Geometry-Oblivious FMM for Compressing Dense SPD Matrices

We present GOFMM (geometry-oblivious FMM), a novel method that creates a hierarchical low-rank approximation, "compression," of an arbitrary dense symmetric positive definite (SPD) matrix. For many applications, GOFMM enables an approximate matrix-vector multiplication in $N \log N$ or even $N$ time, where $N$ is the matrix size. Compression requires $N \log N$ storage and work. In general, our scheme belongs to the family of hierarchical matrix approximation methods. In particular, it generalizes the fast multipole method (FMM) to a purely algebraic setting by only requiring the ability to sample matrix entries. Neither geometric information (i.e., point coordinates) nor knowledge of how the matrix entries have been generated is required, thus the term "geometry-oblivious." Also, we introduce a shared-memory parallel scheme for hierarchical matrix computations that reduces synchronization barriers. We present results on the Intel Knights Landing and Haswell architectures, and on the NVIDIA Pascal architecture for a variety of matrices.Comment: 13 pages, accepted by SC'1

Balancing Ethical Goals in Challenging Individual Participant Scenarios Occurring in a Trial Conducted with Exception from Informed Consent

In 1996, federal regulations were put into effect that allowed enrollment of critically ill or injured patients into Food and Drug Administration (FDA)‐regulated clinical trials using an exception from informed consent (EFIC) under narrowly prescribed research circumstances. Despite the low likelihood that a legally authorized representative (LAR) would be present within the interventional time frame, the EFIC regulations require the availability of an informed consent process, to be applied if an LAR is present and able to provide prospective consent for patient enrollment into the trial. The purpose of this article is to describe a series of unanticipated consent‐related questions arising when a potential surrogate decision‐maker appeared to be available at the time of patient enrollment into a trial proceeding under EFIC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110828/1/acem12602.pd

An Exploratory Analysis of Computer Mediated Communications on Cyberstalking Severity

The interaction between disjunctive interpersonal relationships, those where the parties to the relationship disagree on the goals of the relationship, and the use of computer mediated communications channels is a relatively unexplored domain. Bargh (2002) suggests that CMC channels can amplify the development of interpersonal relationships, and notes that the effect is not constant across communications activities. This proposal suggests a line of research that explores the interaction between computer mediated communications (CMC) and stalking, which is a common form of disjunctive relationships. Field data from cyberstalking cases will be used to look at the effects of CMC channels on stalking case severity, and exploring the relative impacts of CMC channel characteristics on such cases. To accomplish this, a ratio scaled measure of stalking case severity is proposed for use in exploring the relationship between case severity and CMC media characteristics, anonymity, and the prior relationship between the stalker and the victim. Expected results are identified, and follow-up research is proposed

An Exploratory Analysis of Computer Mediated Communications on Cyberstalking Severity

The interaction between disjunctive interpersonal relationships, those where the parties to the relationship disagree on the goals of the relationship, and the use of computer mediated communications channels is a relatively unexplored domain. Bargh (2002) suggests that CMC channels can amplify the development of interpersonal relationships, and notes that the effect is not constant across communications activities. This proposal suggests a line of research that explores the interaction between computer mediated communications (CMC) and stalking, which is a common form of disjunctive relationships. Field data from cyberstalking cases will be used to look at the effects of CMC channels on stalking case severity, and exploring the relative impacts of CMC channel characteristics on such cases. To accomplish this, a ratio scaled measure of stalking case severity is proposed for use in exploring the relationship between case severity and CMC media characteristics, anonymity, and the prior relationship between the stalker and the victim. Expected results are identified, and follow-up research is proposed

Matching Schur complement approximations for certain saddle-point systems

The solution of many practical problems described by mathematical models requires approximation methods that give rise to linear(ized) systems of equations, solving which will determine the desired approximation. This short contribution describes a particularly effective solution approach for a certain class of so-called saddle-point linear systems which arises in different contexts

Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.

Protein-protein interactions (PPIs) are of pivotal importance in the regulation of biological systems and are consequently implicated in the development of disease states. Recent work has begun to show that, with the right tools, certain classes of PPI can yield to the efforts of medicinal chemists to develop inhibitors, and the first PPI inhibitors have reached clinical development. In this Review, we describe the research leading to these breakthroughs and highlight the existence of groups of structurally related PPIs within the PPI target class. For each of these groups, we use examples of successful discovery efforts to illustrate the research strategies that have proved most useful.JS, DES and ARB thank the Wellcome Trust for funding.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nrd.2016.2

Consulting Communities When Patients Cannot Consent: A Multi-Center Study of Community Consultation for Research in Emergency Settings

