The use of mechanistic reasoning in assessing coronavirus interventions

Funder: Marie Curie; Id: http://dx.doi.org/10.13039/501100000654Funder: Wellcome; Id: http://dx.doi.org/10.13039/100010269Funder: MRC: Medical Research CouncilFunder: NIHR: National Institute For Health ResearchAbstract: Rationale: Evidence‐based medicine (EBM), the dominant approach to assessing the effectiveness of clinical and public health interventions, focuses on the results of association studies. EBM+ is a development of EBM that systematically considers mechanistic studies alongside association studies. Aims and objectives: To explore examples of the importance of mechanistic evidence to coronavirus research. Methods: We have reviewed the mechanistic evidence in four major areas that are relevant to the management of COVID‐19. Results and conclusions: (a) Assessment of combination therapy for MERS highlights the need for systematic assessment of mechanistic evidence. (b) That hypertension is a risk factor for severe disease in the case of SARS‐CoV‐2 suggests that altering hypertension treatment might alleviate disease, but the mechanisms are complex, and it is essential to consider and evaluate multiple mechanistic hypotheses. (c) Confidence that public health interventions will be effective requires a detailed assessment of social and psychological components of the mechanisms of their action, in addition to mechanisms of disease. (d) In particular, if vaccination programmes are to be effective, they must be carefully tailored to the social context; again, mechanistic evidence is crucial. We conclude that coronavirus research is best situated within the EBM+ evaluation framework

Incidence trends of colorectal cancer in the early 2000s in Italy. Figures from the IMPATTO study on colorectal cancer screening

We utilised the IMPATTO study's archives to describe the 2000-2008 colorectal cancer (CRC) incidence rate trends in Italy, once screening programmes based on the faecal immunochemical test were implemented in different areas. Data on CRCs diagnosed in Italy from 2000 to 2008 in subjects aged 40-79 years were collected by 23 cancer registries. Incidence rate trends were evaluated as a whole and by macro-area (North-Centre and South-Islands), presence of a screening programme, sex, ten-year age class, anatomic site, stage at diagnosis, and pattern of diagnosis (screen-detected, non-screen-detected). The annual percent change (APC) of incidence rate trends, with 95% confidence intervals (95%CI), were computed. The study included 46,857 CRCs diagnosed in subjects aged 40-79 years, of which 2,806 were screendetected. The incidence rates in the North-Centre were higher than in the South and on the Islands. During the study period, screening programmes had been implemented only in the North-Centre and had a significant effect on incidence rates, with an initial sharp increase in incidence, followed by a decrease that started in the 3rd-4th years of screening. These incidence rate trends were exclusively due to modifications in the rates of stage I cases. After screening programmes started, incidence increased in all anatomic sites, particularly in the distal colon. The differential figures introduced by the implementation of screening programmes warrant a continuous surveillance of CRC incidence and mortality trends to monitor the impact of screening at a national level

Characteristics of the colorectal cancers diagnosed in the early 2000s in Italy. Figures from the IMPATTO study on colorectal cancer screening

The impact of organized screening programmes on colorectal cancer (CRC) can be observed at a population level only several years after the implementation of screening. We compared CRC characteristics by diagnostic modality (screen-detected, non-screen-detected) as an early outcome to monitor screening programme effectiveness. Data on CRCs diagnosed in Italy from 2000 to 2008 were collected by several cancer registries. Linkage with screening datasets made it possible to divide the cases by geographic area, implementation of screening, and modality of diagnosis (screen-detected, non-screen-detected).We compared the main characteristics of the different subgroups of CRCs through multivariate logistic regression models. The study included 23,668 CRCs diagnosed in subjects aged 50-69 years, of which 11.9%were screendetected (N=2,806), all from the North-Centre of Italy. Among screen-detected CRCs, we observed a higher proportion of males, of cases in the distal colon, and a higher mean age of the patients. Compared with pre-screening cases, screen-detected CRCs showed a better distribution by stage at diagnosis (OR for stage III or IV: 0.40, 95%CI: 0.36-0.44) and grading (OR for poorly differentiated CRCs was 0.86, 95%CI: 0.75-1.00). Screen-detected CRCs have more favourable prognostic characteristics than non-screen-detected cases. A renewed effort to implement screening programmes throughout the entire country is recommended

Application of lithogeochemistry to identify stratigraphic units and provenance of the Kanmantoo Group, Kangaroo Island

This item is only available electronically.Geochemical data, including Nd isotope ratios, were used to help establish stratigraphic correlations between Kanmantoo Group sedimentary rocks on the mainland and Kangaroo Island, as well as constrain their provenance. Whole-rock geochemistry of the Kangaroo Island and mainland Kanmantoo Group varied, with little consistency, suggesting a mixed sediment source. The Talisker Formation however has a distinctly higher abundance of mafic detritus compared to other Kanmantoo Group formations. Initial Nd data from the Kangaroo Island Kanmantoo Group is between -12 to -15, compared to those from the mainland which range between -9 and -12 (Turner et al. 1993). The Nd data are similar to basement of the Gawler Craton and east Antarctica (Prydz Bay), which are two possible source terrains for the sediments. Palaeocurrent data on Kangaroo Island indicate a southern provenance. The Nd values of Prydz Bay charnockites and felsic gneisses at around 500 Ma are similar to that of the Kangaroo Island Kanmantoo Group. Results from the outcomes of this study suggest that the Kanmantoo Group was derived from a mixture of sources, including the Gawler Craton, west Antarctica (Ross Orogeny) and Adelaidean rocks. However, there appears to be a dominance of sediment from the east-Gondwana Orogenic belt in east Antarctica.Thesis (B.Sc.(Hons)) -- University of Adelaide, School of Physical Sciences, 200

Constitutional Adjudication Within a European Composite Constitution – A View from The Bench

Constitutional Adjudication Within a European Composite Constitution from Constitutional Jusitices' perspectiv