Relation between socioeconomic deprivation and pathological prognostic factors in women with breast cancer.

OBJECTIVE--To investigate the relation between socioeconomic deprivation and pathological prognostic factors in women with breast cancer as a possible explanation for socioeconomic differences in survival. DESIGN--Retrospective analysis of data from cancer registry and from pathology and biochemistry records. SETTING--Catchment areas of two large teaching hospitals in Glasgow. SUBJECTS--1361 women aged under 75 who had breast cancer diagnosed between 1980 and 1987. MAIN OUTCOME MEASURES--Tumour size, axillary lymph node status, histological grade, and oestrogen receptor concentration in relation to deprivation category of area of residence. RESULTS--There was no significant relation between socioeconomic deprivation and four pathological prognostic factors: 93 (32%) women in the most affluent group presented with tumours less than 20 mm in size compared with 91 (31%) women in the most deprived group; 152 (48%) of the most affluent group presented with negative nodes compared with 129 (46%) of the most deprived group; 23 (22%) of the most affluent group presented with grade I tumours compared with 12 (17%) of the most deprived group; and 142 (51%) of the most affluent group had a low oestrogen receptor concentration at presentation compared with 148 (52%) of the most deprived group. None of these differences was statistically significant. CONCLUSIONS--Differences in survival from breast cancer by socioeconomic deprivation category could not be accounted for by differences in tumour stage or biology. Other possible explanations, such as differences in treatment or in host response, should be investigated.     

The Ecology of Seasonal Stress and the Origins of Agriculture in the Near East

The time, place, and reasons for the first domestication of cereals and legumes in the Near East can now be securely identified using combined evidence from paleoenvironmental studies, models of ecosystem dynamics, and regional archeology. The heartland of domestication was the Jordan Valley and surrounding region in the Southern Levant. Approximately 10,000 years ago, people began planting crops where the wild ancestral species had proliferated over two millenia. Impetus for domestication came from the synergistic effects of climatic change, anthropogenic environmental change, technological change, and social innovation. At the end of the Pleistocene, after a long period of climatic instability, a mediterranean climate more strongly seasonal than any today emerged with hyper-arid summers that selected for annual species of cereals and legumes. This occurred long after people had invented tools suitable for grinding hard seeds, but the new, lengthy dry season and consequent need to use stored foods encouraged sedentism among human groups who subsequently depleted their immediate environments of wild resources. These preconditions facilitated the development of agriculture. The scenario developed here is specific to the Near East, for such case studies of specific factors in independent regions of domestication are essential before we attempt to explain cases all over the world with reference to global causes.     

Evaluation of flurbiprofen in detrusor instability.

Thirty women with detrusor instability (27 cases idiopathic, and three secondary to multiple sclerosis) completed a double-blind, cross-over trial of the prostaglandin synthetase inhibitor flurbiprofen and a placebo, results being evaluated by questionnaire and cystometry. Frequency, urgency, and urge incontinence were all significantly reduced with flurbiprofen (P less than 0.001, P less than 0.025, and P less than 0.025 respectively), as was the detrusor-pressure rise during bladder filling (P less than 0.01). Side effects, however, occurred in 13 patients while taking flurbiprofen compared with five while taking placebo (P less than 0.025). After the trial 19 patients wished to continue with flurbiprofen. Flurbiprofen is a useful treatment for idiopathic detrusor instability and is well tolerated by most patients.     

Alanine radicals,part 3: properties of the components contributing to the EPR spectrum of X-irradiated alanine dosimeters

