bluuebunny/crossref_metadata_2025 huggingface dataset:
A critical role for ABC transporters in persistent lung inflammation in the development of emphysema after smoke exposure
Authors: Sonett Jarrod , Goldklang Monica , Sklepkiewicz Piotr , Gerber Adam , Trischler Jordis , Zelonina Tina , Westerterp Marit , Lemaître Vincent , Okada Yasunori , Armiento Jeanine D’
Published: June 2018

Macrophage infiltration is common to both emphysema and atherosclerosis, and cigarette smoke down‐regulates the macrophage cholesterol efflux transporter ATP binding cassette (ABC)A1. This decreased cholesterol efflux results in lipid‐laden macrophages. We hypothesize that cigarette smoke adversely affects cholesterol transport via an ABCA1‐dependent mechanism in macrophages, enhancing TLR4/myeloid differentiation primary response gene 88 (Myd88) signaling and resulting in matrix metalloproteinase (MMP) up‐regulation and exacerbation of pulmonary inflammation. ABCA1 is significantly down‐regulated in the lung upon smoke exposure conditions. Macrophages exposed to cigarette smoke in vivo and in vitro exhibit impaired cholesterol efflux correlating with significantly decreased ABCA1 expression, up‐regulation of the TLR4/Myd88 pathway, and downstream MMP‐9 and MMP‐13 expression. Treatment with liver X receptor (LXR) agonist restores ABCA1 expression after short‐term smoke exposure and attenuates the inflammatory response; after long‐term smoke exposure, there is also attenuated physiologic and morphologic changes of emphysema. In vitro, treatment with LXR agonist decreases macrophage inflammatory activation in wild‐type but not ABCA1 knockout mice, suggesting an ABCA1‐dependent mechanism of action. These studies demonstrate an important association between cigarette smoke exposure and cholesterol‐mediated pathways in the macrophage inflammatory response. Modulation of these pathways through manipulation of ABCA1 activity effectively blocks cigarette smoke–induced inflammation and provides a potential novel therapeutic approach for the treatment of chronic obstructive pulmonary disease.—Sonett, J., Goldklang, M., Sklepkiewicz, P., Gerber, A., Trischler, J., Zelonina, T., Westerterp, M., Lemaître, V., Okada, V., D’Armiento, J. A critical role for ABC transporters in persistent lung inflammation in the development of emphysema after smoke exposure. FASEB J. 32, 6724–6736 (2018). www.fasebj.org
Aberrant miR‐145–5p/β‐catenin signal impairs osteocyte function in adolescent idiopathic scoliosis
Authors: Zhang Jiajun , Chen Huanxiong , Leung Ross K. K. , Choy Kwong Wai , Lam Tsz‐Ping , Ng Bobby K. W. , Qiu Yong , Feng Jian Q. , Cheng Jack C. Y. , Lee Wayne Y. W.
Published: June 2018

Recently, noncoding RNAs have been thought to play important roles in the sporadic occurrence of spinal deformity of adolescent idiopathic scoliosis (AIS). As a prognostic factor for curve progression, low bone mass has been hypothesized to crosstalk with AIS pathogenesis. Abnormal osteoblasts activities are reported in AIS without a clear mechanism. In this study, bone biopsies from patients with AIS and control subjects and the primary osteoblasts derived from those samples were used to identify the potential microRNA (miRNA) candidates that interfere with osteoblasts and osteocytes function. Microarray analysis identified miRNA‐145–5p (miR‐145) as a potential upstream regulator. miR‐145 and β‐catenin mRNA (CTNNB1) were overexpressed in AIS bone tissues and primary osteoblasts, and their expression correlated positively in AIS. Knockdown of miR‐145 restored impaired osteocyte activity through the down‐regulation of active β‐catenin expression and its transcriptional activity. Significant negative correlations between circulating miR‐145 and serum sclerostin, osteopontin, and osteoprotegerin were noted in patients with AIS, which was in line with our cellular findings. This is the first study to demonstrate the effect of aberrant miRNA expression and its effect on osteocyte function in AIS, which may contribute to the low bone mass. Our findings also provide insight into the development of circulating microRNAs as a bone quality biomarker or even a prognostic biomarker for AIS.—Zhang, J., Chen, H., Leung, R. K. K., Choy, K. W., Lam, T.‐P., Ng, B. K. W., Qiu, Y., Feng, J. Q., Cheng, J. C. Y., Lee, W. Y. W. Aberrant miR‐145–5p/β‐catenin signal impairs osteocyte function in adolescent idiopathic scoliosis. FASEB J. 32, 6537–6549 (2018). www.fasebj.org
CE: Breast Cancer Screening: A Review of Current Guidelines
Authors: Baron Roberta , Drucker Karen , Lagdamen Liza , Cannon Maureen , Mancini Carrie , Fischer-Cartlidge Erica
Published: June 2018

Breast cancer accounts for more than a quarter million diagnoses each year in the United States. Routine screening is the primary method used to detect cancer in its earliest stages, before symptoms develop. Recent changes to national screening guidelines have resulted in a lack of consensus and confusion among health care providers and the public. This article reviews the guidelines of the American Cancer Society, the U.S. Preventive Services Task Force, and the National Comprehensive Cancer Network and provides guidance to nurses as they support and educate patients.
Ulnar Nerve Injury in Pediatric Midshaft Forearm Fractures: A Case Series
Authors: Federer Andrew E. , Murphy Joshua S. , Calandruccio James H. , Devito Dennis P. , Kozin Scott H. , Slappey Greg S. , Lourie Gary M.
Published: June 2018

Objectives:

To describe a midshaft forearm fracture pattern that places the ulnar nerve at risk in the pediatric population and provide 7 clinical case examples describing the injury pattern and treatment methods.

