bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of oxygen flow rate on properties of Cu4O3 thin films fabricated by radio frequency magnetron sputtering
Authors: Patwary Md Abdul Majed , Ho Chun Yuen , Saito Katsuhiko , Guo Qixin , Yu Kin Man , Walukiewicz Wladek , Tanaka Tooru
Published: February 2020

Cu4O3 thin films have been synthesized in an ambient of Ar and O2 plasma using a pure Cu target by radio frequency magnetron sputtering. The structural, electrical, and optical properties of the films were studied systematically as a function of O2 gas flow. The study reveals that O2 flow rate (RO2) during sputtering has major impacts on both the composition and functional properties of the resultant Cu4O3 thin films. X-ray diffraction and Raman spectroscopy measurements suggest that the parameter window for the growth of single-phase Cu4O3 thin films was very narrow. Oxygen partial pressure of 7.9%–9.1% was required to grow the pure phase of Cu4O3. From optical absorption analyses, pure phase Cu4O3 films exhibited a direct transition at Eg = 1.52–1.62 eV. All the Cu4O3 thin films showed p-type conductivity with resistivities in the order of 102–103 Ω cm. An increase of RO2 resulted in the increase of the Hall mobility from 0.01 to 0.25 cm2/V s, which is the highest mobility reported so far for this material. These results indicate clearly that Cu4O3 is a semiconductor with a high potential as absorber materials in low-cost thin film photovoltaics.
Giant trevally (Caranx ignobilis) of Hawaiian Islands can live 25 years
Authors: Andrews Allen H.
Published: February 2020

Giant trevally (Caranx ignobilis) are an iconic reef fish of the Indo-Pacific, and yet knowledge of their life history is incomplete. The species is common in tropical and subtropical waters ranging from the far western Indian Ocean off South Africa to the central Pacific Ocean, where the species attains its greatest recorded size in Hawaii. Despite their broad range, importance as a top predator and attraction among anglers, the age and longevity of giant trevally remain largely undescribed and there are concerns that giant trevally are being fished down in the Hawaiian Islands. The most comprehensive age and growth study was performed in the Hawaiian Islands, but the work was limited to early growth observations. Although a study of daily increments was limited to fish less than maximum size, a model used to describe the growth characteristics was extrapolated to estimate that maximum age may exceed 20 years. In this study, otoliths of giant trevally from the Hawaiian Islands were investigated for annual growth zones, and the validity of the age estimates was tested and validated with bomb 14C dating. Revised growth parameters indicate giant trevally grow rapidly in the Hawaiian Islands and can attain an age of 25 years.
A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans
Authors: Edwards Sarah C. , Sutton Caroline E. , Ladell Kristin , Grant Emma J. , McLaren James E. , Roche Fiona , Dash Pradyot , Apiwattanakul Nopporn , Awad Walid , Miners Kelly L. , Lalor Stephen J. , Ribot Julie C. , Baik Song , Moran Barry , McGinley Aoife , Pivorunas Valerie , Dowding Lori , Macoritto Michael , Paez-Cortez Jesus , Slavin Anthony , Anderson Graham , Silva-Santos Bruno , Hokamp Karsten , Price David A. , Thomas Paul G. , McLoughlin Rachel M. , Mills Kingston H.G.
Published: February 2020

T cells are classically recognized as distinct subsets that express αβ or γδ TCRs. We identify a novel population of T cells that coexpress αβ and γδ TCRs in mice and humans. These hybrid αβ-γδ T cells arose in the murine fetal thymus by day 16 of ontogeny, underwent αβ TCR–mediated positive selection into CD4+ or CD8+ thymocytes, and constituted up to 10% of TCRδ+ cells in lymphoid organs. They expressed high levels of IL-1R1 and IL-23R and secreted IFN-γ, IL-17, and GM-CSF in response to canonically restricted peptide antigens or stimulation with IL-1β and IL-23. Hybrid αβ-γδ T cells were transcriptomically distinct from conventional γδ T cells and displayed a hyperinflammatory phenotype enriched for chemokine receptors and homing molecules that facilitate migration to sites of inflammation. These proinflammatory T cells promoted bacterial clearance after infection with Staphylococcus aureus and, by licensing encephalitogenic Th17 cells, played a key role in the development of autoimmune disease in the central nervous system.
Fundamental limits on key rates in device-independent quantum key distribution
Authors: Kaur Eneet , Wilde Mark M , Winter Andreas
Published: February 2020

In this paper, we introduce intrinsic non-locality and quantum intrinsic non-locality as quantifiers for Bell non-locality, and we prove that they satisfy certain desirable properties such as faithfulness, convexity, and monotonicity under local operations and shared randomness. We then prove that intrinsic non-locality is an upper bound on the secret-key-agreement capacity of any device-independent protocol conducted using a device characterized by a correlation p, while quantum intrinsic non-locality is an upper bound on the same capacity for a correlation arising from an underlying quantum model. We also prove that intrinsic steerability is faithful, and it is an upper bound on the secret-key-agreement capacity of any one-sided-device-independent protocol conducted using a device characterized by an assemblage

ρ

ˆ

. Finally, we prove that quantum intrinsic non-locality is bounded from above by intrinsic steerability.
A Scoping Review of Stress Beliefs: Literature Integration, Measurement Issues, and Theoretical Concerns
Authors: Kilby Christopher J , Sherman Kerry A , Wuthrich Viviana M
Published: February 2020

Background

Individual stress beliefs are associated with stress-related behavioral responses and health consequences. The Common-Sense Model of Self-Regulation may help in understanding the role of stress beliefs in these behavioral responses and consequences.

