bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome Analysis of Dimorphic Fungus Sporothrix schenckii Exposed to Temperature Stress
Authors: He Dan , Zhang Xiaowei , Gao Song , You Hailong , Zhao Yanbing , Wang Li
Published: July 2020

Purpose

Sporothrix schenckii is a thermally dimorphic fungus. In a saprotrophic environment or culturing at 25 °C, it grows as mycelia, whereas in host tissues or culturing at 37 °C, it undergoes dimorphic transition and division into pathogenic yeast cells. S. schenckii can cause serious disseminated sporotrichosis in immunocompromised hosts and presents an emerging global health problem. The mycelium-to-yeast transition was a consequence of the adaptive process to different environment. Some studies showed that the transition was significantly related to the virulence and pathogenesis of dimorphic fungi. However the genetic mechanisms of this complicated biological process are poorly understood.

Method

Our study presented a comparative transcriptomic analysis perspective on temperature stress in a visceral isolates of S. schenckii, obtaining more genetic information related to dimorphic transition.

Results

The 9.38 Gbp dataset was generated and assembled into 14,423 unigenes. Compared with gene and protein databases, 9561 unigenes were annotated. Comparative analysis identified 1259 genes expressed differentially in mycelium and yeast phase, and were categorized into a number of important biological processes, such as synthesis and metabolism, transmembrane transport, biocatalysis, oxidation reduction, and cellular signal transduction.

Conclusions

The findings suggested that temperature-dependent transition was tightly associated with stress adaptation, growth and development, signal regulation, adhesion, and colonization, which was predicted to be related with virulence and pathogenesis. Collection of these data should offer fine-scale insights into the mechanisms of dimorphism and pathogenesis of S. schenckii, and meanwhile facilitate the evolutionary and function studies of other dimorphic fungi.
Contribution of beta diversity in shaping stream macroinvertebrate communities among hydro-ecoregions
Authors: Bo Tiziano , Doretto Alberto , Levrino Marco , Fenoglio Stefano
Published: July 2020

Rivers are heterogeneous and patchy-structured systems in which regional biodiversity of aquatic communities typically varies as a function of local habitat conditions and spatial gradients. Understanding which environmental and spatial constraints shape the diversity and composition of benthic communities is therefore a pivotal challenge for basic and applied research in river ecology. In this study, benthic invertebrates were collected from 27 sites across three hydro-ecoregions with the aim of investigating patterns inα- andβdiversity. We first assessed the contribution to regional biodiversity of different and nested spatial scales, ranging from micro-habitat to hydro-ecoregion. Then, we tested differences inαdiversity, taxonomic composition and ecological uniqueness among hydro-ecoregions. Variance partitioning analysis was used to evaluate the mechanistic effects of environmental and spatial variables on the composition of macroinvertebrate communities. Macroinvertebrate diversity was significantly affected by all the spatial scales, with a differential contribution according to the type of metric. Sampling site was the spatial scale that mostly contributed to the total richness, while the micro-habitat level explained the largest proportion of variance in Shannon–Wiener index. We found significant differences in the taxonomic composition, with 39 invertebrate families significantly associated with one or two hydro-ecoregions. However, effects of environmental and spatial controls were context dependent, indicating that the mechanisms that promote beta diversity probably differ among hydro-ecoregions. Evidence for species sorting, due to natural areas and stream order, was observed for macroinvertebrate communities in alpine streams, while spatial and land-use variables played a weak role in other geographical contexts.
Buy Coal or Kick-Start Green Innovation? Energy Policies in an Open Economy
Authors: Ravetti Chiara , Theoduloz Tania , Valacchi Giulia
Published: July 2020

This paper analyses two unilateral policies available to countries that want to rapidly curb carbon emissions in the global economy, but do not own any fossil fuel resources. If fossil fuel owners do not cooperate in$$\hbox {CO}_2$$CO2emission reduction efforts, the only strategy to reduce their fossil fuels’ use is to exploit the interconnectedness of production given by international trade. We compare a Pigouvian approach, namely a subsidy for renewable energy prices, and a Coasian supply-side strategy, buying extractive rights over fossil fuel deposits abroad. Using a dynamic North–South trade model with endogenous innovation, we show how these policies, designed to prevent an environmental disaster, have different cost and welfare profiles. If fossil fuel deposits can be purchased at their market price, the supply-side policy achieves the highest welfare. If instead the fossil fuel owners require a full compensation for their income loss, subsidies for renewable energy inputs can result in higher welfare, but only if the resource-rich region has less advanced technologies for green energy production than the countries implementing the policy.
Irony, Disruption and Moral Imperfection
Authors: Declercq Dieter
Published: July 2020

