The Parallel Persistent Memory Model

We consider a parallel computational model that consists of $P$ processors, each with a fast local ephemeral memory of limited size, and sharing a large persistent memory. The model allows for each processor to fault with bounded probability, and possibly restart. On faulting all processor state and local ephemeral memory are lost, but the persistent memory remains. This model is motivated by upcoming non-volatile memories that are as fast as existing random access memory, are accessible at the granularity of cache lines, and have the capability of surviving power outages. It is further motivated by the observation that in large parallel systems, failure of processors and their caches is not unusual. Within the model we develop a framework for developing locality efficient parallel algorithms that are resilient to failures. There are several challenges, including the need to recover from failures, the desire to do this in an asynchronous setting (i.e., not blocking other processors when one fails), and the need for synchronization primitives that are robust to failures. We describe approaches to solve these challenges based on breaking computations into what we call capsules, which have certain properties, and developing a work-stealing scheduler that functions properly within the context of failures. The scheduler guarantees a time bound of $O(W/P_A + D(P/P_A) \lceil\log_{1/f} W\rceil)$ in expectation, where $W$ and $D$ are the work and depth of the computation (in the absence of failures), $P_A$ is the average number of processors available during the computation, and $f \le 1/2$ is the probability that a capsule fails. Within the model and using the proposed methods, we develop efficient algorithms for parallel sorting and other primitives.Comment: This paper is the full version of a paper at SPAA 2018 with the same nam

A phase II study of chloroquinoxaline sulfonamide (CQS) in patients with metastatic colorectal carcinoma (MCRC)

Purpose: Phase II multicenter study investigated the efficacy and toxicity of the novel halogenated derivative of sulfaquixonaline Chloroquinoxaline Sulfonamide (CQS) in metastatic colorectal cancer. Experimental design: Eligible patients with metastatic or recurrent colorectal cancer received CQS at a dose schedule of 2000 mg/m 2 over an hour weekly for 4 weeks every 42 days. Treatment was continued until unexpected toxicity or disease progression. Results: A total of seventeen patients were enrolled on this study. 94% of all patients enrolled had prior treatment. Sixteen patients were evaluable for response with fifteen patients showing evidence of disease progression and one patient with prolonged stable disease. One patient had non-evaluable disease. Following this interim analysis, the drug was considered ineffective and the study was terminated early. The most frequent adverse event was anemia. No patients discontinued the treatment because of toxicity. Conclusion: CQS, when given at a dose of 2000 mg/m 2 weekly for 4 weeks every 42 days to patients with metastatic colorectal cancer, does not result in significant tumor regression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43416/1/10637_2005_Article_4827.pd

Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin

The purpose of this study was to evaluate by a retrospective analysis of 53 patients the efficacy of chemotherapy combining etoposide and cisplatin in the treatment of neuroendocrine tumours. The regimen was a combination of etoposide 100 mg m–2 day–1 for 3 days and cisplatin 100 mg m–2 on day 1, given by 2-h intravenous infusion, administered every 21 days. Twelve patients had a well-differentiated and 41 a poorly differentiated neuroendocrine tumour. Toxicity of treatment was assessed in 50 patients and efficacy in 52 patients. Among the 11 patients with a well-differentiated tumour evaluable for tumoural response, only one (9.4%) had a partial response for 8.5 months. Forty-one patients with a poorly differentiated tumour showed an objective response rate of 41.5% (four complete and 13 partial responses); the median duration of response was 9.2 months, the median overall survival 15 months and the median progression-free survival 8.9 months. Haematological grade 3–4 toxicity was observed in 60% of the cases with one treatment-related death, digestive grade 3–4 toxicity in 40% and grade 3 alopecia was constant. No severe renal, hearing and neurological toxicities were observed (grade 1 in 6%, 14%, 72% respectively and no grade >1). We confirm that poorly differentiated neuroendocrine tumours are chemosensitive to the etoposide plus cisplatin combination. However, the prognosis remains poor with a 2-year survival lower than 20% confirming that new therapeutic strategies have to be developed. © 1999 Cancer Research Campaig

Dissociable learning processes, associative theory, and testimonial reviews: A comment on Smith and Church (2018

Smith and Church (Psychonomic Bulletin & Review, 25, 1565–1584 2018) present a “testimonial” review of dissociable learning processes in comparative and cognitive psychology, by which we mean they include only the portion of the available evidence that is consistent with their conclusions. For example, they conclude that learning the information-integration category-learning task with immediate feedback is implicit, but do not consider the evidence that people readily report explicit strategies in this task, nor that this task can be accommodated by accounts that make no distinction between implicit and explicit processes. They also consider some of the neuroscience relating to information-integration category learning, but do not report those aspects that are more consistent with an explicit than an implicit account. They further conclude that delay conditioning in humans is implicit, but do not report evidence that delay conditioning requires awareness; nor do they present the evidence that conditioned taste aversion, which should be explicit under their account, can be implicit. We agree with Smith and Church that it is helpful to have a clear definition of associative theory, but suggest that their definition may be unnecessarily restrictive. We propose an alternative definition of associative theory and briefly describe an experimental procedure that we think may better distinguish between associative and non-associative processes

