bluuebunny/crossref_metadata_2025 huggingface dataset:
Megakaryocyte emperipolesis mediates membrane transfer from intracytoplasmic neutrophils to platelets
Authors: Cunin Pierre , Bouslama Rim , Machlus Kellie R. , Martínez-Bonet Marta , Lee Pui Y. , Nelson-Maney Nathan , Morris Allyn , Guo Li , Weyrich Andrew S. , Sola-Visner Martha , Boilard Eric , Italiano Joseph E. , Nigrovic Peter A.
Published: December 2018

Bone marrow megakaryocytes engulf neutrophils in a phenomenon termed emperipolesis. We show here that emperipolesis is a dynamic process mediated actively by both lineages, in part through the β2-integrin/ICAM-1/ezrin pathway. Tethered neutrophils enter in membrane-bound vesicles before penetrating into the megakaryocyte cytoplasm. Intracytoplasmic neutrophils develop membrane contiguity with the demarcation membrane system, thereby transferring membrane to the megakaryocyte and to daughter platelets. This phenomenon occurs in otherwise unmanipulated marrowin vivo, resulting in circulating platelets that bear membrane from non-megakaryocytic hematopoietic donors. Transit through megakaryocytes can be completed as rapidly as minutes, after which neutrophils egress intact. Emperipolesis is amplified in models of inflammation associated with platelet overproduction, contributing to platelet productionin vitroandin vivo.These findings identify emperipolesis as a new cell-in-cell interaction that enables neutrophils and potentially other cells passing through the megakaryocyte cytoplasm to modulate the production and membrane content of platelets.
Lifespan associated global patterns of coherent neural communication
Authors: Sahoo Bikash , Pathak Anagh , Deco Gustavo , Banerjee Arpan , Roy Dipanjan
Published: December 2018

Healthy ageing is accompanied by changes to spontaneous electromagnetic oscillations. At the macroscopic scale, previous studies have quantified the basic features, e.g., power and frequencies in rhythms of interest from the perspective of attention, perception, learning and memory. On the other hand, signatures and modes of neural communication have recently been argued to be identifiable from global measures applied on neuro-electromagnetic data such as global coherence that quantifies the degree of togetherness of distributed neural oscillations and metastability that parametrizes the transient dynamics of the network switching between successive stable states. Here, we demonstrate that global coherence and metastability can be informative measures to track healthy ageing dynamics over lifespan and together with the traditional spectral measures provides an attractive explanation of neuronal information processing. Finding normative patterns of brain rhythms in resting state MEG would naturally pave the way for tracking task relevant metrics that could crucially determine cognitive flexibility and performance. While previously reported observations of a reduction in peak alpha frequency and increased beta power in older adults are reflective of changes at individual sensors (during rest and task), global coherence and metastability truly pinpoint the underlying coordination dynamics over multiple brain areas across the entire lifespan. In addition to replication of the previous observations in a substantially larger lifespan cohort than what was previously reported, we also demonstrate, for the first time to the best of our knowledge, age related changes in coherence and metastability in signals over time scales of neuronal processing. Furthermore, we observed a marked frequency dependence in changes in global coordination dynamics, which, coupled with the long held view of specific frequency bands sub-serving different aspects of cognition, hints at differential functional processing roles for slower and faster brain dynamics.
ComammoxNitrospiraare the dominant ammonia oxidizers in a mainstream low dissolved oxygen nitrification reactor
Authors: Roots Paul , Wang Yubo , Rosenthal Alex F. , Griffin James S. , Sabba Fabrizio , Petrovich Morgan , Yang Fenghua , Kozak Joseph A. , Zhang Heng , Wells George F.
Published: December 2018

Recent findings show that a subset of bacteria affiliated withNitrospira, a genus known for its importance in nitrite oxidation for biological nutrient removal applications, are capable ofcompleteammoniaoxidation (comammox) to nitrate. Early reports suggested that they were absent or present in low abundance in most activated sludge processes, and thus likely functionally irrelevant. Here we show the accumulation of comammoxNitrospirain a nitrifying sequencing batch reactor operated at low dissolved oxygen (DO) concentrations. Actual mainstream wastewater was used as influent after primary settling and an upstream pre-treatment process for carbon and phosphorus removal. The ammonia removal rate was stable and exceeded that of the treatment plant’s parallel full-scale high DO nitrifying activated sludge reactor. 16S rRNA sequencing showed a steady accumulation ofNitrospirato 53% total abundance and a decline in conventional ammonia oxidizing bacteria to <1% total abundance over 400+ days of operation. After ruling out other known ammonia oxidizers, qPCR confirmed the accumulation of comammoxNitrospirabeginning around day 200, to eventually comprise 94% of all detectedamoAand 4% of total bacteria by day 407. Quantitative fluorescence in-situ hybridization confirmed the increasing trend and high relative abundance ofNitrospira. These results demonstrate that comammox can be metabolically relevant to nitrogen transformation in wastewater treatment, and can even dominate the ammonia oxidizing community. Our results suggest that comammox may be an important functional group in energy efficient nitrification systems designed to operate at low DO levels.
Computational Correction of Spatially-Variant Optical Aberrations in 3D Single Molecule Localization Microscopy
Authors: Yan Ting , Richardson Charles J. , Zhang Mingxing , Gahlmann Andreas
Published: December 2018

