Fostering Diversity and Inclusion in the National Heart, Lung, and Blood Institute's Small Business Program.

The National Heart, Lung, and Blood Institute has developed a strategic approach to fostering diversity and inclusion within its community of small business innovators. The approach is focused on three central goals: 1) Increase awareness of NHLBI's support for small businesses among underrepresented groups through focused outreach; 2) Identify and eliminate barriers to entry into small business funding programs and entrepreneurial activities for minority and female applicants through specific, targeted training and support; and 3) Expand diversity and inclusivity within our networks by providing additional support for NHLBI-funded small businesses to hire members of underrepresented groups. Key partnerships with biomedical accelerators in underserved regions will be leveraged to maximize impact and achieve all three goals. This article describes the historical context and current state of policies in this arena; it also provides details about mechanisms and approaches used to achieve the goals.

Growth and Development at the Sphenoethmoidal Junction in Perinatal Primates.

Integration of the sphenoid and ethmoid bones during early postnatal development is poorly described in the literature. A uniquely prolonged patency of sphenoethmoidal synchondrosis or prespheno-septal synchondrosis (PSept) has been attributed to humans. However, the sphenoethmoidal junction has not been studied using a comparative primate sample. Here, we examined development of the sphenoethmoidal interface using ontogenetic samples of Old and New World monkeys, strepsirrhine primates (lemurs and lorises), and a comparative sample of other mammals. Specimens ranging from late fetal to 1 month postnatal age were studied using histology, immunohistochemistry, and micro-computed tomography methods. Our results demonstrate that humans are not unique in anterior cranial base growth at PSept, as it is patent in all newborn primates. We found two distinctions within our sample. First, nearly all primates exhibit an earlier breakdown of the nasal capsule cartilage that abuts the orbitosphenoid when compared to nonprimates. This may facilitate earlier postnatal integration of the basicranium and midface and may enhance morphological plasticity in the region. Second, the PSept exhibits a basic dichotomy between strepsirrhines and monkeys. In strepsirrhines, the PSept has proliferating chondrocytes that are primarily oriented in a longitudinal plane, as in other mammals. In contrast, monkeys have a convex anterior end of the presphenoid with a radial boundary of cartilaginous growth at PSept. Our findings suggest that the PSept acts as a "pacemaker" of longitudinal facial growth in mammals with relatively long snouts, but may also contribute to facial height and produce a relatively taller midface in anthropoid primates. Anat Rec, 300:2115-2137, 2017. © 2017 Wiley Periodicals, Inc.

Electromyographic analysis of muscle activation during sit-and-reach flexibility tests.

The sit-and-reach test (SRT) has been included in standard fitness test batteries for decades, but empirical evidence of actual muscle activity has been lacking. Furthermore, the positioning of the ankle joint during the execution of this test has received relatively scant attention. Therefore, the purpose of this investigation was to compare surface electromyographic (sEMG) activity of selected lower extremity and back musculature and examine the impact of ankle positioning during the standard SRT and the modified sit-and-reach test (MSRT). Seven male and 7 female subjects performed 3 trials of the SRT and MSRT, each in a dorsiflexed and plantar flexed ankle position. During all trials, muscle activity (sEMG) was measured from the right semimembranous (SM), erector spinae (ES), and gastrocnemius (G). Mean sEMG data from each muscle (SM, ES, and G) were normalized by being expressed as a percent contribution to the total electrical activity (100%). Surface electromyographic activity data were also used to determine muscle activation ratios (e.g., SM to ES). Results revealed significantly higher flexibility scores during the plantar flexion condition for both test modalities. The SM exhibited the greatest percent contribution to total sEMG activity within all testing conditions. The SM to G and SM to ES muscle activation ratios were significantly greater than their inverse counterparts within all 4 testing conditions. Based on the 2 sEMG analysis techniques, the SM seemed to exhibit the greatest muscle activity. This investigation provides direct evidence of sEMG muscle activity during the SRT and MSRT, further confirming these tests to be a valid measure of hamstring flexibility.

The Detection of Motion by Blind Subjects With the Epiretinal 60-Electrode (Argus II) Retinal Prosthesis.

