Multifunctional Organic-Inorganic Hybrid Nanophotonic Devices

The emergence of optical applications, such as lasers, fiber optics, and semiconductor based sources and detectors, has created a drive for smaller and more specialized devices. Nanophotonics is an emerging field of study that encompasses the disciplines of physics, engineering, chemistry, biology, applied sciences and biomedical technology. In particular, nanophotonics explores optical processes on a nanoscale. This dissertation presents nanophotonic applications that incorporate various forms of the organic polymer N-isopropylacrylamide (NIPA) with inorganic semiconductors. This includes the material characterization of NIPA, with such techniques as ellipsometry and dynamic light scattering. Two devices were constructed incorporating the NIPA hydrogel with semiconductors. The first device comprises a PNIPAM-CdTe hybrid material. The PNIPAM is a means for the control of distances between CdTe quantum dots encapsulated within the hydrogel. Controlling the distance between the quantum dots allows for the control of resonant energy transfer between neighboring quantum dots. Whereby, providing a means for controlling the temperature dependent red-shifts in photoluminescent peaks and FWHM. Further, enhancement of photoluminescent due to increased scattering in the medium is shown as a function of temperature. The second device incorporates NIPA into a 2D photonic crystal patterned on GaAs. The refractive index change of the NIPA hydrogel as it undergoes its phase change creates a controllable mechanism for adjusting the transmittance of light frequencies through a linear defect in a photonic crystal. The NIPA infiltrated photonic crystal shows greater shifts in the bandwidth per ºC than any liquid crystal methods. This dissertation demonstrates the versatile uses of hydrogel, as a means of control in nanophotonic devices, and will likely lead to development of other hybrid applications. The development of smaller light based applications will facilitate the need to augment the devices with control mechanism and will play an increasing important role in the future

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Alanine metabolism, transport, and cycling in the brain

Brain glutamate/glutamine cycling is incomplete without return of ammonia to glial cells. Previous studies suggest that alanine is an important carrier for ammonia transfer. In this study, we investigated alanine transport and metabolism in Guinea pig brain cortical tissue slices and prisms, in primary cultures of neurons and astrocytes, and in synaptosomes. Alanine uptake into astrocytes was largely mediated by system L isoform LAT2, whereas alanine uptake into neurons was mediated by Na+-dependent transporters with properties similar to system B0 isoform B0AT2. To investigate the role of alanine transport in metabolism, its uptake was inhibited in cortical tissue slices under depolarizing conditions using the system L transport inhibitors 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid and cycloleucine (1-aminocyclopentanecarboxylic acid; cLeu). The results indicated that alanine cycling occurs subsequent to glutamate/glutamine cycling and that a significant proportion of cycling occurs via amino acid transport system L. Our results show that system L isoform LAT2 is critical for alanine uptake into astrocytes. However, alanine does not provide any significant carbon for energy or neurotransmitter metabolism under the conditions studied

Alanine metabolism, transport, and cycling in the brain

Brain glutamate/glutamine cycling is incomplete without return of ammonia to glial cells. Previous studies suggest that alanine is an important carrier for ammonia transfer. In this study, we investigated alanine transport and metabolism in Guinea pig brain cortical tissue slices and prisms, in primary cultures of neurons and astrocytes, and in synaptosomes. Alanine uptake into astrocytes was largely mediated by system L isoform LAT2, whereas alanine uptake into neurons was mediated by Na+-dependent transporters with properties similar to system B0 isoform B0AT2. To investigate the role of alanine transport in metabolism, its uptake was inhibited in cortical tissue slices under depolarizing conditions using the system L transport inhibitors 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid and cycloleucine (1-aminocyclopentanecarboxylic acid; cLeu). The results indicated that alanine cycling occurs subsequent to glutamate/glutamine cycling and that a significant proportion of cycling occurs via amino acid transport system L. Our results show that system L isoform LAT2 is critical for alanine uptake into astrocytes. However, alanine does not provide any significant carbon for energy or neurotransmitter metabolism under the conditions studied. © 2007 The Authors

PHarmacist Avoidance or Reductions in Medical Costs in Patients Presenting the EMergency Department: PHARM-EM Study

Objectives:. To comprehensively classify interventions performed by emergency medicine clinical pharmacists and quantify cost avoidance generated through their accepted interventions. Design:. A multicenter, prospective, observational study was performed between August 2018 and January 2019. Setting:. Community and academic hospitals in the United States. Participants:. Emergency medicine clinical pharmacists. Interventions:. Recommendations classified into one of 38 intervention categories associated with cost avoidance. Measurements and Main Results:. Eighty-eight emergency medicine pharmacists at 49 centers performed 13,984 interventions during 917 shifts that were accepted on 8,602 patients and generated $7,531,862 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established categories were as follows: adverse drug event prevention (1,631 interventions;$2,225,049 cost avoidance), resource utilization (628; $310,582), individualization of patient care (6,122;$1,787,170), prophylaxis (24; $22,804), hands-on care (3,533;$2,836,811), and administrative/supportive tasks (2,046; $342,881). Mean cost avoidance was$538.61 per intervention, $875.60 per patient, and$8,213.59 per emergency medicine pharmacist shift. The annualized cost avoidance from an emergency medicine pharmacist was $1,971,262. The monetary cost avoidance to pharmacist salary ratio was between$1.4:1 and $10.6:1. Conclusions:. Pharmacist involvement in the care of patients presenting to the emergency department results in significant avoidance of healthcare costs, particularly in the areas of hands-on care and adverse drug event prevention. The potential monetary benefit-to-cost ratio for emergency medicine pharmacists is between$1.4:1 and $10.6:1

Proceedings of the 4th World Conference on Research Integrity

CITATION: O’Brien, S. P., et al. 2016. Proceedings of the 4th World Conference on Research Integrity. Research Integrity and Peer Review, 1:9, doi:10.1186/s41073-016-0012-9.The original publication is available at https://researchintegrityjournal.biomedcentral.comThese Proceedings contain the abstracts of the presentations given at the 4th World Conference in concurrent sessions, partner symposia, and poster sessions. Also included are summaries of the discussions in three focus tracks, which allowed delegates to consider and work on questions about the roles of funders, institutions, and countries in improving research systems and strengthening research integrity. Videos of the plenary presentations are available at the conference website (www.wcri2015.org).https://researchintegrityjournal.biomedcentral.com/articles/10.1186/s41073-016-0012-