Recent attempts to date batches of poorly preserved archaeological bone prompted a re-evaluation of existing protocols for bone sample preparation and ultrafilter cleaning methods at the Keck-Carbon ...Cycle Accelerator Mass Spectrometer (KCCAMS) facility. The emphasis of the study was to optimize decalcification time and ultrafiltration retention efficiency to improve overall collagen yields, especially for poorly preserved bone. Decalcification time and acid strength tests were done on four in-house bone standards of varying states of preservation. Through systematic testing, we found that 200 mg bone chip samples decalcified in 4 mL of 1.0 N HCl over 16 h showed increases of collagen yield across all samples relative to our existing protocol. Ultrafilters precleaned with weak acid (0.01 N HCl) showed greater retention efficiencies than those cleaned by sonication in ultrapure Milli-Q (MQ) water. Collagen produced from each sample were analyzed via AMS dating to check the quality of the collagen.
Abstract
Background
The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the ...potential impact of different treatments, and consequently research and procurement priorities, have not been clear.
Methods
Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care.
Results
The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics.
Conclusions
Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.
Coronavirus disease 2019 (COVID-19) drug development to date has focused on reducing deaths among hospitalized patients, but greater public-health impact could come from drugs delivered to outpatients early in the course of disease, and that prevent hospitalization and/or onwards transmission.
•Equitable global pandemic preparedness requires evidence from all income settings.•We conducted a first-of-a-kind detailed modelling analysis of COVID-19 in a low-income setting.•Infection and ...excess death rates in Kabwe, Zambia were among the highest in Africa.•Constraints in health care and timely vaccination rollout amplified this burden.•Our methods open up novel avenues to infer pandemic dynamics in low-income settings.
Pandemic response in low-income countries (LICs) or settings often suffers from scarce epidemic surveillance and constrained mitigation capacity. The drivers of pandemic burden in such settings, and the impact of limited and delayed interventions remain poorly understood.
We analysed COVID-19 seroprevalence and all-cause excess deaths data from the peri-urban district of Kabwe, Zambia between March 2020 and September 2021 with a novel mathematical model. Data encompassed three consecutive waves caused by the wild-type, Beta and Delta variants.
Across all three waves, we estimated a high cumulative attack rate, with 78% (95% credible interval CrI 71-85) of the population infected, and a high all-cause excess mortality, at 402 (95% CrI 277-473) deaths per 100,000 people. Ambitiously improving health care to a capacity similar to that in high-income settings could have averted up to 46% (95% CrI 41-53) of accrued excess deaths, if implemented from June 2020 onward. An early and accelerated vaccination rollout could have achieved the highest reductions in deaths. Had vaccination started as in some high-income settings in December 2020 and with the same daily capacity (doses per 100 population), up to 68% (95% CrI 64-71) of accrued excess deaths could have been averted. Slower rollouts would have still averted 62% (95% CrI 58-68), 54% (95% CrI 49-61) or 26% (95% CrI 20-38) of excess deaths if matching the average vaccination capacity of upper-middle-, lower-middle- or LICs, respectively.
Robust quantitative analyses of pandemic data are of pressing need to inform future global pandemic preparedness commitments.
IntroductionMortality among children hospitalised for complicated severe acute malnutrition (SAM) remains high despite the implementation of WHO guidelines, particularly in settings of high HIV ...prevalence. Children continue to be at high risk of morbidity, mortality and relapse after discharge from hospital although long-term outcomes are not well documented. Better understanding the pathogenesis of SAM and the factors associated with poor outcomes may inform new therapeutic interventions.Methods and analysisThe Health Outcomes, Pathogenesis and Epidemiology of Severe Acute Malnutrition (HOPE-SAM) study is a longitudinal observational cohort that aims to evaluate the short-term and long-term clinical outcomes of HIV-positive and HIV-negative children with complicated SAM, and to identify the risk factors at admission and discharge from hospital that independently predict poor outcomes. Children aged 0–59 months hospitalised for SAM are being enrolled at three tertiary hospitals in Harare, Zimbabwe and Lusaka, Zambia. Longitudinal mortality, morbidity and nutritional data are being collected at admission, discharge and for 48 weeks post discharge. Nested laboratory substudies are exploring the role of enteropathy, gut microbiota, metabolomics and cellular immune function in the pathogenesis of SAM using stool, urine and blood collected from participants and from well-nourished controls.Ethics and disseminationThe study is approved by the local and international institutional review boards in the participating countries (the Joint Research Ethics Committee of the University of Zimbabwe, Medical Research Council of Zimbabwe and University of Zambia Biomedical Research Ethics Committee) and the study sponsor (Queen Mary University of London). Caregivers provide written informed consent for each participant. Findings will be disseminated through peer-reviewed journals, conference presentations and to caregivers at face-to-face meetings.
This title is part of UC Press's Voices Revived program, which commemorates University of California Press's mission to seek out and cultivate the brightest minds and give them voice, reach, and ...impact. Drawing on a backlist dating to 1893, Voices Revived makes high-quality, peer-reviewed scholarship accessible once again using print-on-demand technology. This title was originally published in 1963.
Herpesvirus replication involves the expression of over 80 viral genes in a well ordered sequence, leading to the production of new virions. Viral genes expressed during the earliest phases of ...replication often regulate both viral and cellular genes. Therefore, they have the potential to bring about dramatic functional changes within the cell. Replication and transcription activator (RTA) is a potent immediate early transcription activator of the γ-herpesvirus family. This family includes Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus, human pathogens associated with malignancy. Here we combine gene array technology with transcription factor profiling to identify the earliest DNA promoter and cellular transcription factor targets of RTA in the cellular genome. We find that expression of RTA leads to both activation and inhibition of distinct groups of cellular genes. The identity of the target genes suggests that RTA rapidly changes the cellular environment to counteract cell death pathways, support growth factor signaling, and also promote immune evasion of the infected cell. Transcription factor profiling of the target gene promoters highlighted distinct pathways involved in gene activation at specific time points. Most notable throughout was the high level of cAMP-response element-binding protein (CREB)-response elements in RTA target genes. We find that RTA can function as either an activator or an inhibitor of CREB-response genes, depending on the promoter context. The association with CREB also highlights a novel connection and coordination between viral and cellular “immediate early” responses.
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