bluuebunny/crossref_metadata_2025 huggingface dataset:
On the individual surrogate paradox
Authors: Ma Linquan , Yin Yunjian , Liu Lan , Geng Zhi
Published: May 2019

When the primary outcome is difficult to collect, a surrogate endpoint is typically used as a substitute. It is possible that for every individual, the treatment has a positive effect on the surrogate, and the surrogate has a positive effect on the primary outcome, but for some individuals, the treatment has a negative effect on the primary outcome. For example, a treatment may be substantially effective in preventing the stroke for everyone, and lowering the risk of stroke is universally beneficial for life expectancy; however, the treatment may still cause death for some individuals. We define such paradoxical phenomenon as the individual surrogate paradox. The individual surrogate paradox is proposed to capture the treatment effect heterogeneity, which is unable to be described by either the surrogate paradox based on average causal effect or that based on distributional causal effect. We investigate the existing surrogate criteria in terms of whether the individual surrogate paradox could manifest. We find that only the strong binary surrogate can avoid such paradox without additional assumptions. Utilizing the sharp bounds, we propose novel criteria to exclude the individual surrogate paradox. Our methods are illustrated in an application to determine the effect of the intensive glycemia on the risk of development or progression of diabetic retinopathy.
Risk stratification of cervical lesions using capture sequencing and machine learning method based on HPV and human integrated genomic profiles
Authors: Tian Rui , Cui Zifeng , He Dan , Tian Xun , Gao Qinglei , Ma Xin , Yang Jian-rong , Wu Jun , Das Bhudev C , Severinov Konstantin , Hitzeroth Inga Isabel , Debata Priya Ranjan , Xu Wei , Zhong Haolin , Fan Weiwen , Chen Yili , Jin Zhuang , Cao Chen , Yu Miao , Xie Weiling , Huang Zhaoyue , Bao Yuxian , Xie Hongxian , Yao Shuzhong , Hu Zheng
Published: May 2019

From initial human papillomavirus (HPV) infection and precursor stages, the development of cervical cancer takes decades. High-sensitivity HPV DNA testing is currently recommended as primary screening method for cervical cancer, whereas better triage methodologies are encouraged to provide accurate risk management for HPV-positive women. Given that virus-driven genomic variation accumulates during cervical carcinogenesis, we designed a 39 Mb custom capture panel targeting 17 HPV types and 522 mutant genes related to cervical cancer. Using capture-based next-generation sequencing, HPV integration status, somatic mutation and copy number variation were analyzed on 34 paired samples, including 10 cases of HPV infection (HPV+), 10 cases of cervical intraepithelial neoplasia (CIN) grade and 14 cases of CIN2+ (CIN2: n = 1; CIN2-3: n = 3; CIN3: n = 9; squamous cell carcinoma: n = 1). Finally, the machine learning algorithm (Random Forest) was applied to build the risk stratification model for cervical precursor lesions based on CIN2+ enriched biomarkers. Generally, HPV integration events (11 in HPV+, 25 in CIN1 and 56 in CIN2+), non-synonymous mutations (2 in CIN1, 12 in CIN2+) and copy number variations (19.1 in HPV+, 29.4 in CIN1 and 127 in CIN2+) increased from HPV+ to CIN2+. Interestingly, ‘common’ deletion of mitochondrial chromosome was significantly observed in CIN2+ (P = 0.009). Together, CIN2+ enriched biomarkers, classified as HPV information, mutation, amplification, deletion and mitochondrial change, successfully predicted CIN2+ with average accuracy probability score of 0.814, and amplification and deletion ranked as the most important features. Our custom capture sequencing combined with machine learning method effectively stratified the risk of cervical lesions and provided valuable integrated triage strategies.
Hepatitis B Core-related Antigen: An Alternative to Hepatitis B Virus DNA to Assess Treatment Eligibility in Africa
Authors: Shimakawa Yusuke , Ndow Gibril , Njie Ramou , Njai Harr Freeya , Takahashi Kazuaki , Akbar Sheikh Mohammad Fazle , Cohen Damien , Nayagam Shevanthi , Jeng Adam , Ceesay Amie , Sanneh Bakary , Baldeh Ignatius , Imaizumi Masayasu , Moriyama Kazushige , Aoyagi Katsumi , D’Alessandro Umberto , Mishiro Shunji , Chemin Isabelle , Mendy Maimuna , Thursz Mark R , Lemoine Maud
Published: May 2019

Background

To eliminate hepatitis B virus (HBV) infection, it is essential to scale up testing and treatment. However, conventional tools to assess treatment eligibility, particularly nucleic acid testing (NAT) to quantify HBV DNA, are hardly available and affordable in resource-limited countries. We therefore assessed the performance of a novel immunoassay, hepatitis B core-related antigen (HBcrAg), as an inexpensive (US$ <15/assay) alternative to NAT to diagnose clinically important HBV DNA thresholds (≥2000, ≥20 000, and ≥200 000 IU/mL) and to select patients for antiviral therapy in Africa.

Methods

Using a well-characterized cohort of treatment-naive patients with chronic HBV infection in The Gambia, we evaluated the accuracy of serum HBcrAg to diagnose HBV DNA levels and to indicate treatment eligibility determined by the American Association for the Study of Liver Diseases, based on reference tests (HBV DNA, hepatitis B e antigen, alanine aminotransferase, liver histopathology, and/or FibroScan).