The amino acid l-alpha-alanine has attracted considerable interest for use in radiation dosimetry and has been formally accepted as a secondary standard for high-dose and transfer dosimetry. Recent results have shown that the alanine EPR spectrum consists of contributions from three different radicals. A set of benchmark spectra describing the essential spectral features of these three radical components was used for reconstructions of the experimental spectra. In the present work, these basis spectra have been used to investigate the differential effects of variations in radiation doses and microwave power, as well as the dependence upon temperature annealing and UV illumination. The results presented here, based solely on relatively low-energy (60-80 keV) X rays, indicate that the three components behave very similarly with respect to radiation dose at room temperature. However, with respect to the thermal annealing/fading behavior and microwave power saturation properties, the three species behave significantly differently. It is concluded that even if it is now realized that three different radicals contribute to the composite EPR alanine spectrum, this has a minor impact on the established protocols for present-day applications (high-dose) of EPR/alanine dosimetry. However, some care should be exercised when e.g. constructing calibration curves, since fading and power saturation behavior may vary over the dose range in question. New results from UV-illumination experiments suggest a possible procedure for experimental spectral separation of the EPR signals due to the three radicals.     

Phylogenetic diversification of immunoglobulin genes and the antibody repertoire

Immunoglobulins are encoded by a large multigene system that undergoes somatic rearrangement and additional genetic change during the development of immunoglobulin-producing cells. Inducible antibody and antibody-like responses are found in all vertebrates. However, immunoglobulin possessing disulfide-bonded heavy and light chains and domain-type organization has been described only in representatives of the jawed vertebrates. High degrees of nucleotide and predicted amino acid sequence identity are evident when the segmental elements that constitute the immunoglobulin gene loci in phylogenetically divergent vertebrates are compared. However, the organization of gene loci and the manner in which the independent elements recombine (and diversify) vary markedly among different taxa. One striking pattern of gene organization is the "cluster type" that appears to be restricted to the chondrichthyes (cartilaginous fishes) and limits segmental rearrangement to closely linked elements. This type of gene organization is associated with both heavy- and light-chain gene loci. In some cases, the clusters are "joined" or "partially joined" in the germ line, in effect predetermining or partially predetermining, respectively, the encoded specificities (the assumption being that these are expressed) of the individual loci. By relating the sequences of transcribed gene products to their respective germ-line genes, it is evident that, in some cases, joined-type genes are expressed. This raises a question about the existence and/or nature of allelic exclusion in these species. The extensive variation in gene organization found throughout the vertebrate species may relate directly to the role of intersegmental (V<==>D<==>J) distances in the commitment of the individual antibody-producing cell to a particular genetic specificity. Thus, the evolution of this locus, perhaps more so than that of others, may reflect the interrelationships between genetic organization and function.      

Evaluating the effectiveness of conservation site networks under climate change: accounting for uncertainty

We forecasted potential impacts of climate change on the ability of a network of key sites for bird conservation (Important Bird Areas; IBAs) to provide suitable climate for 370 bird species of current conservation concern in two Asian biodiversity hotspots: the Eastern Himalaya and Lower Mekong. Comparable studies have largely not accounted for uncertainty, which may lead to inappropriate conclusions. We quantified the contribution of four sources of variation (choice of general circulation models, emission scenarios and species distribution modelling methods and variation in species distribution data) to uncertainty in forecasts and tested if our projections were robust to these uncertainties. Declines in the availability of suitable climate within the IBA network by 2100 were forecast as ‘extremely likely’ for 45% of species, whereas increases were projected for only 2%. Thus, we predict almost 24 times as many ‘losers’ as ‘winners’. However, for no species was suitable climate ‘extremely likely’ to be completely lost from the network. Considerable turnover (median = 43%, 95% CI = 35–69%) in species compositions of most IBAs were projected by 2100. Climatic conditions in 47% of IBAs were projected as ‘extremely likely’ to become suitable for fewer priority species. However, no IBA was forecast to become suitable for more species. Variation among General Circulation Models and Species Distribution Models contributed most to uncertainty among forecasts. This uncertainty precluded firm conclusions for 53% of species and IBAs because 95% confidence intervals included projections of no change. Considering this uncertainty, however, allows robust recommendations concerning the remaining species and IBAs. Overall, while the IBA network will continue to sustain bird conservation, climate change will modify which species each site will be suitable for. Thus, adaptive management of the network, including modified site conservation strategies and facilitating species' movement among sites, is critical to ensure effective future conservation.