3D single-molecule localization microscopy relies on fitting the shape of point-spread-functions (PSFs) recorded on a wide-field detector. However, optical aberrations distort those shapes, which compromise the accuracy and precision of single-molecule localization microscopy. Here we employ a computational phase retrieval based on a vectorial PSF model to quantify the spatially-variance of optical aberrations in a two-channel ultrawide-field single-molecule localization microscope. The use of a spatially-variant PSF model enables accurate and precise emitter localization in x, y- and z- directions throughout the entire field-of-view.
The neural dynamics of hierarchical Bayesian inference in multisensory perception
Authors: Rohe Tim , Ehlis Ann-Christine , Noppeney Uta
Published: December 2018

Transforming the barrage of sensory signals into a coherent multisensory percept relies on solving the binding problem – deciding whether signals come from a common cause and should be integrated, or instead be segregated. Human observers typically arbitrate between integration and segregation consistent with Bayesian Causal Inference, but the neural mechanisms remain poorly understood. We presented observers with audiovisual sequences that varied in the number of flashes and beeps. Combining Bayesian modelling and EEG representational similarity analyses, we show that the brain initially represents the number of flashes and beeps and their numeric disparity mainly independently. Later, it computes them by averaging the forced-fusion and segregation estimates weighted by the probabilities of common and independent cause models (i.e. model averaging). Crucially, prestimulus oscillatory alpha power and phase correlate with observers’ prior beliefs about the world’s causal structure that guide their arbitration between sensory integration and segregation.
scAlign: a tool for alignment, integration and rare cell identification from scRNA-seq data
Authors: Johansen Nelson , Quon Gerald
Published: December 2018

scRNA-seq dataset integration occurs in different contexts, such as the identification of cell type-specific differences in gene expression across conditions or species, or batch effect correction. We present scAlign, an unsupervised deep learning method for data integration that can incorporate partial, overlapping or a complete set of cell labels, and estimate per-cell differences in gene expression across datasets. scAlign performance is state-of-the-art and robust to cross-dataset variation in cell type-specific expression and cell type composition. We demonstrate that scAlign identifies a rare cell population likely to drive malaria transmission. Our framework is widely applicable to integration challenges in other domains.
Full Atomistic Model of Prion Structure and Conversion
Authors: Spagnolli Giovanni , Rigoli Marta , Orioli Simone , Sevillano Alejandro M. , Faccioli Pietro , Wille Holger , Biasini Emiliano , Requena Jesùs R.
Published: December 2018

Prions are unusual protein assemblies that propagate their conformationally-encoded information in absence of nucleic acids. The first prion identified, the scrapie isoform (PrPSc) of the cellular prion protein (PrPC), is the only one known to cause epidemic and epizootic episodes(1). Most aggregates of other misfolding-prone proteins are amyloids, often arranged in a Parallel-In-Register-β-Sheet (PIRIBS)(2) or β-solenoid conformations(3). Similar folding models have also been proposed for PrPSc, although none of these have been confirmed experimentally. Recent cryo-electron microscopy (cryo-EM) and X-ray fiber-diffraction studies provided evidence that PrPSc is structured as a 4-rung β-solenoid (4RβS)(4, 5). Here, we combined different experimental data and computational techniques to build the first physically-plausible, atomic resolution model of mouse PrPSc, based on the 4RβS architecture. The stability of this new PrPSc model, as assessed by Molecular Dynamics (MD) simulations, was found to be comparable to that of the prion forming domain of Het-s, a naturally-occurring β-solenoid. Importantly, the 4RβS arrangement allowed the first simulation of the sequence of events underlying PrPC conversion into PrPSc. Our results provide the most updated, experimentally-driven and physically-coherent model of PrPSc, together with an unprecedented reconstruction of the mechanism underlying the self-catalytic propagation of prions.

Significance

Since the original hypothesis by Stanley Prusiner, prions have represented enigmatic agents diverging from the classical concept of genetic inheritance. However, the structure of PrPSc, the infectious isoform of the cellular prion protein (PrPC), has so far remained elusive, mostly due to technical challenges posed by its aggregation propensity. Here, we present a new high resolution model of PrPSc derived from the integration of a wide array of recent experimental constraints. By coupling the information of such model with a newly developed computational method, we reconstructed for the first time the conformational transition of PrPC to PrPSc. This study offers a unique workbench for designing therapeutics against prion diseases, and a physically-plausible mechanism explaining how protein conformation could self-propagate.
Bioprinted pluripotent stem cell-derived kidney organoids provide opportunities for high content screening
Authors: Higgins J. William , Chambon Alison , Bishard Kristina , Hartung Anke , Arndt Derek , Brugnano Jamie , Er Pei Xuan , Lawlor Kynan T. , Vanslambrouck Jessica M. , Wilson Sean , Combes Alexander N. , Howden Sara E. , Tan Ker Sin , Kumar Santhosh V. , Hale Lorna J. , Shepherd Benjamin , Pentoney Stephen , Presnell Sharon C. , Chen Alice E. , Little Melissa H.
Published: December 2018

