Access to coronary catheterisation: fair shares for all?

OBJECTIVE--To determine the effects of patient''s sex and area''s material deprivation on utilisation rates of coronary catheterisation and angiography in the investigation of ischaemic heart disease. DESIGN--Retrospective analysis of routinely collected hospital statistics. SETTING--Acute hospitals throughout Northern Ireland. SUBJECTS--24,179 episodes of patients discharged from hospital with a primary diagnosis of ischaemic heart disease and 1270 episodes relating to patients with an underlying diagnosis of ischaemic heart disease who had either coronary catheterisation or angiography. MAIN OUTCOME MEASURES--Age standardised admission rates for heart disease and age standardised utilisation rates for catheterisation or angiography, or both, for 566 electoral wards ranked by Townsend "deprivation" scores. RESULTS--Catheterisation-angiography rates in men were over fivefold those of women, ranging from 85.5/100,000 v 16/100,000 in patients from "well off" areas to 123/100,000 v 22/100,000 for patients from deprived areas. After admission rates for heart disease were controlled for, the overall rate ratio for women was 0.48 (95% confidence interval 0.38 to 0.60). After differential admission rates for heart disease and other potential clinical confounders were controlled for, the investigation rates of patients from the least and most "deprived" areas were not significantly different (rate ratio 1.04 (0.87 to 1.25)). CONCLUSION--Although investigation rates were significantly lower in women than in men, further clinical data would be required before labelling this underutilisation as evidence of bias. There was no significant difference in invasive investigation rates for heart disease in areas of varying deprivation or affluence.     

Cryonics for all?

In fascinating recent work, some philosophers have argued that it would be morally permissible and prudentially rational to sign up for cryonics—if you can afford the price tag of the procedure. In this paper I ask: why not share the elixir of extended life with everyone? Should governments financially support, positively encourage, or even require people to undergo cryonics? From a general principle of beneficence, I construct a formal argument for cryonics promotion policies. I consider the objection that a subset of these policies would violate autonomy, but I argue that—to the contrary—considerations of autonomy weigh in their favour. I then consider objections based on cost and population, but argue that neither is fatal. Finally, I raise the objection that I believe poses the most serious challenge: that those who revive the cryonically preserved might inflict suffering upon them.     

Chemokines: extracellular messengers for all occasions?

Movement of leukocytes from peripheral blood into tissues, also called leukocyte extravasation, is absolutely essential for immunity in higher organisms. Over the past decade, our understanding of the molecular mechanisms involved in white blood cell extravasation during both normal immune surveillance and the generation of protective immune responses has taken a great leap forward with the discovery of the chemokine gene superfamily. Chemokines are low-molecular-weight cytokines whose major collective biological activity appears to be that of chemotaxis of both specific and overlapping subsets of leukocytes. They are therefore likely to play a critical role in the directed movement of leukocytes from the bloodstream into tissue. These molecules are almost exclusively secreted and act as extracellular messengers for the immune system. However, emerging data also show that various members of the chemokine gene superfamily exert other biological effects outside the immune system. All nucleated cells and all tissues examined to date are capable of expressing at least some chemokines, and it seems likely therefore that by the time all the chemokines are identified, and all their biological functions elucidated, we will find that, as a family, these molecules perform an extracellular messenger role in all tissues and systems of the body.     

A role for haemoglobin in all plant roots?

Abstract. We have found haemoglobin in plant roots whereas previously it has been recorded only in nitrogen fixing nodules of plants. Haemoglobin occurs not only in the roots of those plants that are capable of nodulation but also in the roots of species that are not known to nodulate. We suggest that a haemoglobin gene may be a component of the genome of all plants. The gene structure and sequence in two unrelated families of plants suggests that the plant haemoglobins have had a single origin and that this origin relates to the haemoglobin gene of the animal kingdom. At present we cannot completely rule out the possibility of a horizontal transfer of the gene from the animal kingdom to a progenitor of the dicotyledonous angiosperms but we favour a single origin of the gene from a progenitor organism to both the plant and animal kingdoms. We speculate about the possible functions of haemoglobin in plant roots and put the case that it is unlikely to have a function in facilitating oxygen diffusion. We suggest that haemoglobin may act as a signal molecule indicating oxygen deficit and the consequent need to shift plant metabolism from an oxidative to a fermentative pathway of energy generation.     