Purpose

To synthesize empirical studies exploring the relationship between stress beliefs and stress-related behavioral responses and health consequences using the Common-Sense Model as a guiding framework.

Methods

Peer-reviewed journal articles on stress beliefs in PsycArticles, PsycINFO, PubMed, Scopus, and Sociological Abstracts were included if they were in English, reported on adult humans. Nineteen of the 1,972 unique articles reporting on 24 studies met inclusion criteria. Study quality was assessed with existing reporting criteria.

Results

Four of the five Common-Sense Model representations were included across the review studies, namely Identity, Cause, Consequences, and Control. Consequences and Control-related stress beliefs are associated with stress-based health and behavioral outcomes. One study explored Identity-related stress beliefs with health outcomes, reporting no relationship. No study assessed the relationship between Cause-related stress beliefs and behaviors or health outcomes. No study has explored any aspect of Timeline-related stress beliefs. Study quality ranged from very low to very high.

Conclusions

There is limited evidence exploring stress-related beliefs and behaviors and health outcomes. According to the Common-Sense Model, the Timeline representations remains to be investigated in the stress context, and Identity and Cause are under-researched. This review highlights future directions for stress beliefs research.
Double-Hit and Triple-Hit Follicular Lymphoma
Authors: Ziemba Jessica B , Wolf Zena , Weinstock Matthew , Asakrah Saja
Published: February 2020

Objectives

To better characterize the clinicopathologic presentation and outcomes of follicular lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit and triple-hit follicular lymphoma), we present three cases from our institution and perform a literature review of 37 published cases.

Methods

Cases were identified using institutional SoftPath software and the MEDLINE database via the PubMed search engine. Clinical and pathologic data were collected with subsequent stratification by histologic grade and treatment for comparison.

Results

Similar to classic follicular lymphoma, patients presented most often with low-grade (1-2) but high-stage (III-IV) disease with absence of B symptoms; however, overall survival was worse than that of traditional follicular lymphoma. In a small sample size, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) achieved better outcomes than a regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Specific pathologic features that might prompt testing for MYC rearrangement include elevated proliferation index out of proportion to cytology and aggressive features such as angioinvasion.

Conclusions

Double-hit and triple-hit follicular lymphoma may be better classified as a distinct entity from classical follicular lymphoma with a worse prognosis. Aggressive therapy with a treatment regimen used for high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements might be beneficial, but more evidence is needed to justify aggressive treatment as standard of care.
Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer’s disease
Authors: Arena John D , Smith Douglas H , Lee Edward B , Gibbons Garrett S , Irwin David J , Robinson John L , Lee Virginia M -Y , Trojanowski John Q , Stewart William , Johnson Victoria E
Published: February 2020

Traumatic brain injury (TBI) is a risk factor for neurodegenerative disease, including chronic traumatic encephalopathy (CTE). Preliminary consensus criteria define the pathognomonic lesion of CTE as patchy tau pathology within neurons and astrocytes at the depths of cortical sulci. However, the specific tau isoform composition and post-translational modifications in CTE remain largely unexplored. Using immunohistochemistry, we performed tau phenotyping of CTE neuropathologies and compared this to a range of tau pathologies, including Alzheimer’s disease, primary age-related tauopathy, ageing-related tau astrogliopathy and multiple subtypes of frontotemporal lobar degeneration with tau inclusions. Cases satisfying preliminary consensus diagnostic criteria for CTE neuropathological change (CTE-NC) were identified (athletes, n = 10; long-term survivors of moderate or severe TBI, n = 4) from the Glasgow TBI Archive and Penn Neurodegenerative Disease Brain Bank. In addition, material from a range of autopsy-proven ageing-associated and primary tauopathies in which there was no known history of exposure to TBI was selected as non-injured controls (n = 32). Each case was then stained with a panel of tau antibodies specific for phospho-epitopes (PHF1, CP13, AT100, pS262), microtubule-binding repeat domains (3R, 4R), truncation (Tau-C3) or conformation (GT-7, GT-38) and the extent and distribution of staining assessed. Cell types were confirmed with double immunofluorescent labelling. Results demonstrate that astroglial tau pathology in CTE is composed of 4R-immunoreactive thorn-shaped astrocytes, echoing the morphology and immunophenotype of astrocytes encountered in ageing-related tau astrogliopathy. In contrast, neurofibrillary tangles of CTE contain both 3R and 4R tau, with post-translational modifications and conformations consistent with Alzheimer’s disease and primary age-related tauopathy. Our observations establish that the astroglial and neurofibrillary tau pathologies of CTE are phenotypically distinct from each other and recapitulate the tau immunophenotypes encountered in ageing and Alzheimer’s disease. As such, the immunohistochemical distinction of CTE neuropathology from other mixed 3R/4R tauopathies of Alzheimer’s disease and ageing may rest solely on the pattern and distribution of pathology.
Atrophy network mapping of transdiagnostic cognitive and neuropsychiatric symptoms
Authors: Veldsman Michele
Published: February 2020

