64 research outputs found

    An Age-Structured Extension to the Vectorial Capacity Model

    Get PDF
    Vectorial capacity and the basic reproductive number (R(0)) have been instrumental in structuring thinking about vector-borne pathogen transmission and how best to prevent the diseases they cause. One of the more important simplifying assumptions of these models is age-independent vector mortality. A growing body of evidence indicates that insect vectors exhibit age-dependent mortality, which can have strong and varied affects on pathogen transmission dynamics and strategies for disease prevention.Based on survival analysis we derived new equations for vectorial capacity and R(0) that are valid for any pattern of age-dependent (or age-independent) vector mortality and explore the behavior of the models across various mortality patterns. The framework we present (1) lays the groundwork for an extension and refinement of the vectorial capacity paradigm by introducing an age-structured extension to the model, (2) encourages further research on the actuarial dynamics of vectors in particular and the relationship of vector mortality to pathogen transmission in general, and (3) provides a detailed quantitative basis for understanding the relative impact of reductions in vector longevity compared to other vector-borne disease prevention strategies.Accounting for age-dependent vector mortality in estimates of vectorial capacity and R(0) was most important when (1) vector densities are relatively low and the pattern of mortality can determine whether pathogen transmission will persist; i.e., determines whether R(0) is above or below 1, (2) vector population growth rate is relatively low and there are complex interactions between birth and death that differ fundamentally from birth-death relationships with age-independent mortality, and (3) the vector exhibits complex patterns of age-dependent mortality and R(0) ∌ 1. A limiting factor in the construction and evaluation of new age-dependent mortality models is the paucity of data characterizing vector mortality patterns, particularly for free ranging vectors in the field

    Serine metabolism remodeling after platinum-based chemotherapy identifies vulnerabilities in a subgroup of resistant ovarian cancers

    Get PDF
    Resistance to platinum-based chemotherapy represents a major clinical challenge for many tumors, including epithelial ovarian cancer. Patients often experience several response-relapse events, until tumors become resistant and life expectancy drops to 12–15 months. Despite improved knowledge of the molecular determinants of platinum resistance, the lack of clinical applicability limits exploitation of many potential targets, leaving patients with limited options. Serine biosynthesis has been linked to cancer growth and poor prognosis in various cancer types, however its role in platinum-resistant ovarian cancer is not known. Here, we show that a subgroup of resistant tumors decreases phosphoglycerate dehydrogenase (PHGDH) expression at relapse after platinum-based chemotherapy. Mechanistically, we observe that this phenomenon is accompanied by a specific oxidized nicotinamide adenine dinucleotide (NAD+) regenerating phenotype, which helps tumor cells in sustaining Poly (ADP-ribose) polymerase (PARP) activity under platinum treatment. Our findings reveal metabolic vulnerabilities with clinical implications for a subset of platinum resistant ovarian cancers

    Interaction of climate change with effects of conspecific and heterospecific density on reproduction

    Get PDF
    We studied the relationship between temperature and the coexistence of great titParus majorand blue titCyanistes caeruleus, breeding in 75 study plots across Europe and North Africa. We expected an advance in laying date and a reduction in clutch size during warmer springs as a general response to climate warming and a delay in laying date and a reduction in clutch size during warmer winters due to density-dependent effects. As expected, as spring temperature increases laying date advances and as winter temperature increases clutch size is reduced in both species. Density of great tit affected the relationship between winter temperature and laying date in great and blue tit. Specifically, as density of great tit increased and temperature in winter increased both species started to reproduce later. Density of blue tit affected the relationship between spring temperature and blue and great tit laying date. Thus, both species start to reproduce earlier with increasing spring temperature as density of blue tit increases, which was not an expected outcome, since we expected that increasing spring temperature should advance laying date, while increasing density should delay it cancelling each other out. Climate warming and its interaction with density affects clutch size of great tits but not of blue tits. As predicted, great tit clutch size is reduced more with density of blue tits as temperature in winter increases. The relationship between spring temperature and density on clutch size of great tits depends on whether the increase is in density of great tit or blue tit. Therefore, an increase in temperature negatively affected the coexistence of blue and great tits differently in both species. Thus, blue tit clutch size was unaffected by the interaction effect of density with temperature, while great tit clutch size was affected in multiple ways by these interactions terms.Peer reviewe

