Tetra-μ-acetato-κ4 O:O′;κ3 O,O′:O;κ3 O:O,O′-bis­[(acetato-κ2 O,O′)(1,10-phenanthroline-κ2 N,N′)europium(III)]

In the title centrosymmetric dinuclear complex, [Eu2(CH3CO2)6(C12H8N2)2], the EuIII atom is nine-coordinated by two N atoms from a 1,10-phenanthroline ligand and seven O atoms from five acetate ligands (two bidentate, three monodentate). The crystal structure is stabilized by π–π stacking inter­actions between the pyridine and benzene rings of adjacent mol­ecules, with a centroid–centroid distance of 3.829 (2) Å

The ₉₅RGD₉₇ sequence on the A alpha chain of fibrinogen is essential for binding to its erythrocyte receptor

Background: Erythrocyte aggregation, a cardiovascular risk factor, is increased by high plasma fibrinogen levels. Here, the effect of different fibrinogen mutations on binding to its human erythrocyte receptor was assessed in order to identify the interaction sites. Methods: Three fibrinogen variants were tested, specifically mutated in their putative integrin recognition sites on the Aα chain (mutants D97E, D574E and D97E/D574E) and compared with wild-type fibrinogen. Results: Atomic force microscopy-based force spectroscopy measurements showed a significant decrease both on the fibrinogen–erythrocyte binding force and on its frequency for fibrinogen with the D97E mutation, indicating that the corresponding arginine–glycine–aspartate sequence (residues 95–97) is involved in this interaction, and supporting that the fibrinogen receptor on erythrocytes has a β3 subunit. Changes in the fibrin clot network structure obtained with the D97E mutant were observed by scanning electron microscopy. Conclusion: These findings may lead to innovative perspectives on the development of new therapeutic approaches to overcome the risks of fibrinogen-driven erythrocyte hyperaggregation

Sensing adhesion forces between erythrocytes and γ’ fibrinogen, modulating fibrin clot architecture and function

Plasma fibrinogen includes an alternatively spliced γ-chain variant (γ’), which mainly exists as a heterodimer (γAγ’) and has been associated with thrombosis. We tested γAγ’ fibrinogen-red blood cells (RBCs) interaction using atomic force microscopy-based force spectroscopy, magnetic tweezers, fibrin clot permeability, scanning electron microscopy and laser scanning confocal microscopy. Data reveal higher work necessary for RBC-RBC detachment in the presence of γAγ’ rather than γAγA fibrinogen. γAγ’ fibrinogen–RBCs interaction is followed by changes in fibrin network structure, which forms an heterogeneous clot structure with areas of denser and highly branched fibrin fibers. The presence of RBCs also increased the stiffness of γAγ’ fibrin clots, which are less permeable and more resistant to lysis than γAγA clots. The modifications on clots promoted by RBCs-γAγ’ fibrinogen interaction could alter the risk of thrombotic disorders

Evaluation of the benefits, harms and cost‐effectiveness of potential alternatives to iFOBT testing for colorectal cancer screening in Australia

