bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrition in the context of the Sustainable Development Goals
Authors: Grosso Giuseppe , Mateo Alberto , Rangelov Natalie , Buzeti Tatjana , Birt Christopher
Published: February 2020

The 2030 Agenda for the Sustainable Development Goals (SDGs) represents a common framework of international cooperation to promote sustainable development. Nutrition is the key point for the SDG 2 ‘End hunger, achieve food security and improved nutrition and promote sustainable agriculture’ and is an essential component for achieving many of the other targets: overall, the nutritional aspects of the SDGs aim to promote healthy and sustainable diets and ensure food security globally. While undernutrition is of minimal concern in the European Union Member States, trends in childhood obesity are still alarming and far from any desirable target. European food production systems have improved over the last years, with immediate impact on several environmental aspects; however, a comprehensive regulatory framework to fulfil the environmental and climate targets is still lacking. Policy actions at multinational level are needed to achieve global nutrition targets designed to guide progress towards tackling all forms of malnutrition while preserving the environment through virtuous food production and food systems.
A minimum set of regulators to thrive in the ocean
Authors: Lambrecht S Joke , Steglich Claudia , Hess Wolfgang R
Published: February 2020

Marine cyanobacteria of the genus Prochlorococcus thrive in high cell numbers throughout the euphotic zones of the world's subtropical and tropical oligotrophic oceans, making them some of the most ecologically relevant photosynthetic microorganisms on Earth. The ecological success of these free-living phototrophs suggests that they are equipped with a regulatory system competent to address many different stress situations. However, Prochlorococcus genomes are compact and streamlined, with the majority encoding only five different sigma factors, five to six two-component systems and eight types of other transcriptional regulators. Here, we summarize the existing information about the functions of these protein regulators, about transcriptomic responses to defined stress conditions, and discuss the current knowledge about riboswitches, RNA-based regulation and the roles of certain metabolites as co-regulators. We focus on the best-studied isolate, Prochlorococcus MED4, but extend to other strains and ecotypes when appropriate, and we include some information gained from metagenomic and metatranscriptomic analyses.
Satellite imaging of the 2015 M7.2 earthquake in the Central Pamir, Tajikistan, elucidates a sequence of shallow strike-slip ruptures of the Sarez-Karakul fault
Authors: Elliott A , Elliott J , Hollingsworth J , Kulikova G , Parsons B , Walker R
Published: February 2020

On 7 December 2015, a shallow Mw 7.2 strike-slip earthquake struck the Murghab River Valley in the Central Pamirs of Tajikistan. Seismologically this event was similar to a large seismic event in 1911 whose causative fault has never been identified. We measure the displacement field of the 2015 event from satellite observations using Sentinel-1 radar interferometry, Landsat-8 optical pixel-tracking, and surface rupture mapping from high resolution SPOT-6/7 imagery to characterize the role this earthquake rupture plays in the accommodation of strain on its causative structure, the Sarez-Karakul fault. We present geomorphic mapping and interpretations of other Quaternary-active reaches of this fault system, which highlight variable rupture history of the different sections. These sections appear to be separated by inherited bedrock structural boundaries. Significantly, the reaches of the fault northeast and southwest of the 2015 rupture exhibit the freshest morphology prior to 2015, indicative of a more recent rupture than elsewhere. Using new high resolution imagery we map fresh scarps at the northern and southern ends of the Sarez-Karakul fault which may represent this 1911 rupture. To test which of these reaches could have been the source of the elusive 1911 event, we compare synthetic seismograms from three plausible fault sources determined from geomorphology, with observed seismic traces from 1911 at early recording stations throughout Europe. We find that the best fitting fault source is in fact southwest of the 2015 rupture, meaning that we have a record of three distinct recent events on the Sarez-Karakul fault system—two of them instrumentally recorded. Our mapping of these separate events reveals a correlation between their boundaries and the active and inherited thrust and suture systems that intersect the northeast striking left-lateral fault, suggesting structural control over the extents of individual ruptures on the active strike-slip fault.
The HOPS complex subunit VPS39 controls ciliogenesis through autophagy
Authors: Iaconis Daniela , Crina Claudia , Brillante Simona , Indrieri Alessia , Morleo Manuela , Franco Brunella
Published: February 2020

Primary cilia are microtubule-based organelles that assemble and protrude from the surface of most mammalian cells during quiescence. The biomedical relevance of cilia is indicated by disorders ascribed to cilia dysfunction, known as ciliopathies, that display distinctive features including renal cystic disease. In this report, we demonstrate that vacuolar protein sorting 39 (VPS39), a component of the homotypic fusion and vacuole protein sorting (HOPS) complex, acts as a negative regulator of ciliogenesis in human renal cells, by controlling the localization of the intraflagellar transport 20 protein at the base of cilia through autophagy. Moreover, we show that VPS39 controls ciliogenesis through autophagy also in vivo in renal tubules of medaka fish. These observations suggest a direct involvement of the HOPS complex in the regulation of autophagy-mediated ciliogenesis and eventually in target selection. Interestingly, we show that the impact of autophagy modulation on ciliogenesis is cell-type dependent and strictly related to environmental stimuli. This report adds a further tile to the cilia-autophagy connection and suggests that VPS39 could represent a new biological target for the recovery of the cilia-related phenotypes observed in the kidneys of patients affected by ciliopathies.
Restructuring Euro Area Sovereign Debt: Have the Options Narrowed?
Authors: Weidemaier W Mark C
Published: February 2020