Results

A total of 284 treatment-naive patients were included in the analysis. The area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of serum HBcrAg were 0.88 (95% confidence interval [CI], .82–.93), 83.3%, and 83.9%, respectively, to diagnose HBV DNA ≥2000 IU/mL; and 0.94 (95% CI, .88–.99), 91.4%, and 93.2% for ≥200 000 IU/mL. A simplified treatment algorithm using HBcrAg without HBV DNA showed high AUROC (0.91 [95% CI, .88–.95]) with a sensitivity of 96.6% and specificity of 85.8%.

Conclusions

HBcrAg might be an accurate alternative to HBV DNA quantification as a simple and inexpensive tool to identify HBV-infected patients in need of antiviral therapy in low- and middle-income countries.
An N-/L-type calcium channel blocker, cilnidipine, suppresses autonomic, electrical, and structural remodelling associated with atrial fibrillation
Authors: Tajiri Kazuko , Guichard Jean-Baptiste , Qi Xiaoyan , Xiong Feng , Naud Patrice , Tardif Jean-Claude , Costa Antoine Da , Aonuma Kazutaka , Nattel Stanley
Published: May 2019

Aims

Autonomic dysfunction can promote atrial fibrillation (AF) and results from AF-related remodelling. N-type Ca2+-channels (NTCCs) at sympathetic nerve terminals mediate Ca2+-entry that triggers neurotransmitter release. AF-associated remodelling plays an important role in AF pathophysiology but the effects of NTCC inhibition on such remodelling is unknown. Here, we investigated the ability of a clinically available Ca2+-channel blocker (CCB) with NTCC-blocking activity to suppress the arrhythmogenic effects of AF-promoting remodelling in dogs.

Methods and results

Mongrel dogs were kept in AF by right atrial tachypacing at 600 bpm. Four groups were studied under short-term AF (7 days): (i) Shams, instrumented but without tachypacing (n = 5); (ii) a placebo group, tachypaced while receiving placebo (n = 6); (iii) a control tachypacing group receiving nifedipine (10 mg orally twice-daily; n = 5), an L-type CCB; and (iv) a cilnidipine group, subjected to tachypacing and treatment with cilnidipine (10 mg orally twice-daily; n = 7), an N-/L-type CCB. With cilnidipine therapy, dogs with 1-week AF showed significantly reduced autonomic changes reflected by heart rate variability (decreases in RMSSD and pNN50) and plasma norepinephrine concentrations. In addition, cilnidipine-treated dogs had decreased extracellular matrix gene expression vs. nifedipine-dogs. As in previous work, atrial fibrosis had not yet developed after 1-week AF, so three additional groups were studied under longer-term AF (21 days): (i) Shams, instrumented without tachypacing or drug therapy (n = 8); (ii) a placebo group, tachypaced while receiving placebo (n = 8); (iii) a cilnidipine group, subjected to tachypacing during treatment with cilnidipine (10 mg twice-daily; n = 8). Cilnidipine attenuated 3-week AF effects on AF duration and atrial conduction, and suppressed AF-induced increases in fibrous-tissue content, decreases in connexin-43 expression and reductions in sodium-channel expression.

Conclusions

Cilnidipine, a commercially available NTCC-blocking drug, prevents AF-induced autonomic, electrical and structural remodelling, along with associated AF promotion.
Atorvastatin enhances the therapeutic efficacy of mesenchymal stem cells-derived exosomes in acute myocardial infarction via up-regulating long non-coding RNA H19
Authors: Huang Peisen , Wang Li , Li Qing , Tian Xiaqiu , Xu Jun , Xu Junyan , Xiong Yuyan , Chen Guihao , Qian Haiyan , Jin Chen , Yu Yuan , Cheng Ke , Qian Li , Yang Yuejin
Published: May 2019

Aims

Naturally secreted nanovesicles, known as exosomes, play important roles in stem cell-mediated cardioprotection. We have previously demonstrated that atorvastatin (ATV) pretreatment improved the cardioprotective effects of mesenchymal stem cells (MSCs) in a rat model of acute myocardial infarction (AMI). The aim of this study was to investigate if exosomes derived from ATV-pretreated MSCs exhibit more potent cardioprotective function in a rat model of AMI and if so to explore the underlying mechanisms.

Methods and results

Exosomes were isolated from control MSCs (MSC-Exo) and ATV-pretreated MSCs (MSCATV-Exo) and were then delivered to endothelial cells and cardiomyocytes in vitro under hypoxia and serum deprivation (H/SD) condition or in vivo in an acutely infarcted Sprague-Dawley rat heart. Regulatory genes and pathways activated by ATV pretreatment were explored using genomics approaches and functional studies. In vitro, MSCATV-Exo accelerated migration, tube-like structure formation, and increased survival of endothelial cells but not cardiomyocytes, whereas the exosomes derived from MSCATV-Exo-treated endothelial cells prevented cardiomyocytes from H/SD-induced apoptosis. In a rat AMI model, MSCATV-Exo resulted in improved recovery in cardiac function, further reduction in infarct size and reduced cardiomyocyte apoptosis compared to MSC-Exo. In addition, MSCATV-Exo promoted angiogenesis and inhibited the elevation of IL-6 and TNF-α in the peri-infarct region. Mechanistically, we identified lncRNA H19 as a mediator of the role of MSCATV-Exo in regulating expression of miR-675 and activation of proangiogenic factor VEGF and intercellular adhesion molecule-1. Consistently, the cardioprotective effects of MSCATV-Exo was abrogated when lncRNA H19 was depleted in the ATV-pretreated MSCs and was mimicked by overexpression of lncRNA H19.

