Dynamic Data Driven Methods for Self-aware Aerospace Vehicles

A self-aware aerospace vehicle can dynamically adapt the way it performs missions by gathering information about itself and its surroundings and responding intelligently. Achieving this DDDAS paradigm enables a revolutionary new generation of self-aware aerospace vehicles that can perform missions that are impossible using current design, flight, and mission planning paradigms. To make self-aware aerospace vehicles a reality, fundamentally new algorithms are needed that drive decision-making through dynamic response to uncertain data, while incorporating information from multiple modeling sources and multiple sensor fidelities.In this work, the specific challenge of a vehicle that can dynamically and autonomously sense, plan, and act is considered. The challenge is to achieve each of these tasks in real time executing online models and exploiting dynamic data streams–while also accounting for uncertainty. We employ a multifidelity approach to inference, prediction and planning an approach that incorporates information from multiple modeling sources, multiple sensor data sources, and multiple fidelities

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

SMN1 dosage analysis in spinal muscular atrophy from India

BACKGROUND: Spinal muscular atrophy (SMA) represents the second most common fatal autosomal recessive disorder after cystic fibrosis. Due to the high carrier frequency, the burden of this genetic disorder is very heavy in developing countries like India. As there is no cure or effective treatment, genetic counseling becomes very important in disease management. SMN1 dosage analysis results can be utilized for identifying carriers before offering prenatal diagnosis in the context of genetic counseling. METHODS: In the present study we analyzed the carrier status of parents and sibs of proven SMA patients. In addition, SMN1 copy number was determined in suspected SMA patients and parents of children with a clinical diagnosis of SMA. RESULTS: wenty nine DNA samples were analyzed by quantitative PCR to determine the number of SMN1 gene copies present, and 17 of these were found to have one SMN1 gene copy. The parents of confirmed SMA patients were found to be obligate carriers of the disease. Dosage analysis was useful in ruling out clinical suspicion of SMA in four patients. In a family with history of a deceased floppy infant and two abortions, both parents were found to be carriers of SMA and prenatal diagnosis could be offered in future pregnancies. CONCLUSION: SMN1 copy number analysis is an important parameter for identification of couples at risk for having a child affected with SMA and reduces unwarranted prenatal diagnosis for SMA. The dosage analysis is also useful for the counseling of clinically suspected SMA with a negative diagnostic SMA test

Review and Unification of Methods for Computing Derivatives of Multidisciplinary Systems

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97061/1/AIAA2012-1589.pd

Ethical considerations in prehospital ambulance based research : qualitative interview study of expert informants

Abstract: Background: Prehospital ambulance based research has unique ethical considerations due to urgency, time limitations and the locations involved. We sought to explore these issues through interviews with experts in this research field. Methods: We undertook semi-structured interviews with expert informants, primarily based in the UK, seeking their views and experiences of ethics in ambulance based clinical research. Participants were questioned regarding their experiences of ambulance based research, their opinions on current regulations and guidelines, and views about their general ethical considerations. Participants were chosen because they were actively involved in, or in their expert capacity (e.g. law) expressed an interest in, ambulance based research. Results: Fourteen participants were interviewed including principal investigators, researchers, ethicists and medical lawyers. Five major themes were identified: Capacity, Consent, Clinical Considerations, Consultation and Regulation. Questions regarding consent and capacity were foremost in the discussions as all participants highlighted these as areas for concern. The challenges and use of multiple consent models reflected the complexity of research in this environment. The clinical theme referred to the role of paramedics in research and how research involving ambulance services is increasingly informing improvements to patient care and outcomes and reducing the burden on hospital services. Most felt that, although current regulations were fit for purpose, more specific guidance on implementing these in the ambulance setting would be beneficial. This related closely to the theme of consultation, which examined the key role of ethics committees and other regulatory bodies, as well as public engagement. Conclusions: By interviewing experts in research or ethics in this setting we were able to identify key concerns and highlight areas for future development such as improved guidance

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

Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial

Importance: SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates lung injury in preclinical models, although data in humans with COVID-19 remain mixed. Objective: To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19. Design, Setting, and Participants: This blinded, placebo-controlled randomized clinical trial was conducted in 13 hospitals in the United States from April 2020 to February 2021. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already using a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible for participation. Data were analyzed from April 19 to August 24, 2021. Interventions: Losartan 50 mg orally twice daily vs equivalent placebo for 10 days or until hospital discharge. Main Outcomes and Measures: The primary outcome was the imputed arterial partial pressure of oxygen to fraction of inspired oxygen (Pao2:Fio2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity; days without supplemental o2, ventilation, or vasopressors; and mortality. Losartan pharmacokinetics and RAAS components (AII, angiotensin-[1-7] and angiotensin-converting enzymes 1 and 2)] were measured in a subgroup of participants. Results: A total of 205 participants (mean [SD] age, 55.2 [15.7] years; 123 [60.0%] men) were randomized, with 101 participants assigned to losartan and 104 participants assigned to placebo. Compared with placebo, losartan did not significantly affect Pao2:Fio2 ratio at 7 days (difference, -24.8 [95%, -55.6 to 6.1]; P = .12). Compared with placebo, losartan did not improve any secondary clinical outcomes and led to fewer vasopressor-free days than placebo (median [IQR], 9.4 [9.1-9.8] vasopressor-free days vs 8.7 [8.2-9.3] vasopressor-free days). Conclusions and Relevance: This randomized clinical trial found that initiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury did not improve Pao2:Fio2 ratio at 7 days. These data may have implications for ongoing clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04312009

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

Characterization of Novel and Uncharacterized p53 SNPs in the Chinese Population – Intron 2 SNP Co-Segregates with the Common Codon 72 Polymorphism

Multiple single nucleotide polymorphisms (SNPs) have been identified in the tumor suppressor gene p53, though the relevance of many of them is unclear. Some of them are also differentially distributed in various ethnic populations, suggesting selective functionality. We have therefore sequenced all exons and flanking regions of p53 from the Singaporean Chinese population and report here the characterization of some novel and uncharacterized SNPs - four in intron 1 (nucleotide positions 8759/10361/10506/11130), three in intron 3 (11968/11969/11974) and two in the 3′UTR (19168/19514). Allelic frequencies were determined for all these and some known SNPs, and were compared in a limited scale to leukemia and lung cancer patient samples. Intron 2 (11827) and 7 (14181/14201) SNPs were found to have a high minor allele frequency of between 26–47%, in contrast to the lower frequencies found in the US population, but similar in trend to the codon 72 polymorphism (SNP12139) that shows a distribution pattern correlative with latitude. Several of the SNPs were linked, such as those in introns 1, 3 and 7. Most interestingly, we noticed the co-segregation of the intron 2 and the codon 72 SNPs, the latter which has been shown to be expressed in an allele-specific manner, suggesting possible regulatory cross-talk. Association analysis indicated that the T/G alleles in both the co-segregating intron 7 SNPs and a 4tagSNP haplotype was strongly associated increased susceptibility to lung cancer in non-smoker females [OR: 1.97 (1.32, 3.394)]. These data together demonstrate high SNP diversity in p53 gene between different populations, highlighting ethnicity-based differences, and their association with cancer risk