Assessing Pandemic Preparedness, Response, and Lessons Learned From the Covid-19 Pandemic in Four South American Countries: Agenda for the Future

INTRODUCTION: The COVID-19 pandemic emerged in a context that lacked adequate prevention, preparedness, and response (PPR) activities, and global, regional, and national leadership. South American countries were among world\u27s hardest hit by the pandemic, accounting for 10.1% of total cases and 20.1% of global deaths. METHODS: This study explores how pandemic PPR were affected by political, socioeconomic, and health system contexts as well as how PPR may have shaped pandemic outcomes in Argentina, Brazil, Colombia, and Peru. We then identify lessons learned and advance an agenda for improving PPR capacity at regional and national levels. We do this through a mixed-methods sequential explanatory study in four South American countries based on structured interviews and focus groups with elite policy makers. RESULTS: The results of our study demonstrate that structural and contextual barriers limited PPR activities at political, social, and economic levels in each country, as well as through the structure of the health care system. Respondents believe that top-level government officials had insufficient political will for prioritizing pandemic PPR and post-COVID-19 recovery programs within their countries\u27 health agendas. DISCUSSION: We recommend a regional COVID-19 task force, post-pandemic recovery, social and economic protection for vulnerable groups, improved primary health care and surveillance systems, risk communication strategies, and community engagement to place pandemic PPR on Argentina, Brazil, Colombia, and Peru and other South American countries\u27 national public health agendas

Red blood cell tension protects against severe malaria in the Dantu blood group.

Malaria has had a major effect on the human genome, with many protective polymorphisms-such as the sickle-cell trait-having been selected to high frequencies in malaria-endemic regions1,2. The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals3-5, a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine. Until now, however, the protective mechanism has been unknown. Here we demonstrate the effect of Dantu on the ability of the merozoite form of the malaria parasite Plasmodium falciparum to invade red blood cells (RBCs). We find that Dantu is associated with extensive changes to the repertoire of proteins found on the RBC surface, but, unexpectedly, inhibition of invasion does not correlate with specific RBC-parasite receptor-ligand interactions. By following invasion using video microscopy, we find a strong link between RBC tension and merozoite invasion, and identify a tension threshold above which invasion rarely occurs, even in non-Dantu RBCs. Dantu RBCs have higher average tension than non-Dantu RBCs, meaning that a greater proportion resist invasion. These findings provide both an explanation for the protective effect of Dantu, and fresh insight into why the efficiency of P. falciparum invasion might vary across the heterogenous populations of RBCs found both within and between individuals.JCR, AM and DK were supported by the Wellcome Trust (206194/Z/17/Z). MPW is funded by a Wellcome Senior Fellowship (108070). TNW is funded through Fellowships awarded by the Wellcome Trust (091758 and 202800). SNK is supported by the Wellcome Trust-funded Initiative to Develop African Research Leaders (IDeAL) early-career postdoctoral fellowship (107769/Z/10/Z), supported through the DELTAS Africa Initiative (DEL-15-003). The Wellcome Trust provides core support to The KEMRI/Wellcome Trust Research Programme, Kilifi, Kenya (084535), Wellcome Sanger Institute, Cambridge, UK (206194/Z/17/Z) and the Wellcome Centre for Human Genetics, Oxford, UK (090532/Z/09/Z, 203141). PC is supported by the Engineering and Physical Sciences Research Council (EPSRC) (EP/R011443/1), and VI is supported by the EPSRC and the Sackler fellowship

Rationale for Utilization of Hydrogel Rectal Spacers in Dose Escalated SBRT for the Treatment of Unfavorable Risk Prostate Cancer

In this review we outline the current evidence for the use of hydrogel rectal spacers in the treatment paradigm for prostate cancer with external beam radiation therapy. We review their development, summarize clinical evidence, risk of adverse events, best practices for placement, treatment planning considerations and finally we outline a framework and rationale for the utilization of rectal spacers when treating unfavorable risk prostate cancer with dose escalated Stereotactic Body Radiation Therapy (SBRT)

Assessing pandemic preparedness, response, and lessons learned from the COVID-19 pandemic in four south American countries: agenda for the future

