bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing door-to-needle times in stroke thrombolysis to 13 min through protocol revision and simulation training: a quality improvement project in a Norwegian stroke centre
Authors: Ajmi Soffien Chadli , Advani Rajiv , Fjetland Lars , Kurz Kathinka Dehli , Lindner Thomas , Qvindesland Sigrunn Anna , Ersdal Hege , Goyal Mayank , Kvaløy Jan Terje , Kurz Martin 
Published: June 2019

BackgroundIn eligible patients with acute ischaemic stroke, rapid revascularisation is crucial for good outcome. At our treatment centre, we had achieved and sustained a median door-to-needle time of under 30 min. We hypothesised that further improvement could be achieved through implementing a revised treatment protocol and in situ simulation-based team training sessions. This report describes a quality improvement project aiming to reduce door-to-needle times in stroke thrombolysis.MethodsAll members of the acute stroke treatment team were surveyed to tailor the interventions to local conditions. Through a review of responses and available literature, the improvement team suggested changes to streamline the protocol and designed in situ simulation-based team training sessions. Implementation of interventions started in February 2017. We completed 14 simulation sessions from February to June 2017 and an additional 12 sessions from November 2017 to March 2018. Applying Kirkpatrick’s four-level training evaluation model, participant reactions, clinical behaviour and patient outcomes were measured. Statistical process control charts were used to demonstrate changes in treatment times and patient outcomes.ResultsA total of 650 consecutive patients, including a 3-year baseline, treated with intravenous thrombolysis were assessed. Median door to needle times were significantly reduced from 27 to 13 min and remained consistent after 13 months. Risk-adjusted cumulative sum charts indicate a reduced proportion of patients deceased or bedridden after 90 days. There was no significant change in balancing measures (stroke mimics, fatal intracranial haemorrhage and prehospital times).ConclusionsImplementing a revised treatment protocol in combination with in situ simulation-based team training sessions for stroke thrombolysis was followed by a considerable reduction in door-to-needle times and improved patient outcomes. Additional work is needed to assess sustainability and generalisability of the interventions.
Mutational profiling and immunohistochemical analysis of a surgical series of ampullary carcinomas
Authors: Harthimmer Mads Rohde , Stolborg Uffe , Pfeiffer Per , Mortensen Michael Bau , Fristrup Claus , Detlefsen Sönke 
Published: June 2019

AimsKnowledge regarding the genetic features of ampullary carcinoma (AC) in European patients is limited. The utility of tumour markers for the establishment of a malignant diagnosis in biopsies from the ampullary region has not been fully elucidated. We aimed to describe the clinical, pathological, immunohistochemical (IHC) and genetic features of a Danish series of surgically resected ACs.MethodsSurgically resected ACs (n=59) were examined regarding (1) clinicopathological features, (2) histological subtypes, (3) expression of IMP3, maspin, MUC5AC and S100P and (4) next-generation sequencing using a hybrid capture-based platform (Illumina HiSeq2500), including 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer. Tumour mutational burden (TMB) and microsatellite instability (MSI) were also evaluated.ResultsPancreatobiliary adenocarcinomas (PB-AC), intestinal adenocarcinomas (INT-AC), other ampullary tumours and mixed adenocarcinomas represented 45.8%, 23.7%, 16.9% and 13.6%. The proportion of IHC-positive ACs (score ≥2) was: Maspin (94.9%), IMP3 (67.8%), S100P (39.0%) and MUC5AC (18.6%). Most frequently altered genes wereTP53(59.3%),KRAS(40.7%),APC(27.8%),SMAD4(20.4%),CDKN2A(16.7%) andARID2/PIK3CA(each 11.1%). MUC5AC and S100P were frequently expressed in PB-AC,APCalterations frequent in INT-AC,SOX9alterations were exclusive in INT-AC andMDM2andFRS2alterations in PB-AC. Four of 49 ACs (8.2%) were TMB-high/MSI-high and showed loss of MLH1 and PMS2.ConclusionsPB-AC was the most frequent histological subtype of AC. Maspin and IMP3 were the IHC tumour markers with the highest sensitivity. Adenocarcinoma subtypes differed regarding several genetic alterations, whose predictive value remains to be evaluated.
Hidden burden of arrhythmias in patients with small atrial septal defects: a nationwide study
Authors: Udholm Sebastian , Nyboe Camilla , Redington Andrew , Nielsen-Kudsk Jens Erik , Nielsen Jens Cosedis , Hjortdal Vibeke Elisabeth 
Published: June 2019