OBJECTIVE: To investigate the ability of 28 blind subjects implanted with a 60-electrode Argus II (Second Sight Medical Products Inc) retinal prosthesis system to detect the direction of a moving object. METHODS: Blind subjects (bare light perception or worse in both eyes) with retinitis pigmentosa were implanted with the Argus II prosthesis as part of a phase 1/2 feasibility study at multiple clinical sites worldwide. The experiment measured their ability to detect the direction of motion of a high-contrast moving bar on a flatscreen monitor in 3 conditions: with the prosthesis system on and a 1-to-1 mapping of spatial information, with the system off, and with the system on but with randomly scrambled spatial information. RESULTS: Fifteen subjects (54%) were able to perform the task significantly better with their prosthesis system than they were with their residual vision, 2 subjects had significantly better performance with their residual vision, and no difference was found for 11 subjects. Of the 15 better-performing subjects, 11 were available for follow-up testing, and 10 of them had significantly better performance with normal rather than with scrambled spatial information. CONCLUSIONS: This work demonstrates that blind subjects implanted with the Argus II retinal prosthesis were able to perform a motion detection task they could not do with their native vision, confirming that electrical stimulation of the retina provides spatial information from synchronized activation of multiple electrodes. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT00407602

What is an appropriate reference standard in the quantitation of plaque surface area by intravascular coronary ultrasound?

We reevaluate the predictive accuracy of intravascular ultrasound (IVUS)-derived per cent plaque area stenosis (PAS) in significant coronary lesions (CLs) with or without proximal and distal reference vessel area adjustment. IVUS is valuable in defining moderate CL severity (30 to 70%) in left main (LM) or non-left main (NLM) coronaries using minimum luminal area (MLA) of ≤5.9 and ≤4 mm(2), respectively. Despite a strong correlation with severe CLs, PAS (≥ 70% for NLM and ≥67% for LM) remains underutilized because of confusion about an appropriate reference standard. We studied 120 patients with symptomatic moderate CLs (74 NLM, 46 LM) who underwent IVUS. In-lesion and adjusted PAS were derived by subtracting MLA from in-lesion and proximal or distal reference's external elastic membrane (EEM) area, respectively, divided by corresponding EEM area multiplied by 100. In-lesion PAS was correlated with MLA cutoffs of ≤5.9 and ≤7.5 mm(2) for LM and ≤4 mm(2) for NLM. Adjusted PAS strongly correlated with in-lesion PAS irrespective of reference segment (proximal reference, r = 0.879, p < 0.001; distal reference, r = 0.833, p < 0.001; mean proximal and distal reference, r = 0.896, p < 0.001). Considering MLA of ≤4 mm(2) (for NLM) and ≤5.9 mm(2) (for LM), in-lesion PAS of ≥70 and ≥67%, respectively, explained the majority of severe CLs but the sensitive LM MLA cutoff of ≤7.5 mm(2) showed higher predictive accuracy. Based on results, both in-lesion PAS and adjusted PAS can be used interchangeably and correlate strongly with MLA.

Preliminary 6 month results from the Argus II epiretinal prosthesis feasibility study.

The Argus II 60 channel epiretinal prosthesis has been developed in order to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. To date the device has been implanted in 21 subjects as part of a feasibility study. In 6 month post-implantation door finding and line tracking orientation and mobility testing, subjects have shown improvements of 86% and 73%, respectively, for system on vs. system off. In high-contrast Square Localization tests using a touch screen monitor 87% of tested subjects performed significantly better with the system on compared with off. These preliminary results show that the Argus II system provides some functional vision to blind subjects.

Brightness as a function of current amplitude in human retinal electrical stimulation.

PURPOSE: With the goal of eventually restoring functional vision in patients with retinal degenerative diseases, USC/Second Sight Medical Products, Inc. chronically implanted blind human subjects with a prototype epiretinal prosthesis consisting of a 4 x 4 array of 16 stimulating electrodes. To accurately represent a visual scene, a visual prosthesis must convey luminance information across a range of brightness levels. To achieve this, the brightness of phosphenes produced by an individual electrode should scale appropriately with luminance, and the same luminance should produce equivalently bright phosphenes across the entire electrode array. The goal was to examine how apparent brightness changes as a function of stimulation intensity across electrodes. METHODS: As described in previous studies, electrical stimulation of intact cells of the neural retina using this prosthetic device reliably elicits visual percepts in human subjects blinded by retinitis pigmentosa. Here, apparent brightness for a range of electrical amplitudes was measured using both subjective magnitude rating and brightness-matching procedures in chronically implanted human subjects. RESULTS: It was found that apparent brightness can be described as a power function of stimulation intensity. The same model can also predict brightness matching across electrodes. CONCLUSIONS: These results suggest that a relatively simple model for scaling current across electrodes may be capable of producing equivalently bright phosphenes across an entire array. (ClinicalTrials.gov number, NCT00279500.).