Anaesthesia and airway management in mucopolysaccharidosis

Abstract This paper provides a detailed overview and dis-cussion of anaesthesia in patients with mucopolysacchari-dosis (MPS), the evaluation of risk factors in these patients and their anaesthetic management, including emergency airway issues. MPS represents a group of rare lysosomal storage disorders associated with an array of clinical mani-festations. The high prevalence of airway obstruction and restrictive pulmonary disease in combination with cardio-vascular manifestations poses a high anaesthetic risk to these patients. Typical anaesthetic problems include airway obstruction after induction or extubation, intubation diffi-culties or failure [can’t intubate, can’t ventilate (CICV)], possible emergency tracheostomy and cardiovascular and cervical spine issues. Because of the high anaesthetic risk, the benefits of a procedure in patients with MPS shoul

Mechanism of trifluorothymidine potentiation of oxaliplatin-induced cytotoxicity to colorectal cancer cells

Oxaliplatin (OHP) is an anticancer agent that acts by formation of Platinum-DNA (Pt-DNA) adducts resulting in DNA-strand breaks and is used for the treatment of colorectal cancer. The pyrimidine analog trifluorothymidine (TFT) forms together with a thymidine phosphorylase inhibitor (TPI) the anticancer drug formulation TAS-102, in which TPI enhances the bioavailability of TFT in vivo. In this in vitro study the combined cytotoxic effects of OHP with TFT were investigated in human colorectal cancer cells as a model for TAS-102 combinations. In a panel of five colon cancer cell lines (WiDr, H630, Colo320, SNU-C4 and SW1116) we evaluated the OHP-TFT drug combinations using the multiple drug–effect analysis with CalcuSyn software, in which the combination index (CI) indicates synergism (CI<0.9), additivity (CI=0.9–1.1) or antagonism (CI>1.1). Drug target analysis was used for WiDr, H630 and SW1116 to investigate whether there was an increase in Pt-DNA adduct formation, DNA damage induction, cell cycle delay and apoptosis. Trifluorothymidine combined with OHP resulted in synergism for all cell lines (all CI<0.9). This was irrespective of schedule in which either one of the drugs was kept at a constant concentration (using variable drug ratio) or when the two drugs were added in a 1 : 1 IC50-based molar ratio. Synergism could be increased for WiDr using sequential drug treatment schedules. Trifluorothymidine increased Pt-DNA adduct formation significantly in H630 and SW1116 (14.4 and 99.1%, respectively; P<0.05). Platinum-DNA adducts were retained best in SW1116 in the presence of TFT. More DNA-strand breaks were induced in SW1116 and the combination increased DNA damage induction (>20%) compared with OHP alone. Exposure to the drugs induced a clear cell-cycle S-phase arrest, but was dose schedule and cell line dependent. Trifluorothymidine (TFT) and OHP both induced apoptosis, which increased significantly for WiDr and SW1116 after TFT–OHP exposure (18.8 and 20.6% respectively; P<0.05). The basal protein levels of ERCC1 DNA repair enzyme were not related to the DNA damage that was induced in the cell lines. In conclusion, the combination of TFT with the DNA synthesis inhibitor OHP induces synergism in colorectal cancer cells, but is dependent on the dose and treatment schedule used

Aging-Aware Request Scheduling for Non-Volatile Main Memory

Modern computing systems are embracing non-volatile memory (NVM) to implement high-capacity and low-cost main memory. Elevated operating voltages of NVM accelerate the aging of CMOS transistors in the peripheral circuitry of each memory bank. Aggressive device scaling increases power density and temperature, which further accelerates aging, challenging the reliable operation of NVM-based main memory. We propose HEBE, an architectural technique to mitigate the circuit aging-related problems of NVM-based main memory. HEBE is built on three contributions. First, we propose a new analytical model that can dynamically track the aging in the peripheral circuitry of each memory bank based on the bank's utilization. Second, we develop an intelligent memory request scheduler that exploits this aging model at run time to de-stress the peripheral circuitry of a memory bank only when its aging exceeds a critical threshold. Third, we introduce an isolation transistor to decouple parts of a peripheral circuit operating at different voltages, allowing the decoupled logic blocks to undergo long-latency de-stress operations independently and off the critical path of memory read and write accesses, improving performance. We evaluate HEBE with workloads from the SPEC CPU2017 Benchmark suite. Our results show that HEBE significantly improves both performance and lifetime of NVM-based main memory.Comment: To appear in ASP-DAC 202

Distractors associated with reward break through the focus of attention

In the present study, we investigated the conditions in which rewarded distractors have the ability to capture attention, even when attention is directed toward the target location. Experiment 1 showed that when the probability of obtaining reward was high, all salient distractors captured attention, even when they were not associated with reward. This effect may have been caused by participants suboptimally using the 100%-valid endogenous location cue. Experiment 2 confirmed this result by showing that salient distractors did not capture attention in a block in which no reward was expected. In Experiment 3, the probability of the presence of a distractor was high, but it only signaled reward availability on a low number of trials. The results showed that those very infrequent distractors that signaled reward captured attention, whereas the distractors (both frequent and infrequent ones) not associated with reward were simply ignored. The latter experiment indicates that even when attention is directed to a location in space, stimuli associated with reward break through the focus of attention, but equally salient stimuli not associated with reward do not