Mass vaccination offers a promising exit strategy for the COVID-19 pandemic. However, as vaccination progresses, demands to lift restrictions increase, despite most of the population remaining ...susceptible. Using our age-stratified SEIRD-ICU compartmental model and curated epidemiological and vaccination data, we quantified the rate (relative to vaccination progress) at which countries can lift non-pharmaceutical interventions without overwhelming their healthcare systems. We analyzed scenarios ranging from immediately lifting restrictions (accepting high mortality and morbidity) to reducing case numbers to a level where test-trace-and-isolate (TTI) programs efficiently compensate for local spreading events. In general, the age-dependent vaccination roll-out implies a transient decrease of more than ten years in the average age of ICU patients and deceased. The pace of vaccination determines the speed of lifting restrictions; Taking the European Union (EU) as an example case, all considered scenarios allow for steadily increasing contacts starting in May 2021 and relaxing most restrictions by autumn 2021. Throughout summer 2021, only mild contact restrictions will remain necessary. However, only high vaccine uptake can prevent further severe waves. Across EU countries, seroprevalence impacts the long-term success of vaccination campaigns more strongly than age demographics. In addition, we highlight the need for preventive measures to reduce contagion in school settings throughout the year 2021, where children might be drivers of contagion because of them remaining susceptible. Strategies that maintain low case numbers, instead of high ones, reduce infections and deaths by factors of eleven and five, respectively. In general, policies with low case numbers significantly benefit from vaccination, as the overall reduction in susceptibility will further diminish viral spread. Keeping case numbers low is the safest long-term strategy because it considerably reduces mortality and morbidity and offers better preparedness against emerging escape or more contagious virus variants while still allowing for higher contact numbers (freedom) with progressing vaccinations.
Without a cure, vaccine, or proven long-term immunity against SARS-CoV-2, test-trace-and-isolate (TTI) strategies present a promising tool to contain its spread. For any TTI strategy, however, ...mitigation is challenged by pre- and asymptomatic transmission, TTI-avoiders, and undetected spreaders, which strongly contribute to "hidden" infection chains. Here, we study a semi-analytical model and identify two tipping points between controlled and uncontrolled spread: (1) the behavior-driven reproduction number Formula: see text of the hidden chains becomes too large to be compensated by the TTI capabilities, and (2) the number of new infections exceeds the tracing capacity. Both trigger a self-accelerating spread. We investigate how these tipping points depend on challenges like limited cooperation, missing contacts, and imperfect isolation. Our results suggest that TTI alone is insufficient to contain an otherwise unhindered spread of SARS-CoV-2, implying that complementary measures like social distancing and improved hygiene remain necessary.
This study evaluated azacitidine as treatment of minimal residual disease (MRD) determined by a sensitive donor chimerism analysis of CD34(+) blood cells to pre-empt relapse in patients with CD34(+) ...myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT). At a median of 169 days after HSCT, 20/59 prospectively screened patients experienced a decrease of CD34(+) donor chimerism to <80% and received four azacitidine cycles (75 mg/m(2)/day for 7 days) while in complete hematologic remission. A total of 16 patients (80%) responded with either increasing CD34(+) donor chimerism to ≥80% (n=10; 50%) or stabilization (n=6; 30%) in the absence of relapse. Stabilized patients and those with a later drop of CD34(+) donor chimerism to <80% after initial response were eligible for subsequent azacitidine cycles. A total of 11 patients (55%) received a median of 4 (range, 1-11) additional cycles. Eventually, hematologic relapse occurred in 13 patients (65%), but was delayed until a median of 231 days (range, 56-558) after initial decrease of CD34(+) donor chimerism to <80%. In conclusion, pre-emptive azacitidine treatment has an acceptable safety profile and can substantially prevent or delay hematologic relapse in patients with MDS or AML and MRD after allogeneic HSCT.
The Role of Vitamin D in Cancer Prevention Garland, Cedric F; Garland, Frank C; Gorham, Edward D ...
American journal of public health (1971),
02/2006, Letnik:
96, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database ...search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects.
Vitamin D for Cancer Prevention: Global Perspective Garland, Cedric F., Dr PH, FACE; Gorham, Edward D., MPH, PhD; Mohr, Sharif B., MPH ...