This article examines the intersection between two key attributes of sovereign debt governance in the Euro Area. First, sovereigns mostly issue bonds governed by their own law. This ‘local law advantage’ should make debt restructuring comparatively easy, as the sovereign can change the law to reduce its debt. The second attribute is the so-called ‘Euro CAC’, which is a contract-based restructuring mechanism mandated by the Treaty Establishing the European Stability Mechanism (the ESM Treaty). The Euro CAC lets a bondholder supermajority approve a restructuring and bind dissenters. Since 2013, nearly all Euro Area sovereign debt has included the clause. Many believe the ESM Treaty requires governments to use the Euro CAC to restructure. But if so, the Treaty is a suicide pact, for the design of the Euro CAC is flawed. In a meaningful subset of cases, the clause will not provide adequate debt relief. This article makes two primary contributions. First, using an Italian restructuring as an example, it explains why the ESM Treaty does not, in fact, require the use of the Euro CAC. Second, it examines the legal constraints—the most pertinent of which derive from the European Convention on Human Rights—that do restrict the use of local-law advantage.
Bayesian Semi-Parametric Realized Conditional Autoregressive Expectile Models for Tail Risk Forecasting
Authors: Gerlach Richard , Wang Chao
Published: February 2020

A new model framework called Realized Conditional Autoregressive Expectile is proposed, whereby a measurement equation is added to the conventional Conditional Autoregressive Expectile model. A realized measure acts as the dependent variable in the measurement equation, capturing the contemporaneous dependence between it and the latent conditional expectile; it also drives the expectile dynamics. The usual grid search and asymmetric least squares optimization, to estimate the expectile level and parameters, suffers from convergence issues leading to inefficient estimation. This article develops an alternative random walk Metropolis stochastic target search method, incorporating an adaptive Markov Chain Monte Carlo sampler, which leads to improved accuracy in estimation of the expectile level and model parameters. The sampling properties of this method are assessed via a simulation study. In a forecast study applied to several market indices and asset return series, one-day-ahead Value-at-Risk and Expected Shortfall forecasting results favor the proposed model class.
The Health and Readiness of Service Members: ACEs to PACEs
Authors: Lamson Angela , Richardson Natalie , Cobb Erin
Published: February 2020

Introduction

Over the past three decades, a growing research base has emerged around the role of adverse childhood experiences (ACEs) in the biological, psychological, social, and relational health and development of children and adults. More recently, the role of ACEs has been researched with military service members. The purpose of this article was to provide a brief description of ACEs and an overview of the key tenets of the theory of toxic stress as well as a snapshot of ACEs and protective and compensatory experiences (PACEs) research with active duty personnel.

Methods

Ninety-seven active duty personnel completed the study including questions pertaining to demographics, adverse childhood experiences, adult adverse experiences, and PACEs survey.

Results

Significant findings pertaining to ACEs and PACEs were found by service member’s sex and rank, with higher ACE scores for men and enlisted service members.

Conclusions

The contrast by rank and sex in relation to ACEs punctuates the need for attention to ACEs and protective factors among early career service members in order to promote sustainable careers in the military.
Continuity in Psychological Health and Role Functioning Across Deployment
Authors: Southwell Kenona H , Coppola Elizabeth C , Topp David B , MacDermid Wadsworth Shelley M
Published: February 2020

Introduction

Scholars have described military deployments as one of the most stressful aspects of life for military couples. Deployment affects multiple roles and family members, yet little is known about the degree to which postdeployment outcomes are accounted for by predeployment functioning independent of deployment experiences.

Methods

Data collection included in-person interviews with National Guard couples experiencing a deployment and a comparison group whose deployment was canceled abruptly. Using hierarchical regression, this study assessed (a) how much variance in postdeployment functioning was explained by predeployment functioning and (b) whether variance accounted for by predeployment functioning differed by domain, respondent, or deployment status. Posthoc analyses revealed which combinations of predeployment functioning accounted for the most variance in postdeployment outcomes.

Results

We found evidence of modest continuity between predeployment and postdeployment functioning, particularly for psychological functioning and partner role functioning, and fewer differences than expected in patterns between groups. Certain demographic characteristics, risk factors, and resources accounted for significant variance in postdeployment outcomes in addition to baseline levels of role functioning.

Conclusions

Study findings reinforce the importance of predeployment preparation, providing families with resources to maximize resilience in response to the stress of deployment.
The Effectiveness of the DoD/VA Mobile Device Outcomes-Based Rehabilitation Program for High Functioning Service Members and Veterans with Lower Limb Amputation
Authors: Gaunaurd Ignacio , Gailey Robert , Springer Barbara , Symsack Allison , Clemens Sheila , Lucarevic Jennifer , Kristal Anat , Bennett Christopher , Isaacson Brad , Agrawal Vibhor , Applegate Brooks , Pasquina Paul
Published: February 2020

Introduction

The objective was to determine if the Mobile Device Outcomes-based Rehabilitation Program (MDORP) improved strength, mobility, and gait quality in service members (SMs) and Veterans with lower limb amputation (LLA).

