bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation and statistical reliability of publicly reported primary care diagnostic activity indicators for cancer: a cross-sectional ecological study of routine data
Authors: Abel Gary , Saunders Catherine L , Mendonca Silvia C , Gildea Carolynn , McPhail Sean , Lyratzopoulos Georgios 
Published: August 2017

ObjectivesRecent public reporting initiatives in England highlight general practice variation in indicators of diagnostic activity related to cancer. We aimed to quantify the size and sources of variation and the reliability of practice-level estimates of such indicators, to better inform how this information is interpreted and used for quality improvement purposes.DesignEcological cross-sectional study.SettingEnglish primary care.ParticipantsAll general practices in England with at least 1000 patients.Main outcome measuresSixteen diagnostic activity indicators from the Cancer Services Public Health Profiles.ResultsMixed-effects logistic and Poisson regression showed that substantial proportions of the observed variance in practice scores reflected chance, variably so for different indicators (between 7% and 85%). However, after accounting for the role of chance, there remained substantial variation between practices (typically up to twofold variation between the 75th and 25th centiles of practice scores, and up to fourfold variation between the 90th and 10th centiles). The age and sex profile of practice populations explained some of this variation, by different amounts across indicators. Generally, the reliability of diagnostic process indicators relating to broader populations of patients most of whom do not have cancer (eg, rate of endoscopic investigations, or urgent referrals for suspected cancer (also known as ‘two week wait referrals’)) was high (≥0.80) or very high (≥0.90). In contrast, the reliability of diagnostic outcome indicators relating to incident cancer cases (eg, per cent of all cancer cases detected after an emergency presentation) ranged from 0.24 to 0.54, which is well below recommended thresholds (≥0.70).ConclusionsUse of indicators of diagnostic activity in individual general practices should principally focus on process indicators which have adequate or high reliability and not outcome indicators which are unreliable at practice level.
Clinical features of seizures after cerebral venous sinus thrombosis and its effect on outcome among Chinese Han population
Authors: Ding Hongyan , Xie Yanan , Li Linxin , Chu Heling , Tang Yuping , Dong Qiang , Cui Mei 
Published: August 2017

Background and purposeClinical features of epileptic seizures after cerebral venous sinus thrombosis (CVST) among Chinese patients are not known, and it is still controversial whether seizures would affect the outcome of CVST.MethodsIn a Chinese hospital-based study of consecutive patients with CVST between 2003 and 2015, we described the clinical features of seizures and determined the predictors of seizure onset using multivariable logistic regression analysis. We also compared the in-hospital case-fatality and short-term functional outcome (modified Rankin Scale (mRS) at discharge) in patients with versus without seizures using ordinal regression analysis.ResultsAmong 151 patients with CVST, 52 (34.4%) presented seizures, of which 42 (80.8%) were generalised seizures. Male gender (OR 6.32, 95% CI 2.06 to 19.35, p=0.001), motor deficits (OR 4.89, 95% CI 1.52 to 15.68, p=0.008), intracerebral haemorrhage (OR 3.93, 95% CI 1.16 to 13.26, p=0.027), cerebral infarction (OR 3.78, 95% CI 1.15 to 12.36, p=0.029) and superior sagittal sinus thrombosis (OR 3.38, 95% CI 91.16 to 9.86, p=0.026) were independent predictors for seizures. The overall in-hospital case-fatality rate was 2.0% (3/151), and 21 (13.9%) had mRS >2 at discharge. Compared with patients without seizures, patients with seizures were more likely to have a worse outcome (p=0.02) at discharge, independent of age, gender, clinical presentation, clot burden and presence of parenchymal lesions.ConclusionsIn Chinese Han patients, compared with patients without seizures, patients with seizures after CVST had a worse outcome. Risk factors such as male gender, paresis, parenchymal lesion and superior sagittal sinus thrombosis were independently associated with seizure onset after CVST. Generalised seizure was the main form of seizures after CVST, which was obviously different to seizures after strokes of arterial origin.
Levetiracetam monotherapy for treatment of structural epilepsy in dogs: 19 cases (2010–2015)
Authors: Kelly Darren , Raimondi Francesca , Shihab Nadia 
Published: August 2017