Irony has a suspicious moral reputation, especially in popular media and internet culture. Jonathan Lear (2011) introduces a proposal which challenges this suspicion and identifies irony as a means to achieve human excellence. For Lear, irony is a disruptive uncanniness which arises from a gap between aspiration and actualisation in our practical identity. According to Lear, such a disruptive experience of ironic uncanniness reorients us toward excellence, because it passionately propels us to really live up to that practical identity. However, Lear’s understanding of irony is idiosyncratic and his proposal overlooks that disruption often results from value incompatibility between different practical identities. The disruption which follows from value incompatibility does not inherently reorient us toward excellence. The point is exactly that achieving excellence in one practical identity is sometimes incompatible with excellence in the other. Pace Lear, I do not identify this disruptive experience as a central example of irony. Instead, I consider irony a virtuous coping strategy for such disruption, because it introduces the necessary distance from our moral imperfection to sustain practical deliberation and maintain good mental health. Such virtuous irony negotiates a golden mean between too little disruption (complete insensitivity toward one’s imperfection) and too much disruption (a complete breakdown of practical deliberation and mental health). I argue that ironic media in popular culture provide a rich source of such virtuous irony, which I demonstrate through analysis of satirical examples.
Treatment of Axial Spondyloarthritis: What Does the Future Hold?
Authors: Poddubnyy Denis , Sieper Joachim
Published: July 2020

Purpose of Review

To provide a summary of the recent and expected developments related to the treatment of axial spondyloarthritis.

Recent Findings

An increasing number of interleukin-17 blocking agents show efficacy in axial spondyloarthritis including both non-radiographic and radiographic forms. Janus kinase inhibitors showed promising results in phase II studies in radiographic axial spondyloarthritis and have, therefore, a potential to become a therapeutic option in this indication in the future. Inhibition of structural damage progression in axial spondyloarthritis seems to be possible in the case of effective and early anti-inflammatory treatment, although there are still open questions related to particular drug classes.

Despite major advances in the field and growing therapeutic options, there are still many open questions related to the optimized treatment strategies and to the individual choice of a drug in axial spondyloarthritis.
SARS-CoV-2 Entry Receptor ACE2 Is Expressed on Very Small CD45− Precursors of Hematopoietic and Endothelial Cells and in Response to Virus Spike Protein Activates the Nlrp3 Inflammasome
Authors: Ratajczak Mariusz Z. , Bujko Kamila , Ciechanowicz Andrzej , Sielatycka Kasia , Cymer Monika , Marlicz Wojciech , Kucia Magda
Published: July 2020

Angiotensin-converting enzyme 2 (ACE2) plays an important role as a member of the renin–angiotensin–aldosterone system (RAAS) in regulating the conversion of angiotensin II (Ang II) into angiotensin (1–7) (Ang [1–7]). But at the same time, while expressed on the surface of human cells, ACE2 is the entry receptor for SARS-CoV-2. Expression of this receptor has been described in several types of cells, including hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs), which raises a concern that the virus may infect and damage the stem cell compartment. We demonstrate for the first time that ACE2 and the entry-facilitating transmembrane protease TMPRSS2 are expressed on very small CD133+CD34+Lin−CD45−cells in human umbilical cord blood (UCB), which can be specified into functional HSCs and EPCs. The existence of these cells known as very small embryonic-like stem cells (VSELs) has been confirmed by several laboratories, and some of them may correspond to putative postnatal hemangioblasts. Moreover, we demonstrate for the first time that, in human VSELs and HSCs, the interaction of the ACE2 receptor with the SARS-CoV-2 spike protein activates the Nlrp3 inflammasome, which if hyperactivated may lead to cell death by pyroptosis. Based on this finding, there is a possibility that human VSELs residing in adult tissues could be damaged by SARS-CoV-2, with remote effects on tissue/organ regeneration. We also report that ACE2 is expressed on the surface of murine bone marrow-derived VSELs and HSCs, although it is known that murine cells are not infected by SARS-CoV-2. Finally, human and murine VSELs express several RAAS genes, which sheds new light on the role of these genes in the specification of early-development stem cells.
The Lifetime Prevalence and Factors Associated with Relapse Among Mentally Ill Patients at Jimma University Medical Center, Ethiopia: Cross Sectional Study
Authors: Agenagnew Liyew , kassaw Chalachew
Published: July 2020

Relapse is a condition of getting back to illness after the recovery from illness. It results in stigma, high cost of treatments, and a decline in functionality both for patients and their families. It is common in mentally ill patients therefore this study attempted to assess lifetime prevalence and factors associated with relapse in a patient with mental illness. Institutional based cross-sectional study design was employed and simple random sampling techniques were used to select 178 study participants. Data were collected through face to face interviews by using a single item question to measure relapse. Data were entered by using Epi-data 3.1 software and exported to the statistical package for social science 22.0 software for analysis. Bivariate logistic regression analysis was conducted to see the association between dependent and independent variables and to identify significant variables associated with the outcome variable at P < 0.05 multivariable logistic regression analysis was done. One hundred seventy-eight mentally ill patients have participated in the study that yields a response rate of 100%. From all 125 (70.2%) of them had relapsed. Non adherance (AOR = 6.35, 95% CI, 2.524–15.852, P < 0.001), high disablity score (AOR = 3.728, 95% CI, 1.434–9.687, P = 0.007) and having single admission history (AOR = 0.196, 95% CI, 0.050–0.761 P = 0.019) were factors which indepedently associated with relapse of mentally ill patients. This study found more than two-thirds of patients had relapsed. Adherence to medication, functional disability, and having single admission were variables that predict the relapse of mentally ill patients.
Para‐tracheal neck dissection – is dissection of the upper part of level Ⅵ necessary?
Authors: Khafif Avi , Yosef Liron Malka
Published: July 2020

