bluuebunny/crossref_metadata_2025 huggingface dataset:
Negotiating a New Social Contract for Work: An Online, Distributed Approach
Authors: Kochan Thomas , Dyer Lee , Cutcher‐Gershenfeld Joel , Kowalski Alexander
Published: April 2018

A massive open online course (MOOC) entitled “Shaping the Future of Work” (offered through MITx, the Massachusetts Institute of Technology's online learning division) has been the context for a multiparty simulation designed to produce classroom negotiation results that will have social impacts. After running the course in the MOOC context three times and in face‐to‐face settings eight times, we noticed that key themes emerged. Participants have brought their own workforce perspectives to their simulation roles as employers, worker representatives, elected officials, and educators. They have called for reciprocal agreements centered on fair treatment and representation in the workplace, improved organizational performance, investments in skills and capabilities, aligned rewards and benefits for workers, and work–life balance in communities. We continue to use the simulation in the classroom and are exploring ways to expand its use. In the meantime, in this article, we discuss how the insights gleaned from this simulation could be used to crystallize and advance a new social contract at a time when the public policies, institutions, and organizational practices governing employment relations have not kept up with the dramatic changes taking place in the workforce, nature of work, and overall economy.
An aspirational diet for dialysis patients: Evidence and theory
Authors: Uribarri Jaime
Published: April 2018

Dialytic renal replacement therapy is now entering into its sixth decade in the United States. Despite major advances in dialysis technology, regimens and protocols, and pharmacological treatments, patients’ restricted dietary intake remains the lynchpin to their well‐being and success. Herein, we review current guidelines that limit dietary intake of nutrients and minerals in dialysis patients and explore potential ways to use them in designing a daily food intake that is not only healthy, but also easy to implement and therefore patient friendly. The main theme behind this review is attempting to emphasize that dietary restriction guidelines can be used in such a way that dialysis patients can eat things they really enjoy as long as they follow some relatively simple general rules.
The full‐length genomic sequence of a novel HLA‐C*07 allele, HLA‐C*07:63, identified in a Chinese individual
Authors: Gao S.‐Q. , Tong G.‐D. , Chen R.‐Z.
Published: April 2018

HLA‐C*07:63 differs from HLA‐C*07:04:01 by a single nonsynonymous change, resulting in an amino acid substitution.
Characterization of the novel HLA‐DQB1*06:02:29 allele by sequencing‐based typing
Authors: Zhang L.‐Q. , Xiao Y. , Zhou X. , Cai J.
Published: April 2018

HLA‐DQB1*06:02:29 differs from HLA‐DQB1*06:02:01:01 by one nucleotide substitution at position 408 (C > T).
Click reception in the harbor porpoise (Phocoena phocoena): Effects of electrode and contact transducer location on the auditory brainstem response
Authors: Mulsow Jason , Finneran James J. , Houser Dorian S. , Nordstrom Chad A. , Barrett-Lennard Lance G. , Burkard Robert F.
Published: April 2018

Unlike terrestrial mammals that have unambiguous aerial sound transmission pathways via the outer ear and tympanum, sound reception pathways in most odontocetes are not well understood. Recent studies have used auditory brainstem response (ABR) measurements to examine sound reception pathways. This study sought to determine how sound source placements, recording electrode arrangements, and ABR peak analyses affect interpretations of sound reception in the harbor porpoise (Phocoena phocoena). Click stimuli were delivered in air from a contact transducer (“jawphone”). Early ABR peaks (representing auditory nerve responses), and later peaks reflecting higher brainstem activity, were analyzed across jawphone and recording electrode positions. Auditory nerve responses were similar for jawphone placements from the ipsilateral posterior mandible to the tip of the rostrum. Later peaks, however, suggested a possible region of highest sensitivity midway between the posterior mandible and the rostrum tip. These findings are generally similar to previous data for porpoises. In contrast to auditory nerve responses that were largest when recorded near the ipsilateral meatus, later ABR peaks were largest when recorded with a contralateral (opposing) electrode. These results provide information on the processes underlying peaks of the ABR, and inform stimulus delivery and ABR recording parameters in odontocete sound reception studies.
Season and Sport-Specific Adolescent Concussions via Online Surveillance in New Jersey Public High Schools 2015–2017
Authors: Shendell Derek G. , Listwan Tracy A. , Gonzalez Lauren , Panchella Joseph
Published: April 2018

Despite increased awareness of concussions among student-athletes, local epidemiologic surveillance efforts are limited, especially among adolescents. We analyzed data reported through a state public-school-based online surveillance tool during the fall (summer preseason and regular season), winter, and spring seasons of the 2015–2017 school years at seven participating public high schools across New Jersey. Concussions were sustained during interscholastic and intramural sports and in physical education classes. There were 208 concussions: 142 in fall (123 regular season), 22 in winter (21 regular season), and 44 in spring. Reports stated 75% were first concussions, but 17% were second and 2% were third concussions.
Head Impact Exposure in Practices Correlates With Exposure in Games for Youth Football Players
Authors: Bellamkonda Srinidhi , Woodward Samantha J. , Campolettano Eamon , Gellner Ryan , Kelley Mireille E. , Jones Derek A. , Genemaras Amaris , Beckwith Jonathan G. , Greenwald Richard M. , Maerlender Arthur C. , Rowson Steven , Duma Stefan M. , Urban Jillian E. , Stitzel Joel D. , Crisco Joseph J.
Published: April 2018