Methods

Seven SMs and 10 Veterans with LLA enrolled and were trained to use a mobile sensor system, called Rehabilitative Lower Limb Orthopedic Analysis Device (ReLOAD). ReLOAD provided participants with real-time assessment of gait deviations, subsequent corrective audio feedback, and exercise prescription for normalizing gait at home and in the community. After baseline testing, prosthetic gait and exercise training, participants took ReLOAD home and completed an 8-week walking and home exercise program. Home visits were conducted every 2 weeks to review gait training and home exercises.

Results

Significant improvements in hip extensor strength, basic and high-level mobility, musculoskeletal endurance, and gait quality (P < 0.05) were found at the completion of the 8-week intervention.

Conclusion

Preliminary MDORP results are promising in its ability to improve basic and high-level mobility, lower limb strength, and gait quality in a group of SMs and Veterans with LLA. In addition, “booster” prosthetic training may be justified in an effort helps maintain an active lifestyle, promotes prosthetic use, and mitigates secondary health effects.
Developing the Prototype Embedded Health Engagement Team
Authors: Burkett Edwin K , Neese Brian , Lawrence Cristina Y
Published: February 2020

Small, well prepared, culturally competent, and embedded health engagement teams (EHET) tailored to work within a partner health system, rather than outside of it, will achieve greater mutual benefit, desired military objectives, and better health outcomes for the United States Department of Defence and its partners. EHETs have significant advantages over traditional methods of choice for health security cooperation and humanitarian assistance missions. These advantages include enhanced capability and capacity building, greater trust through intentional cultural expertise, a ready platform for enduring relationships, enhanced host nation legitimacy, and flexibility to target specific issues with greater fidelity. We must first define a prototype EHET, compare the concept against prior units that have executed health engagement, and test it prospectively in employment. The U.S. military and the civilian business world each have extensive experience in employing small teams that the health community can emulate. The ideal EHET should have the following nine characteristics: 12 people or fewer, skillsets for the tasks, global health knowledge, be multidisciplinary, a balance of experience, local language capability, geopolitical and cultural competence, targeted preparation for specific security and health objectives, and joint representation. This paper will explore these components of the prototype EHET as it will be tested in our research project.
Detection of Retinal Fibrosis in a Rabbit Model of Penetrating Eye Injury
Authors: Greene Whitney , Burke Teresa , Bramblett Gregory , Wang Heuy-Ching
Published: February 2020

Introduction

To establish a rabbit model of posterior penetrating eye injury as a platform to test potential therapeutics.

Materials and Methods

Anesthetized rabbits received posterior penetrating eye injury in one eye, whereas contralateral eyes were maintained as uninjured controls. Rabbits were randomized into two experimental groups. Group A was euthanized on Day 14 postinjury to determine retinal fibrosis at an early phase of disease progression. Group B was euthanized on Day 28 postinjury to examine retinal fibrosis at a late phase of disease progression. We examined animals on postinjury Days 7, 14, 21, and 28 with indirect ophthalmoscope and fundus photography. After euthanasia, eyes were processed for histology and immunofluorescence labeling of fibrotic proteins α-smooth muscle actin and collagen I.

Results

Early fibrosis was detected by Day 14, as indicated by indirect ophthalmoscopy and fundus imaging. Fibrotic membranes were visible at sites of injury. Immunofluorescence analysis detected α-smooth muscle actin and collagen I within the fibrotic membranes.

Conclusions

These data show that ocular fibrosis can be detected within 14 days after initial injury, with more severe fibrosis detected at 28 days postinjury. These results will be used to determine the optimal time points for later studies designed to test treatment strategies.
Impedance Control Strategies for Enhancing Sloped and Level Walking Capabilities for Individuals with Transfemoral Amputation Using a Powered Multi-Joint Prosthesis
Authors: Bhakta Krishan , Camargo Jonathan , Kunapuli Pratik , Childers Lee , Young Aaron
Published: February 2020

Introduction

Powered prostheses are a promising new technology that may help people with lower-limb loss improve their ability to perform locomotion tasks. Developing active prostheses requires robust design methodologies and intelligent controllers to appropriately provide assistance to the user for varied tasks in different environments. The purpose of this study was to validate an impedance control strategy for a powered knee and ankle prosthesis using an embedded sensor suite of encoders and a six-axis load cell that would aid an individual in performing common locomotion tasks, such as level walking and ascending/descending slopes.

Materials and Methods

Three amputees walked on a treadmill and four amputees walked on a ramp circuit to test whether a dual powered knee and ankle prosthesis could generate appropriate device joint kinematics across users.

Results

Investigators found that tuning 2–3 subject-specific parameters per ambulation mode was necessary to render individualized assistance. Furthermore, the kinematic profiles demonstrate invariance to walking speeds ranging from 0.63 to 1.07 m/s and incline/decline angles ranging from 7.8° to 14°.

Conclusion

This work presents a strategy that requires minimal tuning for a powered knee & ankle prosthesis that scales across a nominal range of both walking speeds and ramp slopes.
Telementoring in Leg Fasciotomies via Mixed-Reality: Clinical Evaluation of the STAR Platform
Authors: Rojas-Muñoz Edgar , Cabrera Maria Eugenia , Lin Chengyuan , Sánchez-Tamayo Natalia , Andersen Dan , Popescu Voicu , Anderson Kathryn , Zarzaur Ben , Mullis Brian , Wachs Juan P
Published: February 2020

Introduction

Point-of-injury (POI) care requires immediate specialized assistance but delays and expertise lapses can lead to complications. In such scenarios, telementoring can benefit health practitioners by transmitting guidance from remote specialists. However, current telementoring systems are not appropriate for POI care. This article clinically evaluates our System for Telementoring with Augmented Reality (STAR), a novel telementoring system based on an augmented reality head-mounted display. The system is portable, self-contained, and displays virtual surgical guidance onto the operating field. These capabilities can facilitate telementoring in POI scenarios while mitigating limitations of conventional telementoring systems.

