bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro and in vivo testing of nanofibrous membranes doped with alaptide and L-arginine for wound treatment
Authors: Mikeš Petr , Brož Antonín , Sinica Alla , Asatiani Nikifor , Bačáková Lucie
Published: May 2020

We have prepared a candidate biocompatible construct for skin wound healing based on electrospun polycaprolactone (PCL) nanofibrous membranes. The membrane material was loaded either with L-arginine or with alaptide, or with a mixture of both bioactive components. Alaptide is a spirocyclic synthetic dipeptide, an analogue of melanocyte-stimulating hormone release-inhibiting factor. L-arginine is an amino acid with a basic guanidine side chain. It is a direct precursor of nitric oxide, which plays a pivotal role in skin repair. The presence and the distribution of the additives were proved with high-performance liquid chromatography, Fourier-transform infrared spectroscopy and Raman spectroscopy. The influence of L-arginine and alaptide on the morphology of the membrane was characterized using scanning electron microscopy. No statistically significant correlation between fiber diameter and drug concentration was observed. The membranes were then tested in vitro for their cytotoxicity, using primary human dermal fibroblasts, in order to obtain the optimal concentrations of the additives for in vivo tests in a rat model. The membranes with the highest concentration of L-arginine (10 wt. %) proved to be cytotoxic. The membranes with alaptide in concentrations from 0.1 to 2.5 wt.%, and with the other L-arginine concentrations (1 and 5 wt.%), did not show high toxicity. In addition, there was no observed improvement in cell proliferation on the membranes. The in vivo experiments revealed that membranes with 1.5 wt.% of alaptide or with 1.5 wt.% of alaptide in combination with 5 wt.% of L-arginine markedly accelerated the healing of skin incisions, and particularly the healing of skin burns, i.e. wounds of relatively large extent. These results indicate that our newly-developed nanofibrous membranes are promising for treating wounds with large damaged areas, where a supporting material is needed.
Harmonic extension from the exterior of a cylinder
Authors: Gardiner Stephen , Render Hermann
Published: May 2020

Lethhbe a harmonic function on an annular cylinder. It was recently shown that, ifhhvanishes on the outer cylindrical boundary component, then it has a harmonic extension to a larger annular cylinder formed by radial reflection. This paper shows that a different kind of extension result holds ifhhinstead vanishes on the inner boundary component. As a corollary it is shown that any harmonic function on the exterior of an infinite cylinder which vanishes on the boundary has a harmonic extension to the complement of the axis of the cylinder.
The weighted discrete Gehring classes, Muckenhoupt classes and their basic properties
Authors: Saker Samir , Krnić Mario
Published: May 2020

The main objective of this paper is a study of the structure and basic properties of the weighted discrete Gehring classes, as well as the study of the relationship between discrete Muckenhoupt and Gehring classes. First, we prove that the weighted discrete Muckenhoupt class

A

λ

1

(
C
)

\mathcal {A}_{\lambda }^{1}(C)

,

C
>
1

C>1

, consisting of nonincreasing sequences, belongs to the weighted discrete Gehring class

G

λ

p

(
A
)

\mathcal {G}_{\lambda }^{p}(A)

by giving explicit values of exponent

p
p

and constant

A
A

. Next, we prove the self-improving property of the weighted Gehring class

G

λ

p

(

K
)

\mathcal {G}_{\lambda }^{p}({K)}

,

p
>
1

p>1

,

K
>
1

K>1

, consisting of nonincreasing sequences. The exponent and constant of transition are explicitly given. Finally, utilizing the self-improving property of the weighted Gehring class, we also derive the self-improving property of a discrete Muckenhoupt class

A

p

(
C
)

\mathcal {A}^{p}(C)

,

p
>
1

p>1

,

C
>
1

C>1

, with exact values of exponent and constant of transition.
Mozambique elections 2019: Pernicious polarization, democratic decline, and rising authoritarianism
Authors: Pitcher M Anne
Published: May 2020

Mozambique’s 2019 elections resulted in a landslide victory for the incumbent Frelimo party, but they were also characterized by unprecedented levels of election related violence and other irregularities. The briefing demonstrates that polarization, which has been a common feature of Mozambican politics since independence, has become more pernicious at least since 2013. As is the case in other countries, pernicious polarization is contributing to rising authoritarianism in Mozambique. The briefing traces the roots of pernicious polarization, its shifting dynamics over the last several years, and its impact on the exercise of democratic rights in Mozambique’s recent elections.
Pesticide use is linked to increased body size in a large mammalian carnivore
Authors: Letnic M , Crowther M S
Published: May 2020

Pollution and pesticide use have been linked to evolution of chemical resistance and phenotypic shifts in invertebrates, but less so in vertebrates. Here we provide evidence that poisoning directed towards a mammalian carnivore, the dingo (Canis dingo), is linked to an increase in dingo body mass. We compared the skull length of dingoes, a proxy for size, from three regions where dingo populations were controlled by distributing poisoned meat baits and an unbaited region, before and after the introduction of the toxin sodium fluoroacetate (Compound 1080). Following 1080 introduction, dingo skull length increased in baited regions but not in the unbaited region. We estimate that after 1080 introduction, the skull length of female and male dingoes in baited regions increased by 4.49 and 3.6 mm, respectively. This equates to a 1.02- and 0.86-kg increase in mean body masses of female and male dingoes, respectively. We hypothesize that dingo body size has increased in baited regions due to 1080 selecting for animals with larger body size or because a reduction in dingo abundance in baited areas may have removed constraints on growth imposed by intraspecific competition and prey availability. Our study provides evidence that pesticide use can prompt phenotypic change in comparatively large and long-lived large vertebrates.
Inhibiting an inhibitor: a decoy to recover dexterity after spinal cord injury
Authors: Bradbury Elizabeth J , Oliveira Raquel
Published: May 2020

