bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond resilience: surviving agricultural treadmill in a global village (a case study of farming styles in Ubud, Bali, Indonesia)
Authors: Kurnia G , Sukayat Y , Nugraha A , Judawinata M G
Published: August 2019

Since agricultural modernization, farming practices in Indonesia have been forced to follow the prescriptions, which mostly came from the so-called experts. The proposed ‘modernity’ in agriculture, however, had also showed the ugly side of it. It created problems such market dependency, diminishing local knowledge and unhealthy competitions, which have forced the farmers to run in the ‘treadmill’. In Ubud, one of the touristic villages in Bali, the flow of knowledge that influence its agricultural practices is overwhelming. The question is, to what extent are farmers able to cope with such chaotic constellation? This paper aims to explore how different structures that exist in a global village such as Ubud, are perceived by farmers and what strategies do they came up with in order to maintain their existence. The study was a case study, which applied Actor Oriented Approach in order to analyse the point of view of key actors in responding to their situation. Data were gained through in-depth interview with various key actors. The results showed that the interrelationships between various institutions have shaped the room for manoeuvre for farmers to exercise their agencies, which manifested in various strategies emerged in the micro level. These diversities of farming styles and strategies showed that farmers have capabilities to perceive and cope with their problems. Thus, their capabilities based on their localities is the manifestation of their resilience, which is not to be ignored, as it might be the seed for future agriculture development.
On the conservation of helicity in a chiral medium
Authors: Crimin Frances , Mackinnon Neel , Götte Jörg B , Barnett Stephen M
Published: August 2019

We consider the energy and helicity densities of circularly polarised light within a lossless chiral medium, characterised by the chirality parameter β. A form for the helicity density is introduced, valid to first order in β, that produces a helicity of ±ℏ per photon for right and left circular polarisation, respectively. This is in contrast to the result obtained if we use the form of the helicity density employed for linear media. We examine the helicity continuity equation, and show that this modified form of the helicity density is required for consistency with the dual symmetry condition of a chiral medium with a constant value of ϵ/μ. Extending the results to arbitrary order in β establishes an exact relationship between the energy and helicity densities in a chiral medium.
Ab initio simulation of oxygen vacancies in LiMgPO4
Authors: Medvedeva N I , Kellerman D G , Kalinkin M O
Published: August 2019

The electronic structure of olivine-type LiMgPO4 with neutral and charged oxygen vacancies (F centers) was studied using ab initio density functional theory (DFT) calculations. The F centers introduce the energy states within the band gap, which explain the two-stage experimental absorption spectra, as demonstrated the imaginary part of complex dielectric function calculated for all types of defects. The formation energies of neutral and charged vacancies in nonequivalent oxygen sites were analyzed as a function of the Fermi level. The dominant defects in LiMgPO4 should be doubly charged F
2+ or neutral F
0 depending on the location of the Fermi level in the band gap, while the magnetic F
+ centers appear only in a narrow range of the Fermi energy. These defects may serve as traps during irradiation and induce the thermoluminescence of LiMgPO4.
Unraveling Specific Causes of Neonatal Mortality Using Minimally Invasive Tissue Sampling: An Observational Study
Authors: Madhi Shabir A , Pathirana Jayani , Baillie Vicky , Izu Alane , Bassat Quique , Blau Dianna M , Breiman Robert F , Hale Martin , Mathunjwa Azwifarwi , Martines Roosecelis B , Nakwa Firdose L , Nzenze Susan , Ordi Jaume , Raghunathan Pratima L , Ritter Jana M , Solomon Fatima , Velaphi Sithembiso , Wadula Jeannette , Zaki Sherif R , Chawana Richard
Published: August 2019

Background

Postmortem minimally invasive tissue sampling (MITS) is a potential alternative to the gold standard complete diagnostic autopsy for identifying specific causes of childhood deaths. We investigated the utility of MITS, interpreted with available clinical data, for attributing underlying and immediate causes of neonatal deaths.

Methods

This prospective, observational pilot study enrolled neonatal deaths at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa. The MITS included needle core-biopsy sampling for histopathology of brain, lung, and liver tissue. Microbiological culture and/or molecular tests were performed on lung, liver, blood, cerebrospinal fluid, and stool samples. The “underlying” and “immediate” causes of death (CoD) were determined for each case by an international panel of 12–15 medical specialists.

Results

We enrolled 153 neonatal deaths, 106 aged 3–28 days. Leading underlying CoD included “complications of prematurity” (52.9%), “complications of intrapartum events” (15.0%), “congenital malformations” (13.1%), and “infection related” (9.8%). Overall, infections were the immediate or underlying CoD in 57.5% (n = 88) of all neonatal deaths, including the immediate CoD in 70.4% (58/81) of neonates with “complications of prematurity” as the underlying cause. Overall, 74.4% of 90 infection-related deaths were hospital acquired, mainly due to multidrug-resistant Acinetobacter baumannii (52.2%), Klebsiella pneumoniae (22.4%), and Staphylococcus aureus (20.9%). Streptococcus agalactiae was the most common pathogen (5/15 [33.3%]) among deaths with “infections” as the underlying cause.

