bluuebunny/crossref_metadata_2025 huggingface dataset:
Triage of astrometric binaries – how to find triple systems and dormant black hole secondaries in the Gaia orbits
Authors: Shahaf S , Mazeh T , Faigler S , Holl B
Published: June 2019

Preparing for the expected wealth of Gaia detections, we consider here a simple algorithm for classifying unresolved astrometric binaries with main-sequence (MS) primary into three classes: binaries with a probable MS secondary, with two possible values for the mass ratio; probable hierarchical triple MS systems with an astrometric secondary as a close binary, with a limited range of mass-ratio values; and binaries with a compact-object secondary, with a minimal value of the mass ratio. This is done by defining a unitless observational parameter ‘Astrometric Mass-Ratio Function’ (AMRF), $\mathcal {A}$, of a binary, based on primary-mass estimation, in addition to the astrometric parameters – the angular semimajor axis, the period, and the parallax. We derive the $\mathcal {A}$ value that differentiates the three classes by forward modelling representative binaries of each class, assuming some mass–luminosity relation. To demonstrate the potential of the algorithm, we consider the orbits of 98 Hipparcos astrometric binaries with MS primaries, using the Hipparcos parallaxes and the primary-mass estimates. For systems with known spectroscopic orbital solution, our results are consistent with the spectroscopic elements, validating the suggested approach. The algorithm will be able to identify hierarchical triple systems and dormant neutron star and black hole companions in the Gaia astrometric binaries.
The formation of bimodal dust species in nova ejecta – I. Chemical conditions
Authors: Zhu Chunhua , Liu Helei , Lü Guoliang , Wang Zhaojun , Li Lin
Published: June 2019

It is still not known whether or not bimodal dust species (namely the silicate and amorphous carbon dust grains that are observed in a nova eruption) are formed in nova ejecta. Using the Modules for Experiments in Stellar Astrophysics code and considering the effects of the white dwarf mass, the mass-accretion rate and the chemical profile, which are described by a new parameter (the mixing depth), on the chemical abundances of nova ejecta, we investigate the possibility that bimodal dust species are produced in a nova eruption. We find that the C/O (the ratio of the carbon number density to the oxygen number density) of nova ejecta is affected by the mixing depth. For a model with a small mixing depth, the C/O of nova ejecta can evolve from greater than 1.0 to less than 1.0 over the course of an eruption, thereby providing the chemical conditions for the formation of bimodal dust species.
Analytic computation of the secular effects of encounters on a binary: features arising from second-order perturbation theory
Authors: Hamers Adrian S , Samsing Johan
Published: June 2019

Binary–single interactions play a crucial role in the evolution of dense stellar systems such as globular clusters. In addition, they are believed to drive black hole (BH) binary mergers in these systems. A subset of binary–single interactions are secular encounters, for which the third body approaches the binary on a relatively wide orbit, and such that it is justified to average the equations of motion over the binary’s orbital phase. Previous works used first-order (FO) perturbation theory to compute the effects of such secular encounters on the binary. However, this approach can break down for highly eccentric binaries, which are important for BH binary mergers and gravitational wave sources. Here, we present an analytic computation using second-order perturbation techniques, valid to the quadrupole-order approximation. In our calculation, we take into account the instantaneous back reaction of the binary to the third body, and compute corrections to previous FO results. Using singly averaged and direct three-body integrations, we demonstrate the validity of our expressions. In particular, we show that the eccentricity change for highly eccentric binaries can reach a plateau, associated with a large inclination change, and can even reverse sign. These effects are not captured by previous FO results. We provide a simple script to conveniently evaluate our analytic expressions, including routines for numerical integration and verification.
Observable scattered light features from inclined and non-inclined planets embedded in protoplanetary discs
Authors: Kloster Dylan L , Flock M
Published: June 2019

Over the last few years instruments such as VLT/SPHERE and Subaru/HiCIAO have been able to take detailed scattered light images of protoplanetary discs. Many of the features observed in these discs are generally suspected to be caused by an embedded planet, and understanding the cause of these features requires detailed theoretical models. In this work we investigate disc–planet interactions using the pluto code to run 2D and 3D hydrodynamic simulations of protoplanetary discs with embedded 30 and 300 M⊕ planets on both an inclined (i = 2.86°) and non-inclined orbit, using an α-viscosity of 4 × 10−3. We produce synthetic scattered light images of these discs at H-band wavelengths using the radiative transfer code radmc3d. We find that while the surface density evolution in 2D and 3D simulations of inclined and non-inclined planets remain fairly similar, their observational appearance is remarkably different. Most of the features seen in the synthetic H-band images are connected to density variations of the disc at around 3.3 scale heights above and below the mid-plane, which emphasizes the need for 3D simulations. Planets on sustained orbital inclinations disrupt the disc’s upper atmosphere and produce radically different observable features and intensity profiles, including shadowing effects and intensity variation of the order of 10–20 times the surrounding background. The vertical optical depth to the disc mid-plane for H-band wavelengths is τ ≈ 20 in the disc gap created by the high-mass planet. We conclude that direct imaging of planets embedded in the disc remains difficult to observe, even for massive planets in the gap.
SIRT6 promotes transcription of a subset of NRF2 targets by mono-ADP-ribosylating BAF170
Authors: Rezazadeh Sarallah , Yang David , Tombline Gregory , Simon Matthew , Regan Sean P , Seluanov Andrei , Gorbunova Vera
Published: June 2019