Design:

Retrospective observational case series, review of literature, cadaver dissection, and treatment recommendations.

Setting:

Multi-institutional, Southeast United States.

Patients:

Seven pediatric patients (5 male and 2 female) with mean age of 8.7 years (range, 3–14) who sustained a significantly displaced closed, or grade I open, middle to distal one-third both-bone forearm fracture with subsequent ulnar nerve dysfunction.

Interventions:

Manual reduction and casting of both-bone forearm shaft fractures, operative debridement, fracture fixation, nerve exploration, neurolysis, nerve repair, and nerve grafting.

Main Outcome Measurements:

Radiographic fracture union, clinical ulnar nerve motor and sensory function testing, along with selective electric nerve testing and advanced imaging were monitored throughout follow-up postinjury.

Results:

Five of 7 patients underwent surgical treatment and 2 others were treated with conservative measures. The ulnar nerve was entrapped within the fracture site of one patient with an open fracture along with partial nerve transection, and 4 patients were found to have the nerve encased in hypertrophic scar tissue or bony callus upon surgical exploration at 3–12 months postinjury.

Conclusions:

The ulnar nerve lies in a precarious position in the middle to distal one-third forearm and is bound by anatomic constraints that place the nerve at risk of injury. This article offers a treatment algorithm that includes conservative treatment, acute exploration, early exploration (≤3 months), and late exploration (>3 months).

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Clinical and Molecular Recursive Partitioning Analysis of High-grade Glioma Treated With IMRT
Authors: Sutera Philip , Kalash Ronny , Flickinger John , Engh Johnathan , Heron Dwight E.
Published: June 2018

Introduction:

Despite multimodal treatment for high-grade gliomas, prognosis remains grim. Prior Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) reports indicate based on pretreatment and treatment-related factors, a subset of patients experience a significantly improved survival. Since the development of the RTOG-RPA, high-grade gliomas have seen the widespread introduction of temozolomide and tumor oncogenetics. Here we aimed to determine whether the RTOG-RPA retained prognostic significance in the context of modern treatment, as well as generate an updated RPA incorporating both clinical and genetic variables.

Methods:

Patients with histologically proven glioblastoma, gliosarcoma, anaplastic astrocytoma, and anaplastic oligodendroglioma treated with intensity-modulated radiation therapy (IMRT) between 2004 and 2017 were reviewed. The primary endpoint was overall survival from date of diagnosis. Primary analysis compared actual survival rates to that expected of corresponding RTOG-RPA class. Secondary analysis utilized the rpart function to recursively partition overall survival by numerous clinical and genetic pretreatment and treatment-related variables. A tertiary analysis recursively partitioned a subset of patients in which the status of all genetic markers were known.

Results:

We identified 878 patients with histologically proven high-grade glioma treated with IMRT and 291 patients in our genetic subset. Median overall survival for the entire cohort was 14.2 months (95% confidence interval, 13.1-15.3). Applying the RTOG-RPA to our cohort validated the relative prognostic ordering of the survival classes except class II. Generating our new RPA created 7 significantly different survival classes (P<0.001, χ2=584) with median survival ranging from 96.4 to 2.9 months based on age, histology, O6-methylguanine-DNA methyltransferase methylation status, radiation fractions, tumor location, radiation dose, temozolomide status, and resection status. Our second RPA of our genetic subset generated 5 significantly different survival classes (P<0.001, χ2=166) with survival ranging from 65.3 to 5.6 months based on age, isocitrate dehydrogenase 1 mutation status, O6-methylguanine-DNA methyltransferase methylation status, neurological functional classification, hospitalization during IMRT, temozolomide status, and Karnofsky performance status.

Conclusions:

The RTOG-RPA retains partial prognostic significance, however, should be updated to reflect recent advancements. This series represents a large RPA analyzing both clinical and genetic factors and generated 7 distinct survival classes. Further assessment of patients with fully available genetic markers generated 5 distinct survival classes. These survival classifications need to be validated by a prospective data set and compared against the RTOG-RPA to determine whether they provide improved prognostic power.
PACK-CXL in Reducing the Time to Heal in Suppurative Corneal Ulcers: Observations of a Pilot Study From South India
Authors: Basaiawmoit Priya , Selvin Satheesh Solomon T. , Korah Sanita
Published: June 2018

Purpose:

To assess the usefulness of photoactivated chromophore for infectious keratitis–corneal collagen cross-linking in reducing the time to heal in suppurative corneal ulcers in a South Indian tertiary care center.