Recent advances in the directed differentiation of human pluripotent stem cells to kidney brings with it the prospect of drug screening and disease modelling using patient-derived stem cell lines. Development of such an approach for high content screening will require substantial quality control and improvements in throughput. Here we demonstrate the use of the NovoGen MMX 3D bioprinter for the generation of highly reproducible kidney organoids from as few as 4,000 cells. Histological and immunohistochemical analyses confirmed the presence of renal epithelium, glomeruli, stroma and endothelium, while single cell RNAseq revealed equivalence to the cell clusters present within previously described organoids. The process is highly reproducible, rapid and transferable between cell lines, including genetically engineered reporter lines. We also demonstrate the capacity to bioprint organoids in a 96-well format and screen for response to doxorubicin toxicity as a proof of concept for high content compound screening.
The mutational landscape of normal human endometrial epithelium
Authors: Moore Luiza , Leongamornlert Daniel , Coorens Tim HH , Sanders Mathijs A , Ellis Peter , Dawson Kevin , Maura Franscesco , Nangalia Jyoti , Tarpey Patrick S , Brunner Simon F , Lee-Six Henry , Rahbari Raheleh , Moody Sarah , Hooks Yvette , Mahbubani Krishnaa , Jimenez-Linan Mercedes , Brosens Jan J , Iacobuzio-Donahue Christine , Martincorena Inigo , Saeb-Parsy Kourosh , Campbell Peter J , Stratton Michael R.
Published: December 2018

All normal somatic cells are thought to acquire mutations. However, characterisation of the patterns and consequences of somatic mutation in normal tissues is limited. Uterine endometrium is a dynamic tissue that undergoes cyclical shedding and reconstitution and is lined by a gland-forming epithelium. Whole genome sequencing of normal endometrial glands showed that most are clonal cell populations derived from a recent common ancestor with mutation burdens differing from other normal cell types and manyfold lower than endometrial cancers. Mutational signatures found ubiquitously account for most mutations. Many, in some women potentially all, endometrial glands are colonised by cell clones carrying driver mutations in cancer genes, often with multiple drivers. Total and driver mutation burdens increase with age but are also influenced by other factors including body mass index and parity. Clones with drivers often originate during early decades of life. The somatic mutational landscapes of normal cells differ between cell types and are revealing the procession of neoplastic change leading to cancer.
Three‐parameter Radon transform in layered transversely isotropic media
Authors: Abedi Mohammad Mahdi , Riahi Mohammad Ali , Stovas Alexey
Published: December 2018

Radon transform is a powerful tool with many applications in different stages of seismic data processing, because of its capability to focus seismic events in the transform domain. Three‐parameter Radon transform can optimally focus and separate different seismic events, if its basis functions accurately match the events. In anisotropic media, the conventional hyperbolic or shifted hyperbolic basis functions lose their accuracy and cannot preserve data fidelity, especially at large offsets. To address this issue, we propose an accurate traveltime approximation for transversely isotropic media with vertical symmetry axis, and derive two versions of Radon basis functions, time‐variant and time‐invariant. A time‐variant basis function can be used in time domain Radon transform algorithms while a time‐invariant version can be used in, generally more efficient, frequency domain algorithms. Comparing the time‐variant and time‐invariant Radon transform by the proposed basis functions, the time‐invariant version can better focus different seismic events; it is also more accurate, especially in presence of vertical heterogeneity. However, the proposed time‐invariant basis functions are suitable for a specific type of layered anisotropic media, known as factorized media. We test the proposed methods and illustrate successful applications of them for trace interpolation and coherent noise attenuation.
House Prices and Consumption in the United States
Authors: Vinson Philip
Published: December 2018

I estimate the house price elasticity of consumption using panel data for households in the United States for the years 1999–2013. I find that the average house price elasticity of consumption is positive but modest and varies by age. However, when measuring the elasticity separately for households who are credit constrained, I find that households with a high loan‐to‐value mortgage have a much larger house price elasticity of consumption of about 0.2. I also find that poor hand‐to‐mouth households consume more than others when their house price increases while wealthy hand‐to‐mouth ones do not.
Loss of response to scheduled infliximab therapy for Crohn's disease in adults: A systematic review and meta‐analysis
Authors: Zhang Qi Wei , Shen Jun , Zheng Qing , Ran Zhi Hua
Published: December 2018

Objective

To determine the potential predictors of loss of response (LOR) to infliximab (IFX) maintenance therapy for adult patients with Crohn's disease (CD).

Methods

We searched for English‐language articles published between 1990 and March 2017 in PubMed, Embase, and the Cochrane Library. After identifying eligible studies, data extraction was performed independently by two reviewers. The potential prognostic variables were identified and dichotomized for meta‐analysis. Based on the heterogeneity among study variables, random‐effects models was used in our meta‐analysis.

Results

Twenty‐six studies met our eligibility criteria and consolidated drug response data were obtained from 3212 patients. The pooled rate of LOR to IFX maintenance therapy with a median follow‐up of 1.1 years was 34%. The incidence of LOR to IFX therapy was increased in CD patients with perianal lesions (odds ratio [OR] 1.69, 95% confidence interval [CI] 1.04‐2.75, P = 0.03), colon involvement (OR 2.56, 95% CI 1.20‐5.50, P = 0.02) and younger age at CD onset (standardized mean difference −0.79, 95% CI −1.41 to −0.18, P = 0.01).

