bluuebunny/crossref_metadata_2025 huggingface dataset:
Child maltreatment as a predictor of adult physical functioning in a prospective British birth cohort
Authors: Archer Gemma , Pinto Pereira Snehal , Power Christine
Published: October 2017

Objective

Child maltreatment (abuse and neglect) has established associations with mental health; however, little is known about its relationship with physical functioning. Physical functioning (ie, the ability to perform the physical tasks of daily living) in adulthood is an important outcome to consider, as it is strongly associated with an individual’s ability to work, and future disability and dependency. We aimed to establish whether maltreatment was associated with physical functioning, independent of other early-life factors.

Setting

1958 British birth cohort.

Participants

8150 males and females with data on abuse and who participated at age 50 years.

Outcome measures

The primary outcome was poor physical functioning at 50 years (<65 on the Short-Form 36 survey physical functioning subscale). Secondary outcomes included mental health and self-reported health at 50 years.

Results

23% of participants reported at least one type of maltreatment; 12% were identified with poor physical functioning. Neglect (ORadj1.55, 95% CI 1.24 to 1.93), psychological abuse (ORadj1.49, 1.17–1.88) and sexual abuse (ORadj2.56, 1.66–3.96) were associated with poor physical functioning independent of other maltreatments and covariates, including childhood social class, birth weight and childhood illness. Odds of poor physical functioning increased with multiple types of maltreatment (ptrend<0.001); ORadjranged from 1.49 (1.23–1.82) for a single type to 2.09 (1.53–2.87) for those reporting>3 types of maltreatment, compared with those with none. Associations of similar magnitude were observed for mental and self-reported health outcomes.

Conclusions

Child neglect, psychological and sexual abuse were associated with poor physical functioning at 50 years, with accumulating risk for those with multiple types of maltreatment. Associations were independent of numerous early-life factors and were comparable in magnitude to those observed for mental health and self-rated health. Prevention or alleviation of the ill effects of maltreatment could be an effective policy intervention to promote healthy ageing.
Primary care scribes: writing a new story for safety net clinics
Authors: Lowry Christina , Orr Katherine , Embry Brett , Nguyen Michael , Petersen Amy , James Catherine , Seidel Keith , Ratanawongsa Neda
Published: October 2017

The spread of electronic health records systems (EHRs) poses challenges for both patient and provider care experience. Limited research suggests that scribes offer potential benefits to productivity and clinician satisfaction in emergency health and specialty settings. We conducted this evaluation of trained volunteer scribes for primary care clinics serving a diverse, low-income population in a US safety net system, which implemented a new EHR 2011–2014. The scribe programme trained and managed scribes for 51 providers (25% participation) from 5 of 12 San Francisco Health Network primary care clinics. We evaluated the programme using four measures. Providers reported spending less time out of clinic completing notes after sessions with scribes versus sessions without scribes (14.0 min vs 30.2 min, p<0.01). The rate of incomplete EHR notes at 72 hours was not significantly different for clinics using and not using scribes (16.9% vs 16.7%, p=0.4). Mean visit length using EHR-recorded provider cycle time was shorter for sessions with scribes (24.0 min), compared with sessions without scribes (26.4 min, p<0.01). Patients at clinics using scribes were as likely to recommend their provider (74.5%), compared with patients at clinics not using scribes (74.3%). Limitations of our evaluation include selection bias and possible confounding by clinic- and provider-level factors. In a safety net primary care system, trained volunteer scribes were associated with improved clinician efficiency and experience and no difference in patient satisfaction.
Reorganisation of stroke care and impact on mortality in patients admitted during weekends: a national descriptive study based on administrative data
Authors: Balinskaite Violeta , Bottle Alex , Shaw Louise Johanna , Majeed Azeem , Aylin Paul
Published: October 2017

Objective

To evaluate mortality differences between weekend and weekday emergency stroke admissions in England over time, and in particular, whether a reconfiguration of stroke services in Greater London was associated with a change in this mortality difference.

Design, setting and participants

Risk-adjusted difference-in-difference time trend analysis using hospital administrative data. All emergency patients with stroke admitted to English hospitals from 1 January 2008 to 31 December 2014 were included.

Main outcomes

Mortality difference between weekend and weekday emergency stroke admissions.

Results

We identified 507 169 emergency stroke admissions: 26% of these occurred during the weekend. The 7-day in-hospital mortality difference between weekend and weekday admissions declined across England throughout the study period. In Greater London, where the reorganisation of stroke services took place, an adjusted 28% (relative risk (RR)=1.28, 95% CI 1.09 to 1.47) higher weekend/weekday 7-day mortality ratio in 2008 declined to a non-significant 9% higher risk (RR=1.09, 95% CI 0.91 to 1.32) in 2014. For the rest of England, a 15% (RR=1.15, 95% CI 1.09 to 1.22) higher weekend/weekday 7-day mortality ratio in 2008 declined to a non-significant 3% higher risk (RR=1.03, 95% CI 0.97 to 1.10) in 2014. During the same period, in Greater London an adjusted 12% (RR=1.12, 95% CI 1.00 to 1.26) weekend/weekday 30-day mortality ratio in 2008 slightly increased to 14% (RR=1.14, 95% CI 1.00 to 1.30); however, it was not significant. In the rest of England, an 11% (RR=1.11, 95% CI 1.07 to 1.15) higher weekend/weekday 30-day mortality ratio declined to a non-significant 4% higher risk (RR=1.04, 95% CI 0.99 to 1.09) in 2014. We found no statistically significant association between decreases in the weekend/weekday admissions difference in mortality and the centralisation of stroke services in Greater London.

