bluuebunny/crossref_metadata_2025 huggingface dataset:
The Aldosterone/Renin Ratio Predicts Cardiometabolic Disorders in Subjects Without Classic Primary Aldosteronism
Authors: Vecchiola Andrea , Fuentes Cristóbal Andrés , Barros Eric Raúl , Martínez-Aguayo Alejandro , García Hernán , Allende Fidel , Solari Sandra , Olmos Roberto , Carvajal Cristian , Tapia-Castillo Alejandra , Campino Carmen , Kalergis Alexis Mikes , Baudrand Rene , Fardella Carlos Enrique
Published: February 2019

BACKGROUND

Aldosterone has been linked with obesity, metabolic syndrome (MetS), pro-inflammatory, and prothrombotic states; however, most studies relate these indicators with primary aldosteronism (PA), excluding non-PA patients.

OBJECTIVE

To determine whether aldosterone, renin, or the plasma aldosterone/renin ratio (ARR) are associated with metabolic disorders and inflammatory/vascular biomarkers in a non-PA population.

METHODS

We studied 275 patients including adolescents and adults of both genders and measured plasma and urinary aldosterone and determined the plasma renin activity. In all subjects, the presence of MetS was determined according to Adult Treatment Panel III. Renal, vascular, inflammatory, and mineralocorticoid activity biomarkers were evaluated.

RESULTS

The ARR correlated with the number of variables of MetS (r = 0.191, P = 0.002), body mass index (BMI; r = 0.136, P = 0.026), systolic blood pressure (r = 0.183, P = 0.002), diastolic blood pressure (r = 0.1917, P = 0.0014), potassium excreted fraction (r = 0.174, P = 0.004), low-density lipoprotein (r = 0.156, P = 0.01), plasminogen activator inhibitor type 1 (r = 0.158, P = 0.009), microalbuminuria (r = 0.136, P = 0.029), and leptin (r = 0.142, P = 0.019). In a linear regression model adjusted by age, BMI, and gender, only the ARR was still significant (r = 0.108, P = 0.05). In a logistic regression analysis, the ARR predicted MetS index (odds ratio (OR) = 1.07 [95% confidence interval (CI) = 1.011–1.131], P= 0.02) even after adjusting for age, BMI, and gender. On the other hand, aldosterone showed no association with MetS or inflammatory markers.

CONCLUSION

These results suggest a continuum of cardiometabolic risk beyond the classic PA threshold screening. The ARR could be a more sensitive marker of obesity, MetS, and endothelial damage in non-PA patients than aldosterone or renin alone. Prospective studies are needed to develop future screening cutoff values.
Potential involvement of root auxins in drought tolerance by modulating nocturnal and daytime water use in wheat
Authors: Sadok Walid , Schoppach Rémy
Published: February 2019

Background and Aims

The ability of wheat genotypes to save water by reducing their transpiration rate (TR) at times of the day with high vapour pressure deficit (VPD) has been linked to increasing yields in terminal drought environments. Further, recent evidence shows that reducing nocturnal transpiration (TRN) could amplify water saving. Previous research indicates that such traits involve a root-based hydraulic limitation, but the contribution of hormones, particularly auxin and abscisic acid (ABA), has not been explored to explain the shoot–root link. In this investigation, based on physiological, genetic and molecular evidence gathered on a mapping population, we hypothesized that root auxin accumulation regulates whole-plant water use during both times of the day.

Methods

Eight double-haploid lines were selected from a mapping population descending from two parents with contrasting water-saving strategies and root hydraulic properties. These spanned the entire range of slopes of TR responses to VPD and TRN encountered in the population. We examined daytime/night-time auxin and ABA contents in the roots and the leaves in relation to hydraulic traits that included whole-plant TR, plant hydraulic conductance (KPlant), slopes of TR responses to VPD and leaf-level anatomical traits.

Key Results

Root auxin levels were consistently genotype-dependent in this group irrespective of experiments and times of the day. Daytime root auxin concentrations were found to be strongly and negatively correlated with daytime TR, KPlant and the slope of TR response to VPD. Night-time root auxin levels significantly and negatively correlated with TRN. In addition, daytime and night-time leaf auxin and ABA concentrations did not correlate with any of the examined traits.

Conclusions

The above results indicate that accumulation of auxin in the root system reduces daytime and night-time water use and modulates plant hydraulic properties to enable the expression of water-saving traits that have been associated with enhanced yields under drought.
Sub-Scarpa’s Lipectomy in Abdominoplasty: An Analysis of Risks and Rewards in 723 Consecutive Patients
Authors: Restifo Richard J
Published: February 2019

Background

During the course of performing abdominoplasties, a plastic surgeon will encounter a certain body habitus characterized by a thick, tethered, and excessively redundant upper skin flap. Often these patients also demonstrate diffuse and substantial fascial laxity. One approach to this problem involves direct thinning and release of the flap by resection of the sub-Scarpa’s fat pad. In theory, this resection should be safe from a flap perfusion standpoint. However, the safety of the sub-Scarpa’s resection has not been completely documented.

Objectives

The author sought to assess the safety and efficacy of sub-Scarpa’s lipectomy in abdominoplasty.

Methods

A total 723 patients were retrospectively examined and divided into 2 groups: those with (Group B) and those without (Group A) a sub-Scarpa’s lipectomy component to the abdominoplasty. Because of differences in the baseline characteristics between the 2 groups, data analysis was performed with a logistic regression model and with propensity score matching.