SIRT6 is critical for activating transcription of Nuclear factor (erythroid-derived 2)-like 2 (NRF2) responsive genes during oxidative stress. However, while the mechanism of SIRT6-mediated silencing is well understood, the mechanism of SIRT6-mediated transcriptional activation is unknown. Here, we employed SIRT6 separation of function mutants to reveal that SIRT6 mono-ADP-ribosylation activity is required for transcriptional activation. We demonstrate that SIRT6 mono-ADP-ribosylation of BAF170, a subunit of BAF chromatin remodeling complex, is critical for activation of a subset of NRF2 responsive genes upon oxidative stress. We show that SIRT6 recruits BAF170 to enhancer region of the Heme oxygenase-1 locus and promotes recruitment of RNA polymerase II. Furthermore, SIRT6 mediates the formation of the active chromatin 10-kb loop at the HO-1 locus, which is absent in SIRT6 deficient tissue. These results provide a novel mechanism for SIRT6-mediated transcriptional activation, where SIRT6 mono-ADP-ribosylates and recruits chromatin remodeling proteins to mediate the formation of active chromatin loop.
Rational design of an XNA ligase through docking of unbound nucleic acids to toroidal proteins
Authors: Vanmeert Michiel , Razzokov Jamoliddin , Mirza Muhammad Usman , Weeks Stephen D , Schepers Guy , Bogaerts Annemie , Rozenski Jef , Froeyen Mathy , Herdewijn Piet , Pinheiro Vitor B , Lescrinier Eveline
Published: June 2019

Xenobiotic nucleic acids (XNA) are nucleic acid analogues not present in nature that can be used for the storage of genetic information. In vivo XNA applications could be developed into novel biocontainment strategies, but are currently limited by the challenge of developing XNA processing enzymes such as polymerases, ligases and nucleases. Here, we present a structure-guided modelling-based strategy for the rational design of those enzymes essential for the development of XNA molecular biology. Docking of protein domains to unbound double-stranded nucleic acids is used to generate a first approximation of the extensive interaction of nucleic acid processing enzymes with their substrate. Molecular dynamics is used to optimise that prediction allowing, for the first time, the accurate prediction of how proteins that form toroidal complexes with nucleic acids interact with their substrate. Using the Chlorella virus DNA ligase as a proof of principle, we recapitulate the ligase's substrate specificity and successfully predict how to convert it into an XNA-templated XNA ligase.
Cost-Effectiveness of Preemptive Switching to Efavirenz-Based Antiretroviral Therapy for Children With Human Immunodeficiency Virus
Authors: Desmonde Sophie , Frank Simone C , Coovadia Ashraf , Dahourou Désiré L , Hou Taige , Abrams Elaine J , Amorissani-Folquet Madeleine , Walensky Rochelle P , Strehlau Renate , Penazzato Martina , Freedberg Kenneth A , Kuhn Louise , Leroy Valeriane , Ciaranello Andrea L
Published: June 2019

Background

The NEVEREST-3 (South Africa) and MONOD-ANRS-12206 (Côte d’Ivoire, Burkina Faso) randomized trials found that switching to efavirenz (EFV) in human immunodeficiency virus–infected children >3 years old who were virologically suppressed by ritonavir-boosted lopinavir (LPV/r) was noninferior to continuing o LPV/r. We evaluated the cost-effectiveness of this strategy using the Cost-Effectiveness of Preventing AIDS Complications–Pediatric model.

Methods

We examined 3 strategies in South African children aged ≥3 years who were virologically suppressed by LPV/r: (1) continued LPV/r, even in case of virologic failure, without second-line regimens; continued on LPV/r with second-line option after observed virologic failure; and preemptive switch to EFV-based antiretroviral therapy (ART), with return to LPV/r after observed virologic failure. We derived data on 24-week suppression (<1000 copies/mL) after a switch to EFV (98.4%) and the subsequent risk of virologic failure (LPV/r, 0.23%/mo; EFV, 0.15%/mo) from NEVEREST-3 data; we obtained ART costs (LPV/r, $6–$20/mo; EFV, $3–$6/mo) from published sources. We projected discounted life expectancy (LE) and lifetime costs per person. A secondary analysis used data from MONOD-ANRS-12206 in Côte d’Ivoire.

Results

Continued LPV/r led to the shortest LE (18.2 years) and the highest per-person lifetime cost ($19 470). LPV/r with second-line option increased LE (19.9 years) and decreased per-person lifetime costs($16 070). Switching led to the longest LE (20.4 years) and the lowest per-person lifetime cost ($15 240); this strategy was cost saving under plausible variations in key parameters. Using MONOD-ANRS-12206 data in Côte d’Ivoire, the Switch strategy remained cost saving only compared with continued LPV/r, but the LPV/r with second-line option strategy was cost-effective compared with switching.

Conclusion

For children ≥3 years old and virologically suppressed by LPV/r-based ART, preemptive switching to EFV can improve long-term clinical outcomes and be cost saving.

