bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical activity pattern and its relationship with overweight and obesity in saudi children
Authors: Aliss Eman M. , Sutaih Rima H. , Kamfar Hayat Z. , Alagha Abdulmoeen E. , Marzouki Zuhair M.
Published: April 2020

Background:

Overweight and obesity among children and adolescents are emerging public health problems. Modifiable lifestyle factors such as physical inactivity and eating out are responsible for the increased prevalence of obesity and related health risks.

Objective:

To examine physical activity level and weight status among Saudi children in relation to age and gender.

Study design:

In a cross-sectional study, 200 apparently healthy Saudi children (118 boys and 82 girls), aged 5–15 years, were enrolled from the Pediatric clinics at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. To determine physical activity level, the International Physical Activity Questionnaire-Short Form-A was used. Anthropometric measurements were taken for all participants.

Results:

Central obesity was highly prevalent among adolescents as compared with a higher prevalence of general obesity in children. Physical activity level was significantly higher among adolescent boys than adolescent girls (P<.05). Girls scored almost double the total metabolic equivalent scores. More boys were considered highly active (59% vs. 40%) in contrast with more girls with low physical activity (38% vs. 26%). Among girls, high physical activity score was higher in children than in adolescents (40% vs. 21%) and an increasing number of adolescents were of low physical activity than children (64% vs. 38%). The majority of the study population were spending more than 2 h per day in watching TV and playing electronic games, but a slightly higher number of children showed sedentary behavior than adolescents. Adolescent girls were significantly spending more time watching TV than adolescent boys (P<.01). Significant inverse associations with most anthropometric measures and the time spent in watching TV and doing desk work were demonstrated in both genders.

Conclusion:

This study reports significant influence, by age and gender, contributing to physical inactivity and weight status among Saudi children.
Child maltreatment prevention readiness in Bahrain
Authors: Al-Mahroos Fadheela T. , Alnoaimi Aysha A. , AlAmer Eshraq A. , Jahrami Haitham A. , Saleheen Hassan N. , Almuneef Maha , Al-Eissa Majid A.
Published: April 2020

Background and Objectives:

Child maltreatment (CM) is a major public health problem worldwide. Despite the well-documented cases of all forms of CM and the improvement of the national response to CM in Bahrain, efforts on the prevention of CM are still limited. The objective of this study was to assess the readiness to implement a national evidence-based CM prevention (CMP) program in Bahrain.

Methods:

The cross-sectional study was conducted with 45 key informants who had influence and decision-making power over CMP.

Results:

The overall score indicated low to moderate readiness. The key informants scored the highest on legislation, mandates, and policies (7.9), which was followed by the knowledge of CM prevention (7.2), institutional resources and links (5.2), and informal social resources (noninstitutional) (5.2). However, the lowest scores were the human and technical resources (1.2), attitudes toward CM prevention (3.3), will to address the problem, and material resources (3.8), current programs implementation and evaluation, and scientific data on CM prevention (4.5).

Conclusion:

This research has identified strengths and gaps in the country that needs to be addressed to develop programs that are responsive to the needs of the community. The development of a comprehensive well-resourced CMP program requires the collaborative efforts of legislators, political leaders, and professionals.
Acute cholecystitis in true duplication of the gallbladder
Authors: Hakim Zenaidi , Imen Ben Ismail , Abdelwahed Yahmadi , Sabeur Rebii , Ayoub Zoghlami
Published: April 2020

ABSTRACT

Gallbladder duplication is a rare anatomic anomaly of the biliary tract. Preoperative diagnosis and differentiation of this malformation are important to prevent inadvertent damage to the biliary system. We present a case of a 58 years old female who presented with signs and symptoms of acute cholecystitis. Abdomen ultrasound and magnetic resonance cholangiopancreatography detected a true duplicated gallbladder with cholecystitis in one of them. There were two independent cystic ducts joining CBD separately. Both gallbladders were removed and no post-operative complications we rereported. Accurately laparoscopic cholecystectomy remains the gold standard approach for intervention and these cases should be done by an experienced laparoscopic surgeon.

Highlights:
Microelectrode arrays for monitoring neural activity in neural stem cells with modulation by glutamate in vitro
Authors: Gao Fei , Luo Jinping , Song Yilin , He Enhui , Zhang Yu , Xiao Guihua , Cai Xinxia
Published: April 2020

In this study, a 60-channel microelectrode array (MEA) was fabricated and used to monitor the neural spikes and local field potentials (LFPs) of neurons differentiated from rat neural stem cells in vitro. The neurons were grown on the MEA surface to detect neural signals. Glutamate (Glu) was used to modulate neural activity during experiments. To enhance detection performance, platinum nanoparticles were modified onto the microelectrode site surface. Glutamate stimulated neural spikes and LFPs were recorded using the MEA. The average spike amplitude was approximately 70 μV in the normal state. The spike amplitude increased by 29% from 70 μV to 90 μV with Glu modulation. The firing rate increased by 69% from 4.01 Hz to 6.8 Hz with Glu modulation. The LFP power increased from 326 μW in the normal state to 617 μW with Glu modulation in the 0–10 Hz frequency band. Data analysis shows that neural activity stimulated by Glu modulation was recorded experimentally at high temporal-spatial resolution. These results may provide a new neuron detection method, as well as further understanding of neural stem cell spike firing and associated mechanisms.
Carbon Cycling in the World’s Deepest Blue Hole
Authors: Thompson Elizabeth
Published: April 2020

