Access to Principal Treatment Centres and survival rates for children and young people with cancer in Yorkshire, UK

Background: Principal Treatment Centres (PTC) were established to provide age-appropriate care as well as clinical expertise for children and young people with cancer. However, little is known about the effects of specialist treatment centres on survival outcomes especially for teenagers and young adults. This population-based study aimed to describe access to PTC and the associated trends in survival for 0–24 year olds accounting for stage of disease at presentation and treatment. Methods: Patients diagnosed from 1998–2009 aged 0–24 years were extracted from the Yorkshire Specialist Register of Cancer in Children and Young People, including information on all treating hospitals, followed-up until 31st December 2014. The six commonest cancer types were included: leukaemia (n = 684), lymphoma (n = 558), CNS tumours (n = 547), germ cell tumours (n = 364), soft tissue sarcomas (n = 171) and bone tumours (n = 163). Treatment was categorised into three groups: ‘all’, ‘some’ or ‘no’ treatment received at a PTC. Treatment at PTC was examined by diagnostic group and patient characteristics. Overall survival was modelled using Cox regression adjusting for case-mix including stage, treatment and other socio-demographic and clinical characteristics. Results: Overall 72% of patients received all their treatment at PTC whilst 13% had no treatment at PTC. This differed by diagnostic group and age at diagnosis. Leukaemia patients who received no treatment at PTC had an increased risk of death which was partially explained by differences in patient case-mix (adjusted Hazard Ratio (HR) = 1.73 (95%CI 0.98–3.04)). Soft tissue sarcoma patients who had some or no treatment at PTC had better survival outcomes, which remained after adjustment for patient case-mix (adjusted HR = 0.48 (95%CI 0.23–0.99)). There were no significant differences in outcomes for other diagnostic groups (lymphoma, CNS tumours, bone tumours and germ cell tumours). For leukaemia patients survival outcomes for low risk patients receiving no treatment at PTC were similar to high risk patients who received all treatment at PTC, implying a benefit for care at the PTC. Conclusion: This study demonstrates that for leukaemia patients receiving treatment at a PTC is associated with improved survival that may compensate for a poorer prognosis presentation. However, further information on risk factors is needed for all diagnostic groups in order to fully account for differences in patient case-mix

The Significance of the CC-Numerical Range and the Local CC-Numerical Range in Quantum Control and Quantum Information

This paper shows how C-numerical-range related new strucures may arise from practical problems in quantum control--and vice versa, how an understanding of these structures helps to tackle hot topics in quantum information. We start out with an overview on the role of C-numerical ranges in current research problems in quantum theory: the quantum mechanical task of maximising the projection of a point on the unitary orbit of an initial state onto a target state C relates to the C-numerical radius of A via maximising the trace function |\tr \{C^\dagger UAU^\dagger\}|. In quantum control of n qubits one may be interested (i) in having U\in SU(2^n) for the entire dynamics, or (ii) in restricting the dynamics to {\em local} operations on each qubit, i.e. to the n-fold tensor product SU(2)\otimes SU(2)\otimes >...\otimes SU(2). Interestingly, the latter then leads to a novel entity, the {\em local} C-numerical range W_{\rm loc}(C,A), whose intricate geometry is neither star-shaped nor simply connected in contrast to the conventional C-numerical range. This is shown in the accompanying paper (math-ph/0702005). We present novel applications of the C-numerical range in quantum control assisted by gradient flows on the local unitary group: (1) they serve as powerful tools for deciding whether a quantum interaction can be inverted in time (in a sense generalising Hahn's famous spin echo); (2) they allow for optimising witnesses of quantum entanglement. We conclude by relating the relative C-numerical range to problems of constrained quantum optimisation, for which we also give Lagrange-type gradient flow algorithms.Comment: update relating to math-ph/070200