Clinical Trials Registration

NCT01127204
Dose-Response Relationship Between Neuromuscular Electrical Stimulation and Muscle Function in People With Rheumatoid Arthritis
Authors: Almeida Gustavo J , Khoja Samannaaz S , Piva Sara R
Published: June 2019

Background

Neuromuscular electrical stimulation (NMES) is a viable intervention for improving impaired muscle function in individuals with rheumatoid arthritis (RA). However, there is limited evidence about the dose-response relationship between NMES and muscle function in these individuals.

Objective

The objectives of this study were to investigate the dose-response relationship between NMES and muscle function in individuals with RA and to establish the minimal NMES training intensity for promoting improvements.

Design

This study was a secondary analysis of data obtained before and after an NMES intervention in a randomized study.

Methods

The study took place at a research clinic. Only adults diagnosed with RA were included. The intervention consisted of 36 NMES treatment sessions for the quadriceps muscles over 16 weeks. Muscle function was measured before and after the intervention; quadriceps cross-sectional area and muscle quality were assessed using computed tomography, and strength was measured with an isokinetic dynamometer. NMES training intensity was calculated as a percentage by dividing NMES-elicited quadriceps muscle torque by the maximum voluntary isometric contraction. Improvements in muscle function were calculated using paired-sample t tests. The dose-response relationship was determined using curve estimation regression statistics. The minimum NMES training intensity was defined as that sufficient to significantly improve all muscle function measures.

Results

Twenty-four people (48 legs) participated (75% women; mean [SD] age = 58 [8] years; mean body mass index = 32 [7] kg/m2). Quadriceps cross-sectional area, muscle quality, and strength improved after the intervention. Associations between NMES training intensity and muscle quality (r2 = 0.20) and strength (r2 = 0.23) were statistically significant, but that between NMES training intensity and muscle cross-sectional area was not (r2 = 0.02). The minimum NMES training intensity necessary to improve all measures of muscle function ranged from 11% to 20% of the maximum voluntary isometric contraction.

Limitations

The relatively small sample size was a limitation.

Conclusions

The minimum NMES training intensity for significant gains in muscle function was ∼15%. Higher NMES intensities may promote better muscle quality and strength in individuals with RA.
Effects of Temperature and pH onFusarium oxysporumand Soybean Seedling Disease
Authors: Cruz David R. , Leandro Leonor F. S. , Munkvold Gary P.
Published: June 2019

Fusarium oxysporum (Fo) is an important pathogen that reduces soybean yield by causing seedling disease and root rot. This study assessed the effects of pH and temperature on Fo fungal growth and seedling disease. In an in vitro assay, 14 Fo isolates collected from symptomatic soybean roots across Iowa in 2007 were grown on artificial culture media at five pH levels (4, 5, 6, 7, and 8) and incubated at four temperatures (15, 20, 25, or 30°C). In a rolled-towel assay, soybean seeds from Fo-susceptible cultivar Jack were inoculated with a suspension of a pathogenic or a nonpathogenic Fo isolate; both isolates were previously designated for their relative aggressiveness in causing root rot at 25°C. The seeds were placed in rolled germination paper, and the rolls were incubated in all combinations of buffer solutions at four pH levels (4, 5, 6, and 7), and four temperatures (15, 20, 25, or 30°C). There was a significant interaction between temperature and pH (P < 0.05) for in vitro radial growth and root rot severity. Isolates showed the most in vitro radial growth after incubation at pH 6 and 25°C. For the rolled-towel assay, the pathogenic isolate caused the most severe root rot at pH 6 and 30°C. Gaussian regression analysis estimates for optimal conditions were pH 6.3 at 27.1°C for maximal fungal growth and pH 5.9 at 30°C for maximal root rot severity. These results indicate that optimal pH and temperature conditions are similar for Fo growth and disease in soybean seedlings and suggest that Fo may be a more important seedling pathogen when soybeans are planted under warm conditions in moderately acidic soils.
Genome-Wide Linkage Mapping Reveals Stripe Rust Resistance in Common Wheat (Triticum aestivum) Xinong1376
Authors: Mu Jingmei , Wu Jianhui , Liu Shengjie , Dai Miaofei , Sun Daojie , Huang Shuo , Wang Qilin , Zeng Qingdong , Yu Shizhou , Chen Li , Kang Zhensheng , Han Dejun
Published: June 2019

Stripe rust, also known as yellow rust, is a significant threat to wheat yield worldwide. Adult plant resistance (APR) is the preferred way to obtain durable protection. Chinese winter wheat cultivar Xinong1376 has maintained acceptable APR to stripe rust in field environments. To characterize APR in this cultivar, 190 F10 recombinant inbred lines (RILs) developed from Xiaoyan81 × Xinong1376 were evaluated for infection type and disease severity in fields either artificially or naturally inoculated. The population along with parents were genotyped using the Illumina 90K single-nucleotide polymorphism arrays. Six quantitative trait loci (QTL) were detected using the inclusive composite interval mapping method. QYr.nwafu-4AL and QYr.nwafu-6BL.3 conferred stable resistance in all environments, and likely corresponded to a gene-rich region on the long arm of chromosomes 4A and 6B. QYr.nwafu-5AL, QYr.nwafu-5BL, QYr.nwafu-3BL.1, and QYr.nwafu-3BL.2 were detected only in some environments but enhanced the level of resistance conferred by QYr.nwafu-4AL and QYr.nwafu-6BL.3. Kompetitive allele-specific PCR (KASP) markers developed for QYr.nwafu-4AL and QYr.nwafu-6BL.3 were confirmed in a subset of RILs and 133 wheat genotypes. The QTL on 4AL and 6BL with their linked KASP markers would be useful for marker-assisted selection to improve stripe rust resistance in breeding programs.
Recommendations For Core Outcome Domain Set For Whiplash-Associated Disorders (CATWAD)
Authors: Chen Kenneth , Andersen Tonny , Carroll Linda , Connelly Luke , Côté Pierre , Curatolo Michele , Elliott James , Grant Genevieve , Jull Gwendolen , Kasch Helge , MacDermid Joy , Malmström Eva-Maj , Maujean Annick , McLean Samuel A. , Nielsen Mandy , Rebbeck Trudy , Söderlund Anne , Sterling Joanna , Treleaven Julia , Walton David M. , Westergren Hans , Sterling Michele
Published: June 2019

