bluuebunny/crossref_metadata_2025 huggingface dataset:
Adapting a large database of point of care summarized guidelines: a process description
Authors: Delvaux Nicolas , Van de Velde Stijn , Aertgeerts Bert , Goossens Martine , Fauquert Benjamin , Kunnamo Ilka , Van Royen Paul
Published: August 2015

Rationale, aims and objectives

Questions posed at the point of care (POC) can be answered using POC summarized guidelines. To implement a national POC information resource, we subscribed to a large database of POC summarized guidelines to complement locally available guidelines. Our challenge was in developing a sustainable strategy for adapting almost 1000 summarized guidelines. The aim of this paper was to describe our process for adapting a database of POC summarized guidelines.

Methods

An adaptation process based on the ADAPTE framework was tailored to be used by a heterogeneous group of participants. Guidelines were assessed on content and on applicability to the Belgian context. To improve efficiency, we chose to first aim our efforts towards those guidelines most important to primary care doctors.

Results

Over a period of 3 years, we screened about 80% of 1000 international summarized guidelines. For those guidelines identified as most important for primary care doctors, we noted that in about half of the cases, remarks were made concerning content. On the other hand, at least two‐thirds of all screened guidelines required no changes when evaluating their local usability.

Conclusions

Adapting a large body of POC summarized guidelines using a formal adaptation process is possible, even when faced with limited resources. This can be done by creating an efficient and collaborative effort and ensuring user‐friendly procedures. Our experiences show that even though in most cases guidelines can be adopted without adaptations, careful review of guidelines developed in a different context remains necessary. Streamlining international efforts in adapting international POC information resources and adopting similar adaptation processes may lessen duplication efforts and prove more cost‐effective.
Randomized comparison of daclatasvir + asunaprevir versus telaprevir + peginterferon/ribavirin in Japanese hepatitis C virus patients
Authors: Kumada Hiromitsu , Suzuki Fumitaka , Suzuki Yoshiyuki , Toyota Joji , Karino Yoshiyasu , Chayama Kazuaki , Kawakami Yoshiiku , Fujiyama Shigetoshi , Ito Takayoshi , Itoh Yoshito , Tamura Etsuko , Ueki Tomoko , Ishikawa Hiroki , Hu Wenhua , McPhee Fiona , Linaberry Misti , Hughes Eric
Published: August 2015

Background and Aim

Daclatasvir combined with asunaprevir is the first all‐oral, ribavirin‐free treatment of hepatitis C virus genotype 1b infection in Japan. This study compared the efficacy and safety of daclatasvir plus asunaprevir versus telaprevir plus peginterferon/ribavirin in Japanese treatment‐naive patients infected with hepatitis C virus genotype 1b.

Methods

Treatment‐naive patients (20–70 years; baseline viral load, ≥100,000 IU/mL) were randomly assigned (stratified by IL28B rs8099917 TT/non‐TT status) to receive either daclatasvir 60 mg tablets once daily and asunaprevir 100 mg softgel capsules twice daily for 24 weeks or telaprevir 750 mg (3 × 250 mg tablets) three times daily for 12 weeks and peginterferon/ribavirin per Japanese prescribing information for 24 weeks. A cohort of prior relapsers to peginterferon/ribavirin (20–75 years; baseline viral load, ≥100,000 IU/mL) received daclatasvir plus asunaprevir.

Results

In treatment‐naive patients, sustained virologic response at post‐treatment week 12 in daclatasvir plus asunaprevir recipients was non‐inferior (treatment difference, +25.8% in favor of daclatasvir plus asunaprevir) and higher (89.1%, 106/119) than telaprevir plus peginterferon/ribavirin recipients (62.2%, 69/111); sustained viral response was achieved in 95.5% (n = 21/22) of relapsers. Numerically, fewer patients receiving daclatasvir plus asunaprevir compared with telaprevir plus peginterferon/ribavirin experienced serious adverse events (4.2% vs. 5.4%), adverse events leading to discontinuation of any drug (5.0% vs. 62.2%), grade 3/4 treatment‐related adverse events (14.3% vs. 72.1%), rash‐related events (0% vs. 13.5%), or anemia (0% vs. 47.7%).

Conclusion

Marked differences were observed in the efficacy and safety profile of daclatasvir in combination with asunaprevir, compared with telaprevir plus peginterferon/ribavirin.
Assessment of cytology and mucin 2 in colorectal mucus collected from patients with inflammatory bowel disease: Results of a pilot trial
Authors: Loktionov Alexandre , Chhaya Vivek , Bandaletova Tatiana , Poullis Andrew
Published: August 2015

Background and Aim

Non‐invasive diagnosis of colorectal disease remains problematic, fecal biomarkers presenting the only current option. Colorectal mucus is the diagnostically informative element of stool samples, but its separation from stool is difficult. We aimed to: (i) test a novel method of non‐invasive colorectal mucus sampling in a pilot clinical trial; (ii) evaluate sampling method acceptance by study participants; (iii) characterize the collected material cytologically; and (iv) assess feasibility of quantitative protein analysis in the samples.

Methods

A total of 141 patients with IBD (58), IBS (50), and healthy controls (33) participated in the study. Samples rich in colorectal mucus were self‐collected by swabbing the anal area immediately following defecation. Collected samples were examined cytologically and subjected to quantitative analysis for total protein and mucin 2 (MUC2).

