Can the Severity of Normal Tissue Damage after Radiation Therapy Be Predicted?

Begg discusses a new study by Svensson and colleagues in which the researchers attempted to elucidate genetic factors involved in late radiation toxicity

The Waipounamu Erosion Surface: questioning the antiquity of the New Zealand land surface and terrestrial fauna and flora

The Waipounamu Erosion Surface is a time-transgressive, nearly planar, wave-cut surface. It is not a peneplain. Formation of the Waipounamu Erosion Surface began in Late Cretaceous time following break-up of Gondwanaland, and continued until earliest Miocene time, during a 60 million year period of widespread tectonic quiescence, thermal subsidence and marine transgression. Sedimentary facies and geomorphological evidence suggest that the erosion surface may have eventually covered the New Zealand subcontinent (Zealandia). We can find no geological evidence to indicate that land areas were continuously present throughout the middle Cenozoic. Important implications of this conclusion are: (1) the New Zealand subcontinent was largely, or entirely, submerged and (2) New Zealand's present terrestrial fauna and flora evolved largely from fortuitous arrivals during the past 22 million years. Thus the modern terrestrial biota may not be descended from archaic ancestors residing on Zealandia when it broke away from Gondwanaland in the Cretaceous, since the terrestrial biota would have been extinguished if this landmass was submerged in Oligocene–Early Miocene time. We conclude that there is insufficient geological basis for assuming that land was continuously present in the New Zealand region through Oligocene to Early Miocene time, and we therefore contemplate the alternative possibility, complete submergence of Zealandia

Analysis of Gene Expression Using Gene Sets Discriminates Cancer Patients with and without Late Radiation Toxicity

BACKGROUND: Radiation is an effective anti-cancer therapy but leads to severe late radiation toxicity in 5%–10% of patients. Assuming that genetic susceptibility impacts this risk, we hypothesized that the cellular response of normal tissue to X-rays could discriminate patients with and without late radiation toxicity. METHODS AND FINDINGS: Prostate carcinoma patients without evidence of cancer 2 y after curative radiotherapy were recruited in the study. Blood samples of 21 patients with severe late complications from radiation and 17 patients without symptoms were collected. Stimulated peripheral lymphocytes were mock-irradiated or irradiated with 2-Gy X-rays. The 24-h radiation response was analyzed by gene expression profiling and used for classification. Classification was performed either on the expression of separate genes or, to augment the classification power, on gene sets consisting of genes grouped together based on function or cellular colocalization. X-ray irradiation altered the expression of radio-responsive genes in both groups. This response was variable across individuals, and the expression of the most significant radio-responsive genes was unlinked to radiation toxicity. The classifier based on the radiation response of separate genes correctly classified 63% of the patients. The classifier based on affected gene sets improved correct classification to 86%, although on the individual level only 21/38 (55%) patients were classified with high certainty. The majority of the discriminative genes and gene sets belonged to the ubiquitin, apoptosis, and stress signaling networks. The apoptotic response appeared more pronounced in patients that did not develop toxicity. In an independent set of 12 patients, the toxicity status of eight was predicted correctly by the gene set classifier. CONCLUSIONS: Gene expression profiling succeeded to some extent in discriminating groups of patients with and without severe late radiotherapy toxicity. Moreover, the discriminative power was enhanced by assessment of functionally or structurally related gene sets. While prediction of individual response requires improvement, this study is a step forward in predicting susceptibility to late radiation toxicity

A randomised controlled trial of the effects of a web-based PSA decision aid, Prosdex. Protocol

Contains fulltext : 51771.pdf ( ) (Open Access)BACKGROUND: Informed decision making is the theoretical basis in the UK for men's decisions about Prostate Specific Antigen (PSA) testing for prostate cancer testing. The aim of this study is to evaluate the effect of a web-based PSA decision-aid, Prosdex, on informed decision making in men. The objective is to assess the effect of Prosdex on six specific outcomes: (i) knowledge of PSA and prostate cancer-related issues - the principal outcome of the study; (ii) attitudes to testing; (iii) decision conflict; (iv) anxiety; (v) intention to undergo PSA testing; (vi) uptake of PSA testing. In addition, a mathematical simulation model of the effects of Prosdex will be developed. METHODS: A randomised controlled trial with four groups: two intervention groups, one viewing Prosdex and the other receiving a paper version of the site; two control groups, the second controlling for the potential Hawthorn effect of the questionnaire used with the first control group. Men between the ages of 50 and 75, who have not previously had a PSA test, will be recruited from General Practitioners (GPs) in Wales, UK. The principal outcome, knowledge, and four other outcome measures - attitudes to testing, decision conflict, anxiety and intention to undergo testing - will be measured with an online questionnaire, used by men in three of the study groups. Six months later, PSA test uptake will be ascertained from GP records; the online questionnaire will then be repeated. These outcomes, and particularly PSA test uptake, will be used to develop a mathematical simulation model, specifically to consider the impact on health service resources

