MICROELECTRODE ARRAY FOR CAPACITIVE TRANSDUCTION OF RETINAL RESPONSES

Neural degenerative diseases and traumatic injuries to the eye affect millions of people worldwide, motivating the development of neural prosthetic interfaces to restore sensory or motor function in affected individuals. Advances in neural sensing and stimulation interface technology will allow a more comprehensive understanding of neural function while leading to the development of hybrid biological-electronic sensor devices for robust, functioning neural prosthetic systems. Current techniques of neural activity sensing employ multi-electrode arrays (MEAs) that typically incorporate metal electrodes and measure currents via an electrochemical junction, leading to corrosion and charge transfer across the electrode-tissue interface. High-density neural interface technology will require active circuitry within the implant; the device must withstand corrosion and induce minimal damage at the electrode/tissue interface. The work shown here demonstrates a prototype neural interface device based on capacitive coupling through hafnium oxide encapsulation of a novel 3D device architecture, advancing neural sensing technology toward long-term implantable neural interfaces. The functionalization of biosensors interfaced with neural tissue is important to ensure that the active components of the sensor are fully protected from the surrounding biological environment. Self-assembled monolayers (SAMs) have been extensively studied as coatings for implantable devices due to their ability to tailor surface properties and relative ease of film formation. We report a series of studies aimed at investigating the stability of phosphonate self-assembled monolayers, octdecylphosphonic acid (ODPA) or perfluorophosphonic acid (PFPA) on various oxide surfaces (SiO2, TiO2, Al2O3 and HfO2) to serve as the biotic-abiotic interface of the prototype neural device developed here. The monolayers were deposited by a series of techniques including self-assembly from solution, tethering by aggregation and growth and Langmuir-Blodgett (LB). SAMs prepared by LB were primarily used in our stability investigations because they were found to be the most uniform and reproducible. All films deposited on oxide-coated substrates were characterized by means of water contact angle measurements, spectroscopic ellipsometry, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). XPS data conclusively showed covalent phosphonate formation on all substrates except SiO2, which had background spectra that interfered with the data analysis. AFM images of SAMs formed on SiO2 and TiO2 showed significant surface reorganization upon exposure to water within 30 minutes. SAMs formed on Al2O3 and HfO2 were much more stable upon exposure to water. PFPA SAMs on HfO2 were found to be the most stable SAMs studied here in either water or phosphate buffer at room temperature. This is the first report of a SAM-oxide system showing stability for an extended period of time, greater than 20 days. These data suggest that phosphonate SAMs should be considered for implantable neural devices that require longer-term stability under aqueous conditions. To examine the encoding and processing of information by networks of neurons, microelectrode arrays (MEAs) have been developed and applied, but evolving scientific questions and biomedical applications require higher density sampling and wider spatial coverage. The integration of 3D electrodes can provide closer contact with neurons to facilitate detection and resolution of single cell action potentials. The fabrication methods implemented here allows reliable fabrication of a novel MEA consisting of probes with dimensions of a few microns, unlike most other approaches to 3D electrode arrays, which produce structures on the scale of tens of microns or more. The device incorporates over 3,800 micro pillar electrodes, grouped into 60 independent sensors for compatibility with existing electronics, spread over an area of 750 μm2; each sensor site consists of an 8x8 array of micropillars, interconnected by a lead to an output pad of the device. Individual 3D pillars are 3 μm in diameter with a height of 8 μm. Our experience has suggested that such microstructured probes can achieve more intimate contact with the surface of neural tissue, and enhance the quality of neuronal recordings. Electrochemical impedance spectroscopy (EIS) at 1 kHz measured average magnitude and phase shift of 710 W and 17°, respectively, for a single sensor site. These values confirm the robustness of our fabrication process for developing highly conductive 3D microelectrodes. The results shown here demonstrate high-density, three-dimensional microfabrication technology that was applied to the development of an advanced capacitive sensor array for neural tissue. Applications in sensing technology now require electro-neural interface devices to withstand corrosion and induce minimal damage at the electrode/tissue interface. We have developed a platform suitable for hermetic sealing and have shown encapsulation through atomic layer deposition of hafnium oxide over the active components of the device to overcome the direct current limitations of existing MEA technology. EIS was used to study the oxide deposition on the 3D micro pillar sensor array to ensure a pinhole-free dielectric coating. The characteristic impedance magnitudes increase up to 3 orders of magnitude upon oxide deposition and the phase indicates fully capacitive sensor sites. The fabrication process and electrochemical impedance study shown here, demonstrates the usefulness of such techniques for building high-density 3D arrays that can be fully encapsulated with a protective dielectric coating. This work advances the technology towards capacitive sensing of retinal neurons with a robust, non-invasive sensing device. Sensing retinal neurons with the 3D micropillar array developed here was performed for direct current and capacitive configurations of the device. Electroretinograms (ERGs) were recorded and the overall performance of the device was analyzed. The devices showed good consistency across all 60 Pt electrode clusters during characterization and when interfaced with retinal tissue. ERGs were recorded by more than 80% of the direct current electrode sites and the performance was evenly distributed around the mean response. This performance surpasses previous reports of 3D electrode arrays interfaced with retinal tissue, where typically 1-6 electrode signals are recorded successfully. Encapsulation of the device platform was achieved and successful recordings of ERG signals were shown. This work is the first report of sensing the overall electrical behavior of retinal tissue with a coupled capacitive MEA