Conclusions

There was a steady reduction in weekend/weekday differences in mortality in stroke admissions across England. It appears statistically unrelated to the centralisation of stroke services in Greater London, and is consistent with an overall national focus on improving stroke services.
Pathways of undue influence in health policy-making: a main actor’s perspective
Authors: Hernández-Aguado Ildefonso , Chilet-Rosell Elisa
Published: October 2017

Background

It is crucial to know the extent to which influences lead to policy capture—by which the policy-making process is shifted away from the public interest towards narrow private interests. Using the case study of Spain, our aim was to identify interactions between public administration, civil society and private companies that could influence health policies.

Methods

54 semistructured interviews with key actors related to health policy. The interviews were used to gather information on main policy actors as well as on direct and subtle influences that could modify health policies. The analysis identified and described, from the interviewed persons’ experiences, both the inappropriate influences exerted on the actors and those that they exerted.

Results

Inappropriate influences were identified at all levels of administration and policy. They included actions for personal benefits, pressure for blocking health policies and pressure from high levels of government in favour of private corporations. The private sector played a significant role in these strategies through bribery, personal gifts, revolving doors, negative campaigns and by blocking unfavourable political positions or determining the knowledge agenda. The interviewees reported subtle forms of influence (social events, offers of technical support, invitations, etc) that contributed to the intellectual and cultural capture of health officials.

Conclusion

The health policy decision-making processes in Spain are subject to influences by stakeholders that determine a degree of policy capture, which is avoidable. The private sector uses different strategies, from subtle influences to outright corruption, taking advantage in many cases of flexible legislation.
Genome-wide association study identified copy number variants associated with sporadic colorectal cancer risk
Authors: Thean Lai Fun , Low Yee Syuen , Lo Michelle , Teo Yik-Ying , Koh Woon-Puay , Yuan Jian-Min , Chew Min Hoe , Tang Choong Leong , Cheah Peh Yean
Published: October 2017

Background

Multiple single nucleotide polymorphisms (SNPs) have been associated with colorectal cancer (CRC) risk. The role of structural or copy number variants (CNV) in CRC, however, remained unclear. We investigated the role of CNVs in patients with sporadic CRC.

Methods

A genome-wide association study (GWAS) was performed on 1000 Singapore Chinese patients aged 50 years or more with no family history of CRC and 1000 ethnicity-matched, age-matched and gender-matched healthy controls using the Affymetrix SNP 6 platform. After 16 principal component corrections, univariate and multivariate segmentations followed by association testing were performed on 1830 samples that passed quality assurance tests.

Results

A rare CNV region (CNVR) at chromosome 14q11 (OR=1.92 (95% CI 1.59 to 2.32), p=2.7e-12) encompassing CHD8, and common CNVR at chromosomes 3q13.12 (OR=1.54 (95% CI 1.33 to 1.77), p=2.9e-9) and 12p12.3 (OR=1.69 (95% CI 1.41 to 2.01), p=2.8e-9) encompassing CD47 and RERG/ARHGDIB, respectively, were significantly associated with CRC risk. CNV loci were validated in an independent replication panel using an optimised copy number assay. Whole-genome expression data in matched tumours of a subset of cases demonstrated that copy number loss at CHD8 was significantly associated with dysregulation of several genes that perturb the Wnt, TP53 and inflammatory pathways.

Conclusions

A rare CNVR at 14q11 encompassing the chromatin modifier CHD8 was significantly associated with sporadic CRC risk. Copy number loss at CHD8 altered expressions of genes implicated in colorectal tumourigenesis.
Discordant patient–physician assessments of disease activity and its persistence adversely impact quality of life and work productivity in US Hispanics with rheumatoid arthritis
Authors: Karpouzas George A , Ramadan Sera N , Cost Chelsie E , Draper Taylor L , Hernandez Elizabeth , Strand Vibeke , Ormseth Sarah R
Published: October 2017

Objective

This study was designed to evaluate the determinants of patient and physician global assessments (PtGA and MDGA, respectively) of disease activity, their discordance and change over 2 years in Hispanics with rheumatoid arthritis (RA). We further examined the impact of discordance and its persistence on health-related quality of life (HRQOL) and work productivity on final visit.

Methods

We studied 536 Hispanics with established RA from a single centre. PtGA and MDGA were measured annually on 10 cm visual analogue scales and discordance was defined as absolute difference between them ≥3 cm. Associations between predictors and outcomes of interest were evaluated using multivariable regression and analysis of covariance for cross-sectional and longitudinal data, respectively.

