bluuebunny/crossref_metadata_2025 huggingface dataset:
In search of directionality effectsin the translation processand in the end product
Authors: Whyatt Bogusława
Published: March 2019

This article tackles directionality as one of the most contentious issues in translation studies, still without solid empirical footing. The research presented here shows that, to understand directionality effects on the process of translation and its end product, performance in L2 → L1 and L1 → L2 translation needs to be compared in a specific setting in which more factors than directionality are considered—especially text type. For 26 professional translators who participated in an experimental study, L1 → L2 translation did not take significantly more time than L2 → L1 translation and the end products of both needed improvement from proofreaders who are native speakers of the target language. A close analysis of corrections made by the proofreaders shows that different aspects of translation quality are affected by directionality. A case study of two translators who produced high quality L1 → L2 translations reveals that their performance was affected more by text type than by directionality.
LncRNA POU3F3 promotes proliferation and inhibits apoptosis of cancer cells in triple-negative breast cancer by inactivating caspase 9
Authors: Yang Jun , Meng Xuli , Yu Yong , Pan Lei , Zheng Qinghui , Lin Wei
Published: March 2019

It has been reported that lncRNA POU3F3 was upregulated in esophageal squamous-cell carcinomas, indicating its role as an oncogene in this disease. However, the mechanism of its function and its involvement in other malignancies is unknown. In the present study we found that expression levels of lncRNA POU3F3 were higher in tumor tissues than in adjacent healthy tissues of triple negative breast cancer (TNBC) patients and were significantly and inversely correlated with levels of cleaved caspase 9 only in tumor tissues. In addition, plasma levels of lncRNA POU3F3 were higher in TNBC patients than in healthy controls and were significantly and inversely correlated with levels of cleaved caspase 9 only in TNBC patients. In addition, treatment of exogenous Cleaved Caspase-9 significantly attenuated the effects of lncRNA POU3F3 overexpression on cancer cell proliferation and apoptosis. lncRNA POU3F3 may promote proliferation and inhibit apoptosis of cancer cells in triple-negative breast cancer.
THE POLARIZATION CAPACITY AND RESISTANCE OF VALONIA
Authors: Blinks L. R.
Published: March 2019

On page 685, at the end of the fourth line of the legend for Fig. 4, the sentence should begin "Δr derived" instead of "r derived".

On page 690 in the paragraph beginning in the middle of the page, in the second sentence the reference should be to footnote 12, instead of to footnote 11.
Synthetic 4D-CT of the thorax for treatment plan adaptation on MR-guided radiotherapy systems
Authors: Freedman Joshua N , Bainbridge Hannah E , Nill Simeon , Collins David J , Kachelrieß Marc , Leach Martin O , McDonald Fiona , Oelfke Uwe , Wetscherek Andreas
Published: March 2019

MR-guided radiotherapy treatment planning utilises the high soft-tissue contrast of MRI to reduce uncertainty in delineation of the target and organs at risk. Replacing 4D-CT with MRI-derived synthetic 4D-CT would support treatment plan adaptation on hybrid MR-guided radiotherapy systems for inter- and intrafractional differences in anatomy and respiration, whilst mitigating the risk of CT to MRI registration errors.

Three methods were devised to calculate synthetic 4D and midposition (time-weighted mean position of the respiratory cycle) CT from 4D-T1w and Dixon MRI. The first approach employed intensity-based segmentation of Dixon MRI for bulk-density assignment (sCTD). The second step added spine density information using an atlas of CT and Dixon MRI (sCTDS). The third iteration used a polynomial function relating Hounsfield units and normalised T1w image intensity to account for variable lung density (sCTDSL). Motion information in 4D-T1w MRI was applied to generate synthetic CT in midposition and in twenty respiratory phases. For six lung cancer patients, synthetic 4D-CT was validated against 4D-CT in midposition by comparison of Hounsfield units and dose-volume metrics. Dosimetric differences found by comparing sCTD,DS,DSL and CT were evaluated using a Wilcoxon signed-rank test (p   =  0.05).

Compared to sCTD and sCTDS, planning on sCTDSL significantly reduced absolute dosimetric differences in the planning target volume metrics to less than 98 cGy (1.7% of the prescribed dose) on average. When comparing sCTDSL and CT, average radiodensity differences were within 97 Hounsfield units and dosimetric differences were significant only for the planning target volume D99% metric. All methods produced clinically acceptable results for the organs at risk in accordance with the UK SABR consensus guidelines and the LungTech EORTC phase II trial. The overall good agreement between sCTDSL and CT demonstrates the feasibility of employing synthetic 4D-CT for plan adaptation on hybrid MR-guided radiotherapy systems.
A comparison of low carbon investment needs between China and Europe in stringent climate policy scenarios
Authors: Zhou Wenji , McCollum David L , Fricko Oliver , Gidden Matthew , Huppmann Daniel , Krey Volker , Riahi Keywan
Published: March 2019