To evaluate the efficacy and tolerability of levetiracetam monotherapy in dogs with structural epilepsy. Retrospective case series. Nineteen client‐owned dogs with structural epilepsy. Seizure frequencies after initiation of treatment were used to evaluate the efficacy of levetiracetam monotherapy. Seizure control was considered good if no seizures occurred within three months of starting treatment or poor if seizures returned within one month of starting treatment. Tolerability was evaluated by considering the occurrence and severity of any reported side effects. Ten of the 19 dogs were considered to have a good response to treatment with 7 achieving complete seizure freedom. Nine dogs were considered to have poor response to treatment. There was a statistically significant reduction in the percentage of patients experiencing cluster seizures from 68.4% to 15.8% (p=0.002). Side effects were noted in 8 of the 19 dogs but were considered mild in all cases. Follow‐up times ranged from 12 days to 426 days. When used in conjunction with other appropriate therapies, levetiracetam may be an efficacious option for monotherapy in dogs with structural epilepsy. Its tolerability makes it a suitable option for use in a wide variety of patients.
On D-brane dynamics and moduli stabilization
Authors: Kitazawa Noriaki 
Published: August 2017

We discuss the effect of the dynamics of D-branes on moduli stabilization in type IIB string theory compactifications, with reference to a concrete toy model of [Formula: see text] orientifold compactification with fractional D3-branes and anti-D3-branes at orbifold fixed points. The resulting attractive forces between anti-D3-branes and D3-branes, together with the repulsive forces between anti-D3-branes and O3-planes, can affect the stability of the compact space. There are no complex structure moduli in [Formula: see text] orientifold, which should thus capture some generic features of more general settings where all complex structure moduli are stabilized by three-form fluxes. The simultaneous presence of branes and anti-branes brings along the breaking of supersymmetry. Non-BPS combinations of this type are typical of “brane supersymmetry breaking” and are a necessary ingredient in the KKLT scenario for stabilizing the remaining Kähler moduli. The conclusion of our analysis is that, while mutual D-brane interactions sometimes help Kähler moduli stabilization, this is not always the case.
Preparation of B-doped Si quantum dots embedded in SiNx films for Si quantum dot solar cells
Authors: Chen Xiaobo , Yang Peizhi 
Published: August 2017

Silicon quantum dots (Si-QDs) embedded B-doped SiN[Formula: see text] films were fabricated by magnetron co-sputtering. The effects of B content on the structural, optical and electrical properties of the films were studied. The study found that the amount of B dopant has no significant effect on the crystallization characteristics of the films. B atoms may be doped in the Si-QDs or exist in the silicon nitride or the interface between Si-QDs and the matrix. PL intensity increases with increasing B content, but increases at first and then decreases. The conductivity as a function of the dopant concentration increases at first from a value of 2.71 × 10[Formula: see text] S/cm to 5.83 × 10[Formula: see text] S/cm until 0.9 at.% and then decreases. By employing B-doped Si-QDs films, Si-QDs/c-Si heterojunction solar cells were fabricated and the effect of B doping concentration on the photovoltaic properties was studied. It was found that, with the increase of B doping amount, the photovoltaic performance is improved, when the B doping amount is 0.9 at.%, the efficiency reaches the highest value of 4.26%.
A DETERMINISTIC APPROACH TO THE SYNCHRONIZATION OF NONLINEAR CELLULAR AUTOMATA
Authors: DE ABREU J. , GARCÍA P. , GARCÍA J. 
Published: August 2017

In this work, we introduce a deterministic scheme of synchronization of nonlinear cellular automata with chaotic behavior, connected through a master–slave coupling. By using a definition of Boolean derivative, we utilize the linear approximation of the cellular automata rules to design a deterministic and simple coupling function that ensures synchronization. Our results show that it is possible to synchronize nonlinear chaotic cellular automata using a deterministic coupling function that does not introduce into the slave all the information about the state of the master.
Verified low-level programming embedded in F*
Authors: Protzenko Jonathan , Zinzindohoué Jean-Karim , Rastogi Aseem , Ramananandro Tahina , Wang Peng , Zanella-Béguelin Santiago , Delignat-Lavaud Antoine , Hriţcu Cătălin , Bhargavan Karthikeyan , Fournet Cédric , Swamy Nikhil 
Published: August 2017