Phase transitions in biological membranes

Native membranes of biological cells display melting transitions of their lipids at a temperature of 10-20 degrees below body temperature. Such transitions can be observed in various bacterial cells, in nerves, in cancer cells, but also in lung surfactant. It seems as if the presence of transitions slightly below physiological temperature is a generic property of most cells. They are important because they influence many physical properties of the membranes. At the transition temperature, membranes display a larger permeability that is accompanied by ion-channel-like phenomena even in the complete absence of proteins. Membranes are softer, which implies that phenomena such as endocytosis and exocytosis are facilitated. Mechanical signal propagation phenomena related to nerve pulses are strongly enhanced. The position of transitions can be affected by changes in temperature, pressure, pH and salt concentration or by the presence of anesthetics. Thus, even at physiological temperature, these transitions are of relevance. There position and thereby the physical properties of the membrane can be controlled by changes in the intensive thermodynamic variables. Here, we review some of the experimental findings and the thermodynamics that describes the control of the membrane function.Comment: 23 pages, 15 figure

Major depressive disorder and current psychological distress moderate the effect of polygenic risk for obesity on body mass index

We are grateful to the families who took part in GS:SFHS, the GPs and Scottish School of Primary Care for their help in recruiting them, and the whole GS team, which includes academic researchers, clinic staff, laboratory technicians, clerical workers, IT staff, statisticians and research managers. This work is supported by the Wellcome Trust through a Strategic Award, reference 104036/Z/14/Z. The Chief Scientist Office of the Scottish Government and the Scottish Funding Council provided core support for Generation Scotland. GS:SFHS was funded by a grant from the Scottish Government Health Department, Chief Scientist Office, number CZD/16/6. We acknowledge with gratitude the financial support received for this work from the Dr Mortimer and Theresa Sackler Foundation. PT, DJP, IJD and AMM are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Council and Medical Research Council is gratefully acknowledged. DJM is an NRS Career Fellow, funded by the CSO. Supplementary Information accompanies the paper on the Translational Psychiatry websitePeer reviewedPublisher PD

A composite light-harvesting layer from photoactive polymer and halide perovskite for planar heterojunction solar cells

A new route for fabrication of photoactive materials in organic-inorganic hybrid solar cells is presented in this report. Photoactive materials by blending a semiconductive conjugated polymer with an organolead halide perovskite were fabricated for the first time. The composite active layer was then used to make planar heterojunction solar cells with the PCBM film as the electron-acceptor. Photovoltaic performance of solar cells was investigated by J-V curves and external quantum efficiency spectra. We demonstrated that the incorporation of the conjugated photoactive polymer into organolead halide perovskites did not only contribute to the generation of charges, but also enhance stability of solar cells by providing a barrier protection to halide perovskites. It is expected that versatile of conjugated semi-conductive polymers and halide perovskites in photoactive properties enables to create various combinations, forming composites with advantages offered by both types of photoactive materials

Development of an evidence-based brief 'talking' intervention for non-responders to bowel screening for use in primary care:stakeholder interviews

Bowel cancer is the third most common cause of cancer death worldwide. Bowel screening has been shown to reduce mortality and primary care interventions have been successful in increasing uptake of screening. Using evidence-based theory to inform the development of such interventions has been shown to increase their effectiveness. This study aimed to develop and refine a brief evidence-based intervention for eligible individuals whom have not responded to their last bowel screening invitation (non-responders), for opportunistic use by primary care providers during routine consultations.The development of a brief intervention involving a conversation between primary care providers and non-responders was informed by a multi-faceted model comprising: research team workshop and meetings to draw on expertise; evidence from the literature regarding barriers to bowel screening and effective strategies to promote informed participation; relevant psychological theory, and intervention development and behaviour change guidance. Qualitative telephone interviews with 1) bowel screening stakeholders and 2) patient non-responders explored views regarding the acceptability of the intervention to help refine its content and process.The intervention provides a theory and evidence-based tool designed to be incorporated within current primary care practice. Bowel screening stakeholders were supportive of the intervention and recognised the importance of the role of primary care. Interviews highlighted the importance of brevity and simplicity to incorporate the intervention into routine clinical care. Non-responders similarly found the intervention acceptable, valuing a holistic approach to their care. Moreover, they expected their primary care provider to encourage participation.A theory-based brief conversation for use in a primary care consultation was acceptable to bowel screening stakeholders and potential recipients, reflecting a health promoting primary care ethos. Findings indicate that it is appropriate to test the intervention in primary care in a feasibility study

Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle

Background Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals. Results Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle. Conclusions This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought

Factors related to longitudinal adherence in colorectal cancer screening:qualitative research findings

Background: The effectiveness of screening in colorectal cancer prevention depends on sustained participation rates. The objective of this study was to explore factors related to the longitudinal adherence of screening behavior in the context of a biennial population-based cancer screening program. Methods: Eight focus groups were conducted with individuals who were invited two or three consecutive times to a population-based colorectal cancer screening program using a fecal occult blood test and who agreed to participate in the program at least once (n = 45). The criteria used to select the study members included adherence to fecal occult blood test maintenance, factors regarding their initial participation in the colorectal cancer screening, sex, and contextual educational level. Results: The participants expressed a high level of satisfaction with the program; however, they showed a low level of understanding with respect to cancer screening. Consulting a general practitioner was cited by all participants as an important factor that mediated their final decision or influenced their behavior as a whole with regard to the program. Fear played a different role in the screening behavior for regular and irregular adherent participants. In the adherent participants, fear facilitated their continued participation in the screening program, whereas for the irregular participants, fear led them to avoid or refuse further screening. Having a close person diagnosed with colorectal cancer was a facilitator for the regular adherent participants. The irregular adherent participants showed some relaxation with respect to screening after a negative result and considered that further screening was no longer necessary. Conclusion: Considering the importance of primary healthcare professionals in the decision regarding sustained participation, it is important to better engage them with cancer screening programs, as well as improve the communication channels to provide accurate and balanced information for both health professionals and individuals.</p

Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) protocol : a pragmatic multi-centre randomised controlled trial of cast treatment versus surgical fixation for the treatment of bi-cortical, minimally displaced fractures of the scaphoid waist in adults

BACKGROUND: A scaphoid fracture is the most common type of carpal fracture affecting young active people. The optimal management of this fracture is uncertain. When treated with a cast, 88 to 90 % of these fractures unite; however, for the remaining 10-12 % the non-union almost invariably leads to arthritis. The alternative is surgery to fix the scaphoid with a screw at the outset. METHODS/DESIGN: We will conduct a randomised controlled trial (RCT) of 438 adult patients with a "clear" and "bicortical" scaphoid waist fracture on plain radiographs to evaluate the clinical effectiveness and cost-effectiveness of plaster cast treatment (with fixation of those that fail to unite) versus early surgical fixation. The plaster cast treatment will be immobilisation in a below elbow cast for 6 to 10 weeks followed by mobilisation. If non-union is confirmed on plain radiographs and/or Computerised Tomogram at 6 to 12 weeks, then urgent surgical fixation will be performed. This is being compared with immediate surgical fixation with surgeons using their preferred technique and implant. These treatments will be undertaken in trauma units across the United Kingdom. The primary outcome and end-point will be the Patient Rated Wrist Evaluation (a patient self-reported assessment of wrist pain and function) at 52 weeks and also measured at 6, 12, 26 weeks and 5 years. Secondary outcomes include an assessment of radiological union of the fracture; quality of life; recovery of wrist range and strength; and complications. We will also qualitatively investigate patient experiences of their treatment. DISCUSSION: Scaphoid fractures are an important public health problem as they predominantly affect young active individuals in the more productive working years of their lives. Non-union, if untreated, can lead to arthritis which can disable patients at a very young age. There is a rapidly increasing trend for immediate surgical fixation of these fractures but there is insufficient evidence from existing RCTs to support this. The SWIFFT Trial is a rigorously designed and adequately powered study which aims to contribute to the evidence-base to inform clinical decisions for the treatment of this common fracture in adults. TRIAL REGISTRATION: The trial is registered with the International Standard Randomised Controlled Trial Register ( ISRCTN67901257 ). Date registration assigned was 13/02/2013