This scientific commentary refers to ‘Network localization of clinical, cognitive, and neuropsychiatric symptoms in Alzheimer’s disease’, by Tetreault etal. (doi:10.1093/brain/awaa058).
Maternal and Infant Outcomes Among Pregnant Women Treated for Multidrug/Rifampicin-Resistant Tuberculosis in South Africa
Authors: Loveday Marian , Hughes Jennifer , Sunkari Babu , Master Iqbal , Hlangu Sindisiwe , Reddy Tarylee , Chotoo Sunitha , Green Nathan , Seddon James A
Published: February 2020

Background

Data on safety and efficacy of second-line tuberculosis drugs in pregnant women and their infants are severely limited due to exclusion from clinical trials and expanded access programs.

Methods

Pregnant women starting treatment for multidrug/rifampicin-resistant (MDR/RR)-tuberculosis at King Dinuzulu Hospital in KwaZulu-Natal, South Africa, from 1 January 2013 to 31 December 2017, were included. We conducted a record review to describe maternal treatment and pregnancy outcomes, and a clinical assessment to describe infant outcomes.

Results

Of 108 pregnant women treated for MDR/RR-tuberculosis, 88 (81%) were living with human immunodeficiency virus.. Favorable MDR/RR-tuberculosis treatment outcomes were reported in 72 (67%) women. Ninety-nine (91%) of the 109 babies were born alive, but overall, 52 (48%) women had unfavorable pregnancy outcomes. Fifty-eight (54%) women received bedaquiline, and 49 (45%) babies were exposed to bedaquiline in utero. Low birth weight was reported in more babies exposed to bedaquiline compared to babies not exposed (45% vs 26%; P = .034). In multivariate analyses, bedaquiline and levofloxacin, drugs often used in combination, were both independently associated with increased risk of low birth weight. Of the 86 children evaluated at 12 months, 72 (84%) had favorable outcomes; 88% of babies exposed to bedaquiline were thriving and developing normally compared to 82% of the babies not exposed.

Conclusions

MDR/RR-tuberculosis treatment outcomes among pregnant women were comparable to nonpregnant women. Although more babies exposed to bedaquiline were of low birth weight, over 80% had gained weight and were developing normally at 1 year.
Computed Tomographic Imaging of 3 Patients With Coronavirus Disease 2019 Pneumonia With Negative Virus Real-time Reverse-Transcription Polymerase Chain Reaction Test
Authors: Xu Junqing , Wu Ruodai , Huang Hua , Zheng Weidong , Ren Xinling , Wu Nashan , Ji Bin , Lv Yungang , Liu Yumeng , Mi Rui
Published: February 2020

We reported computed tomographic (CT) imaging findings of 3 patients with coronavirus disease 2019 (COVID-19) pneumonia with initially negative results before CT examination and finally confirmed positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time reverse-transcription polymerase chain reaction assay.
Environmental conditions and call-broadcast influence detection of eastern forest owls during standardized surveys
Authors: Lima Kyle A , Call Erynn M , Hodgman Thomas P , Potter David S , Gallo Susan , Blomberg Erik J
Published: February 2020

Owls play crucial roles in the environment and provide ecosystem services making them important to monitor and study. However, standardized methods for most species do not exist, and we lack understanding of the effects of many environmental variables and call-broadcast on detection of owls during surveys. We performed a multispecies occupancy analysis of owl monitoring data collected from 2004 to 2013 across the state of Maine to examine the effects of environmental variables, conspecific and heterospecific call-broadcast, and general survey protocols on detection of 3 forest owls: Northern Saw-whet Owl (Aegolius acadicus), Barred Owl (Strix varia), and Great Horned Owl (Bubo virginianus). We found that environmental variables such as cloud cover, precipitation, temperature, time of night, and wind had species-specific effects on detection probability, and ambient noise decreased detection probability for all species. Snow cover did not affect detection of any species. We also found that conspecific call-broadcast increased detection of each species, while heterospecific call-broadcast had variable effects. Specifically, we found that Long-eared and Barred owl broadcast increased the detection of Northern Saw-whet Owl, and our results suggest additional heterospecific effects may exist. Our study showed that, compared to the protocol of the Maine Owl Monitoring Program, surveys simultaneously examining all 3 of our focal species can increase efficiency and lower disturbance by only broadcasting Long-eared and Barred owl calls during a 10-min survey. We recommend that future owl surveys take into account species-specific effects of conspecific and heterospecific call-broadcast, and use our results when designing survey protocols that include one or more of our focal species.
Metabonomics and the Gut Microbiome Associated With Primary Response to Anti-TNF Therapy in Crohn’s Disease
Authors: Ding N S , McDonald J A K , Perdones-Montero A , Rees Douglas N , Adegbola S O , Misra R , Hendy P , Penez L , Marchesi J R , Holmes E , Sarafian M H , Hart A L
Published: February 2020

Background and Aims

Anti-tumour necrosis factor [anti-TNF] therapy is indicated for treatment of moderate to severe inflammatory bowel disease [IBD], but has a primary non-response rate of around 30%. We aim to use metabonomic and metataxonomic profiling to identify predictive biomarkers of anti-TNF response in Crohn’s disease.