Conclusion

Exosomes obtained from ATV-pretreated MSCs have significantly enhanced therapeutic efficacy for treatment of AMI possibly through promoting endothelial cell function. LncRNA H19 mediates, at least partially, the cardioprotective roles of MSCATV-Exo in promoting angiogenesis.
The Long-Run Effects of Oil Wealth on Development: Evidence from Petroleum Geology
Authors: Cassidy Traviss
Published: May 2019

We estimate the long-run effects of oil wealth on development by exploiting spatial variation in sedimentary basins—areas where petroleum can potentially form. Instrumental variables estimates indicate that oil production impedes democracy and fiscal capacity development, increases corruption, and raises GDP per capita without significantly harming the non-resource sectors of the economy. We find no evidence that oil production increases internal armed conflict, coup attempts, or political purges. In several specifications failure to account for endogeneity leads to substantial underestimation of the adverse effects of oil, suggesting that countries with higher-quality political institutions and greater fiscal capacity disproportionately select into oil production.
The Causal Effect of Military Conscription on Crime*
Authors: Hjalmarsson Randi , Lindquist Matthew J
Published: May 2019

We study the causal effect of mandatory military conscription in Sweden on the criminal behaviour of men born in the 1970s. We find that military service significantly increases post-service crime (overall and across multiple crime categories) between the ages of 23 and 30. These results are driven primarily by young men who come from low socioeconomic status households and those with pre-service criminal histories, despite evidence of a contemporaneous incapacitation effect of service for the latter group. Much of this crime-inducing effect can be attributed to negative peer effects experienced during service. Worse post-service labour market outcomes may also matter.
Approaching Earth’s core conditions in high-resolution geodynamo simulations
Authors: Aubert Julien
Published: May 2019

The geodynamo features a broad separation between the large scale at which Earth’s magnetic field is sustained against ohmic dissipation and the small scales of the turbulent and electrically conducting underlying fluid flow in the outer core. Here, the properties of this scale separation are analysed using high-resolution numerical simulations that approach closer to Earth’s core conditions than earlier models. The new simulations are obtained by increasing the resolution and gradually relaxing the hyperdiffusive approximation of previously published low-resolution cases. This upsizing process does not perturb the previously obtained large-scale, leading-order quasi-geostrophic (QG) and first-order magneto-Archimedes-Coriolis (MAC) force balances. As a result, upsizing causes only weak transients typically lasting a fraction of a convective overturn time, thereby demonstrating the efficiency of this approach to reach extreme conditions at reduced computational cost. As Earth’s core conditions are approached in the upsized simulations, Ohmic losses dissipate up to 97 per cent of the injected convective power. Kinetic energy spectra feature a gradually broadening self-similar, power-law spectral range extending over more than a decade in length scale. In this range, the spectral energy density profile of vorticity is shown to be approximately flat between the large scale at which the magnetic field draws its energy from convection through the QG-MAC force balance and the small scale at which this energy is dissipated. The resulting velocity and density anomaly planforms in the physical space consist in large-scale columnar sheets and plumes, respectively, co-existing with small-scale vorticity filaments and density anomaly ramifications. In contrast, magnetic field planforms keep their large-scale structure after upsizing. The small-scale vorticity filaments are aligned with the large-scale magnetic field lines, thereby minimizing the dynamical influence of the Lorentz force. The diagnostic outputs of the upsized simulations are more consistent with the asymptotic QG-MAC theory than those of the low-resolution cases that they originate from, but still feature small residual deviations that may call for further theoretical refinements to account for the structuring constraints of the magnetic field on the flow.
The Limitations on Article 43 ICSID Convention: An (Un)limited Instrument of the Tribunal?
Authors: Niemoj Asaf
Published: May 2019

Article 43 of the ICSID Convention provides tribunals with the power to order the production of further evidence. Although that power has not been used frequently, previous cases show that when article 43 is invoked by tribunals, they seem to err in the way in which they use it. This leads to a lack of consistency and clarity in the application of the provision.

This article examines the use of article 43 in two types of cases and suggests two limitations on its use. First, it examines cases in which article 43 was used by tribunals to appoint an independent expert and shows that the provision cannot be used by tribunals to do so.

Second, it looks at scenarios in which article 43 was used by tribunals in a way that added disputed questions, which were not part of the parties’ submissions and which consequently expanded the boundaries of the dispute. It suggests that article 43 cannot be invoked when that is the case. To reach this conclusion, the article will examine cases in which the use of article 43 was considered in order to investigate allegations of corruption.
Article 29—Awards, Orders, Decisions, and Rulings
Authors: Gusy Martin F , Hosking James M
Published: May 2019

This chapter addresses Article 29 of the ICDR Rules. In any arbitration, the tribunal will almost always be required to take certain decisions before it is tasked with rendering a final award. Article 29 provides the tribunal with the broad authority to make such decisions to keep the arbitration advancing and to ultimately resolve the dispute. In addition to the broad powers in Article 29(1), Article 29(2) attempts to address the possibility that a unanimous decision will be unobtainable in an arbitration involving more than a sole arbitrator by permitting any ‘award, order, decision, or ruling’ to be made by a majority of arbitrators, regardless of whether the presiding arbitrator is part of that majority. Meanwhile, Article 29(3) empowers the tribunal to delegate to the presiding arbitrator the authority to make ‘orders, decisions, or rulings on questions of procedure’, subject to revision by the full tribunal.
Part I Introduction, 2 The Concept and Reality of the International Watercourse System
Authors: Stephen C McCaffrey
Published: May 2019

