Update on trials examining effects of night-time blood pressure lowering drug treatment on prevention of cardiovascular disease

Current evidence on benefits of night-time blood pressure (BP) lowering drug treatment on cardiovascular disease (CVD) prevention attributable to the Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy (MAPEC) trial and Bedtime hypertension treatment improves cardiovascular risk reduction (Hygia) trials has raised concern on their validity and methodology. In this commentary, the authors have updated the progress of the ongoing trials that were planned to examine the effect of night-time BP lowering drug treatment on CVD prevention. As compared to MAPEC and Hygia trials, three pragmatic trials the Blood Pressure Medication Timing (BPMedtime) trial (US), the Treatment In Morning versus Evening (TIME) trial (UK), Bedmed and Bedmed-frail (Canada) were planned without ambulatory BP monitoring. The BPMedtime trial was stopped after the pilot phase due to underestimated sample size and insufficient funds. TIME trial (UK) had a similar issue when changing the sample size from 10,269 to more than 20,000 participants. The TIME trial was completed and the initial results showing that protection against heart attack, stroke and vascular death is not affected by whether antihypertensive medications are taken in the morning or evening. The full study of the TIME trial is published in December 2022. Bedmed and Bedmed-frail trials are ongoing and will be completed in 2023. Time of taking BP lowering drug should be determined by patients at their convenience to improve the adherence. There was no difference in adverse effects of taking BP lowering drugs at night or morning. Evidence on the effect of night-time treatment on CVD events is inconsistent. The results from ongoing trials in Canada will contribute evidence to the use of BP lowering drug treatment for the prevention of CVD

On a Conjecture by Baril, Cerbai, Khalil, and Vajnovszki on Two Restricted Stacks

Let $s$ be West's stack-sorting map, and let $s_{T}$ be the generalized stack-sorting map, where instead of being required to increase, the stack avoids subpermutations that are order-isomorphic to any permutation in the set $T$. In 2020, Cerbai, Claesson, and Ferrari introduced the $\sigma$-machine $s \circ s_{\sigma}$ as a generalization of West's $2$-stack-sorting-map $s \circ s$. As a further generalization, in 2021, Baril, Cerbai, Khalil, and Vajnovski introduced the $(\sigma, \tau)$-machine $s \circ s_{\sigma, \tau}$ and enumerated $|\mathrm{Sort}_{n}(\sigma,\tau)|$ -- the number of permutations in $S_n$ that are mapped to the identity by the $(\sigma, \tau)$-machine -- for six pairs of length $3$ permutations $(\sigma, \tau)$. In this work, we settle a conjecture by Baril, Cerbai, Khalil, and Vajnovski on the only remaining pair of length $3$ patterns $(\sigma, \tau) = (132, 321)$ for which $|\mathrm{Sort}_{n}(\sigma, \tau)|$ appears in the OEIS. In addition, we enumerate $|\mathrm{Sort}_n(123, 321)|$, which does not appear in the OEIS, but has a simple closed form

Multifunctional superparamagnetic iron oxide nanoparticles for combined chemotherapy and hyperthermia cancer treatment

Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could generate sufficient heat to raise the local temperature to 43 °C, sufficient to trigger apoptosis in cancer cells. Further, we found that DOX-loaded SPIOs resulted in cell death comparable to free DOX, and that the combined effect of DOX and SPIO-induced hyperthermia enhanced cancer cell death in vitro. This study demonstrates the potential of using phospholipid-PEG coated SPIOs for chemotherapy–hyperthermia combinatorial cancer treatment with increased efficacy

Thai lexical tone perception in native speakers of Thai, English and Mandarin Chinese: An event-related potentials training study