Papillary thyroid carcinoma (PTC) has a high propensity for regional metastases, however, the impact of such metastases on the outcome of the patients is minimal. The central compartment of the neck is considered the first and the most common echelon of metastases from thyroid carcinoma. Physical examination along with ultrasonography are the gold standard pre‐operative evaluation of patients with PTC. Ultrasonography is highly sensitive in evaluating lateral neck nodes, however, its value in evaluating the central compartment is limited, resulting in a relatively high rate of occult metastases in this compartment. The main potential complications of para‐tracheal neck dissection (PTND) are recurrent laryngeal nerve paralysis and hypocalcemia and these may be higher in patients undergoing PTND compared to thyroidectomy alone. New histological data is available showing no evidence of lymph nodes in the central compartment above a level parallel to the inferior border of the cricoid cartilage. These findings support withholding dissection of the upper para‐tracheal region routinely as a part of PTND in patients with well‐differentiated thyroid cancer. By doing that, the complications may be lower and identical to thyroidectomy alone, thus may abolish arguments against more common use of elective PTND in patients with thyroid carcinoma.
Clearly Hazardous, Obscurely Regulated: Lessons from the Basel Convention on Waste Trade
Authors: Ahmad Khan Sabaa
Published: July 2020

As an internationally-traded commodity, plastic waste has long followed the profitability dynamics of the global waste and recycling market, leaving in its trace a disproportionate environmental and health burden on the world's most vulnerable populations. East Asian and Pacific countries, where most globally generated plastic waste has been exported since the late 1980s, are marked by underdeveloped, inefficient, or non-existent waste management infrastructures. Despite the highly visible environmental and human health impacts of plastic pollution, the global plastic waste trade has predominantly operated outside the scope of the Basel Convention on the Control of Transboundary Movements of Hazardous Wastes and Their Disposal. In 2019, however, this treaty was amended to explicitly bring all but a narrow stream of plastic waste within the category of wastes controlled as “hazardous waste,” or “waste requiring special consideration.” This essay explains the international legal implications of the amendment and discusses potential challenges related to its implementation and enforcement. It argues that in order to be effective, the new plastic waste trading rules will require further legal clarity, greater transparency in plastic waste trade that is not regulated under the Convention, and stronger law enforcement cooperation between customs and environmental protection authorities, both within and between countries. Since controlling all plastic waste trade at point of export is, in practice, impossible given the state of global shipping infrastructures and container traffic volume, the most effective approach to curbing plastic waste pollution and illegal trade lies outside the mandate of the Basel Convention, notably, in assigning financial and environmental responsibility for plastic waste within plastic product supply chains.
Variability Predictors of Vasospasm in Subarachnoid Hemorrhage: A Feasibility Study
Authors: Rodriguez Rosendo A. , Herry Christophe L. , English Shane W. , Ramsay Tim , Seely Andrew J.E. , Kenny Glen P. , Shamy Michel
Published: July 2020

Background:

Mean cerebral blood flow velocity (mean-CBFV) obtained from Transcranial Doppler (TCD) poorly predicts cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH). Variability descriptors of mean-CBFV obtained during extended TCD recordings may improve this prediction. We assessed the feasibility of generating reliable linear and non-linear descriptors of mean-CBFV variability using extended recordings in aSAH patients and in healthy controls. We also explored which of those metrics might have the ability to discriminate between aSAH patients and healthy controls, and among patients who would go on to develop vasospasm and those who would not.

Methods:

Bilateral mean-CBFV, blood pressure, and heart rate were continuously recorded for 40 minutes in aSAH patients (n = 8) within the first 5 days after ictus, in age-matched healthy controls (n = 8) and in additional young controls (n = 8). We obtained linear [standard deviation, coefficient of variations, and the very-low (0.003–0.040 Hz), low (0.040–0.150 Hz), and high-frequency (0.15–0.4 Hz) power spectra] and non-linear (Fractality, deterministic Chaos analyses) variability metrics.

Results:

We successfully obtained TCD recordings from patients and healthy controls and calculated the desired metrics of mean-CBFV variability. Differences were appreciable between aSAH patients and healthy controls, as well as between aSAH patients who later developed vasospasm and those who did not.

Conclusions:

A 40-minute TCD recording provides reliable variability metrics in aSAH patients and healthy controls. Future studies are required to determine if mean-CBFV variability metrics remain stable over time, and whether they may serve to identify patients who are at greatest risk of developing cerebral vasospasm after aSAH.
Williamson on Defining Knowledge
Authors: Pérez Otero Manuel
Published: July 2020

In his outstanding book Knowledge and its Limits (2000), Williamson (a) claims that we have inductive evidence for some negative theses concerning the prospects of defining knowledge, like this: knowing cannot be defined in accordance with a determinate traditional conjunctive scheme; (b) defends a theory of mental states, mental concepts and the relations between the two, from which we would obtain additional, not merely inductive, evidence for this negative thesis; and (c) presents an alternative (non-traditional-conjunctive) definition of knowledge. Here I consider these issues and extract two relevant conclusions: (i) Williamson's theory of states and concepts only supports the negative thesis because this theory would explain too much, since it imposes implausible necessary limitations on possible uses of concepts and linguistic expressions. So, there is no appropriate non-inductive evidence for the negative thesis. (ii) Williamson's own definition of knowledge is at risk.
The Mid-Victorian Reform of Britain’s Company Laws and the Moral Economy of Fair Competition
Authors: SMITH DAVID CHAN
Published: July 2020

