bluuebunny/crossref_metadata_2025 huggingface dataset:
Telemedicine usage via WeChat for children with congenital heart disease preoperatively during COVID-19 pandemic: a retrospective analysis
Authors: Zhang Qi-Liang , Xie Wen-Peng , Lei Yu-Qing , Cao Hua , Chen Qiang
Published: April 2021

Objective

During the COVID-19 pandemic, parents of infants having medical problem face challenges of insufficient medical resources at home. The purpose of this study was to investigate the effect of WeChat-based telehealth services on the preoperative follow-up of infants with congenital heart disease (CHD) during the COVID-19 pandemic.

Methods

This study retrospectively analyzed the medical records of 190 infants with CHD who underwent remote follow-up via WeChat from December 2019 to May 2020 in Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University. In addition, the psychological benefits of WeChat on the parents of these infants were analyzed.

Results

In total, 190 infants were involved in this study, including 72 cases of ventricular septal defects, 42 cases of patent ductus arteriosus, 55 cases of atrial septal defects, 3 cases of tetralogy of Fallot, 2 cases of endocardial cushion defects, 12 cases of pulmonary stenosis, 2 cases of total anomalous pulmonary venous connection and 2 cases of aortic arch constriction. During the follow-up period, 48 infants who received surgical indications were hospitalized in time for surgical treatment. It was recommended that 10 infants with respiratory tract infections be treated in local hospitals through the WeChat platform. We provided feeding guidance to 28 infants with dysplasia through the WeChat platform. The psychological evaluation results of parents showed that the median score and range of Self-Rating Depression Scale scores were 42 and 32–58, respectively. Nine parents (4.7%) were clinically depressed, while the majority had mild depression. The median score and range of Self-Rating Anxiety Scale scores were 44 and 31–59, respectively. Twenty parents (10.5%) had clinical anxiety, while the rest had mild anxiety.

Conclusion

During the COVID-19 pandemic, follow-up management and health services for infants with CHD prior to surgery through the WeChat platform were useful in identifying the state of an infant’s condition as well as in identifying and relieving care pressure, anxiety and depression in the parents.
Behavioral and stress responses to feeding time in pregnant sows under limit-fed regime
Authors: Manu Hayford , Lee Suhyup , Keyes Mike C , Cairns Jim , Baidoo Samuel K
Published: April 2021

We investigated the effect of feeding time on behavior and stress responses in pregnant sows under isocaloric conditions. Twenty-four sows were balanced for parity and randomly assigned to 1 of 3 feeding times. Corn–soybean meal-based diet was fed once at: 0730 (Control, T1), 1130 (T2), and 1530 hours (T3). On average, sows received 7,062 kcal ME/d from 2.20 kg of diet formulated to contain SID Lys/ME of 1.71 g/Mcal. The study was conducted for 28 d (21 d acclimation to the feeding regime and 7 d data collection). Saliva samples were collected every 2 hr for 12 hr in stalls on day 52 of pregnancy. Behavior data were collected 24 hr for 7 d from day 53 of gestating by affixing a remote insights ear tag to each sow. Each sow had 120,960 data points categorized into: “Active,” “Feed,” or “Dormant”. Due to housing constraint, all sows were housed in individual stalls in the same barn presenting a potential limitation of the study. Data were analyzed using PROC MIXED and GLIMMIX procedures of SAS 9.4 for cortisol and behavior data, respectively. Sow was the experimental unit. The area under the curve (AUC) is quantitative evaluation of response as threshold varies over all possible values. A 12-hr cortisol total AUC for sows fed once daily at 1130 hours was reduced relative to sow group fed at 1530 hours (P = 0.046) but similar compared with the control sows (P = 0. 323). The control sows (0730 hours) had reduced total (P < 0.001) and feeding (P = 0.001) activity AUCs relative to sows on 1130 hours but did not differ compared with sows on 1530 hours feeding schedules (P > 0.100). Sows on 1130 hours feeding schedule had greater feed anticipatory activity, 24-hr total activity count, total (P < 0.001) and feeding (P < 0.001) activity AUC compared with sows fed daily at 1530 hours. In conclusion, feeding pregnant sows earlier in the morning (0730 hours) appears to minimize sows’ behavior but similar cortisol response. Sows on 1130 hours feeding schedule had greater activities but reduced cortisol concentration, suggesting that elevated sow activity might not necessarily indicate activation of hypothalamic–pituitary–adrenal axis.
A high-order total-variation regularisation method for full-waveform inversion
Authors: Du Zeyuan , Liu Dingjin , Wu Guochen , Cai Jiexiong , Yu Xin , Hu Guanghui
Published: April 2021

Full-waveform inversion (FWI) is among the most effective methods of velocity modelling in seismic exploration. However, because of the strong nonlinearity of the FWI, if the velocity in the target geobody is not sharply different from that in its surroundings, the total variation (TV) of the model will not be sufficiently sparse. To alleviate this issue, we propose a novel TV-regularised FWI method that can consider the sparsity of the high-order regularisation operator and consequently improve the stability of the inversion process and produce more focused model boundaries. We use a split-Bregman algorithm to solve the inversion optimisation problem while building the TV-regularised objective function. We show that stable model updates can be obtained by this algorithm, which proved to be effective and reliable in the numerical tests. These tests also show that the proposed method converges faster, can model the velocity domain better than conventional methods and can effectively identify layer boundaries with a weak velocity contrast. We conclude that the novel FWI method based on high-order TV regularisation is robust and accurate.
Interpreting the Human Rights Field: A Conversation
Authors: Kunreuther Laura , Acharya Shiva , Hunkins Ann , Karki Sachchi Ghimire , Khadka Hikmat , Sangroula Loknath , Turin Mark , Vasily Laurie
Published: April 2021