This scientific commentary refers to ‘Nogo receptor decoy promotes recovery and corticospinal growth in non-human primate spinal cord injury’, by Wang et al. (doi:10.1093/brain/awaa116).
Corollary Discharge Versus Efference Copy: Distinct Neural Signals in Speech Preparation Differentially Modulate Auditory Responses
Authors: Li Siqi , Zhu Hao , Tian Xing
Published: May 2020

Actions influence sensory processing in a complex way to shape behavior. For example, during actions, a copy of motor signals—termed “corollary discharge” (CD) or “efference copy” (EC)—can be transmitted to sensory regions and modulate perception. However, the sole inhibitory function of the motor copies is challenged by mixed empirical observations as well as multifaceted computational demands for behaviors. We hypothesized that the content in the motor signals available at distinct stages of actions determined the nature of signals (CD vs. EC) and constrained their modulatory functions on perceptual processing. We tested this hypothesis using speech in which we could precisely control and quantify the course of action. In three electroencephalography (EEG) experiments using a novel delayed articulation paradigm, we found that preparation without linguistic contents suppressed auditory responses to all speech sounds, whereas preparing to speak a syllable selectively enhanced the auditory responses to the prepared syllable. A computational model demonstrated that a bifurcation of motor signals could be a potential algorithm and neural implementation to achieve the distinct functions in the motor-to-sensory transformation. These results suggest that distinct motor signals are generated in the motor-to-sensory transformation and integrated with sensory input to modulate perception.
Unconscious Number Discrimination in the Human Visual System
Authors: Lucero Ché , Brookshire Geoffrey , Sava-Segal Clara , Bottini Roberto , Goldin-Meadow Susan , Vogel Edward K , Casasanto Daniel
Published: May 2020

How do humans compute approximate number? According to one influential theory, approximate number representations arise in the intraparietal sulcus and are amodal, meaning that they arise independent of any sensory modality. Alternatively, approximate number may be computed initially within sensory systems. Here we tested for sensitivity to approximate number in the visual system using steady state visual evoked potentials. We recorded electroencephalography from humans while they viewed dotclouds presented at 30 Hz, which alternated in numerosity (ranging from 10 to 20 dots) at 15 Hz. At this rate, each dotcloud backward masked the previous dotcloud, disrupting top-down feedback to visual cortex and preventing conscious awareness of the dotclouds’ numerosities. Spectral amplitude at 15 Hz measured over the occipital lobe (Oz) correlated positively with the numerical ratio of the stimuli, even when nonnumerical stimulus attributes were controlled, indicating that subjects’ visual systems were differentiating dotclouds on the basis of their numerical ratios. Crucially, subjects were unable to discriminate the numerosities of the dotclouds consciously, indicating the backward masking of the stimuli disrupted reentrant feedback to visual cortex. Approximate number appears to be computed within the visual system, independently of higher-order areas, such as the intraparietal sulcus.
Increase in Seizure Susceptibility After Repetitive Concussion Results from Oxidative Stress, Parvalbumin-Positive Interneuron Dysfunction and Biphasic Increases in Glutamate/GABA Ratio
Authors: MacMullin Paul , Hodgson Nathaniel , Damar Ugur , Lee Henry Hing Cheong , Hameed Mustafa Q , Dhamne Sameer C , Hyde Damon , Conley Grace M , Morriss Nicholas , Qiu Jianhua , Mannix Rebekah , Hensch Takao K , Rotenberg Alexander
Published: May 2020

Chronic symptoms indicating excess cortical excitability follow mild traumatic brain injury, particularly repetitive mild traumatic brain injury (rmTBI). Yet mechanisms underlying post-traumatic excitation/inhibition (E/I) ratio abnormalities may differ between the early and late post-traumatic phases. We therefore measured seizure threshold and cortical gamma-aminobutyric acid (GABA) and glutamate (Glu) concentrations, 1 and 6 weeks after rmTBI in mice. We also analyzed the structure of parvalbumin-positive interneurons (PVIs), their perineuronal nets (PNNs), and their electroencephalography (EEG) signature (gamma frequency band power). For mechanistic insight, we measured cortical oxidative stress, reflected in the reduced/oxidized glutathione (GSH/GSSG) ratio. We found that seizure susceptibility increased both early and late after rmTBI. However, whereas increased Glu dominated the E/I 1 week after rmTBI, Glu concentration normalized and the E/I was instead characterized by depressed GABA, reduced per-PVI parvalbumin expression, and reduced gamma EEG power at the 6-week post-rmTBI time point. Oxidative stress was increased early after rmTBI, where transient PNN degradation was noted, and progressed throughout the monitoring period. We conclude that GSH depletion, perhaps triggered by early Glu-mediated excitotoxicity, leads to late post-rmTBI loss of PVI-dependent cortical inhibitory tone. We thus propose dampening of Glu signaling, maintenance of redox state, and preservation of PVI inhibitory capacity as therapeutic targets for post-rmTBI treatment.
Associations of Early COVID-19 Cases in San Francisco With Domestic and International Travel
Authors: Gu Wei , Deng Xianding , Reyes Kevin , Hsu Elaine , Wang Candace , Sotomayor-Gonzalez Alicia , Federman Scot , Bushnell Brian , Miller Steve , Chiu Charles Y
Published: May 2020