This study aimed to compare head impact exposures between practices and games in football players ages 9 to 14 years, who account for approximately 70% of all football players in the United States. Over a period of 2 seasons, 136 players were enrolled from 3 youth programs, and 49,847 head impacts were recorded from 345 practices and 137 games. During the study, individual players sustained a median of 211 impacts per season, with a maximum of 1226 impacts. Players sustained 50th (95th) percentile peak linear acceleration of 18.3 (46.9) g, peak rotational acceleration of 1305.4 (3316.6) rad·s−2, and Head Impact Technology Severity Profile of 13.7 (24.3), respectively. Overall, players with a higher frequency of head impacts at practices recorded a higher frequency of head impacts at games (P < .001, r2 = .52), and players who sustained a greater average magnitude of head impacts during practice also recorded a greater average magnitude of head impacts during games (P < .001). The youth football head impact data quantified in this study provide valuable insight into the player exposure profile, which should serve as a key baseline in efforts to reduce injury.
Differences Among Overhand, 3-Quarter, and Sidearm Pitching Biomechanics in Professional Baseball Players
Authors: Escamilla Rafael F. , Slowik Jonathan S. , Diffendaffer Alek Z. , Fleisig Glenn S.
Published: April 2018

The purpose of this study was to assess biomechanical differences among overhand, 3-quarter, and sidearm arm slot professional baseball pitchers. It was hypothesized that kinematic and kinetic differences would be found among the 3 groups, with sidearm pitchers demonstrating greater movement along the transverse plane and overhead pitchers demonstrating greater movement along the sagittal plane. Based upon arm slot angle at ball release, 30 overhand, 156 three-quarter, and 21 sidearm pitchers were tested using a 240-Hz motion analysis system, and 37 kinematic and kinetic parameters were calculated. One-way analyses of variance (α = .01) was employed to assess differences among groups. The comparisons showed the sidearm group had less shoulder anterior force, whereas the overhand group had the least elbow flexion torque. At ball release, trunk contralateral tilt and shoulder abduction were greatest for the overhand group and least for sidearm group. Additionally, the sidearm group demonstrated the lowest peak knee height, most closed foot angle, greatest pelvis angular velocity, and shoulder external rotation. The overhand group had the greatest elbow flexion at foot contact and greatest trunk forward tilt at ball release. The greater elbow flexion torque and shoulder external rotation exhibited by sidearm pitchers may increase their risk of labral injury. Conversely, the lower shoulder anterior force in sidearm pitchers may indicate lower stress on shoulder joint capsule and rotator cuff.
Return to Sport Rates in Physically Active Individuals 6 Months After Arthroscopy for Femoroacetabular Impingement Syndrome
Authors: Glaws Kathryn R. , Ellis Thomas J. , Hewett Timothy E. , Di Stasi Stephanie
Published: April 2018

Context: Six months is the expected time frame to return to sport (RTS) after hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Objective: The primary aims of this study were to (1) report the RTS rate of physically active individuals 6 months after arthroscopic surgery for FAIS and (2) compare the self-reported hip function between those who were able to RTS against those who had not. Design: Cohort study. Setting: The Ohio State University Wexner Medical Center. Patients: A total of 42 physically active individuals scheduled for hip arthroscopy for FAIS. Main Outcome Measures: Self-reported function, including preinjury and current activity levels and ability to participate in sport, were collected on 42 individuals with FAIS prior to surgery and at 6-month follow-up. Participants were allocated into 2 groups based on self-reported RTS status at 6-month follow-up. Separate 2-way analyses of variance were used to test the interaction of groups (those who did/did not RTS). Main effects were reported in the absence of statistically significant interactions (P ≤ .05). Results: Altogether, 28 of 42 participants (66%) returned for 6-month follow-up; 5 of the 14 participants (35.7%) lost to follow-up underwent contralateral hip surgery within the study time frame. At the 6-month follow-up, 16 of the remaining 28 participants (57.1%) reported that they had returned to sport, 5 of whom returned at their prior level of participation. There was no statistically significant interaction of group and time for either hip outcome score subscale (P ≥ .20). Self-reported hip function improved over time, regardless of group (P ≤ .001). Participants in the yRTS group demonstrated higher hip outcome score-sport scores than did the nRTS group, regardless of time (P = .04). Conclusions: Though just over half of participants returned to sport 6 months after hip arthroscopy for FAIS, only 18% returned to their previous level of sports participation. Participants who returned to sport reported better function than those who did not, but self-reported hip function improved over time regardless of group. The most commonly reported reasons for not returning to sport were weakness (69.6%), fear (65.2%), and pain (56.5%).
Design of Eccentric Training System Based on Multiple-Input Single-Output Wiener Nonlinear Model
Authors: Liu Chunbo
Published: April 2018