Results

The sub-Scarpa’s lipectomy technique allowed for substantial thinning of the flap: the average weight of the resected fat pad was 411 g. Wide undermining allowed for substantial fascial correction, and excellent results were obtainable even in challenging cases. The sub-Scarpa’s lipectomy group did not demonstrate an increase in either minor (<5 cm2) or major (>5 cm2) flap necrosis. However, there was a statistically significant increase in fat necrosis and seroma formation in Group B compared with Group A. In both groups, an increasing body mass index was a risk factor for fat necrosis and major flap necrosis.

Conclusions

The implementation of a sub-Scarpa’s lipectomy during abdominoplasty is a useful technique to consider for selected abdominoplasty candidates. The risks of minor and major flap loss do not seem to be increased compared to the standard abdominoplasty, but the risks of fat necrosis and seroma formation may be greater.

Level of Evidence: 4
Finding de novo methylated DNA motifs
Authors: Ngo Vu , Wang Mengchi , Wang Wei
Published: February 2019

Motivation

Increasing evidence has shown that nucleotide modifications such as methylation and hydroxymethylation on cytosine would greatly impact the binding of transcription factors (TFs). However, there is a lack of motif finding algorithms with the function to search for motifs with modified bases. In this study, we expand on our previous motif finding pipeline Epigram to provide systematic de novo motif discovery and performance evaluation on methylated DNA motifs.

Results

mEpigram outperforms both MEME and DREME on finding modified motifs in simulated data that mimics various motif enrichment scenarios. Furthermore we were able to identify methylated motifs in Arabidopsis DNA affinity purification sequencing (DAP-seq) data that were previously demonstrated to contain such motifs. When applied to TF ChIP-seq and DNA methylome data in H1 and GM12878, our method successfully identified novel methylated motifs that can be recognized by the TFs or their co-factors. We also observed spacing constraint between the canonical motif of the TF and the newly discovered methylated motifs, which suggests operative recognition of these cis-elements by collaborative proteins.

Availability and implementation

The mEpigram program is available at http://wanglab.ucsd.edu/star/mEpigram.

Supplementary information

Supplementary data are available at Bioinformatics online.
Incorporating alignment uncertainty into Felsenstein’s phylogenetic bootstrap to improve its reliability
Authors: Chang Jia-Ming , Floden Evan W , Herrero Javier , Gascuel Olivier , Di Tommaso Paolo , Notredame Cedric
Published: February 2019

Motivation

Most evolutionary analyses are based on pre-estimated multiple sequence alignment. Wong et al. established the existence of an uncertainty induced by multiple sequence alignment when reconstructing phylogenies. They were able to show that in many cases different aligners produce different phylogenies, with no simple objective criterion sufficient to distinguish among these alternatives.

Results

We demonstrate that incorporating MSA induced uncertainty into bootstrap sampling can significantly increase correlation between clade correctness and its corresponding bootstrap value. Our procedure involves concatenating several alternative multiple sequence alignments of the same sequences, produced using different commonly used aligners. We then draw bootstrap replicates while favoring columns of the more unique aligner among the concatenated aligners. We named this concatenation and bootstrapping method, Weighted Partial Super Bootstrap (wpSBOOT). We show on three simulated datasets of 16, 32 and 64 tips that our method improves the predictive power of bootstrap values. We also used as a benchmark an empirical collection of 853 one to one orthologous genes from seven yeast species and found wpSBOOT to significantly improve discrimination capacity between topologically correct and incorrect trees. Bootstrap values of wpSBOOT are comparable to similar readouts estimated using a single method. However, for reduced trees by 50 and 95% bootstrap thresholds, wpSBOOT comes out the lowest Type I error (less FP).

Availability and implementation

The automated generation of replicates has been implemented in the T-Coffee package, which is available as open source freeware available from www.tcoffee.org.

Supplementary information

Supplementary data are available at Bioinformatics online.
Structured crowdsourcing enables convolutional segmentation of histology images
Authors: Amgad Mohamed , Elfandy Habiba , Hussein Hagar , Atteya Lamees A , Elsebaie Mai A T , Abo Elnasr Lamia S , Sakr Rokia A , Salem Hazem S E , Ismail Ahmed F , Saad Anas M , Ahmed Joumana , Elsebaie Maha A T , Rahman Mustafijur , Ruhban Inas A , Elgazar Nada M , Alagha Yahya , Osman Mohamed H , Alhusseiny Ahmed M , Khalaf Mariam M , Younes Abo-Alela F , Abdulkarim Ali , Younes Duaa M , Gadallah Ahmed M , Elkashash Ahmad M , Fala Salma Y , Zaki Basma M , Beezley Jonathan , Chittajallu Deepak R , Manthey David , Gutman David A , Cooper Lee A D
Published: February 2019

Motivation

While deep-learning algorithms have demonstrated outstanding performance in semantic image segmentation tasks, large annotation datasets are needed to create accurate models. Annotation of histology images is challenging due to the effort and experience required to carefully delineate tissue structures, and difficulties related to sharing and markup of whole-slide images.

