NOTE The report of the Committee without its annexes appears as Official Records of the General Assembly, Sixty-third Session, Supplement No. 46. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. The country names used in this document are, in most cases, those that were in use at the time the data were collected or the text prepared. In other cases, however, the names have been updated, where this was possible and appropriate, to reflect political changes. Scientific Annexes Annex A. Medical radiation exposures Annex B. Exposures of the public and workers from various sources of radiation INTROdUCTION 1. In the course of the research and development for and the application of atomic energy and nuclear technologies, a number of radiation accidents have occurred. Some of these accidents have resulted in significant health effects and occasionally in fatal outcomes. The application of technologies that make use of radiation is increasingly widespread around the world. Millions of people have occupations related to the use of radiation, and hundreds of millions of individuals benefit from these uses. Facilities using intense radiation sources for energy production and for purposes such as radiotherapy, sterilization of products, preservation of foodstuffs and gamma radiography require special care in the design and operation of equipment to avoid radiation injury to workers or to the public. Experience has shown that such technology is generally used safely, but on occasion controls have been circumvented and serious radiation accidents have ensued. 2. Reviews of radiation exposures from accidents have been presented in previous UNSCEAR reports. The last report containing an exclusive chapter on exposures from accidents was the UNSCEAR 1993 Report [U6]. 3. This annex is aimed at providing a sound basis for conclusions regarding the number of significant radiation accidents that have occurred, the corresponding levels of radiation exposures and numbers of deaths and injuries, and the general trends for various practices. Its conclusions are to be seen in the context of the Committee's overall evaluations of the levels and effects of exposure to ionizing radiation. 4. The Committee's evaluations of public, occupational and medical diagnostic exposures are mostly concerned with chronic exposures of …

sources and effects of ionizing radiation

Objective:To revise the “Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult” published in Critical Care Medicine in 2002.Methods:The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task f

/pdf/clinical-practice-guidelines-for-the-management-of-pain-4810wy3nml.pdf

Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit

It is increasingly proposed that reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a key role in human cancer development [1–6], especially as evidence is growing that antioxidants may prevent or delay the onset of some types of cancer (reviewed in [7,8]). ROS is a collective term often used by biologists to include oxygen radicals [superoxide (O # J−), hydroxyl (OHJ), peroxyl (RO # J) and alkoxyl (ROJ)] and certain nonradicals that are either oxidizing agents and}or are easily converted into radicals, such as HOCl, ozone (O $ ), peroxynitrite (ONOO−), singlet oxygen ("O # ) and H # O # . RNS is a similar collective term that includes nitric oxide radical (NOJ), ONOO−, nitrogen dioxide radical (NO # J), other oxides of nitrogen and products arising when NOJ reacts with O # J−, ROJ and RO # J. ‘Reactive ’ is not always an appropriate term; H # O # , NOJ and O # J− react quickly with very few molecules, whereas OHJ reacts quickly with almost anything. RO # J, ROJ, HOCl, NO # J, ONOO− and O $ have intermediate reactivities. ROS and RNS have been shown to possess many characteristics of carcinogens [4] (Figure 1). Mutagenesis by ROS}RNS could contribute to the initiation of cancer, in addition to being important in the promotion and progression phases. For example, ROS}RNS can have the following effects. (1) Cause structural alterations in DNA, e.g. base pair mutations, rearrangements, deletions, insertions and sequence amplification. OHJ is especially damaging, but "O # , RO # J, ROJ, HNO # , O $ , ONOO− and the decomposition products of ONOO− are also effective [9–13]. ROS can produce gross chromosomal alterations in addition to point mutations and thus could be involved in the inactivation or loss of the second wild-type allele of a mutated proto-oncogene or tumour-suppressor gene that can occur during tumour promotion and progression, allowing expression of the mutated phenotype [4]. (2) Affect cytoplasmic and nuclear signal transduction pathways [14,15]. For example, H # O # (which crosses cell and organelle membranes easily) can lead to displacement of the inhibitory subunit from the cytoplasmic transcription factor nuclear factor κB, allowing the activated factor to migrate to the nucleus [14]. Nitration of tyrosine residues by ONOO− may block phosphorylation. (3) Modulate the activity of the proteins and genes that respond to stress and which act to regulate the genes that are related to cell proliferation, differentiation and apoptosis [4,14–17]. For example, H # O # can stimulate transcription of c-jun

/pdf/damage-to-dna-by-reactive-oxygen-and-nitrogen-species-role-2988jdgpnd.pdf

Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer.