We present Low*, a language for low-level programming and verification, and its application to high-assurance optimized cryptographic libraries. Low* is a shallow embedding of a small, sequential, well-behaved subset of C in F*, a dependently- typed variant of ML aimed at program verification. Departing from ML, Low* does not involve any garbage collection or implicit heap allocation; instead, it has a structured memory model à la CompCert, and it provides the control required for writing efficient low-level security-critical code.
By virtue of typing, any Low* program is memory safe. In addition, the programmer can make full use of the verification power of F* to write high-level specifications and verify the functional correctness of Low* code using a combination of SMT automation and sophisticated manual proofs. At extraction time, specifications and proofs are erased, and the remaining code enjoys a predictable translation to C. We prove that this translation preserves semantics and side-channel resistance.
We provide a new compiler back-end from Low* to C and, to evaluate our approach, we implement and verify various cryptographic algorithms, constructions, and tools for a total of about 28,000 lines of code. We show that our Low* code delivers performance competitive with existing (unverified) C cryptographic libraries, suggesting our approach may be applicable to larger-scale low-level software.
Better living through operational semantics: an optimizing compiler for radio protocols
Authors: Mainland Geoffrey 
Published: August 2017

Software-defined radio (SDR) promises to bring the flexibility and rapid iterative workflow of software to radio protocol design. Many factors make achieving this promise challenging, not least of which are the high data rates and timing requirements of real-world radio protocols. The Ziria language and accompanying compiler demonstrated that a high-level language can compete in this demanding space, but extracting reusable lessons from this success is difficult due to Ziria's lack of a formal semantics. Our first contribution is a core language, operational semantics, and type system for Ziria.
The insight we gained through developing this operational semantics led to our second contribution, consisting of two program transformations. The first is fusion, which can eliminate intermediate queues in Ziria programs. Fusion subsumes many one-off optimizations performed by the original Ziria compiler. The second transformation is pipeline coalescing, which reduces execution overhead by batching IO. Pipeline coalescing relies critically on fusion and provides a much simpler story for the original Ziria compiler's "vectorization" transformation. These developments serve as the basis of our third contribution, a new compiler for Ziria that produces significantly faster code than the original compiler. The new compiler leverages our intermediate language to help eliminate unnecessary memory traffic.
As well as providing a firm foundation for the Ziria language, our work on an operational semantics resulted in very real software engineering benefits. These benefits need not be limited to SDR---the core language and accompanying transformations we present are applicable to other domains that require processing streaming data at high speed.
A relational logic for higher-order programs
Authors: Aguirre Alejandro , Barthe Gilles , Gaboardi Marco , Garg Deepak , Strub Pierre-Yves 
Published: August 2017

Relational program verification is a variant of program verification where one can reason about two programs and as a special case about two executions of a single program on different inputs. Relational program verification can be used for reasoning about a broad range of properties, including equivalence and refinement, and specialized notions such as continuity, information flow security or relative cost. In a higher-order setting, relational program verification can be achieved using relational refinement type systems, a form of refinement types where assertions have a relational interpretation. Relational refinement type systems excel at relating structurally equivalent terms but provide limited support for relating terms with very different structures.
We present a logic, called Relational Higher Order Logic (RHOL), for proving relational properties of a simply typed λ-calculus with inductive types and recursive definitions. RHOL retains the type-directed flavour of relational refinement type systems but achieves greater expressivity through rules which simultaneously reason about the two terms as well as rules which only contemplate one of the two terms. We show that RHOL has strong foundations, by proving an equivalence with higher-order logic (HOL), and leverage this equivalence to derive key meta-theoretical properties: subject reduction, admissibility of a transitivity rule and set-theoretical soundness. Moreover, we define sound embeddings for several existing relational type systems such as relational refinement types and type systems for dependency analysis and relative cost, and we verify examples that were out of reach of prior work.
How to prove your calculus is decidable: practical applications of second-order algebraic theories and computation
Authors: Hamana Makoto 
Published: August 2017

We present a general methodology of proving the decidability of equational theory of programming language concepts in the framework of second-order algebraic theories. We propose a Haskell-based analysis tool SOL, Second-Order Laboratory, which assists the proofs of confluence and strong normalisation of computation rules derived from second-order algebraic theories.
To cover various examples in programming language theory, we combine and extend both syntactical and semantical results of second-order computation in a non-trivial manner. We demonstrate how to prove decidability of various algebraic theories in the literature. It includes the equational theories of monad and lambda-calculi, Plotkin and Power's theory of states, and Stark's theory of pi-calculus.
SpaceSearch: a library for building and verifying solver-aided tools
Authors: Weitz Konstantin , Lyubomirsky Steven , Heule Stefan , Torlak Emina , Ernst Michael D. , Tatlock Zachary 
Published: August 2017