Results

We recruited 25 participants, ranging in experience from senior pathologists to medical students, to delineate tissue regions in 151 breast cancer slides using the Digital Slide Archive. Inter-participant discordance was systematically evaluated, revealing low discordance for tumor and stroma, and higher discordance for more subjectively defined or rare tissue classes. Feedback provided by senior participants enabled the generation and curation of 20 000+ annotated tissue regions. Fully convolutional networks trained using these annotations were highly accurate (mean AUC=0.945), and the scale of annotation data provided notable improvements in image classification accuracy.

Availability and Implementation

Dataset is freely available at: https://goo.gl/cNM4EL.

Supplementary information

Supplementary data are available at Bioinformatics online.
KOnezumi: a web application for automating gene disruption strategies to generate knockout mice
Authors: Kuno Akihiro , Mizuno Seiya , Takahashi Satoru
Published: February 2019

Although gene editing using the CRISPR/Cas9 system enables the rapid generation of knockout mice, constructing an optimal gene disruption strategy is still labourious. Here, we propose KOnezumi, a simple and user-friendly web application, for use in automating the design of knockout strategies for multiple genes. Users only need to input gene symbols, and then KOnezumi returns target exons, gRNA candidates to delete the target exons, genotyping PCR primers, nucleotide sequences of the target exons and coding sequences of expected deletion products. KOnezumi enables users to easily and rapidly apply a rational strategy to accelerate the generation of KO mice using the CRISPR/Cas9 system.

Availability and implementation

This web application is freely available at http://www.md.tsukuba.ac.jp/LabAnimalResCNT/KOanimals/konezumi.html.

Supplementary information

Supplementary data are available at Bioinformatics online.
‘The Perfect Murder’: An Exploratory Study of Staged Murder Scenes and Concealed Femicide
Authors: Bitton Yifat , Dayan Hava
Published: February 2019

Presenting cases of criminologically unidentifiable circumstances, authors point to concealment susceptibility of some femicide cases, overlooked by both the criminal system and by scholars, rendering them ‘concealed femicides’. The paper presents descriptive and criminological analyses of Israeli cases whereby the woman’s murder was followed by scene staging. It extrapolates the common characteristics of femicide victims and perpetrators, offers a typology of homicide scene staging behaviour that facilitates domesticity-related femicide concealment and, eventually, introduces tools to enhance exposure of femicide.
The Vita Alcuini, Asser and Scholarly Service at the Court of Alfred the Great
Authors: Thomas Rebecca
Published: February 2019

Asser’s Life of King Alfred, a biography of Alfred the Great composed by a Welsh monk from St David’s in 893, is a key source for understanding connections between ninth-century Britain and the Continent. Asser’s biography draws on a variety of continental sources, the most famous and widely discussed being Einhard’s Vita Karoli. This article examines parallels between Asser’s Life of King Alfred and another, more obscure, continental source, the anonymous ninth-century Vita Alcuini, a text which has received little scholarly attention. Unlike many of his Carolingian counterparts, Asser’s biography features himself as a major character, providing an account of his journey to Alfred’s service. It has been noted by various scholars that this autobiographical section of the Life bears great similarity to the Vita Alcuini’s description of Alcuin entering the service of Charlemagne. This article provides a thorough examination of the two texts, assessing the possibility of a connection, and investigating the implications for our understanding of Asser and his agenda. As there is no manuscript evidence that the Vita Alcuini ever made it to Britain, this study has the potential to transform our understanding of its transmission and readership in the early Middle Ages, illuminating a further connection Britain England and the continent in the ninth century.
Minimally invasive aortic valve replacement with sutureless and rapid deployment valves: a report from an international registry (Sutureless and Rapid Deployment International Registry)†
Authors: Berretta Paolo , Andreas Martin , Carrel Thierry P , Solinas Marco , Teoh Kevin , Fischlein Theodor , Santarpino Giuseppe , Folliguet Thierry , Villa Emmanuel , Meuris Bart , Mignosa Carmelo , Martinelli Gianluca , Misfeld Martin , Glauber Mattia , Kappert Utz , Savini Carlo , Shrestha Malak , Phan Kevin , Albertini Alberto , Yan Tristan , Di Eusanio Marco
Published: February 2019

OBJECTIVES:

The impact of sutureless and rapid deployment (SURD) valves on the clinical outcomes of patients undergoing minimally invasive aortic valve replacement (MI-AVR) has still to be defined. The aim of this study was to assess clinical characteristics and in-hospital results of patients receiving SURD-AVR through less invasive approaches in the large population of the Sutureless and Rapid Deployment International Registry (SURD-IR).

METHODS:

Of the 1935 patients who received primary isolated SURD-AVR between 2009 and 2018, a total of 1418 (73.3%) underwent MI interventions and were included in this analysis. SURD-AVR was performed using upper ministernotomy in 56.4% (n = 800) of cases and anterior right thoracotomy in 43.6% (n = 618). Perceval S was implanted in 1011 (71.3%) patients and Edwards Intuity or Intuity Elite in 407 (28.7%) patients.

RESULTS:

Overall in-hospital mortality and stroke rates were 1.7% and 2%, respectively. A definitive pacemaker implantation was reported in 9% of cases and significantly decreased over the observational period, from 20.6% to 5.6% (P = 0.002). The Perceval valve was associated with shorter operative times and was more frequently implanted in patients receiving anterior right thoracotomy incision. The Intuity valve was preferred in younger patients and revealed superior postoperative haemodynamic results.

