A Direct-Style Effect Notation for Sequential and Parallel Programs (Artifact)

Modeling sequential and parallel composition of effectful computations has been investigated in a variety of languages for a long time. In particular, the popular do-notation provides a lightweight effect embedding for any instance of a monad. Idiom bracket notation, on the other hand, provides an embedding for applicatives. First, while monads force effects to be executed sequentially, ignoring potential for parallelism, applicatives do not support sequential effects. Composing sequential with parallel effects remains an open problem. This is even more of an issue as real programs consist of a combination of both sequential and parallel segments. Second, common notations do not support invoking effects in direct-style, instead forcing a rigid structure upon the code. In this paper, we propose a mixed applicative/monadic notation that retains parallelism where possible, but allows sequentiality where necessary. We leverage a direct-style notation where sequentiality or parallelism is derived from the structure of the code. We provide a mechanisation of our effectful language in Coq and prove that our compilation approach retains the parallelism of the source program

A Direct-Style Effect Notation for Sequential and Parallel Programs

Modeling sequential and parallel composition of effectful computations has been investigated in a variety of languages for a long time. In particular, the popular do-notation provides a lightweight effect embedding for any instance of a monad. Idiom bracket notation, on the other hand, provides an embedding for applicatives. First, while monads force effects to be executed sequentially, ignoring potential for parallelism, applicatives do not support sequential effects. Composing sequential with parallel effects remains an open problem. This is even more of an issue as real programs consist of a combination of both sequential and parallel segments. Second, common notations do not support invoking effects in direct-style, instead forcing a rigid structure upon the code. In this paper, we propose a mixed applicative/monadic notation that retains parallelism where possible, but allows sequentiality where necessary. We leverage a direct-style notation where sequentiality or parallelism is derived from the structure of the code. We provide a mechanisation of our effectful language in Coq and prove that our compilation approach retains the parallelism of the source program

Multiparty Languages: The Choreographic and Multitier Cases (Pearl)

Choreographic languages aim to express multiparty communication protocols, by providing primitives that make interaction manifest. Multitier languages enable programming computation that spans across several tiers of a distributed system, by supporting primitives that allow computation to change the location of execution. Rooted into different theoretical underpinnings - respectively process calculi and lambda calculus - the two paradigms have been investigated independently by different research communities with little or no contact. As a result, the link between the two paradigms has remained hidden for long. In this paper, we show that choreographic languages and multitier languages are surprisingly similar. We substantiate our claim by isolating the core abstractions that differentiate the two approaches and by providing algorithms that translate one into the other in a straightforward way. We believe that this work paves the way for joint research and cross-fertilisation among the two communities

Multiparty Languages: The Choreographic and Multitier Cases

International audienceChoreographic languages aim to express multiparty communication protocols, by providing primitives that make interaction manifest. Multitier languages enable programming computation that spans across several tiers of a distributed system, by supporting primitives that allow computation to change the location of execution. Rooted into different theoretical underpinnings-respectively process calculi and lambda calculus-the two paradigms have been investigated independently by different research communities with little or no contact. As a result, the link between the two paradigms has remained hidden for long. In this paper, we show that choreographic languages and multitier languages are surprisingly similar. We substantiate our claim by isolating the core abstractions that differentiate the two approaches and by providing algorithms that translate one into the other in a straightforward way. We believe that this work paves the way for joint research and cross-fertilisation among the two communities

An Activity-Rotation Relationship and Kinematic Analysis of Nearby Mid-to-Late-Type M Dwarfs

Using spectroscopic observations and photometric light curves of 238 nearby M dwarfs from the MEarth exoplanet transit survey, we examine the relationships between magnetic activity (quantified by Hα emission), rotation period, and stellar age. Previous attempts to investigate the relationship between magnetic activity and rotation in these stars were hampered by the limited number of M dwarfs with measured rotation periods (and the fact that v sin i measurements probe only rapid rotation). However, the photometric data from MEarth allows us to probe a wide range of rotation periods for hundreds of M dwarf stars (from shorter than than one to longer than 100 days). Over all M spectral types that we probe, we find that the presence of magnetic activity is tied to rotation, including for late-type, fully convective M dwarfs. We also find evidence that the fraction of latetype M dwarfs that are active may be higher at longer rotation periods compared to their early-type counterparts, with several active, late-type, slowly rotating stars present in our sample. Additionally, we find that all M dwarfs with rotation periods shorter than 26 days (early-type; M1-M4) and 86 days (late-type; M5-M8) are magnetically active. This potential mismatch suggests that the physical mechanisms that connect stellar rotation to chromospheric heating may be different in fully convective stars. A kinematic analysis suggests that the magnetically active, rapidly rotating stars are consistent with a kinematically young population, while slow-rotators are less active or inactive and appear to belong to an older, dynamically heated stellar population.Astronom

Association of intravenous thrombolysis and pre-interventional reperfusion: a post hoc analysis of the SWIFT DIRECT trial.