Methods

Patients with luminal Crohn’s disease, commencing anti-TNF therapy, were recruited with urine, faeces, and serum samples being collected at baseline and 3-monthly. Primary response was defined according to a combination of clinical and objective markers of inflammation. Samples were measured using three UPLC-MS assays: lipid, bile acid, and Hydrophillic Interaction Liquid Chromatography [HILIC] profiling with 16S rRNA gene sequencing of faeces.

Results

Samples were collected from 76 Crohn’s disease patients who were anti-TNF naïve and from 13 healthy controls. There were 11 responders, 37 non-responders, and 28 partial responders in anti-TNF-treated Crohn’s patients. Histidine and cysteine were identified as biomarkers of response from polar metabolite profiling [HILIC] of serum and urine. Lipid profiling of serum and faeces found phosphocholines, ceramides, sphingomyelins, and triglycerides, and bile acid profiling identified primary bile acids to be associated with non-response to anti-TNF therapy, with higher levels of phase 2 conjugates in non-responders. Receiver operating curves for treatment response demonstrated 0.94 +/ -0.10 [faecal lipid], 0.81 +/- 0.17 [faecal bile acid], and 0.74 +/- 0.15 [serum bile acid] predictive ability for anti-TNF response in Crohn’s disease.

Conclusions

This prospective, longitudinal cohort study of metabonomic and 16S rRNA gene sequencing analysis demonstrates that a range of metabolic biomarkers involving lipid, bile acid, and amino acid pathways may contribute to prediction of response to anti-TNF therapy in Crohn’s disease.

Podcast

This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast
The 2019 Mw 6.4 and Mw 7.1 Ridgecrest earthquake sequence in Eastern California: rupture on a conjugate fault structure revealed by GPS and InSAR measurements
Authors: Li Shuiping , Chen Gang , Tao Tingye , He Ping , Ding Kaihua , Zou Rong , Li Jingwei , Wang Qi
Published: February 2020

On 4 and 6 July 2019, an Mw 6.4 foreshock and an Mw 7.1 main shock successively struck the city of Ridgecrest in eastern California. These two events are the most significant earthquake sequences to strike in this part of California for the past 20 yr. We used both continuous global positioning system (GPS) measurements and interferometric synthetic aperture radar (InSAR) images taken by the Sentinel-1 and ALOS-2 satellites in four different viewing geometries to fully map the coseismic surface displacements associated with these two earthquakes. Using these GPS and InSAR measurements both separately and jointly, we inverted data to find the coseismic slip distributions and fault dips caused by the two earthquakes. The GPS-constrained slip models indicate that the Mw 7.1 main shock was predominately controlled by right-lateral motions on a series of northwest-trending faults, while the Mw 6.4 foreshock involved both right-lateral slipping on a northwest-trending fault and left-lateral slipping on a northeast-trending fault. The two earthquakes both generate significant surface slip, with the maximum inferred slip of 5.54 m at the surface. We estimate the cumulative geodetic moment of the two earthquakes to have been 4.93 × 1019 Nm, equivalent to Mw 7.1. Furthermore, our calculations of the changes in static Coulomb stress suggest that the Mw 7.1 main shock was promoted significantly by the Mw 6.4 foreshock. This latest Ridgecrest earthquake sequence ruptured only the northern part of the seismic gap between the 1992 Mw 7.3 Landers earthquake and the 1872 M 7.4–7.9 Owens Valley earthquake. The earthquake risk in this area, therefore, remains very high, considering the significant accumulation of strain in the Eastern California Shear Zone, especially in the southern part of the seismic gap.
Understanding the role of antibody glycosylation through the lens of severe viral and bacterial diseases
Authors: Irvine Edward B , Alter Galit
Published: February 2020

Abundant evidence points to a critical role for antibodies in protection and pathology across infectious diseases. While the antibody variable domain facilitates antibody binding and the blockade of infection, the constant domain (Fc) mediates cross talk with the innate immune system. The biological activity of the Fc region is controlled genetically via class switch recombination, resulting in the selection of distinct antibody isotypes and subclasses. However, a second modification is made to all antibodies, via post-translational changes in antibody glycosylation. Studies from autoimmunity and oncology have established the role of immunoglobulin G (IgG) Fc glycosylation as a key regulator of humoral immune activity. However, a growing body of literature, exploring IgG Fc glycosylation through the lens of infectious diseases, points to the role of inflammation in shaping Fc-glycan profiles, the remarkable immune plasticity in antibody glycosylation across pathogen-exposed populations, the canonical and noncanonical functions of glycans and the existence of antigen-specific control over antibody Fc glycosylation. Ultimately, this work provides critical new insights into the functional roles for antibody glycosylation as well as lays the foundation for leveraging antibody glycosylation to drive prevention or control across diseases.
Can social accountability improve access to free public health care for the poor? Analysis of three Health Equity Fund configurations in Cambodia, 2015–17
Authors: Jacobs Bart , Sam Oeun Sam , Ir Por , Rifkin Susan , Van Damme Wim
Published: February 2020