Results

Independent predictors of baseline PtGA were pain, fatigue, depression, general health perceptions and tender joint count. MDGA was predicted by swollen joint count, tender joint count, erythrocyte sedimentation rate, fatigue and depression. Both PtGA and MDGA improved over time (all p<0.001). Discordance was observed in 43% at baseline, with fair stability over 2 years. Higher (worse) patient ratings were most prevalent; their presence at any time and increasing persistence predicted lower physical and mental HRQOL, decreased work productivity and more activity impairment at 2-year follow-up (all p<0.001).

Conclusions

Determinants of PtGA, MDGA and changes over 2 years were disparate in Hispanics with RA yielding significant discordance. Higher patient ratings at any time contributed to worse HRQOL, work productivity and activity impairment on final visit.
Duration of the efficacy of omalizumab after treatment discontinuation in ‘real life’ severe asthma
Authors: Vennera Maria del Carmen , Sabadell Carlos , Picado Cesar
Published: October 2017

Efficacy of omalizumab in severe asthma is well documented; however, the optimal duration of the treatment remains unclear. In an open prospective study, we sought to assess the persistence of response in subjects withdrawing from omalizumab treatment. We evaluated 49 patients who voluntarily accepted to discontinue omalizumab treatment after 6 years of therapy. Asthma relapse was defined as any severe asthma exacerbation associated with loss of asthma control. Twelve patients relapsed in the first year of follow-up, and 7 within 13 and 48 months. These results suggest that the effects of 6 years of omalizumab may persist after discontinuation of therapy in 60% of patients for at least 4 years.
Smoke-free legislation and paediatric hospitalisations for acute respiratory tract infections: national quasi-experimental study with unexpected findings and important methodological implications
Authors: Been Jasper V , Mackay Daniel F , Millett Christopher , Soyiri Ireneous , van Schayck Constant P , Pell Jill P , Sheikh Aziz
Published: October 2017

Objectives

We investigated whether Scottish implementation of smoke-free legislation was associated with a reduction in unplanned hospitalisations or deaths (‘events’) due to respiratory tract infections (RTIs) among children.

Design

Interrupted time series (ITS).

Setting/participants

Children aged 0–12 years living in Scotland during 1996–2012.

Intervention

National comprehensive smoke-free legislation (March 2006).

Main outcome measure

Acute RTI events in the Scottish Morbidity Record-01 and/or National Records of Scotland Death Records.

Results

135 134 RTI events were observed over 155 million patient-months. In our prespecified negative binomial regression model accounting for underlying temporal trends, seasonality, sex, age group, region, urbanisation level, socioeconomic status and seven-valent pneumococcal vaccination status, smoke-free legislation was associated with an immediate rise in RTI events (incidence rate ratio (IRR)=1.24, 95% CI 1.20 to 1.28) and an additional gradual increase (IRR=1.05/year, 95% CI 1.05 to 1.06). Given this unanticipated finding, we conducted a number of post hoc exploratory analyses. Among these, automatic break point detection indicated that the rise in RTI events actually preceded the smoke-free law by 16 months. When accounting for this break point, smoke-free legislation was associated with a gradual decrease in acute RTI events: IRR=0.91/year, 95% CI 0.87 to 0.96.

Conclusions

Our prespecified ITS approach suggested that implementation of smoke-free legislation in Scotland was associated with an increase in paediatric RTI events. We were concerned that this result, which contradicted published evidence, was spurious. The association was indeed reversed when accounting for an unanticipated antecedent break point in the temporal trend, suggesting that the legislation may in fact be protective. ITS analyses should be subjected to comprehensive robustness checks to assess consistency.
The relationship between mineralization and tectonics at the Kainantu gold–copper deposit, Papua New Guinea
Authors: Blenkinsop Tom , Tripp Gerard , Gillen Dave
Published: October 2017

Epithermal veins and breccias at the Kainantu gold–copper deposit in Papua New Guinea, host gold mineralization in NW–SE steeply dipping lodes. The lodes are parallel to a pre-mineralization dextral strike-slip shear-zone network, which is itself parallel in places to an early greenschist-facies cleavage in basement schists. The cleavage, shear zone and veins are all cut by dextral strike-slip faults. High Au grades correlate with areas of obliquity between the shear-zone fabrics and the cleavage, and plunge at approximately 40° SE in the plane of the lodes – coincident with minor fold axes related to a crenulation cleavage in the basement rocks. This clear structural history shows that gold mineralization was confined to a particular late structural event, but lode geometry was influenced by all previous structures, as well as being displaced by post-mineralization faulting. The north–south shortening recorded through most of the tectonic history can be related to Tertiary convergence along the major plate boundary located approximately 15 km north of the mine. However, mineralization occurred under a different tectonic regime from the current north–south convergence, when there was a change of tectonics between 9 and 6 Ma, possibly related to delamination.
Students’ Misconceptions and Other Difficulties in Introductory Programming
Authors: Qian Yizhou , Lehman James
Published: October 2017

Efforts to improve computer science education are underway, and teachers of computer science are challenged in introductory programming courses to help learners develop their understanding of programming and computer science. Identifying and addressing students’ misconceptions is a key part of a computer science teacher's competence. However, relevant research on this topic is not as fully developed in the computer science education field as it is in mathematics and science education. In this article, we first review relevant literature on general definitions of misconceptions and studies about students’ misconceptions and other difficulties in introductory programming. Next, we investigate the factors that contribute to the difficulties. Finally, strategies and tools to address difficulties including misconceptions are discussed.