The radical change in recent global climate governance calls for China and Europe to ramp up their efforts in leading the world to reach the long-term climate goals. By analyzing the results from the state-of-the-art global integrated assessment model, MESSAGEix-GLOBIOM, this paper aims to understand the future levels of financial investment needed for building and maintaining energy-related infrastructure in the two regions for fulfilling stringent targets consistent with ‘well below 2 °C’. The results indicate that a rapid upscaling and structural change of these investments towards decarbonization are necessitated by the climate stringent scenarios. China and Europe need to increase their low carbon investments by 65% and 38% in a scenario reaching the 2° target relative to their respective reference scenarios which assume no such target from 2016–2050. In a more stringent climate policy scenario of the 1.5° target, these investment needs will increase by 149% and 79% for China and Europe respectively. Among all the energy sectors, energy efficiency, renewable electricity generation and electricity transmission and distribution are the three largest investing targets for the two regions. However, those investments will not likely be realized without strong policy incentives. Implications for green finance and multilateral cooperation initiatives are discussed in the context of the scenario results.
Chronic Treatment With Acetylcholinesterase Inhibitors Attenuates Vascular Dysfunction in Spontaneously Hypertensive Rats
Authors: Lataro Renata M , Silva Marcondes A B , Mestriner Fabiola L , Cau Stefany B A , Tostes Rita C A , Salgado Helio C
Published: March 2019

Background

Acetylcholinesterase inhibition prevents autonomic imbalance, reduces inflammation, and attenuates the development of hypertension. Considering that vascular dysfunction is a crucial feature of arterial hypertension, we investigated the effects of chronic administration of acetylcholinesterase inhibitors—pyridostigmine or donepezil—on vascular reactivity of spontaneously hypertensive rats (SHR).

Methods

Endothelium-dependent relaxant responses to acetylcholine (ACh) and contractile responses induced by electric field stimulation (EFS) and alpha-adrenergic agonist were studied in mesenteric resistance arteries from SHR and Wistar Kyoto rats. SHR were treated for 16 weeks with vehicle, pyridostigmine (1.5 mg/kg/day) or donepezil (1.4 mg/kg/day).

Results

Pyridostigmine and donepezil decreased the vasoconstrictor responses to EFS, which were increased in vehicle-treated SHR. Acetylcholinesterase inhibition increased the modulatory effects of nitric oxide (NO) on SHR vascular reactivity, that is, N(ω)-nitro-(L)-arginine methyl ester (L-NAME) increased EFS-induced contractions and reduced ACh-induced relaxation, with more significant effects in pyridostigmine- and donepezil-treated SHR. The acetylcholinesterase inhibitors also decreased vascular reactive oxygen species levels.

Conclusions

This study demonstrates for the first time that long-term administration of acetylcholinesterase inhibitors, pyridostigmine or donepezil, attenuates vascular reactivity dysfunction in SHR by decreasing reactive oxygen species generation and increasing NO bioavailability; possibly via increased endothelial NO synthase activity, and inhibition of NADPH oxidase activity.
The Glutamine Transporter Slc38a1 Regulates GABAergic Neurotransmission and Synaptic Plasticity
Authors: Qureshi Tayyaba , Sørensen Christina , Berghuis Paul , Jensen Vidar , Dobszay Marton B , Farkas Tamás , Dalen Knut Tomas , Guo Caiying , Hassel Bjørnar , Utheim Tor Paaske , Hvalby Øivind , Hafting Torkel , Harkany Tibor , Fyhn Marianne , Chaudhry Farrukh Abbas
Published: March 2019

GABA signaling sustains fundamental brain functions, from nervous system development to the synchronization of population activity and synaptic plasticity. Despite these pivotal features, molecular determinants underscoring the rapid and cell-autonomous replenishment of the vesicular neurotransmitter GABA and its impact on synaptic plasticity remain elusive. Here, we show that genetic disruption of the glutamine transporter Slc38a1 in mice hampers GABA synthesis, modifies synaptic vesicle morphology in GABAergic presynapses and impairs critical period plasticity. We demonstrate that Slc38a1-mediated glutamine transport regulates vesicular GABA content, induces high-frequency membrane oscillations and shapes cortical processing and plasticity. Taken together, this work shows that Slc38a1 is not merely a transporter accumulating glutamine for metabolic purposes, but a key component regulating several neuronal functions.
Genome-wide DNA methylation profiling identifies convergent molecular signatures associated with idiopathic and syndromic autism in post-mortem human brain tissue
Authors: Wong Chloe C Y , Smith Rebecca G , Hannon Eilis , Ramaswami Gokul , Parikshak Neelroop N , Assary Elham , Troakes Claire , Poschmann Jeremie , Schalkwyk Leonard C , Sun Wenjie , Prabhakar Shyam , Geschwind Daniel H , Mill Jonathan
Published: March 2019

Autism spectrum disorder (ASD) encompasses a collection of complex neuropsychiatric disorders characterized by deficits in social functioning, communication and repetitive behaviour. Building on recent studies supporting a role for developmentally moderated regulatory genomic variation in the molecular aetiology of ASD, we quantified genome-wide patterns of DNA methylation in 223 post-mortem tissues samples isolated from three brain regions [prefrontal cortex, temporal cortex and cerebellum (CB)] dissected from 43 ASD patients and 38 non-psychiatric control donors. We identified widespread differences in DNA methylation associated with idiopathic ASD (iASD), with consistent signals in both cortical regions that were distinct to those observed in the CB. Individuals carrying a duplication on chromosome 15q (dup15q), representing a genetically defined subtype of ASD, were characterized by striking differences in DNA methylationacross a discrete domain spanning an imprinted gene cluster within the duplicated region. In addition to the dramatic cis-effects on DNA methylation observed in dup15q carriers, we identified convergent methylomic signatures associated with both iASD and dup15q, reflecting the findings from previous studies of gene expression and H3K27ac. Cortical co-methylation network analysis identified a number of co-methylated modules significantly associated with ASD that are enriched for genomic regions annotated to genes involved in the immune system, synaptic signalling and neuronal regulation. Our study represents the first systematic analysis of DNA methylation associated with ASD across multiple brain regions, providing novel evidence for convergent molecular signatures associated with both idiopathic and syndromic autism.
Honesty, Social Presence and Self-Service in Retail
Authors: Siebenaler Susan , Szymkowiak Andrea , Robertson Paul , Johnson Graham I , Law Jan , Fee Kenneth
Published: March 2019