Circumpolar Diversity and Geographic Differentiation of mtDNA in the Critically Endangered Antarctic Blue Whale (Balaenoptera musculus intermedia)

To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work.\ud This is the publisher’s final pdf. The published article is copyrighted by the Public Library of Science and can be found at: http://www.plosone.org/home.action.The Antarctic blue whale (Balaenoptera musculus intermedia) was hunted to near extinction between 1904 and 1972, declining from an estimated initial abundance of more than 250,000 to fewer than 400. Here, we describe mtDNA control region diversity and geographic differentiation in the surviving population of the Antarctic blue whale, using 218 biopsy samples collected under the auspices of the International Whaling Commission (IWC) during research cruises from 1990-2009. Microsatellite genotypes and mtDNA sequences identified 166 individuals among the 218 samples and documented movement of a small number of individuals, including a female that traveled at least 6,650 km or 131 degrees longitude over four years. mtDNA sequences from the 166 individuals were aligned with published sequences from 17 additional individuals, resolving 52 unique haplotypes from a consensus length of 410 bp. From this minimum census, a rarefaction analysis predicted that only 72 haplotypes (95% CL, 64, 86) have survived in the contemporary population of Antarctic blue whales. However, haplotype diversity was relatively high (0.968 +/- 0.004), perhaps as a result of the longevity of blue whales and the relatively recent timing of the bottleneck. Despite the potential for circumpolar dispersal, we found significant differentiation in mtDNA diversity (F-ST = 0.032, p<0.005) and microsatellite alleles (F-ST = 0.005, p<0.05) among the six Antarctic Areas historically used by the IWC for management of blue whales

Circumpolar Diversity and Geographic Differentiation of mtDNA in the Critically Endangered Antarctic Blue Whale (Balaenoptera musculus intermedia)

The Antarctic blue whale (Balaenoptera musculus intermedia) was hunted to near extinction between 1904 and 1972, declining from an estimated initial abundance of more than 250,000 to fewer than 400. Here, we describe mtDNA control region diversity and geographic differentiation in the surviving population of the Antarctic blue whale, using 218 biopsy samples collected under the auspices of the International Whaling Commission (IWC) during research cruises from 1990-2009. Microsatellite genotypes and mtDNA sequences identified 166 individuals among the 218 samples and documented movement of a small number of individuals, including a female that traveled at least 6,650 km or 131 degrees longitude over four years. mtDNA sequences from the 166 individuals were aligned with published sequences from 17 additional individuals, resolving 52 unique haplotypes from a consensus length of 410 bp. From this minimum census, a rarefaction analysis predicted that only 72 haplotypes (95% CL, 64, 86) have survived in the contemporary population of Antarctic blue whales. However, haplotype diversity was relatively high (0.968 +/- 0.004), perhaps as a result of the longevity of blue whales and the relatively recent timing of the bottleneck. Despite the potential for circumpolar dispersal, we found significant differentiation in mtDNA diversity (F-ST = 0.032, p<0.005) and microsatellite alleles (F-ST = 0.005, p<0.05) among the six Antarctic Areas historically used by the IWC for management of blue whales