Results

The novel sampling technique was assessed as “good” or “adequate” by 96% of study participants. A total of 55% of the collected samples were free of fecal contamination. Cytology showed large numbers of well preserved inflammatory cells in IBD cases. Total protein values varied in all groups, being affected by fecal contamination. MUC2 levels were similar among all IBD‐free individuals (control and IBS groups) and elevated in IBD patients (p < 0.001). MUC2 measurement applied as a test for IBD detection provided sensitivity = 72.4% and specificity = 86.7%.

Conclusions

A novel non‐invasive method for collecting human colorectal mucus has been successfully tested. The method was very well accepted by trial participants. The results have proven high quality of collected samples for both cytological investigation and diagnostic biomarker analysis.
Rebozo Technique for Fetal Malposition in Labor
Authors: Cohen Susanna R. , Thomas Celeste R.
Published: August 2015

Fetal occiput posterior position is associated with increased maternal and fetal morbidities. Currently, clinicians have limited evidence‐based techniques or tools to remedy fetal occiput posterior position. The traditional Mexican rebozo technique of pelvic massage, sifting, or jiggling offers a potentially valuable tool to help correct fetal malposition. This article reviews the adaptation of 3 rebozo techniques that can be used in labor to encourage optimum fetal positioning; outlines hospital considerations for safety, fetal heart rate monitoring, and universal precautions; and reviews the implementation plan to introduce and sustain use of the rebozo in a large academic medical center.
Changes in health‐related quality of life in older patients one year after an intensive care unit stay
Authors: Jeitziner Marie‐Madlen , Zwakhalen Sandra MG , Bürgin Reto , Hantikainen Virpi , Hamers Jan PH
Published: August 2015

Aims and objectives

This study investigates health‐related quality of life in older patients, over one year following an intensive care unit stay.

Background

Health‐related quality of life is an important outcome when assessing long‐term effectiveness of intensive care treatment, and to assist patients, their relatives and healthcare professionals in making treatment decisions.

Design

Prospective non‐randomised longitudinal study.

Methods

The Short Form Health Survey 36 was administered 1 week after an intensive care stay (retrospective baseline), and after six months and 12 months to the study population and to an age‐matched comparison group at recruitment (baseline), and after six months and 12 months. Demographic data, admission diagnosis, length of stay, severity of illness, pain, anxiety, agitation, and intratracheal suctioning, turning and intubation were recorded. Recruitment period: December 2008 to April 2011.

Results

Health‐related quality of life of the older patients was significantly lower than the comparison group, both before and after the intensive care unit stay, and showed great individual variability. Within group scores, however, were stable over the year. Both physical and mental health scores were lower for the older patients. Renal failure, cardiac surgery and illness severity were associated with lower physical health scores. Cardiovascular illness, intratracheal suctioning and turning were associated with lower mental health scores.

Conclusions

Health‐related quality of life was lower in older patients than in the age‐matched group but remained stable over one year.

Relevance to clinical practice

Older patients with severe illnesses, acute renal failure or who have had cardiac surgery, need additional support after hospital discharge due to functional restrictions. Discharge planning should ensure that this support would be provided. Special attention should be given to develop and use methods to reduce distress during routine intensive care interventions such as intratracheal suctioning or turning.
ECONOMIC DETERMINANTS OF WORKERS’ RETIREMENT DECISIONS
Authors: Coile Courtney C.
Published: August 2015

The landscape for older workers has changed dramatically in recent decades. Governments have made cuts to public pension programs, private pensions have shifted from defined benefit to defined contribution plans, equity and housing markets have been unusually volatile, and workers have experienced declining morbidity and mortality. At the same time, the labor force participation rate for older men and women has been rising over the past two decades, implying later retirement. Are these phenomena related? This paper reviews the large and growing body of literature exploring the economic determinants of workers’ retirement decisions, including public and private pensions, wealth and savings, health and health insurance, and labor demand.
The effect of learning goal orientation and communal goal strivings on newcomer proactive behaviours and learning
Authors: Tan Kenny W. T. , Au Al K. C. , Cooper‐Thomas Helena D. , Aw Sherry S. Y.
Published: August 2015

Learning is central to newcomer socialization, but research has rarely investigated the individual motivations that predict learning. Drawing from motivated action theory, this study examines newcomers’ learning goal orientation and communal goal strivings, and their effects on the different domains of learning through two separate routes of information‐seeking and relationship‐building proactive behaviours. In Study 1, we develop and validate a scale for communal goal strivings, demonstrating the empirical distinctiveness of the proposed construct from related constructs of prosocial motivation and need to belong. Study 2 involved a 2‐wave survey of 185 university student interns investigating newcomer learning. The results revealed that learning goal orientation predicted greater information seeking in the form of direct inquiry, which in turn predicted role, organization, and social learning. Communal goal strivings predicted the relationship‐building proactive behaviour of networking, and increased social and organization learning. These results underscore the value of goal strivings during socialization and provide a nuanced understanding of the relationships between goal strivings, proactive behaviours, and newcomer learning. Practical implications are discussed.

Practitioner points

Organizations keen to hire proactive employees can select job applicants high in both learning goal orientation and communal goal strivings.

Organizations should not treat newcomer learning as a single entity. Our results suggest that organizations can encourage specific newcomer proactive behaviours to meet targeted learning objectives in the socialization process.

