The Ice, Cloud, and Land Elevation Satellite - 2 Mission: A Global Geolocated Photon Product Derived From the Advanced Topographic Laser Altimeter System.

The Ice, Cloud, and land Elevation Satellite - 2 (ICESat-2) observatory was launched on 15 September 2018 to measure ice sheet and glacier elevation change, sea ice freeboard, and enable the determination of the heights of Earth's forests. ICESat-2's laser altimeter, the Advanced Topographic Laser Altimeter System (ATLAS) uses green (532 nm) laser light and single-photon sensitive detection to measure time of flight and subsequently surface height along each of its six beams. In this paper, we describe the major components of ATLAS, including the transmitter, the receiver and the components of the timing system. We present the major components of the ICESat-2 observatory, including the Global Positioning System, star trackers and inertial measurement unit. The ICESat-2 Level 1B data product (ATL02) provides the precise photon round-trip time of flight, among other data. The ICESat-2 Level 2A data product (ATL03) combines the photon times of flight with the observatory position and attitude to determine the geodetic location (i.e. the latitude, longitude and height) of the ground bounce point of photons detected by ATLAS. The ATL03 data product is used by higher-level (Level 3A) surface-specific data products to determine glacier and ice sheet height, sea ice freeboard, vegetation canopy height, ocean surface topography, and inland water body height.

Fetal Myelomeningocele After Maternal Methotrexate Administration: A Case Report.

Background: Folate supplementation in women of reproductive age has a well-established role in the prevention of neural tube defects. Methotrexate is a commonly used drug which functions by inhibiting normal folate metabolism in active cells. An association between fetal methotrexate exposure and myelomeningocele might be expected, considering this relationship. However, to our knowledge, no cases of myelomeningocele secondary to in utero methotrexate exposure have been reported. Case: We present the case of a gravid patient who, having received methotrexate for management of an ectopic pregnancy, was lost to follow-up and returned several weeks later carrying an intrauterine pregnancy. The fetus was found prenatally to be suffering from multiple congenital anomalies. At birth the infant demonstrated many of the abnormalities commonly associated with fetal methotrexate syndrome, including craniosynostosis and talipes equinovarus. Most interestingly, the newborn was also diagnosed with a lumbar myelomeningocele and concomitant type II Chiari malformation, as is often associated with such a neural tube defect. Conclusion: Methotrexate exposure may impact the fetal risk of myelomeningocele. Patients should be counseled thoroughly on the importance of follow-up care.

Acidemia versus hypercapnia and risk for severe intraventricular hemorrhage.

In extremely low birth weight (ELBW) infants, levels of hypercapnia (Paco 2) > 60 mm Hg are considered a risk factor for severe intraventricular hemorrhage (IVH). Since cerebral vasoreactivity depends on arterial pH (apH) rather than Paco 2, we hypothesize that the role of mild-to-moderate hypercapnia (45-60 mm Hg) in the occurrence of severe IVH is modulated by the metabolic component of acid-base status. ELBW infants (n = 580, born < 28 wk gestation, and BW < 1,000 g) were separated into "high-base deficit (BD)" (n = 291) and "low-BD" (n = 289) groups if infants' median BD were > 4 mEq/L or ≤4 mEq/L, respectively. Rates of severe IVH were higher in "high-BD" (16%) than "low-BD" (9%) group. Although adjusted risk for severe IVH increased with higher Paco 2 and higher BD, apH was the sole predictor of severe IVH. In ELBW infants, higher degree of acidemia, rather than hypercapnia per se, during the first 48 hours of life, is associated with higher occurrences of severe IVH.

Virtual Multidisciplinary Rounds to Reduce Length of Stay, Decrease Variation, and Promote Accountability.