Methods:

This was an observational cohort study with 2 arms. In the prospective arm, 13 patients with suppurative corneal ulcers who presented to the outpatient department were recruited. Their ulcers were exposed to ultraviolet-A with riboflavin (B2) (photoactivated chromophore for infectious keratitis–corneal collagen cross-linking) up to a maximum of 4 sittings at 3-day intervals. Topical antimicrobial therapy was continued as per the standard department protocol. This cohort was compared with a retrospective cohort of 32 consecutive patients who had been admitted and treated at our department for a similar profile of ulcers in the previous 1 year.

Results:

The ulcers in the prospective arm had an average healing time of 21.6 days, whereas the retrospective arm had an average healing time of 48.8 days. This reduction in the time to heal trends not only toward being statistically significant (P= 0.06) but also highly clinically significant.

Conclusions:

CXL reduced the time to heal in suppurative corneal ulcers less than 6 mm in diameter and can be used as an adjuvant to antimicrobial therapy.
RIGHTS: Response Initiative Guiding Human Trafficking Services
Authors: Vietor Theresa , Hountz Rosanne
Published: June 2018

Human trafficking, including both sex and labor trafficking, is a global issue affecting 20.9 million people worldwide. The National Human Trafficking Hotline identified 36,270 cases of human trafficking in the United States since 2007. Human trafficking affects every community in the United States, no matter the size. The Sexual Assault Response Team (SART) is a crisis intervention model that has shown improved outcomes for sexual assault victims. The SART approach can be modeled to develop a regional community response to human trafficking to improve outcomes for these victims. Historically, SARTs include collaborative responses between forensic nurses, advocates, law enforcement, and the justice system. Forensic nurses have a unique role in participating in solutions that promote healing for this population. This article discusses the development of a task force and a collaborative response to human trafficking that includes healthcare and forensic nurses. Benefits and challenges will be presented.
Familial impairment of vocal cord mobility in childhood with clubfoot
Authors: Shaw Rebecca , Dias Cristina , Ludemann Jeffrey , Rupps Rosemarie , Tsai Vance , Lehman Anna
Published: June 2018

We report on a family with three siblings, male and female, affected by congenital bilateral limitation of vocal cord abduction, with the additional finding of clubfeet in two. The paternal family history suggests an autosomal dominant inheritance. The siblings and father also have mild craniofacial features, which may be an expression of variability or may be unrelated. The association between congenital vocal cord paralysis and clubfeet has been reported with additional major features or in the context of Charcot-Marie-Tooth disease. However, the two in isolation have only been reported in one other family previously. Genomic analyses of the family, including chromosomal microarray and exome sequencing, showed neither a likely pathogenic variant in a known disease gene nor a compelling candidate gene variant. We propose that the association of these two findings constitutes a novel recognizable phenotype, for which a genetic cause remains undetermined.
Defense Styles Mediate the Association Between Empathy and Burnout Among Nurses
Authors: Fitzgerald-Yau Natasha , Egan Jonathan
Published: June 2018

Research has extensively identified empathic skills as essential in health trainings, policies, and recommendations. However, there have been conflicting views of the impact of empathy on burnout. Some studies contend that empathy serves a protective role, whereas other studies have shown that burnout leads to a diminished capacity to empathize. To date, studies have not yet explored whether defense styles mediate associations between empathy and burnout. A total of 442 nurses completed questionnaire measures of empathy, burnout, and defense mechanisms as part of a large-scale research study on nurse burnout. Findings reflected very high levels of emotional exhaustion and depersonalization among the nursing staff. The nurses in this study endorsed a predominantly immature defense style. In addition, immature defense styles mediated the association between empathy and emotional exhaustion and between empathy and depersonalization. The study provides further knowledge about the role of defense styles in nurse burnout and empathy.
Can Religious Coping and Depressive Symptoms Predict Clinical Outcome and Quality of Life in Panic Disorder? A Brazilian Longitudinal Study
Authors: Zimpel Rogério R. , Panzini Raquel Gehrke , Bandeira Denise Ruschel , Heldt Elizeth , Manfro Gisele Gus , Fleck Marcelo P. , da Rocha Neusa Sica
Published: June 2018

Few studies have investigated the relationship between spiritual/religious coping (S/R coping) and panic disorder (PD). This Brazilian longitudinal study evaluated if S/R coping and depressive symptoms can predict PD remission and improved quality of life (QoL). There were 101 outpatients with PD who were followed up for 12 to 16 weeks. The prevalence ratio (PR) between positive S/R coping and negative S/R coping and PD remission was assessed, as well as the association between positive S/R coping and negative S/R coping and QoL. After adjusting for confounding factors, positive S/R coping presented an inverse PR with PD remission, which was not statistically significant (0.88; p = 0.075). There was no association between S/R coping and QoL. Depressive symptoms were negatively associated with PD remission (PR = 0.97; p < 0.01) and were not predictive of a better QoL.
Types of Trauma, Posttraumatic Stress Disorder, and Academic Performance in a Population of University Students
Authors: Pereira Juliana L. , Guedes-Carneiro Gisela Maria , Netto Liana R. , Cavalcanti-Ribeiro Patrícia , Lira Sidnei , Nogueira José F. , Teles Carlos A. , Koenen Karestan C. , Sampaio Aline S. , Quarantini Lucas C.
Published: June 2018