This chapter examines the behavior of Earth’s water system and the concept of the international watercourse. Most of the water on Earth is in constant motion in the hydrologic cycle, which consists of the evaporation of water into the atmosphere, chiefly from the sea, and its return to Earth through precipitation and condensation. Surface waters contained in rivers and lakes are merely one small part of Earth’s hydrologic cycle. Because there is always groundwater underlying, and related to, surface water, any attempt to regulate one without addressing the other would be futile. Moreover, the constant movement of Earth’s water through the hydrologic cycle means that it would be futile for any one state to attempt to subject fresh water within its borders to absolute control.
Part III The Major Cases and Controversies: A Survey of State Practice, 7 Selected Case Studies
Authors: Stephen C McCaffrey
Published: May 2019

This chapter provides descriptions of past or present controversies between states concerning non-navigational uses of international watercourses. Some of the controversies considered have been settled while others are ongoing and show no signs of an imminent resolution. Eight of the eighteen drainage basins examined are now governed by treaties dealing with the problem that gave rise to the dispute in question. In all of the cases reviewed, the disputes were matters of high national interest, engaging the attention of government officials, diplomats, and scholars alike. Indeed, several of the controversies were brought before the United Nations, usually with good effect. Ultimately, some of the basins will probably receive increasing international attention as expanding populations, climate change, and upstream development efforts combine to place further demands on already scarce water resources.
Part IV Fundamental Rights and Obligations, 8 Introduction: The 1997 United Nations Convention and its Precursors
Authors: Stephen C McCaffrey
Published: May 2019

This chapter discusses the 1997 United Nations Watercourses Convention. The Convention on the Law of the Non-Navigational Uses of International Watercourses was adopted by the United Nations General Assembly on May 21, 1997 and entered into force on August 17, 2014. The UN Watercourses Convention represents an effort by the international community to reflect the general principles and rules of international law governing the use by states of shared freshwater resources, except for principles and rules concerning navigation. The working document on the basis of which the Convention was negotiated was the result of twenty years’ work by the International Law Commission, a subsidiary organ of the General Assembly charged with “the progressive development of international law and its codification.” The chapter then provides an overview of the provision of the Convention.
The African Charter on Human and Peoples' Rights
Authors: Murray Rachel
Published: May 2019

The African Charter on Human and Peoples’ Rights (ACHPR) is the principle regional human rights treaty for the African continent. Adopted in 1981, there is now a significant body of jurisprudence and interpretation by its African Commission on Human and Peoples’ Rights and the recently established African Court. This volume provides a comprehensive article-by-article legal analysis of the provisions of the Charter as it draws upon the documents adopted by the African Commission, including resolutions, case law, and concluding observations. Where relevant, case law adopted by the African Court on Human and Peoples’ Rights, and that of other sub-regional courts and tribunals and domestic courts in Africa, are also incorporated. The book examines not only the substantive rights in the African Charter but also the work of the African Commission on Human and Peoples’ Rights and provides a full examination of its mandate. A critical analysis of each of the provisions of the ACHPR is led principally by the jurisprudence and documentation of the African Commission and African Court. The text also identifies the overall development of the ACHPR within the broader regional and international human rights legal arena.
Article 4
Authors: Murray Rachel
Published: May 2019

This section is about Article 4 of the African Charter on Human and Peoples’ Rights dealing with The Right to Life and Integrity of the Person.
Article 6
Authors: Murray Rachel
Published: May 2019

This section is about Article 6 of the African Charter on Human and Peoples’ Rights dealing with Right to Liberty and Security of the Person.
Article 13
Authors: Murray Rachel
Published: May 2019

This section is about Article 13 of the African Charter on Human and Peoples’ Rights dealing with Participation in the Government, Access to the Public Service and to Public Property.
Article 15
Authors: Murray Rachel
Published: May 2019

This section is about Article 15 of the African Charter on Human and Peoples’ Rights dealing with Right to Work.
Article 18
Authors: Murray Rachel
Published: May 2019

This section is about Article 18 of the African Charter on Human and Peoples’ Rights dealing with Protection of the Family, Rights of Women, Older Persons and Persons with Disabilities.
Article 20
Authors: Murray Rachel
Published: May 2019

This section is about Article 20 of the African Charter on Human and Peoples’ Rights dealing with Peoples’ Right to Existence, Self-determination and Freedom from Foreign Domination.
Article 26
Authors: Murray Rachel
Published: May 2019

This section is about Article 26 of the African Charter on Human and Peoples’ Rights dealing with Independence of the Courts and Establishment of National Institution.
Articles 30–40
Authors: Murray Rachel
Published: May 2019

This section is about Articles 30–40 of the African Charter on Human and Peoples’ Rights dealing with The African Commission on Human and Peoples’ Rights.
Articles 45 and 46
Authors: Murray Rachel
Published: May 2019

This section is about Articles 45 and 46 of the African Charter on Human and Peoples’ Rights dealing with Mandate and Procedure of the African Commission.
Articles 47–54
Authors: Murray Rachel
Published: May 2019

This section is about Articles 47–54 of the African Charter on Human and Peoples’ Rights dealing with Inter-State Communications and Activity Reports.
Article 62
Authors: Murray Rachel
Published: May 2019

This section is about Article 62 of the African Charter on Human and Peoples’ Rights dealing with State Reporting.
Articles 63–68
Authors: Murray Rachel
Published: May 2019

This section is about Articles 63–68 of the African Charter on Human and Peoples’ Rights dealing with Signature, Ratification and Adherence, Reservations and Protocols.
Using convolutional neural networks to identify gravitational lenses in astronomical images
Authors: Davies Andrew , Serjeant Stephen , Bromley Jane M
Published: May 2019