Looking for food in all the right places?

Examining a potential functional role for growth hormone secretagogue receptors in the hippocampus, Diano and colleagues (Diano et al., 2006), demonstrate novel actions of the orexigenic peptide ghrelin in hippocampal synaptic architecture, LTP, and learning and memory. These data suggest functional links between metabolic signaling and higher neural function.     

Not all the same after all? Superdiversity as a lens for the study of past migrations

Due to its claim of contemporary exceptionalism, the notion of superdiversity raises suspicion among historians. However, historians would do well to not dismiss the entire superdiversity debate as more hype that does not concern them. As a multidimensional perspective on diversity, encouraging researchers to examine the interplay of many different factors that condition people's lives and to move beyond an ethno-focal perspective, superdiversity could be of interest to historians as well. This article shows how the notion can help historians debunk some of the homogenizing categories that tend to characterize the representation of past immigrant populations. The paper uses a superdiversity lens to examine migration to the city of Ghent from 1960 to 1980. It is an open invitation to historians to accept the challenges that superdiversity poses and to provide a proper historicization of the concept, thus furthering its theoretical development.     

Holding it all together? Candidate proteins for the plant Golgi matrix

A combination of electron microscopy and fluorescence microscopy has provided us with a global picture of the structure of the plant Golgi apparatus. However, the components that shape this structure remain elusive. In other organisms, members of the golgin family of coiled-coil proteins are essential for Golgi structure and organisation. Putative Arabidopsis and rice homologues of some golgin family members can be identified using database searches. Likewise, the heterogeneous group of multi-subunit-tethering complexes is responsible for crucial transport steps that affect Golgi structure and cisternal organisation in animals and yeasts. The Arabidopsis genome harbours possible homologues for the majority of the subunits of these complexes, suggesting that they also operate in the plant kingdom.     

Vitamin D: a hormone for all seasons--how much is enough?

Further understanding of its endocrine mechanisms and increased evidence for autocrine/paracrine actions has recently enhanced our knowledge of the biological activities of the vitamin D metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D). The recognition of the contribution of vitamin D depletion to increased risk of osteoporosis, and most importantly the risk of hip fracture in the elderly, has increased the clinical significance of clinical laboratory testing for vitamin D status. Research has revealed that at least three genes contribute to vitamin D activity within tissues. These are the vitamin D receptor as well as two major vitamin D metabolising enzymes, CYP27B1, responsible for synthesis of 1,25(OH)2D and CYP24, responsible for catabolism of vitamin D metabolites. Current research focuses on the contribution of vitamin D metabolism to increasing vitamin D activity. This is of particular interest in bone forming cells where increased 1,25(OH)2D activity has been proposed to contribute to strengthening the skeleton. As well, solid tumours such as prostate, breast and colon cancers are another increasing area of vitamin D research. The major issues for the clinical laboratory in vitamin D testing include defining clinical decision limits for the interpretation of serum 25-hydroxyvitamin D (25OHD) levels and improving the precision and accuracy of this assay.     

One ring to rule them all? Another cellular responsibility for PCNA

To prevent duplication or loss of genomic regions during DNA replication, it is essential that the entire genome is copied precisely once every S phase. Cells achieve this by mutually exclusive regulation of origin firing and licensing. A crucial protein that is involved in origin licensing is chromatin licensing and DNA replication factor 1 (CDT1) and, therefore, activity of this protein must be strictly controlled. Four recent articles have demonstrated that proliferating cell nuclear antigen (PCNA), an essential sliding clamp used in replication and DNA repair, has a crucial role in this process by mediating the proteasomal degradation of CDT1.     

The successful quest for oral factor Xa inhibitors; learnings for all of medicinal chemistry?

The medicinal chemistry of oral small molecule factor Xa inhibitors is discussed, highlighting key advances that led to clinical candidates and the first licensed medicines. Identification of neutral ligands for the primary specificity pocket was a key discovery; capitalised upon by structure based design and combinatorial methods to deliver many variations on the theme; but it was good medicinal chemistry practice, in the optimisation of physical properties, which ultimately delivered efficacious compounds with adequate oral exposure. As a retrospective appraisal, representative compounds were profiled using the more contemporary concepts of Ligand Efficiency and Property Forecast Indices; which gave clear indications of the value of these principles.