The aim of this work was to investigate the association between traumatic experiences and posttraumatic stress disorder (PTSD) with the academic performance of university students. This is a one-phase study that included 2213 students, enrolled at one of seven college institutions in their first or final semesters in all programs, who filled out the self-response questionnaires. From this student population, 14% presented with PTSD, with 13.3% in their first semester and 14.9% in their final semester. The students who presented lower academic results (low scoring) had a higher prevalence of PTSD in both the first and final semesters. Nonsexual violence was related with low scoring in the first-semester students. Thus, we conclude that students in the PTSD group present worse academic performance. These results indicate a need to pay attention to students who have been through traumatic experiences and gone on to develop PTSD, to ensure their undergraduate success and enable their future performance as professionals.
Rupture of the Corpus Cavernosum in a Pediatric Patient
Authors: Gruenberg Blake C. , Mortel David , Bogie Amanda
Published: June 2018

Pediatric penile pain is an uncommon complaint and is associated with a wide differential diagnosis including infectious, inflammatory, traumatic, and idiopathic conditions. Penile fractures, anatomically known as rupture of the corpus cavernosum, are almost exclusively reported in sexually mature patients and usually involve forceful manipulation during sexual activity. Rupture of the corpus cavernosum is a true urologic emergency. Failure to recognize and treat rupture of the corpus cavernosum has been associated with residual penile angulation, persistent hematoma, abscess, erectile dysfunction, and fibrosis. We present the case of a previously healthy 7-year-old boy who presented to our emergency department with complaints of penile pain with movement after falling and colliding with staircase railing. Examination showed ecchymosis and swelling of the penile shaft; both testicles were palpable and nontender, with no perineal or scrotal bruising. Ultrasound noted discontinuity along the right corpus cavernosum consistent with a rupture of the right corpus cavernosum. Testicles were noted to be in the scrotum with normal Doppler flow. Flexible cystoscopy revealed an uninjured urethra and bladder. Our patient was urgently taken to the operating room for repair of his injury. Thanks to the timely surgical correction, there were no postsurgical complications, and he was discharged home on postoperative day 1. This case demonstrates that although most reports of corpus cavernosum injuries are associated with sexual intercourse, other modes are possible and should be considered for acute-onset penile pain in pediatric patients.
Factors Related to Surgical Treatment and Outcomes of Thai Patients With Septic Arthritis
Authors: Ruangpin Chonlada , Rodchuae Muchima , Katchamart Wanruchada
Published: June 2018

Objective

The aim of this study was to identify factors associated with the surgical treatment of Thai patients with septic arthritis.

Methods

This cohort study used a university hospital database in Thailand to identify 450 adult patients with confirmed septic arthritis. Data related to baseline characteristics, clinical and laboratory findings, treatment, and outcomes were collected. A multivariate analysis identified the factors related to surgical treatment.

Results

The patients had a mean age (±SD) of 53.6 (±17.8) years, and 51% were male. Surgical drainage was performed on 332 patients (74%). The factors identifed as relating to the need for surgical drainage included preexisting joint disease (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.3–4.9), hip involvement (OR, 36.3; 95% CI, 4.1–320.5), abscess formation (OR, 5.6; 95% CI, 1.1–27.1), osteomyelitis (OR, 4; 95% CI, 1.1–14.9), and positive synovial fluid culture (OR, 3.8; 95% CI, 2–7.2). In contrast, patients who were treated with steroids (OR, 0.2; 95% CI, 0.1–0.4) or had septic shock (OR, 0.31; 95% CI, 0.13–0.83) were less likely to undergo surgery. This model correctly predicted 35% of cases. Patients treated with surgical drainage had a significant longer length of stay (median [interquartile range], 21 [11–34] days vs 14 [7–24] days; p < 0.0001) and were less likely to achieve complete recovery (26% vs 53%, p < 0.0001). However, the mortality rate was lower (2.4% vs 10.2%).

Conclusions

Patients with septic arthritis who had underlying joint disease, hip involvement, abscess formation, osteomyelitis, and organisms in their synovial fluid were more likely to undergo surgical intervention with a significantly prolonged length of stay but had a lower mortality rate.
Blood–Brain Barrier Dysfunction After Smoke Inhalation Injury, With and Without Skin Burn
Authors: Randolph Anita C. , Fukuda Satoshi , Ihara Koji , Enkhbaatar Perenlei , Micci Maria-Adelaide
Published: June 2018

