bluuebunny/crossref_metadata_2025 huggingface dataset:
Trajectories of sickness absence after road traffic injury: a Swedish register-based cohort study
Authors: Rissanen Ritva , Liang Yajun , Moeller Jette , Nevriana Alicia , Berg Hans-Yngve , Hasselberg Marie
Published: August 2019

Objectives

Despite much focus on the health impact of road traffic injury (RTI) on life, there is a lack of knowledge of the dynamic process of return to work following RTI and its related factors. The aim of this study was to identify longitudinal patterns of sickness absence (SA) following RTI, to examine the patterns’ interplay with health-related quality of life (HRQoL) and to determine if there are differences, regarding the patterns and interplay, according to injury severity.

Design

A register-based prospective cohort study.

Setting

Administrative data on RTI in Sweden from the Swedish Traffic Accident Data Acquisition System (STRADA) and Swedish Social Insurance data.

Participants

Individuals suffering an RTI (total n=4761) were identified in STRADA between 1 January 2007 and 31 December 2009. A total of 903 of these met the inclusion criteria for the current study and were included.

Primary and secondary outcome measures

The primary outcome measure was SA following RTI. The secondary outcome measure was HRQoL.

Results

Three distinct patterns of SA were identified; ‘Stable’, ‘Quick decrease’ and ‘Gradual decrease’. The patterns differed in the number of initial SA days and the rate of reduction of SA days. After 3 years, all three patterns had almost the same level of SA. Higher injury severity and a higher number of SA days had a negative interplay with HRQoL. Participants who initially had a higher number of SA days were more likely to report a low HRQoL, indicating that people with a slower return to work are more vulnerable.

Conclusion

The study highlights the heterogeneity of return to work after an RTI. People with a more severe injury and slower pace of return to work seem to be more vulnerable with regards to HRQoL loss following RTI.
lncRNA SLC16A1-AS1 as a Novel Prognostic Biomarker in Non-Small Cell Lung Cancer
Authors: Liu Hong Yue , Lu Sheng Rong , Guo Zi Han , Zhang Zhi Sheng , Ye Xuan , Du Qiong , Li Huan , Wu Qiang , Yu Bo , Zhai Qing , Liu Jin Long
Published: August 2019

Long non-coding RNAs (lncRNAs) have proved to act as crucial biomarkers in tumors. Novel biomarkers in non-small cell lung cancer (NSCLC) need to be investigated badly. To identify the differentially expressed lncRNAs between NSCLC tissue and adjacent tissue, microarray analysis was performed. lncRNA SLC16A1-AS1 was significantly less expressed in NSCLC tissue than that in adjacent tissue. Gain-of-function experiments was performed to determine the biological functions of SLC16A1-AS. In situhybridization and survival analysis were applied in lung cancer tissue samples to determine the prognostic role of SLC16A1-AS1. It was showed that SLC16A1-AS1 was remarkably downregulated in NSCLC tissues and cell lines. Functionally, SLC16A1-AS1 overexpression could inhibit the viability and proliferation of lung cancer cell, block the cell cycle and promote cell apoptosis in vitro which may result from reduced phosphorylation of rat sarcoma (RAS)/ proto-oncogene serine/threonine-protein kinase (RAF)/ mitogen-activated protein kinase kinase (MEK)/ extracellular regulated protein kinases (ERK) pathway caused by elevated expression of SLC16A1-AS1. Clinical sample analysis showed that SLC16A1-AS1 had a favorable impact on the overall survival and progression-free survival of patients with NSCLC. Our results suggested that SLC16A1-AS1 may act as a potential biomarker for patients with NSCLC.
Randomised study of the immunomodulatory effects of azithromycin in severely asthmatic horses
Authors: Mainguy‐Seers Sophie , Vargas Amandine , Labrecque Olivia , Bédard Christian , Hélie Pierre , Lavoie Jean‐Pierre
Published: August 2019

Neutrophilic inflammation is believed to contribute to the airway obstruction and remodelling in equine asthma. Azithromycin, an antibiotic with immunomodulatory properties, reduces pulmonary neutrophilia and hyper‐responsiveness in human asthmatics and decreases airway remodelling in rodent models of asthma. It was therefore hypothesised that azithromycin would improve lung function, mucus accumulation and central airway remodelling by decreasing luminal neutrophilia in severe equine asthma. The effects of a 10‐day treatment with either azithromycin or ceftiofur, an antimicrobial without immune‐modulating activity, were assessed using a blind, randomised, crossover design with six severe asthmatic horses in clinical exacerbation. Lung function, tracheal mucus accumulation, tracheal wash bacteriology, bronchial remodelling, airway neutrophilia and mRNA expression of proinflammatory cytokines (interleukin (IL)‐8, IL‐17A, IL‐1β, tumour necrosis factor‐α) in bronchoalveolar lavage fluid were evaluated. Azithromycin decreased the expression of IL‐8 (P=0.03, one‐tailed) and IL‐1β (P=0.047, one‐tailed) but failed to improve the other variables evaluated. Ceftiofur had no effect on any parameter. The reduction of neutrophilic chemoattractants (IL‐8, IL‐1β) justifies further efforts to investigate the effects of a prolonged treatment with macrolides on airway neutrophilia and remodelling. The lack of efficacy of ceftiofur suggests that severe equine asthma should not be treated with antibiotics at first‐line therapy.
Fuel treatments change forest structure and spatial patterns of fire severity, Arizona, U.S.A.
Authors: Johnson Morris C. , Kennedy Maureen C. , Harrison Sarah
Published: August 2019