Conclusions

The meta‐analysis estimates the incidence of LOR among adult CD patients undergoing IFX therapy is 34%. The presence of perianal lesions, younger age at CD onset, and involvement of the colon are relative risk factors of LOR in CD patients received scheduled IFX maintenance therapy.
Climatic Controls on Watershed Reference Evapotranspiration Varied during 1961–2012 in Southern China
Authors: Qin Mengsheng , Hao Lu , Sun Lei , Liu Yongqiang , Sun Ge
Published: December 2018

Reference evapotranspiration (ETo) is an important hydrometeorological term widely used in understanding and projecting the hydrological effects of future climate and land use change. We conducted a case study in the Qinhuai River Basin that is dominated by a humid subtropical climate and mixed land uses in southern China. Long‐term (1961–2012) meteorological data were used to estimate ETo by the FAO‐56 Penman–Monteith model. The individual contribution from each meteorological variable to the trend of ETo was quantified. We found basin‐wide annual ETo decreased significantly (p < 0.05) by 3.82 mm/yr during 1961–1987, due to decreased wind speed, solar radiation, vapor pressure deficit (VPD), and increased relative humidity (RH). However, due to the increased VPD and decreased RH, the ETo increased significantly (p < 0.05) in spring, autumn, and annually at a rate of 2.55, 0.56, and 3.16 mm/yr during 1988–2012, respectively. The aerodynamic term was a dominant factor controlling ETo variation in both two periods. We concluded the key climatic controls on ETo have shifted as a result of global climate change during 1961–2012. The atmospheric demand, instead of air temperature alone, was a major control on ETo. Models for accurately predicting ETo and hydrological change under a changing climate must include VPD in the study region. The shifts of climatic control on the hydrological cycles should be considered in future water resource management in humid regions.
Potential distribution of riffle beetles (Coleoptera: Elmidae) in southern Brazil
Authors: Braun Bruna Marmitt , Gonçalves Alberto Senra , Pires Mateus Marques , Kotzian Carla Bender
Published: December 2018

The diversity and distribution of freshwater insects in South America is poorly known. Riffle beetles (Elmidae) are aquatic Coleoptera that are considered important indicators of environmental integrity. In Brazil, the country with the largest area and highest richness of Elmidae in the Neotropics, the diversity of the family remains incipient. The southern region of Brazil (state of Rio Grande do Sul) reportedly has a higher richness of stream insects than other regions. In this study, we used species distribution models (SDMs) to estimate the potential distribution of riffle beetle taxa in southern Brazil to identify areas with elevated diversity and suggest priority areas for further investigation towards conservation of Elmidae. As most records of Elmidae were represented by larvae, we predicted the potential distribution firstly of genera and secondly of species within the genus Macrelmis because they were available as adults and allowed identification to species level. These were modelled in relation to environmental factors such as climate, topography, hydrography and land cover. Our results suggested that montane regions and basins located within well‐preserved forested regions indicated the highest potential richness of Elmidae. In addition, the areas with higher predicted suitability for the occurrence of genera overlapped with the suitable areas for species of Macrelmis. This result suggests the existence of an elevated ecological similarity among most of the modelled taxa, and that projections for certain Elmidae genera can be useful proxies for estimations of the potential distribution of species in the region. The most important environmental factors related to the predicted distribution of Elmidae taxa were associated with climate (precipitation), landscape (forest cover) and topography. Unsurprisingly, freshwater ecoregions were also suggested as important drivers of Elmidae distribution. Our results indicate that conservation efforts for aquatic insects such as riffle beetles in Brazil should focus on watersheds located in montane and forested regions.
Methods of surgery for pelvic organ prolapse in a nationwide cohort (FINPOP 2015)
Authors: Mattsson Nina K. , Karjalainen Päivi , Tolppanen Anna‐Maija , Heikkinen Anna‐Mari , Jalkanen Jyrki , Härkki Päivi , Nieminen Kari
Published: December 2018

Introduction

The management of pelvic organ prolapse (POP) varies significantly between countries. The objective of this study was to describe the methods used for POP surgery in Finland and to identify the factors that affect clinicians’ choice to use either a native tissue repair (NTR) or a mesh repair method.

Material and Methods

This prospective cohort study included 3535 surgeries covering 83% of all POP operations performed in Finland in 2015. The operative details and patient characteristics, including the Pelvic Floor Distress Inventory (PFDI‐20), were compared between three selected surgical methods: NTR, transvaginal mesh (TVM) and abdominal mesh (AM). The predictive factors for the use of mesh augmentation were also studied with logistic regression analysis.

Results

The most common method was NTR (n = 2855, 81%), followed by TVM (n = 429, 12%) and AM (n = 251, 7%). Approximately 92% of the patients who underwent primary prolapse surgery underwent NTR, and mesh surgery was used mainly for recurrent prolapse. The strongest predictor of mesh surgery was previous POP surgery for the same vaginal compartment (adjusted odds ratio [OR] = 56, 95% confidence interval [CI] = 38‐84 for TVM; adjusted OR = 22, 95% CI = 14‐34 for AM). Other predictive factors for mesh surgery were previous hysterectomy, healthcare district, severe bulge symptoms and advanced prolapse. TVM was associated with advanced anterior prolapse and older age. AM surgery was associated with advanced apical and/or posterior compartment prolapse. PFDI‐20 scores were the highest in the AM group (108 vs 103 in the TVM group and 98 in the NTR group, P = 0.012), which indicates more bothersome symptoms than in the other groups.