BackgroundIn recent Danish nationwide register-based study, adults with small, unrepaired atrial septal defects (ASD) have increased risk of pneumonia, atrial fibrillation (AF) and stroke. Moreover, they revealed higher mortality than the background population.ObjectiveIn this nationwide study, we evaluate the hidden burden of atrial and ventricular arrhythmias in adult patients with a small, unrepaired ASD without a previous diagnosis of AF.MethodsAll Danish patients, aged 18–65, diagnosed between 1953 and 2011 with an unrepaired ASD and no documented AF were invited for 7 days Holter-recording, echocardiography and 6 min walk test. The first 48 hours Holter-recording was completely analysed, while only AF was screened for throughout all 7 days. Furthermore, the entire patient group were characterised using the unique Danish registries.ResultsA total of 151 patients (mean age 32 years) were included. Approximately 80% of the patients had spontaneous closure of their defect. Despite this, occult arrhythmias were frequent. The most common arrhythmia was supraventricular tachycardia (n=24, 16%) with non-sustained atrial arrhythmias in 21 patients and AF in two patients. A considerable number of patients had non-sustained ventricular tachycardia (n=12, 8%). Patients with ASD and tachyarrhythmias had increased right ventricular to left ventricular diastolic area in echocardiography and higher age when compared with ASD patients without arrhythmias.ConclusionAdult patients with small, unrepaired ASD have a hidden burden of both atrial and ventricular tachyarrhythmias. The mechanism likely relates to the residua of previous right-heart volume overload and incomplete reverse remodelling. Our results support guidelines recommending continued follow-up of patients with small, unrepaired ASD.
LAPRA-TY for laparoscopic repair of traumatic diaphragmatic hernia without intracorporeal knot tying
Authors: Choi Jeff , Pan Jenny , Forrester Joseph D , Spain David , Browder Timothy D 
Published: June 2019

Case PresentationA 38-year-old man was brought in by ambulance as a trauma activation after sustaining a self-inflicted stab wound in the left upper quadrant with a kitchen knife. His primary survey was unremarkable and his vital signs were normal. Secondary survey revealed a 2 cm transverse stab wound inferior and medial to the left nipple. Extended focused assessment with sonography for trauma (FAST) did not show intra-abdominal or pericardial fluid and chest X-ray did not show a definite pneumothorax or hemothorax.What would you do?Wound exploration at bedside.Admit for observation and serial examinations.Exploratory laparotomy and open repair of traumatic diaphragmatic injury (TDI).Thoracotomy and open repair of TDI.Diagnostic laparoscopy and laparoscopic repair of TDI.
Combinatorial Register Allocation and Instruction Scheduling
Authors: Lozano Roberto Castañeda , Carlsson Mats , Blindell Gabriel Hjort , Schulte Christian 
Published: July 2019

This article introduces a combinatorial optimization approach to register allocation and instruction scheduling, two central compiler problems. Combinatorial optimization has the potential to solve these problems optimally and to exploit processor-specific features readily. Our approach is the first to leverage this potential
in practice
: it captures the
complete
set of program transformations used in state-of-the-art compilers,
scales
to medium-sized functions of up to 1,000 instructions, and generates
executable
code. This level of practicality is reached by using constraint programming, a particularly suitable combinatorial optimization technique. Unison, the implementation of our approach, is open source, used in industry, and integrated with the LLVM toolchain.