The Australian National Bowel Cancer Screening Program (NBCSP) will fully roll‐out 2‐yearly screening using the immunochemical Faecal Occult Blood Testing (iFOBT) in people aged 50 to 74 years by 2020. In this study, we aimed to estimate the comparative health benefits, harms, and cost‐effectiveness of screening with iFOBT, versus other potential alternative or adjunctive technologies. A comprehensive validated microsimulation model, Policy1‐Bowel, was used to simulate a total of 13 screening approaches involving use of iFOBT, colonoscopy, sigmoidoscopy, computed tomographic colonography (CTC), faecal DNA (fDNA) and plasma DNA (pDNA), in people aged 50 to 74 years. All strategies were evaluated in three scenarios: (i) perfect adherence, (ii) high (but imperfect) adherence, and (iii) low adherence. When assuming perfect adherence, the most effective strategies involved using iFOBT (annually, or biennially with/without adjunct sigmoidoscopy either at 50, or at 54, 64 and 74 years for individuals with negative iFOBT), or colonoscopy (10‐yearly, or once‐off at 50 years combined with biennial iFOBT). Colorectal cancer incidence (mortality) reductions for these strategies were 51–67(74–80)% in comparison with no screening; 2‐yearly iFOBT screening (i.e. the NBCSP) would be associated with reductions of 51(74)%. Only 2‐yearly iFOBT screening was found to be cost‐effective in all scenarios in context of an indicative willingness‐to‐pay threshold of A$50,000/life‐year saved (LYS); this strategy was associated with an incremental cost‐effectiveness ratio of A$2,984/LYS–A$5,981/LYS (depending on adherence). The fully rolled‐out NBCSP is highly cost‐effective, and is also one of the most effective approaches for bowel cancer screening in Australia

Reply: Screening for colorectal cancer with immunological FOBT

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Screen-detected colorectal cancers are associated with an improved outcome compared with stage-matched interval cancers

Background: Colorectal cancers (CRCs) detected through the NHS Bowel Cancer Screening Programme (BCSP) have been shown to have a more favourable outcome compared to non-screen-detected cancers. The aim was to identify whether this was solely due to the earlier stage shift of these cancers, or whether other factors were involved. Methods: A combination of a regional CRC registry (Northern Colorectal Cancer Audit Group) and the BCSP database were used to identify screen-detected and interval cancers (diagnosed after a negative faecal occult blood test, before the next screening round), diagnosed between April 2007 and March 2010, within the North East of England. For each Dukes' stage, patient demographics, tumour characteristics, and survival rates were compared between these two groups. Results: Overall, 322 screen-detected cancers were compared against 192 interval cancers. Screen-detected Dukes' C and D CRCs had a superior survival rate compared with interval cancers (P=0.014 and P=0.04, respectively). Cox proportional hazards regression showed that Dukes' stage, tumour location, and diagnostic group (HR 0.45, 95% CI 0.29-0.69, P<0.001 for screen-detected CRCs) were all found to have a significant impact on the survival of patients. Conclusions: The improved survival of screen-detected over interval cancers for stages C and D suggest that there may be a biological difference in the cancers in each group. Although lead-time bias may have a role, this may be related to a tumour's propensity to bleed and therefore may reflect detection through current screening tests

Understanding non-compliance to colorectal cancer screening: a case control study, nested in a randomised trial [ISRCTN83029072]

BACKGROUND: The major limit to colorectal cancer screening effectiveness is often low compliance. We studied the reasons for non compliance and determinants of compliance to faecal occult blood tests in Lazio, Italy. METHODS: This is a case-control study nested within a trial that tested the effect of type of test and provider on colorectal cancer screening compliance. Non compliant trial subjects were classified as cases, and compliant subjects were classified as controls. We sampled 600 cases and 600 controls matched by their general practitioner, half were invited for screening at the hospital, and the other half directly at their general practitioner's office. Cases and controls answered questions on: distance from test provider, logistical problems, perception of colorectal cancer risk, confidence in screening efficacy, fear of results, presence of colorectal cancer in the family, and gastrointestinal symptoms. RESULTS: About 31% of cases never received the letter offering free screening, and 17% of the sampled population had already been screened. The first reported reason for non-compliance was "lack of time" (30%); the major determinant of compliance was the distance from the test provider: odds ratio >30 minutes vs <15 minutes 0.3 (95%CI = 0.2–0.7). The odds ratio for lack of time was 0.16 (95% IC 0.1–0.26). The effect was stronger if the hospital (0.03 95%CI = 0.01–0.1) rather than the general practitioner (0.3 95%CI = 0.2–0.6) was the provider. Twenty-two percent of controls were accompanied by someone to the test. CONCLUSION: To increase compliance, screening programmes must involve test providers who are geographically close to the target population