Many verification tools build on automated solvers. These tools reduce problems in a specific application domain (e.g., compiler optimization validation) to queries that can be discharged with a highly optimized solver. But the correctness of the reductions themselves is rarely verified in practice, limiting the confidence that the solver's output establishes the desired domain-level property.
This paper presents SpaceSearch, a new library for developing solver-aided tools within a proof assistant. A user builds their solver-aided tool in Coq against the SpaceSearch interface, and the user then verifies that the results provided by the interface are sufficient to establish the tool's desired high-level properties. Once verified, the tool can be extracted to an implementation in a solver-aided language (e.g., Rosette), where SpaceSearch provides an efficient instantiation of the SpaceSearch interface with calls to an underlying SMT solver. This combines the strong correctness guarantees of developing a tool in a proof assistant with the high performance of modern SMT solvers. This paper also introduces new optimizations for such verified solver-aided tools, including parallelization and incrementalization.
We evaluate SpaceSearch by building and verifying two solver-aided tools. The first, SaltShaker, checks that RockSalt's x86 semantics for a given instruction agrees with STOKE's x86 semantics. SaltShaker identified 7 bugs in RockSalt and 1 bug in STOKE. After these systems were patched by their developers, SaltShaker verified the semantics' agreement on 15,255 instruction instantiations in under 2h. The second tool, BGProof, is a verified version of an existing Border Gateway Protocol (BGP) router configuration checker. Like the existing checker, BGProof scales to checking industrial configurations spanning over 240 KLOC, identifying 19 configuration inconsistencies with no false positives. However, the correctness of BGProof has been formally proven, and we found 2 bugs in the unverified implementation. These results demonstrate that SpaceSearch is a practical approach to developing efficient, verified solver-aided tools.
Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40
Authors: Messenheimer David J. , Jensen Shawn M. , Afentoulis Michael E. , Wegmann Keith W. , Feng Zipei , Friedman David J. , Gough Michael J. , Urba Walter J. , Fox Bernard A. 
Published: August 2017

AbstractPurpose: Antibodies specific for inhibitory checkpoints PD-1 and CTLA-4 have shown impressive results against solid tumors. This has fueled interest in novel immunotherapy combinations to affect patients who remain refractory to checkpoint blockade monotherapy. However, how to optimally combine checkpoint blockade with agents targeting T-cell costimulatory receptors, such as OX40, remains a critical question.Experimental Design: We utilized an anti-PD-1–refractory, orthotopically transplanted MMTV-PyMT mammary cancer model to investigate the antitumor effect of an agonist anti-OX40 antibody combined with anti-PD-1. As PD-1 naturally aids in immune contraction after T-cell activation, we treated mice with concurrent combination treatment versus sequentially administering anti-OX40 followed by anti-PD-1.Results: The concurrent addition of anti-PD-1 significantly attenuated the therapeutic effect of anti-OX40 alone. Combination-treated mice had considerable increases in type I and type II serum cytokines and significantly augmented expression of inhibitory receptors or exhaustion markers CTLA-4 and TIM-3 on T cells. Combination treatment increased intratumoral CD4+ T-cell proliferation at day 13, but at day 19, both CD4+ and CD8+ T-cell proliferation was significantly reduced compared with untreated mice. In two tumor models, sequential combination of anti-OX40 followed by anti-PD-1 (but not the reverse order) resulted in significant increases in therapeutic efficacy. Against MMTV-PyMT tumors, sequential combination was dependent on both CD4+ and CD8+ T cells and completely regressed tumors in approximately 30% of treated animals.Conclusions: These results highlight the importance of timing for optimized therapeutic effect with combination immunotherapies and suggest the testing of sequencing in combination immunotherapy clinical trials. Clin Cancer Res; 23(20); 6165–77. ©2017 AACR.See related commentary by Colombo, p. 5999
Neoadjuvant Interferons: Critical for Effective PD-1–Based Immunotherapy in TNBC
Authors: Brockwell Natasha K. , Owen Katie L. , Zanker Damien , Spurling Alex , Rautela Jai , Duivenvoorden Hendrika M. , Baschuk Nikola , Caramia Franco , Loi Sherene , Darcy Phillip K. , Lim Elgene , Parker Belinda S. 
Published: August 2017

