bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics of Simian Immunodeficiency Virus Two-Long-Terminal-Repeat Circles in the Presence and Absence of CD8+Cells
Authors: Policicchio Benjamin B. , Cardozo Erwing Fabian , Sette Paola , Xu Cuiling , Haret-Richter George , Dunsmore Tammy , Apetrei Cristian , Pandrea Ivona , Ribeiro Ruy M. 
Published: April 2018

ABSTRACTCD8+cells play a key role in human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection, but their specific mechanism(s) of action in controlling the virus is unclear. Two-long-terminal-repeat (2-LTR) circles are extrachromosomal products generated upon failed integration of HIV/SIV. To understand the specific effects of CD8+cells on infected cells, we analyzed the dynamics of 2-LTR circles in SIVmac251-infected rhesus macaques (RMs) treated with an integrase inhibitor (INT). Twenty RMs underwent CD8+cell depletion and received raltegravir (RAL) monotherapy or a combination of both. Blood, lymph nodes (LNs), and gut biopsy specimens were routinely sampled. Plasma viral loads (pVLs) and 2-LTR circles from peripheral blood mononuclear cells (PBMCs) and LN lymphocytes were measured with quantitative reverse transcription-PCR (qRT-PCR). In the CD8 depletion group, an ∼1-log increase in pVLs and a slow increase in PBMC 2-LTRs occurred following depletion. In the INT group, a strong decline in pVLs upon treatment initiation and no change in 2-LTR levels were observed. In the INT and CD8+cell depletion group, an increase in pVLs following CD8 depletion similar to that in the CD8 depletion group was observed, with a modest decline following INT initiation, and 2-LTR circles significantly increased in PBMCs and LNs. Analyzing the 2-LTR data across all treatment groups with a mathematical model indicates that the data best support an effect of CD8+cells in killing cells prior to viral integration. Sensitivity analyses of these results confirm that effect but also allow for additional effects, which the data do not discriminate well. Overall, we show that INT does not significantly increase the levels of 2-LTR circles. However, CD8+cell depletion increases the 2-LTR levels, which are enhanced in the presence of an INT.IMPORTANCECD8+T cells play an essential role in controlling HIV and SIV infection, but the specific mechanisms involved remain poorly understood. Due to failed viral infection, HIV and SIV can form 2-LTR extrachromosomal circles that can be quantified. We present novel data on the dynamics of these 2-LTR forms in a SIV-infected macaque model under three different treatment conditions: depletion of CD8+cells, administration of the integrase inhibitor in a monotherapy, which favors the formation of 2-LTR circles, and a combination of the two treatments. We used a new mathematical model to help interpret the data, and the results suggest that CD8+cells exert a killing effect on infected cells prior to virus integration. These results provide new insights into the mechanisms of action of CD8+cells in SIV infection. Confirmation of our results would be an important step in understanding immune control of HIV.
Femoral Nerve Block Intervention in Neck of Femur Fracture (FINOF): a randomised controlled trial
Authors: Rowlands Martin , Walt Gerrie van de , Bradley Jim , Mannings Alexa , Armstrong Sarah , Bedforth Nigel , Moppett Iain K , Sahota Opinder 
Published: April 2018

ObjectiveFractured neck of femur is a severely painful condition with significant mortality and morbidity. We investigated whether early and continuous use of femoral nerve block can improve pain on movement and mobility after surgery in older participants with fragility neck of femur fracture.DesignProspective single-centre, randomised controlled pragmatic trial.SettingSecondary care, acute National Health Service Trust, UK.ParticipantsParticipants admitted with a history and examination suggesting fractured neck of femur.InterventionImmediate continuous femoral nerve block via catheter or standard analgesia.Outcome measuresPrimary outcome measures were Cumulative Dynamic Pain score and Cumulated Ambulation Score from surgery until day 3 postoperatively. Secondary outcome measures included pain scores at rest, cumulative side effects (nausea and constipation), quality of life (measured by EuroQOL 5 D instrument (EQ-5D) score) at day 3 and day 30, and rehabilitation outcome (measured by mobility score).Results141 participants were recruited, with 23 excluded. No significant difference was detected between Cumulative Dynamic Pain Score (standard care (n=56) vs intervention (n=55) 20 (IQR 15–24) vs 20 (15–23), p=0.51) or Cumulated Ambulation Score (standard care vs intervention 6 (5–9) vs 7 (5–10), p=0.76). There were no statistically different differences in secondary outcomes except cumulative pain at rest: 5 (0.5–6.5) in the standard care group and 2 (0–5) in the intervention group (p=0.043).ConclusionsEarly application of continuous femoral nerve block compared with standard systemic analgesia did not result in improved dynamic pain score or superior postoperative ambulation. This technique may provide superior pain relief at rest. Continuous femoral nerve block did not delay initial control of pain or mobilisation after surgery.Trial registration numberISRCTN92946117; Pre-results.
Minimum pupil in pupillary response to light and myopia affect disk halo size: a cross-sectional study
Authors: Zhao Feng , Han Tian , Chen Xun , Chen Zhi , Zheng Ke , Wang Xiaoying , Zhou Xingtao 
Published: April 2018