Retail self-service checkouts (SCOs) can benefit consumers and retailers, providing control and autonomy to shoppers independent from staff. Recent research indicates that the lack of presence of staff may provide the opportunity for consumers to behave dishonestly. This study examined whether a social presence in the form of visual, humanlike SCO interface agents had an effect on dishonest user behaviour. Using a simulated SCO scenario, participants experienced various dilemmas in which they could financially benefit themselves undeservedly. We hypothesized that a humanlike social presence integrated within the checkout screen would receive more attention and result in fewer instances of dishonesty compared to a less humanlike agent. Our hypotheses were partially supported by the results. We conclude that companies adopting self-service technology may consider the implementation of social presence to support ethical consumer behaviour, but that more research is required to explore the mixed findings in the current study.

Research Highlights

A method by Vohs and Schooler (2008) was adapted for investigating dishonesty. Social presence is proposed as a mediator for dishonest behaviour. There is scope for social presence to influence user behaviour in a world that increasingly relies on self-service transactions. The effectiveness of measures of dishonesty needs to be researched further.
Short-lived Parliamentarisation in 19th-century Germany: Parliamentary Government in the Frankfurt Assembly of 1848/1849
Authors: Sieberer Ulrich , Herrmann Michael
Published: March 2019

The article shows that Germany established a short-lived but fully operative parliamentary system of government in its first democratically elected national parliament in 1848—some 70 years earlier than usually assumed. Qualitative evidence shows that the cabinet was responsible to the assembly and that parliamentary majorities forced cabinets to resign. Roll-call analysis reveals behavioural patterns that are typical for parliamentary government such as high party unity, cohesive voting by the governing coalition and substantially higher success rates for cabinet parties. These findings challenge claims of a ‘German exceptionalism’ and demonstrate the danger of hindsight bias in reading historical processes of parliamentarisation backwards. Instead, they suggest that successful parliamentarisation critically depends on the balance of power between democratic and autocratic forces and the degree to which old elites can be integrated in the new democratic order.
Evaluation of a clinical protocol using intranasal fentanyl for treatment of vaso-occlusive crisis in sickle cell patients in the emergency department
Authors: Paquin Hugo , Trottier Evelyne D , Pastore Yves , Robitaille Nancy , Dore Bergeron Marie-Joelle , Bailey Benoit
Published: March 2019

Background

Vaso-occlusive crisis (VOC) is one of the most frequent causes of emergency visits and admission in children with sickle cell disease (SCD).

Objectives

This study aims to evaluate whether the use of a new pain management pathway using intranasal (IN) fentanyl from triage leads to improved care, translated by a decrease in time to first opiate dose.

Methods

We performed a retrospective chart review of patients with SCD who presented to the emergency department (ED) with VOC, in the period pre- (52 patients) and post- (44 patients) implementation period of the protocol. Time to first opiate was the primary outcome and was evaluated pre- and postimplementation. Patients received a first opiate dose within 52.3 minutes of registration (interquantile range [IQR] 30.6, 74.6), corresponding to a 41.4-minute reduction in the opiate administration time (95% confidence interval [CI] −56.1, −27.9). There was also a 43% increase in the number of patients treated with a nonintravenous (IV) opiate as first opiate dose (95% CI 26, 57). In patients who were discharged from the ED, there was a 49% decrease in the number of IV line insertions (95% CI −67, −22). There was no difference in the hospitalization rates (difference of 6 [95% CI −13, 25]).

Conclusions

This study validates the use of our protocol using IN fentanyl as first treatment of VOC in the ED by significantly reducing the time to first opiate dose and the number of IVs.
Diversity, Prevalence, and Virulence ofColletotrichumSpecies Associated with Lima Bean in Brazil
Authors: Cavalcante Gerusa R. S. , Barguil Beatriz M. , Vieira Willie A. S. , Lima Waléria G. , Michereff Sami J. , Doyle Vinson P. , Câmara Marcos P. S.
Published: March 2019

Anthracnose is one of the most important diseases of lima bean in Brazil. Previously, the disease was attributed exclusively to Colletotrichum truncatum. Therefore, this work aimed to characterize the diversity, prevalence, and virulence of Colletotrichum spp. associated with anthracnose in lima bean in Brazil. Here, we report the species C. truncatum, C. brevisporum, C. lobatum, C. plurivorum, and C. musicola in association with anthracnose of lima bean. All species were pathogenic to lima bean. In addition, several strains were found that represent novel lineages, presented here as Colletotrichum lineages 1 to 5. C. truncatum is the prevailing species and more virulent than all other species studied.
Prevalence and Predictive Factors of Concurrent Cervical Spinal Cord Compression in Adult Spinal Deformity
Authors: Shimizu Takayoshi , Lehman Ronald A. , Pongmanee Suthipas , Alex Sielatycki J. , Leung Eric , Riew K. Daniel , Lenke Lawrence G.
Published: March 2019

Study Design.