Only a handful of published reports exist today that describe neurological complications following smoke inhalation injury. In this study, we characterize acute pathophysiological changes in the brain of sheep exposed to smoke inhalation, with- and without third-degree skin burn that models the injuries sustained by human victims of fire accidents. Blood–brain barrier integrity and hemorrhage were analyzed throughout the brain using specific histological stains: Hematoxylin & Eosin, Luxol fast blue, Periodic acid–Schiff (PAS), and Martius, Scarlet and Blue (MSB). Our data show that, following smoke inhalation injury, alone and in combination with third-degree skin burn, there was a significant increase in the number of congested and dilated blood vessels in the frontal cortex, basal ganglia, amygdala, hippocampus, pons, cerebellum, and pituitary gland as compared to sham-injured controls. Positive PAS staining confirmed damage to the basement membrane of congested and dilated blood vessels throughout the brain. Severe rupturing of blood vessels, microvascular hemorrhaging and bleeding throughout the brain was also observed in the injured groups. No significant changes in hemodynamics and PaO2 were observed. Our data demonstrate for the first time that acute smoke inhalation alone results in diffuse blood-brain barrier dysfunction and massive bleeding in the brain in the absence of hypoxia and changes in hemodynamics. These findings provide critical information and prompt further mechanistic and interventional studies necessary to develop effective and novel treatments aimed at alleviating CNS dysfunction in patients with smoke and burn injuries.
Priorities Related to Improving Healthcare Safety Through Simulation
Authors: Paige John T. , Terry Fairbanks Rollin J. , Gaba David M.
Published: June 2018

Summary Statement

Improving healthcare safety is a worthwhile and important endeavor. Simulation-based activities can help with such a goal through research and training. In this manner, it can focus on education and training, assessment and metrics, process improvement, and culture change to help move forward both patient safety and quality of care.

This article will address the following three main topics: (1) designing simulation-based activities to promote high reliability in healthcare, (2) developing simulation-based activities to foster resilience in healthcare systems, and (3) evaluating the impact of adverse events in healthcare and how simulation-based activities can be used to determine and potentially to prevent their cause. These topics will be treated sequentially, providing synopses of concepts and giving examples of research currently being undertaken. It will then highlight current priorities for simulation-based research in this domain by drawing from insights obtained and a targeted literature review.
Narrow Band Imaging: A Novel Technique for Immediate Evaluation of Efficacy in Laparoscopic Radiofrequency Ablation of Exophytic Hepatocellular Carcinoma
Authors: Seleem Mohamed , Hassany Mohamed
Published: June 2018

Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality worldwide. Evolution of laparoscopic techniques helps to a great extent in facilitating and replacing the conventional surgical maneuvers. This article describes the novel use of narrow band imaging (NBI) in laparoscopic radiofrequency ablation (LRFA) of exophytic HCC to ensure its adequate ablation. In total, 11 patients with proven HCC were recruited to perform LRFA; NBI were applied during and after completion of ablation session, with NBI, the exophytic HCC appears dark green or blue in color and after start of LRFA; the tumor capsule turned into red color denoting hemoglobin coagulation and vascular damage; in 5 cases and after completion of ablation; the tumor capsule was still dark green or blue denting viability which necessitates needle repositioning and ablation continuation. NBI helps to a great extent in confirmation of successful ablation of exophytic HCC.
Center-driven and Clinically Driven Variation in US Liver Transplant Maintenance Immunosuppression Therapy: A National Practice Patterns Analysis
Authors: Nazzal Mustafa , Lentine Krista L. , Naik Abhijit S. , Ouseph Rosemary , Schnitzler Mark A. , Zhang Zidong , Randall Henry , Dharnidharka Vikas R. , Segev Dorry L. , Kasiske Bertram L. , Hess Gregory P. , Alhamad Tarek , McAdams-Demarco Mara , Axelrod David A.
Published: June 2018

Background

Variation in the use of immunosuppression regimens after liver transplant has not been well described.

Methods

Immunosuppression regimens used after liver transplant were identified in a novel database integrating national transplant registry and pharmacy fill records for 24 238 recipients (2006-2014). Bilevel hierarchical models were developed to quantify the effects of transplant program, recipient, and donor characteristics on regimen choice.

Results

In the first 6 months after transplant, triple immunosuppression (tacrolimus, antimetabolite, corticosteroids) was the most common regimen (42.9%). By months 7 to 12, immunosuppression regimens were more commonly antimetabolite sparing (33.7%) or steroid sparing (26.9%), followed by triple (14.4%), mammalian target of rapamycin inhibitor (mTORi)-based (12.1%), or cyclosporine-based (9.2%). Based on intraclass correlation analysis, clinical characteristics explained less than 10% of the variation in immunosuppression choice, whereas program preference/practice explained 23% of steroid sparing, 26% of antimetabolite sparing, 28% of mTORi, and 21% of cyclosporine-based regimen use. Although case factors were not dominant practice drivers, triple immunosuppression in months 7 to 12 was more common among retransplant recipients and those with prior acute rejection. Hepatocellular carcinoma as cause of liver failure (adjusted odds ratio [aOR], 2.15; P<0.001), cancer within 6 months (aOR, 6.07; P<0.001), and 6-month estimated glomerular filtration rate less than 30 mL/min per 1.3 m2 (aOR, 1.98; P<0.001) were associated with mTORi use compared with triple immunosuppression in months 7 to 12, whereas acute rejection predicted lower use (aOR, 0.72; P=0.003).