Objective:

Inconsistent reporting of outcomes in clinical trials of treatments for Whiplash-associated Disorders (WAD) hinders effective data pooling and conclusions that can be drawn about the effectiveness of tested treatments. The aim of this study was to provide recommendations for core outcome domains that should be included in clinical trials of WAD.

Materials and Methods:

A 3-step process was used: (1) A list of potential core outcome domains were identified from the published literature. (2) Researchers, health care providers, patients, and insurance personnel participated and rated the importance of each domain via a 3-round Delphi survey. A priori criteria for consensus were established. (3) Experts comprising researchers, health care providers, and a consumer representative participated in a multidisciplinary consensus meeting that made final decisions on the recommended core outcome domains.

Results:

The literature search identified 63 potential core domains. A total of 223 participants were invited to partake in the Delphi surveys, with 41.7% completing round 1, 45.3% round 2, and 51.4% round 3. Eleven core domains met the criteria for inclusion across the entire sample. After the expert consensus meeting, 6 core domains were recommended: Physical Functioning, Perceived Recovery, Work and Social Functioning, Psychological Functioning, Quality of Life, and Pain.

Discussion:

A 3-step process was used to recommend core outcome domains for clinical trials in WAD. Six core domains were recommended: Physical Functioning, Perceived Recovery, Work and Social Functioning, Psychological Functioning, Quality of Life, and Pain. The next step is to determine the outcome measurement instruments for each of these domains.
Prognostic Performance of the 2018 International Federation of Gynecology and Obstetrics Cervical Cancer Staging Guidelines
Authors: Wright Jason D. , Matsuo Koji , Huang Yongmei , Tergas Ana I. , Hou June Y. , Khoury-Collado Fady , St. Clair Caryn M. , Ananth Cande V. , Neugut Alfred I. , Hershman Dawn L.
Published: June 2019

OBJECTIVE:

To examine the prognostic performance of the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) cervical cancer staging schema.

METHODS:

We used the National Cancer Database to identify women with cervical cancer diagnosed from 2004 to 2015. Using clinical and pathologic data, each patient's stage was classified using three staging schemas: American Joint Committee on Cancer 7th edition, FIGO 2009 and FIGO 2018. The FIGO 2018 revised staging classifies stage IB tumors into three substages based on tumor size (IB1–IB3) and classifies patients with positive lymph nodes (pathologically or clinically detected) as stage IIIC1 (positive pelvic nodes) or IIIC2 (positive para-aortic nodes). Five-year survival rates were estimated for each stage grouping. We sought to determine whether the 2018 FIGO staging system was able to offer improved 5-year survival rate differentiation compared with older staging schemas.

RESULTS:

A total of 62,212 women were identified. The classification of stage IB tumors into three substages improved discriminatory ability. Five-year survival in the FIGO 2018 schema was 91.6% (95% CI 90.4–92.6%) for stage IB1 tumors, 83.3% (95% CI 81.8–84.8%) for stage IB2 neoplasms, and 76.1% (95% CI 74.3–77.8%) for IB3 lesions. In contrast, for women with stage III tumors, higher FIGO staging was not consistently associated with worse 5-year survival rates: stage IIIA (40.7%, 95 CI 37.1–44.3%), stage IIIB (41.4%; 95% CI 39.9–42.9%), stage IIIC1 (positive pelvic nodes) was 60.8% (95% CI 58.7–62.8%) and stage IIIC2 37.5% (95% CI 33.3–41.7%).

CONCLUSION:

The FIGO 2018 staging schema provides improved discriminatory ability for women with stage IB tumors; however, classification of all women with positive lymph nodes into a single stage results in a very heterogeneous group of patients with highly variable survival rates.
Ankle Fracture Stability–Based Classification: A Study of Reproducibility and Clinical Prognostic Ability
Authors: Delaney John P. , Charlson Mark D. , Michelson James D.
Published: June 2019

Objective:

To compare the reproducibility and prognostic capacity of 2 commonly used ankle fracture classifications to the stability-based classification.

Methods:

One hundred ninety-three consecutive rotational-type ankle fractures treated during a year at our institution in patients older than 18 years were retrospectively analyzed. Pilon and pathologic fractures were excluded. The fractures were treated by attending physicians who were unaware of the stability-based classification system. Three observers classified injury radiographs using the Lauge-Hansen, Weber/AO, and stability-based classifications systems. Reproducibility (interobserver variation) of each classification system was calculated using kappa statistics. Prognostic values were evaluated by calculating the area under the curve for the receiver-operating characteristic curves (using surgery as the positive outcome).

