Increased diagnosis and detection rates of carcinoma in situ of the breast

The purpose of this study was to identify trends in the diagnosis of carcinoma in situ (CIS) of the breast in the United Kingdom (UK) and the Republic of Ireland (ROI) and to examine the impact of mammography. Data on cases of newly diagnosed CIS of the breast and mode of detection (screen detected or not) were obtained, where available, from regional cancer registries between 1990 and 2007. Age-standardised diagnosis rates for the UK and the ROI, and regional screen detected diagnosis rates were compared by calculating the annual percentage change (APC) over time. The APC of the diagnosis rate amongst women aged 50-64 years (original screening age group) showed a significant 5.9% increase in the UK (1990-2007) and 11.5% increase in the ROI (1994-2007). The rate of diagnosis (50-64 years) stabilized in the UK between 2005 and 2007 and was substantially higher than in other western populations with national screening programmes. The APC of the diagnosis rate amongst those aged 65-69 years showed a significant 12.4% increase in the UK (1990-2007) and 10.3% increase in the ROI (1994-2007). amongst women aged 50-74 years in the UK, approximately 4,300 cases of CIS (˜90% ductal carcinoma in situ) were diagnosed in 2007. Our analyses have shown that screen detected CIS contributed primarily to the increase in diagnosis of CIS of the breast. The high diagnosis rate of screen detected CIS of the breast underlines the need for further research into lesion and patient characteristics that are related to progression of CIS to invasive disease to better target treatment. © 2012 Springer Science+Business Media, LLC.

Rates for repair of pBR 322 DNA radicals by thiols as measured by the gas explosion technique: evidence that counter-ion condensation and co-ion depletion are significant at physiological ionic strength.

Rates of rapair of pBR 322 plasmid DNA radicals by thiols of varying net charge (Z) at pH 7 and physiological ionic strength were measured using the oxygen explosion technique. The extent of conversion of supercoiled to relaxed circular plasmid was measured by HPLC as a function of the time of oxygen exposure before or after irradiation, the time-courses being fitted by a pseudo-first-order kinetic expression with k1 = k2[RSH]. Values of k2 (M-1 S-1) were: 2.1 x 10(5) (GSH, Z = -1), 1.4 x 10(6) (2-mercaptoethanol, Z = 0), 1.2 x 10(7) (cysteamine, Z = +1), 6.6 x 10(7) (WR-1065 or N-(2-mercaptoethyl)-1,3-diamino?? propane, Z = +2). The approximately 6-fold increase in rate with each unit increase in Z is attributed to concentration of cationic thiols near DNA as a consequence of counter-ion condensation and reduced levels of anionic thiols near DNA owing to co-ion depletion. The results are quantitatively consistent with chemical repair as a significant mechanism for radioprotection of cells by neutral and cationic thiols under aerobic conditions, but indicate that repair by GSH will compete effectively with oxygen only at low oxygen tension.

A comparison of the chemical repair rates of free radical precursors of DNA damage and cell killing in Chinese hamster V79 cells.

One of the important temporal stages of radiation action in cellular systems is the chemical phase, where oxygen fixation reactions compete with chemical repair reactions involving reducing agents such as GSH. Using the gas explosion technique it is possible to follow the kinetics of these fast (> 1 ms) reactions in intact cells. We have compared the chemical repair kinetics of the oxygen-dependent free radical precursors leading to DNA single-strand and double-strand breaks, measured using filter elution techniques, with those leading to cell killing in V79 cells. The chemical repair rates for DNA dsb (670s-1 at pH 7.2 and 380s-1 at pH 9.6) and cell killing (530s-1) were similar. This is in agreement with the important role of DNA dsb in radiation induced cell lethality. The rate for DNA ssb precursors was significantly slower (210s-1). The difference in rate between DNA ssb and dsb precursors may be explained on the basis of a dsb free radical precursor consisting of a paired radical, one radical on each strand. The instantaneous probability of one or other of these radicals being chemically repaired and not proceeding to form a dsb will be twice that of a ssb radical precursor. This agrees well with the concept of locally multiply damaged sites (LMDS) produced from clusters of ionizations in DNA (Ward 1985).

The role of non-protein sulphydryls in determining the chemical repair rates of free radical precursors of DNA damage and cell killing in Chinese hamster V79 cells. I

Chinese hamster V79 fibroblasts were irradiated in the gas explosion apparatus and the chemical repair rates of the oxygen-dependent free radical precursors of DNA double-strand breaks (dsb) and lethal lesions measured using filter elution (pH 9.6) and a clonogenic assay. Depletion of cellular GSH levels, from 4.16 fmol/cell to 0.05 fmol/cell, by treatment with buthionine sulphoximine (50 mumol dm-3; 18 h), led to sensitization as regards DNA dsb induction and cell killing. This was evident at all time settings but was particularly pronounced when the oxygen shot was given 1 ms after the irradiation pulse. A detailed analysis of the chemical repair kinetics showed that depletion of GSH led to a reduction in the first-order rate constant for dsb precursors from 385 s-1 to 144 s-1, and for lethal lesion precursors from 533 s-1 to 165 s-1. This is generally consistent with the role of GSH in the repair-fixation model of radiation damage at the critical DNA lesions. However, the reduction in chemical repair rate was not proportional to the severe thiol depletion (down to almost-equal-to 1% for GSH) and a residual repair capacity remained (almost-equal-to 30%). This was found not to be due to compartmentalization of residual GSH in the nucleus, as the repair rate for dsb precursors in isolated nuclei, washed virtually free of GSH, was identical to that found in GSH-depleted cells (144 s-1), also the OER remained substantially above unity. This suggests that other reducing agents may have a role to play in the chemical repair of oxygen-dependent damage. One possible candidate is the significant level of protein sulphydryls present in isolated nuclei.