Conclusions

MITS has potential to address the knowledge gap on specific causes of neonatal mortality. In our setting, this included the hitherto underrecognized dominant role of hospital-acquired multidrug-resistant bacterial infections as the leading immediate cause of neonatal deaths.
Analysis of Pharmacovigilance Databases for Dolutegravir Safety in Pregnancy
Authors: van De Ven Nikolien S , Pozniak Anton L , Levi Jacob A , Clayden Polly , Garratt Anna , Redd Christopher , Mofenson Lynne M , Hill Andrew
Published: August 2019

Background

The Botswana Tsepamo study reported neural tube defects (NTDs) in 4 of 426 (0.94%) infants of women receiving preconception dolutegravir (DTG) antiretroviral therapy (ART) vs 14 of 11 300 (0.12%) receiving preconception non-DTG ART. Data are needed to investigate this potential safety signal. Clinicians, patients, and pharmaceutical companies can report adverse drug reactions (ADRs) to pharmacovigilance databases. Data from ADRs reported to various pharmacovigilance databases were searched for NTDs.

Methods

Four pharmacovigilance databases (World Health Organization [WHO] VigiAccess; United Kingdom Medicines Health Regulatory Authority [UK MHRA]; European Medicines Agency [EMA] EudraVigilance; US Food and Drug Administration Adverse Event Reporting System [FAERS]) with online data availability were analyzed for NTD reports for 4 integrase inhibitors (DTG, raltegravir, elvitegravir, bictegravir), 2 protease inhibitors (darunavir, atazanavir), and 2 nonnucleoside reverse transcriptase inhibitors (nevirapine, efavirenz). Reports in the system organ class “congenital or familial disorders” were searched for NTDs.

Results

NTDs have been reported among infants born from women taking a wide range of antiretrovirals in 4 pharmacovigilance databases (WHO VigiAccess, 116 reactions; UK MHRA, 8 cases; EMA EudraVigilance, 20 cases; FAERS, 44 cases). Six NTDs were identified for DTG across the pharmacovigilance databases. Cases were very hard to interpret, given the lack of clear denominators.

Conclusions

Pharmacovigilance databases have many limitations, most importantly lack of a clear denominator for patients exposed to the drug of interest and duplicate cases that are difficult to identify. Given widespread use of new antiretroviral drugs worldwide and anticipated use of new drugs, prospective follow-up of pregnant women and birth surveillance studies such as Tsepamo are critically needed.
Performance Evaluation of Depth Adjustment and Void Aware Pressure Routing (DA-VAPR) Protocol for Underwater Wireless Sensor Networks
Authors: Ganesh N
Published: August 2019

Underwater wireless sensor network (UWSN) has gained its popularity as a powerful technology for monitoring oceans, sea and river. The sensor node drifting along with ocean current offers 4D (space and time) monitoring for real-time underwater application. However, the main challenge arises from the underwater acoustic communication that results in high propagation delay, packet loss and overhead in the network. In order to overcome these issues, a depth adjustment and void aware pressure routing protocol is proposed for UWSN. A greedy forwarding strategy is used to forward the packet. In case a node fails to forward the packet using greedy forwarding strategy, then it immediately switches to the recovery mode. In the recovery mode, the node determines the new depth using particle swarm optimization technique. The global best value gives the new depth with minimum displacement. The void node forwards the packet with minimum displacement without any packet loss and delay.
Non-coding RNAs in cardiovascular cell biology and atherosclerosis
Authors: Fasolo Francesca , Di Gregoli Karina , Maegdefessel Lars , Johnson Jason L
Published: August 2019

Atherosclerosis underlies the predominant number of cardiovascular diseases and remains a leading cause of morbidity and mortality worldwide. The development, progression and formation of clinically relevant atherosclerotic plaques involves the interaction of distinct and over-lapping mechanisms which dictate the roles and actions of multiple resident and recruited cell types including endothelial cells, vascular smooth muscle cells, and monocyte/macrophages. The discovery of non-coding RNAs (ncRNAs) including microRNAs, long non-coding RNAs, and circular RNAs, and their identification as key mechanistic regulators of mRNA and protein expression has piqued interest in their potential contribution to atherosclerosis. Accruing evidence has revealed ncRNAs regulate pivotal cellular and molecular processes during all stages of atherosclerosis including cell invasion, growth, and survival; cellular uptake and efflux of lipids, expression and release of pro- and anti-inflammatory intermediaries, and proteolytic balance. The expression profile of ncRNAs within atherosclerotic lesions and the circulation have been determined with the aim of identifying individual or clusters of ncRNAs which may be viable therapeutic targets alongside deployment as biomarkers of atherosclerotic plaque progression. Consequently, numerous in vivo studies have been convened to determine the effects of moderating the function or expression of select ncRNAs in well-characterized animal models of atherosclerosis. Together, clinicopathological findings and studies in animal models have elucidated the multifaceted and frequently divergent effects ncRNAs impose both directly and indirectly on the formation and progression of atherosclerosis. From these findings’ potential novel therapeutic targets and strategies have been discovered which may pave the way for further translational studies and possibly taken forward for clinical application.
The role of extracorporeal membrane oxygenation in an acute basal ventricular septal rupture
Authors: Matos Daniel , Madeira Marcio , Nolasco Tiago , Neves José Pedro
Published: August 2019