Based on the review of literature, we found that students exhibit various misconceptions and other difficulties in syntactic knowledge, conceptual knowledge, and strategic knowledge. These difficulties experienced by students are related to many factors including unfamiliarity of syntax, natural language, math knowledge, inaccurate mental models, lack of strategies, programming environments, and teachers’ knowledge and instruction. However, many sources of students’ difficulties have connections with students’ prior knowledge. To better understand and address students’ misconceptions and other difficulties, various instructional approaches and tools have been developed. Nevertheless, the dissemination of these approaches and tools has been limited. Thus, first, we suggest enhancing the dissemination of existing tools and approaches and investigating their long-term effects. Second, we recommend that computing education research move beyond documenting misconceptions to address the development of students’ (mis)conceptions by integrating conceptual change theories. Third, we believe that developing and enhancing instructors’ pedagogical content knowledge (PCK), including their knowledge of students’ misconceptions and ability to apply effective instructional approaches and tools to address students’ difficulties, is vital to the success of teaching introductory programming.
Developing Computational Thinking through a Virtual Robotics Programming Curriculum
Authors: Witherspoon Eben B. , Higashi Ross M. , Schunn Christian D. , Baehr Emily C. , Shoop Robin
Published: October 2017

Computational thinking describes key principles from computer science that are broadly generalizable. Robotics programs can be engaging learning environments for acquiring core computational thinking competencies. However, few empirical studies evaluate the effectiveness of a robotics programming curriculum for developing computational thinking knowledge and skills. This study measures pre/post gains with new computational thinking assessments given to middle school students who participated in a virtual robotics programming curriculum. Overall, participation in the virtual robotics curriculum was related to significant gains in pre- to posttest scores, with larger gains for students who made further progress through the curriculum. The success of this intervention suggests that participation in a scaffolded programming curriculum, within the context of virtual robotics, supports the development of generalizable computational thinking knowledge and skills that are associated with increased problem-solving performance on nonrobotics computing tasks. Furthermore, the particular units that students engage in may determine their level of growth in these competencies.
Efficient and Robust Emergence of Norms through Heuristic Collective Learning
Authors: Hao Jianye , Sun Jun , Chen Guangyong , Wang Zan , Yu Chao , Ming Zhong
Published: October 2017

In multiagent systems, social norms serves as an important technique in regulating agents’ behaviors to ensure effective coordination among agents without a centralized controlling mechanism. In such a distributed environment, it is important to investigate how a desirable social norm can be synthesized in a bottom-up manner among agents through repeated local interactions and learning techniques. In this article, we propose two novel learning strategies under the collective learning framework,
collective learning EV-l
and
collective learning EV-g
, to efficiently facilitate the emergence of social norms. Extensive simulations results show that both learning strategies can support the emergence of desirable social norms more efficiently and be applicable in a wider range of multiagent interaction scenarios compared with previous work. The influence of different topologies is investigated, which shows that the performance of all strategies is robust across different network topologies. The influences of a number of key factors (neighborhood size, actions space, population size, fixed agents and isolated subpopulations) on norm emergence performance are investigated as well.
Self-Checkpoint
Authors: Tang Xiongchao , Zhai Jidong , Yu Bowen , Chen Wenguang , Zheng Weimin
Published: October 2017

Fault tolerance is increasingly important in high performance computing due to the substantial growth of system scale and decreasing system reliability. In-memory/diskless checkpoint has gained extensive attention as a solution to avoid the IO bottleneck of traditional disk-based checkpoint methods. However, applications using previous in-memory checkpoint suffer from little available memory space. To provide high reliability, previous in-memory checkpoint methods either need to keep two copies of checkpoints to tolerate failures while updating old checkpoints or trade performance for space by flushing in-memory checkpoints into disk.