Methods

Twenty participants performed leg fasciotomies on cadaveric specimens under either one of two experimental conditions: telementoring using STAR; or without telementoring but reviewing the procedure beforehand. An expert surgeon evaluated the participants’ performance in terms of completion time, number of errors, and procedure-related scores. Additional metrics included a self-reported confidence score and postexperiment questionnaires.

Results

STAR effectively delivered surgical guidance to nonspecialist health practitioners: participants using STAR performed fewer errors and obtained higher procedure-related scores.

Conclusions

This work validates STAR as a viable surgical telementoring platform, which could be further explored to aid in scenarios where life-saving care must be delivered in a prehospital setting.
Prehospital Use of Ketamine in the Combat Setting: A Sub-Analysis of Patients With Head Injuries Evaluated in the Prospective Life Saving Intervention Study
Authors: Bebarta Vikhyat S , Mora Alejandra G , Bebarta Emma K , Reeves Lauren K , Maddry Joseph K , Schauer Steve G , Lairet Julio R
Published: February 2020

Objectives

Ketamine is used as an analgesic for combat injuries. Ketamine may worsen brain injury, but new studies suggest neuroprotection. Our objective was to report the outcomes of combat casualties with traumatic brain injury (TBI) who received prehospital ketamine.

Methods

This was a post hoc, sub-analysis of a larger prospective, multicenter study (the Life Saving Intervention study [LSI]) evaluating prehospital interventions performed in Afghanistan. A DoD Trauma Registry query provided disposition at discharge and outcomes to be linked with the LSI data.

Results

For this study, we enrolled casualties that were suspected to have TBI (n = 160). Most were 26-year-old males (98%) with explosion-related injuries (66%), a median injury severity score of 12, and 5% mortality. Fifty-seven percent (n = 91) received an analgesic, 29% (n = 46) ketamine, 28% (n = 45) other analgesic (OA), and 43% (n = 69) no analgesic (NA). The ketamine group had more pelvic injuries (P = 0.0302) and tourniquets (P = 0.0041) compared to OA. In comparison to NA, the ketamine group was more severely injured and more likely to require LSI procedures, yet, had similar vital signs at admission and disposition at discharge.

Conclusions

We found that combat casualties with suspected TBI that received prehospital ketamine had similar outcomes to those that received OAs or NAs despite injury differences.
The weak lensing bispectrum induced by gravity
Authors: Munshi D , Namikawa T , Kitching T D , McEwen J D , Takahashi R , Bouchet F R , Taruya A , Bose B
Published: February 2020

Recent studies have demonstrated that secondary non-Gaussianity induced by gravity will be detected with a high signal-to-noise ratio (S/N) by future and even by on-going weak lensing surveys. One way to characterize such non-Gaussianity is through the detection of a non-zero three-point correlation function of the lensing convergence field, or of its harmonic transform, the bispectrum. A recent study analysed the properties of the squeezed configuration of the bispectrum, when two wavenumbers are much larger than the third one. We extend this work by estimating the amplitude of the (reduced) bispectrum in four generic configurations, i.e. squeezed, equilateral, isosceles and folded, and for four different source redshifts zs = 0.5, 1.0, 1.5, 2.0, by using an ensemble of all-sky high-resolution simulations. We compare these results against theoretical predictions. We find that, while the theoretical expectations based on widely used fitting functions can predict the general trends of the reduced bispectra, a more accurate theoretical modelling will be required to analyse the next generation of all-sky weak lensing surveys. The disagreement is particularly pronounced in the squeezed limit.
Blueshifted absorption lines from X-ray reflection in IRAS 13224−3809
Authors: Fabian A C , Reynolds C S , Jiang J , Pinto C , Gallo L C , Parker M L , Lasenby A N , Alston W N , Buisson D J K , Cackett E M , De Marco B , Garcia J , Kara E , Kosec P , Middleton M J , Miller J M , Miniutti G , Walton D J , Wilkins D R , Young A J
Published: February 2020

We explore a disc origin for the highly blueshifted, variable absorption lines seen in the X-ray spectrum of the narrow-line Seyfert 1 galaxy IRAS 13224−3809. The blueshift corresponds to a velocity of ∼0.25c. Such features in other active galactic nuclei are often interpreted as ultrafast outflows. The velocity is of course present in the orbital motions of the inner disc. The absorption lines in IRAS 13224−3809 are best seen when the flux is low and the reflection component of the disc is strong relative to the power-law continuum. The spectra are consistent with a model in which the reflection component passes through a thin, highly ionized absorbing layer at the surface of the inner disc, the blueshifted side of which dominates the flux due to relativistic aberration (the disc inclination is about 70°). No fast outflow need occurs beyond the disc.
Revisiting BeppoSAX and NuSTAR observations of KS 1947+300 and the missing cyclotron line
Authors: Doroshenko R , Piraino S , Doroshenko V , Santangelo A
Published: February 2020