Conclusions

Liver transplant immunosuppression is dominantly driven by program preference, but case factors also affect regimen choice. This variation frames a natural experiment for future evaluations of comparative efficacy.
First Scandinavian Protocol for Controlled Donation After Circulatory Death Using Normothermic Regional Perfusion
Authors: Foss Stein , Nordheim Espen , Sørensen Dag W. , Syversen Torgunn B. , Midtvedt Karsten , Åsberg Anders , Dahl Thorleif , Bakkan Per A. , Foss Aksel E. , Geiran Odd R. , Fiane Arnt E. , Line Pål-Dag
Published: June 2018

Background

Donation after circulatory death (DCD) can increase the pool of available organs for transplantation. This pilot study evaluates the implementation of a controlled DCD (cDCD) protocol using normothermic regional perfusion in Norway.

Methods

Patients aged 16 to 60 years that are in coma with documented devastating brain injury in need of mechanical ventilation, who would most likely attain cardiac arrest within 60 minutes after extubation, were eligible. With the acceptance from the next of kin and their wish for organ donation, life support was withdrawn and cardiac arrest observed. After a 5-minute no-touch period, extracorporeal membrane oxygenation for post mortem regional normothermic regional perfusion was established. Cerebral and cardiac reperfusion was prevented by an aortic occlusion catheter. Measured glomerular filtration rates 1 year postengraftment were compared between cDCD grafts and age-matched grafts donated after brain death (DBD).

Results

Eight cDCD were performed from 2014 to 2015. Circulation ceased median 12 (range, 6-24) minutes after withdrawal of life-sustaining treatment. Fourteen kidneys and 2 livers were retrieved and subsequently transplanted. Functional warm ischemic time was 26 (20-51) minutes. Regional perfusion was applied for 97 minutes (54-106 minutes). Measured glomerular filtration rate 1 year postengraftment was not significantly different between cDCD and donation after brain death organs, 75 (65-76) vs 60 (37-112) mL/min per 1.73 m2 (P = 0.23). No complications have been observed in the 2 cDCD livers.

Conclusion

A protocol for cDCD is successfully established in Norway. Excellent transplant outcomes have encouraged us to continue this work addressing the shortage of organs for transplantation.
Extracellular Vesicles promote host immunity during an M. tuberculosis infection through RNA Sensing
Authors: Cheng Yong , Schorey Jeffery S.
Published: June 2018

Extracellular vesicles (EVs) have been shown to carry microbial components and function in the host defense against infections. In this study, we demonstrate that Mycobacterium tuberculosis (M.tb) RNA is delivered into macrophage-derived EVs through an M.tb SecA2-dependent pathway, and that EVs released from M.tb-infected macrophages stimulate a host RIG-I/MAVS/TBK1/IRF3 RNA sensing pathway, leading to type I interferon production in recipient cells. These EVs also promote, in a RIG-I/MAVS-dependent manner, the maturation of M.tb-containing phagosomes through a noncanonical LC3 modification, leading to increased bacterial killing. Moreover, treatment of M.tb-infected macrophages or mice with a combination of moxifloxacin and EVs, isolated from M.tb-infected macrophages, significantly lowered bacterial burden relative to either treatment alone. We propose that EVs, which are preferentially removed by macrophages in vivo, may be developed in combination with effective antibiotics as a novel approach to treat drug-resistant TB.
Oscillations in spontaneous and visually evoked neuronal activity in the superficial layers of the cat’s superior colliculus
Authors: Foik Andrzej T. , Ghazaryan Anaida , Waleszczyk Wioletta J.
Published: June 2018

Oscillations are ubiquitous features of neuronal activity in sensory systems and are considered as a substrate for the integration of sensory information. Several studies have described oscillatory activity in the geniculate visual pathway, but little is known about this phenomenon in the extrageniculate visual pathway. We describe oscillations in evoked and background activity in the cat’s superficial layers of the superior colliculus, a retinorecipient structure in the extrageniculate visual pathway. Extracellular singleunit activity was recorded during periods with and without visual stimulation under isoflurane anesthesia in the mixture of N2O/O2. Autocorrelation, FFT and renewal density analyses were used to detect and characterize oscillations in the neuronal activity. Oscillations were common in the background and stimulus-evoked activity. Frequency range of background oscillations spanned between 5 – 90 Hz. Oscillations in evoked activity were observed in about half of the cells and could appear in two forms – stimulus-phase-locked (10 – 100 Hz), and stimulus-phase-independent (8 – 100 Hz) oscillations. Stimulus-phase-independent and background oscillatory frequencies were very similar within activity of particular neurons suggesting that stimulus-phase-independent oscillations may be a form of enhanced “spontaneous” oscillations. Stimulus-phase-locked oscillations were present in responses to moving and flashing stimuli. In contrast to stimulus-phase-independent oscillations, the strength of stimulus-phase-locked oscillations was positively correlated with stimulus velocity and neuronal firing rate. Our results suggest that in the superficial layers of the superior colliculus stimulus-phase-independent oscillations may be generated by the same mechanism(s) that lie in the base of “spontaneous” oscillations, while stimulus-phase-locked oscillations may result from interactions within the intra-collicular network and/or from a phase reset of oscillations present in the background activity.
How a well-adapting immune system remembers
Authors: Mayer Andreas , Balasubramanian Vijay , Walczak Aleksandra M. , Mora Thierry
Published: June 2018