Feasibility study of a retinal prosthesis: spatial vision with a 16-electrode implant.

OBJECTIVE: To demonstrate that an epiretinal prosthesis can produce patterned visual perception in patients blinded by photoreceptor degeneration who have no other treatment options. METHODS: A totally blind subject with retinitis pigmentosa had a 16-electrode epiretinal prosthesis implanted. The implant is controlled wirelessly by an external computer or a head-mounted video camera. Spatial vision was assessed by measuring the subject's response to direct stimulation of patterns and by comparing the ability of the subject to identify the orientation of gratings with the system on and off. RESULTS: In response to stimulation of 2 orthogonal rows of electrodes, the subject drew 2 lines with a mean (SEM) angle of 87.4 degrees (1.8 degrees) between them. With the system on, the subject identified the orientation of the grating target up to a spatial resolution that matches the spacing between the adjacent electrodes. In contrast, with the system off, the subject could not detect or identify the target's orientation. CONCLUSION: Synchronized stimulation of different retinal locations with an epiretinal prosthesis implanted long-term can produce spatial vision with an acuity level determined by the distance between the electrodes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00279500.

Predicting visual sensitivity in retinal prosthesis patients.

PURPOSE: With the long-term goal of restoring functional vision in patients with retinal degenerative diseases, the eyes of blind human subjects were implanted chronically with epiretinal prostheses consisting of two-dimensional electrode arrays that directly stimulated cells of the neural retina. METHODS: Psychophysical techniques were used to measure the brightness of electrically generated percepts on single electrodes using a variety of electrical stimulation patterns. RESULTS: It was possible to predict the sensitivity of the human visual system to a wide variety of retinal electrical stimulation patterns using a simple and biologically plausible model. CONCLUSIONS: This is the first study to demonstrate that, on the single-electrode level, retinal electrical stimulation in humans can produce visual qualia that are predictable using a quantitative model, a prerequisite for a successful retinal prosthesis. (ClinicalTrials.gov number, NCT00279500.).

Factors affecting perceptual thresholds in epiretinal prostheses.

PURPOSE: The goal was to evaluate how perceptual thresholds are related to electrode impedance, electrode size, the distance of electrodes from the retinal surface, and retinal thickness in six subjects blind as a result of retinitis pigmentosa, who received epiretinal prostheses implanted monocularly as part of a U.S. Food and Drug Administration (FDA)-approved clinical trial. METHODS: The implant consisted of an extraocular unit containing electronics for wireless data, power recovery, and generation of stimulus current, and an intraocular unit containing 16 platinum stimulating electrodes (260- or 520-microm diameter) arranged in a 4 x 4 pattern. The electrode array was held onto the retina by a small tack. Stimulation was controlled by a computer-based external system that allowed independent control over each electrode. Perceptual thresholds (the current necessary to see a percept on 79% of trials) and impedance were measured for each electrode on a biweekly basis. The distance of electrodes from the retinal surface and retinal thickness were measured by optical coherence tomography on a less regular basis. RESULTS: Stimulation thresholds for detecting phosphenes correlated with the distance of the electrodes from the retinal surface, but not with electrode size, electrode impedance, or retinal thickness. CONCLUSIONS: Maintaining close proximity between the electrode array and the retinal surface is critical in developing a successful retinal implant. With the development of chronic electrode arrays that are stable and flush on the retinal surface, it is likely that the influence of other factors such as electrode size, retinal degeneration, and subject age will become more apparent. (ClinicalTrials.gov number, NCT00279500.).

Enhancement of biogenic sulfide production in a packed-bed bioreactor via critical inoculum design and carrier material selection.