Objectives: The efficacy of eccentric cycling has been proved in research, clinical, and sport training activities. However, several constraints make it difficult to use commercially available eccentric cycle ergometers. This study will stimulate the application of eccentric cycling as an exercise modality. Study Design: University research laboratory. Methods: In this study, the multiple-input single-output (MISO) Wiener nonlinear model was applied to the design of the eccentric training system. Particle Swarm Optimization (PSO) algorithm was then applied to identify the parameters of the MISO Wiener nonlinear model. The computer software embedded with MISO model was programmed for not only controlling and monitoring the running status of the eccentric training system, but also collecting data in a flexible and convenient manner. Results: The correlation coefficient of 0.9985 and root mean square error of 3.3264 between the collected power value and the estimated power value from the model shows the good performance of the model. Conclusion: The proposed method for the design of the eccentric training system using MISO Wiener nonlinear model provides a new way for eccentric research and training.
Bacterial Community Dynamics across the Gastrointestinal Tracts of Dairy Calves during Preweaning Development
Authors: Dias Juliana , Marcondes Marcos Inácio , Motta de Souza Shirley , Cardoso da Mata e Silva Barbara , Fontes Noronha Melline , Tassinari Resende Rafael , Machado Fernanda Samarini , Cuquetto Mantovani Hilário , Dill-McFarland Kimberly A. , Suen Garret
Published: April 2018

Microbial communities play critical roles in the gastrointestinal tracts (GIT) of preruminant calves by influencing performance and health. However, little is known about the establishment of microbial communities in the calf GIT or their dynamics during development. In this study, next-generation sequencing was used to assess changes in the bacterial communities of the rumen, jejunum, cecum, and colon in 26 crossbred calves at four developmental stages (7, 28, 49, and 63 days old). Alpha diversity differed among GIT regions with the lowest diversity and evenness in the jejunum, whereas no changes in alpha diversity were observed across developmental stage. Beta diversity analysis showed both region and age effects, with low numbers of operational taxonomic units (OTUs) shared between regions within a given age group or between ages in a given region. Taxonomic analysis revealed that several taxa coexisted in the rumen, jejunum, cecum, and colon but that their abundances differed considerably by GIT region and age. As calves aged, we observed lower abundances of taxa such asBacteroides,Parabacteroides, andParaprevotellawith higher abundances ofBulleidiaandSucciniclasticumin the rumen. The jejunum also displayed taxonomic changes with increases inClostridiaceaeandTuricibactertaxa in older calves. In the lower gut, taxa such asLactobacillus,Blautia, andFaecalibacteriumdecreased and S24-7,Paraprevotella, andPrevotellaincreased as calves aged. These data support a model whereby early and successive colonization by bacteria occurs across the GIT of calves and provides insights into the temporal dynamics of the GIT microbiota of dairy calves during preweaning development.

IMPORTANCEThe gastrointestinal tracts (GIT) of ruminants, such as dairy cows, house complex microbial communities that contribute to their overall health and support their ability to produce milk. For example, the rumen microbiota converts feed into usable nutrients, while the jejunal microbiota provides access to protein. Thus, establishing a properly functioning GIT microbiota in dairy calves is critical to their productivity as adult cows. However, little is known about the establishment, maintenance, and dynamics of the calf GIT microbiota in early life. In this study, we evaluated the bacterial communities in the rumen, jejunum, cecum, and colon in dairy calves across preweaning development and show that they are highly variable early on in life before transitioning to a stable community. Understanding the dairy calf GIT microbiota has implications for ensuring proper health during early life and will aid in efforts to develop strategies for improving downstream production.
Local Food Systems Food Safety Concerns
Authors: Chapman Benjamin , Gunter Chris
Published: April 2018

Foodborne disease causes an estimated 48 million illnesses and 3,000 deaths annually (Scallan E, et al.,
Emerg Infect Dis
17:7–15, 2011), with U.S. economic costs estimated at $152 billion to $1.4 trillion annually (Roberts T,
Am J Agric Econ
89:1183–1188, 2007; Scharff RL,
http://www.pewtrusts.org/en/research-and-analysis/reports/0001/01/01/healthrelated-costs-from-foodborne-illness-in-the-united-states
, 2010). An increasing number of these illnesses are associated with fresh fruits and vegetables. An analysis of outbreaks from 1990 to 2003 found that 12% of outbreaks and 20% of outbreak-related illnesses were associated with produce (Klein S, Smith DeWaal CS, Center for Science in the Public Interest,
https://cspinet.org/sites/default/files/attachment/ddreport.pdf
, June 2008; Lynch M, Tauxe R, Hedberg C,
Epidemiol Infect
137:307–315, 2009). These food safety problems have resulted in various stakeholders recommending the shift to a more preventative and risk-based food safety system. A modern risk-based food safety system takes a farm-to-fork preventative approach to food safety and relies on the proactive collection and analysis of data to better understand potential hazards and risk factors, to design and evaluate interventions, and to prioritize prevention efforts. Such a system focuses limited resources at the points in the food system with the likelihood of having greatest benefit to public health. As shared kitchens, food hubs, and local food systems such as community supported agriculture are becoming more prevalent throughout the United States, so are foodborne illness outbreaks at these locations. At these locations, many with limited resources, food safety methods of prevention are rarely the main focus. This lack of focus on food safety knowledge is why a growing number of foodborne illness outbreaks are occurring at these locations.
Influence of the Scandinavian climate pattern on the UK asthma mortality: a time series and geospatial study
Authors: Majeed Haris , Moore G W K
Published: April 2018

Objective

It is well known that climate variability and trends have an impact on human morbidity and mortality, especially during the winter. However, there are only a handful of studies that have undertaken quantitative investigations into this impact. We evaluate the association between the UK winter asthma mortality data to a well-established feature of the climate system, the Scandinavian (SCA) pattern.