The Euclid telescope, due for launch in 2021, will perform an imaging and slitless spectroscopy survey over half the sky, to map baryon wiggles and weak lensing. During the survey, Euclid is expected to resolve 100 000 strong gravitational lens systems. This is ideal to find rare lens configurations, provided they can be identified reliably and on a reasonable time-scale. For this reason, we have developed a convolutional neural network (CNN) that can be used to identify images containing lensing systems. CNNs have already been used for image and digit classification as well as being used in astronomy for star-galaxy classification. Here, our CNN is trained and tested on Euclid-like and KiDS (Kilo-Degree Survey)-like simulations from the Euclid Strong Lensing Group, successfully classifying 77 per cent of lenses, with an area under the ROC curve of up to 0.96. Our CNN also attempts to classify the lenses in COSMOS Hubble Space Telescope F814W-band images. After convolution to the Euclid resolution, we find we can recover most systems that are identifiable by eye. The python code is available on Github.
Optical and UV studies of type Ia supernovae SN 2009ig and SN 2012cg
Authors: Chakradhari N K , Sahu D K , Anupama G C
Published: May 2019

We present an extensive optical–ultraviolet photometry and analysis of a series of optical spectra of type Ia supernovae SN 2009ig and SN 2012cg. The observations range from −15 to +185 d for SN 2009ig and from −14 to 316 d for SN 2012cg, with respect to maximum light in B band. Both SN 2009ig and SN 2012cg exhibit similar properties. They have similar decline rate parameter (Δm15(B)true = 0.92 ± 0.04 for SN 2009ig and 0.93 ± 0.06 for SN 2012cg) and B band peak absolute magnitude (−19.45 ± 0.40 mag for SN 2009ig and −19.50 ± 0.31 mag for SN 2012cg). Their early spectra show high-velocity features in Si ii and Ca ii lines. The strong Fe iii, Si iii, and weak Si ii λ5972 line during pre-maximum phase are indicative of hot photosphere. The post-maximum velocity evolution shows a plateau like phase with velocities ∼13 000 km s−1 for SN 2009ig and ∼10 000 km s−1 for SN 2012cg. Both events show spectral evolution similar to normal SNe Ia and fall in LVG and Core Normal subgroup. Both have smaller strength ratio [$\cal R$(Si ii) = 0.17 for SN 2009ig and 0.20 for SN 2012cg] consistent with smaller Δm15(B). Peak bolometric luminosities ($\log L_\text{bol}^\text{max}$) of these events are estimated as 43.17 ± 0.16 and 43.24 ± 0.11 erg s−1 suggesting that 0.60 ± 0.20 M⊙ of 56Ni was synthesized in the explosion of SN 2009ig and 0.72 ± 0.31 M⊙ in SN 2012cg.
Ground-based follow-up observations of TRAPPIST-1 transits in the near-infrared
Authors: Burdanov A Y , Lederer S M , Gillon M , Delrez L , Ducrot E , de Wit J , Jehin E , Triaud A H M J , Lidman C , Spitler L , Demory B-O , Queloz D , Van Grootel V
Published: May 2019

The TRAPPIST-1 planetary system is a favourable target for the atmospheric characterization of temperate earth-sized exoplanets by means of transmission spectroscopy with the forthcoming James Webb Space Telescope (JWST). A possible obstacle to this technique could come from the photospheric heterogeneity of the host star that could affect planetary signatures in the transit transmission spectra. To constrain further this possibility, we gathered an extensive photometric data set of 25 TRAPPIST-1 transits observed in the near-IR J band (1.2 μm) with the UKIRT and the AAT, and in the NB2090 band (2.1 μm) with the VLT during the period 2015–18. In our analysis of these data, we used a special strategy aiming to ensure uniformity in our measurements and robustness in our conclusions. We reach a photometric precision of 0.003 (RMS of the residuals), and we detect no significant temporal variations of transit depths of TRAPPIST-1 b, c, e, and g over the period of 3 yr. The few transit depths measured for planets d and f hint towards some level of variability, but more measurements will be required for confirmation. Our depth measurements for planets b and c disagree with the stellar contamination spectra originating from the possible existence of bright spots of temperature 4500 K. We report updated transmission spectra for the six inner planets of the system which are globally flat for planets b and g and some structures are seen for planets c, d, e, and f.
YZ Phoenicis: a very short period K-type contact binary with variation of the O’Connell effect and orbital period change
Authors: Sarotsakulchai Thawicharat , Qian Sheng-Bang , Soonthornthum Boonrucksar , Zhou Xiao , Zhang Jia , Li Lin-Jia , Reichart Daniel E , Haislip Joshua B , Kouprianov Vladimir V , Poshyachinda Saran
Published: May 2019

YZ Phe is a very short-period contact binary (Sp. = K2 V) with an orbital period of 0.2347 d near the short period limit (0.22 d). We present the complete light curves which photometric data were obtained from the 60 cm telescope of PROMPT-8 at CTIO in Chile during 2016 June to October and 2017 August. The photometric solutions were determined by using the Wilson & Devinney code and the results reveal that YZ Phe is a W-subtype shallow contact binary ($f\sim 10\,$, q = 2.635, or 1/q = 0.379 for W subtype) with rotational motion of a large hot spot on the more massive component, showing a strong O’Connell effect with variation of maxima in photometric time series at period of 4.20 yr and stellar cycle at period of 1.28 yr. By compiling all available eclipse times, the result shows a long-term period decrease at a rate of dP/dt = −2.64(±0.02) × 10−8 d yr−1, superimposed on a cyclic variation (A3 = 0.0081 d and P3 = 40.76 yr). This variation cannot be explained by the Applegate mechanism. Thus, the cyclic change may be interpreted as the light-travel time effect via the presence of a cool third body. Based on photometric solutions, the third light was detected as $2\,$ of the total light in V and I bands. These results support the existence of a third body. The long-term period decrease can be explained by mass transfer from the more massive component ($M_2 \sim 0.74\, M_{\odot }$) to the less massive one ($M_1 \sim 0.28\, M_{\odot }$) or plus angular momentum loss (AML) via magnetic braking. With 1/q < 0.4 and long-term period decrease, all factors suggest that YZ Phe is on the AML-controlled state and its fill-out factor will increase, as well as the system evolving into a deeper normal contact binary.
PD-1+CXCR5−CD4+T cells are correlated with the severity of systemic lupus erythematosus
Authors: Lin Jin , Yu Ye , Ma Jilin , Ren Chunyun , Chen Weiqian
Published: May 2019