This article takes the form of a conversation between an anthropologist and seven interpreters who worked for the UN Office of the High Commissioner for Human Rights (OHCHR) during its mission in Nepal (2005–2011). As any human rights or humanitarian worker knows quite well, an interpreter is essential to any field mission; they are typically the means by which ‘internationals’ are able to speak to any local person. Interpreters make it possible for local events to be transformed into a globally legible register of human rights abuses or cases. Field interpreters are therefore crucial to realizing the global ambitions of any bureaucracy like the UN. Yet rarely do human rights officers or academics (outside of translation studies) hear from interpreters themselves about their experience in the field. This conversation is an attempt to bridge this lacuna directly, in the hope that human rights practitioners and academics might benefit from thinking more deeply about the people upon whom our knowledge often depends.
Guideline adherence for radical cystectomy significantly affects survival outcomes in non-muscle-invasive bladder cancer patients
Authors: Kayama Emina , Shigeta Keisuke , Kikuchi Eiji , Ogihara Koichiro , Hakozaki Kyohei , Iwasawa Tomohiro , Kamisawa Ken , Kanai Kunimitsu , Ide Hiroki , Hara Satoshi , Mizuno Ryuichi , Oya Mototsugu
Published: April 2021

Background

The relationship between guideline adherence for radical cystectomy of non-muscle-invasive bladder cancer and patient prognoses currently remains unclear. We investigated whether guideline adherence at the time of non-muscle-invasive bladder cancer affects the oncological outcomes of bladder cancer patients who underwent radical cystectomy.

Methods

Among 267 cTa-4N0-2M0 bladder cancer patients, 70 who underwent radical cystectomy under the non-muscle-invasive bladder cancer or muscle-invasive bladder cancer status that progressed from non-muscle-invasive bladder cancer were identified. Patients who followed the guidelines from initial transurethral resection of bladder tumors to radical cystectomy were defined as the guideline adherent group (n = 52), while those who did not were the guideline non-adherent group (n = 18).

Results

In the guideline non-adherent group, 8 (44.4%) out of 18 were diagnosed with highest risk non-muscle-invasive bladder cancer for Bacillus Calmette Guérin-naïve patients and 7 (38.9%) had a Bacillus Calmette Guérin unresponsive tumor status. Five-year recurrence-free survival and cancer-specific survival rates for the guideline non-adherent group vs guideline adherent group were 38.9% vs 69.8% (P = 0.018) and 52.7% vs 80.1% (P = 0.006), respectively. A multivariate analysis identified guideline non-adherence as one of independent indicators for disease recurrence (hazard ratio = 2.81, P = 0.008) and cancer-specific death (hazard ratio = 4.04, P = 0.003). In a subgroup analysis of 49 patients with cT1 or less non-muscle-invasive bladder cancer at the time of radical cystectomy, guideline non-adherence remained an independent prognostic factor for cancer-specific survival (hazard ratio = 3.46, P = 0.027).

Conclusions

Guideline adherence during the time course of the non-muscle-invasive bladder cancer stage may result in a favorable prognosis of patients who receive radical cystectomy. Even under non-muscle-invasive bladder cancer status, radical cystectomy needs to be performed with adequate timing under guideline recommendations.
Critical Photoperiod and Its Potential to Predict Mosquito Distributions and Control Medically Important Pests
Authors: Peffers Caitlin S , Pomeroy Laura W , Meuti Megan E
Published: April 2021

Diapause, a period of arrested development that allows mosquitoes to survive inhospitable conditions, is triggered by short daylengths in temperate mosquitoes. Different populations of mosquitoes initiate diapause in response to a specific photoperiod, or daylength, resulting in population-specific differences in annual cycles of abundance. The photoperiod that causes approximately 50% of a population to initiate diapause is known as the critical photoperiod (CPP). The autumn daylength corresponding to the CPP in the field likely marks the day beyond which the photoperiods would trigger and maintain 50% or more diapause incidence in a population, although temperature, diet, and other factors can impact diapause initiation. In the Northern Hemisphere, northern populations of mosquitoes experience lower temperatures earlier in the year and must be triggered into diapause by longer daylengths than southern populations. CPP is genetically based, but also adapts over time responding to the population’s environment. Therefore, CPP has been shown to lengthen with increasing latitude and altitude. While the positive correlation between CPP and latitude/altitude has been established in a few mosquito species, including Aedes albopictus (Skuse, Diptera: Culicidae), Aedes triseriatus, Aedes sierrensis, and Wyeomyia smithii (Coquillett, Diptera: Culicidae), we do not know when most other species initiate their seasonal responses. As several of these species transmit important diseases, characterizing the CPP of arthropod vectors could improve existing control by ensuring that surveillance efforts align with the vector’s seasonally active period. Additionally, better understanding when mosquitoes and other vectors initiate diapause can reduce the frequency of chemical applications, thereby ameliorating the negative impacts to nontarget insects.
Numerical convergence of hot-Jupiter atmospheric flow solutions
Authors: Skinner J W , Cho J Y-K
Published: April 2021

