Safely balancing a double-edged blade: identifying and mitigating emerging biosecurity risks in precision medicine

Tools and methods of precision medicine are developing rapidly, through both iterative discoveries enabled by innovations in biomedical research (e.g., genome editing, synthetic biology, bioengineered devices). These are strengthened by advancements in information technology and the increasing body of data—as assimilated, analyzed, and made accessible—and affectable—through current and emerging cyber—and systems- technologies. Taken together, these approaches afford ever greater volume and availability of individual and collective human data. Machine learning and/or artificial intelligence approaches are broadening this dual use risk; and in the aftermath of COVID-19, there is growing incentive and impetus to gather more biological data from individuals and their environments on a routine basis. By engaging these data—and the interventions that are based upon them, precision medicine offer promise of highly individualized treatments for disease and injury, optimization of structure and function, and concomitantly, the potential for (mis) using data to incur harm. This double-edged blade of benefit and risk obligates the need to safeguard human data from purloinment, through systems, guidelines and policies of a novel discipline, cyberbiosecurity, which, as coupled to ethical precepts, aims to protect human privacy, agency, and safety in ways that remain apace with scientific and technological advances in biomedicine. Herein, current capabilities and trajectories precision medicine are described as relevant to their dual use potential, and approaches to biodata security (viz.- cyberbiosecurity) are proposed and discussed

Three Endocrine Neoplasms: An Unusual Combination of Pheochromocytoma, Pituitary Adenoma, and Papillary Thyroid Carcinoma

Background: Three endocrine neoplasms?bilateral pheochromocytomas, somatotrophic pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid?occurred concurrently in a patient. A genetic mutation was hypothesized. Possible previously described genetic mutations were explored. Methods: Clinical assessments, laboratory data, images of tumors, histopathology, and immunohistochemistry of excised tissues documented the three neoplasms. Clinical assessment of the patient, family history, and a review of the literature sought a familial basis for the disorders. Results: The methods confirmed the presence of three endocrine neoplasms. Each neoplasm was surgically excised and histologically verified. Surgical and 131I treatments reduced the papillary carcinoma, but eventually this tumor progressed to a lethal degree. History, including that of nine siblings, uncovered no familial neoplasms. No similar case was found in the literature, but possible associations with germline mutations were considered. Conclusions: The concurrent development of pheochromocytomas, pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas, strongly suggest a de novo germline mutation in a gene not previously associated with multiple endocrine neoplasia syndromes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98488/1/thy%2E2011%2E0345.pd

The Joint ESA/NASA Galileo/GPS Receiver Onboard the ISS the GARISS Project

ESA and NASA conducted a joint Galileo/GPS space receiver experiment on-board the International Space Station (ISS). The objectives (Enderle 2017) of the joint project were to demonstrate the robustness of a combined Galileo/GPS waveform uploaded to NASA hardware already operating in the challenging space environment - the SCaN (Space Communications and Navigation) software defined radio (SDR) testbed (FPGA) - on-board the ISS. These activities data included the analysis of the Galileo/GPS signal and on-board Position/Velocity/Time (PVT) performance, processing of the Galileo/GPS raw data (code- and carrier phase) for Precise Orbit Determination (POD), and validate the added value of a space-borne dual GNSS receiver compared to a single-system GNSS receiver operating under the same conditions. This paper will provide a general overview of the Galileo/GPS experiment called GARISS - on-board the ISS, describe design, test and validation and also the operations of the experiment. Further, the various analysis conducted in the con is joint project and also the results obtained will be presented with a focus on the (Precise) Orbit Determination results

Discordance between imaging and immunohistochemistry in unilateral primary aldosteronism

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139975/1/cen13442.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139975/2/cen13442_am.pd

