bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of insurance type on national variation in cost of endovascular treatment for unruptured cerebral aneurysms
Authors: Lan Matthews , Liles Campbell , Patel Pious D , Gannon Stephen R , Chitale Rohan V
Published: October 2020

Background

Identifying drivers of nationwide variation in healthcare costs could help reduce overall cost. Endovascular treatment for unruptured cerebral aneurysms (ETUCR) is an elective neurointerventional procedure that allows for detailed analysis of cost variation. This study aimed to investigate the role of insurance type in cost variation of ETUCR.

Methods

A retrospective analysis of patients undergoing ETUCR was done. Demographic and hospital data were obtained from the National Inpatient Sample 2012–2015. Multivariate analysis was done using a generalized linear model. Oaxaca–Blinder decomposition was performed to identify factors driving cost variation.

Results

There was a significant difference in median cost ($25 331.82 vs $25 825.25, respectively, P<0.001) as well as length of stay (P<0.001) and complications (P<0.001) between patients with private insurance and Medicare. In multivariate analysis, insurance type was not predictive of increased cost. Among patients aged 65–75 years there was a higher median cost with private insurance compared to Medicare ($28 373.85 vs $25 558.25, respectively, P<0.001) but no difference in complications or length of stay. Oaxaca–Blinder decomposition showed higher marginal costs associated with private insurance patients at hospitals with greater endovascular operative volume (P=0.015).

Conclusions

In patients aged 65–75 years, private insurance is associated with higher costs compared to Medicare; however, insurance type is not predictive of increased cost in multivariate analysis. Differential treatment of private insurance and Medicare patients at hospitals with greater operative volume seems to influence this difference, likely due to differential reimbursement schemes that lead to weaker cost controls.
Rescue carotid puncture for ischemic stroke treated by endovascular therapy: a multicentric analysis and systematic review
Authors: Allard Julien , Ghazanfari Sam , Mahmoudi Mehdi , Labreuche Julien , Escalard Simon , Delvoye François , Ciccio Gabriele , Smajda Stanislas , Redjem Hocine , Hebert Solène , Consoli Arturo , Costalat Vincent , Desilles Jean-Philippe , Mazighi Mikael , Piotin Michel , Dargazanli Cyril , Lapergue Bertrand , Blanc Raphaël , Maïer Benjamin
Published: October 2020

Background

Endovascular therapy (EVT) for acute ischemic stroke (AIS) can be challenging in older patients with supra-aortic tortuosity. Rescue carotid puncture (RCP) can be an alternative in case of supra-aortic catheterization failure by femoral access, but data regarding RCP are scarce. We sought to investigate the feasibility, effectiveness and safety of RCP for AIS treated by EVT.

Methods

Patients treated by EVT with RCP were included from January 2012 to December 2019 in the Endovascular Treatment in Ischemic Stroke (ETIS) multicentric registry. Main outcomes included reperfusion rates ( ≥ TICI2B), 3 month functional outcome (modified Rankin Scale) and 3 month mortality. We also performed an additional systematic review of the literature according to the PRISMA checklist to summarize previous studies on RCP.

Results

25 patients treated by EVT with RCP were included from the ETIS registry. RCP mainly concerned elderly patients (median age 85 years, range 73–92) with supra-aortic tortuosity (n=16 (64%)). Intravenous thrombolysis (IVT) was used for nine patients (36%). Successful reperfusion was achieved in 64%, 87.5% of patients were dependent at 3 months, and 3 month mortality was 45.8%. The systematic review yielded comparable results. In pooled individual data, there was a shift toward better functional outcome in patients with successful reperfusion (median (IQR) 4 (2–6) vs 6 (4–6), p=0.011).

Conclusion

RCP mainly concerned elderly patients admitted for AIS with anterior LVO with supra-aortic tortuosity. The procedure seemed feasible, notably for patients treated with IVT, and led to significant reperfusion rates at the end of procedure, but with pronounced unfavorable outcomes at 3 months. RCP should be performed under general anesthesia to avoid life-threatening complications and ensure airways safety. Finally, RCP led to low rates of closure complications, emphasizing that this concern should not withhold RCP, if indicated.
Postcastration adhesions: clinical signs, diagnosis, treatment and prognosis in 20 horses
Authors: Robert Mickael Patrice , Couturier Fleur , McGeown Poppy , Geffroy Olivier , Tessier Caroline
Published: October 2020

The main goal of this short communication is to report the clinical signs, diagnostic modalities, surgical treatment and prognosis associated with postcastration adhesions. Twenty horses, castrated on average 30 months prior, presented for back pain, hindlimb lameness, jumping problems, behavioural issues or persistent preputial oedema. Cases displayed a tight fibrous band between the scrotal scar and the superficial inguinal ring. After a complete lameness examination was performed, all horses were operated under general anaesthesia in dorsal recumbency to resect the adhesions using two different techniques. Particular attention was given to haemostasis and to minimise tissue trauma. Five horses were lost to follow‐up. Subjective improvement occurred between one week and six months after surgery in 10 out of 12 of the horses according to owners’ evaluation. Horses with competition records available (n=15) had their first start 180±155 days after surgery. Overall client satisfaction with the technique was good (83 per cent).
No long-term effect of intracoelomic acoustic transmitter implantation on survival, growth, and body condition of a long-lived stenotherm in the wild
Authors: Hubbard Justin A.G. , Hickie Brendan E. , Bowman Jeff , Hrenchuk Lee E. , Blanchfield Paul J. , Rennie Michael D.
Published: October 2020