In early-to-mid March 2020, 20 of 46 (43%) COVID-19 cases at a tertiary care hospital in San Francisco, California were travel related. Cases were significantly associated with travel to either Europe (odds ratio, 6.1) or New York (odds ratio, 32.9). Viral genomes recovered from 9 of 12 (75%) cases co-clustered with lineages circulating in Europe.
Association Between Opioid Agonist Therapy and Testing, Treatment Uptake, and Treatment Outcomes for Hepatitis C Infection Among People Who Inject Drugs: A Systematic Review and Meta-analysis
Authors: Grebely Jason , Tran Lucy , Degenhardt Louisa , Dowell-Day Alexander , Santo Thomas , Larney Sarah , Hickman Matthew , Vickerman Peter , French Clare , Butler Kerryn , Gibbs Daisy , Valerio Heather , Read Phillip , Dore Gregory J , Hajarizadeh Behzad
Published: May 2020

Background

People who inject drugs (PWID) experience barriers to accessing testing and treatment for hepatitis C virus (HCV) infection. Opioid agonist therapy (OAT) may provide an opportunity to improve access to HCV care. This systematic review assessed the association of OAT and HCV testing, treatment, and treatment outcomes among PWID.

Methods

Bibliographic databases and conference presentations were searched for studies that assessed the association between OAT and HCV testing, treatment, and treatment outcomes (direct-acting antiviral [DAA] therapy only) among PWID (in the past year). Meta-analysis was used to pool estimates.

Results

Of 9877 articles identified, 22 studies conducted in Australia, Europe, North America, and Thailand were eligible and included. Risk of bias was serious in 21 studies and moderate in 1 study. Current/recent OAT was associated with an increased odds of recent HCV antibody testing (4 studies; odds ratio (OR), 1.80; 95% confidence interval [CI], 1.36–2.39), HCV RNA testing among those who were HCV antibody–positive (2 studies; OR, 1.83; 95% CI, 1.27–2.62), and DAA treatment uptake among those who were HCV RNA–positive (7 studies; OR, 1.53; 95% CI, 1.07–2.20). There was insufficient evidence of an association between OAT and treatment completion (9 studies) or sustained virologic response following DAA therapy (9 studies).

Conclusions

OAT can increase linkage to HCV care, including uptake of HCV testing and treatment among PWID. This supports the scale-up of OAT as part of strategies to enhance HCV treatment to further HCV elimination efforts.
Influenza Vaccine Does Not Increase the Risk of Coronavirus or Other Noninfluenza Respiratory Viruses: Retrospective Analysis From Canada, 2010–2011 to 2016–2017
Authors: Skowronski Danuta M , Zou Macy , Clarke Quinten , Chambers Catharine , Dickinson James A , Sabaiduc Suzana , Olsha Romy , Gubbay Jonathan B , Drews Steven J , Charest Hugues , Winter Anne-Luise , Jassem Agatha , Murti Michelle , Krajden Mel , De Serres Gaston
Published: May 2020

Influenza vaccine effectiveness against influenza and noninfluenza respiratory viruses (NIRVs) was assessed by test-negative design using historic datasets of the community-based Canadian Sentinel Practitioner Surveillance Network, spanning 2010–2011 to 2016–2017. Vaccine significantly reduced the risk of influenza illness by >40% with no effect on coronaviruses or other NIRV risk.
Farming efficiency, cropland rental market and income effect: evidence from panel data for rural Central Vietnam
Authors: Nguyen Trung Thanh , Tran Viet Tuan , Nguyen Thanh-Tung , Grote Ulrike
Published: May 2020

Understanding the drivers and income effects of land rental markets is important to facilitate agricultural transformation. This study uses a panel dataset of rural households in Vietnam to examine the efficiency, equity and income effects of land rental markets. Probit and tobit models find that land is transferred from less to more efficient farmers and thus removing administrative barriers to the market operation is suggested. However, instrumental variable and quantile regressions show that the poor do not benefit significantly from participation in the markets. This highlights the need to take care of the poor to ensure that they are not left behind. Further analysis might focus on the efficiency thresholds that farmers switch from a market regime to another.
Conducting clinical trials in heart failure during (and after) the COVID-19 pandemic: an Expert Consensus Position Paper from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)
Authors: Anker Stefan D , Butler Javed , Khan Muhammad Shahzeb , Abraham William T , Bauersachs Johann , Bocchi Edimar , Bozkurt Biykem , Braunwald Eugene , Chopra Vijay K , Cleland John G , Ezekowitz Justin , Filippatos Gerasimos , Friede Tim , Hernandez Adrian F , Lam Carolyn S P , Lindenfeld JoAnn , McMurray John J V , Mehra Mandeep , Metra Marco , Packer Milton , Pieske Burkert , Pocock Stuart J , Ponikowski Piotr , Rosano Giuseppe M C , Teerlink John R , Tsutsui Hiroyuki , Van Veldhuisen Dirk J , Verma Subodh , Voors Adriaan A , Wittes Janet , Zannad Faiez , Zhang Jian , Seferovic Petar , Coats Andrew J S
Published: May 2020