ObjectivesTo evaluate the relationship between pupillary response to light, myopia and disk halo size.DesignCross-sectional study.SettingSingle refractive surgery centre.ParticipantsIn this study, 197 right eyes of 197 patients between 20 and 35 years of age were evaluated for disk halo size and pupillary response to light with a vision monitor.Primary and secondary outcome measuresHalo radius, age, spherical equivalent (SE), axial length (AL), initial diameter, amplitude of contraction, latency of contraction, duration of contraction, velocity of contraction, latency of dilation, duration of dilation, velocity of dilation, maximum pupil, minimum pupil, average pupil and dark pupil.ResultsSignificant associations were found between disk halo size and SE (r=−0.219, P=0.002), AL (r=0.152, P=0.033) and minimum pupil (r=0.149, P=0.037). There were no associations between disk halo size and initial diameter, amplitude of contraction, latency of contraction, duration of contraction, velocity of contraction, latency of dilation, duration of dilation, velocity of dilation, maximum pupil, average pupil, dark pupil and age (P>0.05). A significant difference in disk halo size was detected between the low-moderate and high myopia (SE< −6 D) groups (P=0.002) and between the small and large (minimum pupil≥4 mm) minimum pupil size groups (P=0.014).ConclusionsPatients with a high SE and large minimum pupil size (minimum pupil ≥4 mm) suffered more disability glare than those with a low SE and small minimum pupil size.
Effect of intratracheal dexmedetomidine administration on recovery from general anaesthesia after gynaecological laparoscopic surgery: a randomised double-blinded study
Authors: Wang Fei , Zhong Haoxiang , Xie Xiaoyan , Sha Weiping , Li Caili , Li Zhenping , Huang Zhuomei , Chen Chaojin 
Published: April 2018

ObjectivesTo examine the efficacy of intratracheal dexmedetomidine (Dex) injection for the prevention of the laryngeal response on emergence from general anaesthesia following gynaecological laparoscopic surgery.DesignProspective, randomised, double-blinded, controlled trial.SettingA general hospital, Guangdong Province, China.ParticipantsAll patients who underwent elective laparoscopic gynaecological surgery, aged 18–60 years old, 40–80 kg in weight, American Society of Anesthesiologists class I–II were eligible. Patients were excluded if they had respiratory disease, heart disorders which might represent risk factors of potential complications of Dex such as bradycardia, heart block, coronary heart disease, uncontrolled hypertension or the long-term use of sedative drugs.InterventionPatients were randomly allocated to either receive intratracheal Dex (DT), intravenous Dex (DV) or intravenous saline (CON, n=30, respectively). In the DT and DV groups, Dex (0.5 µg/kg) was diluted and mixed in 1 or 20 mL of saline, respectively, and injected via the intratracheal or intravenous route 30 min before the completion of the surgery.Outcome measuresThe primary outcome was the coughing extent among the three groups. Secondary outcomes included awareness time, extubation time, postoperative visual analogue scale and Steward recovery score.ResultsCompared with the CON group, the extent of coughing was significantly reduced in both the DV group and the DT group. Furthermore, the mean time to awareness (13.4 (4.3) vs 8.8 (2.9), p<0.001) and the extubation time (14.3 (4.3) vs 8.4 (3.6), p<0.001) were reduced in the DT group. Patients in the DT group also experienced better early recovery quality and less pain than those in the CON group. Furthermore, intratracheal Dex administration contributed to improved stability in haemodynamics with no significant side effects.ConclusionsIntratracheal Dex administration may avoid untoward laryngeal responses for patients emerging from general anaesthesia after gynaecological laparoscopy.Trial registration numberChiCTR-IOR-15007611.
Fatigue in patients with chronic obstructive pulmonary disease: protocol of the Dutch multicentre, longitudinal, observationalFAntasTIGUEstudy
Authors: Goërtz Yvonne M J , Looijmans Milou , Prins Judith B , Janssen Daisy J A , Thong Melissa S Y , Peters Jeannette B , Burtin Chris , Meertens-Kerris Yvonne , Coors Arnold , Muris Jean W M , Sprangers Mirjam A G , Wouters Emiel F M , Vercoulen Jan H , Spruit Martijn A 
Published: April 2018