We perform an extensive study of numerical convergence for hot-Jupiter atmospheric flow solutions in simulations employing a setup commonly used in extrasolar planet studies – a resting state thermally forced to a prescribed temperature distribution on a short time-scale at high altitudes. Convergence is assessed rigorously with (i) a highly accurate pseudospectral model that has been explicitly verified to perform well under hot-Jupiter flow conditions and (ii) comparisons of the kinetic energy spectra, instantaneous (unaveraged) vorticity fields and temporal evolutions of the vorticity field from simulations that are numerically equatable. In the simulations, the (horizontal as well as vertical) resolution, dissipation operator order, and viscosity coefficient are varied with identical physical and initial setups. All of the simulations are compared against a fiducial reference simulation at high horizontal resolution and dissipation order (T682 and ∇ 16, respectively) – as well as against each other. Broadly, the reference solution features a dynamic, zonally (east–west) asymmetric jet with a copious amount of small-scale vortices and gravity waves. Here, we show that simulations converge to the reference simulation only at T341 resolution and with ∇ 16 dissipation order. Below this resolution and order, simulations either do not converge or converge to unphysical solutions. The general convergence behaviour is independent of the vertical range of the atmosphere modelled, from $\sim 2 \times 10^{-3}$MPa to   $\sim 2 \times 10^1$ MPa. Ramifications for current extrasolar planet atmosphere modelling and observations are discussed.
Magnetohydrodynamic convection in accretion discs
Authors: Held Loren E , Latter Henrik N
Published: April 2021

Convection has been discussed in the field of accretion discs for several decades, both as a means of angular momentum transport and also because of its role in controlling discs’ vertical structure via heat transport. If the gas is sufficiently ionized and threaded by a weak magnetic field, convection might interact in non-trivial ways with the magnetorotational instability (MRI). Recently, vertically stratified local simulations of the MRI have reported considerable variation in the angular momentum transport, as measured by the stress to thermal pressure ratio α, when convection is thought to be present. Although MRI turbulence can act as a heat source for convection, it is not clear how the two instabilities will interact dynamically. Here, we investigate their interplay in controlled numerical experiments and isolate the generic features of their interactions. We perform vertically stratified, 3D magnetohydrodynamic shearing box simulations with a perfect gas equation of state with the conservative, finite-volume code pluto. We find two characteristic outcomes of the interaction between the two instabilities: (a) straight MRI and (b) MRI/convective cycles, with the latter exhibiting alternating phases of convection-dominated and MRI-dominated flow. During the latter phase, we find that α is enhanced by nearly an order of magnitude, reaching peak values of ∼0.08. In addition, we find that convection in the non-linear phase takes the form of large-scale and oscillatory convective cells. Convection can also help the MRI persist to lower Rm than it would otherwise do. Finally, we discuss how our results help interpret simulations of dwarf novae.
Interacting galaxies in the IllustrisTNG simulations – III. (The rarity of) quenching in post-merger galaxies
Authors: Quai Salvatore , Hani Maan H , Ellison Sara L , Patton David R , Woo Joanna
Published: April 2021

Galaxy mergers are traditionally one of the favoured mechanisms for the transformation of spiral galaxies to spheroids and for quenching star formation. To test this paradigm in the context of modern cosmological simulations, we use the IllustrisTNG simulation to investigate the impact of individual merger events on quenching star formation [i.e. star formation rate (SFR) at least 3σ below the star-forming main sequence] within 500 Myr after the coalescence phase. The rate of quenching amongst recently merged galaxies is compared with a control sample that is matched in redshift, stellar mass, SFR, black hole mass, and environment. We find quenching to be uncommon among the descendants of post-merger galaxies, with only ${\sim} 5{{\ \rm per\ cent}}$ of galaxies quenching within 500 Myr after the merger. Despite this low absolute rate, we find that quenching occurs in post-mergers at twice the rate of the control galaxies. The fraction of quenched post-merger descendants 1.5 Gyr after the merger become statistically indistinguishable from that of non-post-mergers, suggesting that mergers could speed up the quenching process in those post-mergers whose progenitors had physical conditions able to sustain effective active galactic nuclei (AGN) kinetic feedback, thus capable of removing gas from galaxies. Our results indicate that although quenching does not commonly occur promptly after coalescence, mergers none the less do promote the cessation of star formation in some post-mergers. We find that, in IllustrisTNG, it is the implementation of the AGN kinetic feedback that is responsible for quenching post-mergers, as well as non-post-merger controls. As a result of the released kinetic energy, galaxies experience gas loss and eventually they will quench. Galaxies with an initially low gas fraction show a preferable pre-disposition towards quenching. The primary distinguishing factor between quenched and star-forming galaxies is gas fraction, with a sharp boundary at fgas ∼ 0.1 in TNG.
Vestiges of the Bacterial Signal Recognition Particle-Based Protein Targeting in Mitochondria
Authors: Pyrih Jan , Pánek Tomáš , Durante Ignacio Miguel , Rašková Vendula , Cimrhanzlová Kristýna , Kriegová Eva , Tsaousis Anastasios D , Eliáš Marek , Lukeš Julius
Published: April 2021