Background:Millions of patients are discharged from intensive care units annually. These intensive care survivors and their families frequently report a wide range of impairments in their health status which may last for months and years after hospital discharge.Objectives:To report on a 2-day Socie

http://c.ymcdn.com/sites/www.acutept.org/resource/resmgr/imported/Zanni%20and%20Kho%20COMBINED.pdf

Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders' conference.

Increases in ultraviolet radiation at the Earth's surface due to the depletion of the stratospheric ozone layer have recently fuelled interest in the mechanisms of various effects it might have on organisms. DNA is certainly one of the key targets for UV-induced damage in a variety of organisms ranging from bacteria to humans. UV radiation induces two of the most abundant mutagenic and cytotoxic DNA lesions such as cyclobutane–pyrimidine dimers (CPDs) and 6–4 photoproducts (6–4PPs) and their Dewar valence isomers. However, cells have developed a number of repair or tolerance mechanisms to counteract the DNA damage caused by UV or any other stressors. Photoreactivation with the help of the enzyme photolyase is one of the most important and frequently occurring repair mechanisms in a variety of organisms. Excision repair, which can be distinguished into base excision repair (BER) and nucleotide excision repair (NER), also plays an important role in DNA repair
in several organisms with the help of a number of glycosylases and polymerases, respectively. In addition, mechanisms such as mutagenic repair or dimer bypass, recombinational repair, cell-cycle checkpoints, apoptosis and certain alternative repair pathways are also operative in various organisms. This review deals with UV-induced DNA damage and the associated repair mechanisms as well as methods of detecting DNA damage and its future perspectives.

/pdf/uv-induced-dna-damage-and-repair-a-review-28aup0s77v.pdf

UV-induced DNA damage and repair: a review

Objective
This prospective observational study was designed to explore the relationships between post-traumatic stress disorder (PTSD), patients' memories of the intensive care unit (ICU) and sedation practices.

Precipitants of post-traumatic stress disorder following intensive care: a hypothesis generating study of diversity in care.

The xeroderma pigmentosum group A complementing protein (XPAC) is involved in an early step of nucleotide excision repair, the main process that removes UV damage and many chemical lesions from DNA. To explore the properties and function of XPAC, recombinant protein encoded by the human XPAC cDNA was expressed with an N-terminal polyhistidine tag in Escherichia coli and purified to homogeneity. The soluble fusion protein could correct the repair defect in vitro of XP-A cell extracts. XPAC protein bound to DNA with a preference for UV-irradiated over nonirradiated DNA, as determined by a gel electrophoresis mobility shift assay with a 258 base pair DNA fragment (the association constant was approximately 3 x 10(6) M-1 for the fragment irradiated with 6 kJ/m2 UV light). Removal of cyclobutane pyrimidine dimers from UV-irradiated DNA by enzymatic photoreactivation did not significantly reduce binding of XPAC to the irradiated fragment, indicating that binding was mostly due to (6-4) photoproducts, with a preference for a (6-4) photoproduct over an undamaged base pair up to 300-fold. Undamaged single-stranded DNA competed about 4-fold more effectively than undamaged double-stranded DNA for binding of XPAC to a UV-irradiated fragment. In addition, XPAC bound to DNA treated with the chemotherapeutic agent cis-diamminedichloroplatinum(II). The results suggest that XPAC functions as a key component in recognition of DNA damage during repair.

Preferential binding of the xeroderma pigmentosum group A complementing protein to damaged DNA.

Plasmid DNA was gamma-irradiated or treated with H2O2 in the presence of Cu2+ to generate oxygen free radical-induced lesions. Open circular DNA molecules were removed by ethidium bromide/CsCl density gradient centrifugation. The closed circular DNA fraction was treated with the Escherichia coli reagent enzymes endonuclease III (Nth protein) and Fpg protein. This treatment converted DNA molecules containing the major base lesions pyrimidine hydrates and 8-hydroxyguanine to a nicked form. Remaining closed circular DNA containing other oxygen radical-induced base lesions was used as a substrate for nucleotide excision-repair in a cell-free system. Extracts from normal human cells, but not extracts from xeroderma pigmentosum cells, catalyzed repair synthesis in this DNA. The repair defect in the latter extracts could be specifically corrected by in vitro complementation. The data suggest that accumulation of endogenous oxidative damage in cellular DNA from xeroderma pigmentosum patients contributes to the increased frequency of internal cancers and the neural degeneration occurring in serious cases of the syndrome.

