The Splenic Injury Outcomes Trial: An American Association For the Surgery of Trauma Multi-Institutional Study

BACKGROUND: Delayed splenic hemorrhage after nonoperative management (NOM) of blunt splenic injury (BSI) is a feared complication, particularly in the outpatient setting. Significant resources, including angiography (ANGIO), are used in an effort to prevent delayed splenectomy (DS). No prospective, long-term data exist to determine the actual risk of splenectomy. The purposes of this trial were to ascertain the 180-day risk of splenectomy after 24 hours of NOM of BSI and to determine factors related to splenectomy. METHODS: Eleven Level I trauma centers participated in this prospective observational study. Adult patients achieving 24 hours of NOM of their BSI were eligible. Patients were followed up for 180 days. Demographic, physiologic, radiographic, injury-related information, and spleen-related interventions were recorded. Bivariate and multivariable analyses were used to determine factors associated with DS. RESULTS: A total of 383 patients were enrolled. Twelve patients (3.1%) underwent in-hospital splenectomy between 24 hours and 9 days after injury. Of 366 discharged with a spleen, 1 (0.27%) required readmission for DS on postinjury Day 12. No Grade I injuries experienced DS. The splenectomy rate after 24 hours of NOM was 1.5 per 1,000 patient-days. Only extravasation from the spleen at time of admission (ADMIT-BLUSH) was associated with splenectomy (odds ratio, 3.6; 95% confidence interval, 1.4–12.4). Of patients with ADMIT-BLUSH (n = 49), 17 (34.7%) did not have ANGIO with embolization (EMBO), and 2 of those (11.8%) underwent splenectomy; 32 (65.3%) underwent ANGIO with EMBO, and 2 of those (6.3%, p = 0.6020 compared with no ANGIO with EMBO) required splenectomy. CONCLUSION: Splenectomy after 24 hours of NOM is rare. After the initial 24 hours, no additional interventions are warranted for patients with Grade I injuries. For Grades II to V, close observation as an inpatient or outpatient is indicated for 10 days to 14 days. ADMIT-BLUSH is a strong predictor of DS and should lead to close observation or earlier surgical intervention. LEVEL OF EVIDENCE: Prognostic/epidemiological study, level III; therapeutic study, level IV

Expansion microscopy of zebrafish for neuroscience and developmental biology studies

Expansion microscopy (ExM) allows scalable imaging of preserved 3D biological specimens with nanoscale resolution on fast diffraction-limited microscopes. Here, we explore the utility of ExM in the larval and embryonic zebrafish, an important model organism for the study of neuroscience and development. Regarding neuroscience, we found that ExM enabled the tracing of fine processes of radial glia, which are not resolvable with diffraction-limited microscopy. ExM further resolved putative synaptic connections, as well as molecular differences between densely packed synapses. Finally, ExM could resolve subsynaptic protein organization, such as ring-like structures composed of glycine receptors. Regarding development, we used ExM to characterize the shapes of nuclear invaginations and channels, and to visualize cytoskeletal proteins nearby. We detected nuclear invagination channels at late prophase and telophase, potentially suggesting roles for such channels in cell division. Thus, ExM of the larval and embryonic zebrafish may enable systematic studies of how molecular components are configured in multiple contexts of interest to neuroscience and developmental biology.National Institutes of Health (U.S.) (Grant 1R01EB024261)National Institutes of Health (U.S.) (Grant 1R01MH110932)National Institutes of Health (U.S.) (Grant 2R01DA029639)National Institutes of Health (U.S.) (Grant 1R01NS087950)National Institutes of Health (U.S.) (Grant 1U01MH106011

PDRs4All III: JWST's NIR spectroscopic view of the Orion Bar

(Abridged) We investigate the impact of radiative feedback from massive stars on their natal cloud and focus on the transition from the HII region to the atomic PDR (crossing the ionisation front (IF)), and the subsequent transition to the molecular PDR (crossing the dissociation front (DF)). We use high-resolution near-IR integral field spectroscopic data from NIRSpec on JWST to observe the Orion Bar PDR as part of the PDRs4All JWST Early Release Science Program. The NIRSpec data reveal a forest of lines including, but not limited to, HeI, HI, and CI recombination lines, ionic lines, OI and NI fluorescence lines, Aromatic Infrared Bands (AIBs including aromatic CH, aliphatic CH, and their CD counterparts), CO2 ice, pure rotational and ro-vibrational lines from H2, and ro-vibrational lines HD, CO, and CH+, most of them detected for the first time towards a PDR. Their spatial distribution resolves the H and He ionisation structure in the Huygens region, gives insight into the geometry of the Bar, and confirms the large-scale stratification of PDRs. We observe numerous smaller scale structures whose typical size decreases with distance from Ori C and IR lines from CI, if solely arising from radiative recombination and cascade, reveal very high gas temperatures consistent with the hot irradiated surface of small-scale dense clumps deep inside the PDR. The H2 lines reveal multiple, prominent filaments which exhibit different characteristics. This leaves the impression of a "terraced" transition from the predominantly atomic surface region to the CO-rich molecular zone deeper in. This study showcases the discovery space created by JWST to further our understanding of the impact radiation from young stars has on their natal molecular cloud and proto-planetary disk, which touches on star- and planet formation as well as galaxy evolution.Comment: 52 pages, 30 figures, submitted to A&

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (< 5 years, 5–10 years, 10–20 years, and > 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (< 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs > 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (< 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs > 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 (< 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs > 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Sense Amplifier-Based Pass Transistor Logic