Scientists find new extremes as they research carbon cycling in the Yongle blue hole.
Walter C. Pitman III (1932–2019)
Authors: Coakley Bernard , Cande Steven , LaBrecque John
Published: April 2020

Pitman pioneered research on seafloor spreading, proposed a scientific backstory to the Great Flood and Noah's Ark, and reveled in spirited discussions of all kinds.
This Week: Guilty Pleasures to Get You Through Quarantine
Authors:   AGU
Published: April 2020

Taking a brief break from Earth and space science for…primal screams and pet pics?
Enhanced global attention upsample decoder based on enhanced spatial attention and feature aggregation module for semantic segmentation
Authors: Yin Lianglu , Hu Haifeng
Published: April 2020

This work designs a simple but effective decoder structure called Enhanced Global Attention Upsample Decoder (EGAUD) based on enhanced spatial attention (SA) and feature aggregation module for semantic segmentation, which is used to recover the prediction rich in detail and semantic information. First, Enhanced SA (ESA) and Feature Aggregation Module (FAM) are used to enhance the details and semantic information of shallow and deep features, respectively. ESA integrates the SA module and residual enhancement module to enrich spatial information while ensuring the effectiveness of backpropagation. FAM uses three parallel pooling operations to expand the receptive field of features, to optimize the semantic information. Then, the authors use Global Attention Upsample (GAU) to recover the feature resolution. From bottom to top, GAU utilises two pooling operations to fully integrate the features of adjacent layers. The results on two datasets, PASCAL VOC 2012 and PASCAL‐Person‐Part, show the effectiveness of the authors’ model.
Interfacial space charge characteristic of PPLP insulation for HVDC cables
Authors: Zhao Xuefeng , Pu Lu , Xu Zhiqiang , Chen George , Duan Wei , Sun Haofei , Ju Zeli
Published: April 2020

High‐voltage DC (HVDC) cables show more efficiency than high‐voltage AC cables over the long distance power transmission and have attracted significant attention recently due to rapid developments in off‐shore wind farm. Polypropylene laminated paper (PPLP) insulation based HVDC cables have provided a reliable operation for many years and are the highest voltage level in operation at the moment. In this study, the authors intend to understand the electrical performance of PPLP insulation system by examining space charge in detail, especially at the interfaces. It has been found that the interface between polypropylene and Kraft paper acts as trap for charge carriers, resulting in an optimal electric field distribution in PPLP insulation system. The optimal electric field distribution enhances overall electrical performance of PPLP insulation, including higher dc breakdown strength and lower electrical conductivity.
Development of single phase 12S‐6P FEFSM and field‐oriented control algorithm based on the effect of rotor position on stator flux pair linkage
Authors: Amin Faisal , Bin Sulaiman Erwan , Utomo Wahyu Mulyo , Bin Omar Mohd Fairoz , Khan Faisal
Published: April 2020

Field excited flux‐switching machines (FEFSMs) falls into advance category of synchronous machine. However, most FEFSM structures are comprised of overlapped stator windings, which ends up in taking more space, more copper losses and material costs. Moreover, FSM works on flux‐switching principle which made the implementation of field‐oriented control (FOC) significantly complex. This study proposes a new structure of single phase FEFSM having segmented rotor and non‐overlapped windings for the elimination of above‐mentioned drawbacks. Additionally, this study also presents a mechanism to implement FOC without the need of magnetomotive force (MMF) in the rotor. Design of this new topology and its performance characteristics have been analysed through two‐dimensional finite element analysis. FOC algorithm has been designed on the basis of sinusoidal variation of stator flux linkage due to rotor position. Experimental results show staggering performance efficiency of about 96% in terms of torque generation when compared to simulation results. Thus, verified the successful implementation of the proposed algorithm on the designed prototype.
Reverberation mapping of AGNs through continuum polarization
Authors: Rojas Lobos P. A. , Goosmann R. W. , Hameury J. M. , Marin F.
Published: April 2020

Context. The size and geometry of the broad-line region (BLR) in active galactic nuclei (AGNs) are among the main ingredients in determining the mass of the accreting black hole. Size and geometry can be constrained by determining the delay between the optical continuum and the flux reprocessed by the BLR, in particular, through the emission lines.

Aims. We propose here that the delay between polarized and unpolarized light can also be used in much the same way to constrain the size of the BLR; we verify that meaningful results can be expected from observations using this technique.

Methods. We used our code STOKES to simulate polarized radiative transfer. We determined the response of the environment of the central source (BLR, dust torus, and polar wind) to randomly generated fluctuations in the central source. We then calculated the cross correlation between the simulated polarized flux and the total flux to estimate the time delay that would be provided by observations using the same method.