To encourage newcomers’ proactivity and learning, greater attention should be accorded to the organizational environment, emphasizing the social aspects of the socialization process. This includes highlighting the importance of teams and workgroups.
The Role of Entrepreneurship in the Context of Career Trajectories: Moving Back into Wage Employment or into Unemployment?
Authors: Debrulle Jonas
Published: August 2015

This study investigates patterns of movement from self‐employment to wage employment or to unemployment inBelgium. Non‐parametric techniques and complimentary log–log analyses are used to determine the significance of stable individual traits (e.g. gender) and of time‐dependent characteristics (e.g. family and organizational context, labour market mobility) in moving back to wage employment or to unemployment. Evidence is provided on the possibility of entrepreneurship acting as a ‘steppingstone’ between long‐term unemployment and paid work. Yet, significant relationships also emerge between ex‐ante time spent in unemployment and the possibility of continued unemployment upon self‐employment exit.
Alors, la Chinoiserie? The Figure of China in Theorizations of World Literature
Authors: Klein Lucas
Published: August 2015

Chinese writing occupies a privileged position in current academic discussions of world literature. While China as defined within world literature serves as a test case for questions of nativist and universalist values, in the process it finds itself defined as a nation par excellence. Arguing that such definition constitutes a kind of 21st century chinoiserie, I proceed to question the place of China in the literary theories that inform the discussions of world literature, pinpointing part of this chinoiserie on confusion about the role and performance of translation. I then offer a tactical approach to how China and Chinese literature can be re‐translated and re‐theorized, pointing a way forward from its current confinement within the chinoiserie described.
Writing China: Gu Wenda, Victor Segalen and Their Steles
Authors: Wong Lorraine C. M.
Published: August 2015

The problem of writing China has been about the difficulty of the West in recognizing China as a contemporaneous reality while conceiving it in terms of cultural difference. This essay examines Gu Wenda's Forest of Stone Steles: Retranslation and Rewriting of Tang Poetry and Victor Segalen's Stèles: Records of Steles Old and New in exploration of a mode of cultural articulation that takes seriously the set of differences associated with writing China in the 21st century. Gu's very gesture of crossing the divide between the Chinese language and the English language reminds us that the idea of a monolingual and homogeneous culture is never adequate for characterizing human activities. Nevertheless, his notion of cultural boundary is limited by categories such as ‘nations’ and ‘civilizations’, and thus, it stops short of disclosing other contact zones of cultures. In contrast, Segalen brings the Chinese language and the French language into an equivocal relationship of ‘origin’ and ‘translation’ as well as exploring a non‐identitarian interweaving of cultures. This essay argues that while China's rapid incorporation into the global economic system seems to portend that the global status quo will bind us in an enclosed space of ever more sameness, be it capitalist economy, information technology or mass‐culture industry, Segalen inspires us to put into play a world in which relations remain to be made and for which differences have yet to be articulated through the enactments of spaces he demonstrates in Stèles.
AvadānasandJātakasin the Newar Tradition of the Kathmandu Valley: Ritual Performances of Mahāyāna Buddhist Narratives
Authors: Lewis Todd
Published: August 2015

Among all the Sanskrit story narratives available in the vast archive of textual collections in the Kathmandu Valley, Nepal, certain Buddhist tales among them found special provenance in the Mahāyāna culture of the Newars, the indigenous inhabitants of this surviving oasis of later Indic Hindu‐Buddhist civilization. This paper will examine how two stories, theSṛṇgabheri Avadānaand the Siṃhalasārthabāhu Avadāna, have been domesticated into the local religious field and adopted with special meaning for subgroups in the local society. The former recounts the consecutive, linked lives of a husband and wife, in a story of karmic retribution and reunion, a narrative that has a role in contemporary Buddhist widow mourning rites at the major stūpa in Nepal, Svayambhu. The latter, among the most popularjātakanarratives in the Buddhist world, relates the fate of a group of Buddhist merchants who are shipwrecked and captured by cannibalistic demonesses; in Nepal, this story was transposed into a tale of trans‐Himalayan conflict, and its central figure is regarded as a hometown hero. Until today, a three‐day festival procession of him circumnavigates the city of Kathmandu. This paper will explore these local domestications of Buddhist stories and analyze how these traditional celebrations have changed in the context of the shifting regional and political landscape of Nepal and the region.
Full‐length coding sequences of three major histocompatibility complex class I‐related chain A alleles, MICA*019, MICA*027 and MICA*045, identified by sequence‐based typing in Chinese individuals
Authors: Xu Y. P. , Gao S. Q. , Tao H.
Published: August 2015

Full‐length coding sequences of three major histocompatibility complex class I‐related chain A alleles, MICA*019, MICA*027 and MICA*045.
A language contact perspective on Indian English phonology
Authors: DOMANGE RAPHAËL
Published: August 2015

The direction taken by research on Indian English (IE) phonology has been largely determined by the ‘non‐native’ status which is attributed to this variety. Its form is generally considered to be governed by the combined effects of an idealised model serving as the target in acquisition, and transfers from the different language backgrounds of the speakers. This article adopts a different perspective on the issue, and intends to show the crucial importance of acknowledging the diachronic dimension when discussing varieties, native and non‐native alike. It is proposed that features of present‐day IE vowel inventory can be traced back to non‐southern British English input in the dialect formation processes, thus suggesting continuity through time rather than ever‐repeated deviations from the hypothesised target.
Time of flight secondary ion mass spectrometry of bone—Impact of sample preparation and measurement conditions
Authors: Henss Anja , Hild Anne , Rohnke Marcus , Wenisch Sabine , Janek Juergen
Published: August 2015