This paper reconstructs the history of the reform of Britain’s company laws during the 1850s and makes three major arguments. First, the Law Amendment Society was the driving force for reform and organized the campaign for change. Second, the advancement of working-class interests and ideas of fairness were central to the conceptualization of these reforms and the course of their advocacy. Company law reform was broadly conceived to include the revision of the law of partnership, corporations, and cooperatives to create a level playing field in which smaller entrepreneurs could compete against established capitalists. Finally, central to this campaign was the institutional logic of “fair competition.” Socialists and liberals both used this logic, demonstrating how moral ideas can shape organizational change.
Molecular characterization and immunodiagnostics ofDicrocoelium dendriticumspecies isolated from sheep of north-west Himalayan region
Authors: Dar J.S. , Shabir U. , Dar S.A. , Ganai B.A.
Published: July 2020

Despite its extensive presence among grazing ruminants, dicrocoeliosis, also known as ‘small liver fluke’ disease, is poorly known and often underestimated by researchers and practitioners in many countries. The accurate identification and prepatent diagnosis ofDicrocoelium dendriticuminfection is an essential prerequisite for its prevention and control. In the present study, the morphologically identified specimens isolated from the bile ducts of sheep (Ovis aries) were validated through molecular data. The sequence analysis of the second internal transcribed spacer (ITS-2) of our isolates showed a high degree of similarity withD. dendriticumusing the BLAST function of the National Center for Biotechnology Information (NCBI). The phylogenetic analysis of our isolates showed a close relationship with previously describedD. dendriticumisolates from different countries. The antigenic profiles of somatic and excretory/secretory (E/S) antigens ofD. dendriticumwere revealed by sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE) and immunoblotting using sera from sheep naturally infected withD. dendriticum.By SDS–PAGE, 16 distinct bands were revealed from crude somatic fraction. Immunoblotting analysis of these proteins with positive sera exhibited six seroreactive bands ranging from 27 to 130 kDa. Among these, the 84 and 130 kDa bands were quite specific, with high diagnostic specificity and sensitivity. The E/S fraction comprised nine distinct bands, as revealed by SDS–PAGE analysis. Immunoblotting analysis of these proteins with positive sera exhibited five antigenic bands ranging from 27 to 130 kDa. Among these, the 130 kDa band was found to be quite specific, with high diagnostic specificity and sensitivity. The present study concludes that the protein bands of 84 and 130 kDa in somatic fraction and 130 kDa in E/S fraction can be used for the immunodiagnostic purpose for this economically important parasite, which may also encourage further studies regarding their vaccine potential.
Mammals of the Bhagirathi basin, Western Himalaya: understanding distribution along spatial gradients of habitats and disturbances
Authors: Pal Ranjana , Thakur Shagun , Arya Shashank , Bhattacharya Tapajit , Sathyakumar Sambandam
Published: July 2020

Understanding the distribution of wildlife species and their response to diverse anthropogenic pressures is important for conservation planning and management of wildlife space in human-dominated landscapes. Assessments of anthropogenic impacts on mammals of the Indian Himalayan Region have mostly been limited to locations inside protected areas. We studied the occurrence of mammals in an unexplored landscape, the 7,586 km2 Bhagirathi basin, at an altitude of 500–5,200 m. The basin encompasses wilderness areas of various habitat types and protection status that are exposed to a range of anthropogenic pressures. Camera trapping at 209 locations during October 2015–September 2017 confirmed the occurrence of 39 species of mammals, nine of which are categorized as threatened (four Vulnerable, five Endangered) and four as Near Threatened on the IUCN Red List. We recorded five mammal species that were hitherto undocumented in Uttarakhand State: the argali Ovis ammon, Tibetan sand fox Vulpes ferrilata, woolly hare Lepus oiostolus, Eurasian lynx Lynx lynx and woolly flying squirrel Eupetaurus cinereus. In addition, we recorded two Endangered species, the dhole Cuon alpinus and tiger Panthera tigris. Threatened species such as the sambar Rusa unicolor, common leopard Panthera pardus and Asiatic black bear Ursus thibetanus occur in a wide variety of habitats despite anthropogenic disturbance. We recorded the snow leopard Panthera uncia in areas with high livestock density but temporally segregated from human activities. The musk deer Moschus spp. and Himalayan brown bear Ursus arctos isabellinus were recorded in subalpine habitats and appeared to be less affected by human and livestock presence. Our findings highlight the potential of the Bhagirathi basin as a stronghold for conservation of several threatened and rare mammal species.
Perceptions and expectations of filial piety among older Chinese immigrants in Canada
Authors: Zhang Weiguo
Published: July 2020

Much of the literature discusses filial piety in general and ambiguous terms. This study, in contrast, investigates specific perceptions of filial piety and parental expectations of filial duty among older Chinese immigrants in Canada. The study is based on thematic analysis of 46 Chinese immigrants in seven focus groups conducted in the Greater Toronto Area. Findings show the perceptions of filial piety varied, but almost all participants had reduced expectations of their children. Nevertheless, they still valued and expected emotional care from their children. The study argues that changes in institutional settings, social policies and welfare systems define parents’ support needs and affect their expectations in the host society, while norms and institutional settings in the place of origin influence their perceptions of filial piety.
The configuration and experience mapping of an accessible VR environment for effective design reviews
Authors: Wodehouse Andrew , Loudon Brian , Urquhart Lewis
Published: July 2020