Fuel reduction treatments are often designed to achieve multiple resource management objectives in addition to reducing potential fire hazard. In the White Mountains of Arizona State (U.S.A.), the 2014 San Juan Fire burned through several thinning prescriptions designed to achieve wildlife habitat objectives. Many studies have documented reduced fire severity for a standard set of fuel treatments, but the range of variability in fuel treatment effectiveness for alternative treatment designs is poorly understood. We used nonlinear mixed-effects modeling to estimate the distance into the treated area at which fire severity decreases and randomization tests to compare forest structure. High-severity fire effects were estimated to be reduced between 114 m and 345 m into the treated area. The range of variability in observed-distance high-severity fire effects persist into the treated area and, in conjunction with estimated relationships between posttreatment forest structure and severity, can inform the design of alternative fuel treatment prescriptions with various target prescriptions. We found that as cover was maintained in a treatment unit for wildlife habitat, the size of the fuel treatment necessary to observe a reduction in severity needs to be larger. Our study will inform decision makers on the size of treatments required to accomplish management objectives.
Gap Junction Dynamics Induces Localized Conductance Bistability in Cardiac Tissue
Authors: Hawks C. , Elorza J. , Witt A. , Laroze D. , Cantalapiedra I. R. , Peñaranda A. , Echebarria B. , Bragard J.
Published: August 2019

Connexins are specialized ionic channels that control the action potential propagation between cardiac myocytes. In this paper, we study the connexin dynamics in a one-dimensional model of cardiac tissue. We show that the connexin dynamics may lead to a spatial organization of the gap junction conductance. In the numerical simulations presented in this paper we have found two different regimes for the spatial organization of the conductances: (a) a spatially uniform conductance; (b) a spatially complex pattern of local values of high and low conductances. In addition, we have observed that, locally, the two final states are limit cycles with a period equal to the period associated with the external excitation of the tissue strand. The conductance dispersion usually takes place on a very large time scale, i.e. thousands of heart beats, and on a very short spatial scale. Due to its simplicity, the one-dimensional setting allows a detailed study of the emerging structure and in particular very long simulations. We have studied the transition between the two aforementioned states as a function of the gap junction conductance characteristics. Furthermore, we have studied the effect of initially added noises on the outcome of the system. Finally, using spatial autocorrelation functions we have characterized the spatial dispersion in conductance values.
Chaotic Behavior of Ionic Transportation Through Synthetic Ion Channels
Authors: Negi Sangeeta , Prasad Awadhesh , Chandra Amita
Published: August 2019

Selective ion transportation through synthetic ion channels in polymeric membranes (which mimic natural systems, e.g. excitable cell membranes) is being reported through this article. The synthetic ion channels have been created by swift heavy ion irradiation of polymeric membranes followed by chemical etching. Since, the transportation of sodium and potassium ions of aqueous electrolytes through synthetic ion channels in polyethylene terephthalate depends on the electrophoretic forces present in the electrolyte; these ion channels are referred to as “voltage activated channels”. For a particular range of applied voltage, these channels behave as K-channels while they act as Na-channels in another voltage range. The channels have been found to switch between high and low conduction states referred to as opening and closing of ion channels with applied potential. A mechanism is being proposed to explain the voltage dependent ion selectivity of the channels in both closed and open states. Nonlinear dynamical analysis of ion transportation and current oscillations confirm its chaotic behavior. Their possible applications as ionic switches and ionic flip-flops are discussed.
A General-Purpose Element-Based Approach to Compute Dispersion Relations in Periodic Materials with Existing Finite Element Codes
Authors: Valencia Camilo , Gomez Juan , Guarín-Zapata Nicolás
Published: August 2019

The numerical determination of dispersion relations in periodic materials via the finite element method is a difficult task in most standard codes. Here, we propose a novel technique which allows the computation of these band structures from local elemental subroutines in contrast with existing methods which impose Bloch boundary conditions on the global arrays. The proposed local approach is thus readily applicable to several physical contexts and space dimensionalities. Here we present the details of this element-based algorithm and provide verification results for three different kinematic assumptions applied to phononic crystals in a classical and a micropolar elastic medium. The paper also includes in the form of supplementary material, a fully-coded user subroutine and a test-problem to be used in a commercial finite element code.
A model-based analysis of autonomic nervous function in response to the Valsalva maneuver
Authors: Randall E. Benjamin , Billeschou Anna , Brinth Louise S. , Mehlsen Jesper , Olufsen Mette S.
Published: August 2019