AbstractThe lack of targeted therapies available for triple-negative breast cancer (TNBC) patients who fail to respond to first-line chemotherapy has sparked interest in immunotherapeutic approaches. However, trials utilizing checkpoint inhibitors targeting the PD-1/PD-L1 axis in TNBC have had underwhelming responses. Here, we investigated the interplay between type I IFN signaling and the PD-1/PD-L1 axis and tested the impact of combining IFN inducers, as immune activators, with anti–PD-1, to induce an antimetastatic immune response. Using models of TNBC, we demonstrated an interplay between type I IFN signaling and tumor cell PD-L1 expression that affected therapeutic response. The data revealed that the type I IFN-inducer poly(I:C) was an effective immune activator and antimetastatic agent, functioning better than anti–PD-1, which was ineffective as a single agent. Poly(I:C) treatment induced PD-L1 expression on TNBC cells, and combined poly(I:C) and anti–PD-1 treatment prolonged metastasis-free survival in a neoadjuvant setting via the induction of a tumor-specific T-cell response. Use of this combination in a late treatment setting did not impact metastasis-free survival, indicating that timing was critical for immunotherapeutic benefit. Together, these data demonstrated anti–PD-1 as an ineffective single agent in preclinical models of TNBC. However, type I IFN inducers were effective immune activators, and neoadjuvant trials combining them with anti–PD-1 to induce a sustained antitumor immune response are warranted. Cancer Immunol Res; 5(10); 871–84. ©2017 AACR.
Subclinical Cerebrovascular Disease Increases the Risk of Incident Stroke and Mortality: The Northern Manhattan Study
Authors: Wright Clinton B. , Dong Chuanhui , Perez Enmanuel J. , De Rosa Janet , Yoshita Mitsuhiro , Rundek Tatjana , DeCarli Charles , Gutierrez Jose , Elkind Mitchell S. V. , Sacco Ralph L. 
Published: August 2017

Background
The effects of white matter hyperintensity volume and subclinical brain infarcts on the risk of incident stroke, its ischemic subtypes, and mortality require further study in diverse samples.

Methods and Results

Stroke‐free participants in the Northern Manhattan Study underwent magnetic resonance imaging (N=1287; mean age 71±9 years, 60% women, 15% non‐Hispanic white, 17% non‐Hispanic black, 68% Hispanic) and were followed for a median of 8 years (interquartile range: 6–9 years). Cox models estimated proportional hazards of incident stroke of all types, ischemic stroke (and its subtypes), and mortality and stratified by race/ethnicity. In total 72 participants (6%) had incident strokes and 244 died (19%). In fully adjusted models, those with larger white matter hyperintensity volume had greater risk of all stroke types (hazard ratio [HR]: 1.4; 95%
CI
, 1.1–1.9), ischemic stroke (
HR
: 1.3; 95%
CI
, 1.0–1.8), and cryptogenic stroke (
HR
: 2.2; 95%
CI
, 1.1–4.4). White and black but not Hispanic participants had increased stroke risk (
P
<0.05 for heterogeneity for all and ischemic stroke). Those with subclinical brain infarct had greater risk for all stroke types (
HR
: 1.9; 95%
CI
, 1.1–3.3), ischemic stroke (
HR
: 2.2; 95%
CI
, 1.3–3.8), lacunar (
HR
: 4.0; 95%
CI
, 1.3–12.3), and cryptogenic stroke (
HR
: 3.6; 95%
CI
, 1.0–12.7), without significant heterogeneity across race/ethnic groups. Greater white matter hyperintensity volume increased both vascular (
HR
: 1.3; 95%
CI
, 1.1–1.7) and nonvascular (
HR
: 1.2; 95%
CI
, 1.0–1.5) mortality among Hispanic and white but not black participants (
P
=0.040 for heterogeneity). Subclinical brain infarct was associated with increased vascular mortality among Hispanic participants only (
HR
: 2.9; 95%
CI
, 1.4–5.8).

Conclusions
In this urban US sample, subclinical cerebrovascular lesions increased the risk of clinical stroke and vascular mortality and varied by race/ethnicity and lesion type.