Time of flight secondary ion mass spectrometry (ToF-SIMS) enables the simultaneous detection of organic and inorganic ions and fragments with high mass and spatial resolution. Due to recent technical developments, ToF-SIMS has been increasingly applied in the life sciences where sample preparation plays an eminent role for the quality of the analytical results. This paper focusses on sample preparation of bone tissue and its impact on ToF-SIMS analysis. The analysis of bone is important for the understanding of bone diseases and the development of replacement materials and new drugs for the cure of diseased bone. The main purpose of this paper is to find out which preparation process is best suited for ToF-SIMS analysis of bone tissue in order to obtain reliable and reproducible analytical results. The influence of the embedding process on the different components of bone is evaluated using principal component analysis. It is shown that epoxy resin as well as methacrylate based plastics (Epon and Technovit) as embedding materials do not infiltrate the mineralized tissue and that cut sections are better suited for the ToF-SIMS analysis than ground sections. In case of ground samples, a resin layer is smeared over the sample surface due to the polishing step and overlap of peaks is found. Beside some signals of fatty acids in the negative ion mode, the analysis of native, not embedded samples does not provide any advantage. The influence of bismuth bombardment and O2 flooding on the signal intensity of organic and inorganic fragments due to the variation of the ionization probability is additionally discussed. As C60 sputtering has to be applied to remove the smeared resin layer, its effect especially on the organic fragments of the bone is analyzed and described herein.
Discrimination between discrete and continuum scattering from the sub-seafloor
Authors: Holland Charles W. , Steininger Gavin , Dosso Stan E.
Published: August 2015

There is growing evidence that seabed scattering is often dominated by heterogeneities within the sediment volume as opposed to seafloor roughness. From a theoretical viewpoint, sediment volume heterogeneities can be described either by a fluctuation continuum or by discrete particles. In at-sea experiments, heterogeneity characteristics generally are not known a priori. Thus, an uninformed model selection is generally made, i.e., the researcher must arbitrarily select either a discrete or continuum model. It is shown here that it is possible to (acoustically) discriminate between continuum and discrete heterogeneities in some instances. For example, when the spectral exponent γ3>4, the volume scattering cannot be described by discrete particles. Conversely, when γ3≤2, the heterogeneities likely arise from discrete particles. Furthermore, in the range 2<γ3≤4 it is sometimes possible to discriminate via physical bounds on the parameter values. The ability to so discriminate is important, because there are few tools for measuring small scale, O(10−2 to 101) m, sediment heterogeneities over large areas. Therefore, discriminating discrete vs continuum heterogeneities via acoustic remote sensing may lead to improved observations and concomitant increased understanding of the marine benthic environment.
Draft Genome Sequence of the Pathogenic Filamentous Fungus
Aspergillus udagawae
Strain IFM 46973
T
Authors: Kusuya Yoko , Takahashi-Nakaguchi Azusa , Takahashi Hiroki , Yaguchi Takashi
Published: August 2015

The incidence of aspergillosis by
Aspergillus
infection has dramatically increased in recent years.
Aspergillus udagawae
, a species related to
Aspergillus fumigatus
, is known as an emerging pathogen of aspergillosis. Here, we present the draft genome sequence of
A. udagawae
strain IFM 46973
T
.
Draft Genome Sequences of Three
Pectobacterium
Strains Causing Blackleg of Potato:
P. carotovorum
subsp.
brasiliensis
ICMP 19477,
P. atrosepticum
ICMP 1526, and
P. carotovorum
subsp.
carotovorum
UGC32
Authors: Panda Preetinanda , Fiers Mark W. E. J. , Lu Ashley , Armstrong Karen F. , Pitman Andrew R.
Published: August 2015

Blackleg is a disease caused by several species of
Pectobacterium
that results in losses to potato crops worldwide. Here, we report the draft genomes of three taxonomically and geographically distinct blackleg-causing strains of
Pectobacterium
:
P. carotovorum
subsp.
brasiliensis
ICMP 19477,
P. atrosepticum
ICMP 1526, and
P. carotovorum
subsp.
carotovorum
UGC32. Comparison of these genomes will support the identification of common traits associated with their capacity to cause blackleg.
Complete Genome Sequence of Escherichia coli NCM3722
Authors: Brown Steven D. , Jun Suckjoon
Published: August 2015

Escherichia coli
NCM3722 is a prototrophic K-12 strain with robust physiologic phenotypes. We report the complete 4,678,045-bp chromosome and 67,545-bp F-like plasmid of this unique model organism.
Genome Sequence of the Moderately Acidophilic Sulfate-Reducing Firmicute Desulfosporosinus acididurans (Strain M1
T
)
Authors: Petzsch Patrick , Poehlein Anja , Johnson D. Barrie , Daniel Rolf , Schlömann Michael , Mühling Martin
Published: August 2015