CONCLUSIONS:

SURD-AVR was largely performed through less invasive approaches and can be considered as a primary indication in MI surgery. In the SURD-IR cohort, MI SURD-AVR using both Perceval and Intuity valves appeared a safe and reproducible procedure associated with promising early results.
Bureaucratic Representation and the Rejection Hypothesis: A Longitudinal Study of the European Commission’s Staff Composition (1980–2013)
Authors: Gravier Magali , Roth Camille
Published: February 2019

This article analyzes the evolution of the staff composition of the European Commission from 1980 to 2013 using the theory of representative bureaucracy. The article first demonstrates how the Commission formulates guidelines which aim at offering fair levels of representation to each member state. However, comparing recruitment targets and actual staffing figures reveals very heterogeneous staff levels. Some member states enjoy unexpectedly high levels of representation whereas others present very low levels. The latter are particularly intriguing and open the door to the formulation of a “rejection hypothesis.” This hypothesis challenges one of the foundations of the theory of representative bureaucracy and leads us to suggest that the theory be enhanced in order to take into account its context of implementation in terms of consolidated or contested statehood, which in turn may explain the phenomena of rejected offers of bureaucratic representation.
Rotavirus Vaccination Coverage During a Rotavirus Outbreak Resulting in a Fatality at a Subacute Care Facility
Authors: Burke Rachel M , Tate Jacqueline E , Han George S , Quenelle Rebecca , Gautam Rashi , Wadford Debra A , Bowen Michael D , Parashar Umesh D
Published: February 2019

Background

The introduction of rotavirus vaccine in the United States has reduced rotavirus disease burden, but outbreaks still occur. Complete-series rotavirus vaccination coverage is <75% in the United States, and it might be lower among vulnerable populations. We describe here the clinical characteristics and vaccination status of children during a rotavirus outbreak in a pediatric subacute care facility in 2017.

Methods

Clinical history, signs and symptoms, and vaccination history were abstracted for the 26 patients residing in the facility during the time of the outbreak. A case-patient was defined as one who experienced 3 or more loose stools in a period of 24 hours with onset between April 17 and May 17, 2017. Stool samples from 14 resident patients were tested for rotavirus with reverse-transcription polymerase chain reaction.

Results

The median patient age at the facility was 2.9 years. Of the 26 resident patients, 22 (85%) met the case definition. One child died. Stool samples from 11 case-patients were positive according to reverse-transcription polymerase chain reaction for rotavirus. Fifteen case-patients were unvaccinated against rotavirus; 3 were partially vaccinated, and 2 were fully vaccinated. Vaccination status could not be completely determined in 2 cases.

Conclusions

An outbreak of rotavirus affected nearly all resident patients of a subacute care facility and caused 1 death. Because of recommendations against giving rotavirus vaccine in an intensive care setting, infants who require a prolonged intensive care stay might age out of rotavirus vaccine eligibility (the first dose must be given before 15 weeks of age according to Advisory Committee on Immunization Practices recommendations). The result is a vulnerable population of unvaccinated infants who might later congregate in another care setting.
Post-Transfusion Purpura Mimicking Idiopathic Thrombocytopenic Purpura: A Case Report
Authors: Milito Chelsea , Masel Debra , Henrichs Kelly , Schmidt Amy E , Kirkley Scott , Aljitawi Omar , Becker Michael , Blumberg Neil , Refaai Majed A
Published: February 2019

The main clinical distinction between post-transfusion purpura (PTP) and idiopathic thrombocytopenic purpura (ITP) is the sudden development of severe thrombocytopenia in the days after transfusion. Herein, we report the case of a 53-year-old Caucasian woman who developed multiple myeloma (MM) after peripheral blood-stem-cell transplant (PBSCT), along with severe thrombocytopenia (with a nadir of 1 × 109/L); she also experienced severe adverse events after each platelet transfusion, including the first one. These reactions were absent with any other transfused blood products. The results of an human leukocyte antigen (HLA) class-1 panel reactive antibody assay were 0%, and the results of a platelet-antibody screening assay were positive for HLA class-1 antibodies and glycoprotein (Gp)IIb/IIIa antibodies. Her platelet count reached 42 × 109 per L on day 50, after rituximab on day 22 and daratumumab on day 29. Her clinical scenario was most consistent with the course of PTP.
Modal operators and toric ideals
Authors: Camerlo Riccardo , Pistone Giovanni , Rapallo Fabio
Published: February 2019

In the present paper, we consider modal propositional logic and look for the constraints that are imposed to the propositions of the special type $\operatorname{\Box } a$ by the structure of the relevant finite Kripke frame. We translate the usual language of modal propositional logic in terms of notions of commutative algebra, namely polynomial rings, ideals and bases of ideals. We use extensively the perspective obtained in previous works in algebraic statistics. We prove that the constraints on $\operatorname{\Box } a$ can be derived through a binomial ideal containing a toric ideal and we give sufficient conditions under which the toric ideal, together with the fact that the truth values are in $\left \{0,1\right \} $, fully describes the constraints.
Digital Medical Humanities and Design Thinking
Authors: Ostherr Kirsten
Published: February 2019

