The Apollo Lunar Orbit Rendezvous Architecture Decision Revisited

This conference features the work of authors from: Georgia Tech’s Space Systems Design Lab, Aerospace Systems Design Lab, School of Aerospace Engineering, Georgia Tech Research Institute; NASA’s Jet Propulsion Laboratory, Marshall Space Flight Center, Goddard Space Flight Center, Langley Research Center; and other aerospace industry and academic institutionsThe 1962 Apollo architecture mode decision process was revisited with modern analysis and systems engineer tools to determine driving selection criteria and technology/operational mode design decisions that may be used for NASA’s current Space Exploration program. Results of the study agreed with the Apollo selection of the Lunar Orbit Rendezvous mode based on the technology maturity and politics in 1962. Using today’s greater emphasis on human safety and improvements in technology and design maturity, a slight edge may be given to the direct lunar mode over lunar orbit rendezvous. Also, the NOVA direct mode and Earth orbit rendezvous mode are not competitive based any selection criteria. Finally, reliability and development, operations, and production costs are major drivers in today’s decision process.AIAA Space Systems Technical Committee ; AIAA Space Transportation Systems Technical Committee ; Space Technology Advanced Research Cente

Vorinostat in advanced prostate cancer patients progressing on prior chemotherapy (National Cancer Institute Trial 6862)

BACKGROUND: This phase 2 trial was designed to evaluate the efficacy of vorinostat in chemotherapy-pretreated patients with metastatic castration-resistant prostate cancer. METHODS: Patients with disease progression on 1 prior chemotherapy, a prostate-specific antigen (PSA) ≥5 ng/mL, and adequate organ function were treated with 400 mg vorinostat orally daily. The primary endpoint was the 6-month progression rate. Secondary endpoints included safety, rate of PSA decline, objective response, overall survival, and effects of vorinostat on serum interleukin-6 (IL-6) levels. RESULTS: Twenty-seven eligible patients were accrued. The median number of cycles delivered was 2 (range, 1-7). All patients were taken off therapy before 6 months. The best objective response in the eligible patient was stable disease in 2 (7%) patients. No PSA decline of ≥50% was observed. There was 1 grade 4 adverse event (AE), and 44% of patients experienced grade 3 adverse events. The most common adverse events were fatigue (81%), nausea (74%), anorexia (59%), vomiting (33%), diarrhea (33%), and weight loss (26%). Median time to progression and overall survival were 2.8 and 11.7 months, respectively. Median IL-6 levels (pg/mL) were higher in patients removed from the protocol for toxicity compared with progression at all time points, including baseline (5.2 vs 2.1, P = .02), Day 15 Cycle 1 (9.5 vs 2.2, P = .01), Day 1 Cycle 2 (9.8 vs 2.2, P = .01), and end of study (11.0 vs 2.9, P = .09). CONCLUSIONS: Vorinostat at this dose was associated with significant toxicities limiting efficacy assessment in this patient population. The significant association between IL-6 levels and removal from the study for toxicities warrants further investigation. Cancer 2009. © 2009 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64445/1/24597_ftp.pd

Maternal Active and Passive Smoking and Hypertensive Disorders of Pregnancy: Risk with Trimester-Specific Exposures

The inverse association between prenatal smoking and preeclampsia is puzzling, given the increased risks of prematurity and low birthweight associated with both smoking and preeclampsia. We analyzed the Norwegian Mother and Child Birth Cohort (MoBa) to determine whether the associations varied by timing of prenatal smoking

Phase 1/2 multiple ascending dose trial of the prostate-specific membrane antigen-targeted antibody drug conjugate MLN2704 in metastatic castration-resistant prostate cancer

This phase 1/2 study evaluated the dose-limiting toxicity and maximum tolerated dose of MLN2704, a humanized monoclonal antibody MLN591 targeting prostate-specific membrane antigen, linked to the maytansinoid DM1 in patients with progressive metastatic castration-resistant prostate cancer

Guidelines of the International Headache Society for controlled trials of pharmacological preventive treatment for persistent post-traumatic headache attributed to mild traumatic brain injury

Background: Persistent headache attributed to traumatic injury to the head is divided into two subtypes, one attributed to moderate or severe traumatic injury and another attributed to mild traumatic injury (i.e., concussion). The latter is much more prevalent, in part because more than 90% of cases with traumatic brain injury are classified as mild. The pathophysiology of persistent post-traumatic headache is poorly understood and the underlying mechanisms are likely multifactorial. There is currently no approved treatment specifically for persistent post-traumatic headache, and management strategies rely on medications used for migraine or tension-type headache. Therefore, high-quality trials are urgently needed to support clinical decision-making and optimize management strategies. International guidelines can facilitate appropriate trial design and ensure the acquisition of high-quality data evaluating the efficacy, tolerability, and safety of available and novel pharmacological therapies for the preventive treatment of persistent post-traumatic headache. Methods: The development of this guideline was based on a literature review of available studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, along with a review of previously published guidelines for controlled trials of preventive treatment for episodic and chronic migraine. The identified literature was critically appraised, and due to the scarcity of scientific evidence, recommendations were primarily based on the consensus of experts in the field. Objective: To provide guidelines for designing state-of-the-art controlled clinical trials aimed at evaluating the effectiveness of preventive treatments for persistent post-traumatic headache attributed to mild traumatic brain injury