IntroductionFatigue is the second most common symptom in patients with chronic obstructive pulmonary disease (COPD). Despite its high prevalence, fatigue is often ignored in daily practice. For this reason, little is known about the underlying determinants of fatigue in patients with COPD. The primary objectives of this study are to chart the course of fatigue in patients with COPD, to identify the physical, systemic, psychological and behavioural factors that precipitate and perpetuate fatigue in patients with COPD, to evaluate the impact of exacerbation-related hospitalisations on fatigue and to better understand the association between fatigue and 2-year all-cause hospitalisation and mortality in patients with COPD. The secondary aim is to identify diurnal differences in fatigue by using ecological momentary assessment (EMA). This manuscript describes the protocol of theFAntasTIGUEstudy and gives an overview of the possible strengths, weaknesses and clinical implications.Methods and analysisA 2-year longitudinal, observational study, enrolling 400 patients with clinically stable COPD has been designed. Fatigue, the primary outcome, will be measured by the subjective fatigue subscale of the Checklist Individual Strength (CIS-Fatigue). The secondary outcome is the day-to-day/diurnal fatigue, registered in a subsample (n=60) by EMA. CIS-Fatigue and EMA will be evaluated at baseline, and at 4, 8 and 12 months. The precipitating and perpetuating factors of fatigue (physical, psychological, behavioural and systemic) will be assessed at baseline and at 12 months. Additional assessments will be conducted following hospitalisation due to an exacerbation of COPD that occurs between baseline and 12 months. Finally, at 18 and 24 months the participants will be followed up on their fatigue, number of exacerbations, exacerbation-related hospitalisation and survival.Ethics and disseminationThis protocol was approved by the Medical research Ethics Committees United, Nieuwegein, the Netherlands (NL60484.100.17).Trial registration numberNTR6933; Pre-results.
Finite Automata Over Infinite Alphabets: Two Models with Transitions for Local Change
Authors: Czyba Christopher , Thomas Wolfgang , Spinrath Christopher 
Published: April 2018

Two models of automata over infinite alphabets are presented, mainly with a focus on the alphabet [Formula: see text]. In the first model, transitions can refer to logic formulas that connect properties of successive letters. In the second, the letters are considered as columns of a labeled grid which an automaton traverses column by column. Thus, both models focus on the comparison of successive letters, i.e. “local changes”. We prove closure (and non-closure) properties, show the decidability of the respective non-emptiness problems, prove limits on decidability results for extended models, and discuss open issues in the development of a generalized theory.
Graph-Grammar-Based IP-Integration (GRIP)—An EDA Tool for Software-Defined SoCs
Authors: Jassi Munish , Hu Yong , Mueller-Gritschneder Daniel , Schlichtmann Ulf 
Published: April 2018