Results:

The stability-based and Weber/AO classifications showed better reproducibility [kappa 0.938 (95% confidence interval 0.921–0.952), kappa 0.97 (0.961–0.976)], respectively, than the Lauge-Hansen [kappa 0.74 (0.664–0.795); P < 0.05]. The stability-based classification was more accurate (P < 0.001) in predicting surgical treatment [area under the curve 0.883 (95% confidence interval 0.852–0.914)] compared with the other 2 classifications [0.626 (0.576–0.675) and 0.698 (0.641–0.755)], respectively.

Conclusions:

The stability-based classification was both highly reproducible (kappa 0.938) and had superior prognostic capacity to identify patients who needed surgical intervention compared with both the Lauge-Hansen and AO/Weber classification systems. Importantly, there were no patients who were classified as stable who failed nonoperative treatment. This extends earlier studies by directly demonstrating its prognostic advantage to other classification systems.
The Predictive Value of the Clinical Frailty Scale on Discharge Destination and Complications in Older Hip Fracture Patients
Authors: Chan Sarah , Wong Eric K. C. , Ward Sarah E. , Kuan David , Wong Camilla L.
Published: June 2019

Objectives:

To determine whether the Clinical Frailty Scale (CFS), a validated frailty tool, was associated with discharge destination. Secondary objectives were to determine whether the CFS was associated with in-hospital complications and length of stay.

Design:

This is a 5-year retrospective cohort study.

Setting:

The study took place at an academic Level 1 trauma center.

Patients/Participants:

All patients 65 years of age and older admitted with an isolated hip fracture were included (N = 423).

Intervention:

Preadmission CFS was determined as part of routine clinical care prospectively and abstracted from the chart.

Main Outcome Measurements:

We collected demographic and process data associated with adverse outcomes (age, sex, time to surgery, and mode of anesthesia) and used multivariable logistic regression to determine the association between CFS with discharge destination, in-hospital complications, and length of stay.

Results:

Preadmission frailty was independently associated with adverse discharge destination (adjusted odds ratio 23.0; 95% confidence interval, 3.0–173.5) and in-hospital complications (adjusted odds ratio 4.8; 95% confidence interval, 2.1–10.8) in greater magnitude than traditional risk factors such as age, male sex, time to surgery, and mode of anesthesia. There was a dose–response relationship between increasing frailty and length of stay (P < 0.001).

Conclusions:

Preadmission frailty as quantified by the CFS is associated with discharge destination, in-hospital complications, and length of stay.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
The Impact of Hemodialysis on Mortality and Personal Independence After Hip Fracture. A Prospective Matched Cohort Study
Authors: Orabona Nicola , Bove Antonio , Smeraglia Francesco , Rizzo Maria , Russo Bruno , Traficante Francesco , Mariconda Massimo
Published: June 2019

Objective:

To determine the cumulative 30-day and 1-year mortality as well as personal independence after hip fracture in patients on hemodialysis.

Design:

Prospective, observational cohort study with matched controls.

Setting:

One teaching hospital, one metropolitan trauma center, one peripheral hospital.

Patients and Intervention:

Study group: a consecutive cohort of 64 patients with end-stage renal disease receiving chronic hemodialysis who had undergone surgery for a trochanteric or femoral neck fracture from June 2008 to November 2016. Control group: subjects without end-stage renal disease who underwent surgery for similar hip fractures.

Main Outcome Measure:

One-year mortality, activities of daily living, and ambulatory activity.

Results:

The 30-day and 1-year mortality rate in patients with a hip fracture undergoing hemodialysis was 25.0% and 57.8%, respectively. Hemodialysis was independently associated with increased 30-day (Hazard ratio 2.933; 95% confidence interval 1.270–6.770;P= 0.018) and 1-year (hazard ratio 2.535; 95% confidence interval, 1.494–4.299;P< 0.001) mortality compared with the matched controls. At the 1-year follow-up, loss of personal independence in comparison with the prefracture status was detected.

Conclusions:

Hemodialysis was associated with increased mortality after hip fracture. A worse prefracture functional status predicted the loss of functional independence at follow-up.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Clozapine Rechallenge Following Neuroleptic Malignant Syndrome
Authors: Lally John , McCaffrey Cathal , O'Murchu Conall , Krivoy Amir , Guerandel Allys , MacCabe James H. , Gaughran Fiona
Published: June 2019

Purpose/Background

Neuroleptic malignant syndrome (NMS) has been described with most antipsychotics, most commonly first generation. Clozapine has also been associated with NMS.

Methods/Procedures

We conducted a systematic review to identify all studies investigating or describing (a) clozapine rechallenge following suspected NMS associated with clozapine, (b) clozapine use after suspected NMS associated with another antipsychotic, and (c) rechallenge with nonclozapine antipsychotics after suspected clozapine-associated NMS.

Findings/Results

We identified 51 reports detailing 67 cases. Thirty-eight described clozapine administration after NMS on a nonclozapine antipsychotic; 12 described a clozapine rechallenge after an NMS on clozapine monotherapy; and 17 described the use of nonclozapine antipsychotics after an NMS on clozapine. The outcome of clozapine rechallenge was favorable (no recurrence of NMS) in 92% (n = 11) of cases after an NMS on clozapine and in 79% (n = 30) of those prescribed clozapine following NMS on a nonclozapine antipsychotic. Most (82%; n = 14) cases after NMS on clozapine had no recurrence of NMS on receiving a nonclozapine antipsychotic.