A 74-year-old man was admitted with a post-acute myocardial infarction basal ventricular septal rupture. Onset of cardiogenic shock led to the implantation of a percutaneous veno-arterial extracorporeal membrane oxygenation (ECMO) system with an additional venous drainage cannula into the right ventricle. The ventricular septal defect was repaired with concomitant tricuspid valvuloplasty and mitral bioprosthesis implantation after 14 days. ECMO support was temporarily converted into a veno-venous system to wean the patient off cardiopulmonary bypass. The patient was discharged 3 weeks after surgery. This case illustrates the role of this extracorporeal life support system in the setting of postinfarction ventricular septal rupture.
Traumatic brachiocephalic trunk dissection of a bovine arch
Authors: Niclauss Lars , Namasivayam Jegaruban , Kirsch Matthias , Prêtre René
Published: August 2019

Aortic dissections after deceleration traumas are mainly located in the region of the proximal descending thoracic aorta. Less common are brachiocephalic trunk ruptures, which are not automatically amenable to an endovascular treatment. We present a poly-traumatized patient with an intimal tear at the origin of the brachiocephalic tunk with intramural haematoma extension to the ascending aorta. In addition, the left common carotid artery originated from the proximal brachiocephalic trunk, forming a ‘bovine arch’. Aortic arch and supra-aortic arteries were successfully replaced. The case demonstrates the importance of an individualized treatment in complex intrathoracic vascular injuries in poly-traumatized patients, including a careful risk assessment.
Populist Governments and International Law
Authors: Krieger Heike
Published: August 2019

The worldwide populist wave has contributed to a perception that international law is currently in a state of crisis. This article examines how far populist governments have challenged prevailing interpretations of international law. The article links structural features of populism with an analysis of populist governmental strategies and argumentative practices. It demonstrates that, in their rhetoric, populist governments promote an understanding of international law as a mere law of coordination. However, this is not entirely reflected in their legal practices where an instrumental, cherry-picking approach prevails. The article concludes that policies of populist governments affect the current state of international law on two different levels: in the political sphere, their practices alter the general environment in which legal rules are interpreted and, in the legal sphere, populist governments push for changes in the interpretation of established international legal rules. The article substantiates these propositions by focusing on the principle of non-intervention and foreign funding for non-governmental organizations.
Microbiomes in an acidic rock–water cave system
Authors: Burow Katja , Grawunder Anja , Harpke Marie , Pietschmann Sebastian , Ehrhardt Ralf , Wagner Lysett , Voigt Kerstin , Merten Dirk , Büchel Georg , Kothe Erika
Published: August 2019

Belowground ecosystems are accessible by mining, where a specific microbial community can be discovered. The biodiversity of a former alum mine rich in carbon, but with a low pH of 2.6–3.7, was evaluated by DNA- and cultivation-dependent methods using samples of the black slate rock material, secondary mineralization phases and seepage water. Pyrite oxidation within the low-grade metamorphic Silurian black slate established high concentrations of Fe and $\rm{SO}_4^{2-}$ forming the extreme conditions visible with acidophilic and Fe-oxidizing microorganisms. In addition, an unexpected predominance of fungi in this C-rich and acidic cave ecosystem, including high numbers of Mucoromycota and Mortierellomycota, was detected. Therefore, fungal cultures were obtained, mainly from the secondary mineral phases that are iron phosphates. Hence, the fungi might well have been involved in phosphate mobilization there. The rock material itself is rich in organic carbon that can be used by oxidase activity. The cultivation setup mimicked the cave conditions (low temperature, low pH, oxic conditions), with one oligotrophic and one medium rich in nutrients that allowed for isolation of different fungal (and eutrophic bacterial) groups. The acidic conditions prevented the occurrence of many basidiomycetes, while the isolated fungi could survive these adverse conditions.
Health Outcomes After Disaster for Older Adults With Chronic Disease: A Systematic Review
Authors: Bell Sue Anne , Horowitz Jennifer , Iwashyna Theodore J
Published: August 2019

Background and Objectives

This review synthesizes the current literature surrounding chronic disease outcomes after weather- and climate-related disasters among older adults. The associations between exposure of older adults to weather- and climate-related disasters and the primary outcomes of diabetes, end-stage renal disease (ESRD), congestive heart failure (CHF), and chronic obstructive pulmonary disease (COPD) were examined.

Research Design and Methods

A systematic review of studies reporting on clinical outcomes of four chronic diseases after disaster exposure was performed. Under the direction of an informationist, the databases PubMed, Scopus, EMBASE, and Web of Science (Science and Social Science Citation Index) were searched from inception to July 2019.

Results

Of 5,229 citations identified, 17 articles met the study criteria. Included articles were retrospective observational in nature and focused on earthquakes (24%, n = 4), hurricane (41%, n = 7), and wildfire (35%, n = 6) disasters. Outcome data by disease process included COPD (35%, n = 6), ESRD (41%, n = 7), CHF (24%, n = 4), and diabetes (29%, n = 5). Three main categories were identified: access to health care, postdisaster health care utilization, and study rigor. The age-stratified analyses reported in this review found multiple instances where disasters have limited or insignificant effects on older adults relative to younger populations.