Motivated by the alleged detection of a cyclotron resonance scattering feature in the X-ray spectrum of the Be-transient KS 1947+300 with NuSTAR, not observed with other observatories, we have revisited the available observations of the source to clarify the origin of the reported feature. We focus on the analysis of observations obtained with the BeppoSAX observatory during the 2001 outburst, and by NuSTAR in 2013, when the discovery of the line was reported. We find that in both cases, the source broad-band X-ray continuum can be well described with a two-component Comptonization model, which does not require an additional absorption-like feature. In addition, we show that low-significance residuals mimicking the line, which appear using different continuum models, are consistent with known calibration uncertainties. We therefore conclude that the reported cyclotron line detection is largely questionable, and thus the question on the strength of the source magnetic field remains open. We briefly discuss the origin of the observed broad-band continuum in the context of the pulse-phase-resolved analysis conducted for BeppoSAX data and speculate that the soft component may be associated with the emission from polar areas of the pulsar irradiated by the accretion column.
The uncertain masses of progenitors of core-collapse supernovae and direct-collapse black holes
Authors: Farrell Eoin J , Groh Jose H , Meynet Georges , Eldridge J J
Published: February 2020

We show that it is not possible to determine the final mass Mfin of a red supergiant (RSG) at the pre-supernova (SN) stage from its luminosity L and effective temperature Teff alone. Using a grid of stellar models, we demonstrate that for a given value of L and Teff, an RSG can have a range of Mfin as wide as 3 to 45 M⊙. While the probability distribution within these limits is not flat, any individual determination of Mfin for an RSG will be degenerate. This makes it difficult to determine its evolutionary history and to map Mfin to an initial mass. Single stars produce a narrower range that is difficult to accurately determine without making strong assumptions about mass-loss, convection, and rotation. Binaries would produce a wider range of RSG Mfin. However, the final Helium core mass $M_{\operatorname{He-core}}$ is well determined by the final luminosity and we find $\log (M_{\operatorname{He-core}}/\mathrm{M}_{\odot }) = 0.659 \log (L/\mathrm{L}_{\odot }) -2.630$. Using this relationship, we derive $M_{\operatorname{He-core}}$ for directly imaged SN progenitors and one failed SN candidate. The value of Mfin for stripped star progenitors of SNe IIb is better constrained by L and Teff due to the dependence of Teff on the envelope mass Menv for Menv ≲ 1 M⊙. Given the initial mass function, our results apply to the majority of progenitors of core-collapse SNe, failed SNe, and direct-collapse black holes.
The prognostic role of BRAF and WNT pathways activation in kinase inhibitors-naïve clinical stage III cutaneous melanoma
Authors: Kowalik Artur , Jurkowska Monika , Mierzejewska Ewa , Ługowska Iwona , Gos Aleksandra , Szumera-Ciećkiewicz Anna , Zięba Sebastian , Koseła-Paterczyk Hanna , van der Oord Joost , Dębiec-Rychter Maria , Szamotulska Katarzyna , Siedlecki Janusz , Rutkowski Piotr
Published: February 2020

The results of local-regional advanced melanoma (stage III) management are still not satisfactory. Particularly, there is no personalized treatment in stage III melanoma patients due to the lack of useful classical pathological markers for prognostication of indolent or aggressive course of the disease. The aim of this study was to explore melanoma genomic landscape by means of the mutational profiling of 50 genes influencing carcinogenesis pathways in the randomly selected 93 kinase inhibitor-naïve (KI-naïve) stage III patients. The genomic alterations were found in 27 out of 50 tested genes and at least one pathogenic variant was detected in 77 out of 93 cases (82.7%). Survival rate was negatively affected by the presence of the somatic mutations inAKT1,ATM,CDH1andSMARCB1, while theBRAF+ status in KI-naïve stage III population correlated with the longer median overall survival. Genomic alterations in WNT pathway correlated with extranodal adipocyte tissue involvement (P = 0.027) and higher number of metastatic lymph nodes (P = 0.045). In terms of survival, the Cox model confirmed the worse prognosis in patients with mutation in the WNT pathway [hazard ratio (HR) = 2.9,P = 0.017], and better prognosis in cases with mutations in BRAF pathway (HR = 0.5,P = 0.004). WNT/β-catenin pathway alteration was associated with more advanced/aggressive disease. From this perspective, the concept of blocking the activity of the WNT pathway in selected cases appears promising and complementary to the BRAF inhibition therapeutic option for the future.
An Open-Label, Prospective Study Evaluating the Clinical and Immunological Effects of Higher Dose Granulocyte Colony–Stimulating Factor in ALS
Authors: Pocock Kristyn , Suresh Niraja , Suradi Yazan , Dang Samuel , Harvey Brittany , Cao Chuanhai , Sutherland Kyle , Lin Xiaoyang , Vu Tuan H. , Gooch Clifton
Published: February 2020

Objective:

We evaluated the safety and tolerability of higher-dose granulocyte colony–stimulating factor (G-CSF) in patients with amyotrophic lateral sclerosis. In addition, rates of disease progression and serum G-CSF levels and other immunological and hematological markers were measured.

Methods:

Three patients with advanced amyotrophic lateral sclerosis were treated with G-CSF subcutaneously at 5 μg/kg twice daily for 5 consecutive days monthly for 4–12 months. Patients were monitored for adverse effects, and disease progression was assessed with ALSFRS-R and other measures.