PURPOSE: Evidence suggests in-person multidisciplinary rounds can help reduce length of stay (LOS) and improve throughput, but there are limited studies about the effectiveness of virtual multidisciplinary rounds on these measures. The authors hypothesized that virtual multidisciplinary rounds could help reduce LOS, improve throughput, promote accountability, and reduce provider variation. METHODS: The research team designed and implemented virtual multidisciplinary rounds by a phone conference call with key stakeholders, including hospitalists, case managers, the clinical documentation improvement team, physical and occupational therapy, and nursing leaders. To track progress in real time, dashboards were created using data from electronic medical records. After several months, unit-based discharge huddles were also implemented to supplement the process and sustain the improvement. RESULTS: The interventions led to more than 60% of discharges below geometric mean LOS after starting the initiative, compared to approximately 52% before the initiative. Mean observation hours went from around 44 hours to 31.9 hours, and the change was sustained for more than a year. In fiscal year 2021, 3,813 excess days were reduced in 10 months, resulting in combined savings of $6.7 million. A decrease in hospitalist provider variation is noted with the initiative, which is a crucial contributor to the results. CONCLUSION: Virtual multidisciplinary rounds combined with other interventions can effectively reduce LOS and observation hours. Decreasing variation among hospitalists and improved key stakeholder engagement can be achieved with virtual multidisciplinary rounds. More studies to test the effectiveness of virtual multidisciplinary rounds in various patient care settings would provide more insights.

Subthalamic nucleus deep brain stimulation driven by primary motor cortex γ2 activity in parkinsonian monkeys.

In parkinsonism, subthalamic nucleus (STN) electrical deep brain stimulation (DBS) improves symptoms, but may be associated with side effects. Adaptive DBS (aDBS), which enables modulation of stimulation, may limit side effects, but limited information is available about clinical effectiveness and efficaciousness. We developed a brain-machine interface for aDBS, which enables modulation of stimulation parameters of STN-DBS in response to γ2 band activity (80-200 Hz) of local field potentials (LFPs) recorded from the primary motor cortex (M1), and tested its effectiveness in parkinsonian monkeys. We trained two monkeys to perform an upper limb reaching task and rendered them parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Bipolar intracortical recording electrodes were implanted in the M1, and a recording chamber was attached to access the STN. In aDBS, the M1 LFPs were recorded, filtered into the γ2 band, and discretized into logic pulses by a window discriminator, and the pulses were used to modulate the interval and amplitude of DBS pulses. In constant DBS (cDBS), constant stimulus intervals and amplitudes were used. Reaction and movement times during the task were measured and compared between aDBS and cDBS. The M1-γ2 activities were increased before and during movements in parkinsonian monkeys and these activities modulated the aDBS pulse interval, amplitude, and dispersion. With aDBS and cDBS, reaction and movement times were significantly decreased in comparison to DBS-OFF. The electric charge delivered was lower with aDBS than cDBS. M1-γ2 aDBS in parkinsonian monkeys resulted in clinical benefits that did not exceed those from cDBS. However, M1-γ2 aDBS achieved this magnitude of benefit for only two thirds of the charge delivered by cDBS. In conclusion, M1-γ2 aDBS is an effective therapeutic approach which requires a lower electrical charge delivery than cDBS for comparable clinical benefits.

Physical Plasticity of the Brain and Deep Brain Stimulation Lead: Evolution in the First Post-operative Week.

Background: Deep brain stimulation (DBS) is a therapy for movement disorders and psychiatric conditions. In the peri-operative period, brain shift occurs as the consequence of events related to the brain surgery which results in post-operative lead deformation. Objective: To quantify post-operative 3-dimensional DBS lead deformation after implantation. Methods: In 13 patients who had DBS lead implantation, we performed preoperative magnetic resonance imaging (MRI), preoperative computed tomography (CT) scans after placement of fiducial markers, and post-operative CT scans immediately, 24-48 h, and 7 days after implantation. The MRI scans were used to define brain orientation and merged with CT scans. Lead deviation was determined relative to a theoretical linear lead path defined by the skull entry and target lead tip points. Results: In the sagittal plane, we distinguished an initial period after surgery (<48 h) characterized by a deviation of the lead toward the rostral direction and a late period (over 1 week) characterized by a lead deviation toward the caudal direction. In the coronal plane, there was higher probability of lead deviation in the lateral than medial direction. During 7 days after implantation, there was net movement of the center of the lead anteriorly, and the half of the lead close to the entry point moved medially. These deviations appeared normative since all patients included in this study had benefits from DBS therapy with total power of charged comparable to those described in literature. Conclusion: DBS lead deviation occurs during 7 days after implantation. The range of deviation described in this study was not associated to adverse clinical effects and may be considered normative. Future multicenter studies would be helpful to define guide lines on DBS lead deformation and its contribution to clinical outcome.