The Valsalva maneuver (VM) is a diagnostic protocol examining sympathetic and parasympathetic activity in patients with autonomic dysfunction (AD) impacting cardiovascular control. Because direct measurement of these signals is costly and invasive, AD is typically assessed indirectly by analyzing heart rate and blood pressure response patterns. This study introduces a mathematical model that can predict sympathetic and parasympathetic dynamics. Our model-based analysis includes two control mechanisms: respiratory sinus arrhythmia (RSA) and the baroreceptor reflex (baroreflex). The RSA submodel integrates an electrocardiogram-derived respiratory signal with intrathoracic pressure, and the baroreflex submodel differentiates aortic and carotid baroreceptor regions. Patient-specific afferent and efferent signals are determined for 34 control subjects and 5 AD patients, estimating parameters fitting the model output to heart rate data. Results show that inclusion of RSA and distinguishing aortic/carotid regions are necessary to model the heart rate response to the VM. Comparing control subjects to patients shows that RSA and baroreflex responses are significantly diminished. This study compares estimated parameter values from the model-based predictions to indices used in clinical practice. Three indices are computed to determine adrenergic function from the slope of the systolic blood pressure in phase II [ α (a new index)], the baroreceptor sensitivity ( β), and the Valsalva ratio ( γ). Results show that these indices can distinguish between normal and abnormal states, but model-based analysis is needed to differentiate pathological signals. In summary, the model simulates various VM responses and, by combining indices and model predictions, we study the pathologies for 5 AD patients.

NEW & NOTEWORTHY We introduce a patient-specific model analyzing heart rate and blood pressure during a Valsalva maneuver (VM). The model predicts autonomic function incorporating the baroreflex and respiratory sinus arrhythmia (RSA) control mechanisms. We introduce a novel index ( α) characterizing sympathetic activity, which can distinguish control and abnormal patients. However, we assert that modeling and parameter estimation are necessary to explain pathologies. Finally, we show that aortic baroreceptors contribute significantly to the VM and RSA affects early VM.
Influence of nasal CPAP on cardiorespiratory control in healthy neonate
Authors: Al-Omar Sally , Le Rolle Virginie , Pladys Patrick , Samson Nathalie , Hernandez Alfredo , Carrault Guy , Praud Jean-Paul
Published: August 2019

The present study aimed to further unravel the effects of nasal continuous positive airway pressure (nCPAP) on the cardiovascular and respiratory systems in the neonatal period. Six-hour polysomnographic recordings were first performed in seven healthy newborn lambs, aged 2–3 days, without and with nCPAP application at 6 cmH2O (nCPAP-6), in randomized order. The effects of nCPAP-6 on heart rate variability, respiratory rate variability, and cardiorespiratory interrelations were analyzed using a semiautomatic signal processing approach applied to ECG and respiration recordings. Thereafter, a cardiorespiratory mathematical model was adapted to the experimental conditions to gain further physiological interpretation and to simulate higher nCPAP levels (8 and 10 cmH2O). Results from the signal processing approach suggest that nCPAP-6 applied in newborns with healthy lungs: 1) increases heart rate and decreases the time and frequency domain indices of heart rate variability, especially those representing parasympathetic activity, while increasing the complexity of the RR-interval time series; 2) prolongs the respiratory cycle and expiration duration and decreases respiratory rate variability; and 3) slightly impairs cardiorespiratory interrelations. Model-based analysis revealed that nCPAP-6 increases the heart rate and decreases respiratory sinus arrhythmia amplitude, in association with a reduced parasympathetic efferent activity. These results were accentuated when simulating an increased CPAP level. Overall, our results provide a further understanding of the effects of nCPAP in neonates, in the absence of lung disease.

NEW & NOTEWORTHY Application of nasal continuous positive airway pressure (CPAP) at 6 cmH2O, a level very frequently used in newborns, alters heart and respiratory rate variability, as well as cardiorespiratory interrelations in a full-term newborn model without lung disease. Moreover, whereas nasal CPAP at 6 cmH2O decreases parasympathetic efferent activity, there is no change in sympathetic efferent activity.
Inactivity and exercise training differentially regulate abundance of Na+-K+-ATPase in human skeletal muscle
Authors: Wyckelsma V. L. , Perry B. D. , Bangsbo J. , McKenna M. J.
Published: August 2019

Physical inactivity is a global health risk that can be addressed through application of exercise training suitable for an individual’s health and age. People’s willingness to participate in physical activity is often limited by an initially poor physical capability and early onset of fatigue. One factor associated with muscle fatigue during intense contractions is an inexcitability of skeletal muscle cells, reflecting impaired transmembrane Na+/K+exchange and membrane depolarization, which are regulated via the transmembranous protein Na+-K+-ATPase (NKA). This short review focuses on the plasticity of NKA in skeletal muscle in humans after periods of altered usage, exploring NKA upregulation with exercise training and downregulation with physical inactivity. In human skeletal muscle, the NKA content quantified by [3H]ouabain binding site content shows robust, yet tightly constrained, upregulation of 8–22% with physical training, across a broad range of exercise training types. Muscle NKA content in humans undergoes extensive downregulation with injury that involves substantial muscular inactivity. Surprisingly, however, no reduction in NKA content was found in the single study that investigated short-term disuse. Despite clear findings that exercise training and injury modulate NKA content, the adaptability of the individual NKA isoforms in muscle (α1–3and β1–3) and of the accessory and regulatory protein FXYD1 are surprisingly inconsistent across studies, for exercise training as well as for injury/disuse. Potential reasons for this are explored. Finally, we provide suggestions for future studies to provide greater understanding of NKA regulation during exercise training and inactivity in humans.
Quality Indexes Design for Online Monitoring Polymer Injection Molding
Authors: Chen Jian-Yu , Tseng Chien-Chou , Huang Ming-Shyan
Published: August 2019

