bluuebunny/crossref_metadata_2025 huggingface dataset:
Protocol for a randomised, single-blind, two-arm, parallel-group controlled trial of the efficacy of rhinothermy delivered by nasal high flow therapy in the treatment of the common cold
Authors: Bird Grace , Braithwaite Irene , Harper James , McKinstry Steven , Koorevaar Iris , Fingleton James , Semprini Alex , Dilcher Meik , Jennings Lance , Weatherall Mark , Beasley Richard
Published: June 2019

Introduction

The common cold is the most common infectious disease affecting humans. It is usually a self-limiting disease; however, the common cold can cause significant morbidity and has a substantial economic impact on society. Human rhinoviruses (HRVs), which cause up to two-thirds of colds, have temperature-dependent replication and most HRV strains replicate optimally at 33°C. Delivery of heated, humidified air to the upper airways has the potential to reduce viral replication, but evidence of the effectiveness of this treatment of the common cold is inconclusive. We plan to test the hypothesis that delivery of humidified air heated to 41°C at high flow, nasal high flow rhinothermy (rNHF), for 2 hours daily for five days is more effective in reducing common cold symptom severity and duration than five days of ‘sham’ rhinothermy.

Methods and analysis

This is a randomised, single-blind, parallel-group trial comparing rNHF to ‘sham’ rhinothermy in the treatment of common cold. We plan to recruit 170 participants within 48 hours of the onset of symptoms of common cold and randomise them 1:1 to receive one of the two treatments for five days. The study duration is 14 days, which includes clinic visits on the first day of randomisation and four days post-randomisation, and a phone call on the 14th day. Participants will complete daily symptom diaries which include a symptom score, the Modified Jackson Score (MJS). The primary outcome is the MJS after four days.

Ethics and dissemination

New Zealand Ethics Registration: 17/STH/174. Results will be published in a peer-reviewed medical journal, presented at academic meetings, and reported to participants.

Trial registration number

U1111-1194-4345 and ACTRN12617001340325; Pre-results.
Factors associated with long-term urinary catheterisation and its impact on urinary tract infection among older people in the community: a population-based observational study in a city in Japan
Authors: Adomi Motohiko , Iwagami Masao , Kawahara Takashi , Hamada Shota , Iijima Katsuya , Yoshie Satoru , Ishizaki Tatsuro , Tamiya Nanako
Published: June 2019

Objectives

This study aimed to identify factors associated with long-term urinary catheterisation (LTUC) in community-dwelling older adults and to evaluate the risk of urinary tract infection (UTI) among people with LTUC.

Design

Population-based observational study.

Setting

Medical and long-term care insurance claims data from one municipality in Japan.

Participants

People aged ≥75 years living at home who used medical services between October 2012 and September 2013 (n=32 617).

Outcome measures

(1) Use of LTUC, defined as urinary catheterisation for at least two consecutive months, to identify factors associated with LTUC and (2) the incidence of UTI, defined as a recorded diagnosis of UTI and prescription of antibiotics, in people with and without LTUC.

Results

The 1-year prevalence of LTUC was 0.44% (143/32 617). Multivariable logistic regression analysis showed that the male sex, older age, higher comorbidity score, previous history of hospitalisation with in-hospital use of urinary catheters and high long-term care need level were independently associated with LTUC. The incidence rate of UTI was 33.8 and 4.7 per 100 person-years in people with and without LTUC, respectively. According to multivariable Poisson regression analysis, LTUC was independently associated with UTI (adjusted rate ratio 2.58, 95% CI 1.68 to 3.96). Propensity score-matched analysis yielded a similar result (rate ratio 2.41, 95% CI 1.45 to 4.00).

Conclusions

We identified several factors associated with LTUC in the community, and LTUC was independently associated with the incidence of UTI.
Evaluating possible intended and unintended consequences of the implementation of alcohol minimum unit pricing (MUP) in Scotland: a natural experiment protocol
Authors: Katikireddi Srinivasa Vittal , Beeston Clare , Millard Andrew , Forsyth Ross , Deluca Paolo , Drummond Colin , Eadie Douglas , Graham Lesley , Hilton Shona , Ludbrook Anne , McCartney Gerry , Phillips Thomas , Stead Martine , Ford Allison , Bond Lyndal , Leyland Alastair H
Published: June 2019

Introduction

Scotland is the first country to carry out a national implementation of minimum unit pricing (MUP) for alcohol. MUP aims to reduce alcohol-related harms, which are high in Scotland compared with Western Europe, and to improve health equalities. MUP is a minimum retail price per unit of alcohol. That approach targets high-risk alcohol users. This work is key to a wider evaluation that will determine whether MUP continues. There are three study components.

Methods and analysis

Component 1 sampled an estimated 2800 interviewees at a baseline and each of two follow-ups from four Emergency Departments in Scotland and Northern England. Research nurses administered a standardised survey to assess alcohol consumption and the proportion of attendances that were alcohol-related.

Component 2 covered six Sexual Health Clinics with similar timings and country allocation. A self-completion survey gathered information on potential unintended effects of MUP on alcohol source and drug use.

Using a natural experiment design and repeated cross-sectional audit, difference between Scotland (intervention) and North England (control) will be tested for outcomes using regression adjusting for differences at baseline. Differential impacts by age, gender and socioeconomic position will be investigated.