An extensive evaluation confirms that Unison generates better code than LLVM while scaling to medium-sized functions. The evaluation uses systematically selected benchmarks from MediaBench and SPEC CPU2006 and different processor architectures (Hexagon, ARM, MIPS). Mean estimated speedup ranges from 1.1% to 10% and mean code size reduction ranges from 1.3% to 3.8% for the different architectures. A significant part of this improvement is due to the integrated nature of the approach. Executing the generated code on Hexagon confirms that the estimated speedup results in actual speedup. Given a fixed time limit, Unison solves optimally functions of up to 946 instructions, nearly an order of magnitude larger than previous approaches.
The results show that our combinatorial approach can be applied in practice to trade compilation time for code quality beyond the usual compiler optimization levels, identify improvement opportunities in heuristic algorithms, and fully exploit processor-specific features.
NOTCH Signaling via WNT Regulates the Proliferation of Alternative, CCR2-Independent Tumor-Associated Macrophages in Hepatocellular Carcinoma
Authors: Ye Yu-Chen , Zhao Jun-Long , Lu Yi-Tong , Gao Chun-Chen , Yang Yang , Liang Shi-Qian , Lu Ying-Ying , Wang Lin , Yue Shu-Qiang , Dou Ke-Feng , Qin Hong-Yan , Han Hua 
Published: July 2019

Abstract

Tumor-associated macrophages (TAM) play pivotal roles in tumor progression and metastasis, but the contribution and regulation of different macrophage populations remain unclear. Here we show that Notch signaling plays distinct roles in regulating different TAM subsets in hepatocellular carcinoma (HCC). Myeloid-specific NOTCH blockade by conditional disruption of recombination signal binding protein Jκ (RBPj cKO) significantly delayed the growth of subcutaneously inoculated Lewis lung carcinoma (LLC), but accelerated orthotopically inoculated hepatic Hepa1-6 tumors in mice. In contrast to subcutaneous LLC, RBPj cKO significantly increased the number of TAMs in hepatic Hepa1-6 tumors despite impeded differentiation of monocyte-derived TAMs (moTAM). The dominating TAMs in orthotopic HCC manifested properties of Kupffer cells (KC) and hence are tentatively named KC-like TAMs (kclTAM). The increased proliferation of RBPj cKO kclTAMs was maintained even in Ccr2−/− mice, in which moTAMs were genetically blocked. NOTCH signaling blockade accelerated proliferation of kclTAMs via enhanced β-catenin–dependent WNT signaling, which also downregulated IL12 and upregulated IL10 expression by kclTAMs likely through c-MYC. In addition, myeloid-specific RBPj cKO facilitated hepatic metastasis of colorectal cancer but suppressed lung metastasis in mice, suggesting that the phenotype of RBPj cKO in promoting tumor growth was liver-specific. In patient-derived HCC biopsies, NOTCH signaling negatively correlated with WNT activation in CD68+ macrophages, which positively correlated with advanced HCC stages. Therefore, NOTCH blockade impedes the differentiation of moTAMs, but upregulates Wnt/β-catenin signaling to promote the proliferation and protumor cytokine production of kclTAMs, facilitating HCC progression and hepatic metastasis of colorectal cancer.

Significance:
These findings highlight the role of NOTCH and WNT signaling in regulating TAMs in hepatocellular carcinoma.
A Randomized Controlled Trial Testing Provision of Fecal and Blood Test Options on Participation for Colorectal Cancer Screening
Authors: Symonds Erin L. , Hughes Donna , Flight Ingrid , Woodman Richard , Chen Gang , Ratcliffe Julie , Pedersen Susanne K. , Fraser Robert J.L. , Wilson Carlene J. , Young Graeme P. 
Published: July 2019

Abstract
Suboptimal participation is commonly observed in colorectal cancer screening programs utilizing fecal tests. This randomized controlled trial tested whether the offer of a blood test as either a “rescue” strategy for fecal test nonparticipants or an upfront choice, could improve participation. A total of 1,800 people (50–74 years) were randomized to control, rescue, or choice groups (n = 600/group). All were mailed a fecal immunochemical test (FIT, OC-Sensor, Eiken Chemical Company) and a survey assessing awareness of the screening tests. The rescue group was offered a blood test 12 weeks after FIT nonparticipation. The choice group was given the opportunity to choose to do a blood test (Colvera, Clinical Genomics) instead of FIT at baseline. Participation with any test after 24 weeks was not significantly different between groups (control, 37.8%; rescue, 36.9%; choice, 33.8%; P &gt; 0.05). When the rescue strategy was offered after 12 weeks, an additional 6.5% participated with the blood test, which was greater than the blood test participation when offered as an upfront choice (1.5%; P &lt; 0.001). Awareness of the tests was greater for FIT than for blood (96.2% vs. 23.1%; P &lt; 0.0001). In a population familiar with FIT screening, provision of a blood test either as a rescue of FIT nonparticipants or as an upfront choice did not increase overall participation. This might reflect a lack of awareness of the blood test for screening compared with FIT.
Hidden Burden of Electronic Health Record‐Identified Familial Hypercholesterolemia: Clinical Outcomes and Cost of Medical Care
Authors: Patel Prashant , Hu Yirui , Kolinovsky Amy , Geng Zhi , Ruhl Jeffrey , Krishnamurthy Sarath , deRichemond Caroline , Khan Ayesha , Kirchner H. Lester , Metpally Raghu , Jones Laney K. , Sturm Amy C. , Carey David , Snyder Susan , Williams Marc S. , Mehra Vishal C. 
Published: June 2019