Health Care Lobbying, Political Action Committees, and Spine Surgery.

STUDY DESIGN: Retrospective review. OBJECTIVE: The aim of this study was to analyze the political contributions and strategies of the Political Action Committee (PACs) lobbying for the political interests of spine surgeons. SUMMARY OF BACKGROUND DATA: In 2016, a presidential election year, $514,224,628 was spent on health care lobbying. Only 16% ($85,061,148) was on behalf of health professionals providing care. Below we chronicle the overlapping contributions between the three different physician-based Political Action Committee (PAC) lobbying entities as it relates specifically to spine surgery. METHODS: Data were abstracted for the PACs of the American Association of Neurological Surgeons (AANS), American Association of Orthopedic Surgeons (AAOS), and the North American Spine Society (NASS). These data were obtained using OpenSecrets (opensecrets.org), and the Federal Election Commission (fec.gov) website. All data points were collected biannually from 2006 to 2018 and statistically analyzed as appropriate. RESULTS: In 2016, the AAOS PAC contributed $2,648,218, the AANS PAC $348,091, and the NASS PAC $183,612. After accounting for respective group size, the AAOS spent >2.34 times that of the AANS. Orthopedists were 3.84 times (95% confidence interval 3.42-4.3) more likely to donate to their PAC than neurosurgeons (P < 0.001) during the 2016 election. The majority of contributions among the three different lobbyist organizations were to federal candidates, followed by fundraising committees, and finally to the national party. Eighty-eight percent of AANS donations went to Republican candidates, whereas AAOS and NASS were 63% and 67%, respectively. From 2008 to 2016, the AAOS PAC had a highest political contributions spend per active member of parent organization ($126.39) as compared to AANS ($80.52) and NASS ($17.81). The AAOS had five surgeons for every donor to the AAOS PAC, whereas the AANS had 14 surgeons and NASS 38 members per each donor. The AANS had a higher percentage of Republican donations with 78.9% of donations going to Republicans as compared to 61.8% of AAOS contributions and 67.9% of NASS contributions. CONCLUSION: Spine surgery is unique in that three different physician-based lobbyist organizations seek to influence legislative priorities with the AAOS having the most substantial fiscal impact and greatest participation. Choreography of donation strategies is essential to maximize physician voice at the policy level. LEVEL OF EVIDENCE: 5.

Novel in vivo Assessment of Unruptured Intracranial Aneurysm Inflammatory Factors.

Background and Purpose: The growth and eventual rupture of intracranial aneurysms may be due to an underlying inflammatory process as evidenced by pathological examination of aneurysm walls. We hypothesize that unruptured aneurysms have an increased inflammatory milieu within their lumen in comparison to the rest of the cerebral arterial vascular system. Methods: Blood was sampled from unruptured aneurysms in patients presenting for aneurysm coil embolization and C3 and C4 complement values from this serum were compared with complement values in the parent artery. Results: Ten patients were enrolled over 32 months with a mean aneurysm size of 9.1 mm. Compared to control samples drawn from peripheral circulation, there were significant decreases of both C3 (p = 0.0003) and C4 (p = 0.0063) levels in aneurysmal blood samples. Conclusions: A state of decreased complement indicative of classic pathway activation was found in all tested aneurysms, thus providing evidence of an ongoing process of complement activation in the blood of live, unruptured aneurysm sacs.