Within the context of universal health coverage, community participation has been identified as instrumental to facilitate access to health services. Social accountability whereby citizens hold providers and policymakers accountable is one popular approach. This article describes one example, that of Community-Managed Health Equity Funds (CMHEFs), as an approach to community engagement in Cambodia to improve poor people’s use of their entitlement to fee-free health care at public health facilities. The objectives of this article are to describe the size of its operations and its ability to enable poor people continued access to health care. Using data collected routinely, we compare the uptake of curative health services by eligible poor people under three configurations of Health Equity Funds (HEFs) during a 24-month period (July 2015–June 2017): Standard HEF that operated without community engagement, Mature CMHEFs established years before the study period and New CMHEFs initiated just before the study period. One year within the study, non-governmental organizations (NGOs) stopped operating the HEF nationwide and only the community-participation aspects of New CMHEF continued receiving technical assistance from an NGO. Using utilization figures for curative services by non-poor people for comparison, following the cessation of HEF management by the NGOs, outpatient consultation figures declined for all three configurations in comparison with the year before but only significantly for Standard HEF. The three HEF configurations experienced a highly statistically significant reduction in monthly inpatient admissions following halting of NGO management of HEFs. This study shows that enhancing access to free health care through social accountability is optimized at health centres through engagement of a wide range of community representatives. Such effect at hospitals was only observed to a limited extent, suggesting the need for more engagement of hospital management authorities in social accountability mechanisms.
Long-Acting Cabotegravir Protects Macaques Against Repeated Penile Simian-Human Immunodeficiency Virus Exposures
Authors: Dobard Charles , Makarova Natalia , Nishiura Kenji , Dinh Chuong , Holder Angela , Sterling Mara , Lipscomb Jonathan , Mitchell James , Deyounks Frank , Garber David , Khalil George , Spreen William , Heneine Walid , García-Lerma J Gerardo
Published: February 2020

We used a novel penile simian-human immunodeficiency virus (SHIV) transmission model to investigate whether long-acting cabotegravir (CAB LA) prevents penile SHIV acquisition in macaques. Twenty-two macaques were exposed to SHIV via the foreskin and urethra once weekly for 12 weeks. Of these, 6 received human-equivalent doses of CAB LA, 6 received oral emtricitabine/tenofovir disoproxil fumarate, and 10 were untreated. The efficacy of CAB LA was high (94.4%; 95% confidence interval, 58.2%–99.3%) and similar to that seen with oral emtricitabine/tenofovir disoproxil fumarate (94.0%; 55.1%–99.2%). The high efficacy of CAB LA in the penile transmission model supports extending the clinical advancement of CAB LA preexposure prophylaxis to heterosexual men.
Global Monetary Order and the Liberal Order Debate
Authors: Norrlof Carla , Poast Paul , Cohen Benjamin J , Croteau Sabreena , Khanna Aashna , McDowell Daniel , Wang Hongying , Winecoff W Kindred
Published: February 2020

The recent “liberal international order” (LIO) debate has been vague about the institutions and issue areas that constitute the order. This is likely driven by competing views of “liberal” and, perhaps more importantly, by security scholars dominating the debate. From the perspective of scholars who explore the elements of the global monetary order (reserve currencies, international financial institutions, and central banks), the picture is different. Where security scholars point to a decline in US influence, scholars of global monetary politics see continued US dominance. Moreover, monetary prominence has been a precondition for the viability of great power projects of order building more generally. This symposium offers such a counter narrative. While the security challenges are real, the crises of the last decade have actually reinforced the centrality of the US dollar and American financial power in the international system.
Efficacy of continuous versus intermittent administration of nanoformulated benznidazole during the chronic phase of Trypanosoma cruzi Nicaragua infection in mice
Authors: Rial M S , Arrúa E C , Natale M A , Bua J , Esteva M I , Prado N G , Laucella S A , Salomon C J , Fichera L E
Published: February 2020

Background

Benznidazole and nifurtimox are effective drugs used to treat Chagas’ disease; however, their administration in patients in the chronic phase of the disease is still limited, mainly due to their limited efficacy in the later chronic stage of the disease and to the adverse effects related to these drugs.

Objectives

To evaluate the effect of low doses of nanoformulated benznidazole using a chronic model of Trypanosoma cruzi Nicaragua infection in C57BL/6J mice.

Methods

Nanoformulations were administered in two different schemes: one daily dose for 30 days or one dose every 7 days, 13 times.

Results

Both treatment schemes showed promising outcomes, such as the elimination of parasitaemia, a reduction in the levels of T. cruzi-specific antibodies and a reduction in T. cruzi-specific IFN-γ-producing cells, as well as an improvement in electrocardiographic alterations and a reduction in inflammation and fibrosis in the heart compared with untreated T. cruzi-infected animals. These results were also compared with those from our previous work on benznidazole administration, which was shown to be effective in the same chronic model.