Quality control is a crucial issue in the injection molding process with target of obtaining a high yield rate and reducing production cost. Consequently, effective methods for monitoring the injection conditions (e.g., pressure, velocity, and temperature) in real-time and adjusting these conditions adaptively as required to ensure a consistent part quality are essential. This study proposes a quality index based on the clamping force increment during the injection cycle, as determined by four strain gauges attached to the tie bars of the injection molding machine. Also, various quality indexes for online quality monitoring and prediction purposes based on the pressure, viscosity, and energy features extracted from the pressure profiles obtained at the load cell, nozzle, and molding cavity, respectively, are compared. The feasibility of the proposed quality indexes is investigated experimentally for various settings of the barrel temperature, back pressure, and rotational speed of the plasticizing screw. It is shown that all of the quality indexes are correlated with the injection-molded quality and hence provide a feasible basis for the realization of an on-line quality monitoring and control system. Particularly, the tie-bar elongation quality index requires no modification or invasion of the injection molding system or cavity and hence provides a particularly attractive solution for monitoring and controlling the part quality.
Variability of Oxaliplatin-Induced Neuropathic Pain Symptoms in Each Cycle and Its Implications on the Management of Colorectal Cancer Patients: A Retrospective Study in South Western Sydney Local Health District Hospitals, Sydney, Australia
Authors: Gebremedhn Endale G. , Shortland Peter J. , Mahns David A.
Published: August 2019

Oxaliplatin-induced neuropathic pain limits treatment compliance. However, the variability of neuropathic pain symptoms in each cycle for individual patients and the impacts on treatment compliance remain untested. Data from 322 adult patients who received oxaliplatin-based chemotherapy were extracted based on pattern of chemotherapy, adverse events, and patient survival. Cox regression and survival analyses were employed. Seventy-eight percent of patients developed neuropathic pain that oscillated between a complete absence and presence on a cycle-by-cycle basis. Consequently, the presence of neuropathy in one cycle did not predict the incidence of neuropathy in subsequent cycles. This implies that neuropathic pain need not be a sufficient criterion to reduce, delay, or cease chemotherapy. In the case of multiple system adverse events during combined drug treatment, the responsible cause for dose reduction was not identified. Cox regression analysis revealed that middle age (61–78 years old,P=0.003) and oxaliplatin cumulative dose <850 mg/m2(P=0.002) were associated with patient mortality. Completion of chemotherapy (8 cycles) and cumulative dose >850 mg/m2of oxaliplatin prolonged the median survival time by 8 and 5 months, respectively. As oxaliplatin-induced neuropathic pain fluctuates across cycles in a manner that varies from patient-to-patient, current assumptions on the predictive nature of the emergence of neuropathy (and its impact on treatment compliance) need to be reconsidered. Detailed patient-by-patient analysis of adverse events should be applied to future studies in order to determine the efficacy of current treatments (and future interventions) and whether neuropathic pain should be retained as a criterion to vary the treatment. Additionally, when two or more system toxicities occurred in cases of combined drug treatment, the causes for drug reduction should be separately recorded.
Effect of Using a Cardiac Catheterization Table-Stabilizing Stick on the Quality of Cardiopulmonary Resuscitation in the Cardiac Catheterization Laboratory: A Simulation-Based Study
Authors: Yamada Tsuyoshi , Ito Morihiro , Urai Hisako , Ueda Yumiko , Maki Hiroaki , Baba Reizo
Published: August 2019

Rapid defibrillation and high-quality cardiopulmonary resuscitation (CPR) are necessary for patients with cardiopulmonary arrest, one of the most serious and frequently encountered complications in cardiac catheterization laboratories. However, when the catheterization table is withdrawn from its neutral position for fluoroscopy, it is unstable and unsuitable for resuscitation because of its cantilever structure. To stabilize the table in its withdrawn position, the use of a table-stabilizing stick might improve CPR quality. To investigate the effect of using a cardiac catheterization table-stabilizing stick on CPR quality, a CPR simulation mannequin was placed on a cardiac catheterization table that was withdrawn from the C-arm of the X-ray machine. CPR quality was assessed with or without the use of a table-stabilizing stick under the table. The CPR quality assessment (Q-CPR) scores were 79.6 ± 11.4% using the table-stabilizing stick and 47.7 ± 30.3% without the use of the stick device (p = 0.02). In this simulation-based study, the use of a table-stabilizing stick in a cardiac catheterization table withdrawn from the C-arm of the X-ray machine improved the quality of CPR.
Design and Construction of Pneumatic Transfer System Controller Unit for Ghana MNSR
Authors: Amponsah-Abu E. O. , Nyarko B. J. B. , Edziah R.
Published: August 2019