No mortality was reported with any of these interventions.

Implications/Conclusions

Our findings suggest that rechallenge following clozapine NMS is possible, and with careful risk-benefit analysis consideration, a clozapine rechallenge can be made. A publication bias in favor of cases in which rechallenge was successful is probable and is an important limitation.
Clozapine-Related Myocarditis and Rechallenge
Authors: Noël Marie-Christine , Powell Valerie , Burton Leah , Panda Roshni , Remington Gary
Published: June 2019

Purpose/Background

That clozapine is the only agent with an indication for treatment-resistant schizophrenia presents real challenges if clozapine-related myocarditis (CIM) occurs. Clinicians have chosen to rechallenge with a second trial of clozapine in the face of CIM. However, there is very limited literature of this topic.

Methods/Procedures

Three cases who underwent clozapine rechallenge after CIM are reviewed and discussed in the context of existing literature and current recommendations.

Findings/Results

We present 3 young male patients with schizophrenia and schizoaffective disorder who developed CIM during a first clozapine trial, stopped treatment, and subsequently underwent a second clozapine trial. In all cases, the rechallenge was discontinued owing to suspected CIM. A review of the literature includes reports of both successful and unsuccessful clozapine rechallenges after CIM and suggests certain risk factors. Clozapine rechallenge after CIM may be undertaken, as now occurs on occasion with agranulocytosis, although rates of success may be lower. Any such undertaking calls for education, careful monitoring, cautious titration, and a multidisciplinary approach. The balance of risk versus benefits must be considered, and strategies may include a drug holiday, more frequent monitoring upon reinitiation, and slower titration.

Implications/Conclusions

Pressure to undertake a rechallenge reflects clozapine's unique role in treatment-resistant schizophrenia and absence of other comparable options. However, it is not without risk, and more research is needed to understand those at increased risk, as well as established strategies that diminish this.
Comparison of Patient Satisfaction Between Composite and Dorsum Augmentation-Only Nasal Reconstructions With Diced Cartilage Graft Wrapped in Fascia
Authors: Çerçi Özkan Aret , Kozanoğlu Erol
Published: June 2019

The comparison of patient satisfaction with the use of diced cartilage graft wrapped in fascia (DCF) graft in composite versus dorsum augmentation-only reconstructions (DAOR), technical hints and complications in our series, affecting the end-result and the patient satisfaction (PS) has been presented.

Between 2013 and 2018 the DC-F graft is used in 32 rhinoplasty cases. Nine of patients have had composite reconstruction (CR). The DAOR has been needed for 23 of patients.

The follow-up period has been 2 months to 3 years. The authors have obtained satisfactory results in 24 cases but some untoward progress in 8 cases. A questionnaire was prepared and asked all patients for the assessment of the satisfaction from appearance, breathing, self-esteem, and positive psychological effect.

The learning curve for rhinoplasty should be calculated for, hump reduction, crooked nose, augmentation rhinoplasty, and so on. separately which is also relevant for the use of a DC-F graft. Placing the DC-F over a straight platform, choosing the accurate graft and fascia material wisely, proper tailoring of DC-F, sliding it under the skin-superficial musculoaponeurotic system properly etc. determine the quality of the end result and the degree of PS. Operating on the DAOR are relatively more comfortable compared to CRs but responses to our questionnaire denote higher degrees of satisfaction in CR cases.

Utilization of the DC-F graft in secondary rhinoplasties for dorsum augmentation provides satisfactory results. The degree of PS with the DC-F reconstruction seems to have an adverse correlation with the extent of deformities that you start with.
Anchoring to Zero Exposure
Authors: Davies Benjamin , Brummett Chad M.
Published: June 2019

Surgeons universally overprescribe opioids even in surgeries that are minimally invasive. Despite some drops in opioid prescribing nationally, surgeons and dentists have not changed their prescribing habits. Opioid guidelines are inherently flawed by the anchoring heuristic and efforts should center on decreasing exposures to opioids through a physician-lead response. No-opioid minimally invasive surgery should be the goal rather than the exception.
Evaluating the Effect of Surgical Skill on Outcomes for Laparoscopic Sleeve Gastrectomy
Authors: Varban Oliver A. , Thumma Jyothi R. , Finks Jonathan F. , Carlin Arthur M. , Ghaferi Amir A. , Dimick Justin B.
Published: June 2019

Background:

Prior studies have demonstrated a correlation between surgical skill and complication rates after laparoscopic Roux-en-Y gastric bypass. However, the impact of surgical skill on a similar but less technically challenging procedure such as sleeve gastrectomy (SG) is unknown.

Methods:

Practicing bariatric surgeons (n = 25) participating in a statewide quality improvement collaborative submitted an unedited deidentified video of a representative laparoscopic SG. Videos were obtained between 2015 and 2016 and were rated by bariatric surgeons in a blinded fashion using a validated instrument that assesses surgical skill. Overall scores were based on a 5-point Likert scale with 5 representing a “master surgeon” and 1 representing a “surgeon-in-training.” Risk-adjusted 30-day complication rates, 1-year weight loss among cases performed during the study period, and operative technique were compared between surgeons rated in the top and bottom quartiles according to skill.