An adaptive agent predicting the future state of an environment must weigh trust in new observations against prior experiences. In this light, we propose a view of the adaptive immune system as a dynamic Bayesian machinery that updates its memory repertoire by balancing evidence from new pathogen encounters against past experience of infection to predict and prepare for future threats. This framework links the observed initial rapid increase of the memory pool early in life followed by a mid-life plateau to the ease of learning salient features of sparse environments. We also derive a modulated memory pool update rule in agreement with current vaccine response experiments. Our results suggest that pathogenic environments are sparse and that memory repertoires significantly decrease infection costs even with moderate sampling. The predicted optimal update scheme maps onto commonly considered competitive dynamics for antigen receptors.
Nucleosomes around a mismatched base pair are excluded via an Msh2-dependent reaction with the aid of SNF2 family ATPase Smarcad1
Authors: Terui Riki , Nagao Koji , Kawasoe Yoshitaka , Taki Kanae , Higashi Torahiko L. , Tanaka Seiji , Nakagawa Takuro , Obuse Chikashi , Masukata Hisao , Takahashi Tatsuro S.
Published: June 2018

Post-replicative correction of replication errors by the mismatch repair (MMR) system is critical for suppression of mutations. Although the MMR system may need to handle nucleosomes at the site of chromatin replication, how MMR occurs in the chromatin environment remains unclear. Here, we show that nucleosomes are excluded from a >1-kb region surrounding a mismatched base pair in Xenopus egg extracts. The exclusion was dependent on the Msh2–Msh6 mismatch recognition complex but not the Mlh1-containing MutL homologs and counteracts both the HIRA- and CAF-1 (chromatin assembly factor 1)-mediated chromatin assembly pathways. We further found that the Smarcad1 chromatin remodeling ATPase is recruited to mismatch-carrying DNA in an Msh2-dependent but Mlh1-independent manner to assist nucleosome exclusion and that Smarcad1 facilitates the repair of mismatches when nucleosomes are preassembled on DNA. In budding yeast, deletion of FUN30, the homolog of Smarcad1, showed a synergistic increase of spontaneous mutations in combination with MSH6 or MSH3 deletion but no significant increase with MSH2 deletion. Genetic analyses also suggested that the function of Fun30 in MMR is to counteract CAF-1. Our study uncovers that the eukaryotic MMR system has an ability to exclude local nucleosomes and identifies Smarcad1/Fun30 as an accessory factor for the MMR reaction.
Predicting human genes susceptible to genomic instability associated with Alu/Alu-mediated rearrangements
Authors: Song Xiaofei , Beck Christine R. , Du Renqian , Campbell Ian M. , Coban-Akdemir Zeynep , Gu Shen , Breman Amy M. , Stankiewicz Pawel , Ira Grzegorz , Shaw Chad A. , Lupski James R.
Published: June 2018

Alu elements, the short interspersed element numbering more than 1 million copies per human genome, can mediate the formation of copy number variants (CNVs) between substrate pairs. These Alu/Alu-mediated rearrangements (AAMRs) can result in pathogenic variants that cause diseases. To investigate the impact of AAMR on gene variation and human health, we first characterized Alus that are involved in mediating CNVs (CNV-Alus) and observed that these Alus tend to be evolutionarily younger. We then computationally generated, with the assistance of a supercomputer, a test data set consisting of 78 million Alu pairs and predicted ∼18% of them are potentially susceptible to AAMR. We further determined the relative risk of AAMR in 12,074 OMIM genes using the count of predicted CNV-Alu pairs and experimentally validated the predictions with 89 samples selected by correlating predicted hotspots with a database of CNVs identified by clinical chromosomal microarrays (CMAs) on the genomes of approximately 54,000 subjects. We fine-mapped 47 duplications, 40 deletions, and two complex rearrangements and examined a total of 52 breakpoint junctions of simple CNVs. Overall, 94% of the candidate breakpoints were at least partially Alu mediated. We successfully predicted all (100%) of Alu pairs that mediated deletions (n = 21) and achieved an 87% positive predictive value overall when including AAMR-generated deletions and duplications. We provided a tool, AluAluCNVpredictor, for assessing AAMR hotspots and their role in human disease. These results demonstrate the utility of our predictive model and provide insights into the genomic features and molecular mechanisms underlying AAMR.
The optical stretcher as a tool for single-particle X-ray imaging and diffraction
Authors: Nicolas Jan-David , Hagemann Johannes , Sprung Michael , Salditt Tim
Published: June 2018