A fundamental assumption of biotelemetry studies is that there are no adverse consequences from the surgical implantation or presence of the acoustic transmitter. In fisheries, most studies have evaluated this assumption over only short time periods (<2 years) in a laboratory setting. Here we compared the survival, growth, and body condition of populations of lake trout (Salvelinus namaycush) in three lakes containing tagged and untagged individuals over a 12-year period (2002–2013). We found no significant negative effects of acoustic telemetry tagging on the long-term survival of fish (estimates of combined annual survival ranged from 67% to 91%) and no negative effect of surgical implantation on growth or body condition for fish of either sex. Additionally, we found no significant effect of transmitter:fish mass ratio on fish survival, growth (with the exception of smaller-bodied fish in one lake), or condition. Our results indicate the use of transmitters weighing <1.25% (in water) of fish mass is a desirable criterion for larger-bodied adult lake trout. Our findings support the assumption that long-lived fish species tagged with acoustic transmitters via intracoelomic surgery survive, grow, and maintain body condition similar to untagged conspecifics over the long term in the wild.
Dysregulation of chromatin organization in pediatric and adult brain tumors: oncoepigenomic contributions to tumorigenesis and cancer stem cell properties
Authors: Paik Seungil , Maule Francesca , Gallo Marco
Published: October 2020

The three-dimensional (3D) organization of the genome is a crucial enabler of cell fate, identity, and function. In this review, we will focus on the emerging role of altered 3D genome organization in the etiology of disease, with a special emphasis on brain cancers. We discuss how different genetic alterations can converge to disrupt the epigenome in childhood and adult brain tumors, by causing aberrant DNA methylation and by affecting the amounts and genomic distribution of histone post-translational modifications. We also highlight examples that illustrate how epigenomic alterations have the potential to affect 3D genome architecture in brain tumors. Finally, we will propose the concept of “epigenomic erosion” to explain the transition from stem-like cells to differentiated cells in hierarchically organized brain cancers.
Erratum to: Inclusive probability of particle creation on classical backgrounds
Authors: Kazinski Peter
Published: October 2020

In the published version of this article, formulas (140) and (142) were improperly corrected.
Edge-Assisted Control for Healthcare Internet of Things
Authors: Anzanpour Arman , Amiri Delaram , Azimi Iman , Levorato Marco , Dutt Nikil , Liljeberg Pasi , Rahmani Amir M.
Published: October 2020

Recent advances in pervasive Internet of Things technologies and edge computing have opened new avenues for development of ubiquitous health monitoring applications. Delivering an acceptable level of usability and accuracy for these healthcare Internet of Things applications requires optimization of both
system-driven
and
data-driven
aspects, which are typically done in a disjoint manner. Although decoupled optimization of these processes yields local optima at each level, synergistic coupling of the system and data levels can lead to a holistic solution opening new opportunities for optimization. In this article, we present an edge-assisted resource manager that dynamically controls the fidelity and duration of sensing w.r.t. changes in the patient’s activity and health state, thus fine-tuning the trade-off between energy efficiency and measurement accuracy. The cornerstone of our proposed solution is an intelligent low-latency real-time controller implemented at the edge layer that detects abnormalities in the patient’s condition and accordingly adjusts the sensing parameters of a reconfigurable wireless sensor node. We assess the efficiency of our proposed system via a case study of the photoplethysmography-based medical early warning score system. Our experiments on a real full hardware-software early warning score system reveal up to 49% power savings while maintaining the accuracy of the sensory data.
Performance-Driven Post-Processing of Control Loop Execution Schedules
Authors: Ghosh Sumana , Dey Soumyajit , Dasgupta Pallab
Published: October 2020

The increasing demand for mapping diverse embedded features onto shared electronic control units has brought about novel ways to co-design control tasks and their schedules. These techniques replace traditional implementations of control with new methods, such as pattern-based scheduling of control tasks and adaptive sharing of bandwidth among control loops through orchestration of their execution patterns. In the current practice of control design, once the static execution schedule is prepared for control tasks, no further control-related optimization is attempted for improving the control performance. We introduce, for the first time, an algorithmic mechanism that re-engineers a recurrent control task by enforcing switching between multiple control laws, which are designed for compensating the non-uniform gaps between successive executions of the control task. We establish that such post-processing of control task schedules may potentially help in improving the combined control performance of the co-scheduled control loops that are executing on a shared platform.
A Systematic Review of Empirical Measures of Workload Capacity
Authors: Thorpe Alexander , Nesbitt Keith , Eidels Ami
Published: October 2020

The usability of the human-machine interface is dependent on the quality of its design and testing. Defining clear criteria that the interface must meet can assist the implementation and evaluation process. These criteria may be based on performance, the quality of users’ experience, error prevention, or the broad utility of the interface. In this article, we motivate the use for
workload capacity
as an empirical measure of usability. We first describe generic and specific uses for workload measures in terms of adaptive interfaces. We then carry out a systematic review of how workload capacity has been empirically measured, based on 172 relevant literature sources from psychology, neuroscience, engineering, and computer science. We then analyse and report on how workload capacity and related constructs, such as perceptual load, attention, and working memory have been defined and measured in these sources. We discuss similarities and differences between constructs and identify opportunities for integrating real-time
workload capacity
measures into dynamic interfaces.
Member spotlight
Authors: Miller Jeffrey
Published: October 2020