Millennial learners live in a digital, highly connected, always-on world, where short-form, real-time visual communication is the preferred form of social engagement. For these students, the boundary between consuming and producing media is virtually nonexistent, largely enabled by user-friendly digital interfaces on their smartphones. These twenty-first-century approaches to interaction present an opportunity for health humanities educators to collaborate with millennial learners in reimagining health communication for the digital age. By engaging in collaborative, participatory design practices focused on solving real-world health communication problems between patients and health professionals, health humanities students can increase their digital literacy, enhance patient engagement, and develop valuable problem-solving and leadership skills. This chapter describes the “Medical Media Arts Lab,” a case study in using digital humanities and design thinking to cultivate twenty-first-century communication skills for future health professionals. It begins by describing the institutional context for the course, the Medical Futures Lab at Rice University. The essay then describes how to approach designing this kind of course and, finally, provides practical guidance on how to teach the course.
A paradigm for psychiatry
Authors: Glannon Walter
Published: February 2019

This chapter examines the idea that psychiatric disorders are disorders of the brain, mind, and the person’s relation to the world. The etiology, pathophysiology, and symptomatology of these disorders are influenced by interactions between the brain, mind, immune and endocrine systems, and the person’s relation to the environment. A biopsychosocial model provides the best account of the development of these disorders and a guide for research and treatment. The chapter also discusses some of the merits and limitations of the symptom-based DSM-5 and the more recent circuit-based RDoC, and defends the view that they can be complementary models in a paradigm for psychiatry research and clinical practice. The chapter defends nonreductive materialism as the theory best able to account for the different dimensions of the brain–mind relation in psychiatry.
Treating psychiatric disorders: Less invasive and noninvasive interventions
Authors: Glannon Walter
Published: February 2019

This chapter analyzes and discusses different types of psychopharmacology. It examines the view that the monoamine hypothesis to explain and treat psychiatric disorders may be mistaken and considers alternative hypotheses. It also questions the distinction between noninvasive and invasive treatments in psychiatry, pointing out that some presumably noninvasive treatments are invasive because they can cause changes in the brain. The chapter discusses the potential benefits, risks and limitations of electroconvulsive therapy, transcranial magnetic stimulation, and transcranial current stimulation. Placebos and neurofeedback are distinct from these interventions because they do not involve psychotropic drugs or neurostimulation. With a view to potential future therapies, the chapter considers novel neuromodulating techniques such as temporal interference.
Psychiatric neurosurgery
Authors: Glannon Walter
Published: February 2019

This chapter discusses functional neurosurgery designed to modulate dysfunctional neural circuits mediating sensorimotor, cognitive, emotional, and volitional capacities. The chapter assesses the comparative benefits and risks of neural ablation and deep brain stimulation as the two most invasive forms of neuromodulation. It discusses the question of whether individuals with a severe or moderately severe psychiatric disorder have enough cognitive and emotional capacity to weigh reasons for and against ablation or deep brain stimulation and give informed consent to undergo it. The chapter also discusses the obligations of investigators conducting these trials to research subjects. In addition, it examines the medical and ethical justification for a sham control arm in psychiatric neurosurgery clinical trials. It considers the therapeutic potential of optogenetics as a novel form of neuromodulation. The fact that this technique manipulates both genetic material and neural circuits and has been tested only in animal models makes it unclear what its benefit–risk ratio would be. The chapter concludes with a brief discussion of the potential of neuromodulation to stimulate endogenous repair and growth mechanisms in the brain.
Intervening in the psychopath’s brain
Authors: Glannon Walter
Published: February 2019

This chapter discusses whether pharmacological intervention in the brains of criminal psychopaths to modify and enable them to control their behavior could be justified as an alternative to continued incarceration. It also considers the question of whether treatment designed to rehabilitate the offender following release from prison could be forced on him against his wishes and whether it would violate his cognitive liberty. The chapter examines the connection between psychiatric disorders and mental integrity and whether mental impairment can weaken the presumed right to noninterference in the brain. It also considers whether direct brain interventions could be justified in adolescents with risk factors for criminal psychopathy. The key issue is weighing the interests and rights of the offender against the interest of society in preventing recidivism and protecting the public from harm.
Euthanasia and assisted suicide for psychiatric disorders
Authors: Glannon Walter
Published: February 2019

This chapter discusses reasons for and against euthanasia and physician-assisted suicide for patients with treatment-resistant depression or other psychiatric disorders. Although these actions may seem anathema to the goal of treating psychiatric patients in order to prevent suicide, there may be cases in which it would be permissible to bring about or assist in the death of a person with one of these disorders. The permissibility of these actions depends on four conditions. First, the patient must be competent enough to weigh the reasons for and against euthanasia and assisted suicide. Second, the patient must make an informed and persistent request for it. Third, the suffering the patient experiences from the disorder must be unbearable and interminable. Fourth, the disorder must be resistant to all indicated treatments given to the patient over many years. There must be a reasonable limit to the time a patient could be expected to wait for a possible treatment that might relieve symptoms. Any right to euthanasia or assisted suicide entails at most a permission and not an obligation for a physician to perform these actions.
My Small but Significant Body of Work
Authors: Wills Emily
Published: February 2019

This chapter presents a poem entitled ‘My Small but Significant Body of Work’.
Considering the Predictive Value of the Risk Assessment Score
Authors: Wills Emily
Published: February 2019