This paper presents a new VR interaction environment for the evaluation of digital prototypes, specifically in designer–client review sessions, and documents its implementation via experience mapping. Usability of VR controllers and basic manipulation remains a barrier for lay users, and a range of typical implementations are reviewed, highlighting the need for an easily accessible interface for this setting. The resulting interface configuration – the Control Carousel – demonstrates how the appropriate use of familiar mechanisms can increase VR accessibility. Three case studies using the Carousel in commercial design projects are described, and the subsequent interface refinements outlined. Finally, the development of an experience map describing the logistical, interactive, and emotive factors affecting the Carousel's implementation is documented. This provides insights on how experience mapping can be used as part of a human-centred design process to ensure VR environments are attuned to the requirements of users, in this instance delivering improved collaborative reviews.
The impacts of maternal childhood adversity, stress, and mental health on child development at 6 months in Taiwan: A follow-up study
Authors: Chang Yi-Ting , Feng Jui-Ying , Chang Hsin-Yi , Chang Yu-Chun , Lee Chia-Kuei
Published: July 2020

Exposure to adverse childhood experiences (ACEs) is not only associated with one's adverse health outcomes in adulthood but also increases the risk of child developmental problems in offspring. However, the mechanisms involved in the transmission of the effects of maternal ACEs to the offspring largely remain unexplored. This study sought to identify possible psychosocial pathways of intergenerational effects of maternal ACEs on child development at 6 months. Data from a longitudinal study on maternal childhood adversity and maternal psychosocial risk during pregnancy as well as maternal mental health problems and child development at 6 months postnatal were used. Structural equation modeling with bootstrapping was used to estimate the indirect effects of maternal ACEs on child development at 6 months. The model showed that maternal ACEs indirectly influenced offspring's development via maternal stressful events during pregnancy and pre- and postnatal mental health problems. This finding highlights the possible interventions at the prenatal and postnatal periods. Early identification of women who have ACEs or who are at psychosocial risk during pre- and postnatal periods is critical to provide interventions to buffer those negative effects on offspring's development. Future studies are needed to longitudinally assess the effects of maternal ACEs on child development over time.
Social endophenotypes in autism spectrum disorder: A scoping review
Authors: Tiede Gabrielle M. , Walton Katherine M.
Published: July 2020

Endophenotypes are measurable markers of genetic vulnerability to current or future disorder. Autism spectrum disorder (ASD) is well-suited to be examined within an endophenotype framework given past and current emphases on the broader autism phenotype and early detection. We conducted a scoping review to identify potential socially-related endophenotypes of ASD. We focused on paradigms related to sociality (e.g., theory of mind (TOM), social attention), which comprise most of this literature. We integrated findings from traditional behavioral paradigms with brain-based measures (e.g., electroencephalography, functional magnetic resonance imaging). Broadly, infant research regarding social attention and responsivity (Research Domain Criteria (RDoC) domain of affiliation) and attention to faces and voices (social communication) finds consistent abnormality in vulnerable infant siblings. Several additional paradigms that have shown differences in vulnerable infants and young children include animacy perception tasks (perception and understanding of others), measures of recognition and response to familiar faces (attachment), and joint attention and false-belief tasks (understanding mental states). Research areas such as alexithymia (the perception and understanding of self), empathic responding, and vocal prosody may hold interest; however, challenges in measurement across populations and age ranges is a limiting factor. Future work should address sex differences and age dependencies, specificity to ASD, and heterogeneous genetic pathways to disorder within samples individuals with ASD and relatives.
The Effect of High Storage Temperature on the Stability and Efficacy of Lyophilized Tenecteplase
Authors: Henkel Emily , Vella Rebecca , Fenning Andrew
Published: July 2020

Introduction:

Tenecteplase is a thrombolytic protein drug used by paramedics, emergency responders, and critical care medical personnel for the prehospital treatment of blood clotting diseases. Minimizing the time between symptom onset and the initiation of thrombolytic treatment is important for reducing mortality and improving patient outcomes. However, the structure of protein drug molecules makes them susceptible to physical and chemical degradation that could potentially result in considerable adverse effects. In locations that experience extreme temperatures, lyophilized tenecteplase transported in emergency service vehicles (ESVs) may be subjected to conditions that exceed the manufacturer’s recommendations, particularly when access to the ambulance station is limited.

Study Objective:

This study evaluated the impact of heat exposure (based on temperatures experienced in an emergency vehicle during summer in a regional Australian city) on the stability and efficacy of lyophilized tenecteplase.

Methods:

Vials containing 50mg lyophilized tenecteplase were stored at 4.0°C (39.2°F), 35.5°C (95.9°F), or 44.9°C (112.8°F) for a continuous period of eight hours prior to reconstitution. Stability and efficacy were determined through assessment of: optical clarity and pH; analyte concentration using UV spectrometry; percent protein monomer and single chain protein using size-exclusion chromatography; and in vitro bioactivity using whole blood clot weight and fibrin degradation product (D-dimer) development.