Conclusions

The Finnish practices follow international guidelines that advocate NTR as the principal surgical method for POP. Synthetic mesh augmentation was mainly used in patients with recurrent and advanced prolapse with severe symptoms. The variation in the rates of mesh augmentation for POP surgery in different hospitals implies a lack of sufficient evidence of the most suitable treatment method and indicates a need for national guidelines.
The effect of screening‐to‐labor interval on the sensitivity of late‐pregnancy culture in the prediction of group B streptococcus colonization at labor: A prospective multicenter cohort study
Authors: Virranniemi Minna , Raudaskoski Tytti , Haapsamo Mervi , Kauppila Jaana , Renko Marjo , Peltola Joanna , Risteli Leila , Laatio Liisa
Published: December 2018

Introduction

The aim of this study was to evaluate the effect of increasing screening‐to‐labor interval on the performance of group B streptococcus (GBS) screening by late‐pregnancy enriched culture compared with intrapartum real‐time polymerase chain reaction (RT‐PCR).

Material and methods

Group B streptococcus colonization was determined in 2624 women with singleton pregnancies by culture at 35‐37 weeks of gestation and at the beginning of labor by culture and RT‐PCR from recto‐vaginal swab samples.

Results

Group B streptococcus colonization rates were 29.0% in late‐pregnancy culture, 29.7% in intrapartum culture and 28.2% in intrapartum PCR. Intrapartum culture was used as a reference, the late‐pregnancy culture had an overall sensitivity of 89.2% (95% CI 88.0%‐90.4%) and specificity of 96.5% (95% CI 95.8%‐97.2%), and intrapartum PCR had sensitivity of 91.5% (95% CI 90.4%‐92.6%) and specificity of 98.5% (95% CI 98.0%‐99.0%). However, up to 4 weeks after screening, the sensitivity of late‐pregnancy culture was equivalent to or higher than that of RT‐PCR. The RT‐PCR was invalid in 0.9% of the women. Between late‐pregnancy screening and labor, GBS colonization changed from negative to positive in 3.2% and from positive to negative in 2.5% of the women.

Conclusions

The late‐pregnancy enriched culture and intrapartum RT‐PCR have comparable sensitivities in the detection of GBS when culture screening is conducted no more than 4 weeks before labor. Late‐pregnancy culture sampling should be postponed to at least 37 weeks of gestation.
Safety and effectiveness of zero antimicrobial prophylaxis protocol for outpatient cystourethroscopy
Authors: Clennon Emily K. , Martinez Acevedo Ann , Sajadi Kamran P.
Published: December 2018

Objectives

To examine compliance and clinical outcomes after implementation of a zero antimicrobial prophylaxis protocol for outpatient cystoscopy in an academic centre.

Patients and Methods

Medical records of all patients who underwent diagnostic cystoscopy in the year preceding and year following protocol implementation were evaluated for urinary tract infection (UTI) diagnosis within 30 days of cystoscopy. Variables compared between groups included age, sex, smoking history, benign prostatic hyperplasia (BPH) diagnosis, diabetes mellitus, immunosuppression, catheter use (indwelling, suprapubic, or intermittent), and previous lower urinary tract reconstruction (augmentation cystoplasty or neobladder). UTI was defined using the National Surgical Quality Improvement Program definition. Rates were compared between groups, and statistical analyses were performed using chi‐squared and Fisher's exact tests and multivariable logistic regression, with significance defined as α < 0.05.

Results

In total, 941 patients were included in the analysis (72% men), 513 before protocol initiation, and 427 after. Groups were similar with regard to demographic variables and potential risk factors for infection. After protocol implementation, there was a significant reduction in patients receiving procedural antimicrobial prophylaxis (30% vs 15%; P < 0.001). The incidence of UTI after cystoscopy was slightly higher in the post‐protocol group (2.9–3.7%), but the difference was not statistically significant (chi‐squared = 0.56, P = 0.45). The incidence of UTI did not significantly differ with procedural antibiotic prophylaxis or with other antibiotic use at time of cystoscopy. Five out of a total of 31 UTIs (16%) over the study period resulted in fever, and four (13%) resulted in urosepsis. The probability of neither complication differed significantly between pre‐ and post‐protocol groups. The only significant patient‐level predictor of post‐cystoscopy UTI was catheter use (odds ratio 1.48, 95% confidence interval 1.06–2.06).

Conclusion

Protocol implementation led to a significant decrease in procedural antimicrobial prophylaxis, indicating protocols may be effective tools in promoting antibiotic stewardship. UTI incidence did not change significantly under the protocol, and antibiotic prophylaxis did not decrease infection rate. Our results support catheter use as a risk factor for post‐cystoscopy infection, but other patient variables, including those present in the American Urological Association Best Practice statement, were not predictive. In total, this analysis suggests that decreasing antibiotic prophylaxis for cystourethroscopy is safe and can be effective in the outpatient setting.
Multicolour imaging for the detection of polypoidal choroidal vasculopathy and age‐related macular degeneration
Authors: Tan Colin S. , Ting Dominic S. , Lim Louis W.
Published: December 2018

Importance

Multicolour is a new imaging technology and its sensitivity for detecting polypoidal choroidal vasculopathy (PCV) and age‐related macular degeneration (AMD) has not been well described.

Background

To evaluate the accuracy of multicolour imaging compared to colour fundus photography (CFP) in differentiating AMD and PCV from normal eyes, and in detecting PCV.

Design

Prospective cohort study at a tertiary referral centre.

Participants

Fifty consecutive patients with PCV or AMD.

Methods

Standardized multimodal imaging, including CFP, multicolour imaging, and fluorescein and indocyanine green angiography, were graded by a Central Reading Center using standardized grading protocols.