Pneumatic Transfer System (PTS) is an auxiliary system of Ghana Research Reactor-1 (GHARR-1) used to transfer sample capsule in and out of the reactor irradiation sites. The PTS’ controller unit design and construction were carried out because the original transfer system was not designed to operate in cyclic NAA. To address these situations, a Programmable Logic Controller (PLC) has been used to design and construct a control unit to facilitate a cyclic neutron activation analysis (CNAA) application for GHARR-1. The design has been simulated successfully using a LOGO Soft Comfort software, version 8. The constructed control unit has been tested experimentally using 220 AC volts electric bulbs to represent solenoid valves. The results show that the sample-IN and sample-OUT bulbs come ON and go OFF to represent the solenoid valves opening and closing for sample transfer. The study has shown that the computer based PLC controller unit for PTS is capable of facilitating both cyclic and conventional NAA application for the GHARR-1.
Investigation of the Prevalence and Diagnosis of Chronic Obstructive Pulmonary Disease in a Group of Elderly Individuals Residing in an Island Area of Ningbo
Authors: Sheng Wei , Huang Youchang , Deng Zaichun , Ma Hongying
Published: August 2019

Objective. This epidemiological investigation aimed at determining the current situation regarding the diagnosis and treatment of chronic obstructive pulmonary disease (COPD), especially missed diagnosis and missed treatment, in a group of individuals residing in an island area of Ningbo. Methods. Adults ≥60 years of age were selected from an island area of Ningbo. All participants completed a COPD-Screening Questionnaire and underwent a post-bronchodilator pulmonary function test. COPD-positive individuals then completed a questionnaire surveying the status of diagnosis and treatment of COPD and the reasons for missed diagnosis and treatment. The data were collated and analyzed using SPSS version 22.0 (IBM Corporation, Armonk, NY, USA). Findings. (1) A total of 1526 individuals were screened, of whom 1371 (89.8%) were eventually included in data analysis. From these, 254 were diagnosed with spirometry-defined COPD, corresponding to an overall prevalence of 18.5%. Prevalence was higher in men (28.9%) than in women (8.3%) among the sample. (2) According to chi-squared test results, risk factors for COPD included sex, age, smoking history (pack-years), cough, and dyspnea. Body mass index, family history of respiratory diseases, and exposure to biomass smoke from cooking were not risk factors for COPD. (3) Multivariate logistic regression analysis revealed that age and smoking were independent risk factors for COPD. (4) Receiver operating curve analysis revealed that, at a cutoff of 19.5, the highest sum of sensitivity and specificity was 69.7% and 75.5%, respectively. The COPD-Screening Questionnaire could be used as a preselection method to screen for COPD in primary care settings. (5) Of 254 individuals diagnosed with COPD, only 10 had a history of COPD and only 35 had a previous diagnosis of pneumonia or bronchitis. These data revealed that the rate of missed diagnosis of COPD in the Ningbo island area was 96.1%. Conclusion. The prevalence of COPD among elderly individuals in the Ningbo island area was significantly higher than in other parts of China. Moreover, the rate of missed diagnosis of COPD in the Ningbo island area was extremely high. Smoking and age were independent factors for the occurrence of COPD.
Can RIPASA Scoring System Predict the Pathological Stage of Acute Appendicitis?
Authors: Karapolat Banu
Published: August 2019

Introduction. Being one of the scoring systems used in the diagnosis of acute appendicitis, the RIPASA score can be used easily with a high diagnostic accuracy. Objective. To evaluate the possible relationship between RIPASA scores and the histopathological examination results of appendectomy materials. Materials and Methods. This study retrospectively reviews 242 patients who were operated in our clinic between January 2016 and January 2018 with a prediagnosis of acute appendicitis, and the RIPASA scores calculated in the preoperative period were compared to the histopathological examination results of the appendectomy specimens. Results. The patients consisted of 124 (51.2%) females and 118 (48.8%) males. The ages of the patients ranged from 15 to 81 years. The patients were divided into 3 groups based on their RIPASA scores as low-score (4-7), intermediate-score (7.5-11.5), and high-score (12 and over) groups. There were 20 (52.6%) catarrhal-stage appendicitis cases and 17 (44.7%) normal appendixes in the low-score group; there were 70 (83.3%) catarrhal-stage appendicitis cases, 9 (10.7%) suppurative-stage appendicitis cases, 4 (4.8%) gangrenous-stage appendicitis cases, and 1 (1.2%) perforated appendicitis case in the intermediate-score group. In the high-score group, there were 53 (44.2%) suppurative-stage appendicitis cases, 51 (42.5%) gangrenous-stage appendicitis cases, 11 (9.2%) perforated appendicitis cases, and 5 (4.2%) catarrhal-stage appendicitis cases. A strong positive correlation was found between the RIPASA scores of the patients and the pathological stage of appendicitis (r=0.889; p<0.001). Conclusion. The RIPASA scoring system can make a correct and prompt diagnosis of acute appendicitis including its possible pathological stage without any need for a computed tomography.
Immune Desertic Landscapes in Hepatocellular Carcinoma Shaped by β-Catenin Activation
Authors: Berraondo Pedro , Ochoa Maria C. , Olivera Irene , Melero Ignacio
Published: August 2019

About one third of cases of hepatocellular carcinoma (HCC) show gain-of-function mutations of CTNNB1 (β-catenin) that correlate with sparse intratumoral T-cell content, as observed previously in an ample spectrum of malignancies, and there is mounting preliminary evidence that such HCC cases are refractory to treatment with PD-1 checkpoint inhibitors. Elegant hepatocarcinogenesis experiments by in vivo gene transfer to mouse hepatocytes show that coexpression of active forms of β-catenin result in poor T-cell infiltrates, faster progression in immunocompetent hosts, and unresponsiveness to immunotherapy with checkpoint inhibitors.