Results:

Patients tolerated higher-dose G-CSF well with no serious adverse events. Adverse effects were mild to moderate with musculoskeletal pain and malaise being most often reported. No significant change in the rate of disease progression was noted for ALSFRS-R or other measures. Bone marrow progenitor cells were rapidly mobilized for a duration of approximately 9 days with transient and variable effect on cytokines.

Conclusions:

Higher-dose G-CSF was well tolerated in this cohort with no apparent effect on disease progression up to 1 year.
Implementation Lessons From a Randomized Trial Integrating Community Asthma Education for Children
Authors: Martin Molly A. , Bisarini Reymundo , Roy Angkana , Mosnaim Giselle , Rosales Genesis , Weinstein Sally , Walton Surrey M.
Published: February 2020

This study characterized and compared the implementation of clinically integrated community health workers (CHWs) to a certified asthma educator (AE-C) for low-income children with asthma. In the AE-C arm (N = 115), 51.3% completed at least one in-clinic education session. In the CHW arm (N = 108), 722 home visits were completed. The median number of visits was 7 (range, 0-17). Scheduled in-clinic asthma education may not be the optimal intervention for this patient population. CHW visit completion rates suggest that the schedule, location, and content of CHW asthma services better met patients' needs. Seven to 10 visits seemed to be the preferred CHW dose.
Safety and efficacy of intracoronary prourokinase administration in patients with high thrombus burden
Authors: Wang Xuechao , Liu Huiliang , Wu Haibo , Xiao Yuyang , Bai Shiru , Li Xinning , Li Xiangming , Zhang Lina , Chen Tianlei , Li Hongxiao , Liu Jia , Du Rongpin
Published: February 2020

Objectives

The study was designed to evaluate the effect of low-dose intracoronary prourokinase administration immediately after thrombus aspiration in patients with ST-segment elevation myocardial infarction (STEMI) presenting with a serious thrombus burden.

Methods

Consecutive STEMI patients with high thrombus burden received thrombus aspiration during primary percutaneous coronary intervention (PCI) were randomly assigned to study group (intracoronary prourokinase administration) or control group (intracoronary 0.9% sodium chloride administration). The primary endpoint was complete ST-segment resolution (STR) at 90 min after primary PCI, and the secondary endpoints included angiographic myocardial perfusion indexes.

Results

Patients in study group had a higher incidence of complete STR and myocardial blush grade 3 compared with those in control group (56.52% vs. 38.89%, P = 0.017 and 57.61% vs. 38.89%, P = 0.041). The peak cardiac troponin I value and corrected thrombolysis in myocardial infarction frame count were significantly lower in study group (52.16 ± 24.67 ng/mL vs. 60.91 ± 28.81 ng/mL, P = 0.029; and 19.57 ± 9.05 vs. 22.91 ± 10.22, P = 0.020). A significant improvement in left ventricular ejection fraction and major adverse cardiac events (MACEs)-free survival was observed in study group (55.22 ± 10.50% vs. 52.18 ± 9.39%, P = 0.041; 10.87% vs. 22.22%, P = 0.039) at the 6-month follow-up. The bleeding complication was similar in both groups (17.39% vs. 12.22%, P = 0.327).

Conclusions

In STEMI patients with high thrombus burden, low-dose prourokinase intracoronary administered immediately after thrombus aspiration improves myocardial perfusion, cardiac function, and MACEs-free survival with no significant increase in major bleeding.
Gastrointestinal taste receptors: could tastants become drugs?
Authors: Behrens Maik , Somoza Veronika
Published: February 2020

Purpose of review

Numerous studies have pointed to profound nongustatory roles of tastants and the corresponding taste receptors expressed in the alimentary canal in the modulation of digestive and metabolic functions. Already in early reports, the intriguing possibility to use tastants as drug-like effectors for the treatment of metabolic diseases was raised. With this review, focusing on the most recent literature, we intend to question how close we meanwhile came to the initial promise – the use of tastants as medicines.

Recent findings

Although the enormous complexity and experimental variability of studies investigating the effects of tastants on physiological functions still has not revealed a common fundament from which subsequent therapeutic measures could be designed, more and more evidence is mounting on an involvement of taste receptors and taste signaling molecules in the maintenance and fine regulation of gastrointestinal functions and immunity.

Although the initial goal – using tastants to treat metabolic disorders – has, by far, not been reached, numerous promising findings suggest that dietary interventions could be devised to support conventional therapies in the future.
PTFE-covered TIPS is an effective treatment for secondary preventing variceal rebleeding in cirrhotic patients with high risks
Authors: Zhou Yongjie , Zhang Wen , Zhang Zihan , Luo Jianjun , Gu Junying , Liu Qingxin , Ma Jingqin , Yan Zhiping , Chen Shiyao , Wang Jian
Published: February 2020

Aim

To compare the effectiveness and safety of transjugular intrahepatic portosystemic shunt (TIPS) with endoscopic therapy plus non-selective β-blockers (NSBBs) for secondary prevention of gasroesophageal variceal bleeding (GEVB) in cirrhotic patients with high-risk factors of treatment failure.