Component 3 used focus groups with young people and heavy drinkers and interviews with stakeholders before and after MUP implementation. The focus groups will allow exploration of attitudes, experiences and behaviours and the potential mechanisms by which impacts arise. The interviews will help characterise the implementation process.

Ethics and dissemination

Study components 1 and 2 have been ethically approved by the NHS, and component 3 by the University of Stirling. Dissemination plans include peer-reviewed journal articles, presentations, policy maker briefings and, in view of high public interest and the high political profile of this flagship policy, communication with the public via media engagement and plain language summaries.

Trial registration number

ISRCTN16039407; Pre-results.
CADDIE2—evaluation of a clinical decision-support system for early detection of systemic inflammatory response syndrome in paediatric intensive care: study protocol for a diagnostic study
Authors: Wulff Antje , Montag Sara , Steiner Bianca , Marschollek Michael , Beerbaum Philipp , Karch André , Jack Thomas
Published: June 2019

Introduction

Systemic inflammatory response syndrome (SIRS) is one of the most critical indicators determining the clinical outcome of paediatric intensive care patients. Clinical decision support systems (CDSS) can be designed to support clinicians in detection and treatment. However, the use of such systems is highly discussed as they are often associated with accuracy problems and ‘alert fatigue’. We designed a CDSS for detection of paediatric SIRS and hypothesise that a high diagnostic accuracy together with an adequate alerting will accelerate the use. Our study will (1) determine the diagnostic accuracy of the CDSS compared with gold standard decisions created by two blinded, experienced paediatricians, and (2) compare the system’s diagnostic accuracy with that of routine clinical care decisions compared with the same gold standard.

Methods and analysis

CADDIE2 is a prospective diagnostic accuracy study taking place at the Department of Pediatric Cardiology and Intensive Care Medicine at the Hannover Medical School; it represents the second step towards our vision of cross-institutional and data-driven decision-support for intensive care environments (CADDIE). The study comprises (1) recruitment of up to 300 patients (start date 1 August 2018), (2) creation of gold standard decisions (start date 1 May 2019), (3) routine SIRS assessments by physicians (starts with recruitment), (4) SIRS assessments by a CDSS (start date 1 May 2019), and (5) statistical analysis with a modified approach for determining sensitivity and specificity and comparing the accuracy results of the different diagnostic approaches (planned start date 1 July 2019).

Ethics and dissemination

Ethics approval was obtained at the study centre (Ethics Committee of Hannover Medical School). Results of the main study will be communicated via publication in a peer-reviewed journal.

Trial registration number

ClinicalTrials.govNCT03661450; Pre-results.
Examining influences on antibiotic prescribing by nurse and pharmacist prescribers: a qualitative study using the Theoretical Domains Framework and COM-B
Authors: Courtenay Molly , Rowbotham Samantha , Lim Rosemary , Peters Sarah , Yates Kathryn , Chater Angel
Published: June 2019

Objectives

Respiratory tract infections are frequently managed by nurse and pharmacist prescribers, and these prescribers are responsible for 8% of all primary care antibiotic prescriptions. Few studies have explored antibiotic prescribing among these prescribers, and interventions to target their antibiotic prescribing behaviour do not exist. Research objectives were to: (1) use the Theoretical Domains Framework to identify the factors that influence nurse and pharmacist prescriber management of respiratory tract infections and (2) identify the behaviour change techniques (BCTs) that can be used as the basis for the development of a theoretically informed intervention to support appropriate prescribing behaviour.

Design

Qualitative design comprising semistructured interviews, using the Theoretical Domains Framework and Capability, Opportunity and Motivation for Behaviour.

Setting

Primary care.

Participants

Twenty one prescribers (4 pharmacists and 17 nurses).

Results

A range of factors across 12 domains of the TDF were found to influence prescriber behaviour, and 40 BCTs were identified as supporting appropriate prescribing. For example, patient expectations (social influence) was identified as a factor influencing prescribing decisions, and a number of BCTs (problem solving, goal setting and information about health consequences) were identified as supporting prescribers in managing these expectations.

Conclusion

With increasing numbers of nurse and pharmacist prescribers managing infections in primary care, these findings will inform theoretically grounded interventions to support appropriate prescribing behaviour by these groups.
Health, well-being and social relations in a changing neighbourhood: protocol for a prospective, multimethods study of the consequences of large structural changes in an ethnic diverse social housing area in Denmark
Authors: Lund Rikke , Christensen Ulla , Mathisen Jimmi , Sørensen Kristine S , Srivarathan Abirami , Molbo Drude , Halby Kristian , Kristiansen Maria
Published: June 2019

Introduction

Residential areas constitute an important arena for health, well-being and social relations. Structural interventions such as demolition and area renewal have been used to reduce inequality in health and well-being in disadvantaged areas. However, the effects of larger structural interventions are inconclusive. In a longitudinal perspective, this study aims to analyse how large-scale structural changes in an ethnic diverse social housing area are associated with the residents’ health, well-being and social relations.

