CAPSTONE: Recovery & Operations of a Tumbling Small Satellite in Deep Space

The Cislunar Autonomous Positioning System Technology Operations and Navigation Experiment (CAPSTONE) satellite, deployed in July 2022, experienced a thruster anomaly in September 2022 during its Ballistic Lunar Transfer (BLT) into the Earth-Moon L2 Near Rectilinear Halo Orbit (NRHO). CAPSTONE\u27s primary mission objective to achieve and maintain NRHO serves to validate the cislunar CONOPS contemplated for NASA\u27s Lunar Gateway. Terran Orbital designed and built CAPSTONE, and serves as the operator of the on-orbit spacecraft. Advanced Space owns and operates the CAPSTONE payload and its software on behalf of NASA, as well as performs mission navigation and maneuver design. This 12U+ lunar nanosatellite contains a pump-fed hydrazine propulsion system from Stellar Exploration, enabling all orbital maneuvers and momentum management for the mission. The CAPSTONE mission is funded by the NASA Space Technology Mission Directorate (STMD) through the Small Spacecraft Technology program, and by the Human Exploration and Operations Mission Directorate (HEOMD) through the Advanced Exploration Systems program. This paper will examine the timeline, innovation, and steps taken by the spacecraft team to recover the vehicle from the thruster anomaly and the resulting high-rate tumble. The high-rate tumble was induced by a valve which became stuck open at the conclusion of Trajectory Correction Maneuver 3 (TCM-3). The timeline discussion includes initial autonomous fault recovery, the evolution of the state of the vehicle, and the recovery actions taken by a small, agile engineering team. The off-nominal attitude and thermal state was determined from a limited data set, requiring the largest assets in NASA\u27s Deep Space Network (DSN) to support communications with the vehicle. Once a determination was made that the hydrazine propellant was freezing, an assessment was made on the minimum amount of heat required to thaw propellant without placing the spacecraft in a power-negative state. The integrated spacecraft team performed root cause analysis and incrementally tested the propulsion system to recommission it in the face of an anomalous thruster valve. The recommissioning approach eventually lead to the development of a new propulsive state machine and Guidance Navigation and Control (GNC) thruster controller for detumbling. After recovering 3-axis attitude control, power and thermal stability, and establishing nominal communications, significant development and testing was required to ensure the vehicle could operate in the presence of a continued thruster anomaly. This effort enabled CAPSTONE to execute future propulsive maneuvers with an open thruster valve. The resultant updates were tested on Terran Orbital\u27s Hardware-in-the-Loop (HITL) platform in partnership with Stellar Exploration. A comparison of GNC subsystem requirements will be presented pre-and post-anomaly, based on the resulting capability and restrictions of the propulsion system to meet mission objectives. Ultimately, the spacecraft was successfully recovered from body rates exceeding 120 deg/s, allowing the CAPSTONE spacecraft to continue its mission, including successful insertion into NRHO in November 2022. An examination of the lessons learned for future deep space small satellite missions is also discussed herein

The impact of the 2022 Ukraine/Russian conflict on cancer clinical trials

Since the invasion of Ukraine in February 2022, clinical trial conduct has become extremely challenging due to damage to the healthcare infrastructure and patient displacement. This current study aimed to estimate the number of cancer clinical trials at risk of impact from the conflict. A descriptive analysis and narrative review were completed using data from cancer clinical trials with sites in Russia or Ukraine using the ‘clinical trials.gov’ online database between February 2022 and May 2022. There were 508 clinical trials involving sites in Ukraine or Russia. Most were multinational studies (470 of 508; 93 %). The majority of studies were phase 3 (344 of 508; 68 %) and these also had the largest sample sizes (median 624, range 12–5637). The most common tumour types were lung (128 of 508; 25 %), urogenital (94 of 508; 19 %) and breast (78 of 508; 15 %). A meaningful number of trials had curative intent (129 of 508; 25 %). The most common intervention was immunotherapy-related (218 of 508; 43 %), followed by other targeted therapy (185 of 508; 36 %). Ukraine and Russia are both large centres for global clinical trial activity. The invasion of Ukraine may result in underpowering of international clinical trial results with loss of future recruitment sites for both countries

Vegetation and environmental patterns on soils derived from Hawkesbury Sandstone and Narrabeen substrata in Ku-ring-gai Chase National Park, New South Wales

[Abstract]: The vegetation patterns in the Central Coast region of New South Wales have been extensively studied with respect to single environmental variables, particularly soil nutrients. However, few data are available on the effects of multiple environmental variables. This study examines the relationships between vegetation and multiple environmental variables in natural vegetation on two underlying rock types, Hawkesbury sandstone and Narrabeen group shales and sandstones, in Ku-ring-gai Chase National Park, Sydney. Floristic composition and 17 environmental factors were characterized using duplicate 500 m2 quadrats from fifty sites representing a wide range of vegetation types. The patterns in vegetation and environmental factors were examined through multivariate analyses: indicator species analysis was used to provide an objective classification of plant community types, and the relationships between vegetation and environmental factors within the two soil types were examined through indirect and direct gradient analyses. Eleven plant communities were identified, which showed strong agreement with previous studies. The measured environmental factors showed strong correlations with vegetation patterns: within both soil types, the measured environmental variables explained approximately 32 - 35% of the variation in vegetation. No single measured environmental variable adequately described the observed gradients in vegetation; rather, vegetation gradients showed strong correlations with complex environmental gradients. These complex environmental gradients included nutrient, moisture and soil physical and site variables. These results suggest a simple 'nutrient' hypothesis regarding vegetation patterns in the Central Coast region is inadequate to explain variation in vegetation within soil types

The genealogical method in epistemology

In 1990 Edward Craig published a book called Knowledge and the State of Nature in which he introduced and defended a genealogical approach to epistemology. In recent years Craig’s book has attracted a lot of attention, and his distinctive approach has been put to a wide range of uses including anti-realist metaepistemology, contextualism, relativism, anti-luck virtue epistemology, epistemic injustice, value of knowledge, pragmatism and virtue epistemology. While the number of objections to Craig’s approach has accumulated, there has been no sustained attempt to develop answers to these objections. In this paper we provide answers to seven important objections in the literature

Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis

Background Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. Methods We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. Findings A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55–2·08], p=5·13×10– ¹⁵) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42–1·71], p=7·65×10– ²⁰) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25–1·48], p=1·69×10– ¹²; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02–8·05]), despite similar baseline disease severity. Interpretation This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. Funding UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

The impact of the 2022 Ukraine/Russian conflict on cancer clinical trials

Since the invasion of Ukraine in February 2022, clinical trial conduct has become extremely challenging due to damage to the healthcare infrastructure and patient displacement. This current study aimed to estimate the number of cancer clinical trials at risk of impact from the conflict. A descriptive analysis and narrative review were completed using data from cancer clinical trials with sites in Russia or Ukraine using the ‘clinical trials.gov’ online database between February 2022 and May 2022. There were 508 clinical trials involving sites in Ukraine or Russia. Most were multinational studies (470 of 508; 93%). The majority of studies were phase 3 (344 of 508; 68%) and these also had the largest sample sizes (median 624, range 12–5637). The most common tumour types were lung (128 of 508; 25%), urogenital (94 of 508; 19%) and breast (78 of 508; 15%). A meaningful number of trials had curative intent (129 of 508; 25%). The most common intervention was immunotherapy-related (218 of 508; 43%), followed by other targeted therapy (185 of 508; 36%). Ukraine and Russia are both large centres for global clinical trial activity. The invasion of Ukraine may result in underpowering of international clinical trial results with loss of future recruitment sites for both countries

Prior Authorization in Total Joint Arthroplasty: A Survey of the American Association of Hip and Knee Surgeons Membership

BACKGROUND: This study surveyed the impact that prior authorization has on the practices of total joint arthroplasty (TJA) members of the American Association of Hip and Knee Surgeons (AAHKS) METHODS: A 24-question survey was approved by the AAHKS Advocacy Committee and distributed to all 2,802 board-certified members of AAHKS. RESULTS: There were 353 survey responses (13%). Ninety-five percent of surgeons noted a 5-year increase in prior authorization. A majority (71%) of practices employ at least one staff member to exclusively work on prior authorization. Average time spent on prior authorization was 15 hours/week (range, 1 to 125) and average number of claims peer week was 18 (range, 1 to 250). Surgeries (99%) were the most common denial. These were denied because non-operative treatment had not been tried (71%) or had not been attempted for enough time (67%). Most (57%) prior authorization processes rarely/never changed the treatment provided. Most (56%) indicated that prior authorization rarely/never followed evidence-based guidelines. A majority (93%) expressed high administrative burden as well as negative clinical outcomes (87%) due to prior authorization including delays to access care (96%) at least sometimes. CONCLUSIONS: Prior authorization has increased in the past 5 years resulting in high administrative burden. Prior authorizations were most common for TJA surgeries because certain nonoperative treatments were not attempted or not attempted for enough time. Surgeons indicated that prior authorization may be detrimental to high value care and lead to potentially harmful delays in care without ultimately changing the management of the patient

2023 American College of Rheumatology and American Association of Hip and Knee Surgeons Clinical Practice Guideline for the Optimal Timing of Elective Hip or Knee Arthroplasty for Patients With Symptomatic Moderate-to-Severe Osteoarthritis or Advanced Symptomatic Osteonecrosis With Secondary Arthritis for Whom Nonoperative Therapy Is Ineffective.

OBJECTIVE: To develop evidence-based consensus recommendations for the optimal timing of hip and knee arthroplasty to improve patient-important outcomes including, but not limited to, pain, function, infection, hospitalization, and death at 1 year for patients with symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis of the hip or knee who have previously attempted nonoperative therapy, and for whom nonoperative therapy was ineffective, and who have chosen to undergo elective hip or knee arthroplasty (collectively referred to as TJA). METHODS: We developed 13 clinically relevant population, intervention, comparator, outcomes (PICO) questions. After a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the quality of evidence (high, moderate, low, or very low), and evidence tables were created. A Voting Panel, including 13 physicians and patients, discussed the PICO questions until consensus was achieved on the direction (for/against) and strength (strong/conditional) of the recommendations. RESULTS: The panel conditionally recommended against delaying TJA to pursue additional nonoperative treatment including physical therapy, nonsteroidal antiinflammatory drugs, ambulatory aids, and intraarticular injections. It conditionally recommended delaying TJA for nicotine reduction or cessation. The panel conditionally recommended delay for better glycemic control for patients who have diabetes mellitus, although no specific measure or level was identified. There was consensus that obesity by itself was not a reason for delay, but that weight loss should be strongly encouraged, and the increase in operative risk should be discussed. The panel conditionally recommended against delay in patients who have severe deformity or bone loss, or in patients who have a neuropathic joint. Evidence for all recommendations was graded as low or very low quality. CONCLUSION: This guideline provides evidence-based recommendations regarding the optimal timing of TJA in patients who have symptomatic and radiographic moderate-to-severe osteoarthritis or advanced symptomatic osteonecrosis with secondary arthritis for whom nonoperative therapy was ineffective to improve patient-important outcomes, including pain, function, infection, hospitalization, and death at 1 year. We acknowledge that the evidence is of low quality primarily due to indirectness and hope future research will allow for further refinement of the recommendations