Discussion and Implications

Disaster research faces unique methodological challenges, and there remains a need for data-driven conclusions on how best to care for older adults before, during, and after disasters. To encourage consistent dialogue among studies, we advocate for the use of rigorous and standardized scientific methodology to examine the health impacts of disasters on adults with chronic disease.
Regional maritime security in the eastern Mediterranean: expectations and reality
Authors: Rubin Aviad , Eiran Ehud
Published: August 2019

Recent developments in the eastern Mediterranean, such as significant gas finds; disagreements over the demarcation of maritime boundaries; large-scale violence and political instability following the Arab Spring; mass migration via sea routes; Great Power dynamics in the region; and environmental hazards, make the political entities along the shores of the eastern Mediterranean part of a regional security complex and create strong incentives for regional coordination on maritime security. Material international relations theories predict that growing security challenges (realism) coupled with expected gains (liberalism) will facilitate regional cooperation. Yet, the political entities in the region rely mainly on unilateral actions, or limited quasi-alliances in response to these challenges. The article shows the puzzling gap between the theoretical expectation and practical outcome in the region and explains why regional cooperation in the maritime domain fails to occur. It argues that cooperation on a regional scale fails to take place due to three complementing reasons: 1) lack of shared ideational features like cultural traits, set of values and regime type; 2) enduring rivalries between political entities in the region (Israel–Palestine; Turkey–Greece–Cyprus) coupled with internal strife within other regional political entities (Libya; Syria); and unequal political standing and lack of sovereignty of some of the political entities in the region (Northern Cyprus; the Palestinian Authority and the Gaza Strip).
An evaluation of some assumptions underpinning the bidomain equations of electrophysiology
Authors: Whiteley Jonathan P
Published: August 2019

Tissue level cardiac electrophysiology is usually modelled by the bidomain equations, or the monodomain simplification of the bidomain equations. One assumption made when deriving the bidomain equations is that both the intracellular and extracellular spaces are in electrical equilibrium. This assumption neglects the disturbance of this equilibrium in thin regions close to the cell membrane known as Debye layers. We first demonstrate that the governing equations at the cell, or microscale, level may be adapted to take account of these Debye layers with little additional complexity, provided the permittivity within the Debye layers satisfies certain conditions that are believed to be satisfied for biological cells. We then homogenize the microscale equations using a technique developed for an almost periodic microstructure. Cardiac tissue is usually modelled as sheets of cardiac fibres stacked on top of one another. A common assumption is that an orthogonal coordinate system can be defined at each point of cardiac tissue, where the first axis is in the fibre direction, the second axis is orthogonal to the first axis but lies in the sheet of cardiac fibres and the third axis is orthogonal to the cardiac sheet. It is assumed further that both the intracellular and extracellular conductivity tensors are diagonal with respect to these axes and that the diagonal entries of these tensors are constant across the whole tissue. Using the homogenization technique we find that this assumption is usually valid for cardiac tissue, but highlight situations where the assumption may not be valid.
Development and Implementation of a Cloud-Based Meningitis Surveillance and Specimen Tracking System in Burkina Faso, 2018
Authors: Diallo Alpha Oumar , Kiemtoré Tanga , Bicaba Brice Wilfried , Medah Isaïe , Tarbangdo Tiga Félix , Sanou Simon , Soeters Heidi M , Novak Ryan T , Aké Honoré Flavien
Published: August 2019

Nationwide case-based meningitis surveillance was established in Burkina Faso following the introduction of meningococcal serogroup A conjugate vaccine in 2010. However, timely tracking and arrival of cerebrospinal fluid specimens for confirmation at national reference laboratories remained suboptimal. To better understand this gap and identify bottlenecks, the Burkina Faso Ministry of Health, along with key partners, developed and implemented a cloud-based System for Tracking Epidemiological Data and Laboratory Specimens (STELAB), allowing for timely nationwide data reporting and specimen tracking using barcodes. STELAB was adapted to Burkina Faso’s infrastructure to ensure suitability, functionality, flexibility, and sustainability. We describe the design, development, and implementation of STELAB. In addition, we discuss strategies used to promote sustainability, lessons learned during the first year of implementation, and future directions. STELAB’s novel design and country-driven approach has the potential to achieve sustainable real-time data reporting and specimen tracking for the first time in sub-Saharan Africa.
Non-interlacing peakon solutions of the Geng–Xue equation
Authors: Shuaib Budor , Lundmark Hans
Published: August 2019

