Hepatobiliary and pancreatic imaging in children—techniques and an overview of non-neoplastic disease entities

Imaging plays a major role in the diagnostic work-up of children with hepatobiliary or pancreatic diseases. It consists mainly of US, CT and MRI, with US and MRI being the preferred imaging modalities because of the lack of ionizing radiation. In this review the technique of US, CT and MRI in children will be addressed, followed by a comprehensive overview of the imaging characteristics of several hepatobiliary and pancreatic disease entities most common in the paediatric age group

Hybridization and hybrid speciation under global change

An unintended consequence of global change is an increase in opportunities for hybridization among previously isolated lineages. Here we illustrate how global change can facilitate the breakdown of reproductive barriers and the formation of hybrids, drawing on the flora of the British Isles for insight. Although global change may ameliorate some of the barriers preventing hybrid establishment, for example by providing new ecological niches for hybrids, it will have limited effects on environment-independent post-zygotic barriers. For example, genic incompatibilities and differences in chromosome numbers and structure within hybrid genomes are unlikely to be affected by global change. We thus speculate that global change will have a larger effect on eroding pre-zygotic barriers (eco-geographical isolation and phenology) than post-zygotic barriers, shifting the relative importance of these two classes of reproductive barriers from what is usually seen in naturally produced hybrids where pre-zygotic barriers are the largest contributors to reproductive isolation. Although the long-term fate of neo-hybrids is still to be determined, the massive impact of global change on the dynamics and distribution of biodiversity generates an unprecedented opportunity to study large numbers of unpredicted, and often replicated, hybridization ‘experiments’, allowing us to peer into the birth and death of evolutionary lineages

An Economic Evaluation Supported by Qualitative Data About the Patient Concerns Inventory (PCI) versus Standard Treatment Pathway in the Management of Patients with Head and Neck Cancer.

Background The head and neck cancer (HNC) Patient Concerns Inventory (PCI) is a condition-specific prompt list that allows patients to raise concerns to cancer consultants that otherwise might be overlooked. Objective This is the first economic evaluation of the PCI in patients with HNC investigating the costs and effects to the health service of not prioritising certain treatment pathways in addition to the primary cancer pathway. Additional costs can be accrued due to delayed referral to other appropriate services, e.g. hospital dentist. Economic evidence could influence future policy direction in this area globally. Methods Alongside a 3-year clustered randomised controlled trial, an economic evaluation was undertaken with Client Service Receipt Inventory data collected at three different time points (baseline and 6 and 12 months post-baseline). Patients were identified by a multidisciplinary team at the trial clinics. This economic analysis compared the PCI intervention versus the non-PCI treatment pathway. A deterministic and probabilistic sensitivity analysis was conducted to investigate the cost per quality-adjusted life-year (QALY) gain of the PCI versus non-PCI intervention treatment pathways. Qualitative data were also collected from seven consultants to triangulate findings from the economic evaluation. Results The analysis used data from 191 patients (66% of the full trial sample). The PCI inventory was low cost, at just over £13 per participant. The PCI intervention was cost effective and also cost saving, with an incremental cost difference of £295.91 over the 12-month follow-up period. The QALY values were higher in the PCI intervention strategy, with a value of 0.79, whereas the non-PCI group had a value of 0.76, thus the PCI intervention was dominant. The sensitivity analysis showed that, at a willingness-to-pay threshold of £20,000 per QALY gained, the probability of being cost effective was 0.85 (95% confidence interval [CI] 0.80–0.83). Qualitative results showed that consultants using the PCI reported an enhanced awareness of patients’ overall post-treatment needs. Discussion The PCI provided an effective means to conduct clinical consultations by avoiding unnecessary healthcare costs and focussing on aspects of care most important to patients. The cost per QALY gain was within the National Institute for Health and Care Excellence guideline threshold. The economic evaluation showed that the PCI intervention strategy was dominant and therefore cost saving to the national health service (NHS) and was more effective in terms of treatment. Conclusion The PCI appears to be a low-cost intervention that generates a cost-effective benefit to patients from a NHS perspective if rolled out as part of routine care. Qualitative evidence has shown that the use of the PCI is supported by consultants in routine practice. Trial Registration Clinical Trials Identifier: NCT03086629