In this feature of the Bulletin, we highlight members of the SIGCSE community. In this issue, Bulletin co-editor Jeffrey Miller interviewed Dr. Valerie Barr.
Multi-threaded memory efficient crossover in C++ for generational genetic programming
Authors: Langdon W. B.
Published: October 2020

C++ code snippets from a multi-core parallel memory-efficient crossover for genetic programming are given here . They may be adapted for separate generation evolutionary algorithms where large chromosomes or small RAM require no more than
M
+ 2 x nthreads simultaneously active individuals.
CO2 Laser Division of Neo-Vallecula Improves Dysphagia in the Postlaryngectomy Patient: A Case Series and Review of the Literature
Authors: Saltagi Mohamad Z. , Wallace Chelsey A. , Mantravadi Avinash V. , Sim Michael W.
Published: October 2020

Objectives. To review the literature on neo-vallecula diagnosis and management and to report our findings regarding 3 patients who developed neo-vallecula in the context of free-flap pharyngeal reconstruction following total laryngectomy. Methods. This case series reports three patients who developed a neo-vallecula following a laryngectomy and free-flap pharyngeal reconstruction. All three patients were treated with a CO2 laser endoscopic procedure. Results. Neo-vallecula formation is thought to be related to tension on the neopharyngeal closure or closure technique following total laryngectomy. Diagnosis may be obtained with swallow studies, videofluoroscopy, or endoscopy. Treatment has included external excision and endoscopic procedures such as stapling, harmonic scalpel excision, and laser removal. We utilized an endoscopic approach entailing the use of a CO2 laser to divide the neo-vallecula, and all our patients reported improvement in their dysphagia. Conclusions. Treatment of an anterior neo-vallecula endoscopically using a CO2 laser is an effective way to treat dysphagia in patients following total laryngectomy with free-flap pharyngeal reconstruction.
Emerging Nutritional Problem of Adult Population: Overweight/Obesity and Associated Factors in Addis Ababa City Communities, Ethiopia—A Community-Based Cross-Sectional Study
Authors: Hailemariam Tsedeke Wolde , Ethiopia Samrawit Solomon , Alamdo Andamlak Gizaw , Hailu Haimanot Ewnetu
Published: October 2020

Background. Obesity is an emerging public health problem in developing countries. There is limited study conducted in Ethiopia to determine the prevalence of obesity and its associated factors among adult population. Therefore, this study aimed at determining the prevalence of overweight/obesity and the associated factors among adults aged 25–64 years in Addis Ababa city community residents, Ethiopia. Methods. A community-based cross-sectional study was conducted from April 10, 2017, to May 20, 2017, in Addis Ababa. A total of 512 adults were recruited. A two-stage cluster followed by a systematic random sampling technique was used for sample selection. Data were collected using questionnaires and anthropometric measurements. The adjusted odds ratio (AOR) with a 95% CI was reported to show the strength of association. APvalue < 0.05 was considered statistically significant. Results. A total of 484 adults participated in the study with a response rate of 94.5%. The prevalence of overweight and obesity among study participants was found to be 99 (21.5%) and 14 (2.9%), respectively. Males were 90% less likely to be obese when compared to females (AOR = 0.10 (95% CI: 0.01–0.84)). Illiterate people were 94% less likely to be obese compared to those who were literate people (AOR = 0.06 (95% CI: 0.01–0.44)). Nonhypertensive individuals were 86% less likely to be obese when compared to hypertensive (AOR = 0.14 (95% CI: 0.03–0.69)). Conclusion. The combined prevalence of overweight and obesity was found to be considerably high in Addis Ababa city residents compared to the national figure. Being female, literate, and presence of hypertension are independent predictors of overweight/obesity in the study population. Thus, the concerned bodies should initiate efforts to tackle the newly emerging public health problem of the country and promote healthy lifestyle behaviors in the inhabitants of city settings.
A Novel Traffic Flow Forecasting Method Based on RNN-GCN and BRB
Authors: Zhu Hailong , Xie Yawen , He Wei , Sun Chao , Zhu Kaili , Zhou Guohui , Ma Ning
Published: October 2020

As an important part of a smart city, intelligent transport can effectively reduce energy consumption and environmental pollution. Traffic flow forecasting provides a reliable traffic dispatch basis for intelligent transport, and most of the existing prediction methods only predict a single saturation or speed and do not use the saturation and speed in a unified way. This paper proposes a new traffic flow prediction method based on RNN-GCN and BRB. First, the belief rule base (BRB) is used for data fusion to obtain new traffic flow data, then the recurrent neural network (RNN) and graph convolution neural network (GCN) model is used to obtain the time correlation of the traffic data, and finally, the traffic flow is predicted by the topology graph. The experimental results show that the method has a better performance than ARIMA, LSTM, and GCN.
Experimental Investigation of the Liquefaction Properties and Post‐Liquefaction Volumetric Strain of Calcareous Sand in Dredger Fill Site
Authors: Zhao Shenghua , Zhao Yanlin , He Jiang , Cao Zhenzhong , Wang Lei
Published: October 2020