Results. The BLR is the main contributor to the delay between the polarized flux and the total flux. This delay is independent of the observation wavelength.

Conclusions. This validates the use of polarized radiation in the optical/UV band to estimate the geometrical properties of the BLR in type I AGNs, in which the viewing angle is close to pole-on and the BLR is not obscured by the dust torus.
Purveyors of fine halos
Authors: Hanke Michael , Koch Andreas , Prudil Zdeněk , Grebel Eva K. , Bastian Ulrich
Published: April 2020

A long-lasting open question in the field of Galactic archeology refers to the size of the contribution from former globular cluster (GC) stars to the formation of the stellar halo of the Milky Way. We contribute to answering this important question by establishing observational links between the present-day halo field star population and GCs. To this end, we combined astrometric information such as space motions and parallaxes from the second data release of theGaiamission (GaiaDR2) with spectroscopic radial velocities and metallicities ([Fe/H]) from the Sloan Digital Sky Survey (SDSS-IV, DR14) to end up with a seven-dimensional chemodynamical information space for more than 3 × 105stars. Moreover, from our previous study, we incorporated the sample of halo giant stars with a distinct chemical signature (strong CN bandheads) that resembles the light-elements anomaly otherwise only seen in the second generation of globular cluster stellar populations. Using three different tagging techniques – among which is the exploration of conservative integrals of motion – we are able to establish unique associations between 151 extratidal stars in the neighborhood of eight GCs, which coincide with earlier findings of stellar envelopes beyond the tidal radius and even beyond (out to several tens of tidal radii). In addition, we trace the possible origin of about 62% of the sample of CN-strong giants to their potential host clusters. We find a connection between several of the involved GCs and the Gaia-Enceladus and Sequoia merger events. By establishing kinematic and chemical connections between 17 CN-strong stars and their surrounding fields, we identify co-moving groups of stars at the same [Fe/H] with a possible cluster origin. Some of these associations contain RR Lyrae variables, which allows meaningful distance inferences to be made. From these, we find strong evidence that four CN-strong stars and their associates are connected to the Sagittarius stream whilst their tightly confined [Fe/H] may hint to a birth site in M 54, the massive cluster in Sagittarius’ core remnant. Finally, by employing the counts of CN-strong and bona-fide CN-normal giants from our novel sample, we provide tentative estimates for the fraction of first-generation cluster stars among all stars lost to the halo. In the immediate cluster vicinity, this value amounts to 50.0 ± 16.7% while the associations in the halo field rather imply 80.2−5.2+4.9%. We speculate that – if proven real by spectroscopic follow-up – the disparity between these numbers could indicate a major contribution of low-mass clusters to the overall number of stars escaped to the halo or could alternatively suggest strong mass loss from the first generation during early cluster dissolution.
Confidence collapse in a multihousehold, self-reflexive DSGE model
Authors: Morelli Federico Guglielmo , Benzaquen Michael , Tarzia Marco , Bouchaud Jean-Philippe
Published: April 2020

Significance

Despite their inability to cope with the global financial crisis, dynamic stochastic general equilibrium (DSGE) models are still at the forefront of monetary policy. Like many standard economic models, DSGE models rely on the figment of representative agents, abolishing the possibility of genuine collective effects (such as the 2008 crisis) induced by heterogeneities and interactions. By allowing feedback of past aggregate consumption on the sentiment of individual households, we construct more realistic DSGE models that allow for large output swings induced by relatively minor variations in economic conditions and amplified by interactions. Our framework elicits the de facto impossibility to price extreme risks and highlights the importance of narratives, as an efficient depression-prevention policy tool whenever confidence collapse is looming.
Categorical versus thetic sentences in the Universal Grammar of Realism
Authors: Leiss Elisabeth
Published: April 2020

The aim of this paper is to outline that the notions of thetic versus categorical sentences are
characteristic of a long tradition of philosophy, especially of the philosophy of Realism. Characteristic of Realism
is a highly developed theory of the copula. Sentences consist of a subject, a rather abstract copula, and a predicate.
Thus, the structure of any sentence and of any judgment is conceived as being triadic in nature. The copula appears –
overtly or covertly – in synthetic sentences as well as in analytic sentences, both of which are categorical sentences
(Roger Bacon 1240/2009: 70), whereby the analytic copula differs from the
synthetic copula with respect to the mode of signifying reality. It will be evidenced that the function of analytic
sentences is to build up a shared system of knowledge (mental lexicon), whereas synthetic sentences represent a
technique to socialize individual experiences. According to the philosophy of Realism, the copula appears even in
thetic sentences. Sentences without a copula are meant to be inconceivable. The working hypothesis is that in contrast
to categorical sentences, thetic sentences are not triadic, but dyadic in structure. According to the Realist
philosopher Lotze, thetic sentences consist of a copula and an amalgam of linguistically unstructured impressions,
compressed in the predicate. In line with the philosophy of Realism, thetic sentences are conceived as some premature
stage in the evolution of language. Thus, thetic sentences represent an embryonic stage of a categorical sentence as
well as of thought (Lotze 1874/1989: 70–74). Thetic sentences are able to
imitate the structure of categorical sentences (pseudo-subject – copula – pseudo-predicate). The conclusion is that
thetic sentences are pseudo-structured “intransitive” judgments. They consist of a copula and one single chunk of
“intransitive experience” only.
Copulas and information structure in Tanti Dargwa
Authors: Sumbatova Nina R.
Published: April 2020