The aim of the present article is to derive explicit formulas for arbitrary non-overlapping pure peakon solutions of the Geng–Xue (GX) equation, a two-component generalization of Novikov’s cubically non-linear Camassa–Holm type equation. By performing limiting procedures on the previously known formulas for so-called interlacing peakon solutions, where the peakons in the two component occur alternatingly, we turn some of the peakons into zero-amplitude ‘ghostpeakons’, in such a way that the remaining ordinary peakons occur in any desired configuration. A novel feature compared to the interlacing case is that the Lax pairs for the GX equation do not provide all the constants of motion necessary for the integration of the system. We also study the large-time asymptotics of the non-interlacing solutions. As in the interlacing case, the peakon amplitudes grow or decay exponentially, and their logarithms display phase shifts similar to those for the positions. Moreover, within a group of adjacent peakons in one component, all peakons but one have the same asymptotic velocity. A curious phenomenon occurs when the number of such peakon groups is odd, namely that the sets of incoming and outgoing velocities are unequal.
Calcium to phosphorus ratio requirement of 26- to 127-kg pigs fed diets with or without phytase1,2
Authors: Vier Carine M , Dritz Steve S , Tokach Mike D , DeRouchey Joel M , Goodband Robert D , Gonçalves Márcio A D , Orlando Uislei A D , Bergstrom Jon R , Woodworth Jason C
Published: August 2019

Two experiments were conducted to determine the effects of calcium to phosphorus (Ca:P) ratio in diets adequate in standardized total tract digestible (STTD) P on performance of 26- to 127-kg pigs fed diets with or without phytase. Pens of pigs (n = 1,134 in Exp. 1 and n = 1,215 in Exp. 2, initially 26.3 and 25.3 kg) were blocked by body weight (BW) and allotted to treatments in a randomized complete block design. There were 27 pigs per pen with 7 and 9 replicates per treatment in Exp. 1 and Exp. 2, respectively. Treatments were formulated to contain 0.75:1, 1.00:1, 1.25:1, 1.50:1, 1.75:1, and 2.00:1 analyzed Ca:P ratios in Exp. 1, and 0.75:1, 1.00:1, 1.25:1, 1.50:1, and 2.00:1 analyzed Ca:P ratios in Exp. 2. These correspond to a range of 0.96:1 to 2.67:1 and 0.95:1 to 2.07:1 STTD Ca:STTD P ratios in Exp. 1 and Exp. 2, respectively. Experiment 2 diets contained 1,000 phytase units of Ronozyme HiPhos 2500 (DSM Nutritional Products, Inc., Parsippany, NJ) with release values of 0.132% STTD P, 0.144% total Ca, and 0.096% STTD Ca. Diets contained 122% of NRC (2012) STTD P estimates for the weight range across 4 phases. In Exp. 1, increasing Ca:P ratio increased (quadratic, P < 0.05) average daily gain (ADG) and average daily feed intake (ADFI). Feed efficiency (G:F) worsened (quadratic, P < 0.05) at the highest ratio. Hot carcass weight (HCW) and bone ash increased (quadratic, P < 0.05) while carcass yield decreased (linear, P < 0.10) with increasing Ca:P ratio. The maximum responses in ADG, HCW, and bone ash were estimated at 1.38:1, 1.25:1, and 1.93:1 analyzed Ca:P and at 1.82:1, 1.64:1, and 2.57:1 STTD Ca:STTD P, respectively. In Exp. 2, increasing Ca:P ratio increased (quadratic, P < 0.05) ADG and bone ash, and improved G:F (linear, P < 0.05). There was a quadratic increase (P < 0.05) in HCW and decrease in carcass yield (P < 0.10). The maximum responses in ADG, HCW, and bone ash were estimated at 1.63:1, 1.11:1 to 1.60:1, and 1.25:1 analyzed Ca:P and at 1.75:1, 1.28:1 to 1.71:1, and 1.40:1 STTD Ca:STTD P, respectively. Expressing ADG on a STTD Ca:STTD P basis provided a more consistent estimate of the ideal Ca:P ratio among the 2 studies than analyzed Ca to analyzed P ratio. A STTD Ca:STTD P ratio between 1.75:1 to 1.82:1 can be used for 26- to 127-kg pigs that are fed diets adequate in STTD P with or without added phytase to maximize growth rate without reducing bone ash.
International Obligations Concerning Disarmament and the Cessation of the Nuclear Arms Race: Justiciability over Justice in the Marshall Islands Cases at the International Court of Justice
Authors: Black-Branch Jonathan
Published: August 2019

The International Court of Justice rulings in cases from the Marshall Islands against India, Pakistan and the UK not only failed to answer important questions regarding obligations to negotiate a nuclear cessation treaty and to disarm, but also raise new questions relating to the existence of a dispute under general international law. The Respondents objected to the Court’s jurisdiction to hear the case on the grounds that there was no justiciable dispute between them and the Marshall Islands, arguing that the issues should not be adjudicated within this forum. The Court agreed, finding there was not sufficient evidence of a dispute, per se, and consequently did not have jurisdiction to hear these cases on their merits as the Respondents were not aware of contentious issues. In the case of the UK, in particular, it was decided by a narrow majority, raising important questions about the Court’s strictly formalistic, and more importantly, unprecedented, approach regarding the existence of a dispute under international law. More significantly, the ruling avoided answering important questions relating to long-standing international obligations regarding disarmament and negotiations toward a treaty to cease the arms race pursuant to Article VI of the Nuclear Non-Proliferation Treaty, 1968. This article provides an overview and analysis of the Marshall Islands cases, examining the main legal issues and arguments, focusing on the Court’s reasoning and highlighting the division within the Court on substantive matters pertaining to obligations of nuclear-armed states.
Out of sight, out of mind
Authors: Dohe Sebastian , Falk Malve Anna
Published: August 2019

