Systems biological and mechanistic modelling of radiation-induced cancer

This paper summarises the five presentations at the First International Workshop on Systems Radiation Biology that were concerned with mechanistic models for carcinogenesis. The mathematical description of various hypotheses about the carcinogenic process, and its comparison with available data is an example of systems biology. It promises better understanding of effects at the whole body level based on properties of cells and signalling mechanisms between them. Of these five presentations, three dealt with multistage carcinogenesis within the framework of stochastic multistage clonal expansion models, another presented a deterministic multistage model incorporating chromosomal aberrations and neoplastic transformation, and the last presented a model of DNA double-strand break repair pathways for second breast cancers following radiation therapy

Paleoclimate and bubonic plague: a forewarning of future risk?

Pandemics of bubonic plague have occurred in Eurasia since the sixth century ad. Climatic variations in Central Asia affect the population size and activity of the plague bacterium's reservoir rodent species, influencing the probability of human infection. Using innovative time-series analysis of surrogate climate records spanning 1,500 years, a study in BMC Biology concludes that climatic fluctuations may have influenced these pandemics. This has potential implications for health risks from future climate change

The inter-observer agreement of examining pre-school children with acute cough: a nested study

BACKGROUND: The presence of clinical signs have implications for diagnosis, prognosis and treatment. Therefore, the aim of this study was to examine the inter-observer agreement of clinical signs in pre-school children presenting to primary care. METHODS: A nested study comparing two clinical assessments within a prospective cohort of 256 pre-school children with acute cough recruited from eight general practices in Leicestershire, UK. We examined agreement (using kappa statistics) between unstandardised and standardised clinical assessments of tachypnoea, chest signs and fever. RESULTS: Kappa values were poor or fair for all clinical signs (range 0.12 to 0.39) with chest signs the most reliable. CONCLUSIONS: Primary care clinicians should be aware that clinical signs may be unreliable when making diagnosis, prognosis and treatment decisions in pre-school children with cough. Future research should aim to further our understanding of how best to identify abnormal clinical signs

Periodic trends and easy estimation of relative stabilities in 11-vertex nido-p-block-heteroboranes and -borates

Density functional theory computations were carried out for 11-vertex nido-p-block-hetero(carba)boranes and -borates containing silicon, germanium, tin, arsenic, antimony, sulfur, selenium and tellurium heteroatoms. A set of quantitative values called “estimated energy penalties” was derived by comparing the energies of two reference structures that differ with respect to one structural feature only. These energy penalties behave additively, i.e., they allow us to reproduce the DFT-computed relative stabilities of 11-vertex nido-heteroboranes in general with good accuracy and to predict the thermodynamic stabilities of unknown structures easily. Energy penalties for neighboring heteroatoms (HetHet and HetHet′) decrease down the group and increase along the period (indirectly proportional to covalent radii). Energy penalties for a five- rather than four-coordinate heteroatom, [Het5k(1) and Het5k(2)], generally, increase down group 14 but decrease down group 16, while there are mixed trends for group 15 heteroatoms. The sum of HetHet′ energy penalties results in different but easily predictable open-face heteroatom positions in the thermodynamically most stable mixed heterocarbaboranes and -borates with more than two heteroatoms

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Talking Less during Social Interactions Predicts Enjoyment: A Mobile Sensing Pilot Study

Can we predict which conversations are enjoyable without hearing the words that are spoken? A total of 36 participants used a mobile app, My Social Ties, which collected data about 473 conversations that the participants engaged in as they went about their daily lives. We tested whether conversational properties (conversation length, rate of turn taking, proportion of speaking time) and acoustical properties (volume, pitch) could predict enjoyment of a conversation. Surprisingly, people enjoyed their conversations more when they spoke a smaller proportion of the time. This pilot study demonstrates how conversational properties of social interactions can predict psychologically meaningful outcomes, such as how much a person enjoys the conversation. It also illustrates how mobile phones can provide a window into everyday social experiences and well-being

Risk factors for pre-term birth in Iraq: a case-control study

BACKGROUND: Preterm birth (PTB)is a major clinical problem associated with perinatal mortality and morbidity. The aim of the present study is to identify risk factors associated with PTB in Mosul, Iraq. METHODS: A case-control study was conducted in Mosul, Iraq, from 1(st )September, 2003 to 28(th )February, 2004. RESULTS: A total of 200 cases of PTB and 200 controls of full-term births were screened and enrolled in the study. Forward logistic regression analysis was used in the analysis. Several significant risk associations between PTB and the following risk factors were identified: poor diet (OR = 4.33), heavy manual work (OR = 1.70), caring for domestic animals (OR = 5.06), urinary tract infection (OR = 2.85), anxiety (OR = 2.16), cervical incompetence (OR = 4.74), multiple pregnancies (OR = 7.51), direct trauma to abdomen (OR = 3.76) and abortion (OR = 6.36). CONCLUSION: The main determinants of PTB in Iraq were low socio-economic status and factors associated with it, such as heavy manual work and caring for domestic animals, in addition to urinary tract infections and poor obstetric history

Patterns of sick-leave and health outcomes in injured workers with back pain

Little is known about the sick-leave experiences of workers who make a workers’ compensation claim for back pain. Our objective is to describe the 1-year patterns of sick-leave and the health outcomes of a cohort of workers who make a workers’ compensation claim for back pain. We studied a cohort of 1,831 workers from five large US firms who made incident workers’ compensation claims for back pain between January 1, 1999 and June 30, 2002. Injured workers were interviewed 1 month (n = 1,321), 6 months (n = 810) and 1 year (n = 462) following the onset of their pain. We described the course of back pain using four patterns of sick-leave: (1) no sick-leave, (2) returned to worked and stayed, (3) multiple episodes of sick-leave and (4) not yet returned to work. We described the health outcomes as back and/or leg pain intensity, functional limitations and health-related quality of life. We analyzed data from participants who completed all follow-up interviews (n = 457) to compute the probabilities of transition between patterns of sick-leave. A significant proportion of workers experienced multiple episodes of sick-leave (30.2%; 95% CI 25.0–35.1) during the 1-year follow-up. The proportion of workers who did not report sick-leave declined from 42.4% (95% CI 39.0–46.1) at 1 month to 33.6% (28.0–38.7) at 1 year. One year after the injury, 2.9% (1.6–4.9) of workers had not yet returned to work. Workers who did not report sick-leave and those who returned and stayed at work reported better health outcomes than workers who experienced multiple episodes of sick-leave or workers who had not returned to work. Almost a third of workers with an incident episode of back pain experience recurrent spells of work absenteeism during the following year. Our data suggest that stable patterns of sick-leave are associated with better health