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has important implications for the safety of participants in clinical trials and the research staff caring for them and, consequently, for the trials themselves. Patients with heart failure may be at greater risk of infection with COVID-19 and the consequences might also be more serious, but they are also at risk of adverse outcomes if their clinical care is compromised. As physicians and clinical trialists, it is our responsibility to ensure safe and effective care is delivered to trial participants without affecting the integrity of the trial. The social contract with our patients demands no less. Many regulatory authorities from different world regions have issued guidance statements regarding the conduct of clinical trials during this COVID-19 crisis. However, international trials may benefit from expert guidance from a global panel of experts to supplement local advice and regulations, thereby enhancing the safety of participants and the integrity of the trial. Accordingly, the Heart Failure Association of the European Society of Cardiology on 21 and 22 March 2020 conducted web-based meetings with expert clinical trialists in Europe, North America, South America, Australia, and Asia. The main objectives of this Expert Position Paper are to highlight the challenges that this pandemic poses for the conduct of clinical trials in heart failure and to offer advice on how they might be overcome, with some practical examples. While this panel of experts are focused on heart failure clinical trials, these discussions and recommendations may apply to clinical trials in other therapeutic areas.
Mapping interventional cardiology in Europe: the European Association of Percutaneous Cardiovascular Interventions (EAPCI) Atlas Project
Authors: Barbato Emanuele , Noc Marko , Baumbach Andreas , Dudek Dariusz , Bunc Matjaz , Skalidis Emmanouil , Banning Adrian , Legutko Jacek , Witt Nils , Pan Manuel , Tilsted Hans-Henrik , Nef Holger , Tarantini Giuseppe , Kazakiewicz Dzianis , Huculeci Radu , Cook Stephane , Magdy Ahmed , Desmet Walter , Cayla Guillaume , Vinereanu Dragos , Voskuil Michiel , Goktekin Omer , Vardas Panos , Timmis Adam , Haude Michael
Published: May 2020

Aims

The European Association of Percutaneous Cardiovascular Interventions (EAPCI) Atlas of Interventional Cardiology has been developed to map interventional practice across European Society of Cardiology (ESC) member countries. Here we present the main findings of a 16-country survey in which we examine the national availability of interventional infrastructure, human resource, and procedure volumes.

Methods and results

Sixteen ESC member countries participated in the EAPCI Atlas survey. Interventional data were collected by the National Cardiac Society of each participating country. An annual median of 5131 [interquartile range (IQR) 4013–5801] diagnostic heart procedures per million people were reported, ranging from <2500 in Egypt and Romania to >7000 in Turkey and Germany. Procedure rates showed significant correlation (r = 0.67, P = 0.013) with gross national income (GNI) per capita. An annual median of 2478 (IQR 1690–2633) percutaneous coronary interventions (PCIs) per million people were reported, ranging from <1000 in Egypt and Romania to >3000 in Switzerland, Poland, and Germany. Procedure rates showed significant correlation with GNI per capita (r = 0.62, P = 0.014). An annual median of 48.2 (IQR 29.1–105.2) transcatheter aortic valve implantation procedures per million people were performed, varying from <25 per million people in Egypt, Romania, Turkey, and Poland to >100 per million people in Denmark, France, Switzerland, and Germany. Procedure rates showed significant correlation with national GNI per capita (r = 0.92, P < 0.001).

Conclusion

The first report from the EAPCI Atlas has shown considerable international heterogeneity in interventional cardiology procedure volumes. The heterogeneity showed association with national economic resource, a reflection no doubt of the technological costs of developing an interventional cardiology service.
Prevalence of sudden arrhythmic death syndrome-related genetic mutations in an Asian cohort of whole genome sequence
Authors: Huang Pang-Shuo , Hsieh Chia-Shan , Chang Sheng-Nan , Chen Jien-Jiun , Chiu Fu-Chun , Wu Cho-Kai , Hwang Juey-Jen , Chuang Eric Y , Tsai Chia-Ti
Published: May 2020

Aims

Recently, the spectrum of background mutation in the genes implicated in sudden arrhythmic death syndrome (SADS), has been elucidated in the Caucasian populations. However, this information is largely unknown in the Asian populations.

Methods and results

We assessed the background rare variants (minor allele frequency < 0.01) of major SADS genes in whole genome sequence data of 1514 healthy Taiwanese subjects from the Taiwan Biobank. We found up to 45% of healthy subjects have a rare variant in at least one of the major SADS genes. Around 3.44% of healthy subjects had multiple mutations in one or multiple genes. The background mutation rates in long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and arrhythmogenic right ventricular cardiomyopathy genes were similar, but those in Brugada syndrome (BrS) (SCN5A) and hypertrophic cardiomyopathy (HCM) genes (MYBPC3, MYH7, and TNNT2) were higher, compared to those reported in the Caucasian populations. Furthermore, the rate of incidental pathogenic variant was highest in MYBPC3 gene. Finally, the number of variant was proportional to the exon length of the gene (R2 = 0.486, P = 0.0056) but not related to its functional or evolutionary importance (degree of evolutionary conservation) (R2 = 0.0008, P = 0.9218), suggesting that the mutation was random. The ratio of variant number over exon nucleotide length was highest in MYBPC3, MYH7, and TNNT2 genes.