The grand-ducal gallery of Oldenburg is a forgotten collection today, though once it enjoyed international fame. In less than a century, the dukes of Oldenburg in Lower Saxony collected an exemplary gallery of Old Masters that attracted the attention and the praise of international connoisseurs and art historians like Wilhelm Bode, Abraham Bredius and Tancred Borenius. Then, after the end of the First World War, the collection fell apart. In 1919, it was disassembled and its masterpieces were sold, once again generating international attention, this time from art dealers, museums and collectors eager to have their share of the plunder. The protests over this sell-out added impetus to the passing of a Kulturgutschutzgesetz, the first German law aimed at the protection of works of art of national value. This article reviews the history of the gallery and presents the results of a recent research project.
Optical counterparts of an ultraluminous X-Ray Source X-1 in NGC 2500
Authors: Aksaker N , Akyuz A , Avdan S , Avdan H
Published: August 2019

We present the results of a search for optical counterparts of ultraluminous X-ray source (ULX) X-1 in the nearby galaxy NGC 2500 by using archival images taken with the Hubble Space Telescope Wide Field Camera (WFC3)/UVIS. We identified four optical sources as possible counterparts within the 2σ error radius of 0$^{\prime \prime }_{.}$3 in the images. However, only two of them were investigated as candidates for counterparts due to their point-like features and their identification in various filters. These two faint candidates have absolute magnitudes of MV ≈ −3.4 and −3.7. The spectral energy distributions of two candidates were modelled by a power-law spectrum with a photon index (α) ∼1.5, but the spectrum of one candidate shows a deviation. This may suggest that at least two components are responsible for the optical emission. The red part of the spectrum could arise from the companion star and the blue part could be interpreted as an evidence of reprocessing of the X-rays from the disc.
Tumoricidal stem cell therapy enables killing in novel hybrid models of heterogeneous glioblastoma
Authors: Satterlee Andrew B , Dunn Denise E , Lo Donald C , Khagi Simon , Hingtgen Shawn
Published: August 2019

Background

Tumor-homing tumoricidal neural stem cell (tNSC) therapy is a promising new strategy that recently entered human patient testing for glioblastoma (GBM). Developing strategies for tNSC therapy to overcome intratumoral heterogeneity, variable cancer cell invasiveness, and differential drug response of GBM will be essential for efficacious treatment response in the clinical setting. The aim of this study was to create novel hybrid tumor models and investigate the impact of GBM heterogeneity on tNSC therapies.

Methods

We used organotypic brain slice explants and distinct human GBM cell types to generate heterogeneous models ex vivo and in vivo. We then tested the efficacy of mono- and combination therapy with primary NSCs and fibroblast-derived human induced neural stem cells (iNSCs) engineered with tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) or enzyme-prodrug therapy.

Results

Optical imaging, molecular assays, and immunohistochemistry revealed that the hybrid models recapitulated key aspects of patient GBM, including heterogeneity in TRAIL sensitivity, proliferation, migration patterns, hypoxia, blood vessel structure, cancer stem cell populations, and immune infiltration. To explore the impact of heterogeneity on tNSC therapy, testing in multiple in vivo models showed that tNSC-TRAIL therapy potently inhibited tumor growth and significantly increased survival across all paradigms. Patterns of tumor recurrence varied with therapeutic (tNSC-TRAIL and/or tNSC–thymidine kinase), dose, and route of administration.

Conclusions

These studies report new hybrid models that accurately capture key aspects of GBM heterogeneity which markedly impact treatment response while demonstrating the ability of tNSC mono- and combination therapy to overcome certain aspects of heterogeneity for robust tumor kill.
Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium
Authors: Takami Hirokazu , Fukuoka Kohei , Fukushima Shintaro , Nakamura Taishi , Mukasa Akitake , Saito Nobuhito , Yanagisawa Takaaki , Nakamura Hideo , Sugiyama Kazuhiko , Kanamori Masayuki , Tominaga Teiji , Maehara Taketoshi , Nakada Mitsutoshi , Kanemura Yonehiro , Asai Akio , Takeshima Hideo , Hirose Yuichi , Iuchi Toshihiko , Nagane Motoo , Yoshimoto Koji , Matsumura Akira , Kurozumi Kazuhiko , Nakase Hiroyuki , Sakai Keiichi , Tokuyama Tsutomu , Shibui Soichiro , Nakazato Yoichi , Narita Yoshitaka , Nishikawa Ryo , Matsutani Masao , Ichimura Koichi
Published: August 2019

Background

We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management.

Methods

Data from the Intracranial Germ Cell Tumor Genome Analysis (iGCT) Consortium were reviewed. A total of 190 cases were classified as primary germ cell tumors (GCTs) based on central pathological reviews.

Results

All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker positive and 6.1% of non-germinomatous GCTs were marker negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better progression-free survival than those at atypical sites (P = 0.03). A molecular clinical association study revealed frequent mitogen-activated protein kinase (MAPK) pathway mutations in males (51.4% vs 14.3%, P = 0.007), and phosphatidylinositol-3 kinase/mammalian target of rapamycin (PI3K/mTOR) pathway mutations in basal ganglia cases (P = 0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance.