Impact of impaired fractional flow reserve after coronary interventions on outcomes: a systematic review and meta-analysis

BACKGROUND: FFR is routinely used to guide percutaneous coronary interventions (PCI). Visual assessment of the angiographic result after PCI has limited efficacy. Even when the angiographic result seems satisfactory FFR after a PCI might be useful for identifying patients with a suboptimal interventional result and higher risk for poor clinical outcome who might benefit from additional procedures. The aim of this meta-analysis was to investigate available data of studies that examined clinical outcomes of patients with impaired vs. satisfactory fractional flow reserve (FFR) after percutaneous coronary interventions (PCI). METHODS: This meta-analysis was carried out according to the Cochrane Handbook for Systematic Reviews. The Mantel-Haenszel method using the fixed-effect meta-analysis model was used for combining the results. Studies were identified by searching the literature through mid-January, 2016, using the following search terms: fractional flow reserve, coronary circulation, after, percutaneous coronary intervention, balloon angioplasty, stent implantation, and stenting. Primary endpoint was the rate of major adverse cardiac events (MACE). Secondary endpoints included rates of death, myocardial infarction (MI), repeated revascularisation. RESULTS: Eight relevant studies were found including a total of 1337 patients. Of those, 492 (36.8 %) had an impaired FFR after PCI, and 853 (63.2 %) had a satisfactory FFR after PCI. Odds ratios indicated that a low FFR following PCI was associated with an impaired outcome: major adverse cardiac events (MACE, OR: 4.95, 95 % confidence interval [CI]: 3.39–7.22, p <0.001); death (OR: 3.23, 95 % CI: 1.19–8.76, p = 0.022); myocardial infarction (OR: 13.83, 95 % CI: 4.75–40.24, p <0.0001) and repeated revascularisation (OR: 4.42, 95 % CI: 2.73–7.15, p <0.0001). CONCLUSIONS: Compared to a satisfactory FFR, a persistently low FFR following PCI is associated with a worse clinical outcome. Prospective studies are needed to identify underlying causes, determine an optimal threshold for post-PCI FFR, and clarify whether simple additional procedures can influence the post-PCI FFR and clinical outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12872-016-0355-7) contains supplementary material, which is available to authorized users

Testing the activitystat hypothesis: a randomised controlled trial protocol

Background: The activitystat hypothesis proposes that when physical activity or energy expenditure is increased or decreased in one domain, there will be a compensatory change in another domain to maintain an overall, stable level of physical activity or energy expenditure. To date, there has been no experimental study primarily designed to test the activitystat hypothesis in adults. The aim of this trial is to determine the effect of two different imposed exercise loads on total daily energy expenditure and physical activity levels. Methods. This study will be a randomised, multi-arm, parallel controlled trial. Insufficiently active adults (as determined by the Active Australia survey) aged 18-60 years old will be recruited for this study (n=146). Participants must also satisfy the Sports Medicine Australia Pre-Exercise Screening System and must weigh less than 150 kg. Participants will be randomly assigned to one of three groups using a computer-generated allocation sequence. Participants in the Moderate exercise group will receive an additional 150 minutes of moderate to vigorous physical activity per week for six weeks, and those in the Extensive exercise group will receive an additional 300 minutes of moderate to vigorous physical activity per week for six weeks. Exercise targets will be accumulated through both group and individual exercise sessions monitored by heart rate telemetry. Control participants will not be given any instructions regarding lifestyle. The primary outcome measures are activity energy expenditure (doubly labeled water) and physical activity (accelerometry). Secondary measures will include resting metabolic rate via indirect calorimetry, use of time, maximal oxygen consumption and several anthropometric and physiological measures. Outcome measures will be conducted at baseline (zero weeks), mid- and end-intervention (three and six weeks) with three (12 weeks) and six month (24 week) follow-up. All assessors will be blinded to group allocation. Discussion. This protocol has been specifically designed to test the activitystat hypothesis while taking into account the key conceptual and methodological considerations of testing a biologically regulated homeostatic feedback loop. Results of this study will be an important addition to the growing literature and debate concerning the possible existence of an activitystat. Trial registration. Australian New Zealand Clinical Trials Registry ACTRN12610000248066

Cost-Effectiveness of a Telephone-Delivered Intervention for Physical Activity and Diet

