Mathematical methods and models for radiation carcinogenesis studies

Research on radiation carcinogenesis requires a twofold approach. Studies of primary molecular lesions and subsequent cytogenetic changes are essential, but they cannot at present provide numerical estimates of the risk of small doses of ionizing radiations. Such estimates require extrapolations from dose, time, and age dependences of tumor rates observed in animal studies and epidemiological investigations, and they necessitate the use of statistical methods that correct for competing risks. A brief survey is given of the historical roots of such methods, of the basic concepts and quantities which are required, and of the maximum likelihood estimates which can be derived for right censored and double censored data. Non-parametric and parametric models for the analysis of tumor rates and their time and dose dependences are explained

Clostridium perfringensepsilon toxin H149A mutant as a platform for receptor binding studies

Clostridium perfringens epsilon toxin (Etx) is a pore-forming toxin responsible for a severe and rapidly fatal enterotoxemia of ruminants. The toxin is classified as a category B bioterrorism agent by the U.S. Government Centres for Disease Control and Prevention (CDC), making work with recombinant toxin difficult. To reduce the hazard posed by work with recombinant Etx, we have used a variant of Etx that contains a H149A mutation (Etx-H149A), previously reported to have reduced, but not abolished, toxicity. The three-dimensional structure of H149A prototoxin shows that the H149A mutation in domain III does not affect organisation of the putative receptor binding loops in domain I of the toxin. Surface exposed tyrosine residues in domain I of Etx-H149A (Y16, Y20, Y29, Y30, Y36 and Y196) were mutated to alanine and mutants Y30A and Y196A showed significantly reduced binding to MDCK.2 cells relative to Etx-H149A that correlated with their reduced cytotoxic activity. Thus, our study confirms the role of surface exposed tyrosine residues in domain I of Etx in binding to MDCK cells and the suitability of Etx-H149A for further receptor binding studies. In contrast, binding of all of the tyrosine mutants to ACHN cells was similar to that of Etx-H149A, suggesting that Etx can recognise different cell surface receptors. In support of this, the crystal structure of Etx-H149A identified a glycan (β-octyl-glucoside) binding site in domain III of Etx-H149A, which may be a second receptor binding site. These findings have important implications for developing strategies designed to neutralise toxin activity

EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2013 . Scientific opinion on Dietary Reference Values for fluoride

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for fluoride, which are provided as Adequate Intake (AI) from all sources, including non-dietary sources. Fluoride is not an essential nutrient. Therefore, no Average Requirement for the performance of essential physiological functions can be defined. Nevertheless, the Panel considered that the setting of an AI is appropriate because of the beneficial effects of dietary fluoride on prevention of dental caries. The AI is based on epidemiological studies (performed before the 1970s) showing an inverse relationship between the fluoride concentration of water and caries prevalence. As the basis for defining the AI, estimates of mean fluoride intakes of children via diet and drinking water with fluoride concentrations at which the caries preventive effect approached its maximum whilst the risk of dental fluorosis approached its minimum were chosen. Except for one confirmatory longitudinal study in US children, more recent studies were not taken into account as they did not provide information on total dietary fluoride intake, were potentially confounded by the use of fluoride-containing dental hygiene products, and did not permit a conclusion to be drawn on a dose-response relationship between fluoride intake and caries risk. The AI of fluoride from all sources (including non-dietary sources) is 0.05 mg/kg body weight per day for both children and adults, including pregnant and lactating women. For pregnant and lactating women, the AI is based on the body weight before pregnancy and lactation. Reliable and representative data on the total fluoride intake of the European population are not available

Application of electrochemical impedance for characterising arrays of Bi2S3 nanowires

Electrochemical Impedance Spectroscopy (EIS) was used to characterise the electrical properties of bismuth sulphide (Bi2S3) nanowires (NWs) templated within anodic aluminium oxide (AAO) membranes. A specially engineered cell, with a nominal electrolyte volume of 0.1–0.2 ml, was used to hold and measure the electrochemical impedance of the fragile NW/AAO samples. An equivalent circuit model was developed to determine the filling density of nanowires within the porous templates. The EIS method can be utilised to probe the nanowire filling density in porous membranes over large sample areas, which is often unobtainable using electron microscopy and conductive atomic force microscopy techniques

Adult domiciliary oxygen therapy. Position statement of the Thoracic Society of Australia and New Zealand

The document attached has been archived with permission from the editor of the Medical Journal of Australia (26 April 2007). An external link to the publisher’s copy is included.• Patients with chronic obstructive pulmonary disease and a stable daytime PaO2 of ≤55 mmHg (7.3kPa) live longer and have a better quality of life if provided with long-term continuous oxygen therapy. • It is reasonable to offer continuous oxygen therapy also to patients with other lung diseases that cause chronic hypoxaemia. • Indications for supplemental oxygen therapy during exercise (ambulatory oxygen therapy) and sleep (nocturnal oxygen therapy) are less clear.Christine F McDonald, Alan J Crockett and Iven H Youn