Parkinsonism Differently Affects the Single Neuronal Activity in the Primary and Supplementary Motor Areas in Monkeys: An Investigation in Linear and Nonlinear Domains.

The changes in neuronal firing activity in the primary motor cortex (M1) and supplementary motor area (SMA) were compared in monkeys rendered parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The neuronal dynamic was characterized using mathematical tools defined in different frameworks (rate, oscillations or complex patterns). Then, and for each cortical area, multivariate and discriminate analyses were further performed on these features to identify those important to differentiate between the normal and the pathological neuronal activity. Our results show a different order in the importance of the features to discriminate the pathological state in each cortical area which suggests that the M1 and the SMA exhibit dissimilarities in their neuronal alterations induced by parkinsonism. Our findings highlight the need for multiple mathematical frameworks to best characterize the pathological neuronal activity related to parkinsonism. Future translational studies are warranted to investigate the causal relationships between cortical region-specificities, dominant pathological hallmarks and symptoms.

Local field potential dynamics in the primate cortex in relation to parkinsonism reveled by machine learning: A comparison between the primary motor cortex and the supplementary area.

The present study compares the cortical local field potentials (LFPs) in the primary motor cortex (M1) and the supplementary motor area (SMA) of non-human primates rendered Parkinsonian with administration of dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The dynamic of the LFPs was investigated under several mathematical frameworks and machine learning was used to discriminate the recordings based on these features between healthy, parkinsonian with off-medication and parkinsonian with on-medication states. The importance of each feature in the discrimination process was further investigated. The dynamic of the LFPs in M1 and SMA was affected regarding its variability (time domain analysis), oscillatory activities (frequency domain analysis) and complex patterns (non-linear domain analysis). Machine learning algorithms achieved accuracy near 0.90 for comparisons between conditions. The TreeBagger algorithm provided best accuracy. The relative importance of these features differed with the cortical location, condition and treatment. Overall, the most important features included beta oscillation, fractal dimension, gamma oscillation, entropy and asymmetry of amplitude fluctuation. The importance of features in discriminating between normal and pathological states, and on- or off-medication states depends on the pair-comparison and it is region-specific. These findings are discussed regarding the refinement of current models for movement disorders and the development of on-demand therapies.

Nuclear translocation kinetics of NF-kappaB in macrophages challenged with pathogens in a microfluidic platform.

We have developed a microfluidic platform for real-time imaging of host-pathogen interactions and cellular signaling events. Host cells are immobilized in a controlled environment for optical interrogation of the kinetics and stochasticity of immune response to pathogenic challenges. Here, we have quantitatively measured activation of the toll-like receptor 4 (TLR4) pathway in RAW264.7 murine macrophage-like cells. This was achieved by measuring the cytoplasm-to-nucleus translocation kinetics of a green fluorescent protein fusion construct to the NF-kappaB transcription factor subunit RelA (GFP-RelA). Translocation kinetics in response to live bacteria and purified lipopolysaccharide (LPS) challenges were measured, and this work presents the first demonstration of live imaging of host cell infection on a microfluidic platform with quantitative analysis of an early (<0.5 h from infection) immune signaling event. Our data show that a 1,000x increase in the LPS dose led to a ~10x increase in a host cell activation metric we developed in order to describe NF-kappaB translocation kinetics. Using this metric, live bacteria challenges were assigned an equivalent LPS dose as a first step towards comparing NF-kappaB translocation kinetics between TLR4-only pathway signaling (activated by LPS) and multiple pathway signaling (activated by whole bacteria). The device also contains a unique architecture for capturing and fluidically isolating single host cells for the purpose of differentiating between primary and secondary immune signaling.

Unilateral Open-lip Schizencephaly with Tonsillar Herniation in a Preterm Infant.