Methods and analysis

In this multimethods study, we examine this aim among middle-aged and older residents in a multiethnic social housing area in a Danish municipality by the inclusion of comprehensive survey (in 2018, 2019 and 2020), register (yearly 2015–2025) and qualitative (2018–2020) data. Municipal Health Profile survey data from 2017 and 2021 will be used for comparison. The area will undergo large structural changes in the built environment during 2018–2021. A ‘natural experiment’ (n=6000) compares differences in health and social outcomes across the study period between the study area and a similar neighbouring area not undergoing structural changes. Through user engagement in the design of the study, throughout the different phases of the study and in the two co-created interventions embedded in the study design, a focus on empowerment and recognition of the resources and perspectives of residents are encouraged.

Ethics and dissemination

The study is registered in the University of Copenhagen’s record of biobanks and research projects containing personal data and will be conducted in accordance with the principles of the Helsinki Declaration. Residential and municipal representatives and local non-governmental organisations are engaged in the design and execution of the study to ensure the usefulness, reflexive interpretation of data, and relevance of interventions. Results will be published in international peer-reviewed scientific journals, presented at conferences and as short reports through the use of both written and visual outputs.
Effects of neurofeedback versus methylphenidate for the treatment of ADHD: systematic review and meta-analysis of head-to-head trials
Authors: Yan Lixia , Wang Siyuan , Yuan Yang , Zhang Junhua
Published: June 2019

Background

The comparative efficacy and tolerability of methylphenidate (MPH) and neurofeedback (NF) in individuals with attention-deficit/hyperactivity disorder (ADHD) remains uncertain. This study aimed to fill this gap by means of a systematic review/meta-analysis.

Methods

PubMed, OVID, ERIC, Web of Science, ClinialTrials.gov and a set of Chinese databases were searched until 22 August 2018. Standardised mean differences (SMD) were pooled using comprehensive meta-analysis software.

Results

18 randomised controlled trials (RCTs) were included (778 individuals with ADHD in the NF arm and 757 in the MPH group, respectively; 13 studies in Chinese, five in English). At the study first endpoint, MPH was significantly more efficacious than NF on ADHD core symptoms (ADHD symptoms combined: SMD=−0.578, 95% CI (−1.063 to –0.092)) and on two neuropsychological parameters (inattention:−0.959 (-1.711 to –0.208); inhibition:−0.469 (-0.872 to –0.066)). Dropouts were significantly lower in NF versus MPH (OR=0.412, 0.186 to 0.913). Results were robust to sensitivity analyses, with two important exceptions: removing Chinese studies and non-funded studies, no differences emerged between MPH and NF, although the number of studies was small. At the study follow-up, MPH was superior to NF in some outcomes, but results were inconsistent across raters.

Conclusions

Due to the risk of bias of included studies, the results of the sensitivity analysis excluding Chinese and non-funded studies, and the mixed findings on at the follow-up endpoint, further high quality studies are needed to assess the comparative efficacy and acceptability of NF and MPH in individuals with ADHD.

Trial registration number

CRD42018090256.
Cosmological wave maps
Authors: Cotsakis Spiros , Miritzis John , Tzanni Koralia
Published: June 2019

We consider theories of gravity that include many coupled scalar fields with arbitrary couplings, in the geometric framework of wave maps. We examine the possibility of obtaining acceptable cosmological solutions without the inclusion of a potential term to the scalar fields. To illustrate the theory, we study two simple models and compare their solutions to those in General Relativity. We also address the issue of the conditions that must be satisfied by the wave maps for an accelerated phase of the Universe.
Diamond-Coated Mechanical Seal Remaining Useful Life Prediction Based on Convolution Neural Network
Authors: Lin Zhibin , Gao Hongli , Zhang Erqing , Cao Weiqing , Li Kesi
Published: June 2019

Reliable remaining useful life (RUL) prediction of industrial equipment key components is of considerable importance in condition-based maintenance to avoid catastrophic failure, promote reliability and reduce cost during the production. Diamond-coated mechanical seal is one of the most critical wearing components in petroleum chemical, nuclear power and other process industries. Estimating the RUL is of critical importance. We consider the data-driven approaches for diamond-coated mechanical seal RUL estimation based on AE sensor data, since it is difficult to construct an explicit mathematical degradation model of seal. The challenges of this work are dealing with the noisy AE sensor data and modeling the degradation process with fluctuation. Faced with these challenges, we propose a pipeline method CDF-CNN to estimate the RUL for mechanical seal: WPD-KLD to raise the signal-to-noise ratio, novel CDF-based statistics to represent seal degradation process and CNN structure to estimate RUL. To acquire AE sensor data, several diamond-coated seals are tested from new to failure in three working conditions. Experimental results demonstrate that the proposed method can accurately predict the RUL of diamond-coated mechanical seal based on AE signals. The proposed prediction method can be generalized to other various mechanical assets.
Ducci iterates and similar ordering of visible points in convex regions
Authors: Li Junxian , Tamazyan Albert , Zaharescu Alexandru
Published: June 2019

Hardy et al. first introduced the notion of similar ordering of pairs of rationals, and Mayer proved that pairs of Farey fractions in [Formula: see text] are similarly ordered when [Formula: see text] is large enough. We generalize Mayer’s result to Ducci iterates of Farey sequence and visible points in certain regions in the plane. We also study the distribution of values of generalized indices of these sequences.
On certain sums concerning the gcd’s and lcm’s of k positive integers
Authors: Hilberdink Titus , Luca Florian , Tóth László
Published: June 2019

