Therapeutic Vaccine for Genital Herpes Simplex Virus-2 Infection: Findings from a Randomized Trial

Background. Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate therapeutic vaccine containing HSV-2 gD2∆TMR and ICP4.2, and Matrix-M2 adjuvant. Methods. Persons with genital herpes were randomized into 3 dose cohorts to receive 3 intramuscular doses 21 days apart of 10 µg, 30 µg, or 100 µg of GEN-003, antigens without adjuvant, or placebo. Participants obtained genital swab specimens twice daily for HSV-2 detection and monitored genital lesions for 28-day periods at baseline and at intervals after the last dose. Results. One hundred and thirty-four persons received all 3 doses. Reactogenicity was associated with adjuvant but not with antigen dose or dose number. No serious adverse events were attributed to GEN-003. Compared with baseline, genital HSV-2 shedding rates immediately after dosing were reduced with GEN-003 (from 13.4% to 6.4% for 30 μg [P < .001] and from 15.0% to 10.3% for 100 µg [P < .001]). Lesion rates were also significantly (P < .01) reduced immediately following immunization with 30 µg or 100 µg of GEN-003. GEN-003 elicited increases in antigen binding, virus neutralizing antibody, and T-cell responses. Conclusions. GEN-003 had an acceptable safety profile and stimulated humoral and cellular immune responses. GEN-003 at doses of 30 µg and 100 µg reduced genital HSV shedding and lesion rates

The relativistic precession of the orbits

The relativistic precession can be quickly inferred from the nonlinear polar orbit equation without actually solving it.Comment: Accepted for publication in Astrophysics & Space Scienc

Combination Service for Time-variable Gravity Fields: operational GRACE-FO combination and validation of Chinese GRACE time-series

The Combination Service for Time-variable Gravity Fields (COST-G) of the International Association of Geodesy (IAG) provides combined monthly gravity fields of its associated and partner Analysis Centers (ACs). In November 2020, the combination of monthly GRACE-FO gravity fields started its operational mode, providing consolidated L2 (spherical harmonics) and L3 (gridded and post-processed) products with a latency of currently 3 months. We present an overview and quality assessment of the available products. COST-G aims at the extension of its service to include further GRACE and GRACE-FO analysis centers. In January 2020 a collaboration with representatives of five Chinese ACs was initiated, who provided GRACE time-series according to the COST-G requirements. We present the results of a test combination with the Chinese AC models, including comparison and quality assessment of all contributing time-series and validation of the combined gravity fields

Combination Service for Time-variable Gravity Fields (COST-G): operations and new developments

Since its start of operations in July 2019, IAGâ?Ts Combination Service for Time-variable Gravity fields (COST-G) is providing a complete time-series of combined monthly GRACE gravity fields and a regularly updated time-series of monthly gravity fields derived from kinematic Swarm orbits. Starting from October 2020, the COST-G product line is complemented by a time-series of operationally combined and monthly updated GRACE-FO gravity fields. All these combinations are performed by variance component estimation on the solution level. We report on new developments, i.e., a planned extension of COST-G to include Chinese analysis centers of GRACE and GRACE-FO data, a re-consideration of the combination strategy to better focus on the range of spherical harmonic coefficients most relevant for the users, and the potential application of COST-G products for orbit determination of altimeter satellites

Current state of quality of life and patient-reported outcomes research

The 5th EORTC Quality of Life in Cancer Clinical Trials Conference presented the current state of quality of life and other patient-reported outcomes (PROs) research from the perspectives of researchers, regulators, industry representatives, patients and patient advocates and health care professionals. A major theme was the assessment of the burden of cancer treatments, and this was discussed in terms of regulatory challenges in using PRO assessments in clinical trials, patients' experiences in cancer clinical trials, innovative methods and standardisation in cancer research, innovative methods across the disease sites or populations and cancer survivorship. Conferees demonstrated that PROs are becoming more accepted and major efforts are ongoing internationally to standardise PROs measurement, analysis and reporting in trials. Regulators are keen to collaborate with all stakeholders to ensure that the right questions are asked and the right answers are communicated. Improved technology and increased flexibility of measurement instruments are making PROs data more robust. Patients are being encouraged to be patient partners. International collaborations are essential, because this work cannot be accomplished on a national level

The effect of chemotherapy on health-related quality of life in mesothelioma: Results from the SWAMP trial

© 2015 Cancer Research UK. All rights reserved. Background: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice. Method: Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13. Results: Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks. Conclusions: HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage