Development of a method for optimal maneuver analysis of complex space missions

A system that allows mission planners to find optimal multiple-burn space trajectories easily is described. Previously developed methods with different gravity assumptions perform the optimization function. The power of these programs is extended by a method of costate estimation. A penalty function method of constraining coast arc times to be positive is included. The capability of the method is demonstrated by finding the optimal control for three different space missions. These include a shuttle abort-once-around mission and two- and three-burn geosynchronous satellite-placement missions

Orbiter/payload proximity operations: Lateral approach technique

The lateral approach is presented for proximity operations associated with the retrieval of free flying payloads. An out of plane final approach emphasizing onboard software support is recommended for all except the latter segment of the final approach in which manual control is considered mandatory. An overall assessment of various candidate proximity operations techniques are made

Orbit targeting specialist function: Level C formulation requirements

A definition of the level C requirements for onboard maneuver targeting software is provided. Included are revisions of the level C software requirements delineated in JSC IN 78-FM-27, Proximity Operations Software; Level C Requirements, dated May 1978. The software supports the terminal phase midcourse (TPM) maneuver, braking and close-in operations as well as supporting computation of the rendezvous corrective combination maneuver (NCC), and the terminal phase initiation (TPI). Specific formulation is contained here for the orbit targeting specialist function including the processing logic, linkage, and data base definitions for all modules. The crew interface with the software is through the keyboard and the ORBIT-TGT display

Constructing a complete landslide inventory dataset for the 2018 monsoon disaster in Kerala, India, for land use change analysis

Event-based landslide inventories are important for analyzing the relationship between the intensity of the trigger (e.g., rainfall, earthquake) and the density of the landslides in a particular area as a basis for the estimation of the landslide probability and the conversion of susceptibility maps into hazard maps required for risk assessment. They are also crucial for the establishment of local rainfall thresholds that are the basis of early warning systems and for evaluating which land use and land cover changes are related to landslide occurrence. The completeness and accuracy of event-based landslide inventories are crucial aspects to derive reliable results or the above types of analyses. In this study, we generated a relatively complete landslide inventory for the 2018 monsoon landslide event in the state of Kerala, India, based on two inventories that were generated using different methods: one based on an object-based image analysis (OBIA) and the other on field surveys of damaging landslides. We used a collaborative mapping approach based on the visual interpretation of pre- and post-event high-resolution satellite images (HRSIs) available from Google Earth, adjusted the two inventories, and digitized landslides that were missed in the two inventories. The reconstructed landslide inventory database contains 4728 landslides consisting of 2477 landslides mapped by the OBIA method, 973 landslides mapped by field survey, 422 landslides mapped both by OBIA and field methods, and an additional 856 landslides mapped using the visual image (Google Earth) interpretation. The dataset is available at line uri \u3ehttps://doi.org/10.17026/dans-x6c-y7x2\u3e (van Westen, 2020). Also, the location of the landslides was adjusted, based on the image interpretation, and the initiation points were used to evaluate the land use and land cover changes as a causal factor for the 2018 monsoon landslides. A total of 45 % of the landslides that damaged buildings occurred due to cut-slope failures, while 34 % of those having an impact on roads were due to road cut-slope failures. The resulting landslide inventory is made available for further studies.

Severe COVID-19 is associated with endothelial activation and abnormal glycosylation of von Willebrand factor in patients undergoing hemodialysis

Background: A major clinical feature of severe coronavirus diease 2019 (COVID-19) is microvascular thrombosis linked to endothelial cell activation. Consistent with this, a number of studies have shown that patients with severe COVID-19 have highly elevated plasma levels of von Willebrand Factor (VWF) that may contribute to the prothrombotic phenotype. In the current study, we investigated the extent of endothelial activation in patients receiving hemodialysis who had either mild or severe COVID-19. Methods: Plasma VWF, ADAMTS-13, angiopoietin-2 (Ang2), and syndecan-1 levels were determined by ELISA. The sialic acid content of VWF was investigated using a modified ELISA to measure elderberry bark lectin, specific for sialic acid residues, binding to VWF. Results: Patients receiving hemodialysis with severe COVID-19 had significantly higher plasma levels of VWF and lower ADAMTS-13. VWF levels peaked and were sustained during the first 10 days after positive confirmation of infection. While Ang2 trended toward being higher in severely ill patients, this did not reach significance; however, severely ill patients had significantly higher soluble syndecan-1 levels, with high levels related to risk of death. Finally, higher VWF levels in severely ill patients were correlated with lower VWF sialic acid content. Conclusions: Severe COVID-19 in patients undergoing hemodialysis is associated with both acute and sustained activation of the endothelium, leading to alteration of the VWF/ADAMTS-13 axis. Lower VWF sialic acid content represents altered VWF processing and further confirms the disturbance caused to the endothelium in COVID-19

Lack of seroresponse to SARS-CoV-2 booster vaccines given early post-transplant in patients primed pre-transplantation