In modern system-on-chip (SoC) designs, IP-reuse is considered a driving force to increase productivity. To support various designs, a huge amount of Intellectual Property (IP) hardware blocks have been developed. The integration of those IPs into an SoC may require significant effort—up to days or weeks depending on experience and complexity. This article presents a novel approach to significantly reduce the design effort to bring-up a working SoC design by automatic IP integration as part of a library-based Software-defined SoC flow. In detail, the IP-supplier prepares a HW-accelerated software library (HASL) for the SoC architect, who wants to use the IP in an SoC design. As a key point of our approach, integration knowledge is encoded in the library as a set of integration rules. These rules are defined in the machine-readable standardized IP-XACT format by the IP supplier, who has a good knowledge of the IP’s hardware details. The library preparation step on the IP supplier’s side is also partly automated in the proposed flow, including a partial generation of configurable HW drivers, schedulers, and the software library functions. For the SoC architect, we have developed the graph-grammar-based IP-integration (GRIP) tool. The software application is developed using the functions supplied in the HASL. According to the calls to the HASL functions, the GRIP tool automatically integrates IP-blocks using the rule information supplied with the library and runs a full Design Space Exploration. For this, the SoC architecture and rules are transformed into the graph domain to apply graph rewriting methods. The GRIP tool is model-driven and based on the Eclipse Modeling Framework. With code generation techniques, SoC candidate architectures can be transformed to hardware descriptions for the target platform. The HW/SW interfaces between SW library functions and IP blocks can be automatically generated for bare-metal or Linux-based applications.
The approach is demonstrated with two case-studies on the Xilinx Zynq-based ZedBoard evaluation board using a HASL for computer vision. It can yield 10×-150× performance improvement for the bare-metal application versions and 4×--7× performance improvement for the Linux-based application versions, when executed on an optimized HW-accelerated SoC architecture compared to a non HW-accelerated SoC. The effort for IP integration is comparable to using a software library, hence, providing a significant advantage over a manual IP integration.
Asymmetric interference between cognitive task components and concurrent sensorimotor coordination
Authors: Baker Joshua , Castro Antonio , Dunn Andrew K. , Mitra Suvobrata 
Published: April 2018

Everyday cognitive tasks are frequently performed under dual-task conditions alongside continuous sensorimotor coordinations (CSCs) such as driving, walking, or balancing. Observed interference in these dual-task settings is commonly attributed to demands on executive function or attentional resources, but the time course and reciprocity of interference are not well understood at the level of information-processing components. Here we used electrophysiology to study the detailed chronometry of dual-task interference between a visual oddball task and a continuous visuomanual tracking task. The oddball task’s electrophysiological components were linked to underlying cognitive processes, and the tracking task served as a proxy for the continuous cycle of state monitoring and adjustment inherent to CSCs. Dual-tasking interfered with the oddball task’s accuracy and attentional processes (attenuated P2 and P3b magnitude and parietal alpha-band event-related desynchronization), but errors in tracking due to dual-tasking accrued at a later timescale and only in trials in which the target stimulus appeared and its tally had to be incremented. Interference between cognitive tasks and CSCs can be asymmetric in terms of timing as well as affected information-processing components. NEW & NOTEWORTHY Interference between cognitive tasks and continuous sensorimotor coordination (CSC) has been widely reported, but this is the first demonstration that the cognitive operation that is impaired by concurrent CSC may not be the one that impairs the CSC. Also demonstrated is that interference between such tasks can be temporally asymmetric. The asynchronicity of this interference has significant implications for understanding and mitigating loss of mobility in old age, and for rehabilitation for neurological impairments.
Multisensory enhancement of burst activity in an insect auditory neuron
Authors: Someya Makoto , Ogawa Hiroto 
Published: April 2018

Detecting predators is crucial for survival. In insects, a few sensory interneurons receiving sensory input from a distinct receptive organ extract specific features informing the animal about approaching predators and mediate avoidance behaviors. Although integration of multiple sensory cues relevant to the predator enhances sensitivity and precision, it has not been established whether the sensory interneurons that act as predator detectors integrate multiple modalities of sensory inputs elicited by predators. Using intracellular recording techniques, we found that the cricket auditory neuron AN2, which is sensitive to the ultrasound-like echolocation calls of bats, responds to airflow stimuli transduced by the cercal organ, a mechanoreceptor in the abdomen. AN2 enhanced spike outputs in response to cross-modal stimuli combining sound with airflow, and the linearity of the summation of multisensory integration depended on the magnitude of the evoked response. The enhanced AN2 activity contained bursts, triggering avoidance behavior. Moreover, cross-modal stimuli elicited larger and longer lasting excitatory postsynaptic potentials (EPSP) than unimodal stimuli, which would result from a sublinear summation of EPSPs evoked respectively by sound or airflow. The persistence of EPSPs was correlated with the occurrence and structure of burst activity. Our findings indicate that AN2 integrates bimodal signals and that multisensory integration rather than unimodal stimulation alone more reliably generates bursting activity.NEW & NOTEWORTHY Crickets detect ultrasound with their tympanum and airflow with their cercal organ and process them as alert signals of predators. These sensory signals are integrated by auditory neuron AN2 in the early stages of sensory processing. Multisensory inputs from different sensory channels enhanced excitatory postsynaptic potentials to facilitate burst firing, which could trigger avoidance steering in flying crickets. Our results highlight the cellular basis of multisensory integration in AN2 and possible effects on escape behavior.
Cardiovascular and Cerebrovascular Emergency Department Visits Associated With Wildfire Smoke Exposure in California in 2015
Authors: Wettstein Zachary S. , Hoshiko Sumi , Fahimi Jahan , Harrison Robert J. , Cascio Wayne E. , Rappold Ana G. 
Published: April 2018

Background
Wildfire smoke is known to exacerbate respiratory conditions; however, evidence for cardiovascular and cerebrovascular events has been inconsistent, despite biological plausibility.