Main Outcomes and Measures

Sensitivity, specificity, positive and negative predictive values (PPV and NPV).

Results

Of 100 eyes, 44 had PCV, 33 had AMD, and 23 were normal. Multicolour imaging had higher specificity (73.9% vs 52.2%) and NPV (94% vs 85.7%) compared to CFP for detecting all types of AMD. For the detection of PCV, multicolour had higher sensitivity (86.4% vs 59.1%) and NPV (89.3% vs 74.3%). Polypoidal lesions were detected in 39 of 44 eyes (88.6%) using multicolour imaging, while the branching vascular network (BVN) was detected in 16 of 44 eyes (36.4%). Using BVN as a parameter, infrared imaging specificity and PPV for detecting PCV were 96.6% and 88.9%, respectively.

Conclusions and Relevance

Multicolour imaging is superior to standard CFP in differentiating AMD and PCV from normal eyes, and in detecting features of PCV. Specific features seen on multicolour imaging can alert ophthalmologists to the likely presence of these diseases so that additional definitive investigations can be performed.
Four‐year results of a minimally invasive transscleral glaucoma gel stent implantation in a prospective multi‐centre study
Authors: Lenzhofer Markus , Kersten‐Gomez Inga , Sheybani Arsham , Gulamhusein Husayn , Strohmaier Clemens , Hohensinn Melchior , Burkhard Dick H , Hitzl Wolfgang , Eisenkopf Lisa , Sedarous Fady , Ahmed Iqbal I. , Reitsamer Herbert A.
Published: December 2018

Importance

The transscleral XEN Glaucoma Gel Microstent (XEN‐GGM, Allergan Plc., Parsippany, New Jersey) is implanted by a minimally invasive ab interno technique.

Background

The present study aims to assess the long‐term clinical outcomes in patients after XEN‐GGM implantation.

Design

This prospective, non‐randomized, multi‐centred study was conducted in three countries (Austria, Canada and Germany).

Participants

Sixty‐four consecutive eyes of 64 patients with open angle glaucoma received the XEN‐GGM (63 μm) without Mitomycin C. Thirty‐five (55%) were solo procedures, and 29 (45%) were combined with cataract surgery.

Methods

Visits were planned at baseline, 6 months, 1, 2, 3 and 4 years postoperatively.

Main Outcome Measures

The main outcome measures were mean intraocular pressure (IOP), mean number of IOP lowering medication. Secondary outcome parameters were: visual acuity, visual fields and complete surgical failure (defined as presence of a secondary IOP lowering procedure or loss of light perception) at 4 years, postoperatively.

Results

Mean best‐medicated baseline IOP was 22.5 ± 4.2 mmHg and decreased significantly to 13.4 ± 3.1 mmHg 4 years postoperatively (−40%, n = 34, P < 0.001). Mean number of IOP lowering medication decreased significantly from 2.4 ± 1.3 preoperatively to 1.2 ± 1.3 (−50%, n = 34, P < 0.001) postoperatively. Visual field mean deviation showed no significant change between preoperative and postoperative examinations. Complete surgical failure rate per year was 10%.

Conclusions and Relevance

The XEN‐GGM resulted in lower IOP and a reduction in medications from baseline over 4 years of follow‐up. There was no detectable decrease in visual fields over the study. The surgical failure rate is comparable to other filtration surgeries.
The genetic pathogenesis, diagnosis and therapeutic insight of rheumatoid arthritis
Authors: Zamanpoor Mansour
Published: December 2018

Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes chronic inflammation of the joints. RA is a heterogeneous disorder caused by an abnormal autoimmune response triggered by the complex interactions of genetic and environmental factors that contribute to RA etiology. However, its underlying pathogenic mechanisms are yet to be fully understood. In this review, I provide an overview of the pathogenesis, diagnosis and therapeutic insight in the clinical management of RA in light of the recent updates to classification criteria and recent discoveries of genetic loci associated with susceptibility for RA.
A randomized controlled trial on the efficiency of free‐handed, pilot‐drill guided and fully guided implant surgery in partially edentulous patients
Authors: Younes Faris , Eghbali Aryan , De Bruyckere Thomas , Cleymaet Roberto , Cosyn Jan
Published: December 2018

Objectives

To compare the effectiveness of free‐handed (FH), pilot‐drill guided (PG) and fully guided (FG) implant surgery by means of the apical global deviation (AGD) in relation to the additional financial cost and time spent.

Materials and methods

Thirty‐three partially edentulous patients in need of ≥2 implants in the posterior maxilla were randomly allocated to one of the following treatment groups: FH, PG and FG. Eleven patients (mean age 57; eight females; altogether 26 implants) were treated by FH surgery, 11 (mean age 53; seven females; altogether 24 implants) by PG surgery and 10 (mean age 60; six females; altogether 21 implants) by FG surgery. The accuracy in implant positioning was assessed by comparing the actual implant position to its planned position with the AGD as the main measure of effectiveness. Cost analysis included data on time investment (pre‐ and per‐operative) and operational cost. The efficiency of PG and FG surgery was assessed by means of the incremental cost‐effectiveness ratio (ICER), defined as the extra investment that is needed per unit reduction in AGD when compared to FH surgery.