Background

Familial hypercholesterolemia (
FH
), is a historically underdiagnosed, undertreated, high‐risk condition that is associated with a high burden of cardiovascular morbidity and mortality. In this study, we use a population‐based approach using electronic health record (
EHR
)‐based algorithms to identify
FH
. We report the major adverse cardiovascular events, mortality, and cost of medical care associated with this diagnosis.

Methods and Results

In our 1.18 million
EHR‐
eligible cohort,
International Classification of Diseases, Ninth Revision
(

ICD
‐9

) code‐defined hyperlipidemia was categorized into
FH
and non‐
FH
groups using an
EHR
algorithm designed using the modified Dutch Lipid Clinic Network criteria. Major adverse cardiovascular events, mortality, and cost of medical care were analyzed. A priori associated variables/confounders were used for multivariate analyses using binary logistic regression and linear regression with propensity score–based weighted methods as appropriate. EHR
FH
was identified in 32 613 individuals, which was 2.7% of the 1.18 million
EHR
cohort and 13.7% of 237 903 patients with hyperlipidemia.
FH
had higher rates of myocardial infarction (14.77% versus 8.33%;
P
<0.0001), heart failure (11.82% versus 10.50%;
P
<0.0001), and, after adjusting for traditional risk factors, significantly correlated to a composite major adverse cardiovascular events variable (odds ratio, 4.02; 95% CI, 3.88–4.16;
P
<0.0001), mortality (odds ratio, 1.20; CI, 1.15–1.26;
P
<0.0001), and higher total revenue per‐year (incidence rate ratio, 1.30; 95% CI, 1.28–1.33;
P
<0.0001).

Conclusions

EHR
‐based algorithms discovered a disproportionately high prevalence of
FH
in our medical cohort, which was associated with worse outcomes and higher costs of medical care. This data‐driven approach allows for a more precise method to identify traditionally high‐risk groups within large populations allowing for targeted prevention and therapeutic strategies.
Decisive Atmospheric Circulation Indices for July–August Precipitation in North China Based on Tree Models
Authors: Tong Xuan , Yan Zhongwei , Xia Jiangjiang , Lou Xiao 
Published: July 2019

Abstract
Numerous circulation indices have been applied in practical climate services focused on regional precipitation. It is beneficial to identify the most influential or decisive indices, but this is difficult with conventional correlation analyses because of the underlying nonlinear mechanisms for precipitation. This paper demonstrates a set of the most influential indices for July–August precipitation in North China, based on the recursive random forest (RRF) method. These decisive circulation indices include the Polar–Eurasia teleconnection, North African subtropical high ridge position, India–Burma trough, Antarctic Oscillation, Northern Hemisphere polar vortex central latitude, North Atlantic Oscillation, and western Pacific subtropical high northern boundary position. Some of these factors have been recognized as directly influential to the regional precipitation, for example, those of the northwestern Pacific subtropical high; however, some are not easily understood. Decision tree (DT) models using these indices were developed to facilitate composite analyses to explain the RRF results. Taking one of the most interesting DT rules as an example, when the North African subtropical high ridge position is sufficiently far south, an anomalous anticyclone occurs in the upstream and an anomalous cyclone in the downstream of North China. This is unfavorable for northward moisture transport in eastern China and hence causes less precipitation in North China than climatology. The present results are not only helpful for improving diagnostic models of regional precipitation, but also enlightening for exploring how global climate change could impact a region by modulating large-scale circulation patterns.
Canine-assisted occupational therapy for children on the autism spectrum: Challenges in practice
Authors: Hill Jessica , Ziviani Jenny , Driscoll Carlie , Cawdell-Smith Judy 
Published: June 2019