Results:

Heat treatment, particularly at 44.9°C, was found to have the greatest impact on tenecteplase solubility; the amount of protein monomer and single chain protein lost (suggesting structural vulnerability); and the capacity for clot lysis in the form of decreased D-dimer production. Meanwhile, storage at 4.0°C preserved tenecteplase stability and in vitro bioactivity.

Conclusion:

The findings indicate that, in its lyophilized form, even relatively short exposure to high temperature can negatively affect tenecteplase stability and pharmacological efficacy. It is therefore important that measures are implemented to ensure the storage temperature is kept below 30.0°C (86.0°F), as recommended by manufacturers, and that repeated refrigeration-heat cycling is avoided. This will ensure drug administration provides more replicable thrombolysis upon reaching critical care facilities.
Methylphenidate and the risk of burn injury among children with attention-deficit/hyperactivity disorder
Authors: Chen Vincent Chin-Hung , Yang Yao-Hsu , Yu Kuo Ting , Lu Mong-Liang , Tseng Wei-Ting , Hou Tsai-Yu , Yeh Jia-Ying , Lee Charles Tzu-Chi , Chen Yi-Lung , Lee Min-Jing , Dewey Michael E. , Gossop Michael
Published: July 2020

Aims

Attention-deficit/hyperactivity disorder (ADHD) is associated with a higher risk of burn injury than in the normal population. Nevertheless, the influence of methylphenidate (MPH) on the risk of burn injury remains unclear. This retrospective cohort study analysed the effect of MPH on the risk of burn injury in children with ADHD.

Method

Data were from Taiwan's National Health Insurance Research Database (NHIRD). The sample comprised individuals younger than 18 years with a diagnosis of ADHD (n = 90 634) in Taiwan's NHIRD between January 1996 and December 2013. We examined the cumulative effect of MPH on burn injury risk using Cox proportional hazards models. We conducted a sensitivity analysis for immortal time bias using a time-dependent Cox model and within-patient comparisons using the self-controlled case series model.

Results

Children with ADHD taking MPH had a reduced risk of burn injury, with a cumulative duration of treatment dose-related effect, compared with those not taking MPH. Compared with children with ADHD not taking MPH, the adjusted hazard ratio for burn injury was 0.70 in children taking MPH for <90 days (95% confidence interval (CI) 0.64–0.77) and 0.43 in children taking MPH for ≥90 days (95% CI 0.40–0.47), with a 50.8% preventable fraction. The negative association of MPH was replicated in age-stratified analysis using time-dependent Cox regression and self-controlled case series models.

Conclusion

This study showed that MPH treatment was associated with a lower risk of burn injury in a cumulative duration of treatment dose-related effect manner.
On O+ Ion Heating by BBELF Waves at Low Altitude: Test Particle Simulations
Authors: Shen Yangyang , Knudsen David J.
Published: July 2020

We investigate mechanisms of wave particle heating of ionospheric O+ ions resulting from broadband extremely low frequency (BBELF) waves using numerical test particle simulations that take into account ion‐neutral collisions, in order to explain observations from the Enhanced Polar Outflow Probe (e‐POP) satellite at low altitudes (∼400 km) (Shen et al., 2018, https://doi.org/10.1002/2017JA024955). We argue that in order to reproduce ion temperatures observed at e‐POP altitudes, the most effective ion heating mechanism is through cyclotron acceleration by short‐scale electrostatic ion cyclotron (EIC) waves with perpendicular wavelengths λ⊥ ≤ 200 m. The interplay between finite perpendicular wavelengths, wave amplitudes, and ion‐neutral collision frequencies collectively determine the ionospheric ion heating limit, which begins to decrease sharply with decreasing altitude below approximately 500 km, where the ratio
becomes larger than 10−3, νc and fci denoting the O+‐O collision frequency and ion cyclotron frequency. We derive, both numerically and analytically, the ion gyroradius limit from heating by an EIC wave at half the cyclotron frequency. The limit is 0.28λ⊥. The ion gyroradius limit from an EIC wave can be surpassed either through adding waves with different λ⊥ or through stochastic “breakout,” meaning ions diffuse in energy beyond the gyroradius limit due to stochastic heating from large‐amplitude waves. Our two‐dimensional simulations indicate that small‐scale (<1 km) Alfvén waves cannot account for the observed ion heating through trapping or stochastic heating.
Multiscale Observation of Two Polar Cap Arcs Occurring on Different Magnetic Field Topologies
Authors: Reidy J. A. , Fear R. C. , Whiter D. K. , Lanchester B. S. , Kavanagh A. J. , Price D. J. , Chadney J. M. , Zhang Y. , Paxton L. J.
Published: July 2020