Methods

Time series analysis of monthly asthma mortality through the period of January 2001 to December 2015 was conducted, where the data were acquired from the UK’s Office for National Statistics. The correlations between indices of important modes of climate variability impacting the UK such as the North Atlantic Oscillation as well as the SCA and the asthma mortality time series were computed. A grid point correlation analysis was also conducted with the asthma data with sea level pressure, surface wind and temperature data acquired from the European Centre for Medium-Range Weather Forecasts.

Results

We find that sea level pressure and temperature fluctuations associated with the SCA explain ~20% (>95% CL) of variance in the UK asthma mortality through a period of 2001–2015. Furthermore, the highest winter peak in asthma mortality occurred in the year 2015, during which there were strong northwesterly winds over the UK that were the result of a sea level pressure pattern similar to that associated with the SCA.

Conclusions

Our study emphasises the importance of incorporating large-scale geospatial analyses into future research of understanding diseases and its environmental impact on human health.
Developmental readiness and leadership development in medicine
Authors: Saxena Anurag , Desanghere Loni , Suryavanshi Palak
Published: April 2018

Purpose

Leadership is a key competency for physicians. Based on the premise that not everyone benefits equally from leadership development programmes, the leader developmental readiness (LDR; ability and motivation to develop) construct has been proposed to account for the differences. The purpose of this project was to explore the relationship between LDR, leadership experience, leader behaviours and leader efficacy in medical learners.

Method

Survey data from 46 medical learners were collected in 2015–2016. Separate one-way analysis of variances, with between-group factors of leadership experience (<12 months, >12 months, 0 month), were carried out on LDR constructs ofabilityandmotivationusing five validated measures: motivation to lead, goal orientation, developmental efficacy, self-awareness and metacognitive ability. Spearman’s rank-order correlations were used to examine the relationship between LDR and experience with leader efficacy and leadership behaviours (transformational and transactional). Statistical significance was determined at p<0.05. Bonferroni corrections were applied for any multiple comparisons.

Results

Significant main effects were observed for both ability and motivation to develop, showing lower scores on these variables for individuals with less leadership experience. Both experience and LDR constructs (motivation and ability) were shown to be significantly positively associated with transformational leadership behaviour (and not transactional leadership behaviour). The LDR constructs, but not leadership experience, were significantly positively associated with leader efficacy.

Conclusions

The positive correlation between LDR, experience, and transformational leadership behaviours and between LDR and leader efficacy is of value in leadership development. Understanding the developmental readiness of learners and how this affects leadership development is paramount to better inform personal leadership development and structure leadership development programmes for medical learners and physicians.
Existence of coupled Kähler–Einstein metrics using the continuity method
Authors: Pritham Pingali Vamsi
Published: April 2018

In this paper, we prove the existence of coupled Kähler–Einstein metrics on complex manifolds whose canonical bundle is ample. These metrics were introduced and their existence in the said case was proven by Hultgren and Nyström using calculus of variations. We prove the result using the method of continuity. In the process of proving estimates, akin to the usual Kähler–Einstein metrics, we reduce existence in the Fano case to a [Formula: see text] estimate.
Reduced Graphene Oxide-Supported Cobalt Phosphide Nanoflowers via in situ Hydrothermal Synthesis as Pt-Free Effective Electrocatalysts for Oxygen Reduction Reaction
Authors: Lv Yang , Wang Xianbao , Mei Tao , Li Jinhua , Wang Jianying
Published: April 2018

Cobalt phosphide (CoP) has aroused extensive research interest in a field of electrochemical application due to its excellent catalytic activities. CoP and its compounds have been widely reported using in hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). However, few reports about CoP as electrocatalysts for oxygen reduction reaction (ORR) were presented. In this work, we prepare reduced graphene-oxide(rGO)-loaded CoP (rGO@CoP) as an electrocatalyst for ORR through in situ hydrothermal treatment. The rGO@CoP as ORR catalyst exhibits excellent activities where its onset potential has a positive increase of 129[Formula: see text]mV, and the ORR potential achieves an increase of 330[Formula: see text]mV at a current density of 1.0[Formula: see text]mA[Formula: see text]cm[Formula: see text] compared with that of pure CoP. The current density is also significantly improved with an increase of 0.51[Formula: see text]mA[Formula: see text]cm[Formula: see text] at [Formula: see text]350[Formula: see text]mV, and the Tafel slope has a decrease of 19[Formula: see text]mV dec[Formula: see text]. Further tests show that the electron transfer number of rGO@CoP is 3.66, which is larger than 2.19 of pure CoP, indicating that it is dominated by a four-electron transfer pathway. Moreover, its stability (remained 98.6% current after working 6000[Formula: see text]s) and methanol tolerance are outstanding. These results show that rGO@CoP may be considered to replace traditional Pt-based ORR catalysts for fuel cells, and rGO loading has been proven to be an effective strategy to enhance the ORR performance of CoP, which may provide a new idea to synthesize transition metal phosphides as ORR catalysts.
On a fractional stochastic Hodgkin–Huxley model
Authors: Coutin Laure , Guglielmi Jean-Marc , Marie Nicolas
Published: April 2018