See related article by Ruiz de Galarreta et al., p. 1124.
Exploring Reperfusion Following Endovascular Thrombectomy
Authors: Kosior Jayme C. , Buck Brian , Wannamaker Robert , Kate Mahesh , Liapounova Natalia A. , Rempel Jeremy L. , Butcher Kenneth
Published: August 2019

Background and Purpose—

Cerebral perfusion in acute ischemic stroke patients is often assessed before endovascular thrombectomy (EVT), but rarely after. Perfusion data obtained following EVT may provide additional prognostic information. We developed a tool to quantitatively derive perfusion measurements from digital subtraction angiography (DSA) data and examined perfusion in patients following EVT.

Methods—

Source DSA images from acute anterior circulation stroke patients undergoing EVT were retrospectively assessed. Following deconvolution, maps of mean transit time (MTT) were generated from post-EVT DSA source data. Thrombolysis in Cerebral Infarction grades and MTT in patients with and without hemorrhagic transformation (HT) at 24 hours were compared. Receiver operating characteristic modeling was used to classify the presence/absence of HT at 24 hours by MTT.

Results—

Perfusion maps were generated in 50 patients using DSA acquisitions that were a median (interquartile range) of 9 (8–10) seconds in duration. The median post-EVT MTT within the affected territory was 2.6 (2.2–3.3) seconds. HT was observed on follow-up computed tomography in 16 (32%) patients. Thrombolysis in Cerebral Infarction grades did not differ in patients with HT from those without (
P
=0.575). Post-EVT MTT maps demonstrated focal areas of hyperperfusion (n=8) or persisting hypoperfusion (n=3) corresponding to the regions where HT later developed. The relationship between MTT and HT was
U
-shaped; HT occurred in patients at both the lowest and highest extremes of MTT. An MTT threshold <2 or >4 seconds was 81% sensitive and 94% specific for classifying the presence of HT at follow-up.

Conclusions—

Perfusion measurements can be obtained using DSA perfusion with minimal changes to current stroke protocols. Perfusion imaging post-recanalization may have additional clinical utility beyond visual assessment of source angiographic images alone.
First records of six species of mantis shrimp (Stomatopoda) from Korea with a key to the Korean species
Authors: Hwang Hee-Seung , Ahyong Shane T. , Kim Won
Published: August 2019

The Stomatopoda of Korea have, in general, been poorly studied, with eight species recorded to date. A recent study of stomatopods collected by SCUBA diving and commercial fishing trawlers from Korean waters, however, resulted in the discovery of first records of six species from the study area. Among them, four belong to the superfamily Squilloidea Latreille, 1802 [Levisquilla inermis (Manning, 1965), Levisquilla jurichi (Makarov, 1979), Anchisquilla fasciata (De Haan, 1844), and Cloridopsis scorpio (Latreille, 1828)], and two belong to the Lysiosquilloidea Giesbrecht, 1910, one each in Tetrasquillidae Manning & Camp, 1993 [Acaenosquilla latifrons (De Haan, 1844)] and Nannosquillidae Manning, 1980 [Acanthosquilla multifasciata (Wood-Mason, 1895)]. Thus, fourteen species of Stomatopoda are now known from Korea. The superfamily Lysiosquilloidea is reported for the first time from Korean waters. A key to the species of Korean mantis shrimps is provided.
The Fluid Nature of Street Culture: Non-Violent Participation, Changes in Adult Life, and Crumbling Ethnic Barriers in Germany
Authors: Zdun Steffen
Published: August 2019

This paper examines changes in the practice of street culture among non-violent young adult men. Many individuals who participate in street culture behave and talk in a pretty rough way among each other and act almost aggressively. This is done for establishing a certain reputation and self-image that relates to street culture rules and it is even widespread among non-violent players of this milieu. A comprehensive look on their behavior includes modifications of street culture practices in adult life. Another aspect of the fluid nature of street culture are crumbling ethnic barriers in this milieu in Germany. The latter contributes to further modifications, for instance, in social contacts and language use. The author provides supportive evidence from the existing literature and field work he has done in Germany.
Impact of Ground-Based Remote Sensing Boundary Layer Observations on Short-Term Probabilistic Forecasts of a Tornadic Supercell Event
Authors: Hu Junjun , Yussouf Nusrat , Turner David D. , Jones Thomas A. , Wang Xuguang
Published: August 2019