Microbial dissimilatory sulfate reduction is commonplace in many anaerobic environments, though few acidophilic bacteria are known to mediate this process. We report the 4.64-Mb draft genome of the type strain of the moderate acidophile
Desulfosporosinus acididurans
, which was isolated from acidic sediment in a river draining the Soufrière volcano, Montserrat.
Draft Genome Sequence of
Frankia
sp. Strain DC12, an Atypical, Noninfective, Ineffective Isolate from
Datisca cannabina
Authors: Tisa Louis S. , Beauchemin Nicholas , Cantor Michael N. , Furnholm Teal , Ghodhbane-Gtari Faten , Goodwin Lynne , Copeland Alex , Gtari Maher , Huntemann Marcel , Ivanova Natalia , Kyrpides Nikos , Markowitz Victor , Mavrommatis Kostas , Mikhailova Natalia , Nouioui Imen , Oshone Rediet , Ovchinnikova Galina , Pagani Ioanna , Palaniappan Krishnaveni , Pati Amrita , Sen Arnab , Shapiro Nicole , Szeto Ernest , Wall Luis , Wishart Jessie , Woyke Tanja
Published: August 2015

Frankia
sp. strain DC12, isolated from root nodules of
Datisca cannabina
, is a member of the fourth lineage of
Frankia
, which is unable to reinfect actinorhizal plants. Here, we report its 6.88-Mbp high-quality draft genome sequence, with a G+C content of 71.92% and 5,858 candidate protein-coding genes.
Clinicopathological characteristics ofRHOAmutations in a Central European gastric cancer cohort
Authors: Röcken Christoph , Behrens Hans-Michael , Böger Christine , Krüger Sandra
Published: August 2015

Genomically stable gastric cancers (GCs) are enriched for the diffuse phenotype and hotspot mutations ofRHOA. Here we aimed to validate the occurrence, phenotype and clinicopathological characteristics ofRHOAmutant GCs in an independent Central European GC cohort consisting of 415 patients. TheRHOAgenotype (exon 2 and 3) was correlated with various genotypic, phenotypic and clinicopathological patient characteristics. Sixteen (3.9%) tumours had aRHOAmutation including four hitherto unreported mutations, that is, p.G17Efs*24, p.V24F, p.T37A and p.L69R.RHOAmutation was more prevalent in women (5.4% vs 2.8%), distal GCs (4.5% vs 2.4%), in poorly differentiated GCs (G3/G4; 4.8% vs 1.1%), T1/T2 tumours (6.2% vs 3.1%) and lacked distant metastases. NineRHOAmutant GCs had a diffuse, four an intestinal, two an unclassified and one a mixed Laurén phenotype.KRASandRHOAmutations were mutually exclusive. A single case showed both aRHOAand aPIK3CAmutation. No significant difference was found in the overall survival betweenRHOAmutant and wildtype GCs. Our study confirms the occurrence and clinicopathological characteristics ofRHOA hotspotmutations in an independent patient cohort. However, we found no evidence for a prognostic or growth advantageous effect ofRHOAmutations in GC.
Modern imaging techniques: applications in the management of acute aortic pathologies
Authors: Nagpal Prashant , Khandelwal Ashish , Saboo Sachin S , Bathla Girish , Steigner Michael L , Rybicki Frank J
Published: August 2015

Acute aortic pathologies include traumatic and non-traumatic life-threatening emergencies of the aorta. Since the clinical manifestation of these entities can be non-specific and may overlap with other conditions presenting with chest pain, non-invasive imaging plays a crucial role in their rapid and accurate evaluation. The early diagnosis and accurate radiological assessment of acute aortic diseases is essential for improved clinical outcomes. Multidetector CT is the imaging modality of choice for evaluation of acute aortic diseases with MRI playing more of a problem-solving role. The management can be medical, endovascular or surgical depending upon pathology, and imaging remains an indispensable management-guiding tool. It is important to understand the pathogenesis, natural history, and imaging principles of acute aortic diseases for appropriate use of advanced imaging modalities. This understanding helps to formulate a more appropriate management and follow-up plan for optimised care of these patients. Imaging reporting pearls for day-to-day radiology as well as treatment options based on latest multidisciplinary guidelines are discussed. With newer techniques of image acquisition and processing, we are hopeful that imaging would further help in predicting aortic disease progression and assessing the haemodynamic parameters based on which decisions on management can be made.
Operational thermal remote sensing and lava flow monitoring at the Hawaiian Volcano Observatory
Authors: Patrick M. R. , Kauahikaua J. , Orr T. , Davies A. , Ramsey M.
Published: August 2015

Hawaiian volcanoes are highly accessible and well monitored by ground instruments. Nevertheless, observational gaps remain and thermal satellite imagery has proven useful in Hawai‘i for providing synoptic views of activity during intervals between field visits. Here we describe the beginning of a thermal remote sensing programme at the US Geological Survey Hawaiian Volcano Observatory (HVO). Whereas expensive receiving stations have been traditionally required to achieve rapid downloading of satellite data, we exploit free, low-latency data sources on the internet for timely access to GOES, MODIS, ASTER and EO-1 ALI imagery. Automated scripts at the observatory download these data and provide a basic display of the images. Satellite data have been extremely useful for monitoring the ongoing lava flow activity on Kīlauea's East Rift Zone at Pu‘u ‘Ō‘ō over the past few years. A recent lava flow, named Kahauale‘a 2, was upslope from residential subdivisions for over a year. Satellite data helped track the slow advance of the flow and contributed to hazard assessments. Ongoing improvement to thermal remote sensing at HVO incorporates automated hotspot detection, effusion rate estimation and lava flow forecasting, as has been done in Italy. These improvements should be useful for monitoring future activity on Mauna Loa.
Dynamic partial order reduction for relaxed memory models
Authors: Zhang Naling , Kusano Markus , Wang Chao
Published: August 2015