The model studied in this paper is a stochastic extension of the so-called neuron model introduced by Hodgkin and Huxley. In the sense of rough paths, the model is perturbed by a multiplicative noise driven by a fractional Brownian motion, with a vector field satisfying the viability condition of Coutin and Marie for [Formula: see text]. An application to the modeling of the membrane potential of nerve fibers damaged by a neuropathy is provided.
A fractional dynamical model for honeybee colony population
Authors: Akman Yıldız Tuğba
Published: April 2018

Bees are the main contributors of pollination and it is predicted that disruption of pollination causes some serious problems in economics, agriculture and ecology. It has been reported that honeybee colony collapse has increased dramatically for some time in different parts of the world. In order to investigate the causes of colony collapse, we establish a fractional multi-order honeybee colony population model. Two different models with Caputo and Caputo–Fabrizio differentiation operators have been compared. We justify the existence and uniqueness of the solution. Stability analysis has been presented. We find the numerical values of the fractional order [Formula: see text] so that the numerical results are close to the experimental findings more than the integer-order case.
Argyll Field: the first oil field to be developed on the UK Continental Shelf
Authors: Gluyas Jon , Tang Longxun , Jones Stuart
Published: April 2018

In June 1975, oil from the Argyll Field became the first to be produced from the UK North Sea. Seventeen years later, the Argyll Field was abandoned with all production facilities removed.

In 2001, two new companies, Acorn Oil & Gas and Tuscan Energy, had identified Argyll as a potential field redevelopment. The UK's Department of Industry was approached with a request to relicense the Argyll Field out of round in order to redevelop the field. No company previously had sought to obtain a licence for production rather than exploration.

In September 2003, a well was drilled on the renamed Ardmore Field. It flowed at 20 000 barrels of oil per day. However, after 2 months of sustained high rate, the well cut water. With a second well on stream, production peaked at 28 000 barrels of oil for 1 day before the facilities, designed for 50 000 barrels of fluid per day, tripped-out. All was not well; facilities and well issues limited production.

In mid-2005, the field was abandoned again: 5 MMbbl (million barrels) from an expected 25 MMbbl was produced. However, the story was not yet finished. By 2013 EnQuest had acquired the licence and drilled six wells. Production restart began in late 2015.
A Natural User Interface for Gestural Expression and Emotional Elicitation to Access the Musical Intangible Cultural Heritage
Authors: Volioti Christina , Manitsaris Sotiris , Hemery Edgar , Hadjidimitriou Stelios , Charisis Vasileios , Hadjileontiadis Leontios , Katsouli Eleni , Moutarde Fabien , Manitsaris Athanasios
Published: April 2018

This article describes a prototype natural user interface, named the Intangible Musical Instrument, which aims to facilitate access to knowledge of performers that constitutes musical Intangible Cultural Heritage using off-the-shelf motion capturing that is easily accessed by the public at large. This prototype is able to capture, model, and recognize musical gestures (upper body including fingers) as well as to sonify them. The emotional status of the performer affects the sound parameters at the synthesis level. Intangible Musical Instrument is able to support both learning and performing/composing by providing to the user not only intuitive gesture control but also a unique user experience. In addition, the first evaluation of the Intangible Musical Instrument is presented, in which all the functionalities of the system are assessed. Overall, the results with respect to this evaluation were very promising.
Challenges and Solutions for Tracing Storage Systems
Authors: Vef Marc-André , Tarasov Vasily , Hildebrand Dean , Brinkmann André
Published: April 2018

IBM Spectrum Scale’s parallel file system General Parallel File System (GPFS) has a 20-year development history with over 100 contributing developers. Its ability to support strict POSIX semantics across more than 10K clients leads to a complex design with intricate interactions between the cluster nodes. Tracing has proven to be a vital tool to understand the behavior and the anomalies of such a complex software product. However, the necessary trace information is often buried in hundreds of gigabytes of by-product trace records. Further, the overhead of tracing can significantly impact running applications and file system performance, limiting the use of tracing in a production system.

In this research article, we discuss the evolution of the mature and highly scalable GPFS tracing tool and present the exploratory study of GPFS’ new tracing interface,
FlexTrace
, which allows developers and users to accurately specify what to trace for the problem they are trying to solve. We evaluate our methodology and prototype, demonstrating that the proposed approach has negligible overhead, even under intensive I/O workloads and with low-latency storage devices.
A Low-cost Disk Solution Enabling LSM-tree to Achieve High Performance for Mixed Read/Write Workloads
Authors: Teng Dejun , Guo Lei , Lee Rubao , Chen Feng , Zhang Yanfeng , Ma Siyuan , Zhang Xiaodong
Published: April 2018

LSM-tree has been widely used in data management production systems for write-intensive workloads. However, as read and write workloads co-exist under LSM-tree, data accesses can experience long latency and low throughput due to the interferences to buffer caching from the compaction, a major and frequent operation in LSM-tree. After a compaction, the existing data blocks are reorganized and written to other locations on disks. As a result, the related data blocks that have been loaded in the buffer cache are invalidated since their referencing addresses are changed, causing serious performance degradations.