This paper presents observations of polar cap arc substructure down to scale sizes of meters and temporal resolution of milliseconds. Two case studies containing polar cap arcs occurring over Svalbard are investigated. The first occurred on 4 February 2016 and is consistent with formation on closed field lines; the second occurred on 15 December 2015 and is consistent with formation on open field lines. These events were identified using global‐scale images from the Special Sensor Ultra‐violet Spectrographic Imager (SSUSI) instruments on board Defense Meteorological Satellite Program (DMSP) spacecraft. Intervals when the arcs passed through the small‐scale field of view of the Auroral Structure and Kinetics (ASK) instrument, located on Svalbard, were then found using all sky images from a camera also located on Svalbard. These observations give unprecedented insight into small‐scale polar cap arc structure. The energy and flux of the precipitating particles above these arcs are estimated using the ASK observations in conjunction with the Southampton Ionospheric model. These estimates are then compared to in situ DMSP particle measurements, as well as data from ground‐based instrumentation, to infer further information about their formation mechanisms. This paper finds that polar cap arcs formed on different magnetic field topologies exhibit different behavior at small‐scale sizes, consistent with their respective formation mechanisms.
Thermokarst Lake to Lagoon Transitions in Eastern Siberia: Do Submerged Taliks Refreeze?
Authors: Angelopoulos Michael , Overduin Pier Paul , Westermann Sebastian , Tronicke Jens , Strauss Jens , Schirrmeister Lutz , Biskaborn Boris K. , Liebner Susanne , Maksimov Georgii , Grigoriev Mikhail N. , Grosse Guido
Published: July 2020

As the Arctic coast erodes, it drains thermokarst lakes, transforming them into lagoons, and, eventually, integrates them into subsea permafrost. Lagoons represent the first stage of a thermokarst lake transition to a marine setting and possibly more saline and colder upper boundary conditions. In this research, borehole data, electrical resistivity surveying, and modeling of heat and salt diffusion were carried out at Polar Fox Lagoon on the Bykovsky Peninsula, Siberia. Polar Fox Lagoon is a seasonally isolated water body connected to Tiksi Bay through a channel, leading to hypersaline waters under the ice cover. The boreholes in the center of the lagoon revealed floating ice and a saline cryotic bed underlain by a saline cryotic talik, a thin ice‐bearing permafrost layer, and unfrozen ground. The bathymetry showed that most of the lagoon had bedfast ice in spring. In bedfast ice areas, the electrical resistivity profiles suggested that an unfrozen saline layer was underlain by a thick layer of refrozen talik. The modeling showed that thermokarst lake taliks can refreeze when submerged in saltwater with mean annual bottom water temperatures below or slightly above 0°C. This occurs, because the top‐down chemical degradation of newly formed ice‐bearing permafrost is slower than the refreezing of the talik. Hence, lagoons may precondition taliks with a layer of ice‐bearing permafrost before encroachment by the sea, and this frozen layer may act as a cap on gas migration out of the underlying talik.
Quantitatively Tracking the Elevation of the Tibetan Plateau Since the Cretaceous: Insights From Whole‐Rock Sr/Y and La/Yb Ratios
Authors: Hu Fangyang , Wu Fuyuan , Chapman James B. , Ducea Mihai N. , Ji Weiqiang , Liu Shuwen
Published: July 2020

Crustal thickness, elevation, and Sr/Y and (La/Yb)N of magmatic rocks are strongly correlated for subduction‐related and collision‐related mountain belts. We quantitatively constrain the paleo‐elevation of the Tibetan Plateau since the Cretaceous using empirically derived equations. The results are broadly consistent with previous estimates based on stable isotope and structural analyses, supporting a complex uplift history. Our data suggest that a protoplateau formed in central Tibet during the Late Cretaceous and was higher than the contemporaneous Gangdese arc. This protoplateau collapsed before the India‐Asia collision, during the same time period that elevation in southern Tibet was increasing. During the India‐Asia collision, northern and southern Tibet were uplifted first followed by renewed uplift in central Tibet, which suggests a more complicated uplift history than commonly believed. We contend that a broad paleovalley formed during the Paleogene in central Tibet and that the whole Tibetan Plateau reached present‐day elevations during the Miocene.
Lunar Titanium and Frequency‐Dependent Microwave Loss Tangent as Constrained by the Chang'E‐2 MRM and LRO Diviner Lunar Radiometers
Authors: Siegler Matthew A. , Feng Jianqing , Lucey Paul G. , Ghent Rebecca R. , Hayne Paul O. , White Mackenzie N.
Published: July 2020