Conclusions

The in-depth findings of this study regarding clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.
Nonsense-Mediated mRNA Decay Deficiency Affects the Auxin Response and Shoot Regeneration in Arabidopsis
Authors: Chiam Nyet-Cheng , Fujimura Tomoyo , Sano Ryosuke , Akiyoshi Nobuhiro , Hiroyama Ryoko , Watanabe Yuichiro , Motose Hiroyasu , Demura Taku , Ohtani Misato
Published: August 2019

Plants generally possess a strong ability to regenerate organs; for example, in tissue culture, shoots can regenerate from callus, a clump of actively proliferating, undifferentiated cells. Processing of pre-mRNA and ribosomal RNAs is important for callus formation and shoot regeneration. However, our knowledge of the roles of RNA quality control via the nonsense-mediated mRNA decay (NMD) pathway in shoot regeneration is limited. Here, we examined the shoot regeneration phenotypes of the low-beta-amylase1 (lba1)/upstream frame shift1-1 (upf1-1) and upf3-1 mutants, in which the core NMD components UPF1 and UPF3 are defective. These mutants formed callus from hypocotyl explants normally, but this callus behaved abnormally during shoot regeneration: the mutant callus generated numerous adventitious root structures instead of adventitious shoots in an auxin-dependent manner. Quantitative RT-PCR and microarray analyses showed that the upf mutations had widespread effects during culture on shoot-induction medium. In particular, the expression patterns of early auxin response genes, including those encoding AUXIN/INDOLE ACETIC ACID (AUX/IAA) family members, were significantly affected in the upf mutants. Also, the upregulation of shoot apical meristem-related transcription factor genes, such as CUP-SHAPED COTYLEDON1 (CUC1) and CUC2, was inhibited in the mutants. Taken together, these results indicate that NMD-mediated transcriptomic regulation modulates the auxin response in plants and thus plays crucial roles in the early stages of shoot regeneration.
Persistent eosinophilia among 21 historic cases of Strongyloides stercoralis infection: a case for routine follow-up and repeat treatment
Authors: Arkell Paul , Cosgrove Catherine , Riley Peter
Published: August 2019

Background

Strongyloidasis affects more than 100 million people worldwide and causes persisting infection.

Methods

We retrospectively reviewed 21 cases of parasitologically confirmed Strongyloides stercoralis infection at our centre.

Results

We found four individuals who had eosinophilia (>0.5x109/litre) more than 6 mo after treatment.

Conclusions

This may represent ongoing or relapsed infection. Our data support the need for continued follow-up of treated individuals, particularly those with abnormal host defences who are at risk of severe forms of the disease.
Development of a Specific Polymerase Chain Reaction System for the Detection of Rice Orange Leaf Phytoplasma
Authors: Wang Zhiyi , Zhu Yingzhi , Li Zhanbiao , Yang Xin , Zhang Tong , Zhou Guohui
Published: August 2019

Rice orange leaf disease (ROLD), caused by rice orange leaf phytoplasma (ROLP), is transmitted by leafhopper vectors Recilia dorsalis and Nephotettix cinticeps. ROLD severely devastates rice production in Asia. Accurate detection of the pathogen is important for disease management. Current nested polymerase chain reaction (nested PCR) method using phytoplasma universal primers is widely used to detect phytoplasmas; however, it has shortcoming of inconvenience and inaccuracy, for it needs two round of PCR reactions and could produce false positive results due to nontarget amplification. In this study, we developed a PCR assay using a set of primers designed based on the ROLP genome sequence to amplify house-keeping gene FtsH-1 in rice and leafhopper vector samples. This method is simple and rapid, and its sensitivity up to 10 pg/μl of total ROLP DNA. It also minimizes the false positive problem produced by nested PCR. This method was used to survey the geographic distribution of ROLD in southern China from 2016 to 2018. The results showed that the distribution areas and vector carrying rate of ROLD had gradually increased.
Sociodemographic Characteristics and the Stigmatization of Prescription Opioid Addiction
Authors: Goodyear Kimberly , Chavanne David
Published: August 2019

Objectives:

The aim of this study was to investigate the relationship between participants’ sociodemographic characteristics and the degree to which they stigmatize people with an opioid addiction.

Methods:

A randomized, between-subjects case vignette study (n = 2605) was conducted with a nationwide online survey. We investigated how the stigmatization toward a hypothetical individual who misused prescription opioids differed across participants’ sociodemographic factors (ie, age, gender, education, race, and income).

Results:

Our results showed that study participants who were male, white, low-income, college graduates, and younger rated the hypothetical individual with an opioid addiction with lower stigma. In addition, we showed that participant gender moderated the relationship between information given about initiation of opioid use (received prescription opioids from a doctor vs took prescription opioids from a friend) and opioid stigma perceptions.