Conclusion

Unique features of background SADS gene mutation in the Asian populations include higher prevalence of incidental variant in HCM, BrS, and long QT 3 (SCN5A) genes. HCM genes have the highest variant number per exon length.
A patient-centredness improvement study for efficacy of behaviour change for healthy lifestyle and weight loss in a student-run free clinic
Authors: Lessans Spencer , Vega Xamil , Foley Brandon , Bossan Alexia , Baker Alexandra , McElroy Mitchell , Crouse Eloisa , Pasarica Magdalena
Published: May 2020

Background

Primary care is the ideal place to implement behaviour change interventions for weight management. However, most primary care physicians are not managing patient weight as a standard of care due to lack of knowledge, skills and reimbursement. Generating more physicians who are familiar and comfortable with providing weight management is essential in leveraging a global change. In our university free clinic, medical students provide healthy lifestyle counselling using shared decision making to each patient at every clinic visit.

Objective

Improve the efficacy of behaviour change interventions via increased patient responsiveness and adherence.

Methods

The needs assessment demonstrated a subpar patient response rate to check-ins regarding behavioural change goals. In the first and second interventions, check-in message structure and contact schedule were varied to maximize patient responsiveness and goal achievement.

Results

In the needs assessment, 58% of patients responded to follow-ups and 58% of patients accomplished their goal. The first intervention cycle resulted in an improvement of responsiveness to 70% and accomplishment of goals to 59%. The second intervention cycle resulted in an improvement of responsiveness to 78% and accomplishment of goals to 74%.

Conclusions

Messages that were frequent, unique, succinct and delivered within 4 weeks after the clinic visit resulted in the highest response rate and goal attainment. Other primary care clinics can use these interventions to increase patient completion of implemented behaviour changes for a healthier lifestyle.
Dynamo-based limit to the extent of a stable layer atop Earth’s core
Authors: Gastine Thomas , Aubert Julien , Fournier Alexandre
Published: May 2020

The existence of a stably stratified layer underneath the core–mantle boundary (CMB) has been recently revived by corroborating evidences coming from seismic studies, mineral physics and thermal evolution models. Such a layer could find its physical origination either in compositional stratification due to the accumulation of light elements at the top or the core or in thermal stratification due to the heat flux becoming locally subadiabatic. The exact properties of this stably stratified layer, namely its size $\mathcal {H}_s$ and the degree of its stratification characterized by the Brunt–Väisälä frequency N, are however uncertain and highly debated. A stable layer underneath the CMB can have crucial dynamical impacts on the geodynamo. Because of the inhibition of the convective motions, a stable layer is expected to primarily act as a low-pass filter on the magnetic field, smoothing out the rapidly varying and small-scale features by skin effect. To investigate this effect more systematically, we compute 70 global geodynamo models varying the size of the stably stratified layer from 0 to 300 km and its amplitude from N/Ω = 0 to N/Ω ≃ 50, Ω being the rotation rate. We show that the penetration of the convective flow in the stably stratified layer is controlled by the typical size of the convective eddies and by the local variations of the ratio N/Ω. Using quantitative measures of the degree of morphological semblance between the magnetic field obtained in numerical models and the geomagnetic field at the CMB, we establish an upper bound for the stable layer thickness $\mathcal {H}_s\lt (N/\Omega )^{-1} \mathcal {L}_s$, $\mathcal {L}_s$ being the horizontal size of the convective flow at the base of the stable layer. This defines a strong geomagnetic constraint on the properties of a stably stratified layer beneath the CMB. Unless unaccounted double-diffusive effects could drastically modify the dynamics of the stable layer, our numerical geodynamo models hence favour no stable stratification atop the core.
Global adjoint tomography—model GLAD-M25
Authors: Lei Wenjie , Ruan Youyi , Bozdağ Ebru , Peter Daniel , Lefebvre Matthieu , Komatitsch Dimitri , Tromp Jeroen , Hill Judith , Podhorszki Norbert , Pugmire David
Published: May 2020

Building on global adjoint tomography model GLAD-M15, we present transversely isotropic global model GLAD-M25, which is the result of 10 quasi-Newton tomographic iterations with an earthquake database consisting of 1480 events in the magnitude range 5.5 ≤ Mw ≤ 7.2, an almost sixfold increase over the first-generation model. We calculated fully 3-D synthetic seismograms with a shortest period of 17 s based on a GPU-accelerated spectral-element wave propagation solver which accommodates effects due to 3-D anelastic crust and mantle structure, topography and bathymetry, the ocean load, ellipticity, rotation and self-gravitation. We used an adjoint-state method to calculate Fréchet derivatives in 3-D anelastic Earth models facilitated by a parsimonious storage algorithm. The simulations were performed on the Cray XK7 ‘Titan’ and the IBM Power 9 ‘Summit’ at the Oak Ridge Leadership Computing Facility. We quantitatively evaluated GLAD-M25 by assessing misfit reductions and traveltime anomaly histograms in 12 measurement categories. We performed similar assessments for a held-out data set consisting of 360 earthquakes, with results comparable to the actual inversion. We highlight the new model for a variety of plumes and subduction zones.
Spatiotemporal analyses of tracking data reveal fine-scale, daily cycles in seabird–fisheries interactions
Authors: Ouled-Cheikh Jazel , Sanpera Carola , Bécares Juan , Arcos José Manuel , Carrasco Josep Lluís , Ramírez Francisco
Published: May 2020