DNA excision-repair defect of xeroderma pigmentosum prevents removal of a class of oxygen free radical-induced base lesions

Complementation group A of xeroderma pigmentosum (XP) represents one of the most prevalent and serious forms of this cancer-prone disorder. Because of a marked defect in DNA excision repair, cells from individuals with XP-A are hypersensitive to the toxic and mutagenic effects of ultraviolet light and many chemical agents. We report here the isolation of the XP-A DNA repair protein by complementation of cell extracts from a repair-defective human XP-A cell line. XP-A protein purified from calf thymus migrates on denaturing gel electrophoresis as a doublet of 40 and 42 kilodaltons. The XP-A protein binds preferentially to ultraviolet light-irradiated DNA, with a preference for damaged over nondamaged nucleotides of approximately 10(3). This strongly suggests that the XP-A protein plays a direct role in the recognition of and incision at lesions in DNA. We further show that this protein corresponds to the product encoded by a recently isolated gene that can restore excision repair to XP-A cells. Thus, excision repair of plasmid DNA by cell extracts sufficiently resembles genomic repair in cells to reveal accurately the repair defect in an inherited disease. The general approach described here can be extended to the identification and isolation of other human DNA repair proteins.

https://www.embopress.org/doi/pdf/10.1002/j.1460-2075.1991.tb04961.x

Complementation of DNA repair in xeroderma pigmentosum group A cell extracts by a protein with affinity for damaged DNA

This paper presents the results of an investigation of the effects of hygrothermal conditioning on the mechanical properties and fatigue behaviour of epoxy-based composites reinforced with carbon, glass and aromatic polyamide fibres. Cross-plied (0$^\circ$/90$^\circ$) laminates of these materials, of nominal fibre volume fraction ca. 0.6, were conditioned by drying, by exposing to a 65% r.h. (relative humidity) atmosphere and by boiling in water. The effects of these treatments on the tensile and shear strengths and on the tensile fatigue response of the laminates when tested orthogonally and at $\pm$ 45$^\circ$ to the fibre lay-up are discussed. The 0$^\circ$/90$^\circ$ tensile properties of the three laminates are relatively little affected by the conditioning treatments except for g.r.p. (glass reinforced plastic) exposed to boiling water, and of K.f.r.p. (Kevlar fibre reinforced plastic) in which the strength is reduced somewhat by complete drying. The shear strengths and $\pm$45$^\circ$ tensile strengths are more sensitive to the effects of moisture, however, and it appears that optimum strengths are developed after conditioning at the intermediate 65% r.h. Tensile fatigue tests have been carried out on laminates in the 0$^\circ$/90$^\circ$ and $\pm$45$^\circ$ orientations. In c.f.r.p. (carbon fibre reinforced plastic) there is no effect of conditioning on the fatigue behaviour of 0$^\circ$/90$^\circ$ samples, and in g.r.p. only the boiling water treatment affects the results. Preloading g.r.p. samples before conditioning has no effect on their fatigue behaviour. The tensile fatigue resistance of 0$^\circ$/90$^\circ$ Kevlar-epoxy laminates is reduced by drying more than by boiling, and in all conditions the stress against logarithm of life curves are characterized by a downward curvature that renders the long term stability of this material suspect. This behaviour is also reflected in differences in the $\pm$45$^\circ$ tensile fatigue response of the three laminates.

Christopher J. Jones

Papers

Precipitants of post-traumatic stress disorder following intensive care: a hypothesis generating study of diversity in care.

Preferential binding of the xeroderma pigmentosum group A complementing protein to damaged DNA.

DNA excision-repair defect of xeroderma pigmentosum prevents removal of a class of oxygen free radical-induced base lesions

Complementation of DNA repair in xeroderma pigmentosum group A cell extracts by a protein with affinity for damaged DNA

The environmental fatigue behaviour of reinforced plastics