Reducing the energy required per operation is the key to building ultra-low energy systems, and the most effective way of achieving this is to reduce the supply voltage. However, operating CMOS circuits at low supply voltages increases circuit delay, leading to lower circuit performance. In this region, the sub-threshold leakage energy component becomes more pronounced and can even dominate the total circuit energy. Increasing threshold voltages reduces the amount of leakage, but this forces operation in the sub-threshold region where performance and variability become exponentially worse. The use of the sense amplifier-based pass transistor logic (SAPTL) topology is one approach to reducing the energy per operation. It uses an inverted pass transistor logic (PTL) tree, which inherently has no gain, and hence no power supply connections, eliminating the sources of sub-threshold leakage current. Reducing the threshold voltages of the PTL transistors improves performance, without the leakage current increase associated with conventional static CMOS logic. This reduced threshold voltage also allows the PTL transistors to operate in the super-threshold region, even for very low supply voltages, avoiding the increased delay and variability associated with the sub-threshold operating regime. Gain is introduced by using drivers and sense amplifiers (SAs) that restore the output voltage swing and provide the appropriate output current to drive the fan-out capacitances. These drivers and SAs are the primary source of sub-threshold leakage, which can be amortized by making the PTL networks complex, and by applying various leakage reduction techniques. SAPTL-based 90nm test circuits using both synchronous and asynchronous timing schemes have been designed, fabricated and tested. These circuits show leakage and energy characteristics better than the equivalent static CMOS circuits. These test chips also demonstrate rudimentary SAPTL-based design flows using commercially available CAD tools. Simulation and measurement results of basic synchronous SAPTL building blocks show a 40X-50X reduction in standby current and a 6X reduction in energy when compared to an equivalent CMOS logic block, at the expense of a 10X-30X increase in delay. Operating the SAPTL asynchronously reduces the average delay by 89%. However, adding the necessary handshaking circuitry increases the energy by 31%.These SAPTL building blocks are used to create a parallel 64-byte asynchronous SAPTL-based CRC generator with a minimum energy point that is 25% lower than that of the static CMOS equivalent, with a 6X delay penalty. Also, due to the nature of the PTL tree, forward-biasing the body of the PTL transistors results in a 10% reduction in delay with no energy penalty.The advantages of the SAPTL over conventional static CMOS is expected to be more significant as technology continues to scale, where subthreshold leakage continue to prevent supply voltages from being aggressively scaled

COST AND EFFECT OF APPLYING REDUNDANCY TO IMPROVE THE RESILIENCY OF A WIRELESS SENSOR NETWORK (WSN)

Wireless sensor networks (WSNs) are an emerging technology that uses small computing elements for an increased contact with the environment, providing more opportunities to reshape interactions between people and computers. With an increasing adoption of these WSNs in critical systems, resiliency has become an important factor when designing these networks. For this research, we define resiliency as the ability of a WSN to continue to operate correctly even in the presence of attacks on the system. After reviewing existing WSNs and the techniques they employed to introduce resiliency, one inherent feature seen is redundancy. Generally, it's been found that with increasing redundancy a WSN becomes more and more fault-tolerant. I we focused on applying redundancy on the node and network level as its effect can propagate to the highest levels of WSN abstraction. Also, the cost of applying redundancy can be clearly seen in the energy consumption of a WSN and would thus have a large impact on how the design goals of network lifetime, sensing reliability and sensing & communication coverage can be met.2 How then do we incorporate these redundancy techniques into WSN design while taking into consideration its energy cost and effects? Energy-saving techniques in WSN are normally applied to the network and sensing subsystem as these consume the most energy.3 Thus, for the first part of the research, we looked into the energy cost and effect of redundancy on communications. To determine this, we first created a basic model of a WSN, which is a single node and a sink. After classifying the types of redundancy techniques (physical and temporal), we applied them on the basic model and on different networks (line and tree, see Figure I) to look at the cost in terms of energy consumption. This was computed based on the number of transmissions needed for all the nodes to send its data to the sink, or one network cycle. For the basic node, the energy cost was the same for all types of redundancy. Then, we applied physical redundancy on the line and tree networks. For the line networks, we found that placing a redundant node with its input farthest from the sink node and its output directly to the sink node will result to the least additional energy cost. For the tree network, placing a redundant node with its input from a leaf node and its output directly to the sink node will result to the least additional energy cost. These results are shown in Table 1. The next part of the research is to determine the effects of applying redundancy. We first defined attack resiliency as the ability of the WSN to handle three types of attacks, namely external, internal and energy loss. We then determined which of the redundancy techniques could withstand the most number of attacks using the basic model. The result was having an additional node and a redundant sink would help the model handle most attacks. For the line and tree networks, we needed to determine where the additional node would be placed for the network to send the most number of transmissions if an attack takes place. This is done by determining how many nodes will be able to send their data to the sink when a node is attacked. Both networks show that the critical node that needs redundancy is the node found nearest to the sink or the node with the most number of connections downline. However, based on the results of cost, these would lead to a higher amount of energy consumption. In conclusion, using redundancy on a WSN to handle attacks introduces additional energy cost. The placement of redundant nodes near the sink can improve the chances of data from other nodes to be received, as seen in the attack resiliency. However, the network will use more energy even if an attack does not occur. Thus, we need to determine how to balance these two if a WSN is constrained in terms of energy resources. Also, the energy cost and effect of redundancy on the sensing subsystem must be investigated as this could introduce more issues. A methodology that would include the overall cost and effect of redundancy when designing would then help in achieving a resilient WSN