The main bacterial pathway for inserting proteins into the plasma membrane relies on the signal recognition particle (SRP), composed of the Ffh protein and an associated RNA component, and the SRP-docking protein FtsY. Eukaryotes use an equivalent system of archaeal origin to deliver proteins into the endoplasmic reticulum, whereas a bacteria-derived SRP and FtsY function in the plastid. Here we report on the presence of homologs of the bacterial Ffh and FtsY proteins in various unrelated plastid-lacking unicellular eukaryotes, namely Heterolobosea, Alveida, Goniomonas, and Hemimastigophora. The monophyly of novel eukaryotic Ffh and FtsY groups, predicted mitochondrial localization experimentally confirmed for Naegleria gruberi, and a strong alphaproteobacterial affinity of the Ffh group, collectively suggest that they constitute parts of an ancestral mitochondrial signal peptide-based protein-targeting system inherited from the last eukaryotic common ancestor, but lost from the majority of extant eukaryotes. The ability of putative signal peptides, predicted in a subset of mitochondrial-encoded N. gruberi proteins, to target a reporter fluorescent protein into the endoplasmic reticulum of Trypanosoma brucei, likely through their interaction with the cytosolic SRP, provided further support for this notion. We also illustrate that known mitochondrial ribosome-interacting proteins implicated in membrane protein targeting in opisthokonts (Mba1, Mdm38, and Mrx15) are broadly conserved in eukaryotes and nonredundant with the mitochondrial SRP system. Finally, we identified a novel mitochondrial protein (MAP67) present in diverse eukaryotes and related to the signal peptide-binding domain of Ffh, which may well be a hitherto unrecognized component of the mitochondrial membrane protein-targeting machinery.
Evolutionary economics under nonconvexity and externalities
Authors: Chavas Jean-Paul , Wang Runhao
Published: April 2021

This article examines the evolutionary behavior of boundedly rational agents under nonconvexity and externalities. While allowing for technical and allocative inefficiency, we evaluate how producer and consumer behavior can use evolutionary rules that eventually lead to Pareto efficient allocations. We study how markets can support the convergence to efficiency, stressing that externalities and nonconvexity can require nonlinear pricing. In an evolutionary economy, we show how pricing and decentralized decisions can support moves toward Pareto efficiency under bounded rationality, nonconvexity and externalities.
Development of a TaqMan PCR assay for the identification of the non-native copepodAcartia tonsa, and detection of this species in Norwegian coastal waters
Authors: Moseid Camilla V S , Falkenhaug Tone , Slettan Audun
Published: April 2021

Molecular based assays for detection of species are a powerful tool to supplement morphological methods that may be time and labor intensive. Here we describe a sensitive TaqMan real time polymerase chain reaction assay that specifically detects the presence of Acartia tonsa in mixed plankton samples. The assay is used to find this non-native copepod in samples collected in Norwegian coastal waters.
Persistent Blessings of Luck: Theory and an Application to Venture Capital
Authors: Cong Lin William , Xiao Yizhou
Published: April 2021

Persistent performance in venture capital is routinely interpreted as evidence for skill. We present a dynamic model of delegated investment with endogenous fund heterogeneity and deal flow, which generates performance persistence without skill differences and predicts mean reversion in long-term performance. Investors working with multiple funds use contingent payments and tiered contracts to induce proper project nurturing and managerial effort. Successful funds receive continuation contracts that tolerate investment failure and encourage innovation, and subsequently finance entrepreneurs through a path-dependent assortative matching favoring incumbents. Recent empirical findings corroborate the model’s general implications, and the economic mechanisms are robust to short-term contracting, endogenous bargaining, and double moral hazard issues.
Collision-avoidance path planning for multi-ship encounters considering ship manoeuvrability and COLREGs
Authors: He Yixiong , Li Zhaoran , Mou Junmin , Hu Weixuan , Li Liling , Wang Bing
Published: April 2021

Ship collision prevention has always been a hot topic of research for navigation safety. Recently, autonomous ships have gained much attention as a means of solving collision problems by machine control with a collision-avoidance algorithm. An important question is how to determine optimal path planning for autonomous ships. This paper proposes a path-planning method of collision avoidance for multi-ship encounters that is easy to realize for autonomous ships. The ship course-control system uses fuzzy adaptive proportion-integral-derivative (PID) control to achieve real-time control of the system. The automatic course-altering process of the ship is predicted by combining the ship-motion model and PID controller. According to the COLREGs, ships should take different actions in different encounter situations. Therefore, a scene-identification model is established to identify these situations. To avoid all the TSs, the applicable course-altering range of the OS is obtained by using the improved velocity obstacle model. The optimal path of collision avoidance can be determined from an applicable course-altering range combined with a scene-identification model. Then, the path planning of collision avoidance is realized in the multi-ship environment, and the simulation results show a good effect. The method conforms to navigation practice and provides an effective method for the study of collision avoidance.
Sensitivity of Rhizoctonia solani Anastomosis Group 2-2 Isolates from Soybean and Sugar Beet to Selected SDHI and QoI Fungicides
Authors: Sharma Pratibha , Malvick Dean K. , Chanda Ashok K.
Published: April 2021

Rhizoctonia solani causes root and stem diseases on soybean and sugar beet, and fungicides are commonly used to manage these diseases. Quinone outside inhibitor (QoI) fungicides (pyraclostrobin and azoxystrobin) have been used for in-furrow and postemergence application since 2000. Succinate dehydrogenase inhibitor (SDHI) fungicides (sedaxane, penthiopyrad, and fluxapyroxad) became popular seed treatments after their registration in Minnesota and North Dakota between 2012 and 2016. Periodic monitoring of sensitivity to these fungicides in R. solani anastomosis group (AG) 2-2 is important to detect potential shifts in sensitivity over time. R. solani AG 2-2 isolates (n = 35) collected from soybean and sugar beet in Minnesota and North Dakota were evaluated in vitro for sensitivity. Isolates were considered as baseline or nonbaseline for the above-mentioned fungicides based on previous potential exposure. The effective concentration (EC50) required to suppress radial fungal growth by 50% was determined. The mean EC50 values for sedaxane, penthiopyrad, fluxapyroxad, and pyraclostrobin were 0.1, 0.15, 0.16, and 0.25 (µg ml−1), respectively. The mean EC50 value for azoxystrobin for 22 isolates was 0.76 to 1.56 µg ml−1; and EC50 could not be determined for 13 isolates because of <50% inhibition at the highest concentrations used. The EC50 values for the QoI fungicides did not differ significantly between baseline and nonbaseline isolates. EC50 values for SDHI fungicides were significantly higher for isolates collected from soybean than from sugar beet, and isolates collected from both crops had similar EC50 values for pyraclostrobin. All SDHI fungicides and pyraclostrobin effectively suppressed R. solani isolates from soybean and sugar beet at low concentrations in vitro.
BRAIN PERIVASCULAR MACROPHAGES CONTRIBUTE TO THE DEVELOPMENT OF HYPERTENSION THROUGH SYMPATHETIC ACTIVATION IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Shinohara Keisuke , Iyonaga Takeshi , Hirooka Yoshitaka , Tsutsui Hiroyuki
Published: April 2021