Human fisheries provide scavengers with abundant and predictable feeding opportunities that may schedule their behavioural patterns. Using miniaturized global positioning system (GPS) tracking technology, we evaluated how Audouin’s gull (Ichthyaetus audouinii), a Mediterranean endemic seabird that makes extensive use of feeding opportunities provided by fisheries, co-occurred (i.e. presumably interacted) with the most important fishing fleets operating off the NE Iberian Peninsula (i.e. diurnal trawlers and nocturnal purse seiners), both in space and time. Results showed that individuals were able to adapt their distribution and activity patterns to the scheduled routines of these fisheries. Waveform analyses based on co-occurring positions revealed that most interactions with trawlers occurred during the afternoon (16:00 h GMT + 1) when discarding occurs as vessels return to port. In contrast, gull-purse seiner interactions largely occurred at night (between 02:00 and 04:00 h) coinciding with the setting and hauling of the nets. Moreover, we found an individual component in seabird–fishery interactions, showing that there may be differential use of fisheries by individuals within the population. In addition to implications for our understanding of the behavioural ecology of this species, these results may have important management implications, particularly under the current European Union Common Fisheries Policy scenario of largely restricting discards.
Spillover of sea scallops from rotational closures in the Mid-Atlantic Bight (United States)
Authors: Hart Deborah R , Munroe Daphne M , Caracappa Joseph C , Haidvogel Dale , Shank Burton V , Rudders David B , Klinck John M , Hofmann Eileen E , Powell Eric N
Published: May 2020

We examined evidence for larval spillover (increased recruitment outside the closures) of Atlantic sea scallops (Placopecten magellanicus) due to rotational closures in the Mid-Atlantic Bight using a 40-year fisheries survey time series and a larval transport model. Since the first closure of the Hudson Canyon South (HCS) area in 1998, mean recruitment in the two areas directly down-current from this closure, Elephant Trunk (ET) and Delmarva (DMV), increased significantly by factors of about 7 and 2, respectively. Stock–recruit plots indicate that low biomasses in HCS were associated with reduced mean recruitment in ET and DMV. Simulations indicate that larvae spawned in HCS often settle in the two downstream areas and that model-estimated settlement (based on gonad biomass in HCS and year-specific larval transport between the areas) is correlated with observed recruitment. This study gives strong evidence that the rotational closure of HCS has induced increased recruitment in down-current areas.
Rescue operation retrieving an incorrectly implanted cardiac event recorder from the left main pulmonary artery
Authors: Selten Koen , Aljalloud Ali , Autschbach Rüdiger , Moza Ajay
Published: May 2020

Continuous heart rhythm monitoring with cardiac event recorders is increasing in clinical practice and may be helpful in diagnosing a wide range of disorders and pathologies. This case study describes the case of an 80-year-old female patient with a medical history of previous cardiac surgery in which a cardiac event recorder had to be retrieved from the left main pulmonary artery.
Uniqueness and Symmetry for the Mean Field Equation on Arbitrary Flat Tori
Authors: Gu Guangze , Gui Changfeng , Hu Yeyao , Li Qinfeng
Published: May 2020

We study the following mean field equation on a flat torus $T:=\mathbb{C}/(\mathbb{Z}+\mathbb{Z}\tau )$: $$\begin{equation*} \varDelta u + \rho \left(\frac{e^{u}}{\int_{T}e^u}-\frac{1}{|T|}\right)=0, \end{equation*}$$where $ \tau \in \mathbb{C}, \mbox{Im}\ \tau>0$, and $|T|$ denotes the total area of the torus. We first prove that the solutions are evenly symmetric about any critical point of $u$ provided that $\rho \leq 8\pi $. Based on this crucial symmetry result, we are able to establish further the uniqueness of the solution if $\rho \leq \min{\{8\pi ,\lambda _1(T)|T|\}}$. Furthermore, we also classify all one-dimensional solutions by showing that the level sets must be closed geodesics.
Kinetics of Plasma HIV Rebound in the Era of Modern Antiretroviral Therapy
Authors: Sneller Michael C , Huiting Erin D , Clarridge Katherine E , Seamon Catherine , Blazkova Jana , Justement Jesse S , Shi Victoria , Whitehead Emily J , Schneck Rachel F , Proschan Michael , Moir Susan , Fauci Anthony S , Chun Tae-Wook
Published: May 2020

Historical data regarding time to viral rebound following analytical treatment interruption (ATI) have been used to determine therapeutic efficacy in HIV cure trials; however, such data were collected from studies conducted a decade or more ago and included participants receiving older antiretroviral therapy (ART) regimens with infrequent virologic monitoring. We conducted a study of 22 HIV-infected participants receiving modern ART to determine the kinetics of plasma viral rebound following ATI. Our data suggest that modern ART does not alter kinetics of viral rebound when compared to previous regimens and that immunologic interventions may be necessary to achieve ART-free virologic remission.

