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BACKGROUND: The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS: Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE: Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.

ABSTRACTObjective: Identify patient experience and preference towards thrombopoietin-receptor agonists (TPO-RAs) in treatment of immune thrombocytopenia (ITP) in the Netherlands.Methods: The Thrombopoietin-Receptor Agonist Patient experience (TRAPeze) survey used a discrete choice experiment (DCE) to elicit patient preferences and a patient burden survey (PBS) to evaluate the clinical and social impact of ITP. TRAPeze collected responses from 6th October to 19th November 2021.Results: Seventy-six respondents completed the DCE: treatment preference appeared to be driven by method of administration (odds ratio [OR] 4.33; 95% confidence interval [CI] 2.88–6.52), frequency of dosing (OR 2.33; 95% CI 1.86–2.92) and drug–food interactions (OR 1.91; 95% CI 1.54–2.37). Respondents preferred therapies delivered orally over subcutaneous injection (OR 4.22; 95% CI 2.76–6.46), dosed once weekly over once daily (OR 2.37; 95% CI 1.58–3.54) and without food restrictions over with restrictions (OR 1.90; 95% CI 1.52–2.38). Sixty-nine respondents completed the DCE and PBS (mean [range] age 53 [19–83] years, 65% female). Seven incomplete PBS responses were excluded from analysis. Respondents were currently, or most recently, receiving eltrombopag (n = 43) or romiplostim (n = 26), of which 30% (n = 21/69) had previously received another TPO-RA. Loss (29%, n = 6/21) and lack (29%, n = 6/21) of response were the most common reasons for switching TPO-RA. Only 28% (n = 18/65) of respondents felt their TPO-RA increased energy levels.Conclusion: Patients preferred therapies delivered orally, dosed less frequently and without food restrictions. QoL of ITP patients on TPO-RAs can be improved; the burden analyses presented can inform future efforts towards this.

ABSTRACTObjective Identify patient preference towards thrombopoietin-receptor agonists (TPO-RAs) and determine the clinical and social impact of immune thrombocytopenia (ITP) in Italy.Methods The Thrombopoietin-Receptor Agonist Patient experience (TRAPeze) survey collected responses from Italian residents from 17th January to 28th February 2022. TRAPeze utilized a discrete choice experiment (DCE) to elicit patient preferences towards TPO-RA attributes and a patient burden survey (PBS) to determine ITP disease characteristics and social impact.Results Seventy-six respondents completed the DCE, of which 69 completed both the DCE and PBS (mean [range] age 45 [18.0–73.0] years, 80% female). TPO-RA attributes with the greatest influence over respondent choice were method of administration (odds ratio [OR] 2.96; 95% confidence interval [CI] 2.16–4.06), drug-food interactions (OR 1.48; 95% CI 1.17–1.86) and frequency of dosing (OR 1.32; 95% CI 1.15–1.52). Respondents were more likely to prefer therapies administered orally over subcutaneous injection (OR 3.76; 95% CI 2.51–5.63), once weekly over once daily (OR 1.83; 95% CI 1.26–2.65), and therapies without food restrictions over with restrictions (OR 1.58; 95% CI 1.17–2.14).The most frequently reported symptoms were bruising (82%), petechiae (65%) and fatigue (64%). Most respondents (84%) felt ITP impacted familial relationships and 71% of employed respondents reported fatigue influencing their ability to work, with 31% reducing working hours.Conclusion Although responses indicated a moderate perception of general health, ITP clearly impacted respondent work and social life. Our findings demonstrate respondents preferred TPO-RAs delivered orally, with less frequent dosing and without food restrictions.

Abstract This study describes the use of cynomolgus macaques of Chinese origin (CCM) to evaluate the efficacy and immunogenicity of the BCG vaccine against high dose aerosol Mycobacterium tuberculosis challenge. Progressive disease developed in three of the unvaccinated animals within 10 weeks of challenge, whereas all six vaccinated animals controlled disease for 26 weeks. Three unvaccinated animals limited disease progression, highlighting the intrinsic ability of this macaque species to control disease in comparison to macaques of other species and genotypes. Low levels of IFNγ were induced by BCG vaccination in CCM suggesting that IFNγ alone does not provide a sufficiently sensitive biomarker of vaccination in this model. An early response after challenge, together with the natural bias towards terminal effector memory T-cell populations and the contribution of monocytes appears to enhance the ability of CCM to naturally control infection. The high dose aerosol challenge model of CCM has value for examination of the host immune system to characterise control of infection which would influence future vaccine design. Although it may not be the preferred platform for the assessment of prophylactic vaccine candidates, the model could be well suited for testing post-exposure vaccination strategies and drug evaluation studies.

Abstract Rhesus (Macaca mulatta) and cynomolgus (Macaca fasicularis) macaques of distinct genetic origin are understood to vary in susceptibility to Mycobacterium tuberculosis, and therefore differences in their immune systems may account for the differences in disease control. Monocyte:lymphocyte (M:L) ratio has been identified as a risk factor for M. tuberculosis infection and is known to vary between macaque species. We aimed to characterise the constituent monocyte and lymphocyte populations between macaque species, and profile other major immune cell subsets including: CD4+ and CD8+ T-cells, NK-cells, B-cells, monocyte subsets and myeloid dendritic cells. We found immune cell subsets to vary significantly between macaque species. Frequencies of CD4+ and CD8+ T-cells and the CD4:CD8 ratio showed significant separation between species, while myeloid dendritic cells best associated macaque populations by M. tuberculosis susceptibility. A more comprehensive understanding of the immune parameters between macaque species may contribute to the identification of new biomarkers and correlates of protection.

Non-human primates are important animal models for studying SARS-CoV-2 infection. Here, Salguero et al. directly compare rhesus and cynomolgus macaques and show that both species represent COVID-19 disease of mild clinical cases, and provide a lung histopathology scoring system.