Annals of epidemiology,
07/2009, Letnik:
19, Številka:
7
Journal Article
Recenzirano
Purpose Higher serum levels of the main circulating form of vitamin D, 25-hydroxyvitamin D (25(OH)D), are associated with substantially lower incidence rates of colon, breast, ovarian, renal, ...pancreatic, aggressive prostate and other cancers. Methods Epidemiological findings combined with newly discovered mechanisms suggest a new model of cancer etiology that accounts for these actions of 25(OH)D and calcium. Its seven phases are disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition (abbreviated DINOMIT). Vitamin D metabolites prevent disjunction of cells and are beneficial in other phases. Results/Conclusions It is projected that raising the minimum year-around serum 25(OH)D level to 40 to 60 ng/mL (100–150 nmol/L) would prevent approximately 58,000 new cases of breast cancer and 49,000 new cases of colorectal cancer each year, and three fourths of deaths from these diseases in the United States and Canada, based on observational studies combined with a randomized trial. Such intakes also are expected to reduce case-fatality rates of patients who have breast, colorectal, or prostate cancer by half. There are no unreasonable risks from intake of 2000 IU per day of vitamin D3 , or from a population serum 25(OH)D level of 40 to 60 ng/mL. The time has arrived for nationally coordinated action to substantially increase intake of vitamin D and calcium.
Aims/hypothesis This study is an analysis of the relationship between ultraviolet B (UVB) irradiance, the primary source of circulating vitamin D in humans, and age-standardised incidence rates of ...type 1 diabetes mellitus in children, according to region of the world. Methods The association of UVB irradiance adjusted for cloud cover to incidence rates of type 1 diabetes in children aged <14 years during 1990-1994 in 51 regions worldwide was assessed using multiple regression. Incidence data were obtained from the Diabetes Mondial Project Group. Results Incidence rates were generally higher at higher latitudes (R ² = 0.25, p < 0.001). According to multiple regression, UVB irradiance adjusted for cloud cover was inversely associated with incidence rates (p < 0.05), while per capita health expenditure (p < 0.004) was positively associated (overall R ² = 0.42, p < 0.0001). Conclusions/interpretation An association was found between low UVB irradiance and high incidence rates of type 1 childhood diabetes after controlling for per capita health expenditure. Incidence rates of type 1 diabetes approached zero in regions worldwide with high UVB irradiance, adding new support to the concept of a role of vitamin D in reducing the risk of the disease.
Kraft pulp fiber reinforced cement-based materials are being increasingly used where performance after exposure to environmental conditions must be ensured. However, significant losses in mechanical ...performance due to wet/dry cycling have been observed in these composites, when portland cement is the only cementitious material used in the matrix. In this research program, the effects of partial portland cement replacement with various supplementary cementitious materials were investigated. Binary, ternary, and quaternary blends of silica fume, slag, Class C fly ash, Class F fly ash, metakaolin, and diatomaceous earth/volcanic ash blends were examined for their effect on the degradation of kraft pulp fiber-cement composite mechanical properties (i.e., strength and toughness) during wet/dry cycling. After 25 wet/dry cycles, it was shown that binary composites containing 90% slag, 30% metakaolin, or greater than 30% silica fume did not exhibit any signs of degradation, as measured through mechanical testing and microscopy. Ternary blends containing 70% slag/10% metakaolin or 70% slag/10% silica fume were also effective in preventing degradation. A reduction in calcium hydroxide content and the stability of the alkali content due to supplementary cementitious material addition were shown to be primary mechanisms for improved durability.
CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we ...screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.
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•The albumin fragment EPI-X4 is a highly specific endogenous CXCR4 antagonist•EPI-X4 blocks CXCL12-mediated CXCR4 signaling and cellular migration•EPI-X4 mobilizes hematopoietic cells and inhibits inflammatory responses in vivo•EPI-X4 is generated under acidic conditions that are a hallmark of inflammation
The CXCL12-CXCR4 axis is involved in many physiological processes. Zirafi et al. show that an endogenous fragment of human serum albumin (LVRYTKKVPQVSTPTL) efficiently suppresses CXCR4 signaling and inhibits infection by CXCR4-tropic HIV-1 strains.
Purpose To review the history of vitamin D and its use in cancer prevention. Methods The literature on published studies of vitamin D and its role in human health was reviewed and summarized. Results ...The modern history of vitamin D began in the mid-1800s, when it was noticed that city children were more likely to have rickets than rural children. Half a century later, Palm reported that children raised in sunny climates virtually never developed rickets. McCollum isolated vitamin D, and Windaus its precursors, receiving the Nobel Prize. Other scientists later observed that people with skin cancer had lower prevalence of nonskin cancers, and that lower overall mortality rates from all internal cancers combined existed in sunnier areas. These observations went largely unnoticed, and the field stagnated until 1970, when maps were created of cancer mortality rates. Through study of these maps, Cedric and Frank Garland of Johns Hopkins University reported a strong latitudinal gradient for colon cancer mortality rates in 1980, and hypothesized that higher levels of vitamin D compounds in the serum of people in the south were responsible, and that calcium intake also would reduce incidence. Edward Gorham and colleagues carried out cohort and nested studies, including the first study that found an association of a serum vitamin D compound with reduced cancer risk. William B. Grant then carried out numerous ecologic studies that extended the vitamin D-cancer theory to other cancers. Conclusions The history of the role of vitamin D in human health is rich and much of that history is yet to be written not only by scientists, but by policy makers with the vision and leadership necessary to bridge the gap between research and policy.
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