For almost half a century, optical tweezers have successfully been used to micromanipulate micrometre and sub-micrometre-sized particles. However, in recent years it has been shown experimentally that, compared with single-beam traps, the use of two opposing and divergent laser beams can be more suitable in studying the elastic properties of biological cells and vesicles. Such a configuration is termed an optical stretcher due to its capability of applying high deforming forces on biological objects such as cells. In this article the experimental capabilities of an optical stretcher as a potential sample delivery system for X-ray diffraction and imaging studies at synchrotrons and X-ray free-electron laser (FEL) facilites are demonstrated. To highlight the potential of the optical stretcher its micromanipulation capabilities have been used to image polymer beads and label biological cells. Even in a non-optimized configuration based on a commercially available optical stretcher system, X-ray holograms could be recorded from different views on a biological cell and the three-dimensional phase of the cell could be reconstructed. The capability of the setup to deform cells at higher laser intensities in combination with, for example, X-ray diffraction studies could furthermore lead to interesting studies that couple structural parameters to elastic properties. By means of high-throughput screening, the optical stretcher could become a useful tool in X-ray studies employing synchrotron radiation, and, at a later stage, femtosecond X-ray pulses delivered by X-ray free-electron lasers.
Explaining how leadership and justice influence employee innovative behaviours
Authors: Khaola Peter , Coldwell David
Published: June 2018

Purpose

The mechanisms through which leaders influence innovative work behaviours (IWB) are important in innovation management. The purpose of this paper is to explain how leadership and justice relate to IWB through the successive mediating roles of affective commitment and organisational citizenship behaviour (OCB).

Design/methodology/approach

The study is based on survey of a random sample of 300 employees selected from 652 employees from a public university, and a convenience sample of 159 employees from predominantly service-based enterprises in Lesotho (n=263). The Statistical Package for Social Sciences and the analysis of moment structures version 24 are used to analyse data. Specifically, the study uses factor analysis; correlation; structural equation modelling and bootstrapping techniques to examine the hypothesised relationships.

Findings

The results suggest that the model that fits data well is the one which shows that the effects of both leadership and organisational justice on IWBs are successively mediated by affective commitment and OCB. Because of its social and affiliation-oriented nature, the study submits that OCB is an effective explanatory factor between predictors and IWBs.

Originality/value

The study makes a novel contribution to the extant literature by evaluating the serial mediating roles of affective commitment and OCB between leadership and IWB on one hand, and justice and IWB on the other hand.
Stating the obvious
Authors: Spencer Thomas , Hayden Jo , Murphy Peter , Glennon Russ
Published: June 2018

Purpose

The purpose of this paper is to examine the form, content and reporting arrangements of “statements of assurance” required from Fire and Rescue Authorities in England since their introduction in 2012 and identify potential improvements for future implementation.

Design/methodology/approach

A multi-method approach was adopted which commenced with an analysis of the current official guidance, an exploration of the accessibility and structure of the current statements produced; followed by a review of those statements through a desk based analysis complemented by a series of elite interviews.

Findings

The current guidance was found to be too broad and open to interpretation to be fit for purpose. This has led to some significant variations in reporting, limiting the statements’ usefulness to key users and stakeholders. Most authorities provided some form of report on their website but inconsistencies in respect of length, structure, name and content, limit their value. The research found that 30 per cent of authorities did not have an up to date statement available online. These findings were supported by the series of interviews. The result has led to confusion amongst authorities as to the statement’s role and the risk of it being perceived as a “box ticking” exercise rather than a real contribution to public assurance.

Practical implications

This paper provides potential lessons which could be adopted to inform future guidance in respect of the preparation and publication of the statement of assurance and its role within the wider public assurance regime for fire and rescue authorities. If adopted, these would improve the accountability, transparency and public assurance of Fire and Rescue Authorities which is a key objective of their governance arrangements.

Originality/value

The statement of assurance has only been a requirement of authorities since the current National Framework for Fire and Rescue was published in July 2012 and has not been subject to independent research since its inception. The government have recently issued a consultation on a new national framework, but this proposes changes to the statements of assurance. The findings will therefore be of value to the government, the fire and rescue sector and the recently appointed regulators for the service Her Majesty’s Inspectorate of Constabulary and Fire and Rescue Services.
Does size matter? Hiring discrimination and firm size
Authors: Baert Stijn , De Meyer Ann-Sofie , Moerman Yentl , Omey Eddy
Published: June 2018

Purpose

The purpose of this paper is to study the association between firm size and hiring discrimination against women, ethnic minorities and older job candidates.

Design/methodology/approach

The authors merge field experimental measures on unequal treatment with firm-level data. The resulting data enable the authors to assess whether discrimination varies by indicators of firm size, keeping other firm characteristics constant.

Findings

In contrast with the theoretical expectations, the authors find no evidence for an association between firm size and hiring discrimination. On the other hand, the authors do find suggestive evidence for hiring discrimination being lower in respect of public or non-profit firms (compared to commercial firms).

Social implications

To effectively combat hiring discrimination, one needs to understand its driving factors. In other words, to design adequate policy actions, targeted to the right employers in the right way, one has to gain insight into when individuals are discriminated in particular, i.e. into the moderators of labour market discrimination. In this study, the authors focus on firm size as a moderator of hiring discrimination.

Originality/value

Former contributions investigated this association within the context of ethnic discrimination only and included hardly any controls for other firm-level drivers of discrimination. The authors are the first to study the heterogeneity in discrimination by firm size with respect to multiple discrimination grounds and control for additional firm characteristics.