Schizencephaly is a rare type of neuronal migration disorder characterized by the presence of a cerebral hemispheric cleft that extends from lateral ventricles to the cortical surface of the brain. We report a rare case of prenatally diagnosed unilateral schizencephaly in a late preterm infant who manifested with rapidly progressive hydrocephalus with massive enlargement of posterior cerebrospinal fluid spaces with tonsillar herniation that was successfully treated with placement of a ventriculoperitoneal shunt.

Rear Admiral (Astronaut) Alan Shepard: Ménière's disease and the race to the moon.

On May 5, 1961, Alan B. Shepard Jr. piloted the Freedom 7 craft into a suborbital flight to become the first American man in space. His promising astronautical career was soon scuttled by spells of dizziness and tinnitus later diagnosed as Ménière's disease, until William F. House-considered the father of neurotology and a pioneer in surgery for vestibular schwannomas-intervened. In 1968 House implanted an endolymphatic-subarachnoid shunt, which at the time was a virtually experimental procedure. Shepard's debilitating Ménière's disease was cured, but not quite in time for him to pilot the doomed Apollo 13 mission; he was reassigned to Apollo 14 and as a result would step foot on the moon on February 5, 1971. This historical vignette depicts the tale of how the career trajectories of Shepard and House-two notable figures in their respective fields-fatefully intersected.

Astronaut Michael Collins, Apollo 8, and the anterior cervical fusion that changed the history of human spaceflight.

In 1961, President John F. Kennedy declared that the United States would send a man to the moon and safely bring him home before the end of the decade. Astronaut Michael Collins was one of those men. He flew to the moon on the historic flight of Apollo 11 while Neil Armstrong and Buzz Aldrin walked on its surface. However, this was not supposed to be the case.Astronaut Collins was scheduled to fly on Apollo 8. While training, in 1968, he started developing symptoms of cervical myelopathy. He underwent evaluation at Wilford Hall Air Force Hospital in San Antonio and was noted to have a C5-6 disc herniation and posterior osteophyte on myelography. Air Force Lieutenant General (Dr.) Paul W. Myers performed an anterior cervical discectomy with placement of iliac bone graft. As a result, Astronaut James Lovell took his place on Apollo 8 flying the uncertain and daring first mission to the moon. This had a cascading effect on the rotation of astronauts, placing Michael Collins on the Apollo 11 flight that first landed men on the moon. It also placed Astronaut James Lovell in a rotation that exposed him to be the Commander of the fateful Apollo 13 flight.Here, the authors chronicle the history of Astronaut Collins' anterior cervical surgery and the impact of his procedure on the rotation of astronaut flight selection, and they review the pivotal historic nature of the Apollo 8 spaceflight. The authors further discuss the ongoing issue of cervical disc herniation among astronauts.

The structure of isolated Synechococcus strain WH8102 carboxysomes as revealed by electron cryotomography.

Carboxysomes are organelle-like polyhedral bodies found in cyanobacteria and many chemoautotrophic bacteria that are thought to facilitate carbon fixation. Carboxysomes are bounded by a proteinaceous outer shell and filled with ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO), the first enzyme in the CO(2) fixation pathway, but exactly how they enhance carbon fixation is unclear. Here we report the three-dimensional structure of purified carboxysomes from Synechococcus species strain WH8102 as revealed by electron cryotomography. We found that while the sizes of individual carboxysomes in this organism varied from 114 nm to 137 nm, surprisingly, all were approximately icosahedral. There were on average approximately 250 RuBisCOs per carboxysome, organized into three to four concentric layers. Some models of carboxysome function depend on specific contacts between individual RuBisCOs and the shell, but no evidence of such contacts was found: no systematic patterns of connecting densities or RuBisCO positions against the shell's presumed hexagonal lattice could be discerned, and simulations showed that packing forces alone could account for the layered organization of RuBisCOs.

Boolean dynamics of genetic regulatory networks inferred from microarray time series data.

