consumption and high precision when compared with a commercial 4-channel bio-signal acquisition and processing system.
•An affective perspective is important in explaining FDI decisions.•Negative national sentiment has a stronger effect on FDI than positive national sentiment.•Accumulated national sentiment has a ...stronger effect on FDI than transient national sentiment
Studies of foreign direct investment (FDI) decisions typically assume that decision makers and stakeholders act rationally. Drawing on studies conducted at the individual level, this study focuses instead on affect and explores theoretically and empirically how national sentiment influences FDI decisions. In particular, we develop a typology for understanding national sentiment along two axes—positive versus negative and accumulated versus transient—and investigate their separate influences on FDI. The results indicate that negative sentiment has a greater influence on FDI than positive sentiment and that accumulated sentiment has a greater influence than transient sentiment. This study complements conventional FDI research by demonstrating that national sentiment offers additional explanatory power beyond the variables known to influence FDI decisions. Moreover, our study shows that research conducted at the individual level can be useful for understanding the influence of affective elements on FDI decisions.
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