This chapter presents a poem entitled ‘Considering the Predictive Value of the Risk Assessment Score’.
Lisbeth Hockey and Annie Altschul
Authors: Hyare Nikita
Published: February 2019

This chapter presents a profile of Lisbeth Hockey and Annie Altschul - two very important women in nursing, particularly mental health nursing. Both had profound influences on the roles of nurses. They were particularly interested in improving research opportunities for nurses, developing the teaching nurses received, and encouraging them to improve their practice in imaginative ways such as community care and valuing the therapeutic relationship.
The Other Women in the Wardrobe
Authors: Wills Emily
Published: February 2019

This chapter presents a poem entitled ‘The Other Women in the Wardrobe’.
‘Out of the Air’: Judith Weir’s Emergence in 1970s Britain, or Interpreting Creative Self-Censorship
Authors: Beard David
Published: February 2019

Most accounts of Judith Weir’s music focus on her mature, apparently postmodern approach. By contrast, my analysis of the early withdrawn works highlights a series of creative dialogues with some of Weir’s older British and Continental contemporaries, and more historical models. These interactions reveal that modernism and the avant-garde were essential to the evolution of Weir’s musical language—a formative experience that has been downplayed in attempts by critics to distance Weir from modernism. The gendered reception of Weir’s music is also noted, in which her natural modesty and withdrawal of early works have been portrayed as symptoms of feminine uncertainty, self-criticism, and anxiety. This discourse is recalibrated by relating it first to creativity theories, in which dialogue, uncertainty, and serendipity are valued, and second to the more widespread practice of withdrawing works, which illustrates how self-censorship is a common and vital part of creative practice, irrespective of gender.
Contribution of ‘clinically negligible’ residual kidney function to clearance of uremic solutes
Authors: Toth-Manikowski Stephanie M , Sirich Tammy L , Meyer Timothy W , Hostetter Thomas H , Hwang Seungyoung , Plummer Natalie S , Hai Xin , Coresh Josef , Powe Neil R , Shafi Tariq
Published: February 2019

Background

Residual kidney function (RKF) is thought to exert beneficial effects through clearance of uremic toxins. However, the level of native kidney function where clearance becomes negligible is not known.

Methods

We aimed to assess whether levels of nonurea solutes differed among patients with ‘clinically negligible’ RKF compared with those with no RKF. The hemodialysis study excluded patients with urinary urea clearance >1.5 mL/min, below which RKF was considered to be ‘clinically negligible’. We measured eight nonurea solutes from 1280 patients participating in this study and calculated the relative difference in solute levels among patients with and without RKF based on measured urinary urea clearance.

Results

The mean age of the participants was 57 years and 57% were female. At baseline, 34% of the included participants had clinically negligible RKF (mean 0.7 ± 0.4 mL/min) and 66% had no RKF. Seven of the eight nonurea solute levels measured were significantly lower in patients with RKF than in those without RKF, ranging from −24% [95% confidence interval (CI) −31 to −16] for hippurate, −7% (−14 to −1) for trimethylamine-N-oxide and −4% (−6 to −1) for asymmetric dimethylarginine. The effect of RKF on plasma levels was comparable or more pronounced than that achieved with a 31% higher dialysis dose (spKt/Vurea 1.7 versus 1.3). Preserved RKF at 1-year follow-up was associated with a lower risk of cardiac death and first cardiovascular event.

Conclusions

Even at very low levels, RKF is not ‘negligible’, as it continues to provide nonurea solute clearance. Management of patients with RKF should consider these differences.
The Pipeline Embolization Device: Changes in Practice and Reduction of Complications in the Treatment of Anterior Circulation Aneurysms in a Multicenter Cohort
Authors: Dmytriw Adam A , Phan Kevin , Salem Mohamed M , Adeeb Nimer , Moore Justin M , Griessenauer Christoph J , Foreman Paul M , Shallwani Hussain , Shakir Hakeem , Siddiqui Adnan H , Levy Elad I , Davies Jason M , Harrigan Mark R , Thomas Ajith J , Ogilvy Christopher S
Published: February 2019

BACKGROUND

The Pipeline Embolization Device (PED; Medtronic, Dublin, Ireland) has become an important tool for the treatment of cerebral aneurysms. Since FDA approval, there are ongoing efforts to increase aneurysm occlusion rates and reduce the incidence of complications.

OBJECTIVE

To assess aneurysm occlusion and complication rates over time.

METHODS

Retrospective analysis of consecutive anterior circulation aneurysms treated with a single PED between 2011 and 2016 at 3 academic institutions in the US was performed. Factors contributing to changes in aneurysm occlusion and complication rates over time were identified and evaluated.

RESULTS

A total of 284 procedures were performed on 321 anterior circulation aneurysms in 284 patients. At a median follow-up of 13 mo (mean 18 mo), complete or near complete occlusion (>90%) was achieved in 85.9% of aneurysms. There was no significant change in aneurysm occlusion rate or procedure length over time. Thromboembolic complication occurred in 8.1% of procedures, and there was a trend toward decreased incidence from 16.3% in 2011/2012 to 3.3% in 2016 (P = .14). Hemorrhagic complications significantly decreased from 8.2% in 2011/2012 to 0 to 1.0% in 2014-2016 (P = .1).