Comparative growth rates and internal banding periodicity of maerl species (Corallinales, Rhodophyta) from northern Europe

Maerl is a type of rhodolith, found in ecologically important beds of high conservation value; a major conservation objective is to establish growth rates. Maerl shows internal banding of controversial periodicity that may contain a high-resolution record of palaeoceanographic-palaeoclimatic data. To investigate growth rates and banding periodicity, we used the vital stain Alizarin Red in combination with scanning electron microscopy (SEM). Three maerl species, Phymatolithon calcareum, Lithothamnion corallioides and L. glaciale, were collected from maerl beds in Ireland. Following staining, maerl was grown in three controlled temperature treatments and at two depths in the field (P. calcareum only), with Corallina officinalis as a control for the stain. Alizarin Red was shown to be a suitable marker for growth in European maerl species and for C. officinalis. The average tip growth rate of P. calcareum from Northern Ireland at 10 m depth and under constant laboratory conditions was c. 0.9 mm yr(-1), double the rates observed at 5 m depth and in L. corallioides. Our measurements and re-examination of reported data allow us to conclude that the three most abundant maerl species in Europe grow about 1 (0.5-1.5) mm per tip per year under a wide range of field and artificial conditions. Internal banding in temperate European maerl revealed by SEM is a result of regular changes in wall thickness; the approximately monthly periodicity of bands in field-grown specimens is consistent with previous suggestions that they may be lunar. The potential for maerl banding to be a high-resolution record of palaeoclimatic and palaeoenvironmental change could be realized with this vital stain in conjunction with isotopic or microgeochemical analyses.

Biological effectiveness on live cells of laser driven protons at dose rates exceeding 109 Gy/s

The ultrashort duration of laser-driven multi-MeV ion bursts offers the possibility of radiobiological studies at extremely high dose rates. Employing the TARANIS Terawatt laser at Queen's University, the effect of proton irradiation at MeV-range energies on live cells has been investigated at dose rates exceeding 109 Gy/s as a single exposure. A clonogenic assay showed consistent lethal effects on V-79 live cells, which, even at these dose rates, appear to be in line with previously published results employing conventional sources. A Relative Biological Effectiveness (RBE) of 1.4±0.2 at 10% survival is estimated from a comparison with a 225 kVp X-ray source.

The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis

STUDY QUESTION Is there an association between high levels of sperm DNA damage and miscarriage?SUMMARY ANSWERMiscarriage rates are positively correlated with sperm DNA damage levels.WHAT IS KNOWN ALREADYMost ejaculates contain a subpopulation of sperm with DNA damage, also referred to as DNA fragmentation, in the form of double or single-strand breaks which have been induced in the DNA prior to or following ejaculation. This DNA damage may be particularly elevated in some subfertile men, hence several studies have examined the link between sperm DNA damage levels and conception and miscarriage rates.STUDY DESIGN, SIZE, DURATIONA systematic review and meta-analysis of studies which examined the effect of sperm DNA damage on miscarriage rates was performed. Searches were conducted on MEDLINE, EMBASE and the Cochrane Library without any language restrictions from database inception to January 2012.PARTICIPANTS/MATERIALS, SETTING, METHODSWe used the terms 'DNA damage' or 'DNA fragmentation' combined with 'miscarriage', 'abortion' or 'pregnancy' to generate a set of relevant citations. Data extraction was performed by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of relative risks of miscarriage was performed with a random effects model. Subgroup analyses were performed by the type of DNA damage test, whether the sperm examined were prepared or from raw semen and for pregnancies resulting from IVF or ICSI treatment.MAIN RESULTS AND THE ROLE OF CHANCEWe identified 16 cohort studies (2969 couples), 14 of which were prospective. Eight studies used acridine orange-based assays, six the TUNEL assay and two the COMET assay. Meta-analysis showed a significant increase in miscarriage in patients with high DNA damage compared with those with low DNA damage [risk ratio (RR) = 2.16 (1.54, 3.03), P <0.00001)]. A subgroup analysis showed that the miscarriage association is strongest for the TUNEL assay (RR = 3.94 (2.45, 6.32), P <0.00001).LIMITATIONS, REASONS FOR CAUTIONThere is some variation in study characteristics, including the use of different assays and different thresholds for DNA damage and the definition of pregnancy loss.WIDER IMPLICATIONS OF THE FINDINGSThe use of methods which select sperm without DNA damage for use in assisted conception treatment may reduce the risk of miscarriage. This finding indicates that assays detecting DNA damage could be considered in those suffering from recurrent pregnancy loss. Further research is necessary to study the mechanisms of DNA damage and the potential therapeutic effects of antioxidant therapy.STUDY FUNDING/COMPETING INTEREST(S)None.

Partial and total multiphoton detachment rates for H- in a perturbative B-spline-based approach

An ab initio approach has been applied to study multiphoton detachment rates for the negative hydrogen ion in the lowest nonvanishing order of perturbation theory. The approach is based on the use of B splines allowing an accurate treatment of the electronic repulsion. Total detachment rates have been determined for two- to six-photon processes as well as partial rates for detachment into the different final symmetries. It is shown that B-spline expansions can yield accurate continuum and bound-state wave functions in a very simple manner. The calculated total rates for two- and three-photon detachment are in good agreement with other perturbative calculations. For more than three-photon detachment little information has been available before now. While the total cross sections show little structure, a fair amount of structure is predicted in the partial cross sections. In the two-photon process, it is shown that the detached electrons mainly have s character. For four- and six-photon processes, the contribution from the d channel is the most important. For three- and five-photon processes p electrons dominate the electron emission spectrum. Detachment rates for s and p electrons show minima as a function of photon energy. © 1994 The American Physical Society.