SARS-CoV-2 vaccines are recommended pre-transplantation, however, waning immunity and evolving variants mandate booster doses. Currently there no data to inform the optimal timing of booster doses post-transplant, in patients primed pre-transplant. We investigated serial serological samples in 204 transplant recipients who received 2 or 3 SARS-CoV-2 vaccines pre-transplant. Spike protein antibody concentrations, [anti-S], were measured on the day of transplantation and following booster doses post-transplant. In infection-naïve patients, post-booster [anti-S] did not change when V3 (1st booster) was given at 116(78-150) days post-transplant, falling from 122(32-574) to 111(34-682) BAU/ml, p=0.78. Similarly, in infection-experienced patients, [anti-S] on Day-0 and post-V3 were 1090(133-3667) and 2207(650-5618) BAU/ml respectively, p=0.26. In patients remaining infection-naïve, [anti-S] increased post-V4 (as 2nd booster) when given at 226(208-295) days post-transplant, rising from 97(34-1074) to 5134(229-5680) BAU/ml, p=0.0016. Whilst in patients who had 3 vaccines pre-transplant, who received V4 (as 1st booster) at 82(49-101) days post-transplant, [anti-S] did not change, falling from 981(396-2666) to 871(242-2092) BAU/ml, p=0.62. Overall, infection pre-transplant and [anti-S] at the time of transplantation predicted post-transplant infection risk. As [Anti-S] fail to respond to SARS-CoV-2 booster vaccines given early post-transplant, passive immunity may be beneficial to protect patients during this period

Invited perspectives: Mountain roads in Nepal at a new crossroads

In Nepal and many developing countries around the world, roads are vehicles for development for communities in rural areas. By reducing travel time on foot, opportunities are opened for quicker transportation of goods and better access to employment, education, health care and markets. Roads also fuel migration and numerous social changes, both positive and negative. Poorly constructed roads in mountainous areas of Nepal have increased erosion and landslide risk as they often cut through fragile geology, destabilizing slopes and altering local hydrological conditions, with costs to lives and livelihoods. The convergence of the newly constituted decentralized Nepali government with China's Belt and Road Initiative is likely to bring more roads to rural communities. The new provincial government administrations now have the opportunity to develop policies and practices, which can realign the current trend of poorly engineered, inefficient and hazardous road construction toward a more sustainable trajectory. This commentary provides an overview of some of the obstacles along the way for a more sustainable road network in Nepal and illustrates how good governance, development and landslide risk are intertwined. The opinion presented in this brief commentary lends little hope that Nepal's current pathway of unsustainable road construction will provide the country with the much-needed sustainable road network, unless checks and balances are put in place to curb noncompliance with existing laws and policies.</p

A case series of patients with isolated IgG4-related hypophysitis treated with rituximab

Context The acute presentation of Immunoglobulin G4 (IgG4)-related hypophysitis can be indistinguishable from other forms of acute hypophysitis and histology remains the diagnostic gold standard. The high recurrence rate necessitates long term immunosuppressive therapy. Rituximab (RTX) has been shown to be effective in systemic IgG4-related disease (IgG4-RD), but experience with isolated pituitary involvement remains limited. Case description We report three female patients with MRI findings suggestive of hypophysitis. All patients underwent transsphenoidal biopsy and fulfilled diagnostic criteria for IgG4-related hypophysitis. Treatment with GCs (GC) resulted in good therapeutic response in patients 1 and 2, but the disease recurred on tapering doses of GCs. GC treatment led to emotional lability in Patient 3 necessitating dose reduction. All three patients received RTX and Patients 2 and 3 received further courses when symptoms returned and B-cells repopulated. Patient 3 did not receive RTX until 12 months from onset of symptoms. Patient 1 was not able to have further RTX treatments due to an allergic reaction when receiving the second dose. RTX treatment resulted in sustained remission and full recovery of anterior pituitary function in Patients 1 and 2 with complete resolution of pituitary enlargement. By contrast, Patient 3 only showed symptomatic response following RTX treatment, but pituitary enlargement and hypofunction persisted. Conclusion RTX treatment for IgG4-related hypophysitis resulted in sustained remission in two patients treated early in the disease process, but only achieved partial response in a patient with chronic disease suggesting that early therapeutic intervention may be crucial to avoid irreversible changes

Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence

Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. We observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19

Efficacy of sub-Tenon's block using an equal volume of local anaesthetic administered either as a single or as divided doses. A randomised clinical trial

<p>Abstract</p> <p>Background</p> <p>Sub-Tenon's anaesthetic is effective and reliable in producing both akinesia and anaesthesia for cataract surgery. Our clinical experience indicates that it is sometimes necessary when absolute akinesia is required during surgery to augment the block with 1–2 ml of local anaesthetic. Hypothesis was that after first injection some of the volume injected may spill out and before second injection the effect of hyaluronidase has taken place and second volume injectate will have desired effect.</p> <p>Methods</p> <p>A prospective, randomised, control trial in which patients were randomly allocated to one of two groups. In group 1, single injection of 5 ml of local anaesthetic was injected. In group 2, 3 ml of the same anaesthetic solution was injected followed by application of gentle orbital pressure for 2 minutes. A further 2 ml of the same anaesthetic solution was injected through the same conjunctival incision. Measurement of movement in four quadrants of eye was done by the surgeon at 3 and 6 minutes. Intraocular pressure, chemosis, and subconjuctival haemorrhage were also measured.</p> <p>Results</p> <p>Significant differences at 3 minutes between groups for overall movement, medial, superior, and lateral quadrants occurred. At 6 minutes no significant group differences emerged for the overall movement or for any of four quadrants.</p> <p>Conclusion</p> <p>Single injection of local anaesthesia for sub-Tenon's block with mixture of lignocaine with adrenaline, bupivacaine and hyaluronidase was found to be superior to provide akinesia of ocular muscles compared to divided dose given by two injections. No difference in groups in terms of haemorrhage, chemosis, patient's satisfaction and intraocular pressure was found.</p> <p>Trial registration</p> <p>Trial registration no-ISRCTN73431052</p