Objective:

Hypertension is associated with systemic inflammation. The activation of the sympathetic nervous system is critically involved in the pathogenesis of hypertension. Brain perivascular macrophages (PVMs) can be affected by circulating inflammatory cytokines and contribute to sympathoexcitaion in a heart failure model. We thus investigated whether brain PVMs contribute to the development of hypertension through sympathoexcitation.

Design and method:

We measured blood pressure and evaluated the number of brain PVMs and the plasma levels of proinflammatory cytokines in stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar–Kyoto rats (WKY) at the ages of 4, 8, and 12 weeks. To determine the contribution of brain PVMs to blood pressure elevation, we intracerebroventricularly injected liposome-encapsulated clodronate, which eliminates macrophages by inducing apoptosis, or vehicle into 8-week-old SHRSP and WKY; we then assessed its effects in 10-week-old rats. We also investigated the effects of clodronate treatment on responses to the acute intravenous injection of proinflammatory cytokines in WKY.

Results:

SHRSP developed hypertension over 8 weeks from 4 to 12 weeks of age. The number of brain PVMs and plasma interleukin-1β levels significantly increased at the ages of 8 and 12 weeks in SHRSP compared with WKY. Clodronate treatment attenuated the increase in blood pressure in SHRSP (δmean blood pressure, 11.6 ± 3.8 mmHg vs. 23.8 ± 1.9 mmHg; clodronate vs. vehicle, n = 7, p < 0.05) but not in WKY. Clodronate treatment reduced the depressor effect of hexamethonium, an index of sympathetic activity; it also reduced the neuronal activity marker c-Fos in sympathetic regulatory nuclei such as the hypothalamic paraventricular nucleus and rostral ventrolateral medulla and reduced the expression of cyclooxygenase-2 and prostaglandin E2, a downstream pathway in activated macrophages, in SHRSP but not in WKY. Furthermore, clodronate treatment attenuated the increase in blood pressure and renal sympathetic nerve activity (RSNA) in response to an acute intravenous injection of interleukin-1β in WKY (δmean blood pressure, 8.8 ± 2.5 mmHg vs. 21.2 ± 4.6 mmHg; integrated RSNA, 125.6 ± 10.4 % vs. 213.1 ± 22.2 %; clodronate vs vehicle, n = 5, p < 0.05).

Conclusions:

Brain PVMs contribute to the development of hypertension via sympathetic activation. PVMs may be activated by increased levels of circulating interleukin-1β.
ORTHOSTATIC BLOOD PRESSURE CHANGES AND SUBCLINICAL MARKERS OF ATHEROSCLEROSIS IN NORMOTENSIVE ADULTS. RESULTS FROM A NATIONAL-REPRESENTATIVE SURVEY
Authors: Fronea Oana Florentina Gheorghe , Darabont Roxana , Pop Calin , Dorobantu Maria
Published: April 2021

Objective:

To evaluate the relationship between orthostatic upright postural blood pressure (BP) changes and subclinical markers of atherosclerosis in normotensive subjects using a simple 3-minutes standing up test.

Design and method:

A total of 1081 normotensive subjects enrolled in SEPHAR III national-representative survey, aged 18–80 years (42,4 ± 16.7 years, 55,3% females) underwent a simple 3 standing-up test involving BP measurement in supine position followed by BP measurements at 1 minute and 3 minutes after standing. We measured: aortic pulse wave velocity (PWVao) using a sfigmomanometric method (Arteriograph), body mass index (BMI), serum lipids, glyceated hemoglobin (HbA1c), urinary albumin-to-creatinine ratio (UACR) in morning spot urine and mean carotid intima-media thickness (IMT) by B-mode Doppler ultrasound. Orthostatic hypotension (OH) was defined by SBP decrease of at least 20mmHg and/or DBP decrease of at least 10mmHg, at 3 minutes after standing.

Results:

SBP and DBP increased when standing, with an average increase of SBP/DBP values when changing position of 3.7 ± 19.5 mm Hg / 9.6 ± 13.5 mm Hg at 1 minutes and 2.9 ± 19.2 mm Hg / 10.1 ± 13.2 mm Hg. Orthostatic hypotension (OH) was recoded in 130 subjects representing 12,4% of the study sample. The PWVao was significantly higher in OH subjects than in those without OH (9,12 ± 2.13m/s vs 8.08 ± 1.86m/s, p = 0,032). Stepwise regression analysis adjusted for age, sex, BMI, baseline SBP, triglycerides, HDL- cholesterol, LDL- cholesterol, fasting glucose, HbA1c, IMT, UACR and PWVao confirmed that PWVao, LDL-cholesterol and TG were independently related to orthostatic BP changes. Multiple regression analyses showed that age, baseline SBP, decrease in SBP at 3-minutes, BMI and fasting glucose were independent determinants of PWVao.