In this paper, we propose a novel in-memory checkpoint method, called self-checkpoint, which can not only achieve the same reliability of previous in-memory checkpoint methods, but also increase the available memory space for applications by almost 50%. To validate our method, we apply the self-checkpoint to an important problem, fault tolerant HPL. We implement a scalable and fault tolerant HPL based on this new method, called SKT-HPL, and validate it on two large-scale systems. Experimental results with 24,576 processes show that SKT-HPL achieves over 95% of the performance of the original HPL. Compared to the state-of-the-art in-memory checkpoint method, it improves the available memory size by 47% and the performance by 5%.
EffiSha
Authors: Chen Guoyang , Zhao Yue , Shen Xipeng , Zhou Huiyang
Published: October 2017

Modern GPUs are broadly adopted in many multitasking environments, including data centers and smartphones. However, the current support for the scheduling of multiple GPU kernels (from different applications) is limited, forming a major barrier for GPU to meet many practical needs. This work for the first time demonstrates that on existing GPUs, efficient preemptive scheduling of GPU kernels is possible even without special hardware support. Specifically, it presents EffiSha, a pure software framework that enables preemptive scheduling of GPU kernels with very low overhead. The enabled preemptive scheduler offers flexible support of kernels of different priorities, and demonstrates significant potential for reducing the average turnaround time and improving the system overall throughput of programs that time share a modern GPU.
Silent Data Corruption Resilient Two-sided Matrix Factorizations
Authors: Wu Panruo , DeBardeleben Nathan , Guan Qiang , Blanchard Sean , Chen Jieyang , Tao Dingwen , Liang Xin , Ouyang Kaiming , Chen Zizhong
Published: October 2017

This paper presents an algorithm based fault tolerance method to harden three two-sided matrix factorizations against soft errors: reduction to Hessenberg form, tridiagonal form, and bidiagonal form. These two sided factorizations are usually the prerequisites to computing eigenvalues/eigenvectors and singular value decomposition. Algorithm based fault tolerance has been shown to work on three main one-sided matrix factorizations: LU, Cholesky, and QR, but extending it to cover two sided factorizations is non-trivial because there are no obvious \textit{offline, problem} specific maintenance of checksums. We thus develop an \textit{online, algorithm} specific checksum scheme and show how to systematically adapt the two sided factorization algorithms used in LAPACK and ScaLAPACK packages to introduce the algorithm based fault tolerance.

The resulting ABFT scheme can detect and correct arithmetic errors \textit{continuously} during the factorizations that allow timely error handling. Detailed analysis and experiments are conducted to show the cost and the gain in resilience. We demonstrate that our scheme covers a significant portion of the operations of the factorizations. Our checksum scheme achieves high error detection coverage and error correction coverage compared to the state of the art, with low overhead and high scalability.
Understanding the GPU Microarchitecture to Achieve Bare-Metal Performance Tuning
Authors: Zhang Xiuxia , Tan Guangming , Xue Shuangbai , Li Jiajia , Zhou Keren , Chen Mingyu
Published: October 2017

In this paper, we present a methodology to understand GPU microarchitectural features and improve performance for compute-intensive kernels. The methodology relies on a reverse engineering approach to crack the GPU ISA encodings in order to build a GPU assembler. An assembly microbenchmark suite correlates microarchitectural features with their performance factors to uncover instruction-level and memory hierarchy preferences. We use SGEMM as a running example to show the ways to achieve bare-metal performance tuning. The performance boost is achieved by tuning FFMA throughput by activating dual-issue, eliminating register bank conflicts, adding non-FFMA instructions with little penalty, and choosing proper width of global/shared load instructions. On NVIDIA Kepler K20m, we develop a faster SGEMM with 3.1Tflop/s performance and 88% efficiency; the performance is 15% higher than cuBLAS7.0. Applying these optimizations to convolution, the implementation gains 39%-62% performance improvement compared with cuDNN4.0. The toolchain is an attempt to automatically crack different GPU ISA encodings and build an assembler adaptively for the purpose of performance enhancements to applications on GPUs.
Combining SIMD and Many/Multi-core Parallelism for Finite State Machines with Enumerative Speculation
Authors: Jiang Peng , Agrawal Gagan
Published: October 2017

Finite State Machine (FSM) is the key kernel behind many popular applications, including regular expression matching, text tokenization, and Huffman decoding. Parallelizing FSMs is extremely difficult because of the strong dependencies and unpredictable memory accesses. Previous efforts have largely focused on multi-core parallelization, and used different approaches, including {\em speculative} and {\em enumerative} execution, both of which have been effective but also have limitations. With increasing width and improving flexibility in SIMD instruction sets, this paper focuses on combining SIMD and multi/many-core parallelism for FSMs. We have developed a novel strategy, called {\em enumerative speculation}. Instead of speculating on a single state as in speculative execution or enumerating all possible states as in enumerative execution, our strategy speculates transitions from several possible states, reducing the prediction overheads of speculation approach and the large amount of redundant work in the enumerative approach. A simple lookback approach produces a set of guessed states to achieve high speculation success rates in our enumerative speculation. We evaluate our method with four popular FSM applications: Huffman decoding, regular expression matching, HTML tokenization, and Div7. We obtain up to 2.5x speedup using SIMD on one core and up to 95x combining SIMD with 60 cores of an Intel Xeon Phi. On a single core, we outperform the best single-state speculative execution version by an average of 1.6x, and in combining SIMD and many-core parallelism, outperform enumerative execution by an average of 2x.
Exploiting Vector and Multicore Parallelism for Recursive, Data- and Task-Parallel Programs
Authors: Ren Bin , Krishnamoorthy Sriram , Agrawal Kunal , Kulkarni Milind
Published: October 2017