Retrospective cross-sectional cohort.

Objective.

To investigate the prevalence and predictive factors of concurrent cervical spinal cord compression (CSCC) in patients with adult spinal deformity (ASD).

Summary of Background Data.

In patients with ASD undergoing major thoracolumbar realignment surgery, concurrent CSCC potentially increases the risk of progression of myelopathy or cervical cord injury due to various perioperative factors including poor intraoperative neck positioning and hypotension. However, the prevalence of CSCC in ASD patients has not been previously studied.

Methods.

This study included ASD patients who were indicated for major thoracolumbar corrective surgery (>5 levels). The presence of CSCC was determined using the modified Cord Compression Index (Grades 0–3) based on the cervical magnetic resonance imaging (MRI). Significant CSCC was defined as Grade>2, and the distribution of compression level as well as the number of Grade>2 segments were investigated in each patient. A multivariate regression analysis was performed to identify the predictors of CSCC with variables being the patients’ characteristics including radiographic sagittal alignment parameters.

Results.

Of 121 patients with ASD, 41 patients (33.8%) demonstrated significant CSCC on MRI. Intramedullary T2 hyper-intensity (myelomalacia) was present in eight patients (6.6%). Thirty-five of 41 patients were asymptomatic or with myelopathy that is difficult to detect. Significant CSCC was most commonly observed at C4/5 level. Four patients (3.3%) underwent cervical decompression and fusion prior to thoracolumbar reconstruction. Multivariate regression analysis revealed old age, increased body mass index (BMI), and PI-LL mismatch independently predicted the CSCC grade.

Conclusion.

The prevalence of concurrent significant cervical cord compression in patients with ASD is relatively high at 33.8%. Preoperative evaluation of cervical MRI and examinations for signs/symptoms of myelopathy are essential for patients with (1) older age, (2) increased BMI, and (3) high PI-LL mismatch to avoid progressive myelopathy or cord injury during ASD surgery.

Level of Evidence: 4
The Change in Sway and Neuromuscular Activity in Adult Degenerative Scoliosis Patients Pre and Post Surgery Compared With Controls
Authors: Haddas Ram , Lieberman Isador H.
Published: March 2019

Study Design.

Prospective cohort study.

Objective.

The purpose of this study is to quantify the extent of change in sway associated with maintaining a balanced posture within the cone of economy (CoE), in a group of adult degenerative scoliosis (ADS) patients’ pre and postsurgery and compare them to matched non-scoliotic controls.

Summary of Background Data.

Patients with spinal deformities adopt a variety of postural changes in the spine, pelvis, and lower extremities in their effort to compensate for the anterior shift in the gravity line. ADS patients are known to exhibit an increased sway within their CoE. Greater sway expends more energy while standing when compared with healthy controls. Spinal alignment surgery has been shown to improve sagittal vertical axis and balance.

Methods.

Thirty-three ADS patients and performed a series of functional balance tests a week before and 3 months after surgery along with 20 non-scoliotic control.

Results.

ADS patients demonstrated more initial CoM (P = 0.001) and head (P = 0.011) displacements. Postoperatively ADS patients exhibited less CoM sway (P = 0.043) and head sway (P = 0.050), in comparison to their presurgery measures. Postsurgical ADS patients demonstrated more CoM (P = 0.002) and head (P = 0.012) displacements and increased muscle activity in comparison to non-scoliotic controls.

Conclusion.

Surgical alignment reduced the amount of sway, reduced the center of mass displacement, and reduced spine and lower extremity energy expenditure in ADS’ patients. In symptomatic preoperative ADS patients, sagittal sway increased along with greater lumbar spine and lower extremity neuromuscular activity in comparison to a non-scoliotic control. Although surgical alignment improved ADS functional parameters during a dynamic balance test, these parameters approached but did not fully achieve non-scoliotic control parameters when measured 3 months after surgery.

Level of Evidence: 3
Edaravone prevents memory impairment in an animal model of post-traumatic distress
Authors: Alzoubi Karem H. , Shatnawi Alaa , Al-Qudah Mohammad A. , Alfaqih Mahmoud A.
Published: March 2019

Post-traumatic stress disorder (PTSD) is a mental health problem that develops in a proportion of individuals after experiencing a potential life-threatening traumatic stress event. Edaravone is a free radical scavenger, with a neuroprotective effect against cognitive impairment in several animal models. In the present study, the protective effect of edaravone on PTSD-induced memory impairment was investigated. Single prolonged stress was used as an animal model of PTSD, comprising 2 h of restrain, 20-min forced swimming, 15-min rest, and 1–2-min diethyl ether exposure. Concurrently, edaravone was given at a dose of 6 mg/kg/day, intraperitoneally, for 21 days. The radial arm water maze was used to assess learning and memory. Antioxidant biomarkers were measured in hippocampus tissues. Chronic administration of edaravone prevented impairment of short-term and long-term memory. Edaravone also prevented the stress-induced decrease in the ratio of reduced glutathione/oxidized glutathione and the activities of glutathione peroxidase and catalase enzymes in the hippocampus, as well as increases in the levels of oxidized glutathione and thiobarbituric acid reactive substances. In conclusion, edaravone ameliorated oxidative stress and cognitive impairment associated with a PTSD model, probably by supporting antioxidant mechanism in the hippocampus.
Long-Term Wound Palliation to Manage Exposed Hardware in the Setting of Peripheral Arterial Disease
Authors: Zamani Nader , Barshes Neal R.
Published: March 2019