Conclusions:

Our results have shown that increased arterial stiffness is associated with OH during a 3- minutes standing-up test. Also, arterial stiffness may contribute to greater BP responses to postural changes from standing in normotensive subjects.
CIRCULATING METABOLIC BIOMARKERS AS POTENTIAL LEADS FOR GLOBAL PREVENTION OF RENAL DYSFUNCTION – A FLEMISH COHORT STUDY
Authors: Zhang Zhen -Yu , Marrachelli Vannina , Yang Wen-Yi , Thijs Lutgarde , Monleon Daniel , Verhamme Peter , Redón Josep , Staessen Jan
Published: April 2021

Objective:

Studies of people with normal or slightly impaired renal function offer a unique setting to explore the metabolic profiles associated with the early renal dysfunction.

Design and method:

In 578 randomly recruited Flemish, we assessed at a 5 year interval the multivariable-adjusted associations of estimated glomerular filtration rate (eGFR, ml/min/1.73 m2) with 43 circulating metabolites quantified by non-targeted nuclear magnetic resonance spectroscopy. Significance of associations, expressed per 1-SD increment in the metabolites, were Bonferroni corrected.

Results:

At baseline (2005–2010), glycine was associated with a 1.81 lower eGFR (P = 0.011). At follow-up (2009–2013), threonine (-2.14) and glycine (-1.73) were cross-sectionally associated with lower eGFR (P < = 0.02) and aspartate (+2.23), leucine (+2.30) and 2 aminobutyrate (+2.12) with higher eGFR (P < = 0.0033). At follow-up, the odds ratio of having eGFR < 60 was 1.62 for threonine and 1.44 for glycine (P < = 0.039). Partial least squares analyses of baseline and follow-up data were confirmatory. For baseline glycan N acetylglucosamine residues (GlycA), a marker of systemic inflammation, the odds ratio of progressing towards follow-up eGFR < 60 vs. non-progressing (n = 49 vs. 529) was 1.85 (P = 0.0086). Baseline GlycA was a better predictor than 24 h microalbuminuria, increasing (P < = 0.0001) the integrated discrimination (+3.4%) and net reclassification (+40.1%) indexes. Pathway analysis pointed to aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, valine, leucine and isoleucine metabolism, and glycolysis or gluconeogenesis.

Conclusions:

The glycine to threonine pathway and systemic inflammation as reflected by GlycA are markers of early renal dysfunction, whereas protection against oxidative stress and anaplerotic energy supply from the catabolism of branched amino acids (leucine) might be protective.
THE ERYTHROCYTE MEMBRANES BETA-ADRENOREACTIVITY CHANGES AFTER RENAL DENERVATION AS A PROGNOSTIC FACTOR FOR THE LONG-TERM ANTIHYPERTENSIVE EFFICACY OF THE INTERVENTION
Authors: Zyubanova Irina , Falkovskaya Alla , Mordovin Viktor , Manukyan Masheg , Pekarskiy Stanislav , Lichikaki Valeria , Rebrova Tatyana , Afanasiev Sergej
Published: April 2021

Objective:

To study the functional state of the sympathoadrenal system (SAS) assessed by the erythrocyte membranes beta-adrenoreactivity (beta-ARM) level, 7 days and 2 years after renal denervation (RD), to assess the prognostic capabilities of this indicator in relation to the long-term antihypertensive efficacy of the treatment.

Design and method:

The study included 48 patients, 18 men and 30 women with resistant hypertension (RH) on stable antihypertensive therapy. The levels of mean daily systolic (SBP) and diastolic blood pressure (DBP), and level of beta-ARM at baseline, 7 days and 2 years after RD were studied. The beta-ARM determination based on erythrocytes hemolysis inhibition by the beta-blocker adding in hypoosmotic medium, that prevents their destruction by binding to erythrocyte membranes beta-adrenergic receptors. An increase in the beta-ARM value reflects a decrease in erythrocyte membranes beta-adrenergic receptors number on the background of prolonged sympathetic hyperactivation.

Results:

The average daily blood pressure levels decreased from 160.4 ± 16.0/88.1 ± 14.6 mm Hg to 145.3 ± 19.3/79.4 ± 13.6 mm Hg (p = 0.000) for 2 years. The beta-ARM dynamics was as follows: 43.8 ± 19.9 conventional units (CE) initially, decreased to 40.5 ± 17.0 CE after 7 days (p > 0.05), and increased to 55.3 ± 19.0 CE (p = 0.008) after 2 years. At the same time, the beta-ARM decrease after 7 days was significant in the responders group (p = 0.028), whose blood pressure after 2 years decreased by 10 mm Hg or more, and was absent in the non-responders group. There was a correlation between the dynamics of beta-ARM after 7 days and SBP and DBP after 2 years (r = -0.54, p < 0.05). This makes it possible to predict the RD long-term effectiveness.

