Development of Tools and Techniques for Processing STORRM Flight Data

While at JSC for the summer of 2011, I was assigned to work on the sensor test for Orion relative-navigation risk mitigation (STORRM) development test objective (DTO). The STORRM DTO was flown on-board Endeavor during STS-134. The objective of the STORRM DTO is to test the visual navigation system (VNS), which will be used as the primary relative navigation sensor for the Orion spacecraft. The VNS is a flash lidar system intended to provide both line of sight and range information during rendezvous and proximity operations. The STORRM DTO also serves as a testbed for the high-resolution docking camera. This docking camera will be used to provide piloting cues for the crew during proximity operations. These instruments were mounted next to the trajectory control sensor (TCS) in Endeavour s payload bay. My principle objective for the summer was to generate a best estimated trajectory (BET) for Endeavor using the flight data collected by the VNS during rendezvous and the unprecedented re-rendezvous with the ISS. I processed the raw images from the VNS to produce range and bearing measurements. I then aggregated these measurements and extracted the measurements corresponding to individual reflectors. I combined the information contained in these measurements with data from the Endeavour's inertial sensors using Kalman smoothing techniques to ultimately produce a BET. This work culminated with a final presentation of the result to division management. Development of this tool required that traditional linear smoothing techniques be modified in a novel fashion to permit for the inclusion of non-linear measurements. This internship has greatly helped me further my career by providing exposure to real engineering projects. I also have benefited immensely from the mentorship of the engineers working on these projects. Many of the lessons I learned and experiences I had are of particular value because then can only be found in a place like JSC

Procalcitonin and Other Common Biomarkers Do Not Reliably Identify Patients at Risk for Bacterial Infection After Congenital Heart Surgery

Objectives: Following surgery, it is difficult to distinguish a postoperative inflammatory reaction from infection. This study examined the predictive value of the biomarkers; procalcitonin, C-reactive protein, lactate, neutrophils, lymphocytes, platelets, and the biphasic activated partial thromboplastin time waveform in diagnosing bacterial infection following cardiac surgery. Design: Prospective, observational study. Setting: A regional, PICU in the United Kingdom. Patients: Three-hundred sixty-eight children under the age of 16 admitted to the PICU for elective cardiac surgery were enrolled in the study. Interventions: All biomarker measurements were determined daily until postoperative day 7. Children were assessed for postoperative infection until day 28 and divided into four groups: bacterial infection, culture-negative sepsis, viral infection, and no infection. We used the Kruskal-Wallis test, chi-square test, analysis of variance, and area under the curve in our analysis. Measurements and Main Results: In total, 71 of 368 children (19%) developed bacterial infection postoperatively, the majority being surgical site infections. In those with bacterial infection, procalcitonin was elevated on postoperative days 1–3 and the last measurement prior to event compared with those without bacterial infection. The most significant difference was the last measurement prior to event; 0.72 ng/mL in the bacterial infection group versus 0.13 ng/mL in the no infection group (for all groups; p and#60; 0.001). Longitudinal profiles of all biomarkers were indistinct in the bacterial infection and nonbacterial infection groups except in those with culture-negative infections who had distinct procalcitonin kinetics on postoperative days 1–4. Children with culture-negative sepsis required longer ventilatory support and PICU stay and were more likely to develop complications than the other groups. Conclusions: None of the biomarkers studied within 3 days of infection distinguished between infection and postoperative inflammatory reaction. However, procalcitonin kinetics peaked on postoperative day 2 and fell more sharply than C-reactive protein kinetics, which peaked at postoperative day 3. The monitoring of procalcitonin kinetics following cardiac surgery may help guide rational antimicrobial use

Ventral striatum dopamine release encodes unique properties of visual stimuli in mice

The mesolimbic dopamine system is an evolutionarily conserved set of brain circuits that play a role in attention, appetitive behavior, and reward processing. In this circuitry, ascending dopaminergic projections from the ventral midbrain innervate targets throughout the limbic forebrain, such as the ventral striatum/nucleus accumbens (NAc). Dopaminergic signaling in the NAc has been widely studied for its role in behavioral reinforcement, reward prediction error encoding, and motivational salience. Less well characterized is the role of dopaminergic neurotransmission in the response to surprising or alerting sensory events. To address this, we used the genetically encoded dopamine sensor dLight1 and fiber photometry to explore the ability of striatal dopamine release to encode the properties of salient sensory stimuli in mice, such as threatening looming discs. Here, we report that lateral NAc (LNAc) dopamine release encodes the rate and magnitude of environmental luminance changes rather than the visual stimulus threat level. This encoding is highly sensitive, as LNAc dopamine could be evoked by light intensities that were imperceptible to human experimenters. We also found that light-evoked dopamine responses are wavelength-dependent at low irradiances, independent of the circadian cycle, robust to previous exposure history, and involve multiple phototransduction pathways. Thus, we have further elaborated the mesolimbic dopamine system’s ability to encode visual information in mice, which is likely relevant to a wide body of scientists employing light sources or optical methods in behavioral research involving rodents

Diurnal regulation of metabolism by Gs-alpha in hypothalamic QPLOT neurons.