Exposed orthopedic hardware in the lower extremity complicated by peripheral arterial disease typically demands multiple operative procedures by several disciplines to maintain skeletal integrity and achieve complete wound healing. For ambulatory patients that are either not candidates for lower extremity revascularization or prefer not to pursue surgical attempts at limb preservation, wound palliation is a potential management strategy. We discuss a patient with a history of severe peripheral arterial disease and a left pilon fracture previously treated with open reduction and internal fixation. He presented with a 2-month history of open wounds and exposed hardware over his left tibia. Though he initially underwent surgical revascularization to improve circulation to his lower extremity, the arterial bypass occluded within 6 months of the operation. At that point, the patient decided to forego any additional surgical intervention, including hardware removal, in favor of local wound care and expectant management. Remarkably, the wound remained stable in size over the next 14 years, he remained ambulatory, and never developed a deep wound infection. Though palliative wound care alone is understandably not the recommended first-line therapy for managing nonhealing wounds, it may be a safe and potentially durable alternative to major lower extremity amputation when revascularization and soft-tissue coverage cannot be achieved.
Iodine Deficiency and Supplementation in Pregnancy
Authors: CHITTIMOJU SANJITA B. , PEARCE ELIZABETH N.
Published: March 2019

Iodine deficiency during pregnancy is an important global public health issue and the leading preventable cause of neurodevelopmental impairments worldwide. The effects of severe iodine deficiency during pregnancy, including adverse obstetric outcomes and decreased child intelligence quotient, have been clearly established. However, the effects of mild-to-moderate deficiency remain less well understood. Pregnant and lactating women have higher iodine requirements than other adults; intakes of 220 to 250 µg/d in pregnancy and 250 to 290 µg/d in lactation. In this article, we describe iodine metabolism, iodine requirements in pregnancy and lactation, the effects of both iodine deficiency and excessive iodine intakes in pregnancy, and the efficacy of iodine supplementation.
Evaluation of Chemokine mRNA Expression to Assess Allergic Inflammation of the Ocular Surface in Chronic Allergic Conjunctival Diseases
Authors: Aso Hiroshi , Shoji Jun , Shiraki Yukiko , Inada Noriko , Yamagami Satoru
Published: March 2019

Purpose:

We validated the use of chemokine messenger RNA (mRNA) expression analysis for the assessment of ocular surface allergic inflammation in chronic allergic conjunctival diseases (ACDs) with proliferative lesions, including giant papillae and gelatinous infiltration of the limbus.

Methods:

This prospective sectional study included 19 patients with chronic ACDs and 10 healthy volunteers as controls. Patients with chronic ACDs were divided into 2 subgroups according to the severity of the clinical score: active stage ACD subgroup (n = 9) and stable stage ACD subgroup (n = 10). Impression cytology using a filter paper for each upper tarsal conjunctiva of the patients with chronic ACDs and control subjects was performed, and the expression levels of IL1A, CXCL8, IL16, and CCL24 mRNAs encoding interleukin (IL)-1α, CXCL8/IL-8, IL-16, and CCL24/eotaxin-2, respectively, were determined by quantitative real-time polymerase chain reaction using impression cytology specimens.

Results:

CCL24 and IL16 mRNA levels in the active ACD subgroup were significantly higher than those in the control group (P = 0.003 and 0.004, respectively). IL1A and CXCL8 expression levels in the active ACD subgroup were significantly higher than those in the stable ACD (P = 0.008 and 0.029, respectively) and control (P = 0.008 and 0.014, respectively) subgroups. Furthermore, significant correlations were detected between IL16 and CCL24 mRNA levels (r = 0.76, P = 0.0001) and between IL1A and CXCL8 (r = 0.67, P = 0.0004).

Conclusions:

At least 2 kinds of inflammatory reactions, IL-1α- and CXCL8-associated inflammation and CCL24- and IL-16-associated inflammation, may be involved in the exacerbation of chronic ACDs.
Education Empowers Emergency Department Nurses During Pediatric Traumas
Authors: Tracy Brett , Ott Mickey , Hamrick Miller , Bailey Kathryn
Published: March 2019