We use elementary arguments to prove results on the order of magnitude of certain sums concerning the gcd’s and lcm’s of [Formula: see text] positive integers, where [Formula: see text] is fixed. We refine and generalize an asymptotic formula of Bordellès [Mean values of generalized gcd-sum and lcm-sum functions, J. Integer Seq. 10 (2007) Article ID:07.9.2, 13[Formula: see text]pp], and extend certain related results of Hilberdink and Tóth [On the average value of the least common multiple of [Formula: see text] positive integers, J. Number Theory 169 (2016) 327–341]. We also formulate some conjectures and open problems.
Editorial
Authors: Bonald Thomas , Duffield Nick
Published: June 2019

The Proceedings of the ACM series present the highest quality research conducted in diverse areas of computer science, as represented by the ACM Special Interest Groups (SIGs). The ACM Proceedings of the ACM on Measurement and Analysis of Computing Systems (POMACS) focuses on the measurement and performance evaluation of computer systems and operates in close collaboration with the Special Interest Group SIGMETRICS. All the papers in the last three issues of POMACS will be presented during the joint ACM SIGMETRICS / IFIP Performance 2019 conference. Despite the extraordinary progress of networks and computer systems in the last decades, these are far from perfect. There are still performance issues and security threats, and the complexity of these systems make them often difficult to manage and operate. Research is expected to contribute to the further improvements of these systems, to make them more efficient, more robust, more flexible and more predictable. In the era of global warming, there is also an urgent need to make the digital economy more green, and thus beneficial to all in the long term. The papers that have appeared in POMACS during the past year reflect the ability of the journal to attract high-quality submissions in this area. The last three issues have included papers on mainstream topics of the ACM SIGMETRICS / IFIP Performance communities, including load balancing, scheduling, resource allocation, performance evaluation and measurement, as well as emerging topics that have become prominent in recent years, such as virtualization, network science, and machine learning. As part of a new initiative to highlight work from outside the SIGMETRICS community that may spur research within the community, the 2019 conference will include a Highlights Beyond SIGMETRICS session featuring leading papers from conferences in neighboring disciplines. We thank Adam Wierman for leading this initiative.
A Structural Result for Personalized PageRank and its Algorithmic Consequences
Authors: Vial Daniel , Subramanian Vijay
Published: June 2019

Many systems, such as the Internet, social networks, and the power grid, can be represented as graphs. When analyzing graphs, it is often useful to compute scores describing the relative importance or distance between nodes. One example is Personalized PageRank (PPR), which assigns to each node v a vector whose i-th entry describes the importance of the i-th node from the perspective of v. PPR has proven useful in many applications, such as recommending who users should follow on social networks (if this i-th entry is large, v may be interested in following the i-th user). Unfortunately, computing n PPR vectors exactly for a graph of n nodes has complexity O(n^3), which is infeasible for many graphs of interest. In this work, we devise a scheme to estimate all n PPR vectors with bounded l_1 error and complexity O(n
c
), where c < 2 depends on the degrees of the graph at hand, the desired error tolerance, and a parameter that defines PPR. This improves upon existing methods, the best of which have complexity O(n
2
łog n) in our setting. Our complexity guarantee holds with high probability, for certain choices of the PPR parameter, and for a certain class of random graphs (roughly speaking, the sparse directed configuration model with heavy-tailed in-degrees); our accuracy guarantee holds with probability 1 and for arbitrary graphs and PPR parameters. The complexity result arises as a consequence of our main (structural) result, which shows that the dimensionality of the set of PPR vectors scales sublinearly in n with high probability, for the same class of random graphs and for a notion of dimensionality similar to matrix rank. It is this coupling of the PPR vectors for the nodes on a common underlying graph that allows for estimating them faster. Hence, at a high level, our scheme is analogous to (but distinct from) low-rank matrix approximation. We also note that our scheme is similar to one that was proposed in [Jeh and Widom 2003] but lacked accuracy and complexity guarantees, so another contribution of our paper is to address this gap in the literature.
Inferring Catchment in Internet Routing
Authors: Sermpezis Pavlos , Kotronis Vasileios
Published: June 2019

BGP is the de-facto Internet routing protocol for exchanging prefix reachability information between Autonomous Systems (AS). It is a dynamic, distributed, path-vector protocol that enables rich expressions of network policies (typically treated as secrets). In this regime, where complexity is interwoven with information hiding, answering questions such as "what is the expected catchment of the anycast sites of a content provider on the AS-level, if new sites are deployed?", or "how will load-balancing behave if an ISP changes its routing policy for a prefix?", is a hard challenge. In this work, we present a formal model and methodology that takes into account policy-based routing and topological properties of the Internet graph, to predict the routing behavior of networks. We design algorithms that provide new capabilities for informative route inference (e.g., isolating the effect of randomness that is present in prior simulation-based approaches). We analyze the properties of these inference algorithms, and evaluate them using publicly available routing datasets and real-world experiments. The proposed framework can be useful in a number of applications: measurements, traffic engineering, network planning, Internet routing models, etc. As a use case, we study the problem of selecting a set of measurement vantage points to maximize route inference. Our methodology is general and can capture standard valley-free routing, as well as more complex topological and routing setups appearing in practice.
Queue and Loss Distributions in Finite-Buffer Queues
Authors: Ciucu Florin , Poloczek Felix , Rizk Amr
Published: June 2019