Conclusions

In this experimental model, intermittently administered benznidazole nanoformulations were as effective as those administered continuously; however, the total dose administered in the intermittent scheme was lower, indicating a promising therapeutic approach to Chagas’ disease.
Autonomy, Consent, and the “Nonideal” Case
Authors: Lillehammer Hallvard
Published: February 2020

According to one influential view, requirements to elicit consent for medical interventions and other interactions gain their rationale from the respect we owe to each other as autonomous, or self-governing, rational agents. Yet, the popular presumption that consent has a central role to play in legitimate intervention extends beyond the domain of cases where autonomous agency is present to cases where far from fully autonomous agents make choices that, as likely as not, are going to be against their own best interest. The question of how we should understand the rationale for eliciting consent in this range of “nonideal” cases is comparatively ill understood. In this paper, I explore the prospects of accounting for consent requirements in such “nonideal” cases by appealing to a set of agency-based interests, including an interest in playing a meaningful part in joint decisions affecting ourselves and others.
Generation and Characterization of Novel Monoclonal Antibodies Targeting p62/sequestosome-1 Across Human Neurodegenerative Diseases
Authors: Trejo-Lopez Jorge A , Sorrentino Zachary A , Riffe Cara J , Prokop Stefan , Dickson Dennis W , Yachnis Anthony T , Giasson Benoit I
Published: February 2020

Human neurodegenerative diseases can be characterized as disorders of protein aggregation. As a key player in cellular autophagy and the ubiquitin proteasome system, p62 may represent an effective immunohistochemical target, as well as mechanistic operator, across neurodegenerative proteinopathies. In this study, 2 novel mouse-derived monoclonal antibodies 5G3 and 2A5 raised against residues 360–380 of human p62/sequestosome-1 were characterized via immunohistochemical application upon human tissues derived from cases of C9orf72-expansion spectrum diseases, Alzheimer disease, progressive supranuclear palsy, Lewy body disease, and multiple system atrophy. 5G3 and 2A5 reliably highlighted neuronal dipeptide repeat, tau, and α-synuclein inclusions in a distribution similar to a polyclonal antibody to p62, phospho-tau antibodies 7F2 and AT8, and phospho-α-synuclein antibody 81A. However, antibodies 5G3 and 2A5 consistently stained less neuropil structures, such as tau neuropil threads and Lewy neurites, while 2A5 marked fewer glial inclusions in progressive supranuclear palsy. Both 5G3 and 2A5 revealed incidental astrocytic tau immunoreactivity in cases of Alzheimer disease and Lewy body disease with resolution superior to 7F2. Through their unique ability to highlight specific types of pathological deposits in neurodegenerative brain tissue, these novel monoclonal p62 antibodies may provide utility in both research and diagnostic efforts.
3D numerical experiment for EUV waves caused by flux rope eruption
Authors: Mei Z X , Keppens R , Cai Q W , Ye J , Xie X Y , Li Y
Published: February 2020

We present a 3D magnetohydrodynamic numerical experiment of an eruptive magnetic flux rope (MFR) and the various types of disturbances it creates, and employ forward modelling of extreme ultraviolet (EUV) observables to directly compare numerical results and observations. In the beginning, the MFR erupts and a fast shock appears as an expanding 3D dome. Under the MFR, a current sheet grows, in which magnetic field lines reconnect to form closed field lines, which become the outermost part of an expanding coronal mass ejection (CME) bubble. In our synthetic SDO/AIA images, we can observe the bright fast shock dome and the hot MFR in the early stages. Between the MFR and the fast shock, a dimming region appears. Later, the MFR expands so its brightness decays and it becomes difficult to identify the boundary of the CME bubble and distinguish it from the bright MFR in synthetic images. Our synthetic images for EUV disturbances observed at the limb support the bimodality interpretation for coronal disturbances. However, images for disturbances propagating on-disc do not support this interpretation because the morphology of the bright MFR does not lead to circular features in the EUV disturbances. At the flanks of the CME bubble, slow shocks, velocity vortices and shock echoes can also be recognized in the velocity distribution. The slow shocks at the flanks of the bubble are associated with a 3D velocity separatrix. These features are found in our high-resolution simulation, but may be hard to observe as shown in the synthetic images.
Vertical distribution of HMXBs in NGC 55: constraining their centre-of-mass velocity
Authors: Politakis Babis , Zezas Andreas , Andrews Jeff J , Williams Stephen J
Published: February 2020

We analyse the vertical distribution of high-mass X-ray binaries (HMXBs) in NGC 55, the nearest edge-on galaxy to the Milky Way (MW), based on X-ray observations by Chandra. Adopting a statistical approach, we estimate the difference between the scale height of the vertical distribution of HMXBs and the vertical distribution of star-forming activity between 0.33 and 0.57 kpc. The spatial offsets can be explained by a momentum kick the X-ray binaries receive during the formation of the compact object after a supernova explosion of the primary star. Determining the vertical distribution of HMXBs in the MW using Gaia DR2 astrometry, we find that the corresponding difference is considerably lower at 0.036 ± 0.003 kpc, attributed to the greater gravitational potential of the MW. We also calculate the centre-of-mass transverse velocities of HMXBs in NGC 55, using traveltime information from binary population synthesis codes and for different star formation histories (SFHs). For a flat SFH model (typical of spiral galaxies like NGC 55), we find that HMXBs are moving with a typical transverse velocity between 34 and 48 km s−1, consistent with space velocities of MW HMXBs. For an exponentially declining SFH model, HMXBs are moving at a velocity of 21 km s−1, consistent with the corresponding velocity of HMXBs in the Small Magellanic Cloud and Large Magellanic Cloud. Finally, we estimate the formation efficiency of HMXBs in NGC 55 at 299$_{-46}^{+50}$ (systems/M⊙ yr−1), consistent within the errors with the Magellanic Clouds but significantly higher than the MW, a difference that can be explained by the subsolar metallicity of NGC 55.
Dust dynamics and vertical settling in gravitoturbulent protoplanetary discs
Authors: Riols A , Roux B , Latter H , Lesur G
Published: February 2020