Neurons in the hypothalamic preoptic area (POA) regulate multiple homeostatic processes, including thermoregulation and sleep, by sensing afferent input and modulating sympathetic nervous system output. The POA has an autonomous circadian clock and may also receive circadian signals indirectly from the suprachiasmatic nucleus. We have previously defined a subset of neurons in the POA termed QPLOT neurons that are identified by the expression of molecular markers (Qrfp, Ptger3, LepR, Opn5, Tacr3) that suggest receptivity to multiple stimuli. Because Ptger3, Opn5, and Tacr3 encode G-protein coupled receptors (GPCRs), we hypothesized that elucidating the G-protein signaling in these neurons is essential to understanding the interplay of inputs in the regulation of metabolism. Here, we describe how the stimulatory Gs-alpha subunit (Gnas) in QPLOT neurons regulates metabolism in mice. We analyzed Opn5cre; Gnasfl/fl mice using indirect calorimetry at ambient temperatures of 22°C (a historical standard), 10°C (a cold challenge), and 28°C (thermoneutrality) to assess the ability of QPLOT neurons to regulate metabolism. We observed a marked decrease in nocturnal locomotion of Opn5cre; Gnasfl/fl mice at both 28°C and 22°C, but no overall differences in energy expenditure, respiratory exchange, or food and water consumption. To analyze daily rhythmic patterns of metabolism, we assessed circadian parameters including amplitude, phase, and MESOR. Loss-of-function GNAS in QPLOT neurons resulted in several subtle rhythmic changes in multiple metabolic parameters. We observed that Opn5cre; Gnasfl/fl mice show a higher rhythm-adjusted mean energy expenditure at 22°C and 10°C, and an exaggerated respiratory exchange shift with temperature. At 28°C, Opn5cre; Gnasfl/fl mice have a significant delay in the phase of energy expenditure and respiratory exchange. Rhythmic analysis also showed limited increases in rhythm-adjusted means of food and water intake at 22°C and 28°C. Together, these data advance our understanding of Gαs-signaling in preoptic QPLOT neurons in regulating daily patterns of metabolism

A three-dimensional computed tomography study to determine the ideal method for fluoroscopically-guided bone marrow aspiration from the iliac crest

Bone marrow aspiration (BMA) through the iliac crest is potentially unsafe due to the vicinity of neurovascular structures in the greater sciatic notch. Our objective was to investigate the safety of a recently described BMA technique, specifically a trajectory from the posterior superior iliac spine (PSIS) to the anterior inferior iliac spine (AIIS). We conducted a chart review of 260 patients, analyzing three-dimensional reconstructed computed tomography images of the pelvis and sacrum to validate that this new approach offers a wide safety margin from the greater sciatic notch. Analysis of three-dimensional computed tomography scans demonstrated that the PSIS to AIIS trajectory never crossed the greater sciatic notch. The trajectory was noted to be at least one cm away from the greater sciatic notch in all measurements. The new trajectory entered the PSIS at 25.29 ± 4.34° (left side) and 24.93 ± 4.15° (right side) cephalad from the transverse plane, and 24.58 ± 4.99° (left side) and 24.56 ± 4.67° (right side) lateral from the mid-sagittal plane. The area of bone marrow encountered with the new approach was approximately 22.5 cm2. Utilizing the same CT scans, the trajectory from the traditional approach crossed the greater sciatic notch in all scans, highlighting the potential for violating the greater sciatic notch boundary and damaging important neurovascular structures. Statistically significant sex-related differences were identified in needle trajectory angles for both approaches. We conclude that based on this three-dimensional computed tomography study, a trajectory from the PSIS to the AIIS for BMA may offer a wide safety margin from the greater sciatic notch

A Phase I First-in-Human Study of ABBV-383, a B-Cell Maturation Antigen × CD3 Bispecific T-Cell Redirecting Antibody, in Patients With Relapsed/Refractory Multiple Myeloma

PurposeABBV-383, a B-cell maturation antigen × CD3 T-cell engaging bispecific antibody, has demonstrated promising results in an ongoing first-in-human phase I study (ClinicalTrials.gov identifier: NCT03933735) in patients with relapsed/refractory multiple myeloma (RRMM). Herein, we report safety and efficacy outcomes of this phase I dose escalation/expansion study.MethodsPatients with RRMM (≥ three prior lines including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody) were eligible. ABBV-383 was administered intravenously over 1-2 hours once every 3 weeks, without any step dosing. A 3 + 3 design with backfilling for dose escalation was used (intrapatient escalation to highest safe dose permitted) followed by initiation of dose expansion.ResultsAs of January 8, 2022, 124 patients (dose escalation [0.025-120 mg], n = 73; dose expansion [60 mg], n = 51) have received ABBV-383; median age was 68 years (range, 35-92 years). The most common hematologic treatment-emergent adverse events (TEAEs) were neutropenia (all grades: 37%) and anemia (29%). The most common nonhematologic TEAEs were cytokine release syndrome (57%) and fatigue (30%). Seven deaths from TEAEs were reported with all considered unrelated to study drug by the investigator. For all efficacy-evaluable patients (n = 122; all doses), the objective response rate (ORR) was 57% and very good partial response (VGPR) or better (≥ VGPR) rate was 43%. In the 60 mg dose expansion cohort (n = 49), the ORR and ≥ VGPR rates were 59% and 39%, respectively; and in the ≥ 40 mg dose escalation plus dose expansion cohorts (n = 79) were 68% and 54%, respectively.ConclusionABBV-383 in patients with RRMM was well tolerated with an ORR of 68% at doses ≥ 40 mg. This novel therapy's promising preliminary antitumor activity in heavily pretreated patients warrants further clinical evaluation