To re-enable high-speed buffer caching during intensive writes, we propose Log-Structured buffered-Merge tree (simplified as LSbM-tree) by adding a
compaction buffer
on disks to minimize the cache invalidations on buffer cache caused by compactions. The compaction buffer efficiently and adaptively maintains the frequently visited datasets. In LSbM, strong locality objects can be effectively kept in the buffer cache with minimum or no harmful invalidations. With the help of a small on-disk compaction buffer, LSbM achieves a high query performance by enabling effective buffer caching, while retaining all the merits of LSM-tree for write-intensive data processing and providing high bandwidth of disks for range queries. We have implemented LSbM based on LevelDB. We show that with a standard buffer cache and a hard disk, LSbM can achieve 2x performance improvement over LevelDB. We have also compared LSbM with other existing solutions to show its strong cache effectiveness.
Rumor Spreading and Conductance
Authors: Chierichetti Flavio , Giakkoupis George , Lattanzi Silvio , Panconesi Alessandro
Published: April 2018

In this article, we study the completion time of the PUSH-PULL variant of rumor spreading, also known as randomized broadcast. We show that if a network has
n
nodes and conductance ϕ then, with high probability, PUSH-PULL will deliver the message to all nodes in the graph within
O
(log
n
/ϕ) many communication rounds. This bound is best possible. We also give an alternative proof that the completion time of PUSH-PULL is bounded by a polynomial in log
n
/ϕ, based on graph sparsification. Although the resulting asymptotic bound is not optimal, this proof shows an interesting and, at the outset, unexpected connection between rumor spreading and graph sparsification. Finally, we show that if the degrees of the two endpoints of each edge in the network differ by at most a constant factor, then both PUSH and PULL alone attain the optimal completion time of
O
(log
n
/ϕ), with high probability.
Cardioprotection by intermittent hypoxia conditioning: evidence, mechanisms, and therapeutic potential
Authors: Mallet Robert T. , Manukhina Eugenia B. , Ruelas Steven Shea , Caffrey James L. , Downey H. Fred
Published: April 2018

The calibrated application of limited-duration, cyclic, moderately intense hypoxia-reoxygenation increases cardiac resistance to ischemia-reperfusion stress. These intermittent hypoxic conditioning (IHC) programs consistently produce striking reductions in myocardial infarction and ventricular tachyarrhythmias after coronary artery occlusion and reperfusion and, in many cases, improve contractile function and coronary blood flow. These IHC protocols are fundamentally different from those used to simulate sleep apnea, a recognized cardiovascular risk factor. In clinical studies, IHC improved exercise capacity and decreased arrhythmias in patients with coronary artery or pulmonary disease and produced robust, persistent, antihypertensive effects in patients with essential hypertension. The protection afforded by IHC develops gradually and depends on β-adrenergic, δ-opioidergic, and reactive oxygen-nitrogen signaling pathways that use protein kinases and adaptive transcription factors. In summary, adaptation to intermittent hypoxia offers a practical, largely unrecognized means of protecting myocardium from impending ischemia. The myocardial and perhaps broader systemic protection provided by IHC clearly merits further evaluation as a discrete intervention and as a potential complement to conventional pharmaceutical and surgical interventions.
Acute effects of device-guided slow breathing on sympathetic nerve activity and baroreflex sensitivity in posttraumatic stress disorder
Authors: Fonkoue Ida T. , Marvar Paul J. , Norrholm Seth D. , Kankam Melanie L. , Li Yunxiao , DaCosta Dana , Rothbaum Barbara O. , Park Jeanie
Published: April 2018

Patients with posttraumatic stress disorder (PTSD) have elevated sympathetic nervous system reactivity and impaired sympathetic and cardiovagal baroreflex sensitivity (BRS). Device-guided slow breathing (DGB) has been shown to lower blood pressure (BP) and sympathetic activity in other patient populations. We hypothesized that DGB acutely lowers BP, heart rate (HR), and improves BRS in PTSD. In 23 prehypertensive veterans with PTSD, we measured continuous BP, ECG, and muscle sympathetic nerve activity (MSNA) at rest and during 15 min of DGB at 5 breaths/min ( n = 13) or identical sham device breathing at normal rates of 14 breaths/min (sham; n = 10). Sympathetic and cardiovagal BRS was quantified using pharmacological manipulation of BP via the modified Oxford technique at baseline and during the last 5 min of DGB or sham. There was a significant reduction in systolic BP (by −9 ± 2 mmHg, P < 0.001), diastolic BP (by −3 ± 1 mmHg, P = 0.019), mean arterial pressure (by −4 ± 1 mmHg, P = 0.002), and MSNA burst frequency (by −7.8 ± 2.1 bursts/min, P = 0.004) with DGB but no significant change in HR ( P > 0.05). Within the sham group, there was no significant change in diastolic BP, mean arterial pressure, HR, or MSNA burst frequency, but there was a small but significant decrease in systolic BP ( P = 0.034) and MSNA burst incidence ( P = 0.033). Sympathetic BRS increased significantly in the DGB group (−1.08 ± 0.25 to −2.29 ± 0.24 bursts·100 heart beats−1·mmHg−1, P = 0.014) but decreased in the sham group (−1.58 ± 0.34 to –0.82 ± 0.28 bursts·100 heart beats−1·mmHg−1, P = 0.025) (time × device, P = 0.001). There was no significant difference in the change in cardiovagal BRS between the groups (time × device, P = 0.496). DGB acutely lowers BP and MSNA and improves sympathetic but not cardiovagal BRS in prehypertensive veterans with PTSD.