Gravitational instability (GI) controls the dynamics of young massive protoplanetary discs. Apart from facilitating gas accretion on to the central protostar, it must also impact on the process of planet formation: directly through fragmentation, and indirectly through the turbulent concentration of small solids. To understand the latter process, it is essential to determine the dust dynamics in gravitoturbulent flow. For that purpose, we conduct a series of 3D shearing box simulations of coupled gas and dust, including the gas’s self-gravity and scanning a range of Stokes numbers, from 10 −3 to ∼0.2. First, we show that the vertical settling of dust in the mid-plane is significantly impeded by gravitoturbulence, with the dust scale height roughly 0.6 times the gas scale height for centimetre grains. This is a result of the strong vertical diffusion issuing from (i) small-scale inertial-wave turbulence feeding off the GI spiral waves and (ii) the larger scale vertical circulations that naturally accompany the spirals. Second, we show that at R  = 50 au concentration events involving submetre particles and yielding order 1 dust-to-gas ratios are rare and last for less than an orbit. Moreover, dust concentration is less efficient in 3D than in 2D simulations. We thus conclude that GI is not especially prone to the turbulent accumulation of dust grains. Finally, the large dust scale height measured in simulations could be, in the future, compared with that of edge-on discs seen by ALMA, thus aiding detection and characterization of GI in real systems.
The Tessellation-Level-Tree: characterizing the nested hierarchy of density peaks and their spatial distribution in cosmological N-body simulations
Authors: Busch Philipp , White Simon D M
Published: February 2020

We use the Millennium and Millennium-II simulations to illustrate the Tessellation-Level-Tree  (tlt), a hierarchical tree structure linking density peaks in a field constructed by voronoi tessellation of the particles in a cosmological N-body simulation. The tlt uniquely partitions the simulation particles into disjoint subsets, each associated with a local density peak. Each peak is a subpeak of a unique higher peak. The tlt can be persistence filtered to suppress peaks produced by discreteness noise. Thresholding a peak’s particle list at $\sim 80\left \langle \rho \right \rangle \,$ results in a structure similar to a standard friend-of-friends halo and its subhaloes. For thresholds below $\sim 7\left \langle \rho \right \rangle \,$, the largest structure percolates and is much more massive than other objects. It may be considered as defining the cosmic web. For a threshold of $5\left \langle \rho \right \rangle \,$, it contains about half of all cosmic mass and occupies $\sim 1{{\ \rm per\ cent}}$ of all cosmic volume; a typical external point is then ∼7h−1 Mpc from the web. We investigate the internal structure and clustering of tlt peaks. Defining the saddle point density ρlim  as the density at which a peak joins its parent peak, we show the median value of ρlim  for FoF-like peaks to be similar to the density threshold at percolation. Assembly bias as a function of ρlim  is stronger than for any known internal halo property. For peaks of group mass and below, the lowest quintile in ρlim  has b ≈ 0, and is thus uncorrelated with the mass distribution.
Towards a complete description of spectra and polarization of black hole accretion discs: albedo profiles and returning radiation
Authors: Taverna R , Zhang W , Dovčiak M , Bianchi S , Bursa M , Karas V , Matt G
Published: February 2020

Accretion discs around stellarmass black holes (BHs) emit radiation peaking in the soft X-rays when the source is in the thermal state. The emerging photons are polarized and, for symmetry reasons, the polarization integrated over the source is expected to be either parallel or perpendicular to the (projected) disc symmetry axis, because of electron scattering in the disc. However, due to general relativity effects photon polarization vectors will rotate with respect to their original orientation, by an amount depending on both the BH spin and the observer’s inclination. Hence, X-ray polarization measurements may provide important information about strong gravity effects around these sources. Along with the spectral and polarization properties of radiation which reaches directly the observer once emitted from the disc, in this paper we also include the contribution of returning radiation, i.e. photons that are bent by the strong BH gravity to return again on the disc, where they scatter until eventually escaping to infinity. A comparison between our results and those obtained in previous works by different authors shows an overall good agreement, despite the use of different code architectures. We finally consider the effects of absorption in the disc material by including more realistic albedo profiles for the disc surface. Our findings in this respect show that considering also the ionization state of the disc may deeply modify the behaviour of polarization observables.
The acute myeloid leukemia variant DNMT3A Arg882His is a DNMT3B-like enzyme
Authors: Norvil Allison B , AlAbdi Lama , Liu Bigang , Tu Yu Han , Forstoffer Nicole E , Michie Amie R , Chen Taiping , Gowher Humaira
Published: February 2020