We derive simple bounds on the queue distribution in finite-buffer queues with Markovian arrivals. Our technique relies on a subtle equivalence between tail events and stopping times orderings. The bounds capture a truncated exponential behavior, involving joint horizontal and vertical shifts of an exponential function; this is fundamentally different than existing results capturing horizontal shifts only. Using the same technique, we obtain similar bounds on the loss distribution, which is a key metric to understand the impact of finite-buffer queues on real-time applications. Simulations show that the bounds are accurate in heavy-traffic regimes, and improve existing ones by orders of magnitude. In the limiting regime with utilization ρ=1 and iid arrivals, the bounds on the queue size distribution are insensitive to the arrivals distribution.
A New Flexible Multi-flow LRU Cache Management Paradigm for Minimizing Misses
Authors: Quan Guocong , Tan Jian , Eryilmaz Atilla , Shroff Ness
Published: June 2019

The Least Recently Used (LRU) caching and its variants are used in large-scale data systems in order to provide high-speed data access for a wide class of applications. Nonetheless, a fundamental question still remains open: in order to minimize miss probabilities, how should the cache space be organized to serve multiple data flows? Commonly used strategies can be categorized into two designs: pooled LRU (PLRU) caching and separated LRU (SLRU) caching. However, neither of these designs can satisfactorily solve this problem. PLRU caching is easy to implement and self-adaptive, but does not often achieve optimal or even efficient performance because its set of feasible solutions are limited. SLRU caching can be statically configured to achieve optimal performance for stationary workload, which nevertheless could suffer in a dynamically changing environment and from a cold-start problem. To this end, we propose a new insertion based pooled LRU paradigm, termed I-PLRU, where data flows can be inserted at different positions of a pooled cache. This new design can achieve the optimal performance of the static SLRU, and retains the adaptability of PLRU in virtue of resource sharing. Theoretically, we characterize the asymptotic miss probabilities of I-PLRU, and prove that, for any given SLRU design, there always exists an I-PLRU configuration that achieves the same asymptotic miss probability, and vice versa. We next design a policy to minimize the miss probabilities. However, the miss probability minimization problem turns out to be non-convex under the I-PLRU paradigm. Notably, we utilize an equivalence mapping between I-PLRU and SLRU to efficiently find the optimal I-PLRU configuration. We prove that I-PLRU outperforms PLRU and achieves the same miss probability as the optimal SLRU for stationary workload. Engineeringly, the flexibility of I-PLRU avoids separating the memory space, supports dynamic and refined configurations, and alleviates the cold-start problem, potentially yielding better performance than both SLRU and PLRU.
Learning Graphs from Noisy Epidemic Cascades
Authors: Hoffmann Jessica , Caramanis Constantine
Published: June 2019

We consider the problem of learning the weighted edges of a graph by observing the noisy times of infection for multiple epidemic cascades on this graph. Past work has considered this problem when the cascade information, i.e., infection times, are known exactly. Though the noisy setting is well motivated by many epidemic processes (e.g., most human epidemics), to the best of our knowledge, very little is known about when it is solvable. Previous work on the no-noise setting critically uses the ordering information. If noise can reverse this -- a node's reported (noisy) infection time comes after the reported infection time of some node it infected -- then we are unable to see how previous results can be extended. We therefore tackle two versions of the noisy setting: the limited-noise setting, where we know noisy times of infections, and the extreme-noise setting, in which we only know whether or not a node was infected. We provide a polynomial time algorithm for recovering the structure of bidirectional trees in the extreme-noise setting, and show our algorithm matches lower bounds established in the no-noise setting, and hence is optimal. We extend our results for general degree-bounded graphs, where again we show that our (poly-time) algorithm can recover the structure of the graph with optimal sample complexity. We also provide the first efficient algorithm to learn the weights of the bidirectional tree in the limited-noise setting. Finally, we give a polynomial time algorithm for learning the weights of general bounded-degree graphs in the limited-noise setting. This algorithm extends to general graphs (at the price of exponential running time), proving the problem is solvable in the general case. All our algorithms work for any noise distribution, without any restriction on the variance.
Load Balancing Guardrails
Authors: Grosof Isaac , Scully Ziv , Harchol-Balter Mor
Published: June 2019

Load balancing systems, comprising a central dispatcher and a scheduling policy at each server, are widely used in practice, and their response time has been extensively studied in the theoretical literature. While much is known about the scenario where the scheduling at the servers is First-Come-First-Served (FCFS), to minimize mean response time we must use Shortest-Remaining-Processing-Time (SRPT) scheduling at the servers. Much less is known about dispatching polices when SRPT scheduling is used. Unfortunately, traditional dispatching policies that are used in practice in systems with FCFS servers often have poor performance in systems with SRPT servers. In this paper, we devise a simple fix that can be applied to any dispatching policy. This fix, called guardrails, ensures that the dispatching policy yields optimal mean response time under heavy traffic when used in a system with SRPT servers. Any dispatching policy, when augmented with guardrails, becomes heavy-traffic optimal. Our results yield the first analytical bounds on mean response time for load balancing systems with SRPT scheduling at the servers.
Serum IL-6 and sIL-6R in type 2 diabetes contribute to impaired capillary-like network formation
Authors: Landers-Ramos Rian Q. , Blumenthal Jacob B. , Prior Steven J.
Published: June 2019