Localized Mucosal Response to Intranasal Live Attenuated Influenza Vaccine in Adults

Background. Influenza virus infection is a major public health burden worldwide. Available vaccines include the inactivated intramuscular trivalent vaccine and, more recently, an intranasal live attenuated influenza vaccine (LAIV). The measure of successful vaccination with the inactivated vaccine is a systemic rise in immunoglobulin G (IgG) level, but for the LAIV no such correlate has been established

Assignment of epidemiological lineages in an emerging pandemic using the pangolin tool.

Funder: Oxford Martin School, University of OxfordThe response of the global virus genomics community to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been unprecedented, with significant advances made towards the 'real-time' generation and sharing of SARS-CoV-2 genomic data. The rapid growth in virus genome data production has necessitated the development of new analytical methods that can deal with orders of magnitude of more genomes than previously available. Here, we present and describe Phylogenetic Assignment of Named Global Outbreak Lineages (pangolin), a computational tool that has been developed to assign the most likely lineage to a given SARS-CoV-2 genome sequence according to the Pango dynamic lineage nomenclature scheme. To date, nearly two million virus genomes have been submitted to the web-application implementation of pangolin, which has facilitated the SARS-CoV-2 genomic epidemiology and provided researchers with access to actionable information about the pandemic's transmission lineages

Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD):a multicentre, open-label, phase 2 trial

Background: Metastatic castration-resistant prostate cancers are enriched for DNA repair gene defects (DRDs) that can be susceptible to synthetic lethality through inhibition of PARP proteins. We evaluated the anti-tumour activity and safety of the PARP inhibitor niraparib in patients with metastatic castration-resistant prostate cancers and DRDs who progressed on previous treatment with an androgen signalling inhibitor and a taxane. Methods: In this multicentre, open-label, single-arm, phase 2 study, patients aged at least 18 years with histologically confirmed metastatic castration-resistant prostate cancer (mixed histology accepted, with the exception of the small cell pure phenotype) and DRDs (assessed in blood, tumour tissue, or saliva), with progression on a previous next-generation androgen signalling inhibitor and a taxane per Response Evaluation Criteria in Solid Tumors 1.1 or Prostate Cancer Working Group 3 criteria and an Eastern Cooperative Oncology Group performance status of 0–2, were eligible. Enrolled patients received niraparib 300 mg orally once daily until treatment discontinuation, death, or study termination. For the final study analysis, all patients who received at least one dose of study drug were included in the safety analysis population; patients with germline pathogenic or somatic biallelic pathogenic alterations in BRCA1 or BRCA2 (BRCA cohort) or biallelic alterations in other prespecified DRDs (non-BRCA cohort) were included in the efficacy analysis population. The primary endpoint was objective response rate in patients with BRCA alterations and measurable disease (measurable BRCA cohort). This study is registered with ClinicalTrials.gov, NCT02854436. Findings: Between Sept 28, 2016, and June 26, 2020, 289 patients were enrolled, of whom 182 (63%) had received three or more systemic therapies for prostate cancer. 223 (77%) of 289 patients were included in the overall efficacy analysis population, which included BRCA (n=142) and non-BRCA (n=81) cohorts. At final analysis, with a median follow-up of 10·0 months (IQR 6·6–13·3), the objective response rate in the measurable BRCA cohort (n=76) was 34·2% (95% CI 23·7–46·0). In the safety analysis population, the most common treatment-emergent adverse events of any grade were nausea (169 [58%] of 289), anaemia (156 [54%]), and vomiting (111 [38%]); the most common grade 3 or worse events were haematological (anaemia in 95 [33%] of 289; thrombocytopenia in 47 [16%]; and neutropenia in 28 [10%]). Of 134 (46%) of 289 patients with at least one serious treatment-emergent adverse event, the most common were also haematological (thrombocytopenia in 17 [6%] and anaemia in 13 [4%]). Two adverse events with fatal outcome (one patient with urosepsis in the BRCA cohort and one patient with sepsis in the non-BRCA cohort) were deemed possibly related to niraparib treatment. Interpretation: Niraparib is tolerable and shows anti-tumour activity in heavily pretreated patients with metastatic castration-resistant prostate cancer and DRDs, particularly in those with BRCA alterations. Funding: Janssen Research & Development

Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial

Angela Cheung and colleagues investigate whether vitamin K1 can prevent bone loss among postmenopausal women with osteopenia