In this study, dynamic triaxial cyclic tests were conducted to examine the liquefaction properties and post‐liquefaction volumetric strain of calcareous sand from a dredger fill site in the midst of the islands and reefs of the South China Sea. The test results indicated that there were some differences in micromorphology and composition between the calcareous sand obtained via dredging and natural calcareous sand. Axial cyclic stress attenuation can lead to higher cyclic vibration than actual liquefaction vibration, and the modified method can eliminate the effect of axial cyclic stress attenuation. Saturated calcareous sand liquefies under undrained and cyclic loading conditions, and the liquefaction resistance of the calcareous sand decreases with an increase of the effective confining pressure in the dense state. Calcareous sand obtained via dredging exhibited a higher liquefaction resistance compared with other types of calcareous sand. Furthermore, the proposed pore pressure development modified model better describes the pore pressure growth of the calcareous sand from the filling site. The fitting parameters of this model exhibited a high correlation with the relative density. Moreover, the post‐liquefaction volumetric strain of the calcareous sand is larger than that of quartz sand, exhibiting a linear relationship with relative density.
Novel IDS Variants Identified in Three Unrelated Pakistani Patients Affected with Mucopolysaccharidosis Type II (Hunter Syndrome)
Authors: Zubaida Bibi , Batool Hajira , Cheema Huma Arshad , Waheed Nadia , Naeem Muhammad
Published: October 2020

Introduction: Mucopolysaccharidosis type II (MPS-II) or Hunter syndrome is a rare X-linked recessive disorder caused by genetic lesions in the IDS gene, encoding the iduronate-2-sulfatase (IDS) enzyme, disrupting the metabolism of certain sulfate components of the extracellular matrix. Thus, the undegraded components, also known as glycosaminoglycans, accumulate in multiple tissues resulting in multisystemic abnormalities. Objective: To uncover causative genetic lesions in probands of three unrelated Pakistani families affected with rare X-linked recessive Hunter syndrome. Methods: Screening of the IDS gene was performed in six individuals (three patients and their mothers) through whole genomic DNA extraction from peripheral blood followed by PCR and Sanger sequencing. MutationTaster, PROVEAN, Human Splicing Finder, Swiss-Model, and SwissPdbViewer were used for in silico analysis of identified variants. Results: All probands were presented with coarse facies, recurrent respiratory tract infection, and reduced IDS activity. Molecular screening of IDS identified three different pathogenic variants including a novel duplication variant c.114_117dupCGTT, a novel splice site variant c.1006 + 1G>C, and a nonsense variant c.1165C>T. In silico analysis unanimously revealed the pathogenic nature of the variants due to their deleterious effects upon the encoded enzyme. Conclusion: Identified variants predictably lead to either the expression of a nonfunctional enzyme due to partial loss of SD1 and complete loss of SD2 subdomains or a complete lack of the IDS enzyme as a result of nonsense-mediated mRNA decay. Our study provides the first genetic depiction of MPS-II in Pakistan, expands the global IDS mutation spectrum, may provide insights into the three-dimensional structure of IDS, and should benefit the affected families in genetic counseling and prenatal diagnosis.
Adiponectin Signaling and Impaired GTPase Rab5 Expression in Adipocytes of Adolescents with Obesity
Authors: Karvela Alexia , Kostopoulou Eirini , Rojas Gil Andrea Paola , Avgeri Aikaterini , Pappa Aliki , Barrios Vicente , Lambrinidis George , Dimopoulos Ioannis , Georgiou George , Argente Jesús , Spiliotis Bessie
Published: October 2020

Introduction: Abnormalities in adipose tissue AdipoR1; adaptor protein, phosphotyrosine interaction, PH domain, and leucine zipper containing 1 (APPL1); GTPase Rab5; adiponectin; leptin; and visfatin in adults with obesity have been associated with metabolic disturbances. Objective: The objective of this study was to examine whether pediatric obesity disrupts elements of the adiponectin signaling pathway and GTPase Rab5 in adipose tissue. Methods: Primary adipocyte cultures of subcutaneous abdominal tissue were obtained from 96 lean and 66 children and adolescents with obesity (AO). AdipoR1, APPL1, and GTPase Rab5 mRNA levels were measured by RT-PCR and their protein content by Western immunoblotting. Serum total and high-molecular-weight adiponectin, leptin, leptin soluble receptor (sOB-R), and visfatin were measured by ELISA. Results: The mRNA expression and protein content of AdipoR1 and APPL1 did not differ significantly with obesity, age, or puberty. However, GTPase Rab5 protein was increased in the adipocytes of younger prepubertal children with obesity but decreased in AO. Leptin was increased in AO compared to lean adolescents (AL) and in older prepubertal lean (OPL) children and AL compared to younger prepubertal lean and obese children. sOB-R was higher in OPL children and in the AL and AO. Serum visfatin was increased in the younger prepubertal children and AO. Conclusions: In contrast to adults, obesity did not change the expression of AdipoR1 and APPL1 in cultured adipocytes from biopsies of subcutaneous abdominal adipose tissue of children and adolescents. Similar to adipose tissue studies in adults with obesity and metabolic dysfunction, the AO in our study showed reduced adipocyte GTPase Rab5 expression.
SARS-CoV-2 Detection on Bronchoalveolar Lavage: An Italian Multicenter experience
Authors: Patrucco Filippo , Albera Carlo , Bellocchia Michela , Foci Valentina , Gavelli Francesco , Castello Luigi Mario , Bellan Mattia , Sainaghi Pier Paolo , Airoldi Chiara , Balbo Piero Emilio , Solidoro Paolo
Published: October 2020