Methods and Results

A population‐based epidemiologic analysis was conducted for daily cardiovascular and cerebrovascular emergency department (
ED
) visits and wildfire smoke exposure in 2015 among adults in 8 California air basins. A quasi‐Poisson regression model was used for
zip
code‐level counts of
ED
visits, adjusting for heat index, day of week, seasonality, and population. Satellite‐imaged smoke plumes were classified as light, medium, or dense based on model‐estimated concentrations of fine particulate matter. Relative risk was determined for smoky days for lag days 0 to 4. Rates of
ED
visits by age‐ and sex‐stratified groups were also examined. Rates of all‐cause cardiovascular
ED
visits were elevated across all lags, with the greatest increase on dense smoke days and among those aged ≥65 years at lag 0 (relative risk 1.15, 95% confidence interval [1.09, 1.22]). All‐cause cerebrovascular visits were associated with smoke, especially among those 65 years and older, (1.22 [1.00, 1.49], dense smoke, lag 1). Respiratory conditions were also increased, as anticipated (1.18 [1.08, 1.28], adults >65 years, dense smoke, lag 1). No association was found for the control condition, acute appendicitis. Elevated risks for individual diagnoses included myocardial infarction, ischemic heart disease, heart failure, dysrhythmia, pulmonary embolism, ischemic stroke, and transient ischemic attack.

Conclusions

Analysis of an extensive wildfire season found smoke exposure to be associated with cardiovascular and cerebrovascular
ED
visits for all adults, particularly for those over aged 65 years.
Dominic of Flanders’ Critique of John Duns Scotus’ Primary Argument for the Univocity of Being
Authors: D’Ettore Domenic 
Published: April 2018

Abstract
This article considers the attempt by a prominent fifteenth-century follower of Thomas Aquinas, Dominic of Flanders (a.k.a. Flandrensis, 1425-1479), to address John Duns Scotus’ most famous argument for the univocity of being. According to Scotus, the intellect must have a concept of being that is univocal to substantial and accidental being, and to finite and infinite being, on the grounds that an intellect cannot be both certain and doubtful through the same concept, but an intellect can be certain that something is a being while doubting whether it is a substance or accident, finite or infinite. The article shows how Flandrensis’ reply in defence of analogy of being hinges on a more fundamental disagreement with Scotus over the division of the logically one. It also shows how Flandrensis’ answer to this question commits him to a position on the unity of the concept of being that lies between the positions of Scotus and of Flandrensis’ earlier Thomistic sources.
Driving with Parkinson’s disease: Cut points for clinical predictors of on-road outcomes
Authors: Alvarez Liliana , Classen Sherrilene 
Published: April 2018

Background. Parkinson’s disease (PD) is a common neurodegenerative disorder that impacts a person’s fitness to drive. Practitioners require a sensitive and predictive battery of clinical tests to identify at-risk drivers. Purpose. This study aimed to identify clinical predictors and their optimal cut points, sensitivity, specificity, and predictive values of on-road outcomes in drivers with PD. Method. Participants ( N = 101) underwent a comprehensive driving evaluation. We identified predictors of pass/fail outcomes through logistic regression and computed optimal cut points through receiver operating characteristic curves and corresponding Youden indexes. Findings. The Trail Making Test Part B (Trails B; sensitivity = .89, specificity = .74; positive predictive value [PPV] = .71; negative predictive value [NPV] = .91) and contrast sensitivity (sensitivity = .82, specificity = .63; PPV = .61; NPV = .84) emerged as significant predictors. The optimal cut point for the Trails B was 108 s (area under the curve = .86). Implications. Occupational therapists can benefit from implementing Trails B and contrast sensitivity screening as part of in-office screening of potentially at-risk drivers with PD.