MOTIVATION: Methods available for the inference of genetic regulatory networks strive to produce a single network, usually by optimizing some quantity to fit the experimental observations. In this article we investigate the possibility that multiple networks can be inferred, all resulting in similar dynamics. This idea is motivated by theoretical work which suggests that biological networks are robust and adaptable to change, and that the overall behavior of a genetic regulatory network might be captured in terms of dynamical basins of attraction. RESULTS: We have developed and implemented a method for inferring genetic regulatory networks for time series microarray data. Our method first clusters and discretizes the gene expression data using k-means and support vector regression. We then enumerate Boolean activation-inhibition networks to match the discretized data. Finally, the dynamics of the Boolean networks are examined. We have tested our method on two immunology microarray datasets: an IL-2-stimulated T cell response dataset and a LPS-stimulated macrophage response dataset. In both cases, we discovered that many networks matched the data, and that most of these networks had similar dynamics. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Impedimetric and optical interrogation of single cells in a microfluidic device for real-time viability and chemical response assessment.

We report here a non-invasive, reversible method for interrogating single cells in a microfluidic flow-through system. Impedance spectroscopy of cells held at a micron-sized pore under negative pressure is demonstrated and used to determine the presence and viability of the captured cell. The cell capture pore is optimized for electrical response and mechanical interfacing to a cell using a deposited layer of parylene. Changes in the mechanical interface between the cell and the chip due to chemical exposure or environmental changes can also be assessed. Here, we monitored the change in adhesion/spreading of RAW264.7 macrophages in response to the immune stimulant lipopolysaccharide (LPS). This method enables selective, reversible, and quantitative long-term impedance measurements on single cells. The fully sealed electrofluidic assembly is compatible with long-term cell culturing, and could be modified to incorporate single cell lysis and subsequent intracellular separation and analysis.

Computed tomographic method to quantify electrode lead deformation and subdural gap after lead implantation for deep brain stimulation.

BACKGROUND: Deep brain stimulation is an effective treatment for movement disorders and psychiatric conditions. Intra-operative and post-operative events can result in brain tissue deformation (i.e. subdural gaps) which may cause lead deformation and its displacement from optimal target. We developed a method to quantify postoperative lead deformation and we present two DBS cases to illustrate the phenomena of lead deformation resulting from the development of subdural gaps. NEW METHOD: We present a semi-automatic computational algorithm using Computed Tomography scanning with reconstruction to determine lead curvature relative to a theoretical straight lead between the skull entry site and lead tip. Subdural gap was quantified from the CT scan. RESULTS: In 2 patients who had leads implanted, analysis of CT scans was completed within 5 min each. The maximum deviation of the observed lead from the theoretical linear path was 1.1 and 2.6 mm, and the subdural gap was 5.5 and 9.6 mL, respectively. COMPARISON WITH EXISTING METHOD(S): This is the first method allowing a comprehensive characterization of the lead deformation in situ. CONCLUSIONS: The computational algorithms provide a simple, semiautomatic method to characterize in situ lead curvature related to brain tissue deformation after lead placement.

Identification of expression patterns of IL-2-responsive genes in the murine T cell line CTLL-2.

Interleukin-2 (IL-2) influences T cell proliferation and differentiation through regulation of a number of genes. Many such genes are known, yet their expression profiles have remained elusive. Using Affymetrix mouse genome arrays and the mouse T cell line CTLL-2, we studied the transcriptional response to IL-2 stimulation. A total of 2813 genes (represented by 3838 probes) showed > or =2-fold changes in expression level at one or more time points (10 were analyzed) during the first 24 h poststimulation. Cluster analyses indicated that these 2813 genes showed nine different expression patterns. Of these genes, approximately 1400 were not previously known to be regulated by interleukin-2 (IL-2). In the control, 666 genes with > or =2-fold changes at the mRNA level were identified in cells without IL-2 stimulation; 222 of them were among the 2813 IL-2-responsive genes. Possibly, the expression of these genes was altered because of changes in cell density or cell growth rate. The newly identified IL-2-responsive genes play roles in a variety of biologic processes, including signal transduction, apoptosis, cell cycle regulation, and transcription. Our data will be useful for studying biochemical events in IL-2 signaling.