Background: Bronchoscopy with bronchoalveolar lavage (BAL) during the SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) pandemic should be reserved to a limited number of clinical indications. The yield of BAL for the diagnosis of suspected or confirmed pulmonary SARS-CoV-2 infection is still unknown. Objectives: We aimed to evaluate the diagnostic ratio of BAL in detecting SARS-CoV-2 pulmonary infection in patients undergoing bronchoscopy for different indications as well as describe the clinical, radiological, and endoscopic characteristics of patients with SARS-CoV-2 on BAL. Method: We conducted a multicenter retrospective study including all patients who underwent bronchoscopy for the detection of SARS-CoV-2 on BAL. Clinical, computed tomography (CT), endoscopic, and microbiologic data were gathered from March 16th to May 27th, 2020. Results: 131 patients were included. Bronchoscopy was performed for suspected SARS-CoV-2 infection (65.5%), alternative diagnosis (12.9%), suspected superinfections (19.8%), and lung atelectasis (1.5%). SARS-CoV-2 was isolated on BAL 43 times (32.8%) and the highest isolation rate was in patients with suspected SARS-CoV-2 infection (74.4%); 76% of positive patients had a double-negative nasopharyngeal swab. Peripheral, posterior and multilobar CT opacities were more frequent in SARS-CoV-2 patients, and the number of CT findings was higher in positive patients, particularly those with suspected SARS-CoV-2 infection. We recorded a progressive reduction of SARS-CoV-2 isolation during the observation period. Conclusions: In our centers, the rate of detection of SARS-CoV-2 on BAL in patients with suspected infection was 37.2%. The agreement of BAL with nasopharyngeal swabs was high; CT alterations could predict the pretest probability of SARS-CoV-2 infection, but suspicion of viral infection should be always considered.
Nicht kleinzelliges Lungenkarzinom: Einfluss von Treibermutationen bei Immuncheckpoint-Inhibition erkennen
Authors: Horter Susanne , Schütte Wolfgang
Published: October 2020

Aims: Non-small cell lung cancer (NSCLC) patients with EGFR mutations do not respond well to checkpoint inhibitors. However, little is known about the activity of immunotherapy in NSCLC with other driver mutations. The increasing use of next-generation sequencing (NGS) leads to molecular findings that face the clinician with problems while choosing the best treatment. This study aims at analyzing response of NSCLC with driver mutations to immunotherapy. Patients and Methods: We retrospectively included 84 NSCLC patients diagnosed and treated at 2 German tertiary-care lung cancer centers using NGS and treatment with immunotherapy. Response to immunotherapy was analyzed in correlation to molecular findings. Results: 51 patients harbored at least 1 driver mutation. PIK3CA, EGFR, and STK11 mutations did not respond to immunotherapy. KRAS, TP53, and MET exon 14 skipping mutations responded well. One patient with NF-1 mutation showed durable response. Conclusions: Molecular testing may be of use in guiding treatment decision making in NSCLC.
The American Heart Association’s Call to Action for Reducing the Global Burden of Rheumatic Heart Disease: A Policy Statement From the American Heart Association
Authors: Beaton Andrea , Kamalembo Flavia B. , Dale James , Kado Joseph H. , Karthikeyan Ganesan , Kazi Dhruv S. , Longenecker Chris T. , Mwangi Jeremiah , Okello Emmy , Ribeiro Antonio Luiz P. , Taubert Kathryn A. , Watkins David A. , Wyber Rosemary , Zimmerman Meghan , Carapetis Jonathan ,   On behalf of the American Heart Association Young Hearts Rheumatic Fever, Endocarditis and Kawasaki Disease Committee of the Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Advocacy Coordinating Committee; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology
Published: October 2020

Rheumatic heart disease (RHD) affects ≈40 million people and claims nearly 300 000 lives each year. The historic passing of a World Health Assembly resolution on RHD in 2018 now mandates a coordinated global response. The American Heart Association is committed to serving as a global champion and leader in RHD care and prevention. Here, we pledge support in 5 key areas: (1) professional healthcare worker education and training, (2) technical support for the implementation of evidence-based strategies for rheumatic fever/RHD prevention, (3) access to essential medications and technologies, (4) research, and (5) advocacy to increase global awareness, resources, and capacity for RHD control. In bolstering the efforts of the American Heart Association to combat RHD, we hope to inspire others to collaborate, communicate, and contribute.
Comprehensive Metabolic Phenotyping Refines Cardiovascular Risk in Young Adults
Authors: Murthy Venkatesh L. , Reis Jared P. , Pico Alexander R. , Kitchen Robert , Lima Joao A.C. , Lloyd-Jones Donald , Allen Norrina B. , Carnethon Mercedes , Lewis Gregory D. , Nayor Matthew , Vasan Ramachandran S. , Freedman Jane E. , Clish Clary B. , Shah Ravi V.
Published: October 2020

Background:

Whereas cardiovascular disease (CVD) metrics define risk in individuals >40 years of age, the earliest lesions of CVD appear well before this age. Despite the role of metabolism in CVD antecedents, studies in younger, biracial populations to define precise metabolic risk phenotypes are lacking.