BACKGROUND A potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there are few data on the occurrence of pre-interventional reperfusion in patients randomized to IVT or no IVT before MT. METHODS SWIFT DIRECT (Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA vs DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke) was a randomized controlled trial including acute ischemic stroke IVT eligible patients being directly admitted to a comprehensive stroke center, with allocation to IVT with MT versus MT alone. The primary endpoint of this analysis was the occurrence of pre-interventional reperfusion, defined as a pre-interventional expanded Thrombolysis in Cerebral Infarction score of ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. RESULTS Of 396 patients, pre-interventional reperfusion occurred in 20 (10.0%) patients randomized to IVT with MT, and in 7 (3.6%) patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (adjusted OR 2.91, 95% CI 1.23 to 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture time (p for interaction=0.33), although the effect tended to be stronger in patients with a Randomization-to-Groin-Puncture time >28 min (adjusted OR 4.65, 95% CI 1.16 to 18.68). There were no significant differences in rates of functional outcomes between patients with and without pre-interventional reperfusion. CONCLUSION Even for patients with proximal large vessel occlusions and direct access to MT, IVT resulted in an absolute increase of 6% in rates of pre-interventional reperfusion. The influence of time strata on the occurrence of pre-interventional reperfusion should be studied further in an individual patient data meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER clinicaltrials.gov NCT03192332

Smoking, Variation In N-acetyltransferase 1 (nat1) And 2 (nat2), And Risk Of Non-hodgkin Lymphoma: A Pooled Analysis Within The Interlymph Consortium

Studies of smoking and risk of non-Hodgkin lymphoma (NHL) have yielded inconsistent results, possibly due to subtype heterogeneity and/or genetic variation impacting the metabolism of tobacco-derived carcinogens, including substrates of the N-acetyltransferase enzymes NAT1 and NAT2. We conducted a pooled analysis of 5,026 NHL cases and 4,630 controls from seven case-control studies in the international lymphoma epidemiology consortium to examine associations between smoking, variation in the N-acetyltransferase genes NAT1 and NAT2, and risk of NHL subtypes. Smoking data were harmonized across studies, and genetic variants in NAT1 and NAT2 were used to infer acetylation phenotype of the NAT1 and NAT2 enzymes, respectively. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for risk of NHL and subtypes were calculated using joint fixed effects unconditional logistic regression models. Current smoking was associated with a significant 30 % increased risk of follicular lymphoma (n = 1,176) but not NHL overall or other NHL subtypes. The association was similar among NAT2 slow (OR 1.36; 95 % CI 1.07-1.75) and intermediate/rapid (OR 1.27; 95 % CI 0.95-1.69) acetylators (p (interaction) = 0.82) and also did not differ by NAT1*10 allelotype. Neither NAT2 phenotype nor NAT1*10 allelotype was associated with risk of NHL overall or NHL subtypes. The current findings provide further evidence for a modest association between current smoking and follicular lymphoma risk and suggest that this association may not be influenced by variation in the N-acetyltransferase enzymes

Low T-cell proportion in the tumor microenvironment is associated with immune escape and poor survival in diffuse large B-cell lymphoma

The tumor microenvironment (TME) is important in the pathogenesis and prognosis of lymphoma. Previous studies have demonstrated that features of the diffuse large B-cell lymphoma (DLBCL) TME can be associated with prognosis, but questions remain about the mechanisms underlying these TME features, and the interplay between tumor cells and the local TME. Therefore, we performed multispectral immunofluorescence (mIF) using two 6-color panels to interrogate the cellular proportions of T-cell subsets, macrophages, and natural killer cells in 57 cases of de novo DLBCL treated with R-CHOP chemotherapy. We found that very low CD3+ T-cell proportion and low CD4+PD1+ and CD8+PD1+ T cells have poor survival compared to those with a high T-cell proportion. Also, cases with concurrently low TIM3 and PD1 have a poor prognosis. This poor prognosis with low T-cell proportion was validated using immune deconvolution of gene expression profiling data from 351 cases of DLBCL and an additional cohort of 53 cases of DLBCL using routine immunohistochemistry. In addition, cases with loss of B2M, HLA I and/or HLA II protein expression on the tumor cells also had a low T-cell proportion, providing evidence that lack of these proteins allows for immune evasion. Overall, our results show that patients with DLBCL with a low T-cell proportion in the TME have a poor survival when treated with R-CHOP and exhibit mechanisms of immune escape

Time to treatment with bridging intravenous alteplase before endovascular treatment:subanalysis of the randomized controlled SWIFT-DIRECT trial.

BACKGROUND We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT). METHODS We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours. RESULTS We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short. CONCLUSIONS We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER URL: https://www. CLINICALTRIALS gov ; Unique identifier: NCT03192332