Radiotherapy in the presence of contrast agents: a general figure of merit and its application to gold nanoparticles

Delivering sufficient dose to tumours while sparing surrounding tissue is one of the primary challenges of radiotherapy, and in common practice this is typically achieved by using highly penetrating MV photon beams and spatially shaping dose. However, there has been a recent increase in interest in the possibility of using contrast agents with high atomic number to enhance the dose deposited in tumours when used in conjunction with kV x-rays, which see a significant increase in absorption due to the heavy element's high-photoelectric cross-section at such energies. Unfortunately, the introduction of such contrast agents significantly complicates the comparison of different source types for treatment efficacy, as the dose deposited now depends very strongly on the exact composition of the spectrum, making traditional metrics such as beam quality less valuable. To address this, a 'figure of merit' is proposed, which yields a value which enables the direct comparison of different source types for tumours at different depths inside a patient. This figure of merit is evaluated for a 15 MV LINAC source and two 150 kVp sources (both of which make use of a tungsten target, one with conventional aluminium filtration, while the other uses a more aggressive thorium filter) through analytical methods as well as numerical models, considering tissue treated with a realistic concentration and uptake ratio of gold nanoparticle contrast agents (10 mg ml(-1) concentration in 'tumour' volume, 10: 1 uptake ratio). Finally, a test case of human neck phantom is considered with a similar contrast agent to compare the abstract figure to a more realistic treatment situation. Good agreement was found both between the different approaches to calculate the figure of merit, and between the figure of merit and the effectiveness in a more realistic patient scenario. Together, these observations suggest that there is the potential for contrast-enhanced kilovoltage radiation to be a useful therapeutic tool for a number of classes of tumour on dosimetric considerations alone, and they point to the need for further research in this area.

Networks for systems biology: conceptual connection of data and function

The purpose of this study is to survey the use of networks and network-based methods in systems biology. This study starts with an introduction to graph theory and basic measures allowing to quantify structural properties of networks. Then, the authors present important network classes and gene networks as well as methods for their analysis. In the last part of this study, the authors review approaches that aim at analysing the functional organisation of gene networks and the use of networks in medicine. In addition to this, the authors advocate networks as a systematic approach to general problems in systems biology, because networks are capable of assuming multiple roles that are very beneficial connecting experimental data with a functional interpretation in biological terms.

Regenerative Medicine and New Labour Life Science Policy: Rhetorics of Success, Narratives of Sustainability and Survival

Advances in stem cell science and tissue engineering are being turned into applications and products through a novel medical paradigm known as regenerative medicine. This paper begins by examining the vulnerabilities and risks encountered by the regenerative medicine industry during a pivotal moment in its scientific infancy: the 2000s. Under the auspices of New Labour, British medical scientists and life science innovation firms associated with regenerative medicine, received demonstrative rhetorical pledges of support, aligned with the publication of a number of government initiated reports presaged by Bioscience 2015: Improving National Health, Increasing National Wealth. The Department of Health and the Department of Trade and Industry (and its successors) held industry consultations to determine the best means by which innovative bioscience cultures might be promoted and sustained in Britain. Bioscience 2015 encapsulates the first chapter of this sustainability narrative. By 2009, the tone of this storyline had changed to one of survivability. In the second part of the paper, we explore the ministerial interpretation of the ‘bioscience discussion cycle’ that embodies this narrative of expectation, using a computer-aided content analysis programme. Our analysis notes that the ministerial interpretation of these reports has continued to place key emphasis upon the distinctive and exceptional characteristics of the life science industries, such as their ability to perpetuate innovations in regenerative medicine and the optimism this portends – even though many of the economic expectations associated with this industry have remained unfulfilled.

General practice-recorded depression and antidepressant use in young people with newly diagnosed Type 1 diabetes: a cohort study using the Clinical Practice Research Datalink

Aims - To investigate whether young people with Type 1 diabetes have an increased rate of depression andantidepressant use and whether their risk varies by age group, time from diabetes diagnosis, calendar period ofdiagnosis or complications status. Methods - A cohort of incident cases of patients with Type 1 diabetes diagnosed before 35 years of age (n = 5548) wasidentified within the Clinical Practice Research Datalink and individually age and sex matched with up to two controlsubjects without diabetes (n = 10 657). Patients with depression were identified through general practice-recordeddepression codes and antidepressant prescriptions. Cox regression models gave hazard ratios for depression in peoplewith Type 1 diabetes compared with control subjects. Results - People with Type 1 diabetes were twice as likely to have a record of antidepressant use and generalpractice-diagnosed depression as their matched control subjects (hazard ratio 2.08, 95% CI 1.73–2.50, P < 0.001).These associations varied by time from diagnosis, with marked increases observed within the first 5 years of diagnosis(hazard ratio 2.14, 95% CI 1.51–3.03, P < 0.001), and by age at diabetes diagnosis, with excesses noted even in the 10-to 19-year age group (hazard ratio 1.45, 95% CI 1.06–1.98, P = 0.02). Conclusions - This population-based study shows that people with Type 1 diabetes have higher rates of generalpractice-recorded depression and antidepressant use. The excess is present within 5 years of diabetes diagnosis,suggesting psychological input for patients is warranted in the early years of their condition.

Molecular Medicine and Molecular Pathology for Haematologists:I. Gene Speak made Easy: An Overview of Genes and Gene Expression

Molecular Medicine and Molecular Pathology are integral parts of Haematology as we enter the new millennium. Their origins can be linked to fundamental developments in the basic sciences, particularly genetics, chemistry and biochemistry. The structure of DNA and the genetic code that it encrypts are the critical starting points to our understanding of these new disciplines. The genetic alphabet is a simple one, consisting of just 4 letters, buts its influence is crucial to human development and differentiation. The concept of a gene is not a new one but the Human Genome Project (a joint world-wide effort to characterise our entire genetic make-up) is providing an invaluable understanding of how genes function in normal cellular processes and pinpointing how disruption of these processes can lead to disease. Transcription and translation are the key events by which our genotype is converted to our phenotype (via a messenger RNA intermediate), producing the myriad proteins and enzymes which populate the cellular factory of our body. Unlike the bacterial or prokaryotic genome, the human genome contains a large amount of non coding DNA (less than 1% of our genome codes for proteins), and our genes are interrupted, with the coding regions or exons separated by non coding introns. Precise removal of the intronic material after transcription (though a process called splicing) is critical for efficient translation to occur. Incorrect splicing can lead to the generation of mutant proteins, which can have a dilaterious effect on the phenotype of the individual. Thus the 100,000-200,000 genes which are present in each cell in our body have a defined control mechanism permitting efficient and appropriate expression of proteins and enzymes and yet a single base change in just one of those genes can lead to diseases such as haemophilia or fanconis anaemia.