In January 2017, the Emergency Trauma Advocate (ETA) program was piloted at our Level 1 trauma center to promote patient advocacy, particularly in pediatric patients. The goal was to empower emergency department nurses by improving their knowledge base through interactive didactic sessions. This study reviews the preliminary findings of the program. Surveys were administered after each teaching session to participating ETA nurses to determine their personal academic interests and how to improve the program. We then performed a retrospective review of pediatric trauma admissions from January 2017 through April 2017 to delineate the most common injury patterns. Survey responses demonstrated the greatest nursing interest in learning critical care (n = 11), orthopedic management (n = 11), and neurosurgical trauma education (n = 9). During this study period, 113 pediatric patients arrived and had a mean age of 7.8 ± 5.2 years. The most common injury patterns were orthopedic (n = 38) and neurosurgical (n = 28), and 35 patients required critical care management. Bivariate analysis revealed a significant and positive relationship between injury frequency and educational interests (R
2 = 98.8%, p = .0057). A nurse's interest in educational topics directly correlates with recent pediatric trauma injury patterns. Future work should focus on determining what impact the ETA program has had on pediatric outcomes.
Building a Case for Pediatric Fall Prevention
Authors: Lombard Kimberly J. , Elsbernd Terri A. , Bews Katherine A. , Klinkner Denise B.
Published: March 2019

Falls are the leading cause of traumatic injury and injury-related emergency department visits in the state of Minnesota for children aged 0–14 years. We hypothesize that few of the Minnesota trauma centers and public health departments responsible for injury prevention (IP) efforts in the community are focusing on fall prevention interventions for children. The purpose of this study was to examine the current state of childhood IP interventions in Minnesota, identify potential partners to collectively address pediatric fall prevention, and utilize survey results to lead future IP efforts. An electronic survey was administered to state/American College of Surgeons verified trauma center and county health department staff in Minnesota. We compared opinions related to leading causes of traumatic injury, current IP efforts, data sources used to prioritize IP efforts, barriers to implementing childhood fall prevention interventions, and partnerships among trauma centers and health departments. Completed surveys were analyzed, with 37 responses from trauma centers and 25 from county health departments. On the basis of opinion, 47% of trauma center staff listed falls as the number one cause of traumatic injury to children compared with 25% of health department staff. Eighteen percent of survey respondents report that they have, or are, providing fall prevention programing. Limited resources were listed as the leading barrier. Significant variation exists regarding opinions related to the leading cause of pediatric traumatic injury. The feedback generated from this survey will be shared with Minnesota stakeholders in an effort to encourage collective action toward fall prevention interventions for Minnesota children.
Influence of Autopsy Reports on Trauma Registry Accuracy
Authors: Santos Adora Tricia , Sang Whiyie , Nugent William
Published: March 2019

The trauma registry is a locally maintained database with information on all trauma patients, including patient demographics and injury data. One essential field is the injury severity score (ISS). Patients who expire on arrival, either in the emergency department or soon after, often cannot undergo a complete evaluation of their injuries. As a result, many injuries remain undiagnosed, resulting in an erroneously low ISS, and autopsies can identify these unrecognized injuries. The objective of this study was to determine whether and how autopsy data improve the accuracy of the trauma registry data. The population included in the study was seen in the emergency department between January 2014 and August 2017 after a traumatic injury who expired on arrival, while in the ED, or within 48 hr of arrival. The ISS of each case was calculated prior to autopsy report and then adjusted according to autopsy data. The magnitude of this change was then compared. The mean ISS of these cases without autopsy data was 13, whereas the mean ISS of these cases including autopsy data was 49 (p ≤ .001). The mean ISS without autopsy data in those who died before and after 15 min was 7 and 23, respectively. In comparison, the mean autopsy-adjusted ISS in those who died before and after 15 min was 50 and 39, respectively (p ≤ .001). Our study identified the importance of obtaining autopsies in trauma patients. Having accurate registry data for trauma deaths further guides the development of performance improvement, injury prevention, and trauma research.
Living or deceased donor kidney transplantation in children
Authors: Sigurjonsdottir Vaka Kristin , Grimm Paul Charles
Published: March 2019

Purpose of review

Kidney transplantation is the preferred treatment modality for children with end-stage renal disease. In this review, we discuss the factors affecting the selection of the appropriate donor to ensure the best possible short and long-term outcomes.

Recent findings

Outcomes of pediatric renal transplantation from living donors are superior to those obtained from deceased donors. Despite this, the rate of living donor kidney transplantation has declined over the last decade. Living donation is considered to be safe but long-term outcomes, especially for parents who are often young donors, are not well understood. Living donation can also cause a financial impact to the donor and family. Barriers to living donation must be sought and defeated. Deceased donor organs are now the primary source of kidneys. How the risk of extended time on dialysis must be weighed against the improved outcomes that may accrue from better matching is controversial. Increasing the donor pool may be accomplished by reassessing sources that are currently avoided, such as donation after cardiac death and infant kidneys transplanted en bloc.

The pediatric nephrologist must balance waiting for the highest quality kidney against the need for the shortest possible waiting time.
Chimeric antigen receptor T-cell toxicity
Authors: Baymon DaMarcus E. , Boyer Edward W.
Published: March 2019

Purpose of review

Chimeric antigen receptor -(CAR) T-cell therapy has become a commonly used immunotherapy originally used in the treatment of B-cell leukemias but which are now applied broadly across tumor classes. Although high rates of remission are associated with CAR T-cell therapy, toxicities associated with these novel treatment regimens can be lethal if not recognized in a timely manner.

Recent findings

Cytokine release syndrome and neurotoxicity are the two most common toxicities associated with CAR T-cell therapy. Cytokine release syndrome is characterized by a flu-like illness accompanied by significant hemodynamic instability; treatments include administration of tocilizumab and corticosteroids. Neurotoxicity is associated with nonpattern-specific neurological changes and can rapidly progress to a comatose state from cerebral edema and death. Other potential toxicities from CAR T-cell therapy include tumor lysis syndrome, B-cell aplasia, graft versus host disease, and dermatological eruptions.