Background: Given escalating rates of chronic disease, broad-reach and cost-effective interventions to increase physical activity and improve dietary intake are needed. The cost-effectiveness of a Telephone Counselling intervention to improve physical activity and diet, targeting adults with established chronic diseases in a low socio-economic area of a major Australian city was examined. Methodology/Principal Findings: A cost-effectiveness modelling study using data collected between February 2005 and November 2007 from a cluster-randomised trial that compared Telephone Counselling with a “Usual Care” (brief intervention) alternative. Economic outcomes were assessed using a state-transition Markov model, which predicted the progress of participants through five health states relating to physical activity and dietary improvement, for ten years after recruitment. The costs and health benefits of Telephone Counselling, Usual Care and an existing practice (Real Control) group were compared. Telephone Counselling compared to Usual Care was not cost-effective ($78,489 per quality adjusted life year gained). However, the Usual Care group did not represent existing practice and is not a useful comparator for decision making. Comparing Telephone Counselling outcomes to existing practice (Real Control), the intervention was found to be cost-effective ($29,375 per quality adjusted life year gained). Usual Care (brief intervention) compared to existing practice (Real Control) was also cost-effective ($12,153 per quality adjusted life year gained). Conclusions/Significance: This modelling study shows that a decision to adopt a Telephone Counselling program over existing practice (Real Control) is likely to be cost-effective. Choosing the ‘Usual Care’ brief intervention over existing practice (Real Control) shows a lower cost per quality adjusted life year, but the lack of supporting evidence for efficacy or sustainability is an important consideration for decision makers. The economics of behavioural approaches to improving health must be made explicit if decision makers are to be convinced that allocating resources toward such programs is worthwhile

Fields with no recent legume cultivation have sufficient nitrogen-fixing rhizobia for crops of faba bean (Vicia faba L.)

Purpose (1) To assess the biological N fixation (BNF) potential of varieties of faba bean (Vicia faba L.) cropped with or without compost in an experimental field-scale rotation with no recent history of legumes, (2) to enumerate soil populations of Rhizobium leguminosarum sv. viciae (Rlv), and to genetically characterize the nodulating Rlv strains, (3) compare BNF with other sites in Britain. Methods BNF was evaluated from 2012–2015 using 15N natural abundance. Treatments were either PK fertilizer or compost. Soil rhizobial populations were determined using qPCR, the symbiotic rhizobia genotyped (16S rRNA, nodA and nodD genes), and their BNF capacity assessed ex situ. The reliance of legumes on BNF at other British sites was estimated in a single season, and their nodulating symbionts examined. Results Faba bean obtained most of its N through BNF (>80%) regardless of variety or year. N-accumulation by cvs Babylon and Boxer increased with compost treatment in 2014/2015. Rhizobial populations were c. 105-106 Rlv cells g-1 soil regardless of field or treatment. 157 Rlv microsymbionts grouped into two large nodAD clades; one mainly from V. faba, and the other from various legumes. All isolates nodulated, and some performed better than commercial inoculant strains. Conclusions Faba bean can provide most of its nitrogen through BNF and leave economically valuable residual N for subsequent crops. Recent legume cropping in northern Europe is not essential for effective nodulation: rhizobia may persist in a range of farmland locations. Nevertheless, there is the potential to apply elite rhizobial strains as inoculants in some soils

Development of a Halotolerant Community in the St. Lucia Estuary (South Africa) during a Hypersaline Phase

Background: The St. Lucia Estuary, Africa’s largest estuarine lake, is currently experiencing unprecedented freshwater deprivation which has resulted in a northward gradient of drought effects, with hypersaline conditions in its northern lakes. Methodology/Principal Findings: This study documents the changes that occurred in the biotic communities at False Bay from May 2010 to June 2011, in order to better understand ecosystem functioning in hypersaline habitats. Few zooplankton taxa were able to withstand the harsh environmental conditions during 2010. These were the flatworm Macrostomum sp., the harpacticoid copepod Cletocamptus confluens, the cyclopoid copepod Apocyclops cf. dengizicus and the ciliate Fabrea cf. salina. In addition to their exceptional salinity tolerance, they were involved in a remarkably simple food web. In June 2009, a bloom of an orange-pigmented cyanobacterium (Cyanothece sp.) was recorded in False Bay and persisted uninterruptedly for 18 months. Stable isotope analysis suggests that this cyanobacterium was the main prey item of F. cf. salina. This ciliate was then consumed by A. cf. dengizicus, which in turn was presumably consumed by flamingos as they flocked in the area when the copepods attained swarming densities. On the shore, cyanobacteria mats contributed to a population explosion of the staphylinid beetle Bledius pilicollis. Although zooplankton disappeared once salinities exceeded 130, many taxa are capable of producing spores or resting cysts to bridge harsh periods. The hypersaline community was disrupted by heavy summer rains in 2011, which alleviated drought conditions and resulted in a sharp increase in zooplankton stock an