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154675/1/art41191.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154675/2/art41191_am.pd

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

MICROELECTRODE ARRAY FOR CAPACITIVE TRANSDUCTION OF RETINAL RESPONSES

Neural degenerative diseases and traumatic injuries to the eye affect millions of people worldwide, motivating the development of neural prosthetic interfaces to restore sensory or motor function in affected individuals. Advances in neural sensing and stimulation interface technology will allow a more comprehensive understanding of neural function while leading to the development of hybrid biological-electronic sensor devices for robust, functioning neural prosthetic systems. Current techniques of neural activity sensing employ multi-electrode arrays (MEAs) that typically incorporate metal electrodes and measure currents via an electrochemical junction, leading to corrosion and charge transfer across the electrode-tissue interface. High-density neural interface technology will require active circuitry within the implant; the device must withstand corrosion and induce minimal damage at the electrode/tissue interface. The work shown here demonstrates a prototype neural interface device based on capacitive coupling through hafnium oxide encapsulation of a novel 3D device architecture, advancing neural sensing technology toward long-term implantable neural interfaces. The functionalization of biosensors interfaced with neural tissue is important to ensure that the active components of the sensor are fully protected from the surrounding biological environment. Self-assembled monolayers (SAMs) have been extensively studied as coatings for implantable devices due to their ability to tailor surface properties and relative ease of film formation. We report a series of studies aimed at investigating the stability of phosphonate self-assembled monolayers, octdecylphosphonic acid (ODPA) or perfluorophosphonic acid (PFPA) on various oxide surfaces (SiO2, TiO2, Al2O3 and HfO2) to serve as the biotic-abiotic interface of the prototype neural device developed here. The monolayers were deposited by a series of techniques including self-assembly from solution, tethering by aggregation and growth and Langmuir-Blodgett (LB). SAMs prepared by LB were primarily used in our stability investigations because they were found to be the most uniform and reproducible. All films deposited on oxide-coated substrates were characterized by means of water contact angle measurements, spectroscopic ellipsometry, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). XPS data conclusively showed covalent phosphonate formation on all substrates except SiO2, which had background spectra that interfered with the data analysis. AFM images of SAMs formed on SiO2 and TiO2 showed significant surface reorganization upon exposure to water within 30 minutes. SAMs formed on Al2O3 and HfO2 were much more stable upon exposure to water. PFPA SAMs on HfO2 were found to be the most stable SAMs studied here in either water or phosphate buffer at room temperature. This is the first report of a SAM-oxide system showing stability for an extended period of time, greater than 20 days. These data suggest that phosphonate SAMs should be considered for implantable neural devices that require longer-term stability under aqueous conditions. To examine the encoding and processing of information by networks of neurons, microelectrode arrays (MEAs) have been developed and applied, but evolving scientific questions and biomedical applications require higher density sampling and wider spatial coverage. The integration of 3D electrodes can provide closer contact with neurons to facilitate detection and resolution of single cell action potentials. The fabrication methods implemented here allows reliable fabrication of a novel MEA consisting of probes with dimensions of a few microns, unlike most other approaches to 3D electrode arrays, which produce structures on the scale of tens of microns or more. The device incorporates over 3,800 micro pillar electrodes, grouped into 60 independent sensors for compatibility with existing electronics, spread over an area of 750 µm2; each sensor site consists of an 8x8 array of micropillars, interconnected by a lead to an output pad of the device. Individual 3D pillars are 3 µm in diameter with a height of 8 µm. Our experience has suggested that such microstructured probes can achieve more intimate contact with the surface of neural tissue, and enhance the quality of neuronal recordings. Electrochemical impedance spectroscopy (EIS) at 1 kHz measured average magnitude and phase shift of 710 W and 17°, respectively, for a single sensor site. These values confirm the robustness of our fabrication process for developing highly conductive 3D microelectrodes. The results shown here demonstrate high-density, three-dimensional microfabrication technology that was applied to the development of an advanced capacitive sensor array for neural tissue. Applications in sensing technology now require electro-neural interface devices to withstand corrosion and induce minimal damage at the electrode/tissue interface. We have developed a platform suitable for hermetic sealing and have shown encapsulation through atomic layer deposition of hafnium oxide over the active components of the device to overcome the direct current limitations of existing MEA technology. EIS was used to study the oxide deposition on the 3D micro pillar sensor array to ensure a pinhole-free dielectric coating. The characteristic impedance magnitudes increase up to 3 orders of magnitude upon oxide deposition and the phase indicates fully capacitive sensor sites. The fabrication process and electrochemical impedance study shown here, demonstrates the usefulness of such techniques for building high-density 3D arrays that can be fully encapsulated with a protective dielectric coating. This work advances the technology towards capacitive sensing of retinal neurons with a robust, non-invasive sensing device. Sensing retinal neurons with the 3D micropillar array developed here was performed for direct current and capacitive configurations of the device. Electroretinograms (ERGs) were recorded and the overall performance of the device was analyzed. The devices showed good consistency across all 60 Pt electrode clusters during characterization and when interfaced with retinal tissue. ERGs were recorded by more than 80% of the direct current electrode sites and the performance was evenly distributed around the mean response. This performance surpasses previous reports of 3D electrode arrays interfaced with retinal tissue, where typically 1-6 electrode signals are recorded successfully. Encapsulation of the device platform was achieved and successful recordings of ERG signals were shown. This work is the first report of sensing the overall electrical behavior of retinal tissue with a coupled capacitive MEA.Los Alamos National Laboratory LDRD, NSF CAREER (CBET 0844645)Nanoscience and Microsystems EngineeringDoctoralUniversity of New Mexico. Nanoscience and Microsystems ProgramPetsev, DimiterDattelbaum, AndrewSibbett, ScottGraves, Steve