Modern hardware contains parallel execution resources that are well-suited for data-parallelism-vector units-and task parallelism-multicores. However, most work on parallel scheduling focuses on one type of hardware or the other. In this work, we present a scheduling framework that allows for a unified treatment of task- and data-parallelism. Our key insight is an abstraction, task blocks, that uniformly handles data-parallel iterations and task-parallel tasks, allowing them to be scheduled on vector units or executed independently as multicores. Our framework allows us to define schedulers that can dynamically select between executing task- blocks on vector units or multicores. We show that these schedulers are asymptotically optimal, and deliver the maximum amount of parallelism available in computation trees. To evaluate our schedulers, we develop program transformations that can convert mixed data- and task-parallel pro- grams into task block-based programs. Using a prototype instantiation of our scheduling framework, we show that, on an 8-core system, we can simultaneously exploit vector and multicore parallelism to achieve 14×-108× speedup over sequential baselines.
Model-based Iterative CT Image Reconstruction on GPUs
Authors: Sabne Amit , Wang Xiao , Kisner Sherman J. , Bouman Charles A. , Raghunathan Anand , Midkiff Samuel P.
Published: October 2017

Computed Tomography (CT) Image Reconstruction is an important technique used in a variety of domains, including medical imaging, electron microscopy, non-destructive testing and transportation security. Model-based Iterative Reconstruction (MBIR) using Iterative Coordinate Descent (ICD) is a CT algorithm that produces state-of-the-art results in terms of image quality. However, MBIR is highly computationally intensive and challenging to parallelize, and has traditionally been viewed as impractical in applications where reconstruction time is critical. We present the first GPU-based algorithm for ICD-based MBIR. The algorithm leverages the recently-proposed concept of SuperVoxels, and efficiently exploits the three levels of parallelism available in MBIR to better utilize the GPU hardware resources. We also explore data layout transformations to obtain more coalesced accesses and several GPU-specific optimizations for MBIR that boost performance. Across a suite of 3200 test cases, our GPU implementation obtains a geometric mean speedup of 4.43X over a state-of-the-art multi-core implementation on a 16-core iso-power CPU.
POSTER
Authors: Cohen Nachshon , Herlihy Maurice , Petrank Erez , Wald Elias
Published: October 2017

State teleportation
is a new technique for exploiting hardware transactional memory (HTM) to improve existing synchronization and memory management schemes for highly-concurrent data structures. When applied to fine-grained locking, a thread holding the lock for a node launches a hardware transaction that traverses multiple successor nodes, acquires the lock for the last node reached, and releases the lock on the starting node, skipping lock acquisitions for intermediate nodes. When applied to lock-free data structures, a thread visiting a node protected by a hazard pointer launches a hardware transaction that traverses multiple successor nodes, and publishes the hazard pointer only for the last node reached, skipping the memory barriers needed to publish intermediate hazard pointers. Experimental results show that these applications of state teleportation can substantially increase the performance of both lock-based and lock-free data structures.
POSTER
Authors: Chowdhury Rezaul , Ganapathi Pramod , Tang Yuan , Tithi Jesmin Jahan
Published: October 2017

Standard cache-oblivious recursive divide-and-conquer algorithms for evaluating dynamic programming recurrences have optimal serial cache complexity but often have lower parallelism compared with iterative wavefront algorithms due to artificial dependencies among subtasks. Very recently cache-oblivious recursive wavefront (COW) algorithms have been introduced which do not have any artificial dependencies. Though COW algorithms are based on fork-join primitives, they extensively use atomic operations, and as a result, performance guarantees provided by state-of-the-art schedulers for programs with fork-join primitives do not apply.

In this work, we show how to systematically transform standard cache-oblivious recursive divide-and-conquer algorithms into recursive wavefront algorithms to achieve optimal parallel cache complexity and high parallelism under state-of-the-art schedulers for fork-join programs. Unlike COW algorithms these new algorithms do not use atomic operations. Instead, they use closed-form formulas to compute at what time each recursive function must be launched in order to achieve high parallelism without losing cache performance. The resulting implementations are arguably much simpler than implementations of known COW algorithms.
POSTER
Authors: Arbel-Raviv Maya , Brown Trevor
Published: October 2017

Lock-free algorithms guarantee progress by having threads help one another. Complex lock-free operations facilitate helping by creating descriptor objects that describe how other threads should help them. In many lock-free algorithms, a new descriptor is allocated for each operation. After an operation completes, its descriptor must be reclaimed by a memory reclamation scheme. Allocating and reclaiming descriptors introduces significant space and time overhead.