NEW & NOTEWORTHY Posttraumatic stress disorder is characterized by augmented sympathetic reactivity, impaired baroreflex sensitivity, and an increased risk for developing hypertension and cardiovascular disease. This is the first study to examine the potential beneficial effects of device-guided slow breathing on hemodynamics, sympathetic activity, and arterial baroreflex sensitivity in prehypertensive veterans with posttraumatic stress disorder.
Emerging applications of genome-editing technology to examine functionality of GWAS-associated variants for complex traits
Authors: Smith Andrew J. P. , Deloukas Panos , Munroe Patricia B.
Published: April 2018

Over the last decade, genome-wide association studies (GWAS) have propelled the discovery of thousands of loci associated with complex diseases. The focus is now turning toward the function of these association signals, determining the causal variant(s) among those in strong linkage disequilibrium, and identifying their underlying mechanisms, such as long-range gene regulation. Genome-editing techniques utilizing zinc-finger nucleases (ZFN), transcription activator-like effector nucleases (TALENs), and clustered regularly-interspaced short palindromic repeats with Cas9 nuclease (CRISPR-Cas9) are becoming the tools of choice to establish functionality for these variants, due to the ability to assess effects of single variants in vivo. This review will discuss examples of how these technologies have begun to aid functional analysis of GWAS loci for complex traits such as cardiovascular disease, Type 2 diabetes, cancer, obesity, and autoimmune disease. We focus on analysis of variants occurring within noncoding genomic regions, as these comprise the majority of GWAS variants, providing the greatest challenges to determining functionality, and compare editing strategies that provide different levels of evidence for variant functionality. The review describes molecular insights into some of these potentially causal variants and how these may relate to the pathology of the trait and look toward future directions for these technologies in post-GWAS analysis, such as base-editing.
The Importance of Body Composition in Explaining the Overweight Paradox in Cancer—Counterpoint
Authors: Caan Bette J. , Cespedes Feliciano Elizabeth M. , Kroenke Candyce H.
Published: April 2018

Despite a greater risk of cancer associated with higher BMI, overweight (BMI 25–<30 kg/m2) and class I obese (BMI 30–<35 kg/m2) patients often have a paradoxically lower risk of overall mortality after a cancer diagnosis, a phenomenon called the “obesity paradox.” Only when patients exceed a BMI ≥35 kg/m2 are elevations in mortality risk consistently noted. This paradox has been dismissed as the result of methodologic bias, which we will describe and debate here. However, even if such bias influences associations, there is growing evidence that body composition may in part explain the paradox. This phenomenon may more accurately be described as a BMI paradox. That is, BMI is a poor proxy for adiposity and does not distinguish muscle from adipose tissue, nor describe adipose tissue distribution. Low muscle mass is associated with higher risk of recurrence, overall and cancer-specific mortality, surgical complications, and treatment-related toxicities. Patients with who are overweight or obese have on average higher levels of muscle than their normal-weight counterparts. Also, there is some evidence that patients with moderate levels of subcutaneous adipose tissue may have lower mortality. More research utilizing body composition is needed to clarify the effects of adiposity on cancer mortality. Cancer Res; 78(8); 1906–12. ©2018 AACR.
Photodynamic Therapy Using Indocyanine Green Loaded on Super Carbonate Apatite as Minimally Invasive Cancer Treatment
Authors: Tamai Koki , Mizushima Tsunekazu , Wu Xin , Inoue Akira , Ota Minori , Yokoyama Yuhki , Miyoshi Norikatsu , Haraguchi Naotsugu , Takahashi Hidekazu , Nishimura Junichi , Hata Taishi , Matsuda Chu , Doki Yuichiro , Mori Masaki , Yamamoto Hirofumi
Published: April 2018

Minimally invasive treatment is getting more and more important in an aging society. The purpose of this study was to explore the possibility of ICG loaded on super carbonate apatite (sCA) nanoparticles as a novel photodynamic therapy (PDT) against cancers. Using colon cancer cells, ICG uptake and anti-tumor effects were examined between the treatments of ICG and sCA-ICG. Reactive oxygen species (ROS) production and temperature rise were also evaluated to explore the underlying mechanism. Atomic force microscopy revealed that the size of sCA-ICG ranged from 10 to 20 nm. In aqueous solution with 0.5% albumin, the temperature increase after laser irradiation was 27.1°C and 23.1°C in sCA-ICG and ICG, respectively (control DW: 5.7°C). A significant increase in ROS generation was noted in cell cultures treated with sCA-ICG plus irradiation compared with those treated with ICG plus irradiation (P < 0.01). Uptake of ICG in the tumor cells significantly increased in sCA-ICG compared with ICG in vitro and in vivo. The fluorescence signals of ICG in the tumor, liver, and kidney faded away in both treatments by 24 hours. Finally, the HT29 tumors treated with sCA-ICG followed by irradiation exhibited drastic tumor growth retardation (P < 0.01), whereas irradiation of tumors after injection of ICG did not inhibit tumor growth. This study shows that sCA is a useful vehicle for ICG-based PDT. Quick withdrawal of ICG from normal organs is unique to sCA-ICG and contrasts with the other nanoparticles remaining in normal organs for a long time. Mol Cancer Ther; 17(7); 1613–22. ©2018 AACR.
Clinical Next-Generation Sequencing for Precision Oncology in Rare Cancers
Authors: Groisberg Roman , Hong David S. , Roszik Jason , Janku Filip , Tsimberidou Apostolia M. , Javle Milind , Meric-Bernstam Funda , Subbiah Vivek
Published: April 2018

The European Society for Medical Oncology defines rare cancers as 5 or fewer cases per 100,000 persons per year. For many rare cancers, no standard of care exists, and treatment is often extrapolated. Identifying potentially targetable genomic alterations in rare tumors is a rational approach to improving treatment options. We sought to catalog these mutations in rare tumors and to assess their clinical utility.