Objectives

PD-1+CXCR5−CD4+T peripheral helper (Tph) cells, a recently identified T cell subset, are proven to promote B cell responses and antibody production in rheumatoid arthritis, but their role in the pathogenesis of SLE is unknown. We explored the role of Tph in lupus disease development.

Methods

This cohort study included 68 patients with SLE and 41 age- and sex-matched healthy individuals. The frequency of PD-1+CXCR5−CD4+T cells was analysed in peripheral blood by flow cytometry. Inducible T-cell costimulator, CD38, MHC-II, IL-21, CXCR3 and CCR6 expression were measured in Tph cells. Comparisons between the two groups were performed, and correlations between Tph cells and other parameters were investigated.

Results

We revealed a markedly expanded population of Tph cells (8.31 ± 5.45 vs 2.86 ± 1.31%, P < 0.0001) in the circulation of patients with SLE (n = 68), compared with healthy controls (n = 41). Tph cells were much higher in the active group than in the inactive group (14.21 ± 5.21 vs 5.49 ± 2.52%, P < 0.0001). Tph cells were significantly associated with SLEDAI score (r = 0.802), ESR (r = 0.415), IgG (r = 0.434), C3 (r = −0.543), C4 (r = −0.518) and IL-21 level (r = 0.628), and ANA titre (r = 0.272). Furthermore, Tph cells were much higher in lupus patients with arthritis, nephritis, rash, alopecia, pleuritis, pericarditis and haematological involvement. Tph cells were associated with CD138+/CD19+ plasma cells (r = 0.518). Furthermore, MHC-II, inducible T-cell costimulator, CD38, and IL-21 expression were all higher in Tph cells from SLE patients compared with healthy controls. CXCR3+CCR6−Tph (Tph1) cells were expanded in the SLE patients.

Conclusion

Our data show that relative number of Tph cells is correlated with disease measures in patients with SLE, suggesting an important role in lupus disease development.
Interactions of Dichlorodiphenyltrichloroethane (DDT) and Dichlorodiphenyldichloroethylene (DDE) With Skeletal Muscle Ryanodine Receptor Type 1
Authors: Truong Kim M , Cherednichenko Gennady , Pessah Isaac N
Published: May 2019

Dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE) are ubiquitous in the environment and detected in tissues of living organisms. Although DDT owes its insecticidal activity to impeding closure of voltage-gated sodium channels, it mediates toxicity in mammals by acting as an endocrine disruptor (ED). Numerous studies demonstrate DDT/DDE to be EDs, but studies examining muscle-specific effects mediated by nonhormonal receptors in mammals are lacking. Therefore, we investigated whether o,p′-DDT, p,p′-DDT, o,p′-DDE, and p,p′-DDE (DDx, collectively) alter the function of ryanodine receptor type 1 (RyR1), a protein critical for skeletal muscle excitation-contraction coupling and muscle health. DDx (0.01–10 µM) elicited concentration-dependent increases in [3H]ryanodine ([3H]Ry) binding to RyR1 with o,p′-DDE showing highest potency and efficacy. DDx also showed sex differences in [3H]Ry-binding efficacy toward RyR1, where [3H]Ry-binding in female muscle preparations was greater than male counterparts. Measurements of Ca2+ transport across sarcoplasmic reticulum (SR) membrane vesicles further confirmed DDx can selectively engage with RyR1 to cause Ca2+ efflux from SR stores. DDx also disrupts RyR1-signaling in HEK293T cells stably expressing RyR1 (HEK-RyR1). Pretreatment with DDx (0.1–10 µM) for 100 s, 12 h, or 24 h significantly sensitized Ca2+-efflux triggered by RyR agonist caffeine in a concentration-dependent manner. o,p′-DDE (24 h; 1 µM) significantly increased Ca2+-transient amplitude from electrically stimulated mouse myotubes compared with control and displayed abnormal fatigability. In conclusion, our study demonstrates DDx can directly interact and modulate RyR1 conformation, thereby altering SR Ca2+-dynamics and sensitize RyR1-expressing cells to RyR1 activators, which may ultimately contribute to long-term impairments in muscle health.
Prenatal Exposure to Bisphenol A, E, and S Induces Transgenerational Effects on Female Reproductive Functions in Mice
Authors: Shi Mingxin , Whorton Allison E , Sekulovski Nikola , MacLean James A , Hayashi Kanako
Published: May 2019