Conclusions:

The decrease in beta-ARM 7 after RD indicates the effectiveness of the procedure and allows us to expect a significant blood pressure decrease in the long term after surgery. Nevertheless, 2 years after RD a decrease in the erythrocyte membranes adrenergic receptors density is observed, probably through a negative feedback mechanism in response to ongoing sympathetic stimulation even against the background of a blood pressure decrease
LONG TERM BENEFITS OF BLOOD PRESSURE TREATMENT ON THE INCIDENCE OF ATRIAL FIBRILLATION, HEART FAILURE AND CARDIOVASCULAR MORBIDITY AND MORTALITY: 20-YEARS FOLLOW-UP OF ASCOT-LEGACY
Authors: Gupta Ajay , Whiteley William , Godec Thomas , Rostamian Somayeh , Whitehouse Andrew , Mackay Judith , Sever Peter
Published: April 2021

Objective:

Previously, we reported 16-year cardiovascular (CV) mortality associated with either atenolol- or amlodipine-based treatment regimen; but without data on non-fatal CV events. We now report longer morbidity and mortality including the impact of BP-treatment on the incidence of atrial fibrillation and heart failure

Design and method:

In the ASCOT-Legacy Study, 8580 hypertensive patients (4275 assigned to atenolol+/-diuretic-based and 4305 to amlodipine+/-perindopril-based treatment) were followed in the UK for the maximum duration of 21 years (IQR: 9.1–19.3 years). All fatal/non-fatal CV events during the trial period and the post-trial mortality events were independently adjudicated. Post-trial morbidity events were evaluated using electronic health records. Cox proportional hazards were estimated for the first occurrence of atrial fibrillation, fatal/non-fatal HF, non-fatal/fatal stroke (stroke), non-fatal /fatal-coronary heart disease (CHD), total coronary events and total CV events in two treatment arms. Analyses were adjusted for a-priori confounders (See table). Interaction, if any, with associated statin therapy was evaluated. We also did a sensitivity analysis using only post-trial data.

Results:

During the in-trial period of 5.5 years, the cumulative mean SBP was marginally higher for those on atenolol-based treatment compared to those on amlodipine-based treatment (138.0 [SD,10.8] and 136.3 [9.9] mm Hg, respectively). Table 1 shows the crude and adjusted hazard ratios (HRs) associated with the two treatment regimens. Those on amlodipine-based (vs. atenolol-based) treatment had significantly reduced risk of atrial fibrillation [0.91, 95% CI, 0.83 to 0.99], total coronary events [092, 0.86 to 0.99], stroke [0.82, 0.72 to 0.93] and total CV events [0.93, 0.88 to 0.98]. There was no significant difference in the incidence of heart failure or CHD, although there was a nominal reduction. No evidence of interaction with statin therapy was noted. Post-trial significant differences were apparent for stroke, total coronary events and total CV events.

Conclusions:

Allocation to an amlodipine-based treatment has a long-term beneficial CV effect, particularly on stroke and total coronary and CV events. Reduction in the risk new-onset atrial fibrillation may be an important mediator of this legacy effect.
SAFETY, PHARMACODYNAMICS, AND BLOOD PRESSURE EFFECTS OF ALN-AGT, AN RNA INTERFERENCE THERAPEUTIC TARGETING ANGIOTENSINOGEN, IN A RANDOMIZED SINGLE ASCENDING DOSE STUDY OF HYPERTENSIVE ADULTS
Authors: Huang Stephen A. , Taubel Jorg , Fiore Giuseppe , Dewland Peter , Webb David J. , Bakris George L. , Desai Akshay S. , Cheng Yansong , Agarwal Sagar , Harrop Jamie , Nguyen Huy V. , Lu Jiandong , Foster Don , Fujita Kenji
Published: April 2021

Objective:

Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides and plays a key role in hypertension pathogenesis. We evaluated the effect of ALN-AGT, a subcutaneous investigational RNA interference (RNAi) therapeutic targeting hepatic AGT synthesis, on blood pressure in hypertensive patients.

Design and Method:

As part of a phase 1 program designed to assess the safety and tolerability of ALN-AGT, we conducted a multicenter study randomizing patients aged 18–65 years with mild to moderate hypertension (mean seated systolic blood pressure [SBP] of > 130 and ?165 mmHg after washout of antihypertensive medication) 2:1 to ascending single doses of ALN-AGT or placebo. Change from baseline in BP at 8 weeks was measured by ambulatory BP monitoring (ABPM). We report interim results as of Oct 27, 2020.

Design and method:

Eighty-four patients (mean age 53 years, 39% female, mean baseline 24 h SBP 139.7 +/- 8.9 mm Hg) were enrolled in ascending dose cohorts of 10 mg, 25 mg, 50 mg, 100 mg, 200 mg, 400 mg or 800 mg. Dose-related reductions in serum AGT levels were observed (figure), with mean reductions of > 90% at doses ?100 mg. AGT remained durably reduced through 12 weeks after single dose administration (data pending for 800 mg cohort). Concomitant reductions in BP from baseline were observed with AGT knockdown, with mean reductions in 24-hour SBP of > 10 mm Hg observed at Week 8 after single doses of 100 mg or higher. No treatment-related serious adverse events or clinically significant elevations in blood creatinine or potassium were seen. No patient required intervention for low blood pressure.

Results:

Single dose administration of ALN-AGT to hypertensive patients was generally well tolerated and resulted in dose-related reductions in serum AGT and BP over 8 weeks. Durable AGT knockdown to 12 weeks supports further evaluation of once quarterly or potentially less frequent dose administration.
SELF-MONITORING OF BLOOD PRESSURE IN WOMEN WITH PREGNANCY HYPERTENSION: THE BUMP2 MULTICENTRE RANDOMISED CONTROLLED TRIAL
Authors: Chappell Lucy , Tucker Katherine , Yu Ly-Mee , Mcmanus Richard
Published: April 2021

Objective:

Self-monitoring of blood pressure (BP), in conjunction with co-interventions, is associated with clinically significant BP reduction in the general adult population. No adequately powered trials have been conducted in women with pregnancy hypertension. The BUMP2 trial aimed to evaluate whether BP self-monitoring in women with pregnancy hypertension improved BP control.