For this retrospective analysis, we selected rare tumor patients from a dataset of patients who underwent clinical tumor genomic profiling. Sarcomas were excluded. To index potentially actionable alterations, patients' reports were reviewed for mutations in cancer-associated genes and pathways. Respective clinical records were abstracted to appraise the benefit of using a targeted therapy approach. Actionable alterations were defined as targeted by a drug available on-label, off-label, or in clinical trials.

The 95 patients analyzed had 40 different tumor subtypes, most common being adenoid cystic (13%), cholangiocarcinoma (7%), and metaplastic breast (6%). At least one genomic alteration was identified in 87 patients (92%). The most common identifiable mutations were in TP53 (23%), KRAS (10%), PIK3CA (9%), CDKN2A/B (8%), BRAF (7%), MLL (7%), and ARID1A (6%). Thirty-six patients (38%) with 21 different tumors had at least one potentially actionable alteration. Thirteen patients received targeted therapy. Of these, 4 had a partial response, 6 had stable disease, and 3 had progressive disease as the best response.

The addition of genomic profiling to management of rare cancers adds a potential line of therapy for cancers that have little or no standard of care. In our analysis, tumors with a BRAF alteration responded well to BRAF inhibitors. Mol Cancer Ther; 17(7); 1595–601. ©2018 AACR.
A Short BRCA2-Derived Cell-Penetrating Peptide Targets RAD51 Function and Confers Hypersensitivity toward PARP Inhibition
Authors: Trenner Anika , Godau Julia , Sartori Alessandro A.
Published: April 2018

Under conditions of genotoxic stress, cancer cells strongly rely on efficient DNA repair to survive and proliferate. The human BRCA2 tumor suppressor protein is indispensable for the repair of DNA double-strand breaks by homologous recombination (HR) by virtue of its ability to promote RAD51 loading onto single-stranded DNA. Therefore, blocking the interaction between BRCA2 and RAD51 could significantly improve the efficacy of conventional anticancer therapies. However, targeting protein–protein interaction (PPI) interfaces has proven challenging because flat and large PPI surfaces generally do not support binding of small-molecule inhibitors. In contrast, peptides are more potent for targeting PPIs but are otherwise difficult to deliver into cells. Here, we report that a synthetic 16-mer peptide derived from the BRC4 repeat motif of BRCA2 is capable of blocking RAD51 binding to BRCA2. Efficient noncytotoxic cellular uptake of a nona-arginine (R9)-conjugated version of the BRC4 peptide interferes with DNA damage–induced RAD51 foci formation and HR. Moreover, transduction of the BRC4 peptide impairs replication fork–protective function of BRCA2 and triggers MRE11-dependent degradation of nascent DNA in response to DNA replication stress. Finally, the BRC4 cell-penetrating peptide (CPP) confers selective hypersensitivity to PARP inhibition in cancer cells but spares noncancerous cells. Taken together, our data highlight an innovative approach to develop novel peptide-based DNA repair inhibitors and establish BRCA2-derived CPPs as promising anticancer agents. Mol Cancer Ther; 17(7); 1392–404. ©2018 AACR.
Findings of Optical Coherence Tomography Angiography in Best Vitelliform Macular Dystrophy
Authors: Wang Xiao Na , You Qi Sheng , Li Qian , Li Yang , Mao Yu , Hu Feng , Zhao Hui Ying , Tsai Frank F. , Peng Xiao Yan
Published: April 2018

Purpose: To evaluate the vascular anatomy of eyes with Best vitelliform macular dystrophy (BVMD) using optical coherence tomography angiography (OCTA). Methods: This retrospective case-control study enrolled 11 consecutive BVMD patients and 13 age-matched healthy participants. Both eyes of each participant were imaged using a macular OCTA scan (3 × 3 mm) by 70-kHz 840-nm spectral-domain OCT. The flow signal was calculated using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Results: Qualitative analysis showed uneven hypo- and hyperintense signal changes at the choriocapillary level in OCTA images of BVMD patients. Quantitative analysis showed significant reductions in the flow density of the superficial vascular layer (whole: 49.2% vs. 53.9%, p < 0.001) and the choriocapillary flow area (5.1 vs. 5.5 mm2, p = 0.02) in BVMD patients compared to controls. The choriocapillary flow area in the postvitelliform group was reduced compared to that of the vitelliform group. There was a statistically significant association between choriocapillary flow area and superficial vascular flow density (p = 0.045), choriocapillary flow area and foveal avascular zone area (p = 0.03). Conclusions: Vascular changes in BVMD were apparent in the choriocapillary layer. The changes became more striking in late stages of the disease. OCTA provides useful quantitative measurements for staging and monitoring the progression of BVMD.