IntroductionThe COVID-19 pandemic emerged in a context that lacked adequate prevention, preparedness, and response (PPR) activities, and global, regional, and national leadership. South American countries were among world’s hardest hit by the pandemic, accounting for 10.1% of total cases and 20.1% of global deaths.MethodsThis study explores how pandemic PPR were affected by political, socioeconomic, and health system contexts as well as how PPR may have shaped pandemic outcomes in Argentina, Brazil, Colombia, and Peru. We then identify lessons learned and advance an agenda for improving PPR capacity at regional and national levels. We do this through a mixed-methods sequential explanatory study in four South American countries based on structured interviews and focus groups with elite policy makers.ResultsThe results of our study demonstrate that structural and contextual barriers limited PPR activities at political, social, and economic levels in each country, as well as through the structure of the health care system. Respondents believe that top-level government officials had insufficient political will for prioritizing pandemic PPR and post-COVID-19 recovery programs within their countries’ health agendas.DiscussionWe recommend a regional COVID-19 task force, post-pandemic recovery, social and economic protection for vulnerable groups, improved primary health care and surveillance systems, risk communication strategies, and community engagement to place pandemic PPR on Argentina, Brazil, Colombia, and Peru and other South American countries’ national public health agendas

Intensity Modulated Radiation Therapy With Stereotactic Body Radiation Therapy Boost for Unfavorable Prostate Cancer: Five-Year Outcomes

PURPOSE: Intensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost. MATERIALS AND METHODS: Between 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45-50.4 Gy) according to an institutional protocol. For the first year, the patient\u27s PSA level was monitored every 3 months, biannually for 2 years, and annually thereafter. Failure was defined as nadir + 2 ng/mL or a rising PSA with imaging suggestive of recurrence. Detection of recurrence also included digital rectal examination and imaging studies, such as MRI, CT, PET/CT, and/or bone scans. PFS and PCSS were calculated using the Kaplan-Meier method. RESULTS: The median follow-up period was 71 months. According to the NCCN risk classification, 5% (13/255) of the patients had favorable intermediate-risk disease, 23% (57/255) had unfavorable intermediate-risk disease, 40% (102/255) had high-risk disease, and 32% (83/255) had very high-risk disease. Androgen deprivation therapy was administered to 80% (204/255) of the patients. Elective pelvic lymph node IMRT was performed in 28 (10%) patients. The PFS for all patients at 5 years was 81% (favorable intermediate risk, 91%; unfavorable intermediate risk, 89%; high-risk, 78%; and very-high risk, 72%). The PCSS for all patients at 5 years was 97% (favorable intermediate risk, 100%; unfavorable intermediate risk, 100%; high risk, 100%; and very high risk, 89%). CONCLUSION: The incidence of failure following IMRT plus SBRT for unfavorable prostate cancer remains low at 5 years

Intensity modulated radiation therapy with stereotactic body radiation therapy boost for unfavorable prostate cancer: five-year outcomes

PurposeIntensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost.Materials and methodsBetween 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45–50.4 Gy) according to an institutional protocol. For the first year, the patient’s PSA level was monitored every 3 months, biannually for 2 years, and annually thereafter. Failure was defined as nadir + 2 ng/mL or a rising PSA with imaging suggestive of recurrence. Detection of recurrence also included digital rectal examination and imaging studies, such as MRI, CT, PET/CT, and/or bone scans. PFS and PCSS were calculated using the Kaplan–Meier method.ResultsThe median follow-up period was 71 months. According to the NCCN risk classification, 5% (13/255) of the patients had favorable intermediate-risk disease, 23% (57/255) had unfavorable intermediate-risk disease, 40% (102/255) had high-risk disease, and 32% (83/255) had very high-risk disease. Androgen deprivation therapy was administered to 80% (204/255) of the patients. Elective pelvic lymph node IMRT was performed in 28 (10%) patients. The PFS for all patients at 5 years was 81% (favorable intermediate risk, 91%; unfavorable intermediate risk, 89%; high-risk, 78%; and very-high risk, 72%). The PCSS for all patients at 5 years was 97% (favorable intermediate risk, 100%; unfavorable intermediate risk, 100%; high risk, 100%; and very high risk, 89%).ConclusionThe incidence of failure following IMRT plus SBRT for unfavorable prostate cancer remains low at 5 years

The James Webb Space Telescope Mission: Optical Telescope Element Design, Development, and Performance

The James Webb Space Telescope (JWST) is a large, infrared space telescope that has recently started its science program which will enable breakthroughs in astrophysics and planetary science. Notably, JWST will provide the very first observations of the earliest luminous objects in the Universe and start a new era of exoplanet atmospheric characterization. This transformative science is enabled by a 6.6 m telescope that is passively cooled with a 5-layer sunshield. The primary mirror is comprised of 18 controllable, low areal density hexagonal segments, that were aligned and phased relative to each other in orbit using innovative image-based wavefront sensing and control algorithms. This revolutionary telescope took more than two decades to develop with a widely distributed team across engineering disciplines. We present an overview of the telescope requirements, architecture, development, superb on-orbit performance, and lessons learned. JWST successfully demonstrates a segmented aperture space telescope and establishes a path to building even larger space telescopes.Comment: accepted by PASP for JWST Overview Special Issue; 34 pages, 25 figure

Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.

Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29