Design and method:

This multicentre, non-masked, randomised controlled trial recruited pregnant women with chronic or gestational hypertension up to 37 weeks’ gestation. Participating women were randomised to either BP self-monitoring with telemonitoring and usual care or usual care alone. An app provided real time feedback advising women of appropriate actions to take at each blood pressure threshold. The primary outcome was mean systolic BP between baseline and delivery recorded by a healthcare professional. Secondary outcomes included maternal and perinatal outcomes, quality of life, and adverse maternal and fetal events. A sample size of 512 (256/group) at 90% power was required to detect a 5 mm Hg difference in systolic BP between groups (SD 16 mmHg), assuming 15% attrition, subsequently inflated to allow for analysis by hypertension type. Trial Registration: NCT03334149

Results:

850 women (454 with chronic hypertension (CH) and 396 with gestational hypertension (GH)) were randomised to either BP self-monitoring (CH n = 233; GH n = 197) or usual care (CH n = 221; GH n = 199). Primary outcome data were available from 821 (97%) women. Baseline characteristics were similar. Mean systolic BP between randomisation and delivery was not significantly different in women with chronic hypertension between self-monitoring (mean 133.8 (SD 10.3) mmHg) and usual care (133.6 (11.1) mmHg) groups; mean difference 0.03 (-1.73 to 1.79), p = 0.97 or in women with gestational hypertension (137.6 (12.1) mmHg vs. 137.2 (10.8) mmHg; mean difference -0.03 (-2.29 to 2.24), p = 0.98. There were no differences in other maternal and fetal outcomes or in Serious Adverse Events.

Conclusions:

BP self-monitoring in women with pregnancy hypertension does not improve BP control, but appears to be safe when used alongside usual care. Further work will elucidate whether empowering some women with BP self-monitoring may alter behaviour of clinicians or women in initiating or titrating antihypertensive medications.
ESTABLISHING SERUM REFERENCE RANGES OF ANTIHYPERTENSIVE DRUGS
Authors: Rognstad Stine , Søraas Camilla Lund , Bergland Ola Undrum , Høieggen Aud , Strømmen Magnus , Helland Arne , Opdal Mimi Stokke
Published: April 2021

Objective:

Therapeutic drug monitoring (TDM) is the measurement of serum drug concentrations to optimize pharmacotherapy. Traditionally, blood pressure measurements alone, and not TDM, have been used to evaluate the antihypertensive drug response. However, approximately 50 % of hypertensive patients treated by lifestyle changes and antihypertensive drugs fail to achieve blood pressure control. Serum drug concentration measurements could be useful to select the optimal drugs in adjusted doses and to identify non-adherence. Implementation of TDM in clinical routine for antihypertensive drugs depends on established serum reference ranges.

Design and method:

Commonly used antihypertensive drugs were identified based on prescription data. The authors performed a review of authoritative literature on reported serum drug concentrations and calculated expected concentrations from previously reported pharmacokinetic parameters with commonly prescribed daily doses. Finally, serum drug concentrations in samples from patients undergoing antihypertensive treatment were measured.

Results:

Serum reference ranges for 24 frequently used antihypertensive drugs were established based on results from three approaches and are shown in the table.

Conclusions:

Serum drug concentrations, interpreted in light of the established reference ranges, together with blood pressure measurements and other clinical data, may help identify non-adherent patients and tailor individual antihypertensive treatment when deviant drug responses appear, in line with the concept of personalized medicine.
SELF-TESTING OF BLOOD PRESSURE ACCORDING TO THE DEPISTHTA® PROTOCOL IN THE POPULATION OF THE FRENCH LEAGUE AGAINST HYPERTENSION SURVEY 2019
Authors: Girerd X. , Pathak A. , Vaïsse B. , Hanon O.
Published: April 2021

Objective: The FLAHS 2019 survey was organized to determine the distribution of blood pressure in the adult population over 35 years of age through the use of self-screening.

Design and method: FLAHS surveys are conducted by a self-administered questionnaire sent by mail to individuals from the Kantar Health Metascope permanent sampling frame (panel representing the population living in metropolitan France). Among the positive respondents to the question: Do you have a device to measure blood pressure at home? It was obtained measurements according to the depistHTA® protocol (3 consecutive measurements leaving an interval of 1 minute between each measurement while keeping the sitting position, without getting up between each measurement). The average of the last 2 measurements was taken to define the subject's BP.

Results: Of the 7627 subjects aged 35 and over, 1706 had a blood pressure monitor. Self-testing was possible in 50% of subjects taking antihypertensive treatments (938 subjects) and 15% of untreated patients (767 subjects).

Among the untreated: 18.8% had BP > = 140 or 90; 29.1% had BP > = 135 or 85 and 64.9% had BP > = 120 or 80. Among subjects taking antihypertensive drugs: 64.1% had BP < 140 and 90; 50.4% had BP < 135 and 85 and 14.6% had BP < 120 and 80.

Among untreated people aged 35 to 54 years: 16.1% had BP > = 140 or 90; 25.7% had BP > = 135 or 85 and 59.2% had BP > = 120 or 80.

Among those treated with antihypertensive drugs and aged 35 to 54 years: 68.5% had BP < 140 and 90; 54.8% had BP < 135 and 85 and 25.0% had BP < 120 and 80.

Conclusions: Self-screening for blood pressure is possible in the general population. When the depistHTA® protocol is used, BP > = 140 or 90 is observed in 18.8% of untreated subjects aged 35 and over, or 5 million subjects in metropolitan France. In treated hypertensive patients, BP < 135 and 85 is noted in 50.4% of patients, indicating that control of treated hypertension is not improving in France.

depistHTA® is available on stores.