CONCLUSION

We report a notable drop in the rate of hemorrhagic and to a lesser extent thromboembolic complications with increased experience with PED in a multicenter cohort. Multiple factors are believed to contribute to this drop, including the evolved interpretation of platelet function testing, the switching of clopidogrel nonresponders to ticagrelor, and the reduced use of adjunctive coiling.
Supramolecular nanoscale drug-delivery system with ordered structure
Authors: Jin Xin , Zhu Lijuan , Xue Bai , Zhu Xinyuan , Yan Deyue
Published: February 2019

Supramolecular chemistry provides a means to integrate multi-type molecules leading to a dynamic organization. The study of functional nanoscale drug-delivery systems based on supramolecular interactions is a recent trend. Much work has focused on the design of supramolecular building blocks and the engineering of supramolecular integration, with the goal of optimized delivery behavior and enhanced therapeutic effect. This review introduces recent advances in supramolecular designs of nanoscale drug delivery. Supramolecular affinity can act as a main driving force either in the self-assembly of carriers or in the loading of drugs. It is also possible to employ strong recognitions to achieve self-delivery of drugs. Due to dynamic controllable drug-release properties, the supramolecular nanoscale drug-delivery system provides a promising platform for precision medicine.
Third-generation cephalosporin-resistant urinary tract infections in children presenting to the paediatric emergency department
Authors: Kang Kristopher T , Ng Karen , Kendrick Jennifer , Tilley Peter , Ting Joseph , Rassekh Shahrad , Murthy Srinivas , Roberts Ashley
Published: February 2019

Background

The incidence of antibiotic-resistant urinary tract infections (UTIs) in children is increasing. The purpose of this study was to describe the incidence, clinical characteristics, and risk factors for third-generation cephalosporin-resistant UTIs presenting to the paediatric emergency department (ED).

Methods

This was a retrospective cohort study conducted at British Columbia Children’s Hospital. Children aged 0 to 18 years old presenting to the ED between July 1, 2013 and June 30, 2014 and were found to have UTI due to Enterobacteriaceae and Pseudomonas species were included. Patient demographics, clinical features, laboratory findings, and outcomes were compared using standard statistical analyses. Risk factors for resistant UTIs were analyzed using multiple logistic regression analysis.

Results

There were 294 eligible patients. The median age was 27.4 months. A third-generation cephalosporin-resistant organism was identified in 36 patients (12%). Patients with resistant UTI had lower rates of appropriate empiric antibiotic therapy (25% versus 95.3%, P<0.05), higher rates of hospitalization (38.9% versus 21.3%, P<0.05), higher rates of undergoing a voiding cystourethrogram (19.4% versus 5.0%, P<0.05), and higher rates of UTI recurrence within 30 days (13.9% versus 4.7%, P<0.05). In multivariate analysis, recent hospitalization (odds ratio [OR] 4.3, confidence interval [CI] 1.2 to 16) and antibiotic therapy (OR 3.5, CI 1.5 to 8.5) within the previous 30 days were risk factors for resistant UTI.

Conclusions

Third-generation cephalosporin-resistant organisms account for a significant proportion of community-acquired paediatric UTIs. Recent hospitalization and antibiotic use are associated with increased risk of resistant UTI.
The earliest well-documented occurrence of sexual dimorphism in extinct sloths: evolutionary and palaeoecological insights
Authors: Boscaini Alberto , Gaudin Timothy J , Toledo Néstor , Quispe Bernardino Mamani , Antoine Pierre-Olivier , Pujos François
Published: February 2019

Sexual dimorphism (SD) is extremely common in species that have reproductive roles segregated into separate sexes, and it has been recognized in several mammalian lineages, both extant and extinct. Sexual dimorphism is low to moderate in living sloths, but it had a more important role for extinct sloth taxa. The presence of SD in extinct sloths was first suggested at the end of the 19th century and it is now commonly advocated as a possible explanation of high intraspecific variation in many extinct sloth species. In this paper, we report the presence of SD in Simomylodon uccasamamensis, a Late Miocene to Late Pliocene sloth from the Bolivian Altiplano. We present evidence of SD in the morphology of cranial and postcranial remains, representing the earliest unequivocal occurrence of size-based SD in an extinct sloth species. Differences between sexes are mainly observed in the morphology of the feeding apparatus and general body size. Comparisons with extant large mammals allow us to hypothesize different food selection between the two sexes, with probable divergent habitat use and concomitant niche separation. This, in turn, could have represented an important selective factor for adaptation to environmental changes experienced by the Bolivian Altiplano in Late Neogene times.
'Candidatus Ornithobacterium hominis': insights gained from draft genomes obtained from nasopharyngeal swabs
Authors: Salter Susannah J. , Scott Paul , Page Andrew J. , Tracey Alan , de Goffau Marcus C. , Cormie Claire , Ochoa-Montaño Bernardo , Ling Clare L. , Tangmanakit Jiraporn , Turner Paul , Parkhill Julian
Published: February 2019

‘Candidatus Ornithobacterium hominis’ represents a new member of the

Flavobacteriaceae

detected in 16S rRNA gene surveys of people from South-East Asia, Africa and Australia. It frequently colonizes the infant nasopharynx at high proportional abundance, and we demonstrate its presence in 42 % of nasopharyngeal swabs from 12-month-old children in the Maela refugee camp in Thailand. The species, a Gram-negative bacillus, has not yet been cultured, but the cells can be identified in mixed samples by fluorescent hybridization. Here, we report seven genomes assembled from metagenomic data, two to improved draft standard. The genomes are approximately 1.9 Mb, sharing 62 % average amino acid identity with the only other member of the genus, the bird pathogen