We present a transformation for a class of lock-free algorithms that allows each thread to efficiently reuse a single descriptor. Experiments on a variety of workloads show that our transformation yields significant improvements over implementations that reclaim descriptors.
The Ethnopharmacologic Contribution to Bioprospecting Natural Products
Authors: Buenz Eric J. , Verpoorte Rob , Bauer Brent A.
Published: October 2017

Descriptions of the use of natural products in traditional medicine have served as starting points for new therapeutics. The details of the traditional use of these organisms can provide important information for future drug discovery and development efforts. Recent technologic advances provide the framework to leverage ethnopharmacologic data in the drug discovery process. Information on the traditional harvest, preparation, storage, and administration of the organisms, and the natural products they contain, provides valuable details regarding characteristics of the active compounds. Importantly, researchers can now rapidly analyze and identify the multiple, and often synergistic, compounds contained in these natural products. Although we are entering the acme of ethnopharmacology, where information regarding the traditional use of organisms can provide valuable natural product leads and accelerate the identification of new therapeutics, this ethnopharmacologic resource is threatened by the loss of traditional medicine knowledge and extinction of organisms.
Dual mTOR Kinase Inhibitor MLN0128 Sensitizes HR+/HER2+ Breast Cancer Patient-Derived Xenografts to Trastuzumab or Fulvestrant
Authors: Hsu Pei-Yin , Wu Victoria Shang , Kanaya Noriko , Petrossian Karineh , Hsu Hang-Kai , Nguyen Duc , Schmolze Daniel , Kai Masaya , Liu Chun-Yu , Lu Hannah , Chu Peiguo , Vito Courtney A. , Kruper Laura , Mortimer Joanne , Chen Shiuan
Published: October 2017

Purpose: Therapeutic strategies against hormonal receptor–positive (HR+)/HER2+ breast cancers with poor response to trastuzumab need to be optimized.

Experimental Design: Two HR+/HER2+ patient-derived xenograft (PDX) models named as COH-SC1 and COH-SC31 were established to explore targeted therapies for HER2+ breast cancers. RNA sequencing and RPPA (reverse phase protein array) analyses were conducted to decipher molecular features of the two PDXs and define the therapeutic strategy of interest, validated by in vivo drug efficacy examination and in vitro cell proliferation analysis.

Results: Estrogen acted as a growth driver of trastuzumab-resistant COH-SC31 tumors but an accelerator in the trastuzumab-sensitive COH-SC1 model. In vivo trastuzumab efficacy examination further confirmed the consistent responses between PDXs and the corresponding tumors. Integrative omics analysis revealed that mammalian target of rapamycin (mTOR) and ERα signaling predominantly regulate tumor growth of the two HR+/HER2+ PDXs. Combination of the dual mTOR complex inhibitor MLN0128 and anti-HER2 trastuzumab strongly suppressed tumor growth of COH-SC1 PDX accompanied by increasing ER-positive cell population in vivo. Instead, MLN0128 in combination with antiestrogen fulvestrant significantly halted the growth of HR+/HER2+ cancer cells in vitro and trastuzumab-resistant COH-SC31 as well as trastuzumab-sensitive COH-SC1 tumors in vivo.

Conclusions: Compared with the standard trastuzumab treatment, this study demonstrates alternative therapeutic strategies against HR+/HER2+ tumors through establishment of two PDXs coupled with integrative omics analyses and in vivo drug efficacy examination. This work presents a prototype of future “co-clinical” trials to tailor personalized medicine in clinical practice. Clin Cancer Res; 24(2); 395–406. ©2017 AACR.
Conversion of PRPS Hexamer to Monomer by AMPK-Mediated Phosphorylation Inhibits Nucleotide Synthesis in Response to Energy Stress
Authors: Qian Xu , Li Xinjian , Tan Lin , Lee Jong-Ho , Xia Yan , Cai Qingsong , Zheng Yanhua , Wang Hongxia , Lorenzi Philip L. , Lu Zhimin
Published: October 2017

Tumors override energy stress to grow. However, how nucleotide synthesis is regulated under energy stress is unclear. We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production. Knock-in of nonphosphorylatable PRPS1/2 mutants, which have uninhibited activity, in brain tumor cells under energy stress exhausts cellular ATP and NADPH and increases reactive oxygen species levels, thereby promoting cell apoptosis. The expression of those mutants inhibits brain tumor formation and enhances the inhibitory effect of the glycolysis inhibitor 2-deoxy-d-glucose on tumor growth. Our findings highlight the significance of recalibrating tumor cell metabolism by fine-tuning nucleotide and NAD synthesis in tumor growth.

Significance: Our findings elucidate an instrumental function of AMPK in direct regulation of nucleic acid and NAD synthesis in tumor cells in response to energy stress. AMPK phosphorylates PRPS1/2, converts PRPS1/2 hexamers to monomers, and inhibits PRPS1/2 activity and subsequent nucleotide and NAD synthesis to maintain tumor cell growth and survival. Cancer Discov; 8(1); 94–107. ©2017 AACR.