Sulfate reducing bacteria (SRB) are commonly used in environmental bioprocesses for the treatment of acid mine drainage and sulfate wastewaters. Biogenic H(2)S is also a potential source of H(2) fuel with the recent development of H(2)S splitting technologies. In this study, a sulfate reducing packed bed bioreactor (PBR) capable of rapidly achieving high volumetric productivities was developed using a novel method of rational inoculum design and the selection of improved biomass carrier materials. An inoculum with initial composition of approximately 95% Desulfovibrio desulfuricans (ATCC 7757) and 5% SRB consortium was designed based on the pure strain's superior immobilization potential and the SRB consortium's superior kinetics. Diatomaceous earth (DE) pellets, porous glass beads, polyurethane foam and bone char were evaluated as potential biomass carrier materials. The DE pellets immobilized the most biomass and were employed in two packed bed bioreactor fermentations. Using the designed inoculum and DE pellets, a packed bed bioreactor achieved a volumetric productivity of 493 mol H(2)S m(-3) day(-1) (based on a 308 mL working volume) with a dissolved sulfide concentration of 9.9 mM. This occurred after 8.3 days of operation and represents a tenfold reduction in the start-up period compared to other sulfate reducing PBRs described in the literature.

Gas phase H(2)S product recovery in a packed bed bioreactor with immobilized sulfate-reducing bacteria.

An N(2) strip gas was used in a packed bed sulfate-reducing bioreactor to recover the dissolved sulfide product and improve sulfate conversion. The highest volumetric productivity obtained was 261 mol H(2)S m(-3) d(-1). Lowering the initial pH of the medium from 7 to 6 increased the H(2)S content of the strip gas from 3.6 to 5.8 mol%. The ratio of strip gas to liquid flow rates (G/L) was found be to a suitable basis for scaling the process. Calculations indicated that modest G/L values (<10(2)) were required to recover the residual dissolved sulfide in a downstream stripping column.

The classical receptive field surround of primate parasol ganglion cells is mediated primarily by a non-GABAergic pathway.

Although the center-surround receptive field is a fundamental property of retinal ganglion cells, the circuitry that mediates surround inhibition remains controversial. We examined the contribution of horizontal cells and amacrine cells to the surround of parasol ganglion cells of macaque and baboon retina by measuring receptive field structure before and during the application of drugs that have been shown previously to affect surrounds in a range of mammalian and nonmammalian species. Carbenoxolone and cobalt, thought to attenuate feedback from horizontal cells to cones, severely reduced the surround. Tetrodotoxin, which blocks sodium spiking in amacrine cells, and picrotoxin, which blocks the inhibitory action of GABA, only slightly reduced the surround. These data are consistent with the hypothesis that the surrounds of light-adapted parasol ganglion cells are generated primarily by non-GABAergic horizontal cell feedback in the outer retina, with a small contribution from GABAergic amacrine cells of the inner retina.

L and M cone contributions to the midget and parasol ganglion cell receptive fields of macaque monkey retina.

Analysis of cone inputs to primate parvocellular ganglion cells suggests that red-green spectral opponency results when connections segregate input from long wavelength (L) or middle wavelength (M) sensitive cones to receptive field centers and surrounds. However, selective circuitry is not an obvious retinal feature. Rather, cone receptive field surrounds and H1 horizontal cells get mixed L and M cone input, likely indiscriminately sampled from the randomly arranged cones of the photoreceptor mosaic. Red-green spectral opponency is consistent with random connections in central retina where the mixed cone ganglion cell surround is opposed by a single cone input to the receptive field center, but not in peripheral retina where centers get multiple cone inputs. The selective and random connection hypotheses might be reconciled if cone type selective circuitry existed in inner retina. If so, the segregation of L and M cone inputs to receptive field centers and surrounds would increase from horizontal to ganglion cell, and opponency would remain strong in peripheral retina. We measured the relative strengths of L and M cone inputs to H1 horizontal cells and parasol and midget ganglion cells by recording intracellular physiological responses from morphologically identified neurons in an in vitro preparation of the macaque monkey retina. The relative strength of L and M cone inputs to H1 and ganglion cells at the same locations matched closely. Peripheral midget cells were nonopponent. These results suggest that peripheral H1 and ganglion cells inherit their L and M cone inputs from the photoreceptor mosaic unmodified by selective circuitry.

The origin of the oblique effect examined with pattern adaptation and masking.

The decreased visibility of obliquely oriented patterns as compared to horizontal or vertical ones is termed the oblique effect. The origin of the oblique effect in the chain of visual processing was examined by comparing the potency of oblique adapting gratings to the potency of horizontal ones. Oblique gratings (which were less visible but of equal physical contrast) were as powerful or more powerful than horizontal gratings as adapting stimuli. Obliquely oriented stimuli also produced a slightly stronger tilt aftereffect than stimuli near the cardinal axes. These results suggest that the diminished neural representation of oblique stimuli arises in the human cortex, rather than from impairments of sensitivity or resolution in the initial geniculo-cortical projection.