Necrotizing Enterocolitis: A Narrative Review of Updated Therapeutic and Preventive Interventions

Context Necrotizing enterocolitis (NEC) remains one of the most common causes of morbidity and mortality for premature infants in the neonatal intensive care unit (NICU). Many theories concerning its pathophysiology and inciting factors have been suggested but progression in preventing the onset of NEC has been minimal. While this article highlights the pathophysiology, management, and outcomes of NEC, it mainly serves as a narrative review to discuss the emerging methods of treatment and prevention. Evidence Acquisition A literature search was done using Medline/Pub Med, Cochrane Database of Systematic Reviews via Ovid, and CINAHL Complete with focus on articles published between 2000 and 2016. Searched terms included the following: necrotizing enterocolitis, pathogenesis, prevention, management, breast milk, formula, probiotics, prebiotics, and treatment. Results Intestinal barrier dysfunction, hypoxic ischemic injury, receipt of packed red blood cells, immature intestinal immunity and alterations of the gut microbiome of the premature infant were reviewed factors that have been studied related to the pathophysiology of NEC. The presentation, staging and management remain relatively unchanged in the last few decades, though there have been a few studies evaluating different surgical options, various antibacterial regimen, and recently use of moderate hypothermia and amniotic fluid stem cells to treat NEC. Use of breast milk, use of pre-, pro- and postbiotics show promise in the prevention of NEC. Conclusions NEC is a likely multifactorial illness of the gastrointestinal tract affecting mostly premature infants. Recent studies have focused on preventative strategies, with promise in pre-, pro- and postbiotics; however continued research is imperative

Sremba_AntBmu_410_52

Alignment of 52 Antarctic blue whale mtDNA control region haplotypes described from 410 bp in Sremba et al. 2012. File contains key for lab ID codes and GenBank codes for each haplotype not described in LeDuc et al. 2007