Clinical awareness of CAR T-cell toxicities is important because prompt treatment leads to improved survival and remission rates.
A Pilot to Improve the Pain Medication Education Experience in Hospice
Authors: Hay Brittany B. , Marcelin Jackie N. , Buck Harleah G.
Published: March 2019

Pain is one of the most feared symptoms experienced by patients at the end of life and one of the most difficult to manage. Families identify patient comfort as a priority in hospice, yet many have concerns regarding pain management and medication side effects. Timely, open, and ongoing communication with hospice teams can assuage concerns to improve care and outcomes relevant to pain medication use in hospice. A pilot project was undertaken to improve the patient and family/caregiver experience in end-of-life care relevant to communication regarding pain medication side effects and management within an inpatient hospice. A 5% improvement in the Consumer Assessment of Healthcare Providers & Services (CAHPS) Hospice quality indicator 18 (Understanding Side Effects) was sought. An evidence-based, interprofessional educational protocol and tool were designed and implemented to guide pertinent conversations. A 6.6% increase in favorable responses to the CAHPS Hospice target indicator occurred over the course of the pilot. Feedback from staff revealed positive responses to the tool with recommended expansion of use across hospice settings. Educational programming holds promise to support communication with hospice patients and families regarding pain medication side effects and management to improve experiential care quality as reflected in CAHPS Hospice surveys.
Planting the Seeds
Authors: Hagwood Dell N. , Larson Kim L.
Published: March 2019

Latinos are less likely to have an advance care plan, use hospice or palliative care services, and have conversations about end of life than the general population. This article describes processes and outcomes of a Latino lay health advisor advance care planning training program in eastern North Carolina. An exploratory case study was used to understand the perspectives of Latino leaders. Two Latino leaders completed an advance care planning training in 2016. Data were generated from field notes, interviews, and observations. A description of the social and contextual conditions in the study setting facilitated data analysis. The primary finding, “planting the seeds,” was the strategy that began the conversation of advance care planning. “Planting the seeds” meant introducing the topic carefully to ensure the person is ready to listen, the information will be accepted, and capacity will be gained to make informed decisions. Training Latino lay health advisors in advance care planning has the potential to eliminate health disparities.
PGR Gene Fusions Identify a Molecular Subset of Uterine Epithelioid Leiomyosarcoma With Rhabdoid Features
Authors: Chiang Sarah , Samore Wesley , Zhang Lei , Sung Yun-Shao , Turashvili Gulisa , Murali Rajmohan , Soslow Robert A. , Hensley Martee L. , Swanson David , Dickson Brendan C. , Stewart Colin J.R. , Oliva Esther , Antonescu Cristina R.
Published: March 2019

Genetic aberrations among uterine epithelioid leiomyosarcomas are unknown. Following identification of an index case withNR4A3-PGRfusion demonstrating monomorphic morphologic features, we interrogated additional uterine tumors demonstrating similar histology and sought to describe the morphologic and immunohistochemical characteristics ofPGR-rearranged sarcomas. Targeted next-generation RNA sequencing was performed on RNA extracted from formalin-fixed paraffin-embedded tissue of the index case. Fluorescence in situ hybridization using custom probes flankingPGRandNR4A3genes was applied to 17 epithelioid leiomyosarcomas, 6 endometrial stromal tumors, and 3 perivascular epithelioid cell tumors.NR4A3-PGRfusion (n=4) andPGRrearrangement (n=2) were detected in 6 (35%) epithelioid leiomyosarcomas. Median patient age was 45 years, and all presented with FIGO stage I or II tumors, 2 being alive with disease at 75 and 180 months. All tumors were centered in the cervical stroma or myometrium and consisted of cells with abundant eosinophilic cytoplasm (epithelioid), including many displaying dense intracytoplasmic inclusions (rhabdoid). Myxoid matrix and hydropic change imparted a microcystic growth pattern in 4 tumors. Five also showed a minor spindle cell component which was low-grade in 3, consisting of bland spindle cells with low mitotic activity. High-grade spindle cell morphology was seen in 2 tumors, exhibiting a storiform pattern of atypical spindle cells associated with brisk mitotic activity. Desmin, estrogen receptor, and progesterone receptor were positive in all 6 tumors, while CD10 and HMB45 were negative.PGRrearrangements define a genetic subset of epithelioid leiomyosarcomas with often biphasic morphology consisting of epithelioid and rhabdoid as well as spindle cell components.
A Proposal to Revise the Histopathologic Grading System of Early Oral Tongue Cancer Incorporating Tumor Budding
Authors: Elseragy Amr , Salo Tuula , Coletta Ricardo D. , Kowalski Luiz P. , Haglund Caj , Nieminen Pentti , Mäkitie Antti A. , Leivo Ilmo , Almangush Alhadi
Published: March 2019