This study was performed to examine the transgenerational effects of bisphenol (BP) A analogs, BPE, and BPS on female reproductive functions using mice as a model. CD-1 mice (F0) were orally exposed to control treatment (corn oil), BPA, BPE, or BPS (0.5 or 50 µg/kg/day) from gestational day 7 (the presence of vaginal plug = 1) to birth. Mice from F1 and F2 offspring were used to generate F3 females. Prenatal exposure to BPA, BPE, and BPS accelerated the onset of puberty and exhibited abnormal estrous cyclicity in F3 females, and those females exhibited mating difficulties starting at 6 months of age. Various fertility problems including reduced pregnancy rates, parturition, and nursing issues were also observed starting at 6 months, which worsened at 9 months. The levels of serum estradiol-17β were elevated by BPA or BPS exposure at the age of 6 months, whereas testosterone levels were not affected. The dysregulated expression of steroidogenic enzymes was observed in the ovary at 3 or 6 months of age by BPE or BPS exposure. However, BPA, BPE, and BPS exposure did not affect neonatal follicular development such as germ cell nest breakdown or follicle numbers in the ovary on postnatal day 4. These results suggest that prenatal exposure to BPA analogs, BPE and BPS, have transgenerational effects on female reproductive functions in mice.
Management trends for postcatheterization femoral artery pseudoaneurysms
Authors: Madia Carol
Published: May 2019

Femoral artery pseudoaneurysm is the most common complication of femoral artery access. Since the 1990s, use of femoral artery access has increased along with cardiac and peripheral interventions. Conservative management with observation is an option for some patients with femoral artery pseudoaneurysms. Open surgical repair was the mainstay of therapy before 1990 but was replaced by ultrasound-guided compression, which in turn has been replaced by ultrasound-guided thrombin injection because of its high success rate and low rate of complications. This article describes femoral artery pseudoaneurysms and their management.
How to recognize caffeine overdose
Authors: Carreon Christian “CJ” , Parsh Bridget
Published: May 2019

Caffeine is the most widely consumed stimulant in the world and can offer a variety of benefits when consumed in moderation. But consuming caffeine in extremely high amounts can lead to an overdose. This article examines how nurses can recognize the signs and symptoms of caffeine overdose and educate patients on how to prevent this common problem.
Positive End-expiratory Pressure and Postoperative Atelectasis
Authors: Östberg Erland , Thorisson Arnar , Enlund Mats , Zetterström Henrik , Hedenstierna Göran , Edmark Lennart
Published: May 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Positive end-expiratory pressure (PEEP) increases lung volume and protects against alveolar collapse during anesthesia. During emergence, safety preoxygenation preparatory to extubation makes the lung susceptible to gas absorption and alveolar collapse, especially in dependent regions being kept open by PEEP. We hypothesized that withdrawing PEEP before starting emergence preoxygenation would limit postoperative atelectasis formation.

Methods

This was a randomized controlled evaluator-blinded trial in 30 healthy patients undergoing nonabdominal surgery under general anesthesia and mechanical ventilation with PEEP 7 or 9 cm H2O depending on body mass index. A computed tomography scan at the end of surgery assessed baseline atelectasis. The study subjects were thereafter allocated to either maintained PEEP (n = 16) or zero PEEP (n = 14) during emergence preoxygenation. The primary outcome was change in atelectasis area as evaluated by a second computed tomography scan 30 min after extubation. Oxygenation was assessed by arterial blood gases.

Results

Baseline atelectasis was small and increased modestly during awakening, with no statistically significant difference between groups. With PEEP applied during awakening, the increase in atelectasis area was median (range) 1.6 (−1.1 to 12.3) cm2 and without PEEP 2.3 (−1.6 to 7.8) cm2. The difference was 0.7 cm2 (95% CI, −0.8 to 2.9 cm2; P = 0.400). Postoperative atelectasis for all patients was median 5.2 cm2 (95% CI, 4.3 to 5.7 cm2), corresponding to median 2.5% of the total lung area (95% CI, 2.0 to 3.0%). Postoperative oxygenation was unchanged in both groups when compared to oxygenation in the preoperative awake state.

Conclusions

Withdrawing PEEP before emergence preoxygenation does not reduce atelectasis formation after nonabdominal surgery. Despite using 100% oxygen during awakening, postoperative atelectasis is small and does not affect oxygenation, possibly conditional on an open lung during anesthesia, as achieved by intraoperative PEEP.
Risk Factors for Postoperative Distal Adding-on in Lenke Type 1B and 1C and its Influence on Residual Lumbar Curve
Authors: Fujii Takeshi , Daimon Kenshi , Fujita Nobuyuki , Yagi Mitsuru , Michikawa Takehiro , Hosogane Naobumi , Nagoshi Narihito , Tsuji Osahiko , Kaneko Shinjiro , Tsuji Takashi , Nakamura Masaya , Matsumoto Morio , Watanabe Kota
Published: May 2019

Background:

Distal adding-on (DA) in adolescent idiopathic scoliosis is a radiographic complication that can negatively affect clinical results. However, the risk factors for DA and the influences of DA on the residual lumbar curves have not been fully elucidated in Lenke type 1B and 1C curves. The objective of this study was to investigate risk factors for postoperative DA in Lenke type 1B and 1C curves, and the influence of DA on residual lumbar curves.

Methods:

We retrospectively evaluated 46 adolescent idiopathic scoliosis patients with Lenke type 1B or 1C curves who underwent posterior correction and fusion surgery with selective thoracic fusion. Patients were grouped according to the presence or absence of DA on radiographs at the 2-year follow-up. We compared coronal radiographic parameters between the 2 groups, including the Cobb angle, L4 tilt angle, apical translation, and relative positions of the end vertebra (EV), stable vertebra (SV), neutral vertebra (NV), and last touching vertebra (LTV) to the lower instrumented vertebra (LIV).