We have previously shown that the highly prevalent acute myeloid leukemia (AML) mutation, Arg882His, in DNMT3A disrupts its cooperative mechanism and leads to reduced enzymatic activity, thus explaining the genomic hypomethylation in AML cells. However, the underlying cause of the oncogenic effect of Arg882His in DNMT3A is not fully understood. Here, we discovered that DNMT3A WT enzyme under conditions that favor non-cooperative kinetic mechanism as well as DNMT3A Arg882His variant acquire CpG flanking sequence preference akin to that of DNMT3B, which is non-cooperative. We tested if DNMT3A Arg882His could preferably methylate DNMT3B-specific target sites in vivo. Rescue experiments in Dnmt3a/3b double knockout mouse embryonic stem cells show that the corresponding Arg878His mutation in mouse DNMT3A severely impairs its ability to methylate major satellite DNA, a DNMT3A-preferred target, but has no overt effect on the ability to methylate minor satellite DNA, a DNMT3B-preferred target. We also observed a previously unappreciated CpG flanking sequence bias in major and minor satellite repeats that is consistent with DNMT3A and DNMT3B specificity suggesting that DNA methylation patterns are guided by the sequence preference of these enzymes. We speculate that aberrant methylation of DNMT3B target sites could contribute to the oncogenic potential of DNMT3A AML variant.
Performance of the T2Candida Panel for the Diagnosis of Intra-abdominal Candidiasis
Authors: Lamoth Frederic , Clancy Cornelius J , Tissot Frederic , Squires Kevin , Eggimann Philippe , Flückiger Ursula , Siegemund Martin , Orasch Christina , Zimmerli Stefan , Calandra Thierry , Marchetti Oscar , Nguyen Minh H , Bochud Pierre-Yves
Published: February 2020

Performance of T2Candida for detecting intra-abdominal candidiasis (IAC) was assessed in 48 high-risk patients. T2Candida sensitivity/specificity and positive/negative predictive values were 33%/93% and 71%/74%, respectively. IAC was present in 100% of cases with concordant positive T2Candida/1,3-beta-d-glucan and absent in 90% of concordant negative results. Combination T2Candida/1,3-beta-d-glucan may help guide treatment decisions.
Chemical Evolution of Calc-alkaline Magmas during the Ascent through Continental Crust: Constraints from Methana, Aegean Arc
Authors: Schoenhofen Milena V , Haase Karsten M , Beier Christoph , Woelki Dominic , Regelous Marcel
Published: February 2020

Quaternary calc-alkaline andesitic to dacitic lavas effusively erupted on top of about 30 km thick accreted continental crust at Methana peninsula in the western Aegean arc. We present new data of major and trace element concentrations as well as of Sr–Nd–Pb isotope ratios along with mineral compositions of Methana lavas and their mafic enclaves. The enclaves imply a parental basaltic magma and fractional crystallization processes with relatively little crustal assimilation in the deep part of the Methana magma system. The composition of amphibole in some mafic enclaves and lavas indicates deeper crystallization at ∼25 km depth close to the Moho compared with the evolved lavas that formed at <15 km depth. The presence of amphibole and low Ca contents in olivine suggest high water contents of ∼4 wt% in the primitive magmas at Methana. The compositions of andesitic and dacitic lavas reflect fractional crystallization, assimilation of sedimentary material, and magma mixing in the upper 15 km of the crust. The Methana magmas have fO2 of FMQ + 1 to FMQ + 2 (where FMQ is the fayalite–magnetite–quartz buffer) at temperatures of 1200 to 750 °C and the fO2 does not vary systematically from mafic to felsic compositions, suggesting that the mantle wedge was oxidized by sediment subduction. Amphibole is an important fractionating phase in the more evolved Methana magmas and causes significant changes in incompatible element ratios. Although xenocrysts and mineral compositions indicate magma mixing, the major and trace element variation implies only limited mixing between dacitic and basaltic melts.
Proportions of B-cell subsets are altered in incomplete systemic lupus erythematosus and correlate with interferon score and IgG levels
Authors: Henning Svenja , Lambers Wietske M , Doornbos-van der Meer Berber , Abdulahad Wayel H , Kroese Frans G M , Bootsma Hendrika , Westra Johanna , de Leeuw Karina
Published: February 2020

Objectives

Incomplete SLE (iSLE) patients display symptoms typical for SLE but have insufficient criteria to fulfil the diagnosis. Biomarkers are needed to identify iSLE patients that will progress to SLE. IFN type I activation, B-cell-activating factor (BAFF) and B-cell subset distortions play an important role in the pathogenesis of SLE. The aim of this cross-sectional study was to investigate whether B-cell subsets are altered in iSLE patients, and whether these alterations correlate with IFN scores and BAFF levels.

Methods

iSLE patients (n = 34), SLE patients (n = 41) with quiescent disease (SLEDAI ≤4) and healthy controls (n = 22) were included. Proportions of B-cell subsets were measured with flow cytometry, IFN scores with RT-PCR and BAFF levels with ELISA.

Results

Proportions of age-associated B-cells were elevated in iSLE patients compared with healthy controls and correlated with IgG levels. In iSLE patients, IFN scores and BAFF levels were significantly increased compared with healthy controls. Also, IFN scores correlated with proportions of switched memory B-cells, plasma cells and IgG levels, and correlated negatively with complement levels in iSLE patients.

Conclusion

In this cross-sectional study, distortions in B-cell subsets were observed in iSLE patients and were correlated with IFN scores and IgG levels. Since these factors play an important role in the pathogenesis of SLE, iSLE patients with these distortions, high IFN scores, and high levels of IgG and BAFF may be at risk for progression to SLE.