Due to lack of high spatial and temporal resolution boundary layer (BL) observations, the rapid changes in the near-storm environment are not well represented in current convective-scale numerical models. Better representation of the near-storm environment in model initial conditions will likely further improve the forecasts of severe convective weather. This study investigates the impact of assimilating high temporal resolution BL retrievals from two ground-based remote sensing instruments for short-term forecasts of a tornadic supercell event on 13 July 2015 during the Plains Elevated Convection At Night field campaign. The instruments are the Atmospheric Emitted Radiance Interferometer (AERI) that retrieves thermodynamic profiles and the Doppler lidar (DL) that measures horizontal wind profiles. Six sets of convective-scale ensemble data assimilation (DA) experiments are performed: two control experiments that assimilate conventional and WSR-88D radar observations using either relaxation-to-prior-spread (RTPS) or the adaptive inflation (AI) technique and four experiments similar to the control but that assimilate either DL or AERI or both observations in addition to all other observations that are in the control experiments. Results indicate a positive impact of AERI and DL observations in forecasting convective initiation (CI) and early evolution of the supercell storm. The experiment that employs the AI technique to assimilate BL observations in DA enhances the humidity in the near-storm environment and low-level convergence, which in turn helps forecasting CI. The forecast improvement is most pronounced during the first ~3 h. Results also indicate that the AERI observations have a larger impact compared to DL in predicting CI.
Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance
Authors: Stagg Helen R. , Bothamley Graham H. , Davidson Jennifer A. , Kunst Heinke , Lalor Maeve K. , Lipman Marc C. , Loutet Miranda G. , Lozewicz Stefan , Mohiyuddin Tehreem , Abbara Aula , Alexander Eliza , Booth Helen , Creer Dean D. , Harris Ross J. , Kon Onn Min , Loebinger Michael R. , McHugh Timothy D. , Milburn Heather J. , Palchaudhuri Paramita , Phillips Patrick P.J. , Schmok Erik , Taylor Lucy , Abubakar Ibrahim
Published: August 2019

Introduction

2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance.

Methods

This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009–2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence).

Results

Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60–1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14–2.28) when Hr genotype was included, but this analysis lacked power (p=0.42).

Conclusions

In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations.
Painful Inguinal Angiomyomatous Hamartoma Responsive to Conservative Pain Management: A Case Report
Authors: Woolley Christopher A. , Oswald Jessica , Chen Jeffrey
Published: August 2019

Angiomyomatous hamartoma (AMH) is a rare and benign mixed-tissue tumor of the lymphatic system. The majority of AMH tumors are removed surgically for cosmetic reasons or during workup of lymphadenopathy. There are few reported cases of this condition in the literature; AMH does not cause pain, and there are no published reports of AMH recurring after surgical excision. Here, we report a unique case of inguinal AMH recurring after surgical excision and causing a painful compression neuropathy. Our report also describes the patient’s successful but transient response to nonsurgical pain management.
MicroRNA-138 negatively regulates the hypoxia-inducible factor 1α to suppress melanoma growth and metastasis
Authors: Qiu Haijiang , Chen Fangchao , Chen Minjun
Published: August 2019

Melanoma with rapid progression towards metastasis has become the deadliest form of skin cancer. However, the mechanism of melanoma growth and metastasis is still unclear. Here, we found that miRNA-138 was lowly expressed and hypoxia-inducible factor 1α (HIF1α) was highly expressed in patients’ melanoma tissue compared with the paracancerous tissues, and they had a significant negative correlation (r=−0.877, P<0.001). Patients with miRNA-138low/HIF1αhigh signatures were predominant in late stage III/IV of melanoma. Further, bioinformatic analysis demonstrated that miRNA-138 directly targeted HIF1α. We found that the introduction of pre-miRNA-138 sequences to A375 cells reduced HIF1α mRNA expression and suppressed cell proliferation, migration and invasion. Overexpression of miRNA-138 or inhibition of HIF1α significantly suppressed the growth and metastasis of melanoma in vivo. Our study demonstrates the role and clinical relevance of miRNA-138 and HIF1α in melanoma cell growth and metastasis, providing a novel therapeutic target for suppression of melanoma growth and metastasis.
Should We Tax Sugar-Sweetened Beverages? An Overview of Theory and Evidence
Authors: Allcott Hunt , Lockwood Benjamin B. , Taubinsky Dmitry
Published: August 2019

Taxes on sugar-sweetened beverages are growing in popularity and have generated an active public debate. Are they a good idea? If so, how high should they be? Are such taxes regressive? People in the United States and some other countries consume remarkable quantities of sugar-sweetened beverages, and the evidence suggests that this generates significant health costs. Building on recent work, we review the basic economic principles that determine the socially optimal sugar-sweetened beverage tax. The optimal tax depends on (1) externalities, or uninternalized health system costs from diseases caused by sugary drink consumption; (2) internalities, or costs consumers impose on themselves by consuming too many sugary drinks due to poor nutrition knowledge and/or lack of self-control; and (3) regressivity, or how much the financial burden and the internality benefits from the tax fall on the poor. We summarize the empirical evidence about the key parameters that determine how large the tax should be. Our calculations suggest that sugar-sweetened beverage taxes are welfare enhancing and indeed that the optimal sugar-sweetened beverage tax rate may be higher than the 1 cent per ounce rate most commonly used in US cities. We end with seven concrete suggestions for policymakers considering a sugar-sweetened beverage tax.
The quantitative neuroradiology initiative framework: application to dementia
Authors: Goodkin Olivia , Pemberton Hugh , Vos Sjoerd B , Prados Ferran , Sudre Carole H , Moggridge James , Cardoso M. Jorge , Ourselin Sebastien , Bisdas Sotirios , White Mark , Yousry Tarek , Thornton John , Barkhof Frederik
Published: August 2019