Clinical Trials Registration ClinicaTrials.gov identifier: NCT03225118.
Insights Into the Pathophysiology of Liver Disease in HCV/HIV: Does it End With HCV Cure?
Authors: Jeyarajan Andre J , Chung Raymond T
Published: May 2020

HCV-HIV coinfected patients exhibit rapid progression of liver damage relative to HCV monoinfected patients. The availability of new directly acting antiviral agents has dramatically improved outcomes for coinfected patients as sustained virologic response rates now exceed 95% and fibrosis-related parameters are improved. Nevertheless, coinfected patients still have a higher mortality risk and more severe hepatocellular carcinoma compared to HCV monoinfected patients, implying the existence of pathways unique to people living with HIV that continue to promote accelerated liver disease. In this article, we review the pathobiology of liver disease in HCV-HIV coinfected patients in the directly acting antiviral era and explore the mechanisms through which HIV itself induces liver damage. Since liver disease is one of the leading causes of non-AIDS-related mortality in HIV-positive patients, enhancing our understanding of HIV-associated fibrotic pathways will remain important for new diagnostic and therapeutic strategies to slow or reverse liver disease progression, even after HCV cure.
The descriptive pattern of physical activity in Saudi Arabia: analysis of national survey data
Authors: Alqahtani Bader A , Alenazi Aqeel M , Alhowimel Ahmed S , Elnaggar Ragab K
Published: May 2020

Background

Over recent decades, there has been a dramatic transformation in mechanization reaching all aspects of people's lives in Saudi Arabia. In the light of this, there was a significant change in physical behavior in the community. The aim of the current study was to investigate the national and regional distribution of physical activity practice among adults aged ≥15 y across Saudi Arabia.

Methods

Data from the Bulletin of Household Sports Practice National Survey were used to determine the physical activity practice distribution. A total of 26 000 families from 13 administrative regions across Saudi Arabia were surveyed.

Results

The proportion of the total Saudi population who were practitioners of physical activity (i.e. ≥150 min per week) among Saudi adults aged ≥15 y was 17.40%, while the proportion of non-practitioners was 82.60%.

Conclusion

This study found a low level of physical activity among Saudi adults who meet physical activity guidelines. These findings suggest that interventions and promotional programs should be developed to increase physical activity among the Saudi population.
Implementing a quick Sequential (Sepsis-Related) Organ Failure Assessment sepsis screening tool: an interrupted times series study
Authors: Alberto Laura , Aitken Leanne M , Walker Rachel M , Pálizas Fernando , Marshall Andrea P
Published: May 2020

Objective

The aim of this study was to evaluate the outcomes of implementing a sepsis screening (SS) tool based on the quick Sequential [Sepsis-Related] Organ Failure Assessment (qSOFA) and the presence of confirmed/suspected infection. The implementation of the 6-h bundle was also evaluated.

Design

Interrupted times series with prospective data collection.

Setting

Five hospital wards in a developing nation, Argentina.

Participants

A total of 1151 patients (≥18 years) recruited within 24–48 h of hospital admission.

Intervention

The qSOFA-based SS tool and the 6-h bundle.

Main outcome measures

The primary outcome was the timing of implementation of the first 6-h bundle element. Secondary outcomes were related to the adherence to the screening procedures.

Results

Of 1151 patients, 145 (12.6%) met the qSOFA-based SS tool criteria, among them intervention (39/64) patients received the first 6-h bundle element earlier (median 8 h; 95% confidence interval (CI): 0.1–16) than baseline (48/81) patients (median 22 h; 95% CI: 3–41); these times, however, did not differ significantly (P = 0.525). Overall, 47 (4.1%) patients had sepsis; intervention patients (18/25) received the first 6-h bundle element sooner (median 5 h; 95% CI: 4–6) than baseline patients (15/22) did (median 12 h; 95% CI: 0–33); however, times were not significantly different (P = 0.470). While intervention patients were screened regularly, only one-third of patients who required sepsis alerts had them activated.

Conclusion

The implementation of the qSOFA-based SS tool resulted in early, but not significantly improved, provision of 6-h bundle care. Screening procedures were regularly conducted, but sepsis alerts rarely activated. Further research is needed to better understand the implementation of sepsis care in developing settings.
Discovery and characterization of New Delhi metallo-β-lactamase-1 inhibitor peptides that potentiate meropenem-dependent killing of carbapenemase-producing Enterobacteriaceae
Authors: Kazi Misha I , Perry Blair W , Card Daren C , Schargel Richard D , Ali Hana B , Obuekwe Victor C , Sapkota Madhab , Kang Katie N , Pellegrino Mark W , Greenberg David E , Castoe Todd A , Boll Joseph M
Published: May 2020

Objectives

Metallo-β-lactamases (MBLs) are an emerging class of antimicrobial resistance enzymes that degrade β-lactam antibiotics, including last-resort carbapenems. Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are increasingly prevalent, but treatment options are limited. While several serine-dependent β-lactamase inhibitors are formulated with commonly prescribed β-lactams, no MBL inhibitors are currently approved for combinatorial therapies. New compounds that target MBLs to restore carbapenem activity against CPE are therefore urgently needed. Herein we identified and characterized novel synthetic peptide inhibitors that bound to and inhibited NDM-1, which is an emerging β-lactam resistance mechanism in CPE.