Results:

Surgeon ratings for skill varied between 2.73 and 4.60. Ratings for skill did not correlate with overall 30-day risk-adjusted complication rates (Pearson correlation coefficient, 0.213, P = 0.303). However, surgeons with higher skill ratings had lower rates of specific surgical complications, including postoperative obstruction (0.13% vs 0.3%, P = 0.017), hemorrhage (0.85% vs 1.27%, P = 0.005), and reoperation (0.24% vs 0.92%, P < 0.0001). Surgeons ranked in the top quartile for skill had faster operating times for SG (59.0 vs 82.1 min, P < 0.0001) and higher annual case volumes for both SG and any bariatric procedure (224.3 cases/yr vs 73.4 cases/yr, P = 0.009 and 244.9 cases/yr and 93.9 cases/yr, P = 0.009) when compared with surgeons in the bottom quartile. When comparing operative technique, top rated surgeons were noted to have a higher likelihood of using buttressing (83.3% vs 0%, P = 0.0041) and intraoperative endoscopy (83.3% vs 0%, P = 0.0041).

Conclusions:

Peer ratings for surgical skill varied for laparoscopic sleeve gastrectomy but did not have a significant impact on overall complication rates. Top rated surgeons had lower rates of obstruction, hemorrhage, and reoperation; however, severe morbidity remained extremely low among all surgeons.
Local habitat, not phylogenetic relatedness, predicts gut microbiota better within folivorous than frugivorous lemur lineages
Authors: Greene Lydia K. , Clayton Jonathan B. , Rothman Ryan S. , Semel Brandon P. , Semel Meredith A. , Gillespie Thomas R. , Wright Patricia C. , Drea Christine M.
Published: June 2019

Both host phylogenetic placement and feeding strategy influence the structure of the gut microbiome (GMB); however, parsing their relative contributions presents a challenge. To meet this challenge, we compared GMB structure in two genera of lemurs characterized by different dietary specializations, the frugivorous brown lemurs (
Eulemur
spp.) and the folivorous sifakas (
Propithecus
spp.). These genera sympatrically occupy similar habitats (dry forests and rainforests) and diverged over similar evolutionary timescales. We collected fresh faeces from 12 species (six per host genus), at seven sites across Madagascar, and sequenced the 16S rRNA gene to determine GMB membership, diversity and variability. The lemurs' GMBs clustered predominantly by host genus; nevertheless, within genera, host relatedness did not predict GMB distance between species. The GMBs of brown lemurs had greater evenness and diversity, but were more homogeneous across species, whereas the GMBs of sifakas were differentiated between habitats. Thus, over relatively shallow timescales, environmental factors can override the influence of host phylogenetic placement on GMB phylogenetic composition. Moreover, feeding strategy can underlie the relative strength of host–microbiome coadaptation, with Madagascar's folivores perhaps requiring locally adapted GMBs to facilitate their highly specialized diets.
Challenges of biofilm control and utilization: lessons from mathematical modelling
Authors: Dzianach Paulina A. , Dykes Gary A. , Strachan Norval J. C. , Forbes Ken J. , Pérez-Reche Francisco J.
Published: June 2019

This article reviews modern applications of mathematical descriptions of biofilm formation. The focus is on theoretically obtained results which have implications for areas including the medical sector, food industry and wastewater treatment. Examples are given as to how models have contributed to the overall knowledge on biofilms and how they are used to predict biofilm behaviour. We conclude that the use of mathematical models of biofilms has demonstrated over the years the ability to significantly contribute to the vast field of biofilm research. Among other things, they have been used to test various hypotheses on the nature of interspecies interactions, viability of biofilm treatment methods or forces behind observed biofilm pattern formations. Mathematical models can also play a key role in future biofilm research. Many models nowadays are analysed through computer simulations and continue to improve along with computational capabilities. We predict that models will keep on providing answers to important challenges involving biofilm formation. However, further strengthening of the ties between various disciplines is necessary to fully use the tools of collective knowledge in tackling the biofilm phenomenon.
Introduction: Rethinking Joseph Banks
Authors: Werrett Simon
Published: June 2019

Following a series of workshops funded by AHRC (Arts and Humanities Research Council), the papers in this special issue provide new perspectives on the naturalist Sir Joseph Banks (1743–1820). Moving beyond a focus on Banks's work with Captain Cook's first voyage of exploration to the Pacific, the papers expand on, while challenging, views of Banks as a ‘centre of calculation’ and all-powerful agent of science and imperialism in Georgian Britain. Banks is shown to have relied on a variety of expert men and women as actors and audiences for botany, operating with more diversified agendas and practices than previous pictures of him have suggested.
Unravelling the gender productivity gap in science: a meta-analytical review
Authors: Astegiano Julia , Sebastián-González Esther , Castanho Camila de Toledo
Published: June 2019