Results

FG surgery was most effective (mean AGD: 0.97 mm) and FH surgery was least effective (mean AGD: 2.11 mm) in terms of surgical accuracy. As a result, 5/26 implants had to be restored with a cement‐retained restoration following FH surgery, although screw‐retention was planned for all implants in every group. The total time investment did not differ significantly between the 3 groups (p = 0.811). A significant additional cost per implant was found for PG and FG as compared to FH surgery pointing to 8.29% (€176.54) and 10.45% (€222.52), respectively (p < 0.001). The ICER revealed an additional cost of €5.48 and €4.12 per per cent reduction in AGD for PG and FG surgery, respectively.

Conclusion

The extra operational cost for guided implant surgery is acceptable and clinically justified since cementation can be avoided. FG surgery is the most efficient surgical approach, even though the absolute operational cost is higher when compared to PG and FH surgery.
Differential impact of age on survival in head and neck cancer according to classic Cox regression and decision tree analysis
Authors: Yang Ching‐Chieh , Su Yu‐Chieh , Lin Yu‐Wei , Huang Chung‐I , Lee Ching‐Chih
Published: December 2018

Objectives

To assess the impact of age on the survival of patients with head and neck squamous cell carcinoma (HNSCC) using different statistical methods.

Design

A retrospective population‐based study.

Setting

Surveillance, Epidemiology, and End Results database.

Subjects and methods

A total of 28 639 patients with newly diagnosed HNSCC were enrolled between 1 January 2007 and 31 December 2013. The effect of age on 5‐year disease‐specific survival was calculated using a Kaplan‐Meier method and compared using log‐rank tests. A Cox proportional hazards model was used for a multivariate analysis. A classification and regression tree (CART) analysis that partitioned patients with significantly different Kaplan‐Meier curves was introduced to identify the important cancer‐related parameters influencing survival.

Results

Uni‐ and multivariate analyses indicated that patients who were older than 60 years had poorer 5‐year disease‐specific survival regardless of tumour subsite and tumor‐node‐metastasis (TNM) stage. However, the CART analysis determined that age played only a minor role in survival after comparing with other prognosticators. The relative importance of age using the Gini index was as follows: 3.21% for oral cancer, 8.32% for oropharyngeal cancer, 2.56% for hypopharyngeal cancer and 16.51% for laryngeal cancer.

Conclusions

Different to traditional statistical methods, the CART analysis which was used to identify homogeneous populations revealed that the impact of age varied for different patient groups according to the presence or absence of other prognosticators. This important information could help to guide our clinical decisions and future researches.
Understanding and bridging the conservation‐genetics gap in marine conservation
Authors: Sandström Annica , Lundmark Carina , Andersson Klas , Johannesson Kerstin , Laikre Linda
Published: December 2018

Article impact statement: Upgrading policy on, resources for, and knowledge and communication of genetic diversity closes the conservation‐genetics gap.
Disparity in access to kidney allograft offers among transplant candidates with human immunodeficiency virus
Authors: Cohen Jordana B. , Locke Jayme E. , Shelton Brittany , Reed Rhiannon D. , Mustian Margaux , MacLennan Paul , Forde Kimberly A. , Reese Peter P. , Sawinski Deirdre
Published: December 2018

Background

Despite a survival benefit from transplantation and acceptable outcomes, patients with human immunodeficiency virus (HIV+) face barriers to kidney transplantation. Little is known about the acceptance or decline of organ offers on their behalf because waitlist registry data do not include HIV serostatus.

Methods

We performed a retrospective cohort study using match run data from the Organ Procurement and Transplantation Network, including every kidney offer from May 1, 2007, to July 3, 2013. HIV and hepatitis C virus (HCV) serostatus were obtained by merging the match run with clinical data from a large dialysis provider. We used Cox proportional hazards modeling to evaluate differences in time to the first organ offer and to transplantation. A total of 35 646 uninfected, 2213 HCV+, 418 HIV+, and 71 HIV+/HCV+ candidates received organ offers during the study period.

Results

Compared to uninfected candidates, HIV+ candidates had a significantly lower likelihood of receiving a first offer (adjusted hazard ratio [aHR] 0.88, 95% confidence interval [CI] 0.79‐0.99) and undergoing transplantation (aHR 0.82, 95% CI: 0.68‐0.98) after receiving a first offer; HCV+ candidates had a similar likelihood of receiving a first offer (aHR 0.98, 95% CI: 0.92‐1.03) and greater likelihood of transplantation after receiving a first offer (aHR 1.23, 95% CI: 1.12‐1.36).

Conclusions

HIV+ candidates had a significantly longer wait until their first organ offer and to transplantation. Efforts to increase their access to transplantation are needed.
Incidence and variables associated with 30‐day mortality after lung transplantation
Authors: Banga Amit , Mohanka Manish , Mullins Jessica , Bollineni Srinivas , Kaza Vaidehi , Huffman Lynn , Peltz Matthias , Bajona Pietro , Wait Michael , Torres Fernando
Published: December 2018

Background

With the introduction of the lung allocation score (LAS), sicker patients are prioritized for lung transplantation (LT). There is a lack of data regarding variables independently associated with 30‐day mortality after LT.

Methods

We queried the UNOS database for adult patients undergoing LT between 1989 and 2014. Patients with dual organ or previous transplantation and those with missing survival data were excluded. Mortality during the first 30 days after LT was the primary outcome variable.