Methods

We leveraged Surface Localized Antimicrobial displaY (SLAY) to identify and characterize peptides that inhibit NDM-1, which is a primary carbapenem resistance mechanism in CPE. Lead inhibitor sequences were chemically synthesized and MBCs and MICs were calculated in the presence/absence of carbapenems. Kinetic analysis with recombinant NDM-1 and select peptides tested direct binding and supported NDM-1 inhibitor mechanisms of action. Inhibitors were also tested for cytotoxicity.

Results

We identified approximately 1700 sequences that potentiated carbapenem-dependent killing against NDM-1 Escherichia coli. Several also enhanced meropenem-dependent killing of other CPE. Biochemical characterization of a subset indicated the peptides penetrated the bacterial periplasm and directly bound NDM-1 to inhibit enzymatic activity. Additionally, each demonstrated minimal haemolysis and cytotoxicity against mammalian cell lines.

Conclusions

Our approach advances a molecular platform for antimicrobial discovery, which complements the growing need for alternative antimicrobials. We also discovered lead NDM-1 inhibitors, which serve as a starting point for further chemical optimization.
Natural 15N abundance in specific amino acids indicates associations between transamination rates and residual feed intake in beef cattle
Authors: Cantalapiedra-Hijar Gonzalo , Guarnido Pablo , Schiphorst Anne-Marie , Robins Richard J , Renand Gilles , Ortigues-Marty Isabelle
Published: May 2020

Improving the ability of animals to convert feed resources into food for humans is needed for more sustainable livestock systems. Genetic selection for animals eating less while maintaining their performance (i.e., low residual feed intake [RFI]) appears a smart strategy but its effectiveness relies on high-throughput animal phenotyping. Here, we explored plasma nitrogen (N) isotope ratios in an attempt to identify easily superior young bulls in terms of RFI. For this, 48 Charolais young bulls fed two contrasting diets (corn vs. grass silage diets) were selected from a larger population as extreme RFI animals (24 low-RFI vs. 24 high-RFI) and their plasma analyzed for natural 15N abundance (δ15N) in the whole protein (bulk protein) and in the individual protein-bound amino acids (PbAA). For the first time, we showed that the δ 15N in plasma bulk protein differed (P = 0.007) between efficient (low-RFI) and inefficient (high-RFI) cattle regardless of diet. Furthermore, most analyzed PbAA followed the same trend as the bulk protein, with lower (P < 0.05) δ 15N values in more efficient (low-RFI) compared with less efficient (high-RFI) cattle, again regardless of diet. The only three exceptions were Phe, Met, and Lys (P > 0.05) for which the first metabolic reaction before being catabolized does not involve transamination, a pathway known naturally to enrich AAs in 15N. The contrasted isotopic signatures across RFI groups only in those PbAA undergoing transamination are interpreted as differences in transamination rates and N-use efficiency between low- and high-RFI phenotypes. Natural isotopic N signatures in bulk proteins and specific PbAA can be proposed as biomarkers of RFI in growing beef cattle fed different diets. However, the current study cannot delineate whether this effect only occurs post-absorption or to some extent also in the rumen. Our data support the conclusion that most efficient cattle in terms of RFI upregulate N conservation mechanisms compared with less efficient cattle and justify future research on this topic.
The Dynamics of Domestic Human Rights Implementation: Lessons from Qualitative Research in Europe
Authors: Donald Alice , Speck Anne-Katrin
Published: May 2020

It is widely acknowledged that the implementation of international human rights judgments is conditioned by domestic factors; yet the means by which judgments exert—or fail to exert—influence on domestic actors and processes is less well understood. This article presents qualitative research undertaken in three European states between 2016 and 2018 to trace the path between selected judgments involving structural or systemic violations and subsequent action by both state and non-state actors. The rich account of the implementation process thereby constructed reveals, in some cases, a direct—and even immediate—causal path between a decision and actions leading to compliance and, in others, a more indirect or uncertain relationship. The article reveals the dynamic and iterative nature of the implementation process, which may at times stall and at other times accelerate and which may be punctuated by extraneous developments that cause the political space for implementation to widen or narrow. It proceeds to examine the strategies employed by actors who either advance or obstruct implementation, and concludes by advocating the formation of the broadest possible compliance ‘partnerships’ in each case, supported by well-functioning domestic structures to coordinate the state’s response.
mHealth Apps: Disruptive Innovation, Regulation, and Trust—A Need for Balance
Authors: Sheppard Maria K
Published: May 2020

mHealth, the use of mobile and wireless technologies in healthcare, and mHealth apps, a subgroup of mHealth, are expected to result in more person-focussed healthcare. These technologies are predicted to make patients more motivated in their own healthcare, reducing the need for intensive medical intervention. Thus, mHealth app technology might lead to a redesign of existing healthcare architecture making the system more efficient, sustainable, and less expensive. As a disruptive innovation, it might destabilise the existing healthcare organisation through a changed role for healthcare professionals with patients accessing care remotely or online. This account coincides with the broader narrative of National Health Service policy-makers, which focusses on personalised healthcare and greater patient responsibility with the potential for significant cost reductions. The article proposes that while the concept of mHealth apps as a disruptive technology and the narrative of personalisation and responsibilisation might support a transformation of the healthcare system and a reduction of costs, both are dependent on patient trust in the safety and security of the new technology. Forcing trust in this field may only be achieved with the application of traditional and other regulatory mechanisms and with this comes the risk of reducing the effect of the technology’s disruptive potential.