The paper describes the basic types of independent clauses in the Tanti dialect of Dargwa
(Nakh-Dagestanian (= East Caucasian), Russian Federation). Most independent clauses in Tanti are headed either by the
identificational copula or a finite verb form. Less frequently, we meet sentences headed by one of the four
existential copulas. There are also some independent clauses headed by a non-finite verb form or a non-verbal
predicate and containing no copula. The paper shows that the basic difference between the sentences with different
copula types and without any copulas is the type of information structure of the relevant sentence. The
identificational copula is a feature of categorical sentences; the position of the copula points at the focused
constituent. The existential copulas tend to head thetic structures. Copula-less converbal clauses are often
interpreted as mirative sentences, which can also be analyzed as thetic, but differ from the existential structures by
the moment when the speaker obtains the knowledge of the situation.
Adjectives and mode of expression
Authors: Muroi Yoshiyuki
Published: April 2020

The German psych-adjectives glücklich (happy) and traurig (sad)
and their Japanese counterparts shiawase and kanashii are considered here with
regard to their semantics, the hierarchy of thematic roles, and the mode of expression. The attributive usage has a
semantic structure with broad focus on the entire structure, which shows a similarity to thetic judgments despite its
nonpropositional status. By contrast, the predicative usage with the subject/topic as the stimulus denotes a permanent
property of the entity evoking the emotion and consists of two components respectively with narrow focus, which
corresponds to the double judgment of categoricals. This structure is possible owing to the property of the copulative
predication that it gives the sentence definiteness, but does not give any semantic role to the arguments.
Pseudocategorical or purely thetic?
Authors: Fujinawa Yasuhiro
Published: April 2020

According to Marty (1918), thetic statements differ
from categorical ones in making a simple existential recognition or rejection rather than a predication. In Japanese,
where two subject particles, ga and wa, are presumably available for this
differentiation (Kuroda 1972), the point can be expounded especially by the
fact that da ‘to be’ hardly appears as an existential verb in ga-marked, but only in
wa-marked sentences. Moreover, the same holds true for German optatives. I conclude from these
observations that thetic statements find their expression not only pseudocategorically, as originally assumed by Marty (1918), but also in a purely thetic manner in natural languages, provided
(at least) there is no personal deictic agreement at work between a syntactic subject and a syntactic predicate.
The thetic/categorical distinction as difference in common ground update
Authors: Wilson Daniel J.
Published: April 2020

The distinction between thetics and categoricals in natural language has been observed in more and
more languages recently. The theoretical discussion about the thetic/categorical distinction has also become
increasingly relevant. This article presents a few challenges to an assertion/judgment-based analysis of the
thetic/categorical distinction and offers instead an analysis based on common ground update within a theory of
alternative semantics. In this approach, I follow Murray (2009, 2010, 2014) and Roberts (2012) that each sentence offers different kinds of update to the common ground based on
the question(s) under discussion (or at-issue/not-at-issue content). I suggest that thetics present a
unique type of update which explains why sentences such as It is raining, prosodically inflected
sentences (known as those with sentence focus), existentials, and presentatives have been called thetics. Each
statement contributes to (or updates) the information interlocutors use, and this common ground shapes the assertions
they make. I ultimately propose that the thetic/categorical distinction may no longer be helpful for a description of
natural language. Instead, these phenomena can be situated within the increasingly robust frameworks which bridge the
syntax-semantics-pragmatics interfaces. Finally, I apply this proposal to a construction type in Biblical Hebrew which
I previously labelled a thetic construction in Wilson (2017, 2019).
No effect of probiotics on leptin levels. An updated mini review.
Authors: Papandreou Dimitrios
Published: April 2020

Many human studies have reported controversial results on the benefit of probiotics on leptin levels. White adipose tissue (WAT) secretes leptin and plays an important role in energy balance and glucose homeostasis by decreasing food consumption and acting on fatty acid oxidation and weight reduction. Evidence on probiotics suggests that supplementation may have beneficial effects on lipid metabolism and leptin levels by altering the gut microbiota. However, most of the recent data have shown opposite results.
The circular economy concept application to livestock systems: an agroecological approach
Authors: Bona D. , Iussig G. , Silvestri S.
Published: April 2020