Results

The yearly trends indicate a statistically significant reduction in the 30‐day mortality during the study period (P < 0.001, overall mortality: 5.5%) which has continued in the post‐LAS era (P = 0. 014, overall mortality: 3.6%). Among patients with 30‐day mortality, “primary non‐function” (n = 118, 72.8%) was reported as the most common etiology. Transplant indication of vascular diseases, history of non‐transplant cardiac or lung surgery, mean pulmonary pressures >35 mm Hg, disabled functional status, ECMO support, high LAS, ischemic time >6 hours, and blunt injury as the mechanism of donor death are independently associated with 30‐day mortality.

Conclusion

The incidence of early mortality after LT continues to decline in the post‐LAS era. Apart from the mechanism of donor death and ischemic time, early mortality appears to be primarily driven by the recipient characteristics.
Factors associated with disordered eating behaviours in adolescents with Type 1 diabetes
Authors: Cecilia‐Costa R. , Volkening L. K. , Laffel L. M.
Published: December 2018

Aims

To assess the occurrence of disordered eating behaviours in teenagers with Type 1 diabetes and to compare characteristics according to level of disordered eating behaviours.

Methods

In this cross‐sectional study, we collected adolescents’ demographic and diabetes management data by parent–youth interview and chart review. Teenagers completed psychosocial surveys, including the Diabetes Eating Problem Survey‐Revised (DEPS‐R), a diabetes‐specific measure of disordered eating behaviours. We categorized teenagers according to level of disordered eating behaviours: low, DEPS‐R score <10; moderate, DEPS‐R score 10–19; and high, DEPS‐R score ≥20.

Results

The 178 teenagers (48% girls) were aged 14.9±1.3 years, with diabetes duration of 7.4±3.7 years. Most (59%) had low, 26% had moderate, and 15% had high levels of disordered eating behaviours. Several biomedical and psychosocial characteristics differed by level of disordered eating behaviours. There were more girls in the moderate (62%) and high (65%) than in the low level of disordered eating behaviours group (37%; P=0.003) and more obese teenagers in the moderate (13%) and high (27%) groups than in the low group (4%; P=0.0003). Frequency of daily blood glucose monitoring decreased (P=0.0006) and HbA1c level increased (P=0.01) with greater level of disordered eating behaviours. A greater level of disordered eating behaviours was also associated with poorer treatment adherence, more negative affect regarding blood glucose monitoring, poorer quality of life, and more depressive symptoms (all P<0.0001), along with more diabetes‐specific family conflict (P=0.01).

Conclusions

Identifying teenagers with Type 1 diabetes who have moderate and high levels of disordered eating behaviours may prevent progression to eating disorders and substantial morbidity by directing support and intervention efforts to those in need.
Treatment patterns and healthcare resource utilization in patients withFLT3‐mutated and wild‐type acute myeloid leukemia: A medical chart study
Authors: Griffin James D. , Yang Hongbo , Song Yan , Kinrich David , Shah Manasee V. , Bui Cat N.
Published: December 2018

Objectives

To assess real‐world treatment patterns and healthcare resource utilization (HRU) among patients withFLT3–mutated (FLT3mut) andFLT3–wild‐type (FLT3wt) acute myeloid leukemia (AML).

Methods

Data were abstracted from medical charts of patients with AML from 10 countries. Patients were grouped based on theirFLT3mutation status, age (18‐64 or ≥65), and whether they were newly diagnosed (ND) or relapsed/refractory (R/R).

Results

Charts of 1027 AML patients were included (183FLT3mut18‐64 ND; 136FLT3mut≥65 ND; 181FLT3mutR/R; 186FLT3wt18‐64 ND; 159FLT3wt≥65 ND; 182FLT3wtR/R). Substantial heterogeneity was observed in treatment patterns for AML. Among ND patients 18‐64, the most common initial treatment was standard‐to‐intermediate dose cytarabine‐based therapies (43.2% forFLT3mutand 55.9% forFLT3wt); among ND patients ≥65, the most common initial treatment was hypomethylating agent‐based therapies (36.0% and 47.2%). Among R/R patients, the most common initial treatment after R/R was best supportive care only (39.8% and 24.7%). HRU was substantial across cohorts during both event‐free and post‐event periods.

Conclusions

Treatment patterns of AML were heterogeneous andFLT3mutAML was treated more aggressively thanFLT3wtdisease. HRU was substantial for all cohorts, particularly after relapse or treatment failure.
Molecular pathogenesis of myelodysplastic syndromes with deletion 5q
Authors: Lee Jung‐hoon , List Alan , Sallman David A.
Published: December 2018

The molecular pathogenesis of deletion 5q (del(5q)) myelodysplastic syndrome (MDS) has recently been realized as a result of major advances in our understanding of the mechanisms responsible for clinical phenotype. Identification of commonly deleted genes such as RPS14, miRNA‐145, HSPA9, CD78, and CSNK1a1 have elucidated the precise biological changes responsible for the anemia, leukopenia, and thrombocytosis that characterizes del(5q) MDS and highlighted the importance of allelic haploinsufficiency in the hematological phenotype. Recent elegant investigations have also identified a critical role of innate immune signaling in del(5q) pathogenesis. TP53 and Wnt/β‐catenin pathways have also been found to be involved in clonal expansion and progression of the disease as well as resistance and poor outcomes to available therapy. Understanding the molecular pathogenesis of the disease has provided a critical foundation in identifying the biological targets of lenalidomide in del(5q) MDS, which has led to the development of novel therapeutic agents in hematologic malignancies as well as potential alternative targets to exploit in patients who have failed lenalidomide treatment.