Ornithobacterium rhinotracheale

. The draft genomes encode multiple antibiotic-resistance genes, competition factors,

Flavobacterium johnsoniae
-like gliding motility genes and a homologue of the

Pasteurella multocida

mitogenic toxin. Intra- and inter-host genome comparison suggests that colonization with this bacterium is both persistent and strain exclusive.
Supervised classification enables rapid annotation of cell atlases
Authors: Pliner Hannah A. , Shendure Jay , Trapnell Cole
Published: February 2019

Single cell technologies for profiling tissues or even entire organisms are rapidly being adopted. However, the manual process by which cell types are typically annotated in the resulting data is labor-intensive and increasingly rate-limiting for the field. Here we describe Garnett, an algorithm and accompanying software for rapidly annotating cell types in scRNA-seq and scATAC-seq datasets, based on an interpretable, hierarchical markup language of cell type-specific genes. Garnett successfully classifies cell types in tissue and whole organism datasets, as well as across species.
SLC19A1 is a cyclic dinucleotide transporter
Authors: Luteijn Rutger D. , Zaver Shivam A. , Gowen Benjamin G. , Wyman Stacia , Garelis Nick , Onia Liberty , McWhirter Sarah M. , Katibah George E. , Corn Jacob E. , Woodward Joshua J. , Raulet David H.
Published: February 2019

The accumulation of DNA in the cytosol serves as a key immunostimulatory signal associated with infections, cancer and genomic damage1,2. Cytosolic DNA triggers immune responses by activating the cGAS/STING pathway3. The binding of DNA to the cytosolic enzyme cGAMP synthase (cGAS), activates its enzymatic activity, leading to the synthesis of a second messenger, cyclic[G(2’,5’)pA(3’,5’)] (2’3’-cGAMP)4–8. 2’3’-cGAMP, a cyclic dinucleotide (CDN), activates the protein ‘stimulator of interferon genes’ (STING)9, which in turn activates the transcription factors IRF3 and NF-κB promoting the transcription of genes encoding type I interferons and other cytokines and mediators that stimulate a broader immune response. Exogenous 2’3’-cGAMP and other CDNs, including CDNs produced by bacteria and synthetic CDNs used in cancer immunotherapy, must traverse the cell membrane to activate STING in target cells. How these charged CDNs pass through the lipid bilayer is unknown. Here we used a genome-wide CRISPR interference screen to identify the reduced folate carrier SLC19A1 as the major CDN transporter for uptake of synthetic and naturally occurring CDNs. CDN uptake and functional responses are inhibited by depleting SLC19A1 from cells and enhanced by overexpressing SLC19A1. In both cell lines and primary cells ex vivo, CDN uptake is inhibited competitively by folate and blocked by the SLC19A1 inhibitor sulfasalazine, a medication approved for the treatment of inflammatory diseases. The identification of SLC19A1 as the major transporter of CDNs into cells has far reaching implications for the immunotherapeutic treatment of cancer10, transport of 2’3’-cGAMP from tumor cells to other immune cells to trigger the anti-tumor immune response11, host responsiveness to CDN-producing pathogenic microorganisms12, and potentially in certain inflammatory diseases.
Deep-learning based three-dimensional label-free tracking and analysis of immunological synapses of chimeric antigen receptor T cells
Authors: Lee Moosung , Lee Young-Ho , Song Jinyeop , Kim Geon , Jo YoungJu , Min HyunSeok , Kim Chan Hyuk , Park YongKeun
Published: February 2019

We propose and experimentally validate a label-free, volumetric, and automated assessment method of immunological synapse dynamics using a combinational approach of optical diffraction tomography and deep learning-based segmentation. The proposed approach enables automatic and quantitative spatiotemporal analyses of immunological synapse kinetics regarding morphological and biochemical parameters related to the total protein densities of immune cells, thus providing a new perspective for studies in immunology.
Revealing neural correlates of behavior without behavioral measurements
Authors: Rubin Alon , Sheintuch Liron , Brande-Eilat Noa , Pinchasof Or , Rechavi Yoav , Geva Nitzan , Ziv Yaniv
Published: February 2019

Measuring neuronal tuning curves has been instrumental for many discoveries in neuroscience but requires a-priori assumptions regarding the identity of the encoded variables. We applied unsupervised learning to large-scale neuronal recordings in behaving mice from circuits involved in spatial cognition, and uncovered a highly-organized internal structure of ensemble activity patterns. This emergent structure allowed defining for each neuron an ‘internal tuning-curve’ that characterizes its activity relative to the network activity, rather than relative to any pre-defined external variable – revealing place-tuning in the hippocampus and head-direction tuning in the thalamus and postsubiculum, without relying on measurements of place or head-direction. Similar investigation in prefrontal cortex revealed schematic representations of distances and actions, and exposed a previously unknown variable, the ‘trajectory-phase’. The structure of ensemble activity patterns was conserved across mice, allowing using one animal’s data to decode another animal’s behavior. Thus, the internal structure of neuronal activity itself enables reconstructing internal representations and discovering new behavioral variables hidden within a neural code.