Methods and material:

A total of 122 cirrhotic patients with history of gasroesophageal variceal bleeding and high factors including hepatic vein pressure gradient (HVPG) ≥ 20 mmHg, portal vein thrombosis (PVT), gastrorenal shunt (GRS), or extraluminal para-gastric veins (ep-GVs) detected by endoscopic ultrasound, were analyzed retrospectively. Seventy-seven patients underwent TIPS with PTFE-covered stent (group A) and 102 patients received endoscopic therapy combined with nonselective β-blockers (NSBBs) (group B). According to above high-risk factors, both groups were stratified into four paired subgroups (A1–A4 and B1–B4). Two-year rebleeding rate, overt hepatic encephalopathy, overall survival, and procedure-related adverse events were compared between the two groups and paired subgroups.

Results:

The 2-year cumulative probability of free of variceal rebleeding was higher in group A than group B (93 vs. 62%, P < 0.001). Similarly, the 2-year cumulative probability of free of variceal rebleeding was also higher in the subgroups A1–A4 than the subgroups B1–B4 (91 vs. 67%, P = 0.022, 90 vs. 67%, P = 0.021, 94 vs. 59%, P = 0.029, and 90 vs. 58%, P = 0.016, respectively). There was no significant difference between the two groups and corresponding subgroups in overt hepatic encephalopathy and survival.

Conclusion:

Compared to secondary prophylaxis with endoscopic therapy plus NSBBs, polytetrafluoroethylene-covered TIPS could significantly reduce the variceal rebleeding rate in cirrhotic patients with HVPG ≥ 20 mmHg, PVT, GRS, or ep-GVs, without increasing the incidence of hepatic encephalopathy.
Diagnostic pathways in major trauma patients admitted to Italian hospitals: survey and discussion points from the trauma update 2019
Authors: Tartaglione Marco , Gamberini Lorenzo , Coniglio Carlo , Lupi Cristian , Montanari Nicola , Bardi Tommaso , Chiarini Valentina , Giugni Aimone , Gordini Giovanni
Published: February 2020

Background

Major trauma is a leading cause of mortality, morbidity, and disability. Severe trauma patients are taken to hospital with multiple suspected injuries and need urgent diagnosis in order to achieve focused and lifesaving interventions. The primary endpoint of this survey was to evaluate the intrahospital diagnostic paths that trauma patients undergo in Italian hospitals. Thus, during the 14th Italian Trauma Network Congress (Trauma UpDate, Bologna, February 2019), we collected and discussed data from Italian hospitals regarding the usual diagnostic pathway for major trauma patients.

Methods

Three sets of multiple closed questions, designed to measure the structure, protocols, and habits of Italian hospitals were sent prior to the congress. The questionnaire was developed on the basis of the available literature and expert opinion, regarding: (1) the role of E-FAST, chest and pelvis radiographs in stable major trauma patients; (2) diagnostic pathways after the first-level imaging in major trauma patients, focused on a number of clinical scenarios; (3) diffusion and knowledge of trauma-specific computed tomography (CT) protocols and fast radiologic reporting.

Results

We obtained a total of 232 responses to our survey. A remarkable heterogeneity was found between hub and spoke hospitals regarding the indications to the first- and second-level diagnostics, and their use before centralization to trauma centers of patients admitted to peripheral hospitals.

Conclusion

Italian hospitals show a high heterogeneity in the diagnostic pathways proposed to major trauma victims, an interdisciplinary revision of local protocols taking into account hospital capabilities, new evidence, and emergency system geographical distribution is strongly recommended.
‘Stop sign’ position for subclavian ultrasound: a single-blinded observational study of subclavian vein dimensions
Authors: Lister Rachel B. , Welfare Oliver W.d’A. , Cheri Thomas , Park Michael A.J.
Published: February 2020

Objective

Right subclavian vein (SCV) dimensions were evaluated on ultrasound and whether these change when the right upper limb is in a neutral position compared with the ‘stop sign’ position (shoulder abducted and externally rotated to 90°, elbow flexed to 90°), and when patients were positioned 30° head-up compared with lying supine.

Methods

Images of transverse and longitudinal views of the right SCV in patients ≥18 years, presenting with a range of conditions to a Regional Hospital Emergency Department, were recorded by two physicians in a randomly assigned, nonsequential order and measured blinded. Data were analysed with paired Student’s t tests. N = 62.

Results

Primary outcome: cross-sectional area (CSA) of the right SCV in transverse images. Secondary outcomes: depth of SCV to skin and diameter of SCV on longitudinal images. There was no significant difference in CSA of the SCV in supine patients when the arm was in the stop sign position compared with neutral (mean CSA: 1.20 ± 0.42 and 1.15 ± 0.39 cm2, respectively; P = 0.3). In patients positioned 30° head-up, the stop sign position significantly increased CSA from 0.65 ± 0.33 to 1.00 ± 0.38 cm2 (P < 0.0001).

Conclusions

Utilizing the stop sign position does not change SVC dimensions when patients are supine, however, may improve dimensions when lying supine is contraindicated.
Protein-losing enteropathy
Authors: Elli Luca , Topa Matilde , Rimondi Alessandro
Published: February 2020

Purpose of review

The present review offers its readers a practical overview of protein-losing enteropathy, particularly with regard to diagnostic and therapeutic approaches. The aim is to support clinicians in their daily practice with a practical tool to deal with protein-losing enteropathy.