Statement of context: Canine-assisted occupational therapy for children on the autism spectrum has been proposed as a means of enhancing goal-directed interventions, yet there remain no clear guidelines of its safe and ethical practice. Critical reflection on practice: Introducing a therapy dog into occupational therapy practices with children on the autism spectrum was found to require a complex and multifaceted set of skills requiring additional training to support the safety and wellbeing of both the client and the therapy dog. Implications for practice: Canine-assisted occupational therapy with children on the autism spectrum requires clear practice guidelines, as well as continuing professional development opportunities.
Epidemiology of Interpersonal Trauma among Women and Men Psychiatric Inpatients: A Population-Based Study
Authors: Gatov Evgenia , Koziel Nicole , Kurdyak Paul , Saunders Natasha R. , Chiu Maria , Lebenbaum Michael , Chen Simon , Vigod Simone N. 
Published: July 2019

Objective: Small clinical samples suggest that psychiatric inpatients report a lifetime history of interpersonal trauma. Since past experiences of trauma may complicate prognosis and treatment trajectories, population-level knowledge is needed about its prevalence and correlates among inpatients. Methods: Using health-administrative databases comprising all adult psychiatric inpatients in Ontario, Canada (2009 to 2016, n = 160,436, 49% women), we identified those who reported experiencing physical, sexual, and/or emotional trauma in their lifetime, 1 year, and 30 days preceding admission. We described the prevalence of each type of trauma, comparing women and men using modified Poisson regression, and identified individual-level characteristics associated with lifetime trauma history using multivariable logistic regression. Results: 31.7% of inpatients reported experiencing trauma prior to admission. Lifetime prevalence was higher in women (39.6% vs. 24.1%; age-adjusted prevalence ratio [aPR] = 1.68; 95% CI, 1.65 to 1.71), including sexual (22.7% vs. 8.4%; aPR = 2.81; 95% CI, 2.73 to 2.89), emotional (33.3% vs. 19.4%; aPR = 1.76; 95% CI, 1.72 to 1.79), and physical trauma (24.2% vs. 14.8%; aPR = 1.68; 95% CI, 1.65 to 1.72). Factors most prominently associated with lifetime trauma were witnessing parental substance use (adjusted odds ratio [aOR] = 8.68; 95% CI, 8.39 to 8.99), female sex (aOR = 2.29; 95% CI, 2.23 to 2.35), and number of recent stressful life events (aOR = 1.62; 95% CI, 1.59 to 1.65). Conclusions: These results suggest that trauma-informed approaches are essential to consider in the design and delivery of inpatient psychiatric services for both women and men.
Biomechanical evaluation of an independent acromioclavicular ligament repair for acromioclavicular joint reconstruction
Authors: Ibrahim Daniel K , Lam Patrick H , Aveledo Anzola Ricardo J , Murrell George AC 
Published: June 2019

Background A number of surgical techniques for the treatment of acromioclavicular joint separations have been described; however, few have been able to create a strong intra-operative construct that provides minimal joint translation. A biomechanical study was conducted to examine joint translation in an independent acromioclavicular ligament repair. Methods Three variations of a novel independent acromioclavicular ligament repair technique underwent testing using a Sawbones model. The technique involves threading sutures through two acromial bone tunnels in a suture-bridge configuration and anchoring them into the distal clavicle. Three groups of eight specimens underwent reconstruction; group 1 using FiberTape, group 2 using FiberWire and group 3 using FiberTape in a modified (under-over) suture-bridge configuration. Superior, anterior and posterior translation was tested at loads of 10, 20 and 30 N. Results Group 3 repair yielded the least translation in both anterior–posterior and superior–inferior planes, with a two-fold decrease in superior translation compared to groups 1 and 2 (P < .05). Both groups 1 and 3 using FiberTape resulted in significantly less anterior and posterior translation compared to the FiberWire group (P < .05). Discussion The independent acromioclavicular ligament repair, without repair of the coracoclavicular ligament, demonstrated significant translational stability in the anterior–posterior and superior–inferior planes.