This article is highlighted in the In This Issue feature, p. 1
Evaluation of Vestibular Functions in Patients with Vogt-Koyanagi-Harada Disease
Authors: Fujiwara Keishi , Morita Shinya , Hoshino Kimiko , Fukuda Atsushi , Nakamaru Yuji , Homma Akihiro
Published: October 2017

Vogt-Koyanagi-Harada (VKH) disease is an idiopathic, multisystem autoimmune disorder characterized by bilateral, diffuse granulomatous uveitis associated with neurological, audiovestibular, and dermatological manifestations. The purpose of this study is to investigate vestibular functions in patients with VKH disease. A total of 43 patients with VKH disease in Hokkaido University Hospital were enrolled in this study. Subjective symptoms such as dizziness or vertigo and the results of various vestibular examinations including nystagmus testing, caloric testing, and vestibular-evoked myogenic potential (VEMP) testing were investigated. Eight of 42 patients (19.0%) complained of subjective vestibular symptoms. On the other hand, 12 of 28 patients (42.9%) showed nystagmus, and 7 of 15 patients (46.7%) showed unilateral or bilateral weakness in the caloric test. VEMP testing was performed for 16 patients. Seven (43.8%) and 8 (50.0%) patients were evaluated as abnormal in cervical VEMP and ocular VEMP testing, respectively. The rate of detection of nystagmus was significantly higher than that of subjective symptoms. As vestibular dysfunction in patients with VKH disease cannot be detected through history taking alone, nystagmus testing, caloric testing, and VEMP testing should be performed to evaluate vestibular functions associated with VKH disease. It is considered that abnormal VEMP findings are associated with otolith organ dysfunction.
The influence of thiacloprid on the feeding behaviour of the copepod, Diacyclops bicuspidatus, preying on nematodes
Authors: Arican Cansu , Traunspurger Walter , Spann Nicole
Published: October 2017

Nowadays, neonicotinoids are the most widespread insecticides. As neurotoxins with high toxicity to many arthropods, they provide effective pest control, but it also became apparent that they are impacting non-target organisms in freshwater habitats. This study investigated the influence of the neonicotinoid thiacloprid on the behaviour of the copepod, Diacyclops bicuspidatus, feeding on different nematode species (Caenorhabditis elegans, Plectus aquatilis, Panagrolaimus sp.) and on a natural nematode community. All experiments demonstrated that thiacloprid led to decreased feeding of D. bicuspidatus (EC50 values 116-158 μg l−1). In addition, in the experiment where nematodes from a natural sediment were offered as prey, copepod feeding was significantly reduced. The copepod feeding response was a more sensitive endpoint than acute and chronic toxicity tests with daphnids that are routinely used for regulatory risk assessment. An impact on feeding is also a parameter with immediate relevance for the copepod population (reduced fitness) and the associated ecosystem.
Public Theology and Liberal Education
Authors: Alexander Hanan A.
Published: October 2017

This essay explores the conditions necessary for religious and nonreligious worldviews to facilitate dialogue across difference in the public discourse of diverse democracies, and for a pedagogy that prepares citizens to participate in that discourse. Following Nel Noddings, I call those prepared to learn from one another through this sort of dialogue ‘intelligent’. They acknowledge the possible fallibility of their beliefs and behaviors and the human capacity to change course when one has strayed from a chosen path. By way of illustration the essay considers how such an intelligent viewpoint might be conceived from the perspective of my own Jewish faith.
Responsibility for Bystanders in Mass Crimes: Towards a Duty to Rescue in International Criminal Justice
Authors: Botte-Kerrison Auriane
Published: October 2017

This article examines the viability of integrating the duty to rescue concept in international criminal justice to deal with the responsibility of bystanders. Despite the fact that they often contribute to create the social context in which mass crimes occur, bystanders are almost absent from the scope of international criminal justice, focusing mainly on the perpetrators and the victims. This article explores a possible avenue to fill this gap so that the attribution of responsibility for mass crimes can be more coherent with their collective dimension. It assesses whether the duty to rescue concept, commonly found in the legislation of civil law countries, could provide a ‘ready-made’ solution to deal with bystander responsibility. Following a comparative analysis of the different approaches to the duty to rescue in civil law and common law countries, it examines how the duty to rescue would fit with similar concepts in international criminal law.
Typifications and nomenclatural clarifications in South American Tagetes (Asteraceae, Tageteae)
Authors: SCHIAVINATO DARIO J. , GUTIÉRREZ DIEGO G. , BARTOLI ADRIANA
Published: October 2017

During the course of the revision (in progress) of the South American species of Tagetes, we detected the need for nomenclatural clarifications and typifications in order to correct application of taxa´s names. We analyzed protologues, biographies of authors and collectors, original and common materials, and morphological traits. As a result we clarified author citations of T. anisata and T. pseudomicrantha, and type localities of several taxa. In addition, we designated 12 lectotypes and two epitypes for the following plant names: T. anisata, T. bonariensis, T. campanulata, T. dianthiflora, T. mandonii, T. maxima, T. microglossa, T. multiflora var. rupestris, T. peduncularis, T. porophyllum, T. pseudomicrantha, T. tenuifolia, and T. zypaquirensis.