Under a relaxed memory model such as TSO or PSO, a concurrent program running on a shared-memory multiprocessor may observe two types of nondeterminism: the nondeterminism in thread scheduling and the nondeterminism in store buffering. Although there is a large body of work on mitigating the scheduling nondeterminism during runtime verification, methods for soundly mitigating the store buffering nondeterminism are lacking. We propose a new dynamic partial order reduction (POR) algorithm for verifying concurrent programs under TSO and PSO. Our method relies on modeling both types of nondeterminism in a unified framework, which allows us to extend existing POR techniques to TSO and PSO without overhauling the verification algorithm. In addition to sound POR, we also propose a buffer-bounding method for more aggressively reducing the state space. We have implemented our new methods in a stateless model checking tool and demonstrated their effectiveness on a set of multithreaded C benchmarks.
Provably correct peephole optimizations with alive
Authors: Lopes Nuno P. , Menendez David , Nagarakatte Santosh , Regehr John
Published: August 2015

Compilers should not miscompile. Our work addresses problems in developing peephole optimizations that perform local rewriting to improve the efficiency of LLVM code. These optimizations are individually difficult to get right, particularly in the presence of undefined behavior; taken together they represent a persistent source of bugs. This paper presents Alive, a domain-specific language for writing optimizations and for automatically either proving them correct or else generating counterexamples. Furthermore, Alive can be automatically translated into C++ code that is suitable for inclusion in an LLVM optimization pass. Alive is based on an attempt to balance usability and formal methods; for example, it captures---but largely hides---the detailed semantics of three different kinds of undefined behavior in LLVM. We have translated more than 300 LLVM optimizations into Alive and, in the process, found that eight of them were wrong.
Blame and coercion: together again for the first time
Authors: Siek Jeremy , Thiemann Peter , Wadler Philip
Published: August 2015

C#, Dart, Pyret, Racket, TypeScript, VB: many recent languages integrate dynamic and static types via gradual typing. We systematically develop three calculi for gradual typing and the relations between them, building on and strengthening previous work. The calculi are: λB, based on the blame calculus of Wadler and Findler (2009); λC, inspired by the coercion calculus of Henglein (1994); λS inspired by the space-efficient calculus of Herman, Tomb, and Flanagan (2006) and the threesome calculus of Siek and Wadler (2010). While λB is little changed from previous work, λC and λS are new. Together, λB, λC, and λS provide a coherent foundation for design, implementation, and optimisation of gradual types. We define translations from λB to λC and from λC to λS. Much previous work lacked proofs of correctness or had weak correctness criteria; here we demonstrate the strongest correctness criterion one could hope for, that each of the translations is fully abstract. Each of the calculi reinforces the design of the others: λC has a particularly simple definition, and the subtle definition of blame safety for λB is justified by the simple definition of blame safety for λC. Our calculus λS is implementation-ready: the first space-efficient calculus that is both straightforward to implement and easy to understand. We give two applications: first, using full abstraction from λC to λS to validate the challenging part of full abstraction between λB and λC; and, second, using full abstraction from λB to λS to easily establish the Fundamental Property of Casts, which required a custom bisimulation and six lemmas in earlier work.
Defining the undefinedness of C
Authors: Hathhorn Chris , Ellison Chucky , Roşu Grigore
Published: August 2015

We present a ``negative'' semantics of the C11 language---a semantics that does not just give meaning to correct programs, but also rejects undefined programs. We investigate undefined behavior in C and discuss the techniques and special considerations needed for formally specifying it. We have used these techniques to modify and extend a semantics of C into one that captures undefined behavior. The amount of semantic infrastructure and effort required to achieve this was unexpectedly high, in the end nearly doubling the size of the original semantics. From our semantics, we have automatically extracted an undefinedness checker, which we evaluate against other popular analysis tools, using our own test suite in addition to a third-party test suite. Our checker is capable of detecting examples of all 77 categories of core language undefinedness appearing in the C11 standard, more than any other tool we considered. Based on this evaluation, we argue that our work is the most comprehensive and complete semantic treatment of undefined behavior in C, and thus of the C language itself.
Declarative programming over eventually consistent data stores
Authors: Sivaramakrishnan KC , Kaki Gowtham , Jagannathan Suresh
Published: August 2015

User-facing online services utilize geo-distributed data stores to minimize latency and tolerate partial failures, with the intention of providing a fast, always-on experience. However, geo-distribution does not come for free; application developers have to contend with weak consistency behaviors, and the lack of abstractions to composably construct high-level replicated data types, necessitating the need for complex application logic and invariably exposing inconsistencies to the user. Some commercial distributed data stores and several academic proposals provide a lattice of consistency levels, with stronger consistency guarantees incurring increased latency and throughput costs. However, correctly assigning the right consistency level for an operation requires subtle reasoning and is often an error-prone task. In this paper, we present QUELEA, a declarative programming model for eventually consistent data stores (ECDS), equipped with a contract language, capable of specifying fine-grained application - level consistency properties. A contract enforcement system analyses contracts, and automatically generates the appropriate consistency protocol for the method protected by the contract. We describe an implementation of QUELEA on top of an off-the-shelf ECDS that provides support for coordination-free transactions. Several benchmarks including two large web applications, illustrate the effectiveness of our approach.
Automatic error elimination by horizontal code transfer across multiple applications
Authors: Sidiroglou-Douskos Stelios , Lahtinen Eric , Long Fan , Rinard Martin
Published: August 2015