Methods:

We studied 2330 White and Black young adults (mean age, 32 years; 45% Black) in the CARDIA study (Coronary Artery Risk Development in Young Adults) to identify metabolite profiles associated with an adverse CVD phenome (myocardial structure/function, fitness, vascular calcification), mechanisms, and outcomes over 2 decades. Statistical learning methods (elastic nets/principal components analysis) and Cox regression generated parsimonious, metabolite-based risk scores validated in >1800 individuals in the Framingham Heart Study.

Results:

In the CARDIA study, metabolite profiles quantified in early adulthood were associated with subclinical CVD development over 20 years, specifying known and novel pathways of CVD (eg, transcriptional regulation, brain-derived neurotrophic factor, nitric oxide, renin–angiotensin). We found 2 multiparametric, metabolite-based scores linked independently to vascular and myocardial health, with metabolites included in each score specifying microbial metabolism, hepatic steatosis, oxidative stress, nitric oxide modulation, and collagen metabolism. The metabolite-based vascular scores were lower in men, and myocardial scores were lower in Black participants. Over a nearly 25-year median follow-up in CARDIA, the metabolite-based vascular score (hazard ratio, 0.68 per SD [95% CI, 0.50–0.92];
P
=0.01) and myocardial score (hazard ratio, 0.60 per SD [95% CI, 0.45–0.80];
P
=0.0005) in the third and fourth decades of life were associated with clinical CVD with a synergistic association with outcome (
P
interaction
=0.009). We replicated these findings in 1898 individuals in the Framingham Heart Study over 2 decades, with a similar association with outcome (including interaction), reclassification, and discrimination. In the Framingham Heart Study, the metabolite scores exhibited an age interaction (
P
=0.0004 for a combined myocardial–vascular score with incident CVD), such that young adults with poorer metabolite-based health scores had highest hazard of future CVD.

Conclusions:

Metabolic signatures of myocardial and vascular health in young adulthood specify known/novel pathways of metabolic dysfunction relevant to CVD, associated with outcome in 2 independent cohorts. Efforts to include precision measures of metabolic health in risk stratification to interrupt CVD at its earliest stage are warranted.
Microbiota Introduced to Germ-Free Rats Restores Vascular Contractility and Blood Pressure
Authors: Joe Bina , McCarthy Cameron G. , Edwards Jonnelle M. , Cheng Xi , Chakraborty Saroj , Yang Tao , Golonka Rachel M. , Mell Blair , Yeo Ji-Youn , Bearss Nicole R. , Furtado Janara , Saha Piu , Yeoh Beng San , Vijay-Kumar Matam , Wenceslau Camilla F.
Published: October 2020

Commensal gut microbiota are strongly correlated with host hemodynamic homeostasis but only broadly associated with cardiovascular health. This includes a general correspondence of quantitative and qualitative shifts in intestinal microbial communities found in hypertensive rat models and human patients. However, the mechanisms by which gut microbes contribute to the function of organs important for blood pressure (BP) control remain unanswered. To examine the direct effects of microbiota on BP, we conventionalized germ-free (GF) rats with specific pathogen-free rats for a short-term period of 10 days, which served as a model system to observe the dynamic responses when reconstituting the holobiome. The absence of microbiota in GF rats resulted with relative hypotension compared with their conventionalized counterparts, suggesting an obligatory role of microbiota in BP homeostasis. Hypotension observed in GF rats was accompanied by a marked reduction in vascular contractility. Both BP and vascular contractility were restored by the introduction of microbiota to GF rats, indicating that microbiota could impact BP through a vascular-dependent mechanism. This is further supported by the decrease in actin polymerization in arteries from GF rats. Improved vascular contractility in conventionalized GF rats, as indicated through stabilized actin filaments, was associated with an increase in cofilin phosphorylation. These data indicate that the vascular system senses the presence (or lack of) microbiota to maintain vascular tone via actin polymerization. Overall, these results constitute a fundamental discovery of the essential nature of microbiota in BP regulation.
Bathyraja (Arctoraja) sexoculata sp. nov., a new softnose skate (Rajiformes: Arhynchobatidae) from Simushir Island, Kuril Islands (western North Pacific), with special reference to geographic variations in Bathyraja (Arctoraja) smirnovi
Authors: MISAWA RYO , ORLOV ALEXEI M. , ORLOVA SVETLANA Y. , GORDEEV ILYA I. , ISHIHARA HAJIME , HAMATSU TOMONORI , UEDA YUJI , FUJIWARA KUNIHIRO , ENDO HIROMITSU , KAI YOSHIAKI
Published: October 2020