Recent findings

The literature covering protein-losing enteropathy does not appear to be quite recent and also guidelines are scanty. The main innovations during the last decade probably regard the introduction of enteroscopic techniques in the diagnostic flowchart. The use of video-capsule and device-assisted enteroscopy has enabled the direct exploration of the small bowel and the identification of the damage causing the loss of proteins from the gastrointestinal tract. Other innovations are to do with the therapies of the disorder underlying protein-losing enteropathy, although the support with nutritional supplementation are the direct remedies to tackle the protein loss.

Protein-losing enteropathy represents an important clinical aspect of different gastrointestinal and extra-intestinal diseases. An established flowchart is still unavailable, but the use of enteroscopy has deeply changed the modern diagnostic approach. Nutritional support and therapy of the underlying disease are pivotal to patients’ management.
Current status of pediatric intestinal transplant in Europe
Authors: Andres Ane M. , Ramos Esther , Hernandez Francisco
Published: February 2020

Purpose of review

This review features articles published during 2018 and 2019 regarding pediatric visceral transplantation in Europe. In this biannual review, the authors identify and summarize key articles pertinent to clinical and research areas.

Recent findings

There is a trend to a lower use of intestinal transplantation in pediatric population in Europe. Most articles were focused in long-term follow-up. The burden of the disease 10 years after intestinal transplantation is still significant, including the need of several medications, readmissions, and the need of specific follow-up, mostly because of psychiatric problems. Regarding eating behaviors, promoting eating pretransplant may be protective and there may be eating difficulty predictors that could be used to facilitate targeted interventions. Two different articles were consistent in the identification of C1q-fixing DSA as a marker of poor outcome, and capillaritis was identified as a predictor of C4d positivity in intestinal graft biopsies. The inclusion of the liver emerged as the main protective factor against dnDSA development. The incidence of PTLD (specially the monomorphic type) was significantly higher following ITx than after LTx (14.9 vs. 2.8%). The European societies and the EU have made an effort to promote networking, collaborative registries, and sharing of knowledge in pediatric transplantation.

Recent articles focused mostly on long-term follow-up issues, although translational research has also been sustained by some groups.
Tolerance studies in liver transplantation: are we fooling ourselves?
Authors: Tran Lillian , Humar Abhinav
Published: February 2020

Purpose of review

This article will summarize outcomes of prior immunosuppression withdrawal trials in pediatric and adult liver transplantation and provide updates on the current status of ongoing clinical tolerance studies including evolving strategies, such as identification of reliable biomarkers or immunomodulation to achieve an earlier onset and more robust level of operational tolerance.

Recent findings

Clinical tolerance studies in liver transplantation have previously been limited by inconsistent and delayed success of immunosuppressive withdrawal, lack of substantial histological analysis from liver tissue biopsy, and the inability to translate mechanistic studies to reproducible clinical outcomes. Current clinical trials are attempting to overcome these hurdles through more comprehensive and guided immunosuppression withdrawal protocols. Novel and emerging technologies are enabling investigators to identify and validate potential biomarkers of tolerance in order to predict patient subpopulations disposed towards operational tolerance. Immune cell therapy using the adoptive transfer of various cell products have been shown to be feasible and well tolerated in early phase clinical trials and ongoing.

Tolerance studies in liver transplantation are evolving and substantial progress has been made in overcoming the challenges that have prevented the widespread implementation of immunosuppression withdrawal protocols in the clinic. Identifying more sensitive and specific predictors of immunosuppression withdrawal success and tolerance induction strategies that will allow for early tolerance will advance the field tremendously towards the goal of promoting long-term allograft survival without immunosuppression.
Hospital admissions in individuals with HTLV-1 infection in Spain
Authors: Ramos José-Manuel , de Mendoza Carmen , Aguilera Antonio , Barreiro Pablo , Benito Rafael , Eiros Jose M. , Soriano Vicente
Published: February 2020

Objective:

To examine the clinical burden and disease spectrum, as well as time trends for human T-cell leukemia virus type 1 (HTLV-1) and HTLV type 2 (HTLV-2) hospital admissions.

Design:

Retrospective, observational study using the Spanish National Hospital Discharge Database.

Methods:

Information for the diagnostic codes HTLV-1 and HTLV-2 using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) was retrieved from the national public registry since 1997--2015.

Results:

From a total of 66 462 136 nationwide hospital admissions recorded during the study period, 135 included HTLV diagnosis, being HTLV-1 in 115 (85.2%) and HTLV-2 in 20 (14.8%). The overall hospital admission rate because of HTLV was 2.03 per million, without significant yearly changes. First admissions represented 104 (77%) whereas 31 (23%) were re-admissions. The median in-hospital stay for HTLV patients was 9 days. In-hospital death occurred in 11 (8.1%). The median age of individuals with HTLV admission was 48 years and 60 (44.4%) were women. HTLV was recorded as the main diagnosis in 20%. The most frequent clinical conditions recorded alongside HTLV diagnosis were myelopathy (61; 45.2%), leukemia/lymphoma (30; 22.2%), solid organ transplantation (14; 10.4%) and child delivery (7; 5.2%).

Conclusion:

The rate of HTLV diagnosis in hospitalized patients in Spain is low, roughly of two per million admissions. Despite continuous large immigrant flows from HTLV-1 endemic areas, no significant rising in hospitalizations because of HTLV-1 associated illnesses were noticed during the last two decades. Classical clinical complications of HTLV-1 infection, such as myelopathy and lymphoma account for more than two-thirds of cases.