    Effects of interspecific coexistence on laying date and clutch size in two closely related species of hole-nesting birds

    Get PDF
    Coexistence between great tits Parus major and blue tits Cyanistes caeruleus, but also other hole‐nesting taxa, constitutes a classic example of species co‐occurrence resulting in potential interference and exploitation competition for food and for breeding and roosting sites. However, the spatial and temporal variations in coexistence and its consequences for competition remain poorly understood. We used an extensive database on reproduction in nest boxes by great and blue tits based on 87 study plots across Europe and Northern Africa during 1957–2012 for a total of 19,075 great tit and 16,729 blue tit clutches to assess correlative evidence for a relationship between laying date and clutch size, respectively, and density consistent with effects of intraspecific and interspecific competition.In an initial set of analyses, we statistically controlled for a suite of site‐specific variables. We found evidence for an effect of intraspecific competition on blue tit laying date (later laying at higher density) and clutch size (smaller clutch size at higher density), but no evidence of significant effects of intraspecific competition in great tits, nor effects of interspecific competition for either species.To further control for site‐specific variation caused by a range of potentially confounding variables, we compared means and variances in laying date and clutch size of great and blue tits among three categories of difference in density between the two species. We exploited the fact that means and variances are generally positively correlated. If interspecific competition occurs, we predicted a reduction in mean and an increase in variance in clutch size in great tit and blue tit when density of heterospecifics is higher than the density of conspecifics, and for intraspecific competition, this reduction would occur when density of conspecifics is higher than the density of heterospecifics. Such comparisons of temporal patterns of means and variances revealed evidence, for both species, consistent with intraspecific competition and to a smaller extent with interspecific competition.These findings suggest that competition associated with reproductive behaviour between blue and great tits is widespread, but also varies across large spatial and temporal scales.</div

    CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

    Get PDF
    BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC

    Epidemiological and ecological determinants of Zika virus transmission in an urban setting.

    Get PDF
    The Zika virus has emerged as a global public health concern. Its rapid geographic expansion is attributed to the success of Aedes mosquito vectors, but local epidemiological drivers are still poorly understood. Feira de Santana played a pivotal role in the Chikungunya epidemic in Brazil and was one of the first urban centres to report Zika infections. Using a climate-driven transmission model and notified Zika case data, we show that a low observation rate and high vectorial capacity translated into a significant attack rate during the 2015 outbreak, with a subsequent decline in 2016 and fade-out in 2017 due to herd-immunity. We find a potential Zika-related, low risk for microcephaly per pregnancy, but with significant public health impact given high attack rates. The balance between the loss of herd-immunity and viral re-importation will dictate future transmission potential of Zika in this urban setting

    Variation in clutch size in relation to nest size in birds

    Get PDF
    Peer reviewe

    The potential of Eucalyptus hybrids in farm forestry in the semi-arid winter rainfall region of South Africa