Results:

DA was present in 11 patients (24%) at the 2-year follow-up, and the mean LIV-EV, LIV-NV, LIV-SV, and LIV-LTV relative positions were significantly smaller in the DA than in the non-DA group. Preoperative radiographic parameters were similar between the 2 groups, including the mean L4 tilt angle (non-DA, −8±4 degrees; DA, −7±4 degrees). At the 2-year follow-up, the mean apical translation of the lumbar curve was smaller in the DA group (non-DA, −16±8 mm; DA, −7±11 mm) and the mean L4 tilt angle was significantly more horizontalized (non-DA, −8±4 degrees; DA, −1±5 degrees). Multivariate analysis showed that the number of levels between the LIV and LTV (LIV-LTV) was significantly associated with DA.

Conclusions:

A LIV at or cranial to the LTV was a significant risk factor for postoperative DA in Lenke type 1B and 1C curves. Spontaneous correction of the residual lumbar curve was superior in patients with DA.

Level of Evidence:

Level III.
Repair of Pars Interarticularis Defect Utilizing a Pedicle and Laminar Screw Construct: A Technique Discussion and Case Series
Authors: Snowden Ryan , Sasso Rick
Published: May 2019

Introduction:

Lumbar isthmic spondylolysis is a common disorder in young adults and adolescents. Following failure of nonoperative measures, multiple nonfusion techniques have been described to repair the spondylotic defect with varying results. Recently a new pedicle screw-laminar screw construct has been described and found comparable to other pedicle screw constructs in biomechanical testing. We describe the use of the pedicle screw-lamina screw constructs using image guidance and 3-dimensional imaging in the surgical management of isthmic spondylolysis. We also present a case series of patients undergoing treatment of isthmic spondylolysis. All patients undergoing pedicle screw-laminar screw pars repair construct from 2012 to 2017 by the senior author.

Materials and Methods:

All patients undergoing pedicle screw-laminar screw pars repair by the senior author from 2012 to 2017 were included. Patients were excluded for spondylolisthesis, disc degeneration at the level of spondylolysis, advanced age (>25), evidence of nerve root compression or significant signs of degenerative osteoarthritis. All patients failed a standardized course of nonoperative treatment before surgery. Patients were followed until full, pain-free activity had resumed. Six patients successfully underwent pedicle screw-laminar screw pars repair using intraoperative computed tomography guidance. There were no intraoperative or postoperative complications. All patients returned to full athletic activity at an average of 5.17 months. Final radiographs showed complete or near complete resolution of the defect in all cases. We are the first to describe the use of the pedicle screw-lamina screw constructs using image guidance and 3-dimensional imaging in the surgical management of isthmic spondylolisthesis in a clinical situation. The combination of pedicle screw and laminar screw provides a construct with robust fixation while allowing for ample bone grafting surface area. Furthermore, the utilization of intraoperative navigations provides an added measure of safety when placing both screws.
Adductor Tendon Repair: Case Report and Description of a Novel Approach for Improved Exposure
Authors: Gerhardt Michael , Sherman Benjamin , Trentacosta Natasha , Hobart Sarah , Hutchinson William , Chahla Jorge
Published: May 2019

Groin pain is one of the most common and challenging diagnoses for a sports medicine physician. Up to 64% of groin injuries involve the adductor tendons, which can be very difficult to treat with or without surgical intervention. The purpose of this article is to report the 2-year outcomes of a patient that presented with an acute proximal adductor tendon injury and to describe a novel surgical approach. This is a case of a 36-year-old elite athlete that presented with an acute adductor longus tear. The patient was treated with surgical repair using a parainguinal approach and bioabsorbable suture anchors into the adductor longus anatomic footprint. The patient had a full return to sport at 8 weeks postoperatively. At 2 years the patient was symptom free and still participating in the same elite level of sport. Adductor repair using a parainguinal approach and bioabsorbable suture anchors is a viable surgical option for patients in the acute setting.
Estimated risk of progression of lentigo maligna to lentigo maligna melanoma
Authors: Menzies Scott W. , Liyanarachchi Sakitha , Coates Elliot , Smith Annika , Cooke-Yarborough Claire , Lo Serigne , Armstrong Bruce , Scolyer Richard A. , Guitera Pascale
Published: May 2019

Little is known about the risk of progression of lentigo maligna to lentigo maligna melanoma. We determine the annual risk of progression of lentigo maligna to lentigo maligna melanoma by analysing a prospective population-based survey of recently diagnosed anterior (visible in a mirror) head and neck lentigo malignas and lentigo maligna melanomas. Six hundred eighty-two consecutive patients aged 18–80 years with non-recurrent lentigo maligna or lentigo maligna melanoma, diagnosed between 1 July 2015 and 20 April 2016, were identified from pathology notifications to the New South Wales Cancer Registry (Australia) and sent survey questionnaires soon after diagnosis (median 4.6 months interquartile range: 3.8–5.7). Details of the time the lesion was present and when changes to it were noticed before diagnostic biopsy were ascertained by surveying the patients, of whom 53.5% agreed to participate. There was little difference between the proportions of lentigo maligna melanoma and lentigo maligna in the consenting and non-consenting patients (P = 0.56). Two hundred twenty-eight lentigo maligna (median age 67 years, range: 38–80) and 33 lentigo maligna melanoma (70 years, 43–80) were surveyed. There was no difference between the time lentigo maligna melanoma was present on the skin (median 18 months, range: 0–690) and the time lentigo maligna was (18 months, 0–665) (P = 0.972). The estimated risk of progression of lentigo maligna to lentigo maligna melanoma was 3.5% per year (95% confidence interval: 2.5–5.0). This equates to an average time for lentigo maligna to progress to lentigo maligna melanoma of 28.3 years (95% confidence interval: 20.0–40.5) in this population. Although our data suggests that the annual progression rate of lentigo maligna is more than 25 times greater than previously suggested, the rate is still low.