We hypothesized that the serum from individuals with type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT) would reduce in vitro capillary-like network formation compared with normal glucose tolerance (NGT) serum and that this would occur along with higher serum concentrations of inflammatory cytokines and lower concentrations of angiogenic growth factors. Subjects were sedentary, older (55–65 yr) adults with NGT, IGT, or T2DM ( n = 10/group) matched for body mass index. Human retroviral telomerized endothelial cells (HRVT-ECs) or coronary artery endothelial cells (CECs) were used in a capillary-like network formation assay using endothelial basal medium supplemented with 7.5% serum. Quantification of HRVT-EC network length indicated that serum from the T2DM group resulted in 32 and 35% lower network formation than when using serum from the NGT and IGT groups, respectively ( P < 0.05). Serum from T2DM subjects resulted in CEC network formation that was 11 and 8% lower than when using serum from NGT and IGT subjects, respectively ( P < 0.05). Analysis of serum cytokines indicated that IL-6 was 41% and 49% higher in the IGT and T2DM groups, respectively, compared with the NGT group ( P < 0.05) and there was a trend for higher soluble interleukin-6 receptor (sIL-6R; P = 0.06) and IL-8 ( P = 0.08) in the T2DM serum compared with NGT. The use of recombinant IL-6 and sIL-6R at concentrations detected in the T2DM serum also reduced capillary network formation compared with NGT concentrations ( P < 0.05). These results suggest that IL-6 and sIL-6R present in the serum of T2DM individuals impair in vitro endothelial cell function across different cell lines. Our findings may have implications for the microvascular complications associated with T2DM.

NEW & NOTEWORTHY Higher concentrations of serum factors, specifically Interleukin-6 and its soluble receptor found in individuals with type 2 diabetes (T2DM) appear to impair endothelial cell capillary-like network formation compared with those present in serum from individuals with impaired glucose tolerance and normal glucose tolerance. This may have implications for the vascular complications associated with T2DM.
Sex differences in blood pressure regulation during ischemic isometric exercise: the role of the β-adrenergic receptors
Authors: Samora Milena , Incognito Anthony V. , Vianna Lauro C.
Published: June 2019

We sought to investigate whether the β-adrenergic receptors play a pivotal role in sex-related differences in arterial blood pressure (BP) regulation during isometric exercise. Sixteen volunteers (8 women) performed 2 min of ischemic isometric handgrip exercise (IHE) and 2 min of postexercise circulatory occlusion (PECO). Heart rate (HR) and beat-to-beat arterial BP were continuously measured. Beat-to-beat estimates of stroke volume (ModelFlow) were obtained and matched with HR to calculate cardiac output (Q̇) and total peripheral resistance (TPR). Two trials were randomly conducted between placebo and nonselective β-adrenergic blockade (40 mg propranolol). Under the placebo condition, the magnitude of the BP response in IHE was lower in women compared with men. During PECO, the BP remained elevated and the sex differences persisted. The β-blockade attenuated the BP response during IHE in men (∆57 ± 4 vs. ∆45 ± 7 mmHg, P = 0.025) due to a reduction in Q̇ (∆3.7 ± 0.5 vs. ∆1.8 ± 0.2 L/min, P = 0.012) while TPR was not affected. In women, however, the BP response during IHE was unchanged (∆27 ± 3 vs. ∆28 ± 3 mmHg, P = 0.889), despite attenuated Q̇ (∆2.7 ± 0.4 vs. ∆1.3 ± 0.2 L/min, P = 0.012). These responses were mediated by a robust increase in TPR under β-blockade (∆−0.2 ± 0.4 vs. ∆2.2 ± 0.7 mmHg·L−1·min, P = 0.012). These findings demonstrate that the sex differences in arterial BP regulation during ischemic IHE are mediated by β-adrenergic receptors.

NEW & NOTEWORTHY We found that the blood pressure response during isometric exercise in women is mediated by increases in cardiac output, whereas in men it is mediated by increases in both cardiac output and total peripheral resistance. In addition, women showed a robust increase in total peripheral resistance under β-blockade during isometric exercise and muscle metaboreflex activation. These findings demonstrate that sex differences in blood pressure regulation during isometric exercise are mediated by β-adrenergic receptors.
Ribosome biogenesis in skeletal muscle: coordination of transcription and translation
Authors: von Walden Ferdinand
Published: June 2019

Skeletal muscle mass responds in a remarkable manner to alterations in loading and use. It has long been clear that skeletal muscle hypertrophy can be prevented by inhibiting RNA synthesis. Since 80% of the cell’s total RNA has been estimated to be rRNA, this finding indicates that de novo production of rRNA via transcription of the corresponding genes is important for such hypertrophy to occur. Transcription of rDNA by RNA Pol I is the rate-limiting step in ribosome biogenesis, indicating in turn that this biogenesis strongly influences the hypertrophic response. The present minireview focuses on 1) a brief description of the key steps in ribosome biogenesis and the relationship of this process to skeletal muscle mass and 2) the coordination of ribosome biogenesis and protein synthesis for growth or atrophy, as exemplified by the intracellular AMPK and mTOR pathways.
Effects of caffeine and sex on muscle performance and delayed-onset muscle soreness after exercise-induced muscle damage: a double-blind randomized trial
Authors: Chen Hou-Yu , Chen Yung-Chih , Tung Kang , Chao Hsiao-Han , Wang Ho-Seng
Published: June 2019