Over the last century, livestock systems
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have undergone a progressive intensification process, which brought to light many environmental and agronomical issues, mainly related to manure management. An agroecological approach has also been advocated to develop more sustainable systems and ensure a balanced relationship between environmental, social and economic goals. The circular economy (CE) concept was placed next to that of agroecology, and its application to manure management was finalized to reduce the input and use of natural resources, increase sharing of energy and natural resources and reduce pollution. This review comprehensively reports the more interesting opportunities for European Cattle breeding, considering that its waste management plays an important role from the agroecological point of view. Many technologies based on biological and/or thermochemical processes are currently available and different studies on how to improve their efficiency are under way. The biorefinery concept concerns the lignocellulosic fraction exploitation for biofuels, by-products and biochar/hydrochar production. The enhancement of farm nutrient utilization could restore the balance between input and output. The knowledge of the fertilizing/amendment properties of the manure and its by-products could create a synergistic development at landscape scale considering other agricultural production (crops, orchards, vineyards, etc.). Some ecological services such as soil fertility, biological regulations, soil erosion and biological diversity provided by animal farming could be a product of the transition towards circular economy. By adopting an agroecological approach, the enhancement of the energetic, agronomic and biochemical exploitation of manure will be sustainable.
Improving coffee species for pathogen resistance
Authors: Maghuly Fatemeh , Jankowicz-Cieslak Joanna , Bado Souleymane
Published: April 2020

Pathogens are the major limiting factors in coffee productions. Approximately 26% of the global annual coffee production is lost due to diseases, threatening the income of nearly 125 million people worldwide. Therefore, reducing coffee yield losses by improving the resistance of coffee plants to disease and insect attack will provide a major contribution to agricultural sustainability and disease management of many regions. Breeding
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varieties that are resistant to a broad spectrum of pathogens, genetically stable and high yielding, requires strategies that will overcome challenges known by coffee breeders. Recently developed genomic tools allow a better understanding of coffee-pathogen interaction and help to identify genes involved in pathogen resistance or susceptibility. Understanding the influence of individual factors and their interaction will help to select interesting accessions and to accelerate breeding strategies for coffee improvement. Additional information on the quantitative effect of pest and disease on coffee crop losses and the understanding of their impact are essential to develop the best pest management strategy. This review provides an overview of the current knowledge of coffee production and recent advances in resistance breeding programs, with emphasis on induced mutagenesis, genomic tools, and genome editing. The focus is on the origin, domestication, evolution, and gene pools of coffee. Moreover
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, answers will be given toward: how we can benefit from establishing a genetically diverse coffee population; how genomic resources can play an important role in host resistance; and what are the major pathogens affecting coffee.
Family farming between its past and potential future with the focus on multifunctionality and sustainability
Authors: Quendler Erika , Ikerd John , Driouech Noureddin
Published: April 2020

Sustainability may be defined in the most general terms as the ability to meet the needs of the present without diminishing opportunities for the future. It is also generally conceded that sustainability is multidimensional in that it depends on ecological, social and economic integrity—the three cornerstones of sustainability. It is no surprise then that the functionality of family farming is increasingly being discussed in scholarly literature as an important element in promoting the multiple ecological, social and economic benefits of a sustainable agriculture. This paper provides a review of that body of literature. By examining literature relevant to the European Union (EU) and the United States (US), this paper also explores the economic and social evolution of farming within these two historical and political contexts, giving specific attention to its motivation and functionality. Whereas in the past family farms have been very diverse in motivation and multifunctional in operation, more recent trends have been veering towards monofunctional farms that are primarily, if not solely, economically motivated. The literature review reveals the potential for multifunctional family farms to alter or reverse this development of agriculture towards unsustainable, monofunctional agri-businesses. This review also highlights the potential of agroecology as the scientific foundation for multifunctional family farming as a means of achieving sustainable agriculture. The essential premise of this review is that multifunctional family farming provides the logical rationale and political rhetoric for farm policies that promote and support the multiple benefits of an agriculture that is sustainable.
Cervical spine fragility fractures in older people: 5-year experience at a regional spine centre
Authors: Tarawneh Ahmad , Taqvi Syed , Salem Khalid , Sahota Opinder
Published: April 2020

Background

cervical spine fractures are particularly prevalent in older people and commonly occur following a fall from standing height or less. Atlanto-axial complex (AAC) and, particularly, odontoid process (OP) fractures are the most prevalent injuries.

Objective

to investigate the incidence and characteristics of cervical spine fractures in older patients presenting to a regional spine centre.

Methods

a retrospective review of the clinical records and imaging of all patients aged 70 years and over presenting to a regional spinal unit with a cervical injury over a 5-year period was performed. Patient demographics, mechanism of injury, level of fracture, stability of the fracture, treatment modality, imaging modality and mortality rates were collected and analysed.

Results

during the period between 2015 and 2019, a total of 209 patients aged 70 years and over were presented to the regional spine unit. The mean age at presentation was 82.4 (±7.5) years. Low-energy trauma was the commonest mechanism of injury (n = 169; 80.9%). MRI was undertaken in a quarter of the patients. One-hundred and fifty-one patients (72.2%) suffered an AAC Injury with OP fractures forming the majority of this group (n = 119; 78.8%). One-hundred and ninety-nine patients were treated conservatively, and the overall 30-day mortality rate was 8.1%.