A new species of softnose skate (Arhynchobatidae), Bathyraja sexoculata Misawa, Orlov, Orlova, Gordeev and Ishihara is described on the basis of five specimens collected from off the east coast of Simushir Island, Kuril Islands, located in the western North Pacific. The specimens conformed to the genus Bathyraja by having the anteriormost pectoral-fin skeleton almost reaching the snout tip, and a slender unsegmented rostral cartilage. Within Bathyraja, the new species belongs to the subgenus Arctoraja (currently with four valid species) due to the relatively short tail (79–86% of disc width), high count of predorsal caudal vertebrae (more than 86), and large strong nuchal and scapular thorns. It is most similar to Bathyraja (Arctoraja) smirnovi, distributed in the Seas of Japan and Okhotsk, in having tail thorns not extending to the nuchal area, median thorns discontinuous from the nape to the tail, and no mid-dorsal thorns. However, B. sexoculata can be distinguished from B. smirnovi by the following characters: three pairs of white blotches on the dorsal disc surface (vs. blotches absent, or a pair of white or dark blotches in B. smirnovi), dark blotch around cloaca, dark bands along mid ventral line of tail (vs. dark blotch and band usually absent ventral disc surface in B. smirnovi), 86–93 predorsal caudal vertebrae (vs. 80–87 in B. smirnovi), and a unique mitochondrial DNA cytochrome c oxidase subunit I sequence. Proportional measurements, including disc width, disc length, head length, preoral length, prenarial length, internarial distance, eye diameter, and tail length, also differ between the two species. For the referential purpose, geographical variations of B. smirnovi distributed in the Seas of Japan and Okhotsk are analyzed and clarified based on morphological and genetic data. Significant morphological and genetic differences were found between local populations in the Seas of Japan and Okhotsk.
Graph-Guided Regularized Regression of Pacific Ocean Climate Variables to Increase Predictive Skill of Southwestern U.S. Winter Precipitation
Authors: Stevens Abby , Willett Rebecca , Mamalakis Antonios , Foufoula-Georgiou Efi , Tejedor Alejandro , Randerson James T. , Smyth Padhraic , Wright Stephen
Published: October 2020

Understanding the physical drivers of seasonal hydroclimatic variability and improving predictive skill remains a challenge with important socioeconomic and environmental implications for many regions around the world. Physics-based deterministic models show limited ability to predict precipitation as the lead time increases, due to imperfect representation of physical processes and incomplete knowledge of initial conditions. Similarly, statistical methods drawing upon established climate teleconnections have low prediction skill due to the complex nature of the climate system. Recently, promising data-driven approaches have been proposed, but they often suffer from overparameterization and overfitting due to the short observational record, and they often do not account for spatiotemporal dependencies among covariates (i.e., predictors such as sea surface temperatures). This study addresses these challenges via a predictive model based on a graph-guided regularizer that simultaneously promotes similarity of predictive weights for highly correlated covariates and enforces sparsity in the covariate domain. This approach both decreases the effective dimensionality of the problem and identifies the most predictive features without specifying them a priori. We use large ensemble simulations from a climate model to construct this regularizer, reducing the structural uncertainty in the estimation. We apply the learned model to predict winter precipitation in the southwestern United States using sea surface temperatures over the entire Pacific basin, and demonstrate its superiority compared to other regularization approaches and statistical models informed by known teleconnections. Our results highlight the potential to combine optimally the space–time structure of predictor variables learned from climate models with new graph-based regularizers to improve seasonal prediction.
Managing renal forniceal rupture secondary to ureteric calculi in line with the NICE 2019 Renal and Ureteric Stone Guidelines
Authors: Harvey NJ , Rudman HA , Gall ZJ
Published: October 2020

Objective:

To synthesise all available data to determine the best management for urolithiasis-related renal forniceal rupture (RFR), with particular reference to the National Institute for Health and Care Excellence (NICE) 2019 Renal and Ureteric Stone Guidelines.

Methods:

PubMed search to March 2020 using permutations of renal, forniceal, fornix, calyceal, calyx and rupture. Non-English abstracts, editorial comments, letters to the editor and abstracts of conference proceedings were excluded.

Results:

An initial PubMed search retrieved 126 titles which were screened for relevance and five further titles were added from associated references. 64 abstracts were subsequently assessed, with 25 articles proceeding to full paper review.

Conclusions:

In cases of RFR secondary to ureteric calculi, management options, including conservative management, for the stone should be considered without the decision being influenced by the presence of the rupture. Perirenal abscesses secondary to RFR are rare, occurring in less than 0.25% of cases. Evidence supports restricting antibiotic prophylaxis to patients with a history of recurrent urinary tract infections or a positive urine culture, in line with the European Association of Urology’s antibiotic stewardship general management principle. RFR is not inherently a contraindication to primary ureteroscopy, which has particularly relevance with the drive to meet the 2019 NICE recommendations.

Level of evidence:

Not applicable to this literature review.
Ultra-High Throughput Screening
Authors: Shumate Chris , Beckey Scott , Coassin Peter , Stylli Harry
Published: October 2020

Aurora Biosciences Corporation designs and develops proprietary drug discovery systems, services and technologies to accelerate and enhance the discovery of new pharmaceuticals. Aurora is developing an integrated technology platform centered around two technologies; 1) a portfolio of proprietary fluorescent assay technologies and, 2) an ultra-high throughput screening (“UHTS”) system designed to allow assay miniaturization and to overcome many of the limitations associated with the traditional drug discovery process. This approach takes advantage of the opportunities created by recent advances in genomics and combinatorial chemistry that have generated many new therapeutic targets and an abundance of new small molecule compounds. Aurora believes its integrated platform will accelerate the drug discovery process by shortening the time required to identify high quality lead compounds and to optimize those compounds into drug development candidates.
Virtual Barcodes Use Radio Waves
Authors: Lopez Luciana
Published: October 2020