The present study aims to investigate effects of caffeine ingestion and sex difference on muscle performance, delayed-onset muscle soreness (DOMS), and various biomarkers under exercise-induced muscle damage (EIMD). Twenty (10 male and 10 female) healthy elite college athletes were recruited. Participants ingested either caffeine (6 mg/kg) or a placebo in a randomized, double-blind, and counterbalanced fashion at 24 and 48 h following EIMD. Muscle performance, DOMS, and blood samples were taken an hour before and an hour after supplementation. Caffeine ingestion restored impaired maximal voluntary isometric contractions (MVIC: 10.2%; MVICpost: 7.2%, both P < 0.05) during EIMD across both sexes. Following caffeine ingestion during MVIC, while affected by EIMD, an interaction was found in DOMS and serum K+ (both P < 0.05), with males showing greater attenuation (21.5 and 16.9%, respectively) compared with females (4.6 and 1.3%, respectively). DOMS demonstrated an inverse correlation with MVIC after caffeine ingestion both overall and among male athletes ( r = −0.34 and −0.54, respectively; P < 0.05) but not among female athletes ( r = −0.11; P > 0.05) under EIMD. In addition, caffeine ingestion increased postexercise serum glucose and lactate concentrations across both sexes (both P < 0.05). This is the first study to show that male athletes, compared with female athletes, experience a greater reduction in DOMS during enhanced MVIC when caffeine was consumed, suggesting men might receive greater ergogenic effects from caffeine when affected by EIMD. Furthermore, caffeine ingestion was able to restore impaired muscle power among elite collegiate athletes across both sexes.

NEW & NOTEWORTHY Exercise-induced muscle damage (EIMD) reduces anaerobic/aerobic performance and increases delayed-onset muscle soreness (DOMS) during exercise. We show that acute caffeine supplementation at a dosage of 6 mg/kg seems to facilitate recovery of anaerobic muscle power and attenuate DOMS after EIMD across both sexes. Furthermore, male athletes, compared with female athletes, when caffeine was prescribed, experience a greater reduction in DOMS with better restoration of impaired maximal voluntary isometric contractions. This suggests that male athletes might benefit from the ergogenic effect of acute caffeine supplementation after the onset of EIMD.
Changes in Mannitol Content, Regulation of Genes Involved in Mannitol Metabolism, and the Protective Effect of Mannitol onVolvariella volvaceaat Low Temperature
Authors: Zhao Xu , Yu Changxia , Zhao Yan , Liu Shunjie , Wang Hong , Wang Chenguang , Guo Ligang , Chen Mingjie
Published: June 2019

The mechanism of autolysis ofVolvariella volvacea(V. volvacea) at low temperature has not been fully explained. As mannitol is among the most important osmotic adjustment substances in fungal resistance, this study sampled mycelia of strains V23 and VH3 treated at 0°C for 0, 2, 4, 8, and 10 h to analyze changes in intracellular mannitol content by high-performance anion chromatography with pulsed amperometric detection (HAPEC-PAD). Reverse transcription quantitative PCR (RT-qPCR) analysis was applied to assess differences in the transcript levels of genes associated with mannitol metabolism under low-temperature stress. A mannitol solution was added to cultures ofV. volvaceafruiting bodies, and effects on the hypothermic resistance of these organs were explored by evaluating variations in sensory properties during cryogenic storage after harvest. The results suggested that in the initial stage of low-temperature treatment, intracellular mannitol was largely catabolized as an energy storage material and the expression of genes encoding enzymes involved in synthetic reactions was inhibited. However, low-temperature resistance was induced with further treatment, with activation of mannitol synthesis and inhibition of degradation; the cells accumulated mannitol, leading to osmoregulation. No significant elongation ofV. volvaceafruiting bodies during storage at 4°C was observed, and these organs tended to shrink and collapse. The sensory quality of mannitol-treated fruiting bodies was much better than that of control fruiting bodies. Application of a mannitol solution at the cultivation stage ofV. volvaceasomewhat improved the low-temperature resistance of the fruiting bodies, verifying the correlation between mannitol and resistance to this stress inV. volvacea. The results of this study lay a foundation for a deeper understanding of the autolysis mechanism ofV. volvacea, providing technical support for increasing the cryopreservation time of this species and extending the postharvest shelf life of its fruiting bodies. In addition, the mechanism underlying the low-temperature tolerance of the VH3 strain should be further explained at the molecular level.
Aortic Dissection in a Pregnant Patient without Other Risk Factors
Authors: Patel Priya V. , Alter Raanan , Frenn Recia , Waters Thaddeus P.
Published: June 2019