<p>Abstract</p> <p>Background</p> <p>Tone languages such as Thai and Mandarin Chinese use differences in fundamental frequency (F₀, pitch) to distinguish lexical meaning. Previous behavioral studies have shown that native speakers of a non-tone language have difficulty discriminating among tone contrasts and are sensitive to different F₀dimensions than speakers of a tone language. The aim of the present ERP study was to investigate the effect of language background and training on the non-attentive processing of lexical tones. EEG was recorded from 12 adult native speakers of Mandarin Chinese, 12 native speakers of American English, and 11 Thai speakers while they were watching a movie and were presented with multiple tokens of low-falling, mid-level and high-rising Thai lexical tones. High-rising or low-falling tokens were presented as deviants among mid-level standard tokens, and vice versa. EEG data and data from a behavioral discrimination task were collected before and after a two-day perceptual categorization training task.</p> <p>Results</p> <p>Behavioral discrimination improved after training in both the Chinese and the English groups. Low-falling tone deviants versus standards elicited a mismatch negativity (MMN) in all language groups. Before, but not after training, the English speakers showed a larger MMN compared to the Chinese, even though English speakers performed worst in the behavioral tasks. The MMN was followed by a late negativity, which became smaller with improved discrimination. The High-rising deviants versus standards elicited a late negativity, which was left-lateralized only in the English and Chinese groups.</p> <p>Conclusion</p> <p>Results showed that native speakers of English, Chinese and Thai recruited largely similar mechanisms when non-attentively processing Thai lexical tones. However, native Thai speakers differed from the Chinese and English speakers with respect to the processing of late F₀contour differences (high-rising versus mid-level tones). In addition, native speakers of a non-tone language (English) were initially more sensitive to F₀onset differences (low-falling versus mid-level contrast), which was suppressed as a result of training. This result converges with results from previous behavioral studies and supports the view that attentive as well as non-attentive processing of F₀contrasts is affected by language background, but is malleable even in adult learners.</p

Structural Capacity Analysis of Corroded Steel Girder Bridges

More than 9% of the bridges in the United States were labeled structurally deficient according to the 2017 American Society of Civil Engineers’ infrastructure report card. The main causes of bridge deterioration are repeated vehicular loads and adverse environmental exposure. The most dominant deterioration form for steel bridges is corrosion, which is characterized by the loss of metal area resulting in reduction of structural capacity. Corrosion in steel multi-girder bridges is common in cold regions because of the frequent use of deicing chemicals during the winter season as well as leakage caused by bridge joint damage. At times, the rust is serious enough to disconnect the web from the flanges of the girder. This poses significant concerns for load capacity especially at girder ends. The consequences of bridge failure can be disastrous. This research investigates the structural capacity of these corroded steel girders. The mechanical behaviors of deteriorated girders are studied by 3-D finite element models built in ABAQUS and by lab testing. Our analysis is focused on web area loss and web thinning due to corrosion, and their consequences for load capacity reduction. The effects of location, size, and shape of area loss on shear and web buckling resistance will be studied. Lab tests on steel girder models will be conducted to verify the results from finite element modeling. Based on our analysis and findings, a simple and dependable rating method to evaluate deteriorated steel girder bridges will be developed

Measuring Three-Dimensional Temperature Distributions in Steel-Concrete Composite Slabs Subjected to Fire using Distributed Fiber Optic Sensors

Detailed information about temperature distribution can be important to understand structural behavior in fire. This study develops a method to image three-dimensional temperature distributions in steel–concrete composite slabs using distributed fiber optic sensors. The feasibility of the method is explored using six 1.2 m × 0.9 m steel–concrete composite slabs instrumented with distributed sensors and thermocouples subjected to fire for over 3 h. Dense point clouds of temperature in the slabs were measured using the distributed sensors. The results show that the distributed sensors operated at material temperatures up to 960◦C with acceptable accuracy for many structural fire applications. The measured non-uniform temperature distributions indicate a spatially distributed thermal response in steel–concrete composite slabs, which can only be adequately captured using approaches that provide a high density of through-depth data points

IFN-γ Attenuates Eosinophilic Inflammation but Is Not Essential for Protection against RSV-Enhanced Asthmatic Comorbidity in Adult Mice

The susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 cytokine IFN-γ is essential for protection against RSV and RSV-associated comorbidities in adult mice. We found that, distinct from influenza virus, prior RSV infection does not induce significant IFN-γ production and susceptibility to secondary Streptococcus pneumoniae infection in adult wild-type (WT) mice. In ovalbumin (OVA)-induced asthmatic mice, RSV super-infection increases airway neutrophil recruitment and inflammatory lung damage but has no significant effect on OVA-induced eosinophilia. Compared with WT controls, RSV infection of asthmatic Ifng-/- mice results in increased airway eosinophil accumulation. However, a comparable increase in eosinophilia was detected in house dust mite (HDM)-induced asthmatic Ifng-/- mice in the absence of RSV infection. Furthermore, neither WT nor Ifng-/- mice exhibit apparent eosinophil infiltration during RSV infection alone. Together, these findings indicate that, despite its critical role in limiting eosinophilic inflammation during asthma, IFN-γ is not essential for protection against RSV-induced exacerbation of asthmatic inflammation in adult mice