We present Code Phage (CP), a system for automatically transferring correct code from donor applications into recipient applications that process the same inputs to successfully eliminate errors in the recipient. Experimental results using seven donor applications to eliminate ten errors in seven recipient applications highlight the ability of CP to transfer code across applications to eliminate out of bounds access, integer overflow, and divide by zero errors. Because CP works with binary donors with no need for source code or symbolic information, it supports a wide range of use cases. To the best of our knowledge, CP is the first system to automatically transfer code across multiple applications.
Profile-guided meta-programming
Authors: Bowman William J. , Miller Swaha , St-Amour Vincent , Dybvig R. Kent
Published: August 2015

Contemporary compiler systems such as GCC, .NET, and LLVM incorporate profile-guided optimizations (PGOs) on low-level intermediate code and basic blocks, with impressive results over purely static heuristics. Recent work shows that profile information is also useful for performing source-to-source optimizations via meta-programming. For example, using profiling information to inform decisions about data structures and algorithms can potentially lead to asymptotic improvements in performance. We present a design for profile-guided meta-programming in a general-purpose meta-programming system. Our design is parametric over the particular profiler and meta-programming system. We implement this design in two different meta-programming systems---the syntactic extensions systems of Chez Scheme and Racket---and provide several profile-guided meta-programs as usability case studies.
Light: replay via tightly bounded recording
Authors: Liu Peng , Zhang Xiangyu , Tripp Omer , Zheng Yunhui
Published: August 2015

Reproducing concurrency bugs is a prominent challenge. Existing techniques either rely on recording very fine grained execution information and hence have high runtime overhead, or strive to log as little information as possible but provide no guarantee in reproducing a bug. We present Light, a technique that features much lower overhead compared to techniques based on fine grained recording, and that guarantees to reproduce concurrent bugs. We leverage and formally prove that recording flow dependences is the necessary and sufficient condition to reproduce a concurrent bug. The flow dependences, together with the thread local orders that can be automatically inferred (and hence not logged), are encoded as scheduling constraints. An SMT solver is used to derive a replay schedule, which is guaranteed to exist even though it may be different from the original schedule. Our experiments show that Light has only 44% logging overhead, almost one order of magnitude lower than the state of the art techniques relying on logging memory accesses. Its space overhead is only 10% of those techniques. Light can also reproduce all the bugs we have collected whereas existing techniques miss some of them.
Lightweight, flexible object-oriented generics
Authors: Zhang Yizhou , Loring Matthew C. , Salvaneschi Guido , Liskov Barbara , Myers Andrew C.
Published: August 2015

The support for generic programming in modern object-oriented programming languages is awkward and lacks desirable expressive power. We introduce an expressive genericity mechanism that adds expressive power and strengthens static checking, while remaining lightweight and simple in common use cases. Like type classes and concepts, the mechanism allows existing types to model type constraints retroactively. For expressive power, we expose models as named constructs that can be defined and selected explicitly to witness constraints; in common uses of genericity, however, types implicitly witness constraints without additional programmer effort. Models are integrated into the object-oriented style, with features like model generics, model-dependent types, model enrichment, model multimethods, constraint entailment, model inheritance, and existential quantification further extending expressive power in an object-oriented setting. We introduce the new genericity features and show that common generic programming idioms, including current generic libraries, can be expressed more precisely and concisely. The static semantics of the mechanism and a proof of a key decidability property can be found in an associated technical report.
Soluble guanylate cyclase modulators blunt hyperoxia effects on calcium responses of developing human airway smooth muscle
Authors: Britt Rodney D. , Thompson Michael A. , Kuipers Ine , Stewart Alecia , Vogel Elizabeth R. , Thu James , Martin Richard J. , Pabelick Christina M. , Prakash Y. S.
Published: August 2015

Exposure to moderate hyperoxia in prematurity contributes to subsequent airway dysfunction and increases the risk of developing recurrent wheeze and asthma. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic GMP (cGMP) axis modulates airway tone by regulating airway smooth muscle (ASM) intracellular Ca2+ ([Ca2+]i) and contractility. However, the effects of hyperoxia on this axis in the context of Ca2+/contractility are not known. In developing human ASM, we explored the effects of novel drugs that activate sGC independent of NO on alleviating hyperoxia (50% oxygen)-induced enhancement of Ca2+ responses to bronchoconstrictor agonists. Treatment with BAY 41–2272 (sGC stimulator) and BAY 60-2770 (sGC activator) increased cGMP levels during exposure to 50% O2. Although 50% O2 did not alter sGCα1 or sGCβ1 expression, BAY 60-2770 did increase sGCβ1 expression. BAY 41-2272 and BAY 60-2770 blunted Ca2+ responses to histamine in cells exposed to 50% O2. The effects of BAY 41-2272 and BAY 60-2770 were reversed by protein kinase G inhibition. These novel data demonstrate that BAY 41-2272 and BAY 60-2770 stimulate production of cGMP and blunt hyperoxia-induced increases in Ca2+ responses in developing ASM. Accordingly, sGC stimulators/activators may be a useful therapeutic strategy in improving bronchodilation in preterm infants.
CCL5-Mediated Th2 Immune Polarization Promotes Metastasis in Luminal Breast Cancer
Authors: Zhang Qianfei , Qin Jilong , Zhong Lin , Gong Lei , Zhang Bing , Zhang Yan , Gao Wei-Qiang
Published: August 2015