Background. An aortic dissection is a life-threatening condition in which the intima of the artery tears causing separation of the intima and media. Pregnancy places women at a significantly increased risk of common vascular events including venous thromboembolism, myocardial infarction, and stroke, while also increasing the risk of rarer vascular events such as aortic dissection and aortic rupture. Case. A 30-year-old previously healthy multiparous woman presenting at 36 weeks of pregnancy with a Type A aortic dissection. She underwent a combined emergent cesarean delivery followed by repair of her aortic root. Conclusions. Aortic dissection should be high on the differential for pregnant patients presenting with the characteristic complaints and physical exam findings given the high mortality rate associated with this vascular event. Teaching Points. (1) This report reviews the characteristic presentation, risk factors, and physical exam findings in a patient with an aortic dissection. (2) The report includes treatment options for pregnant patients based on the classification of the dissection.
Characterization of Different Sources of Human MSCs Expanded in Serum-Free Conditions with Quantification of Chondrogenic Induction in 3D
Authors: Fabre Hugo , Ducret Maxime , Degoul Olivier , Rodriguez Jonathan , Perrier-Groult Emeline , Aubert-Foucher Elisabeth , Pasdeloup Marielle , Auxenfans Céline , McGuckin Colin , Forraz Nico , Mallein-Gerin Frédéric
Published: June 2019

Mesenchymal stem cells (MSCs) represent alternative candidates to chondrocytes for cartilage engineering. However, it remains difficult to identify the ideal source of MSCs for cartilage repair since conditions supporting chondrogenic induction are diverse among published works. In this study, we characterized and evaluated the chondrogenic potential of MSCs from bone marrow (BM), Wharton’s jelly (WJ), dental pulp (DP), and adipose tissue (AT) isolated and cultivated under serum-free conditions. BM-, WJ-, DP-, and AT-MSCs did not differ in terms of viability, clonogenicity, and proliferation. By an extensive polychromatic flow cytometry analysis, we found notable differences in markers of the osteochondrogenic lineage between the 4 MSC sources. We then evaluated their chondrogenic potential in a micromass culture model, and only BM-MSCs showed chondrogenic conversion. This chondrogenic differentiation was specifically ascertained by the production of procollagen IIB, the only type II collagen isoform synthesized by well-differentiated chondrocytes. As a pilot study toward cartilage engineering, we encapsulated BM-MSCs in hydrogel and developed an original method to evaluate their chondrogenic conversion by flow cytometry analysis, after release of the cells from the hydrogel. This allowed the simultaneous quantification of procollagen IIB and α10, a subunit of a type II collagen receptor crucial for proper cartilage development. This work represents the first comparison of detailed immunophenotypic analysis and chondrogenic differentiation potential of human BM-, WJ-, DP-, and AT-MSCs performed under the same serum-free conditions, from their isolation to their induction. Our study, achieved in conditions compliant with clinical applications, highlights that BM-MSCs are good candidates for cartilage engineering.
Weiqi Decoction Attenuated Chronic Atrophic Gastritis with Precancerous Lesion through Regulating Microcirculation Disturbance and HIF-1α Signaling Pathway
Authors: Yin Jing , Yi Jinyu , Yang Chun , Xu Bo , Lin Jiang , Hu Hongyi , Wu Xiaojun , Shi Hailian , Fei Xiaoyan
Published: June 2019

Aim. Chronic atrophic gastritis (CAG), the precancerous lesions of gastric cancer, plays an important role in the stepwise process of gastric cancer. The ancient Chinese medicine believes in that Qi deficiency and blood stasis are involved in the pathogenesis of CAG. Weiqi decoction, a classical formula from Longhua Hospital, could supplement Qi and activate blood circulation of human beings and has been used for treating CAG in clinic over twenty years. The study aims to clarify the effect and underlying molecular mechanism of Weiqi decoction on CAG rats. Methods. Forty-eight male Wistar rats were divided randomly into six groups: control group, model group, folic acid group, and WQD-treated groups at doses of 4 g/kg, 2 g/kg, and 1 g/kg, with eight rats in each group. MNNG and saturated NaCl were used to induce CAG rat with precancerous lesion (intestinal metaplasia and dysplasia). After 40 weeks, gastric mucosal blood flow was measured using Laser Doppler Flowmetry. The pathological changes of the gastric mucosa were identified by H&E staining and AB-PAS staining. The protein expression of COX-2, HIF-1α, VEGFR1, VEGFR2, Ki67, and cleaved caspase 3 in the gastric tissues was measured by western blotting approach. Gene expression of COX-2, HIF-1α, VEGF, VEGFR1, VEGFR2, Ang-1, and Ang-2 was detected by using Quantitative PCR method. The PGE2 concentrations in serum were detected by ELISA method. The protein expression of Ki67 in gastric mucosa was also detected by immunohistochemistry. Results. Compared with control rats, atrophy and intestinal metaplasia as well as the microcirculation disturbance of gastric mucosa were induced in the stomach of CAG rats identified by the H&E and AB-PAS staining as well as microcirculation measurement, which could be significantly attenuated by WQD treatment. Moreover, compared with the control group, the protein and gene expression of COX-2, HIF-1α, VEGFR1, and VEGFR2 in gastric tissues of pylorus was obviously increased and the serum PGE2 level was significantly deceased in CAG rats, which could be significantly counteracted by WQD administration. However, the gene expression of Ang-1 and Ang-2 was not significant difference between control rats and CAG rats, and WQD also had no significant effect on the gene expression of Ang-1 and Ang-2. Furthermore, the increased cell proliferation marked by upregulated protein expression of Ki67 and decreased cell apoptosis marked by downregulated protein expression of cleaved caspase 3 in stomach of pylorus in CAG rats were obviously reversed by WQD treatment. Conclusion. WQD attenuated CAG with precancerous lesion through regulating gastric mucosal blood flow disturbance and HIF-1α signaling pathway.