Factors in perioperative care that determine blood loss in liver surgery

AbstractObjectivesExcessive blood loss during liver surgery contributes to postoperative morbidity and mortality and the minimizing of blood loss improves outcomes. This study examines pre- and intraoperative factors contributing to blood loss and identifies areas for improvement.MethodsAll patients who underwent elective hepatic resection between June 2007 and June 2009 were identified. Detailed information on the pre- and perioperative clinical course was analysed. Univariate and multivariate analyses were used to identify factors associated with intraoperative blood loss.ResultsA total of 175 patients were studied, of whom 95 (54%) underwent resection of three or more segments. Median blood loss was 782ml. Greater blood loss occurred during major resections and prolonged surgery and was associated with an increase in postoperative complications (P= 0.026). Peak central venous pressure (CVP) of >10cm H2O was associated with increased blood loss (P= 0.01). Although no differences in case mix were identified, blood loss varied significantly among anaesthetists, as did intraoperative volumes of i.v. fluids and transfusion practices.ConclusionsThis study confirms a relationship between CVP and blood loss in hepatic resection. Intraoperative CVP values were higher than those described in other studies. There was variation in the intraoperative management of patients. Collaboration between surgical and anaesthesia teams is required to minimize blood loss and the standardization of intraoperative anaesthesia practice may improve outcomes following liver surgery

Pressure-induced inclusion of neon in the crystal structure of a molecular Cu2(pacman) complex at 4.67 GPa

Crystals of a Cu complex of the macrocyclic Schiff-base calixpyrrole or 'Pacman' ligand, Cu2(L), do not contain any solvent-accessible void space at ambient pressure, but adsorb neon at 4.67 GPa, forming Cu2(L)·3.5Ne

Cytotoxicity models of Huntington's disease and relevance of hormetic mechanisms: A critical assessment of experimental approaches and strategies.

Abstract This paper assesses in vivo cytotoxicity models of Huntington's disease (HD). Nearly 150 agents were found to be moderately to highly effective in mitigating the pathological sequelae of cytotoxic induction of HD features in multiple rodent models. Typically, rodents are treated with a prospective HD-protective agent before, during, or after the application of a chemical or transgenic process for inducing histopathological and behavioral symptoms of HD. Although transgenic and knockout rodent models (1) display relatively high construct and face validity, and (2) are ever more routinely employed to mimic genetic-to-phenotypic expression of HD features, toxicant models are also often employed, and have served as valuable test beds for the elucidation of biochemical processes and discovery of therapeutic targets in HD. Literature searches of the toxicant HD rodent models yielded nearly 150 agents that were moderately to highly effective in mitigating pathological sequelae in multiple mouse and rat HD models. Experimental models, study designs, and exposure protocols (e.g., pre- and post-conditioning) used in testing these agents were assessed, including dosing strategies, endpoints, and dose-response features. Hormetic-like biphasic dose responses, chemoprotective mechanisms, and the translational relevance of the preclinical studies and their therapeutic implications are critically analyzed in the present report. Notably, not one of the 150 agents that successfully delayed onset and progression of HD in the experimental models has been successfully translated to the treatment of humans in a clinical setting. Potential reasons for these translational failures are (1) the inadequacy of dose-response analyses and subsequent lack of useful dosing data; (2) effective rodent doses that are too high for safe human application; (3) key differences between the experimental models and humans in pharmacokinetic/pharmacodynamic features, ages and routes of agent administration; (4) lack of robust pharmacokinetic, mechanistic or systematic approaches to probe novel treatment strategies; and (5) inadequacies of the chemically induced HD model in rats to mimic accurately the complex genetic and developmental origin and progression of HD in humans. These deficiencies need to be urgently addressed if pharmaceutical agents for the treatment of HD are going to be successfully developed in experimental models and translated with fidelity to the clinic

A perspective on using experiment and theory to identify design principles in dye-sensitized solar cells

Dye-sensitized solar cells (DSCs) have been the subject of wide-ranging studies for many years because of their potential for large-scale manufacturing using roll-to-roll processing allied to their use of earth abundant raw materials. Two main challenges exist for DSC devices to achieve this goal; uplifting device efficiency from the 12 to 14% currently achieved for laboratory-scale ‘hero’ cells and replacement of the widely-used liquid electrolytes which can limit device lifetimes. To increase device efficiency requires optimized dye injection and regeneration, most likely from multiple dyes while replacement of liquid electrolytes requires solid charge transporters (most likely hole transport materials – HTMs). While theoretical and experimental work have both been widely applied to different aspects of DSC research, these approaches are most effective when working in tandem. In this context, this perspective paper considers the key parameters which influence electron transfer processes in DSC devices using one or more dye molecules and how modelling and experimental approaches can work together to optimize electron injection and dye regeneration. This paper provides a perspective that theory and experiment are best used in tandem to study DSC device