Storm evolution characterization for analysing stone armour damage progression

Storm evolution is fundamental for analysing the damage progression of the different failure modes and establishing suitable protocols for maintaining and optimally sizing structures. However, this aspect has hardly been studied and practically the whole of the studies dealing with the subject adopt the Equivalent triangle storm. As against this approach, two new ones are proposed. The first is the Equivalent Triangle Magnitude Storm model (ETMS), whose base, the triangular storm duration, D, is established such that its magnitude (area describing the storm history above the reference threshold level which sets the storm condition),HT, equals the real storm magnitude. The other is the Equivalent Triangle Number of Waves Storm (ETNWS), where the base is referred in terms of the real storm's number of waves,Nz. Three approaches are used for estimating the mean period, Tm, associated to each of the sea states defining the storm evolution, which is necessary to determine the full energy flux withstood by the structure in the course of the extreme event. Two are based on the Jonswap spectrum representativity and the other uses the bivariate Gumbel copula (Hs, Tm), resulting from adjusting the storm peaks. The representativity of the approaches proposed and those defined in specialised literature are analysed by comparing the main armour layer's progressive loss of hydraulic stability caused by real storms and that relating to theoretical ones. An empirical maximum energy flux model is used for this purpose. The agreement between the empirical and theoretical results demonstrates that the representativity of the different approaches depends on the storm characteristics and point towards a need to investigate other geometrical shapes to characterise the storm evolution associated with sea states heavily influenced by swell wave components

EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA); Scientific Opinion on principles for deriving and applying Dietary Reference Values

This Opinion of the EFSA Panel on Dietetic products, Nutrition, and Allergies (NDA) deals with the general principles for development and application of Dietary Reference Values (DRVs). These quantitative reference values for nutrient intakes for healthy individuals and populations are based on health criteria. Derived from DRVs, nutrients goals and recommendations take into account other criteria such as food composition or dietary habits, and may be used for assessment and planning of diets. It is proposed to derive the following DRVs: 1) Population Reference Intakes (PRI), 2) Average Requirement (AR), 3) Lower Threshold Intake (LTI), 4) Adequate Intake (AI), 5) Reference Intake ranges for macronutrients (RI). Nutrient requirements differ with age, sex and physiological condition. The Panel proposes to define the age ranges used for each nutrient on a case-by-case basis depending on the available data. For the age group < 6 months requirements are considered to be equal to the supply from breast- milk, except in those cases where this does not apply. Separate reference values will be established for pregnant and lactating women. Interpolation or extrapolation between population groups will be used in instances where no data are available for defined age and sex groups

EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA); Scientific Opinion on Dietary reference values for water

This Opinion of the EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) deals with the setting of dietary reference values for water for specific age groups. Adequate Intakes (AI) have been defined derived from a combination of observed intakes in population groups with desirable osmolarity values of urine and desirable water volumes per energy unit consumed. The reference values for total water intake include water from drinking water, beverages of all kind, and from food moisture and only apply to conditions of moderate environmental temperature and moderate physical activity levels (PAL 1.6). AIs for infants in the first half of the first year of life are estimated to be 100-190 mL/kg per day. For infants 6-12 months of age a total water intake of 800-1000 mL/day is considered adequate. For the second year of life an adequate total water intake of 1100-1200 mL/day is defined by interpolation, as intake data are not available. AIs of water for children are estimated to be 1300 mL/day for boys and girls 2-3 years of age; 1600 mL/day for boys and girls 4-8 years of age; 2100 mL/day for boys 9-13 years of age; 1900 mL/day for girls 9-13 years of age. Adolescents of 14 years and older are considered as adults with respect to adequate water intake. Available data for adults permit the definition of AIs as 2.0 L/day (P 95 3.1 L) for females and 2.5 L/day (P95 4.0 L) for males. The same AIs as for adults are defined for the elderly. For pregnant women the same water intake as in non-pregnant women plus an increase in proportion to the increase in energy intake (300 mL/day) is proposed. For lactating women adequate water intakes of about 700 mL/day above the AIs of non-lactating women of the same age are derive

Efficacy of pharmacological interventions: a systematic review informing the 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases

OBJECTIVE: To identify the best evidence on the efficacy of pharmacological interventions in reducing fatigue in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and to summarise their safety in the identified studies to inform European Alliance of Associations for Rheumatology recommendations for the management of fatigue in people with I-RMDs. METHODS: Systematic review of adults with I-RMDs conducted according to the Cochrane Handbook. Search strategy ran in Medline, Embase, Cochrane Library, CINAHL Complete, PEDro, OTseeker and PsycINFO. Only randomised controlled trials (RCTs) or controlled clinical trials were eligible. Assessment of risk of bias, data extraction and synthesis performed by two reviewers independently and in duplicate. Data pooled in statistical meta-analyses. RESULTS: From 4151 records, 455 were selected for full-text review, 99 fulfilled the inclusion criteria and 19 RCTs were included in meta-analyses. Adalimumab was superior to placebo in reducing fatigue at 12 and 52 weeks in rheumatoid arthritis (RA) (n=3 and 2 RCTs; mean difference (MD)= -3.03, p<0.001; MD=-2.25, p=0.03, respectively). Golimumab (n=2 RCTs; 24 weeks: MD=-5.27, p<0.001), baricitinib (n=2 RCTs; 24 weeks: MD=-4.06, p<0.001), sarilumab (n=2 RCTs; 24 weeks: MD=-3.15, p<0.001), tocilizumab (n=3 RCTs; 24 weeks: MD=-3.69, p<0.001) and tofacitinib (n=3 RCTs; 12 weeks: MD=-4.44, p<0.001) were also superior to placebo in reducing fatigue in RA. A dose/effect relationship was observed for sarilumab, tocilizumab and tofacitinib. In spondyloarthritis (excluding psoriatic arthritis), secukinumab was superior to placebo in reducing fatigue at 16 weeks (n=2 RCTs; MD=-4.15, p<0.001), with a dose/effect relationship also observed. The narrative results of the RCTs not included in the meta-analysis indicated that several other pharmacological interventions were efficacious in reducing fatigue, with reassuring safety results. CONCLUSIONS: Several pharmacological interventions are efficacious and generally safe for managing fatigue in people with I-RMDs