The holographic principle

There is strong evidence that the area of any surface limits the information content of adjacent spacetime regions, at 10^(69) bits per square meter. We review the developments that have led to the recognition of this entropy bound, placing special emphasis on the quantum properties of black holes. The construction of light-sheets, which associate relevant spacetime regions to any given surface, is discussed in detail. We explain how the bound is tested and demonstrate its validity in a wide range of examples. A universal relation between geometry and information is thus uncovered. It has yet to be explained. The holographic principle asserts that its origin must lie in the number of fundamental degrees of freedom involved in a unified description of spacetime and matter. It must be manifest in an underlying quantum theory of gravity. We survey some successes and challenges in implementing the holographic principle.Comment: 52 pages, 10 figures, invited review for Rev. Mod. Phys; v2: reference adde

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol

Early changes in the haemostatic and procoagulant systems after chemotherapy for breast cancer

Venous thromboembolism (VTE) following breast cancer chemotherapy is common. Chemotherapy-induced alterations in markers of haemostasis occur during chemotherapy. It is unclear how rapidly this occurs, whether this is upregulated in patients developing VTE and whether changes predict for VTE. Markers of haemostasis, functional clotting assays and vascular endothelial growth factor were measured before chemotherapy and at 24 h, 4 days, 8 days and 3 months following commencement of chemotherapy in early and advanced breast cancer patients and in age- and sex-matched controls. Duplex ultrasound imaging was performed after 1 month or if symptomatic. Of 123 patients, 9.8% developed VTE within 3 months. Activated partial thromboplastin time (APTT), prothrombin time (PT), D-dimer, fibrinogen, platelet count, VEGF and fibrinogen were increased in cancer. Fibrinogen, D-dimer, VEGF and tissue factor were increased, at baseline, in patients subsequently developing VTE. D-dimer of less than 500 ng ml−1 has a negative predictive value of 97%. Activated partial thromboplastin time, PT and thrombin–antithrombin showed significantly different trends, as early as within 24 h, in response to chemotherapy in patients subsequently developing VTE. Markers of coagulation and procoagulants are increased, before chemotherapy, in patients who subsequently develop VTE. A group of patients at minimal risk of VTE can be identified, allowing targeted thrombopropylaxis to the higher risk group

The predictive value of p53, p53R2, and p21 for the effect of chemoradiation therapy on oesophageal squamous cell carcinoma

The p53 family regulates cell-cycle arrest, triggers apoptosis or is involved in repair of DNA damage. In the present study, we analysed the expression of some p53 family proteins and their responses to chemoradiation therapy (CRT) in cases of oesophageal squamous cell carcinoma (ESCC). We immunohistochemically investigated the relationship between p53, p53R2, and p21 expression in biopsy specimens of untreated primary tumours and their clinical and histological responses to CRT in 62 patients with ESCC. Chemoradiation therapy consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation. The rates of clinical and histological responses (complete or partial) to CRT were 71.0% (clinical) and 52.8% (histological). The rate of positive expression was 43.5% for p53, 37.1% for p53R2, and 54.8% for p21 expression. Statistically significant correlations were found between p53 or p53R2 expression and favourable response to CRT (P=0.0001 or 0.041 clinical, P=0.016 or 0.0018 histological, respectively). Furthermore, in p53-negative tumours, CRT was more effective in tumours with p53R2 negative expression than those with p53R2 positive expression (P=0.0014). We demonstrated that the negative expression of p53 and p53R2 expression was closely related to the effect of CRT and should predict the CRT outcome in patients with ESCC

Overdiagnosis and overtreatment of early detected prostate cancer

Early detection of prostate cancer is associated with the diagnosis of a considerable proportion of cancers that are indolent, and that will hardly ever become symptomatic during lifetime. Such overdiagnosis should be avoided in all forms of screening because of potential adverse psychological and somatic side effects. The main threat of overdiagnosis is overtreatment of indolent disease. Men with prostate cancer that is likely to be indolent may be offered active surveillance. Evaluation of active surveillance studies and validation of new biological parameters for risk assessment are expected