There are numerous challenges to identifying, developing and implementing quantitative techniques for use in clinical radiology, suggesting the need for a common translational pathway. We developed the quantitative neuroradiology initiative (QNI), as a model framework for the technical and clinical validation necessary to embed automated segmentation and other image quantification software into the clinical neuroradiology workflow. We hypothesize that quantification will support reporters with clinically relevant measures contextualized with normative data, increase the precision of longitudinal comparisons, and generate more consistent reporting across levels of radiologists’ experience. The QNI framework comprises the following steps: (1) establishing an area of clinical need and identifying the appropriate proven imaging biomarker(s) for the disease in question; (2) developing a method for automated analysis of these biomarkers, by designing an algorithm and compiling reference data; (3) communicating the results via an intuitive and accessible quantitative report; (4) technically and clinically validating the proposed tool pre-use; (5) integrating the developed analysis pipeline into the clinical reporting workflow; and (6) performing in-use evaluation. We will use current radiology practice in dementia as an example, where radiologists have established visual rating scales to describe the degree and pattern of atrophy they detect. These can be helpful, but are somewhat subjective and coarse classifiers, suffering from floor and ceiling limitations. Meanwhile, several imaging biomarkers relevant to dementia diagnosis and management have been proposed in the literature; some clinically approved radiology software tools exist but in general, these have not undergone rigorous clinical validation in high volume or in tertiary dementia centres. The QNI framework aims to address this need. Quantitative image analysis is developing apace within the research domain. Translating quantitative techniques into the clinical setting presents significant challenges, which must be addressed to meet the increasing demand for accurate, timely and impactful clinical imaging services.
The impact of city-wide deployment of Wolbachia-carrying mosquitoes on arboviral disease incidence in Medellín and Bello, Colombia: study protocol for an interrupted time-series analysis and a test-negative design study
Authors: Velez Ivan D. , Santacruz Eduardo , Kutcher Simon C. , Duque Sandra L. , Uribe Alexander , Barajas Jovany , Gonzalez Sandra , Patino Ana Cristina , Zuluaga Lina , Martínez Luis , Mejia María Camila , Arbelaez María Patricia , Pulido Henry , Jewell Nicholas P. , O'Neill Scott L. , Simmons Cameron P. , Anders Katherine L. , Tanamas Stephanie K.
Published: August 2019

Background: Dengue, chikungunya and Zika are viral infections transmitted by Aedes aegypti mosquitoes, and present major public health challenges in tropical regions. Traditional vector control methods have been ineffective at halting disease transmission. The World Mosquito Program has developed a novel approach to arbovirus control using Ae. aegypti stably transfected with the Wolbachia bacterium, which have significantly reduced ability to transmit dengue, Zika and chikungunya in laboratory experiments. Field releases in eight countries have demonstrated Wolbachia establishment in local Ae. aegypti populations.

Methods: We describe a pragmatic approach to measuring the epidemiological impact of city-wide Wolbachia deployments in Bello and Medellín, Colombia. First, an interrupted time-series analysis will compare the incidence of dengue, chikungunya and Zika case notifications before and after Wolbachia releases, across the two municipalities. Second, a prospective case-control study using a test-negative design will be conducted in one quadrant of Medellín. Three of the six contiguous release zones in the case-control area were allocated to receive the first Wolbachia deployments in the city and three to be treated last, approximating a parallel two-arm trial for the >12-month period during which Wolbachia exposure remains discordant. Allocation, although non-random, aimed to maximise balance between arms in historical dengue incidence and demographics. Arboviral disease cases and arbovirus-negative controls will be enrolled concurrently from febrile patients presenting to primary care, with case/control status classified retrospectively following laboratory diagnostic testing. Intervention effect is estimated from an aggregate odds ratio comparing Wolbachia-exposure odds among test-positive cases versus test-negative controls.

Discussion: The study findings will add to an accumulating body of evidence from global field sites on the efficacy of the Wolbachia method in reducing arboviral disease incidence, and can inform decisions on wider public health implementation of this intervention in the Americas and beyond.

Trial registration: ClinicalTrials.gov: NCT03631719. Registered on 15 August 2018.
Recursive Calculation Model for a Special Multivariate Normal Probability of First-Order Stationary Sequence
Authors: Xie Jietao , Wu Juan
Published: August 2019

The consecutive hit probability of antiaircraft artillery corresponds to the multivariate normal probability distribution. The computational complexity depends on the length of the firing error sequence (i.e., the integral dimension may exceed 100). The traditional numerical integration and the Monte Carlo method are too slow for this calculation. This paper established the state equation of the firing error sequence, which was the bridge between the multivariate normal probability distribution and stochastic process theory. The recursive calculation model was given after the rigorous derivation process. The accuracy and computational complexity of the model were quantified by theoretical analysis and expressed intuitively by examples. The model shows the upper bound for the absolute error, and the computational efficiency is significantly improved.