Conclusions:

Our results support previous findings that stigmatizing attitudes towards drug use vary across participant sociodemographic characteristics. The findings from our study provide a better understanding of how stigmatizing attitudes towards prescription opioid use differ across sociodemographic characteristics and can serve to improve negative perceptions of those with an opioid addiction.
Diagnosis and treatment of myasthenia gravis
Authors: Mantegazza Renato , Cavalcante Paola
Published: August 2019

Purpose of review

This article provides an update on the most recent advances in diagnostic procedures and therapeutic approaches for myasthenia gravis, spanning from autoantibody and neuroelectrophysiological tests as diagnostic tools, to innovative and promising treatments based on biological drugs.

Recent findings

Novel studies performed by cell-based assays (CBAs) indicate an improvement in the chance of identifying serum autoantibodies in myasthenic patients. Clinical trials on the use of biological drugs were recently concluded, providing important data on safety and efficacy of eculizumab, efgartigimod and amifampridine phosphate: the first, a complement blocker, showed long-term safety and efficacy in acetylcholine receptor (AChR)-positive myasthenic patients with refractory generalized disease; the second, the neonatal Fc receptor blocker, was well tolerated and clinically effective in both AChR-specific and muscle-specific kinase receptor (MuSK)-positive patients; the third, a blocker of presynaptic potassium channels, was found to be well tolerated and effective in MuSK-positive patients.

CBAs can lead to a significant reduction of seronegative patients, improving myasthenia gravis diagnostic process. New biological drugs offer innovative approaches to treat myasthenic patients with generalized disease, promising to change the paradigm of treatment and to significantly enhance therapeutic success within a precision medicine framework.
General Principles in the Consensus of SSI Management After Spine Surgery
Authors: Kepler Christopher K. , Divi Srikanth N. , Bronson Wesley H. , Boody Barrett S. , Segar Anand H. , Russo Glenn S. , Kaye Ian David , Sirch Frank J. , Galetta Matthew S. , Goyal Dhruv K.C. , Fang Taolin , Schroeder Gregory D. , Vaccaro Alexander R.
Published: August 2019

In July of 2018, the Second International Consensus Meeting (ICM) on Musculoskeletal Infection convened in Philadelphia, PA was held to discuss issues regarding infection in orthopedic patients and to provide consensus recommendations on these issues to practicing orthopedic surgeons. During this meeting, attending delegates divided into subspecialty groups to discuss topics specifics to their respective fields, which included the spine. At the spine subspecialty group meeting, delegates discussed and voted upon the recommendations for 63 questions regarding the prevention, diagnosis, and treatment of infection in spinal surgery. Of the 63 questions, 8 questions focused on general principles in spine surgery, for which this article provides the recommendations, voting results, and rationales.
Ultra-Protective Ventilation Reduces Biotrauma in Patients on Venovenous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome*
Authors: Rozencwajg Sacha , Guihot Amélie , Franchineau Guillaume , Lescroat Mickael , Bréchot Nicolas , Hékimian Guillaume , Lebreton Guillaume , Autran Brigitte , Luyt Charles-Edouard , Combes Alain , Schmidt Matthieu
Published: August 2019

Introduction:

Ventilator settings for patients with severe acute respiratory distress syndrome supported by venovenous extracorporeal membrane oxygenation are currently set arbitrarily. The impact on serum and pulmonary biotrauma markers of the transition to ultra-protective ventilation settings following extracorporeal membrane oxygenation implantation, and different mechanical ventilation strategies while on extracorporeal membrane oxygenation were investigated.

Design:

Randomized clinical trial.

Settings:

Nine-month monocentric study.

Patients:

Severe acute respiratory distress syndrome patients on venovenous extracorporeal membrane oxygenation.

Interventions:

After starting extracorporeal membrane oxygenation, patients were switched to the bi-level positive airway pressure mode with 1 second of 24 cm H2O high pressure and 2 seconds of 12 cm H2O low pressure for 24 hours. A computer-generated allocation sequence randomized patients to receive each of the following three experimental steps: 1) high pressure 24 cm H2O and low pressure 20 cm H2O (very high positive end-expiratory pressure–very low driving pressure); 2) high pressure 24 cm H2O and low pressure 5 cm H2O (low positive end-expiratory pressure–high driving pressure); and 3) high pressure 17 cm H2O and low pressure 5 cm H2O (low positive end-expiratory pressure–low driving pressure). Plasma and bronchoalveolar lavage soluble receptor for advanced glycation end-products, plasma interleukin-6, and monocyte chemotactic protein-1 were sampled preextracorporeal membrane oxygenation and after 12 hours at each step.

Measurements and Main Results:

Sixteen patients on ECMO after 7 days (1–11 d) of mechanical ventilation were included. “Ultra-protective” mechanical ventilation settings following ECMO initiation were associated with significantly lower plasma sRAGE, interleukin-6, and monocyte chemotactic protein-1 concentrations. Plasma sRAGE and cytokines were comparable within each on-ECMO experimental step, but the lowest bronchoalveolar lavage sRAGE levels were obtained at minimal driving pressure.

Conclusions:

ECMO allows ultra- protective ventilation, which combines significantly lower plateau pressure, tidalvolume, and driving pressure. This ventilation strategy significantly limited pulmonary biotrauma, which couldtherefore decrease ventilator-induced lung injury. However, the optimal ultra-protective ventilation strategy once ECMO is initiated remains undetermined and warrants further investigations. (Crit Care Med 2019; 47:1505–1512)