The wrong additive in a specimen vial, for example, could not only give completely invalid results, it could also waste a given sample. While the automation, robotics, and electronics industries have been consistently helping laboratories improve identification and classification problems over the years, there has always been room for improvement. Now, however, a new technology stands poised to take identification solutions to a new level: radio frequency identification.
Individualisierung in der Personalentwicklung (PE)
Authors: Kick Thomas , Scherm Ewald
Published: October 2020

Die steigenden Anforderungen an die Mitarbeiter und die Folgen des Wertewandels dürfen in der PE nicht unberücksichtigt bleiben. Die Konsequenz bildet deshalb – ausgehend von einer stärkeren Berücksichtigung der Ziele der einzelnen Mitarbeiter in der Unternehmung – eine Individualisierung der PE. Dazu werden zunächst der Begriff “Individualisierung” definiert und Anforderungskriterien vorgestellt, die diese Individualisierung konkretisieren. Diese Kriterien werden dann auf die PE-Bedarfsermittlung, die PE-Maßnahmen und die PE-Erfolgskontrolle angewendet, um Individualisierungspotentiale aufzuzeigen. Auch wenn eine Reihe offener Probleme bestehen bleibt und der “optimale” Individualisierungsgrad nicht generell bestimmt werden kann, erscheint eine stärkere Individualisierung in der PE als ein Schritt in die “richtige” Richtung.
Inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study
Authors: van Koningsbruggen-Rietschel Silke , Davies Jane C. , Pressler Tacjana , Fischer Rainald , MacGregor Gordon , Donaldson Scott H. , Smerud Knut , Meland Nils , Mortensen Jann , Fosbøl Marie Ø. , Downey Damian G. , Myrset Astrid H. , Flaten Hugo , Rye Philip D.
Published: October 2020

Background

OligoG is a low molecular-weight alginate oligosaccharide that improves the viscoelastic properties of cystic fibrosis (CF) mucus and disrupts biofilms, thereby potentiating the activity of antimicrobial agents. The efficacy of inhaled OligoG was evaluated in adult patients with CF.

Methods

A randomised, double-blind, placebo-controlled multicentre crossover study was used to demonstrate safety and efficacy of inhaled dry powder OligoG. Subjects were randomly allocated to receive OligoG 1050 mg per day (10 capsules three times daily) or matching placebo for 28 days, with 28-day washout periods following each treatment period. The primary end-point was absolute change in percentage predicted forced expiratory volume in 1 s (FEV1) at the end of 28-day treatment. The intention-to-treat (ITT) population (n=65) was defined as randomised to treatment with at least one administration of study medication and post-dosing evaluation.

Results

In this study, 90 adult subjects were screened and 65 were randomised. Statistically significant improvement in FEV1was not observed in the ITT population. Adverse events included nasopharyngitis, cough and pulmonary exacerbation. The number and proportions of patients with adverse events and serious adverse events were similar between OligoG and placebo group.

Conclusions

Inhalation of OligoG-dry powder over 28 days was safe in adult CF subjects. Statistically significant improvement of FEV1was not reached. The planned analyses did not indicate a significant treatment benefit with OligoG compared to placebo.Post hocexploratory analyses showed subgroup results that indicate that further studies of OligoG in this patient population are justified.
Impact of season and geography on CompEx Asthma: a composite end-point for exacerbations
Authors: Jauhiainen Alexandra , Scheepers Lieke E.J.M. , Fuhlbrigge Anne L. , Harrison Tim , Zangrilli James , Garcia Gil Esther , Gustafson Per , Fagerås Malin , Da Silva Carla A.
Published: October 2020

Background

CompEx Asthma, a novel composite end-point combining severe exacerbations (SevEx) with asthma-worsening events, was recently developed. Further characterisation of CompEx Asthma is needed to illustrate the applicability of this end-point. The objective was to evaluate CompEx Asthma as a rate end-point to determine how seasonal and geographical factors impact this novel outcome.

Methods

Seven 24–56-week randomised controlled trials of budesonide/formoterol (BUD/FORM) and benralizumab were analysed. Annualised event rates (AERs) and treatment effects (hazard ratio (HR)) were analysed with Poisson and Andersen–Gill models, respectively. Seasonality was analysed by month and five geographical regions were evaluated.

Results

The studies included 10 815 patients (63% female, mean age 42–49 years). CompEx Asthma AER mirrored seasonal variations in SevEx AER. CompEx Asthma AERs were higherversusSevEx in BUD/FORM and benralizumab trials (range 2.7–4.5-fold and 1.3–2.0-fold increase, respectively) and were less variableversusSevEx between regions (ratios of greatest:smallest AERs: 1.36 for CompExversus2.28 for SevEx (BUD/FORM); 1.81 for CompExversus2.22 for SevEx (benralizumab)). Treatment effects for CompEx Asthma and SevEx were generally similar across regions and months. However, in Eastern Europe, where SevEx rates were lowest, treatment effect was greater with CompEx AsthmaversusSevEx, reaching statistical significance in the benralizumab studies (HR (95% CI): 0.67 (0.53–0.85)versus0.87 (0.65–1.15)).

Conclusion

This study confirmed the reliability of CompEx Asthma as a rate end-point and allowed detection of variations in seasonal SevEx rates, reduction of variation in rates across regions and potential greater sensitivity to treatment effects.