    Get PDF
    Thesis (MScFor)--Stellenbosch University, 2018.ENGLISH ABSTRACT: The aim of this study was to investigate Eucalyptus hybrids as a source of woody biomass in the semi-arid winter rainfall region of South Africa. The study focuses on an experimental planting at 10 years of age and the coppice crop from this experiment grown for nine months after clear felling. The trial investigated the survival, potential production (growth) and coppicability of several Eucalyptus hybrids, namely E. grandis x camaldulensis, E. grandis x resinifera, E. grandis x tereticornis and E. saligna x urophylla, which were compared to the control of E. cladocalyx and commercial controls of E. dunnii and E. grandis x camaldulensis. The survival and potential production were explored on a taxa and provenance, genotype and stand level, while the coppice results were ranked on a genotype level. Overall, the survival on the site was above 75 %, excluding the controls of E. cladocalyx and E. dunnii, which did not perform well. At 10 years of age, the experimental stand achieved a mean annual increment (MAI) of 17.24 m3.ha-1.a-1. Basal area growth was used to rank the growth response of the tested genotypes. The basal area was upscaled from single tree plots which meant that the mean value yielded a useful estimate, however, the upscaled value of individual genotypes from the single tree plots were only reliable to rank genotypes and not to estimate growth potential in field. The upscaled basal area ranged between 12 m2.ha-1 and 55 m2.ha-1. Several of the tested hybrids were well suited to the semi-arid site, namely: E. gxc Albacutya CSS01659 (9), E. gxc Albacutya CSS01682 (13), E. gxt (AUS) seed SR0046xT32 (84) and E. gxt (AUS) seed AG049xT08 (83) and E. gxc (SA) seed SGR1231xC42 (76). Slightly less than 50% of the genotypes had good coppicability. The biomass produced in coppice shoots was not significantly different among the taxa at nine months of age. The potential for deploying the newly tested genotypes in farm forestry projects in semi-arid climates of the Western Cape is discussedAFRIKAANSE OPSOMMING: Die doel van hierdie studie was om Eucalyptus-hibriede te ondersoek as ‘n bron van houtagtige biomassa in die halfdorre winterreĂ«nvalgebied van Suid-Afrika. The studie fokus op Ɖ 10-jaar-oue eksperimentele aanplanting, asook die stomplootverjonging en daaropvolgende groei tot en met nege maande na kaalkap. Die proef ondersoek die oorlewing, potensiĂ«le produktiwiteit (groei) en vermoĂ« van stomplootverjonging van verskeie Eucalyptus-hibriede, naamlik E. grandis x camaldulensis, E. grandis x resinifera, E. grandis x tereticornis en E. saligna x urophylla. Dit word vergelyk met die E. cladocalyx-kontrole en kommersiĂ«le E. dunnii- en E. grandis x camaldulensis-kontroles. Die oorlewing en potensiĂ«le produktiwiteit is ondersoek op ’n takson-, herkoms-, genotipe- en opstandsvlak, terwyl die resultate van die stomplootverjongings gerangskik is van groot na klein op ’n genotipe-vlak. Oor die algemeen was die oorlewing op die eksperimentele eenheid bo 75 %, behalwe vir die kontroles van E. cladocalyx en E. dunnii, wat nie goed gevaar het nie. ’n Gemiddelde jaarlikse aanwas van 17.24 m3.ha-1.jaar-1 is behaal op die opstand oor die 10 jaar periode. Basale oppervlakte was gebruik om die rang van die groei respons van die genotipes te toets. Die basale oppervlakte was van enkelboomplotte opgeskaal wat beteken dat die gemiddelde waarde ‘n goeie indikator van groei was. Die opgeskaalde basale oppervlakte van individuele genotipes was egter net betroubaar vir rang en nie vir die skatting groei potensiaal in die veld nie. Die opgeskaalde basale oppervlakte het gewissel van 12 tot 55 m3.ha-1. Verskeie van die getoetste hibriede is skynbaar goed aangepas by die groeiplek, naamlik: E. gxc Albacutya CSS01659 (9), E. gxc Albacutya CSS01682 (13), E. gxt (AUS) seed SR0046xT32 (84) and E. gxt (AUS) seed AG049xT08 (83) and E. gxc (SA) seed SGR1231xC42 (76). Amper 50% van die genotipes het ’n goeie stomplootverjongingsvermoĂ« gehad. Die resultate vir die stomplootbiomassa het nie beduidend tussen taksa verskil op nege-maande-oue ouderdom nie. Die potensiaal vir die ontplooĂŻng van die nuut getoetsde genotipes in plaasbosbouprojekte in die semi-ariede Wes-Kaap word bespreek
    • 

    corecore