Conclusion

cervical spine fractures are not uncommon amongst older people and are mostly the result of low-energy trauma and predominantly affect the axial cervical spine. The majority of these injuries are managed conservatively with an orthosis. The fractures nevertheless are a serious injury, with a high mortality rate at 30 days.
Cardiovascular Disease and All-Cause Mortality in Male Twins With Discordant Cardiorespiratory Fitness: A Nationwide Cohort Study
Authors: Ballin Marcel , Nordström Anna , Nordström Peter
Published: April 2020

Whether genetic and familial factors influence the association between cardiorespiratory fitness (CRF) and cardiovascular disease (CVD) is unknown. Two cohorts were formed based on data from 1,212,295 men aged 18 years who were conscripted for military service in Sweden during 1972–1996. The first comprised 4,260 twin pairs in which the twins in each pair had different CRF (≥1 watt). The second comprised 90,331 nonsibling pairs with different CRF and matched on birth year and year of conscription. Incident CVD and all-cause mortality were identified using national registers. During follow-up (median 32 years), there was no difference in CVD and mortality between fitter twins and less fit twins (246 vs. 251 events; hazard ratio (HR) = 1.00, 95% confidence interval (CI): 0.83, 1.20). The risks were similar in twin pairs with ≥60-watt difference in CRF (HR = 0.96, 95% CI: 0.57, 1.64). In contrast, in the nonsibling cohort, fitter men had a lower risk of the outcomes than less fit men (4,444 vs. 5,298 events; HR = 0.83, 95% CI: 0.79, 0.86). The association was stronger in pairs with ≥60-watt difference in CRF (HR = 0.65, 95% CI: 0.59, 0.71). These findings indicate that genetic and familial factors influence the association of CRF with CVD and mortality.
Unravelling the enigma of cortical tremor and other forms of cortical myoclonus
Authors: Latorre Anna , Rocchi Lorenzo , Magrinelli Francesca , Mulroy Eoin , Berardelli Alfredo , Rothwell John C , Bhatia Kailash P
Published: April 2020

Cortical tremor is a fine rhythmic oscillation involving distal upper limbs, linked to increased sensorimotor cortex excitability, as seen in cortical myoclonus. Cortical tremor is the hallmark feature of autosomal dominant familial cortical myoclonic tremor and epilepsy (FCMTE), a syndrome not yet officially recognized and characterized by clinical and genetic heterogeneity. Non-coding repeat expansions in different genes have been recently recognized to play an essential role in its pathogenesis. Cortical tremor is considered a rhythmic variant of cortical myoclonus and is part of the ‘spectrum of cortical myoclonus’, i.e. a wide range of clinical motor phenomena, from reflex myoclonus to myoclonic epilepsy, caused by abnormal sensorimotor cortical discharges. The aim of this update is to provide a detailed analysis of the mechanisms defining cortical tremor, as seen in FCMTE. After reviewing the clinical and genetic features of FCMTE, we discuss the possible mechanisms generating the distinct elements of the cortical myoclonus spectrum, and how cortical tremor fits into it. We propose that the spectrum is due to the evolution from a spatially limited focus of excitability to recruitment of more complex mechanisms capable of sustaining repetitive activity, overcoming inhibitory mechanisms that restrict excitatory bursts, and engaging wide areas of cortex. Finally, we provide evidence for a possible common denominator of the elements of the spectrum, i.e. the cerebellum, and discuss its role in FCMTE, according to recent genetic findings.
Investigating the cumulative effects of Δ9-tetrahydrocannabinol and repetitive mild traumatic brain injury on adolescent rats
Authors: Bhatt Dhyey , Hazari Ali , Yamakawa Glenn R , Salberg Sabrina , Sgro Marissa , Shultz Sandy R , Mychasiuk Richelle
Published: April 2020

The prevalence of mild traumatic brain injury is highest amongst the adolescent population and can lead to complications including neuroinflammation and excitotoxicity. Also pervasive in adolescents is recreational cannabis use. Δ9-Tetrahydrocannabinol, the main psychoactive component of cannabis, is known to have anti-inflammatory properties and serves as a neuroprotective agent against excitotoxicity. Thus, we investigated the effects of Δ9-tetrahydrocannabinol on recovery when administered either prior to or following repeated mild brain injuries. Male and female Sprague-Dawley rats were randomly assigned to receive Δ9-tetrahydrocannabinol or vehicle either prior to or following the repeated injuries. Rats were then tested on a behavioural test battery designed to measure post-concussive symptomology. The hippocampus, nucleus accumbens and prefrontal cortex were extracted from all animals to examine mRNA expression changes (Bdnf, Cnr1, Comt, GR, Iba-1 and Vegf-2R). We hypothesized that, in both experiments, Δ9-tetrahydrocannabinol administration would provide neuroprotection against mild injury outcomes and confer therapeutic benefit. Δ9-Tetrahydrocannabinol administration following repeated mild traumatic brain injury was beneficial to three of the six behavioural outcomes affected by injury (reducing anxiety and depressive-like behaviours while also mitigating injury-induced deficits in short-term working memory). Δ9-Tetrahydrocannabinol administration following injury also showed beneficial effects on the expression of Cnr1, Comt and Vegf-2R in the hippocampus, nucleus accumbens and prefrontal cortex. There were no notable benefits of Δ9-tetrahydrocannabinol when administered prior to injury, suggesting that Δ9-tetrahydrocannabinol may have potential therapeutic benefit on post-concussive symptomology when administered post-injury, but not pre-injury.
Brain sterol flux mediated by cytochrome P450 46A1 affects membrane properties and membrane-dependent processes
Authors: Petrov Alexey M , Mast Natalia , Li Young , Denker John , Pikuleva Irina A
Published: April 2020