Women underrepresentation in science has frequently been associated with women being less productive than men (i.e. the gender productivity gap), which may be explained by women having lower success rates, producing science of lower impact and/or suffering gender bias. By performing global meta-analyses, we show that there is a gender productivity gap mostly supported by a larger scientific production ascribed to men. However, women and men show similar success rates when the researchers' work is directly evaluated (i.e. publishing articles). Men's success rate is higher only in productivity proxies involving peer recognition (e.g. evaluation committees, academic positions). Men's articles showed a tendency to have higher global impact but only if studies include self-citations. We detected gender bias against women in research fields where women are underrepresented (i.e. those different from Psychology). Historical numerical unbalance, socio-psychological aspects and cultural factors may influence differences in success rate, science impact and gender bias. Thus, the maintenance of a women-unfriendly academic and non-academic environment may perpetuate the gender productivity gap. New policies to build a more egalitarian and heterogeneous scientific community and society are needed to close the gender gap in science.
Neuroimaging ‘will to fight’ for sacred values: an empirical case study with supporters of an Al Qaeda associate
Authors: Hamid Nafees , Pretus Clara , Atran Scott , Crockett Molly J. , Ginges Jeremy , Sheikh Hammad , Tobeña Adolf , Carmona Susanna , Gómez Angel , Davis Richard , Vilarroya Oscar
Published: June 2019

Violent intergroup conflicts are often motivated by commitments to abstract ideals such as god or nation, so-called ‘sacred’ values that are insensitive to material trade-offs. There is scant knowledge of how the brain processes costly sacrifices for such cherished causes. We studied willingness to fight and die for sacred values using fMRI in Barcelona, Spain, among supporters of a radical Islamist group. We measured brain activity in radicalized individuals as they indicated their willingness to fight and die for sacred and non-sacred values, and as they reacted to peers' ratings for the same values. We observed diminished activity in dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus, and parietal cortex while conveying willingness to fight and die for sacred relative to non-sacred values—regions that have previously been implicated in calculating costs and consequences. An overlapping region of the dlPFC was active when viewing conflicting ratings of sacred values from peers, to the extent participants were sensitive to peer influence, suggesting that it is possible to induce flexibility in the way people defend sacred values. Our results cohere with a view that ‘devoted actors’ motivated by an extreme commitment towards sacred values rely on distinctive neurocognitve processes that can be identified.
Biomimetic synthesis of nanostructured WO
3
· H
2
O particles and subsequent thermal conversion to WO
3
Authors: Uchiyama Hiroaki , Mizuguchi Shouta , Hirano Shiho
Published: June 2019

Nanostructured tungsten oxide (WO
3
) particles were prepared in aqueous solution by mimicking biomineralization. Precursor WO
3
· H
2
O particles were generated by ageing a 60°C (NH
4
)
10
W
12
O
41
· 5H
2
O solution containing gelatin. This was followed by heating to 600°C in air for thermal conversion to WO
3
. The addition of gelatin led to the formation of layered structures consisting of WO
3
· H
2
O platy particles, which contained segmented, block-like nanoscale units. The macroscopic layered structure was preserved after thermal conversion to WO
3
, while the morphology of the block-like units changed to orthogonally crossed nanorods.
Unexpected spatial population ecology of a widespread terrestrial salamander near its southern range edge
Authors: Hernández-Pacheco Raisa , Sutherland Chris , Thompson Lily M. , Grayson Kristine L.
Published: June 2019

Under the current amphibian biodiversity crisis, common species provide an opportunity to measure population dynamics across a wide range of environmental conditions while examining the processes that determine abundance and structure geographical ranges. Studying species at their range limits also provides a window for understanding the dynamics expected in future environments under increasing climate change and human modification. We quantified patterns of seasonal activity, density and space use in the eastern red-backed salamander (Plethodon cinereus) near its southern range edge and compare the spatial ecology of this population to previous findings from the core of their range. This southern population shows the expected phenology of surface activity based on temperature limitations in warmer climates, yet maintains unexpectedly high densities and large home ranges during the active season. Our study suggests that ecological factors known to strongly affect amphibian populations (e.g. warm temperature and forest fragmentation) do not necessarily constrain this southern population. Our study highlights the utility of studying a common amphibian as a model system for investigating population processes in environments under strong selective pressure.
Mechanotransmission of haemodynamic forces by the endothelial glycocalyx in a full-scale arterial model
Authors: Sáez P. , Gallo D. , Morbiducci U.
Published: June 2019

The glycocalyx has been identified as a key mechano-sensor of the shear forces exerted by streaming blood onto the vascular endothelial lining. Although the biochemical reaction to the blood flow has been extensively studied, the mechanism of transmission of the haemodynamic shear forces to the endothelial transmembrane anchoring structures and, consequently, to the subcellular elements in the cytoskeleton, is still not fully understood. Here we apply a multiscale approach to elucidate how haemodynamic shear forces are transmitted to the transmembrane anchors of endothelial cells. Wall shear stress time histories, as obtained from image-based computational haemodynamics models of a carotid bifurcation, are used as a load and a continuum model is applied to obtain the mechanical response of the glycocalyx all along the cardiac cycle. The main findings of this
in silico
study are that: (1) the forces transmitted to the transmembrane anchors are in the range of 1–10 pN, which is in the order of magnitude reported for the different conformational states of transmembrane mechanotranductors; (2) locally, the forces transmitted to the anchors of the glycocalyx structure can be markedly different from the near-wall haemodynamic shear forces both in amplitude and frequency content. The findings of this
in silico
approach warrant future studies focusing on the actual forces transmitted to the transmembrane mechanotransductors, which might outperform haemodynamic descriptors of disturbed shear as localizing factors of vascular disease.