Long-term clinical safety and efficacy of drug-eluting stents in real-world patients

Since the fi rst balloon angioplasty was performed in the late 1970’s, percutaneous coronary intervention (PCI) has undergone rapid transformation to become an essential treatment option for coronary artery disease as an alternative to surgery. PCI is now widely accepted across the globe, with over half a million procedures being performed annually in the United States alone. Coronary stents were developed in the mid-1980s, and the fi rst randomized trials comparing stenting to balloon angioplasty demonstrated improved angiographic and clinical outcomes. Consequently, coronary artery stenting has progressively replaced balloon angioplasty as the preferred method of PCI. In these initial trials, acute stent thrombosis was a major concern because of high morbidity and mortality. The introduction of dual-antiplatelet therapy with aspirin and a thienopyridine (such as Clopidogrel) as well as impro

Backpropagation for long sequences: beyond memory constraints with constant overheads

Naive backpropagation through time has a memory footprint that grows linearly in the sequence length, due to the need to store each state of the forward propagation. This is a problem for large networks. Strategies have been developed to trade memory for added computations, which results in a sublinear growth of memory footprint or computation overhead. In this work, we present a library that uses asynchronous storing and prefetching to move data to and from slow and cheap stor- age. The library only stores and prefetches states as frequently as possible without delaying the computation, and uses the optimal Revolve backpropagation strategy for the computations in between. The memory footprint of the backpropagation can thus be reduced to any size (e.g. to fit into DRAM), while the computational overhead is constant in the sequence length, and only depends on the ratio between compute and transfer times on a given hardware. We show in experiments that by exploiting asyncronous data transfer, our strategy is always at least as fast, and usually faster than the previously studied "optimal" strategies

Caecal herniation through the foramen of Winslow

published_or_final_versio

Phosphodiesterase-5 inhibition and cardioprotection: potential role of hydrogen sulfide

Background Our laboratory has shown that phosphodiesterase-5 (PDE-5) inhibitors including sildenafil, vardenafil and tadalafil induce powerful protection against myocardial ischemia-reperfusion injury. We have shown that sildenafil protects through activation PKC, expression of eNOS/iNOS, protein kinase G (PKG) and opening of mitochondrial KATP (mitoKATP) channels [1]. Hydrogen sulfide (H2S) is a gaseous molecule that is produced enzymatically and exerts physiological actions in the cardiovascular system. Similar to PKG, H2S has been shown to protect the heart via opening of mitoKATP channel [2]. In the current study, we hypothesized that tadalafil, the long acting inhibitor of PDE-5 mediates cardioprotection through H2S signaling in a PKG-dependent fashion. Methods and results After baseline transthoracic echocardiography (TTE), adult ICR mice were injected i.p. with vehicle (10% DMSO) or tadalafil (1 mg/kg) with or without KT5823 (KT, PKG blocker, 1 mg/kg) or dl-propargylglycine [PAG, Cystathionine-γ-lyase (CSE, H2S-producing enzyme) blocker; 50 mg/kg] 1 h prior to coronary artery ligation for 30 min and reperfusion for 24 h, whereas C57BL-wild type and CSE-knockout mice were treated with either vehicle or tadalafil. After reperfusion, TTE was performed and hearts were collected for infarct size (IS) measurement using TTC staining. Survival was increased with tadalafil (95%) compared with control (65%, P \u3c 0.05). Infarct size was reduced with tadalafil (13.2 ± 1.7%) compared to vehicle (40.6 ± 2.5%; P \u3c 0.05). KT and PAG abolished tadalafil-induced protection (IS: 39.2 ± 1% and 51.2 ± 2.4%, respectively) similar to genetic deletion of CSE (47.2 ± 5.1%). Moreover, tadalafil preserved fractional shortening (FS: 31 ± 1.5%) compared to control (FS: 22 ± 4.8%, P \u3c 0.05). Baseline FS was 44 ± 1.7%. KT and PAG abrogated the preservation of LV function with tadalafil by decline in FS to 17 ± 1% and 23 ± 3%, respectively. Compared to vehicle, myocardial H2S production was significantly increased with tadalafil and was abolished with KT. Conclusion PKG activation with tadalafil limits myocardial infarction and preserves LV function through H2S signaling

A comparative study to determine the clinical efficacy of Ramipril versus combination of Ramipril and Telmisartan in reducing microalbuminuria associated with grade 2 hypertension

Inhibition of the renin-angiotensin system causes a reduction in urinary protein excretion. It is uncertain whether Angiotensin receptor blockers (ARBs) are equally effective antiproteinuric agents as Angiotensin converting Enzyme (ACE) inhibitors, or whether the combination of ACE inhibitors with ARBs is preferable to ACE inhibitor alone? Microalbuminuria is a prognostic marker for cardiovascular and renal risk. The objective of the study was to compare the clinical efficacy of Ramipril alone versus combination of Ramipril and Telmisartan by assessing the fall in B.P. and the improvement in the degree of microalbuminuria in stage II hypertensive patients. 60 patients of stage II hypertension without having any other cause of microalbuminuria were selected as subjects for the present study and were randomly distributed in to 2 groups- Group A included 30 patients who were given Ramipril 5 mg/ day and Group B included the same number of patients who were given a combination of Ramipril 5 mg/day and Telmisartan 40 mg/day. Baseline parameters included were measurement of Systolic, diastolic blood pressure and mean arterial pressure; microalbuminuria, blood urea, serum creatinine and serum potassium estimations. The drugs under trial were given for 20 weeks. Microalbuminuria was determined at 0 and 20 weeks. The mean percentage fall in microalbuminuria and mean arterial pressure were statistically highly significant (p<0.0001) with combination of Ramipril and Telmisartan (Group B) in comparison to Ramipril (Group A) alone. A highly significant (p‹ 0.0001) mean percentage increase in potassium level was observed in group B at the end of 20 weeks. The side effects were less observed in the combination group. Thus to conclude the combination of Ramipril and Telmisartan provides superior blood pressure (BP) lowering and target organ protection than Ramipril alone, hence the combination of Ramipril and Telmisartan is a better choice to treat and to prevent the progression of the disease.Keywords: Hypertension; Microalbuminuria; Ramipril; Telmisarta

Combining checkpointing and data compression for large scale seismic inversion

Seismic inversion and imaging are adjoint-based optimization problems that processes up to terabytes of data, regularly exceeding the memory capacity of available computers. Data compression is an effective strategy to reduce this memory requirement by a certain factor, particularly if some loss in accuracy is acceptable. A popular alternative is checkpointing, where data is stored at selected points in time, and values at other times are recomputed as needed from the last stored state. This allows arbitrarily large adjoint computations with limited memory, at the cost of additional recomputations. In this paper we combine compression and checkpointing for the first time to compute a realistic seismic inversion. The combination of checkpointing and compression allows larger adjoint computations compared to using only compression, and reduces the recomputation overhead significantly compared to using only checkpointing

High-level python abstractions for optimal checkpointing in inversion problems

Inversion and PDE-constrained optimization problems often rely on solving the adjoint problem to calculate the gradient of the objec- tive function. This requires storing large amounts of intermediate data, setting a limit to the largest problem that might be solved with a given amount of memory available. Checkpointing is an approach that can reduce the amount of memory required by redoing parts of the computation instead of storing intermediate results. The Revolve checkpointing algorithm o ers an optimal schedule that trades computational cost for smaller memory footprints. Integrat- ing Revolve into a modern python HPC code and combining it with code generation is not straightforward. We present an API that makes checkpointing accessible from a DSL-based code generation environment along with some initial performance gures with a focus on seismic applications