The tumor-promoting chemokine CCL5 has been implicated in malignant transformation of breast epithelial cells, with studies to date focusing mainly on basal-type breast cancers. In this study, we investigated the consequences of CCL5 deletion in the MMTV-PyMT transgenic mouse model of luminal breast cancer. In this model, primary tumor burden and pulmonary metastases were reduced significantly in CCL5-deficient subjects, an effect found to be associated with a deficit of Th2 (IL4+CD4+ T) cells. Mechanistic investigations revealed that CCL5 activates CCR3, a highly expressed chemokine receptor on CD4+ T cells, and also boosts Gfi1 expression to promote the differentiation of Th2 cells, which enhance the prometastatic activity of tumor-associated myeloid cells. Clinically, polarization toward this immunosuppressive Th2 phenotype was also evident in patients with advanced luminal breast cancer. Thus, our findings showed that CCL5/CCR3 signaling promotes metastasis by inducing Th2 polarization of CD4+ T cells, with implications for prognosis and immunotherapy of luminal breast cancer. Cancer Res; 75(20); 4312–21. ©2015 AACR.
A Multicenter, Open-Label Phase II Clinical Trial of Combined MEK plus EGFR Inhibition for Chemotherapy-Refractory Advanced Pancreatic Adenocarcinoma
Authors: Ko Andrew H. , Bekaii-Saab Tanios , Van Ziffle Jessica , Mirzoeva Olga M. , Joseph Nancy M. , Talasaz AmirAli , Kuhn Peter , Tempero Margaret A. , Collisson Eric A. , Kelley R. Kate , Venook Alan P. , Dito Elizabeth , Ong Anna , Ziyeh Sharvina , Courtin Ryan , Linetskaya Regina , Tahiri Sanaa , Korn W. Michael
Published: August 2015

Purpose: On the basis of preclinical evidence of synergistic activity between MEK and EGFR inhibitors in pancreatic ductal adenocarcinoma (PDAC), we evaluated the safety and efficacy of selumetinib, a MEK1/2 inhibitor, plus erlotinib in patients with previously treated advanced PDAC.

Experimental Design: In this single-arm phase II trial, eligible patients received the combination of erlotinib 100 mg plus selumetinib 100 mg daily in 3-week cycles. Study assessments included measurement of clinical outcomes, with a primary endpoint of overall survival, and exploration of potential molecular predictors of treatment benefit.

Results: Forty-six patients were enrolled and received a median of two cycles (range, 1–7). Although no objective responses were observed, 19 patients (41%) showed evidence of stable disease for ≥6 weeks, and 13 of 34 patients (38%) had a CA19-9 decline ≥50%. Median progression-free survival was 1.9 months [95% confidence interval (CI), 1.4–3.3 months], with a median overall survival of 7.3 months (95% CI, 5.2–8.0 months). Common adverse events included rash, diarrhea, and nausea/vomiting. Patients with tumors exhibiting an epithelial phenotype (demonstrated by a high level of E-cadherin expression) were more likely to be sensitive to study treatment. Tumor-derived DNA was detectable in plasma from the majority of patients using next-generation digital DNA sequencing, and its relative abundance correlated with tumor burden.

Conclusions: A therapeutic strategy of dual targeted inhibition of the MEK and EGFR pathways shows modest antitumor activity in pancreatic cancer. Specific molecular subtypes may derive greatest benefit from this combination. Further exploration, both with more potent MEK inhibitors and in molecularly enriched patient subsets, is warranted. Clin Cancer Res; 22(1); 61–68. ©2015 AACR.
Predicting Suitable Habitats for the Vulnerable Eastern Hoolock Gibbon, Hoolock leuconedys, in India Using the MaxEnt Model
Authors: Sarma Kuladip , Kumar Awadhesh , Krishna Murali , Medhi Mintu , Tripathi Om Prakash
Published: August 2015

The eastern hoolock gibbon, Hoolock leuconedys, is categorized as Vulnerable on the IUCN Red List and assessed as a Schedule I species of the Wildlife (Protection) Act of 1972 in India. We predict the potential habitat of H. leuconedys in the state of Arunachal Pradesh, India, using the Maximum Entropy (MaxEnt) distribution modelling algorithm. The model was developed using 90 known localities of H. leuconedys in the state. Nineteen environmental parameters along with 12 normalized difference vegetation index (NDVI) layers, elevation and land use and land cover (LULC) were used in the modelling. Amongst the environmental input variables, the precipitation of the coldest quarter (BIO 19) had the highest contribution to the model (26.03%) and the twelve NDVI layers collectively contributed 60.91%. Two districts, Lower Dibang Valley and Lohit, which are known to contain H. leuconedys, occupied 64.75% of the predicted distribution area of the species. Thus, we aid in the identification of suitable areas for the reintroduction program of H. leuconedys that is planned by the Gibbon Conservation Breeding Centre, Biological Park, Itanagar, Arunachal Pradesh, India.