The World Health Organization (WHO) grading system has a low prognostic value for early-stage oral tongue squamous cell carcinoma; greater prognostic power has been shown with tumor budding analysis. In this study, we combined tumor budding analysis with histopathologic grading according to WHO 2017. In our proposal, a revised grade I tumor is defined as a “well differentiated cohesive tumor”; revised grade II as a “moderately differentiated and/or slightly dissociated tumor”; and revised grade III as a “poorly differentiated and/or dissociated tumor.” We evaluated the prognostic value of this proposed grading system in a multicenter cohort of 311 cases of early oral tongue squamous cell carcinoma. The proposed grading system showed significant prognostic value in multivariable analysis for disease-specific survival with a hazard ratio of 3.86 and a 95% confidence interval of 1.36-10.9 (P=0.001). For disease-free survival, the proposed grading system showed good predictive power in multivariable analysis (hazard ratio, 2.07; 95% confidence interval, 1.00-4.27; P=0.009). The conventional WHO grading system showed a low prognostic value for disease-specific survival and disease-free survival (P>0.05). In conclusion, the prognostic power of the WHO histopathologic grading improved significantly with incorporation of tumor budding. Our proposed grading system can be easily included in pathology reports.
Perineal Assessment Tool (PAT-C)
Authors: Li Yi-Min , Lee Henry Hsin-Chung , Lo Yu-Ling , Chao Hui-Lin
Published: March 2019

PURPOSE:

The purpose of this study was to evaluate content validity and feasibility of the Chinese language perineal assessment tool (PAT-C), to assess its use in the clinical setting, and establish an optimal cut point for identifying patients at high risk for incontinence-associated dermatitis (IAD).

DESIGN:

Psychometric evaluation of existing instrument.

SUBJECTS AND SETTING:

The sample comprised 440 patients managed in intensive care units of 3 hospitals across the island of Taiwan and an affiliated home care service. One hundred three nurses practicing throughout Taiwan participated in the workshops in the third phase of the experiment.

METHODS:

The content validity of the PAT-C was evaluated by 3 experienced nurses using the content validity index statistic. We calculated a receiver operating characteristics (ROC) curve to determine a cut point of high-risk IAD. The curve was based on assessment of patients from receiving care from the intensive care unit and home care service of Cathay General Hospital (located in Taipei, New Paipei and Hsinchu). Nurse perceptions on the feasibility of PAT-C were assessed using an investigator-developed survey.

RESULTS:

Three experienced nurses rated the PAT-C and gave a robust overall content validity index score of 97.22%. The cut point for identifying patients at high risk for developing IAD via ROC curve analysis of 440 patients was 7.5 (sensitivity: 0.85; specificity: 0.79, area under curve: 0.82, P value < .001). One hundred three enrolled nurses attended the workshops and evaluated the feasibility using the PAT-C. Most of the participants considered the PAT-C as necessary (97.90%), 49.7% of participants suggested IAD risk assessment should be implemented by first-line (generalist) nurses, and 40% of participants recommended assessment on a daily basis.

CONCLUSIONS:

Study findings indicate robust content validity, and results of the investigator survey of nurse perceptions of the PAT-C indicate the potential for its widespread use in the clinical setting. We found that a cut point score 8 or more indicates a high risk for developing IAD.
Whisking asymmetry signals motor preparation and the behavioral state of mice
Authors: Dominiak Sina E. , Nashaat Mostafa A. , Sehara Keisuke , Oraby Hatem , Larkum Matthew E. , Sachdev Robert N.S.
Published: March 2019

A central function of the brain is to plan, predict and imagine the effect of movement in a dynamically changing environment. Here we show that in mice head fixed in a plus-maze, floating on air, and trained to pick lanes based on visual stimuli, the asymmetric movement and position of whiskers on the two sides of the face signals whether the animal is moving, turning, expecting reward or licking. We show that 1) we can decode and predict the behavioral state of the animal based on this asymmetry, 2) that tactile input from whiskers indicates little about the behavioral state, and 3) that movement of the nose correlates with asymmetry, indicating that facial expression of the mouse is itself correlated with behavioral state. Amazingly, the movement of whiskers – a behavior that is not instructed or necessary in the task--informs an observer about what a mouse is doing in the maze. Thus, these mobile tactile sensors reflect a behavioral and movement-preparation state of the mouse.
The evolutionary dynamics and fitness landscape of clonal haematopoiesis
Authors: Watson Caroline J. , Papula Alana , Poon Yeuk P. G. , Wong Wing H. , Young Andrew L. , Druley Todd E. , Fisher Daniel S. , Blundell Jamie R.
Published: March 2019

Somatic mutations acquired in healthy tissues as we age are major determinants of cancer risk. Whether variants confer a fitness advantage or rise to detectable frequencies by chance, however, remains largely unknown. Here, by combining blood sequencing data from ∼50,000 individuals, we reveal how mutation, genetic drift and fitness differences combine to shape the genetic diversity of healthy blood (‘clonal haematopoiesis’). By analysing the spectrum of variant allele frequencies we quantify fitness advantages for key pathogenic variants and genes and provide bounds on the number of haematopoietic stem cells. Positive selection, not drift, is the major force shaping clonal haematopoiesis. The remarkably wide variation in variant allele frequencies observed across individuals is driven by chance differences in the timing of mutation acquisition combined with differences in the cell-intrinsic fitness effect of variants. Contrary to the widely held view that clonal haematopoiesis is driven by ageing-related alterations in the stem cell niche, the data are consistent with the age dependence being driven simply by continuing risk of mutations and subsequent clonal expansions that lead to increased detectability at older ages.