Passive microwave frequency (~300 MHz to 300 GHz) observations of the Moon have a long history and have been suggested as a plausible orbital instrument for the Moon and other bodies. However, global, orbital multifrequency measurements of lunar passive microwave emission have only recently been made by the Chinese Chang'E‐1 and ‐2 microwave radiometer (MRM) instruments. These missions carried nearly identical 4‐channel (3.0, 7.8, 19.35, and 37 GHz) instruments into lunar orbit in 2007–2009 and 2010–2011, respectively. Over the same time period, the ongoing Lunar Reconnaissance Orbiter (LRO) mission carried the Diviner Lunar Radiometer, which collected surface temperature measurements in the far infrared (~7.8–400 μm) from 2009 to present. By combining these data and associated thermal models, we provide new constraints on the relationship between physical temperature and microwave brightness temperature to reveal novel information about regolith thermal and dielectric properties which can reveal unique geologic information about the Moon. Here, we describe several first‐order global results to come from this combined data set, focusing primarily on the ability to detect, map, and quantify dielectric loss tangent variations of the Moon, including those from the presence of titanium‐bearing ilmenite. We update the loss tangent models for both highlands and mare and identify a clear frequency dependence that differs in sign between the two. We use the correlation with visible wavelength TiO2 mapping to provide a means to separate out the loss from rocks and from that of composition.
Clouds and Convective Self‐Aggregation in a Multimodel Ensemble of Radiative‐Convective Equilibrium Simulations
Authors: Wing Allison A. , Stauffer Catherine L. , Becker Tobias , Reed Kevin A. , Ahn Min‐Seop , Arnold Nathan P. , Bony Sandrine , Branson Mark , Bryan George H. , Chaboureau Jean‐Pierre , De Roode Stephan R. , Gayatri Kulkarni , Hohenegger Cathy , Hu I‐Kuan , Jansson Fredrik , Jones Todd R. , Khairoutdinov Marat , Kim Daehyun , Martin Zane K. , Matsugishi Shuhei , Medeiros Brian , Miura Hiroaki , Moon Yumin , Müller Sebastian K. , Ohno Tomoki , Popp Max , Prabhakaran Thara , Randall David , Rios‐Berrios Rosimar , Rochetin Nicolas , Roehrig Romain , Romps David M. , Ruppert James H. , Satoh Masaki , Silvers Levi G. , Singh Martin S. , Stevens Bjorn , Tomassini Lorenzo , van Heerwaarden Chiel C. , Wang Shuguang , Zhao Ming
Published: July 2020

The Radiative‐Convective Equilibrium Model Intercomparison Project (RCEMIP) is an intercomparison of multiple types of numerical models configured in radiative‐convective equilibrium (RCE). RCE is an idealization of the tropical atmosphere that has long been used to study basic questions in climate science. Here, we employ RCE to investigate the role that clouds and convective activity play in determining cloud feedbacks, climate sensitivity, the state of convective aggregation, and the equilibrium climate. RCEMIP is unique among intercomparisons in its inclusion of a wide range of model types, including atmospheric general circulation models (GCMs), single column models (SCMs), cloud‐resolving models (CRMs), large eddy simulations (LES), and global cloud‐resolving models (GCRMs). The first results are presented from the RCEMIP ensemble of more than 30 models. While there are large differences across the RCEMIP ensemble in the representation of mean profiles of temperature, humidity, and cloudiness, in a majority of models anvil clouds rise, warm, and decrease in area coverage in response to an increase in sea surface temperature (SST). Nearly all models exhibit self‐aggregation in large domains and agree that self‐aggregation acts to dry and warm the troposphere, reduce high cloudiness, and increase cooling to space. The degree of self‐aggregation exhibits no clear tendency with warming. There is a wide range of climate sensitivities, but models with parameterized convection tend to have lower climate sensitivities than models with explicit convection. In models with parameterized convection, aggregated simulations have lower climate sensitivities than unaggregated simulations.
Recent Trends in Individual and Multivariate Compound Flood Drivers in Canada's Coasts
Authors: Jalili Pirani F. , Najafi M. R.
Published: July 2020

Over half of the global population and the majority of the cities in coastal zones are at risk of coastal flooding. Changes in the occurrence of individual extremes and the interactions between hydrological and coastal variables can exacerbate flood risks. While extensive research has been conducted to understand and predict different types of flood hazards in isolation, spatial and temporal trends and variability of compound flooding, that is, flooding caused by multiple drivers, remain an open question. This study investigates the individual and joint temporal variations of multiple drivers that can cause compound flooding in Canada's coasts including total water level, storm surge, precipitation, and streamflow. Long‐term changes in the frequency and intensity of extremes are analyzed over the Atlantic, Pacific, and the Great Lakes regions. Univariate and multivariate trend tests including Mann Kendall, Covariance Inversion Test, Covariance Sum Test, and Covariance Eigenvalue Test are applied. In addition, a new multivariate index based on the contributing flood drivers transformed into a probability space is proposed, and its application to study compound flooding is investigated. Overall, results show increased risks of individual and compound flooding over the Atlantic coast and varying trends in the Pacific and Great Lakes regions. The multivariate trend indices show consistent results in most scenarios. The proposed index provides a simple and flexible measure to analyze the spatial and temporal variation of compound flooding risks at different thresholds. The results highlight the importance of considering nonstationary compound flood events to develop resilience strategies in coastal environments.
Room-temperature lasing from nanophotonic topological cavities
Authors: Smirnova Daria , Tripathi Aditya , Kruk Sergey , Hwang Min-Soo , Kim Ha-Reem , Park Hong-Gyu , Kivshar Yuri
Published: July 2020

The study of topological phases of light underpins a promising paradigm for engineering disorder-immune compact photonic devices with unusual properties. Combined with an optical gain, topological photonic structures provide a novel platform for micro- and nanoscale lasers, which could benefit from nontrivial band topology and spatially localized gap states. Here, we propose and demonstrate experimentally active nanophotonic topological cavities incorporating III–V semiconductor quantum wells as a gain medium in the structure. We observe room-temperature lasing with a narrow spectrum, high coherence, and threshold behaviour. The emitted beam hosts a singularity encoded by a triade cavity mode that resides in the bandgap of two interfaced valley-Hall periodic photonic lattices with opposite parity breaking. Our findings make a step towards topologically controlled ultrasmall light sources with nontrivial radiation characteristics.