Cytochrome P450 46A1 encoded by CYP46A1 catalyzes cholesterol 24-hydroxylation and is a CNS-specific enzyme that controls cholesterol removal and turnover in the brain. Accumulating data suggest that increases in cytochrome P450 46A1 activity in mouse models of common neurodegenerative diseases affect various, apparently unlinked biological processes and pathways. Yet, the underlying reason for these multiple enzyme activity effects is currently unknown. Herein, we tested the hypothesis that cytochrome P450 46A1-mediated sterol flux alters physico-chemical properties of the plasma membranes and thereby membrane-dependent events. We used 9-month-old 5XFAD mice (an Alzheimer’s disease model) treated for 6 months with the anti-HIV drug efavirenz. These animals have previously been shown to have improved behavioural performance, increased cytochrome P450 46A1 activity in the brain, and increased sterol flux through the plasma membranes. We further examined 9-month-old Cyp46a1−/− mice, which have previously been observed to have cognitive deficits and decreased sterol flux through brain membranes. Synaptosomal fractions from the brain of efavirenz-treated 5XFAD mice had essentially unchanged cholesterol levels as compared to control 5XFAD mice. However with efavirenz treatment in these mice, there were changes in the membrane properties (increased cholesterol accessibility, ordering, osmotic resistance and thickness) as well as total glutamate content and ability to release glutamate in response to mild stimulation. Similarly, the cholesterol content in synaptosomal fractions from the brain of Cyp46a1−/− mice was essentially the same as in wild-type mice but knockout of Cyp46a1 was associated with changes in membrane properties and glutamate content and its exocytotic release. Changes in Cyp46a1−/− mice were in the opposite direction to those observed in efavirenz-treated versus control 5XFAD mice. Incubation of synaptosomal fractions with the inhibitors of glycogen synthase kinase 3, cyclin-dependent kinase 5, protein phosphatase 1/2 A, and protein phosphatase 2B revealed that increased sterol flux in efavirenz-treated versus control 5XFAD mice affected the ability of all four enzymes to modulate glutamate release. In contrast, in Cyp46a1−/− versus wild-type mice, decreased sterol flux altered the ability of only cyclin-dependent kinase 5 and protein phosphatase 2B to regulate the glutamate release. Collectively, our results support cytochrome P450 46A1-mediated sterol flux as an important contributor to the fundamental properties of the membranes, protein phosphorylation and synaptic transmission. Also, our data provide an explanation of how one enzyme, cytochrome P450 46A1, can affect multiple pathways and processes and serve as a common potential target for several neurodegenerative disorders.
Agalsidase beta treatment slows estimated glomerular filtration rate loss in classic Fabry disease patients: results from an individual patient data meta-analysis
Authors: Ortiz Alberto , Kanters Steve , Hamed Alaa , DasMahapatra Pronabesh , Poggio Eugene , Maski Manish , Aguiar Mario , Ponce Elvira , Jansen Jeroen P , Ayers Dieter , Goldgrub Rachel , Desnick Robert J
Published: April 2020

Background

Fabry disease is a rare, X-linked genetic disorder that, if untreated in patients with the Classic phenotype, often progresses to end-stage kidney disease. This meta-analysis determined the effect of agalsidase beta on loss of estimated glomerular filtration rate (eGFR) in the Classic phenotype using an expansive evidence base of individual patient-level data.

Methods

The evidence base included four Sanofi-Genzyme studies and six studies from a systematic literature review. These were restricted to Classic Fabry patients meeting the eligibility criteria from Phases III and IV agalsidase beta trials, including 315 patients (161 treated). Linear regression was first used to model annual change in eGFR for each patient and the resulting annualized eGFR slopes were modelled with treatment and covariates using quantile regression. These results were then used to estimate median annualized eGFR change in agalsidase beta treated versus untreated groups.

Results

Imbalances across treatment groups were found in baseline age, sex and proteinuria, but not in the use of renin–angiotensin system blockers. The adjusted model suggests that treated (agalsidase beta) patients experienced a slower median eGFR decrease [2.46 mL/min/1.73 m2/year slower; 95% confidence interval (CI) 0.63–4.29; P = 0.0087] than comparable untreated patients. The median eGFR decrease was 2.64 mL/min/1.73 m2/year slower (95% CI 0.53–4.78; P = 0.0141) in treated Classic males.