OBJECTIVE: To assess the range of responses to community consultation efforts conducted within a large network and the impact of different consultation methods on acceptance of exception from informed consent (EFIC) research and understanding of the proposed study. DESIGN: A cognitively pre-tested survey instrument was administered to 2,612 community consultation participants at 12 US centers participating in a multi-center trial of treatment for acute traumatic brain injury (TBI). SETTING: Survey nested within community consultation for a Phase III, randomized controlled trial of treatment for acute TBI conducted within a multi-center trial network and using EFIC. SUBJECTS: Adult participants in community consultation events. INTERVENTIONS: Community consultation efforts at participating sites. MEASUREMENTS AND MAIN RESULTS: Acceptance of EFIC in general, attitude toward personal EFIC enrollment, and understanding of the study content were assessed. 54% of participants agreed EFIC was acceptable in the proposed study; 71% were accepting of personal EFIC enrollment. Participants in interactive versus non-interactive community consultation events were more accepting of EFIC in general (63% vs. 49%) and personal EFIC inclusion (77% vs. 67%). Interactive community consultation participants had high-level recall of study content significantly more often than non-interactive consultation participants (77% vs. 67%). Participants of interactive consultation were more likely to recall possible study benefits (61% vs. 45%) but less likely to recall potential risks (56% vs. 69%). CONCLUSIONS: Interactive community consultation methods were associated with increased acceptance of EFIC and greater overall recall of study information but lower recall of risks. There was also significant variability in EFIC acceptance among different interactive consultation events. These findings have important implications for IRBs and investigators conducting EFIC research and for community engagement efforts in research more generally

Meta-Analysis of the Association between Transforming Growth Factor-Beta Polymorphisms and Complications of Coronary Heart Disease

Objective: To investigate the association between common transforming growth factor beta (TGF-β) single nucleotide polymorphisms (SNP) and significant complications of coronary heart disease (CHD).\ud \ud Method: We performed a meta-analysis of published case-control studies assessing the association of TGF-β SNPs with a range of CHD complications. A random effects model was used to calculate odds ratios and confidence intervals. Analyses were conducted for additive, dominant and recessive modes of inheritance.\ud \ud Results: Six studies involving 5535 cases and 2970 controls examining the association of common SNPs in TGF-β1 with CHD were identified. Applying a dominant model of inheritance, three TGF-β1 SNPs were significantly associated with CHD complications: The T alleles of rs1800469 (OR = 1.125, 95% CI 1.016–1.247, p = 0.031) and rs1800470 (OR = 1.146, 95% CI 1.026–1.279, p = 0.021); and the C allele of rs1800471 (OR = 1.207, 95% CI 1.037–1.406, p = 0.021).\ud \ud Conclusion: This meta-analysis suggests that common genetic polymorphisms in TGF-β1 are associated with complications of CHD

Simultaneously Bound Guests and Chiral Recognition: A Chiral Self-Assembled Supramolecular Host Encapsulates Hydrophobic Guests

Driven by the hydrophobic effect, a water-soluble, chiral, self-assembled supramolecular host is able to encapsulate hydrophobic organic guests in aqueous solution. Small aromatics can be encapsulated in the supramolecular assembly, and the simultaneous encapsulation of multiple guests is observed in many cases. The molecular host assembly is able to recognize different substitutional isomers of disubstituted benzenes with ortho substitution leading to the encapsulation of two guests, but meta or para substitution leading to the encapsulation of only one guest. The scope of hydrophobic guest encapsulation is further explored with chiral natural product guests. Upon encapsulation of chiral guests into the racemic host, diastereomeric host-guest complexes are formed with observed diastereoselectivities of up to 78:22 in the case of fenchone

Informed consent for clinical trials in acute coronary syndromes and stroke following the European Clinical Trials Directive: investigators' experiences and attitudes

<p>Abstract</p> <p>Background</p> <p>During clinical trials in emergency medicine, providing appropriate oral and written information to a patient is usually a challenge. There is little published information regarding patients' opinions and competence to provide informed consent, nor on physicians' attitudes towards the process. We have investigated the problem of obtaining consent from patients in emergency-setting clinical trials (such as acute coronary syndromes (ACS) and stroke) from a physicians' perspective.</p> <p>Methods</p> <p>A standardised anonymous 14-item questionnaire was distributed to Polish cardiac and stroke centres.</p> <p>Results</p> <p>Two hundred and fourteen informative investigator responses were received. Of these investigators, 73.8% had experience with ACS and 25.2% had experience with acute stroke trials (and 1% with both fields). The complete model of informed consent (embracing all aspects required by Good Clinical Practice (GCP) and law) was used in 53.3% of cases in emergency settings, whereas the legal option of proxy consent was not used at all. While less than 15% of respondents considered written information to have been fully read by patients, 80.4% thought that the amount of information being given to emergency patients is too lengthy. Although there is no legal obligation, more than half of the investigators sought parallel consent (assent) from patients' relatives. Most investigators confirmed that they would adopt the model proposed by the GCP guidelines: abbreviated verbal and written consent in emergency conditions with obligatory "all-embracing" deferred consent to continue the trial once the patient is able to provide it. However, this model would not follow current Polish and European legislation.</p> <p>Conclusion</p> <p>An update of national and European regulations is required to enable implementation of the emergency trial consent model referred to in GCP guidelines.</p