Conclusions

Using an expansive evidence base and robust modelling approach, these data indicate that agalsidase beta-treated patients with the Classic phenotype conserve their renal function better than untreated patients.
Testing exogeneity in nonparametric instrumental variables models identified by conditional quantile restrictions
Authors: Fu Jia-Young Michael , Horowitz Joel L , Parey Matthias
Published: April 2020

This paper presents a test for exogeneity of explanatory variables in a nonparametric instrumental variables (IV) model whose structural function is identified through a conditional quantile restriction. Quantile regression models are increasingly important in applied econometrics. As with mean-regression models, an erroneous assumption that the explanatory variables in a quantile regression model are exogenous can lead to highly misleading results. In addition, a test of exogeneity based on an incorrectly specified parametric model can produce misleading results. This paper presents a test of exogeneity that does not assume that the structural function belongs to a known finite-dimensional parametric family and does not require estimation of this function. The latter property is important because nonparametric estimates of the structural function are unavoidably imprecise. The test presented here is consistent whenever the structural function differs from the conditional quantile function on a set of nonzero probability. The test has nontrivial power uniformly over a large class of structural functions that differ from the conditional quantile function by $O({n^{ - 1/2}})$. The results of Monte Carlo experiments and an empirical application illustrate the performance of the test.
‘So Much Grief and not a Tongue’: Trauma and Intertextuality in Shakespeare’s The Rape of Lucrece
Authors: Wiltshire Harvey
Published: April 2020

In her 2008 monograph Unto the Breach: Martial Formations, Historical Trauma, and the Early Modern Stage, Patricia A. Cahill argues that critics of Renaissance literature have thus far failed to ‘reckon with the fact that early modern traumatic experience is defined not only by its subject matter … but also by what can be described as its “belated” and “latent” temporal structure’. Which is to say that the hallmark of trauma – both early modern and modern – is the delayed manifestation of the signs and symptoms that evince the originary experience having taken place; as such, trauma is defined by the period of latency that follows the instigating event, known only by the belated arrival of symptoms attesting to it. Since then, scholars have begun to interrogate the ways in which early modern literature appears to anticipate later cultural and theoretical configurations of trauma. By examining the significance of trauma and intertextuality in Shakespeare’s The Rape of Lucrece (1594), this essay builds on the insights of a strong and diverse body of research that continues to attend to the complex role of trauma in early modern literature. By reading The Rape of Lucrece in the context of and also through Shakespeare’s Ovidian source material, this essay suggests that the very act of returning to Ovid formally encodes the distinctive and disturbing structure of trauma into Shakespeare’s depiction of responses to extreme experience.
Chimeric Antigen Receptors Targeting Human Cytomegalovirus
Authors: Ali Ayub , Chiuppesi Flavia , Nguyen Minh , Hausner Mary Ann , Nguyen Jenny , Kha Mindy , Iniguez Angelina , Wussow Felix , Diamond Don J , Yang Otto O
Published: April 2020

Human cytomegalovirus (CMV) is a ubiquitous pathogen that causes significant morbidity in some vulnerable populations. Individualized adoptive transfer of ex vivo expanded CMV-specific CD8+ T cells has provided proof-of-concept that immunotherapy can be highly effective, but a chimeric antigen receptor (CAR) approach would provide a feasible method for broad application. We created 8 novel CARs using anti-CMV neutralizing antibody sequences, which were transduced via lentiviral vector into primary CD8+ T cells. All CARs were expressed. Activity against CMV-infected target cells was assessed by release of cytokines (interferon-γ and tumor necrosis factor–α), upregulation of surface CD107a, proliferation, cytolysis of infected cells, and suppression of viral replication. While some CARs showed varying functional activity across these assays, 1 CAR based on antibody 21E9 was consistently superior in all measures. These results support development of a CMV-specific CAR for therapeutic use against CMV and potentially other applications harnessing CMV-driven immunotherapies.
Securing Reproductive Health: A Matter of International Peace and Security
Authors: Davies Sara E , Harman Sophie
Published: April 2020

Failure to access reproductive health care is a threat to the security of women around the world. This article offers three propositions to recognize reproductive health as a matter of international peace and security. The first is to recognize current processes of advancement and backlash politics as a silent security dilemma that undermines rights, justice, and public health based approaches to reproductive health. The second is to draw on the human security origins of global health security to reorient the concept away from protecting states to protecting individuals. Finally, a feminist approach to security is incomplete without recognising reproductive health as a threat to women's security and as a barrier to their participation in international peace and security processes. Reproductive health is central to effective peacebuilding yet remains curiously absent from the international peace and security discourse. We discuss how and why reproductive security should become integrated within the Women, Peace, and Security (WPS) agenda in order to hold states to account for reproductive health access. Reproductive security defines the urgency and threat of restricted reproductive health care to the lives of women, health-care providers, and sustained international peace and security.