Treatment of the elderly colorectal cancer patient: SIOG expert recommendations.

Colorectal cancer (CRC) is one of the commonest malignancies of Western countries, with approximately half the incidence occurring in patients >70 years of age. Elderly CRC patients, however, are understaged, undertreated and underrepresented in clinical trials. The International Society of Geriatric Oncology created a task force with a view to assessing the potential for developing guidelines for the treatment of elderly (geriatric) CRC patients. A review of the evidence presented by the task force members confirmed the paucity of clinical trial data in elderly people and the lack of evidence-based guidelines. However, recommendations have been proposed on the basis of the available data and on the emerging evidence that treatment outcomes for fit, elderly CRC patients can be similar to those of younger patients. It is hoped that these will pave the way for formal treatment guidelines based upon solid scientific evidence in the future.

Energetics, lifestyle, and reproduction in birds

Theoretical and empirical studies of life history aim to account for resource allocation to the different components of fitness: survival, growth, and reproduction. The pioneering evolutionary ecologist David Lack [(1968) Ecological Adaptations for Breeding in Birds (Methuen and Co.,London)] suggested that reproductive output in birds reflects adaptation to environmental factors such as availability of food and risk of predation, but subsequent studies have not always supported Lack’s interpretation. Here using a dataset for 980 bird species (Dataset S1), a phylogeny, and an explicit measure of reproductive productivity, we test predictions for how mass-specific productivity varies with body size, phylogeny,and lifestyle traits. We find that productivity varies negatively with body size and energetic demands of parental care and positively with extrinsic mortality. Specifically: (i) altricial species are 50% less productive than precocial species; (ii) species with female-only care of offspring are about 20% less productive than species with other methods of parental care; (iii) nonmigrants are 14% less productive than migrants; (iv) frugivores and nectarivores are about 20% less productive than those eating other foods; and (v) pelagic foragers are 40% less productive than those feeding in other habitats. A strong signal of phylogeny suggests that syndromes of similar life-history traits tend to be conservative within clades but also to have evolved independently in different clades. Our results generally support both Lack’s pioneering studies and subsequent research on avian life history.

Candidate genes for obesity-susceptibility show enriched association within a large genome-wide association study for BMI

Before the advent of genome-wide association studies (GWASs), hundreds of candidate genes for obesity-susceptibility had been identified through a variety of approaches. We examined whether those obesity candidate genes are enriched for associations with body mass index (BMI) compared with non-candidate genes by using data from a large-scale GWAS. A thorough literature search identified 547 candidate genes for obesity-susceptibility based on evidence from animal studies, Mendelian syndromes, linkage studies, genetic association studies and expression studies. Genomic regions were defined to include the genes ±10 kb of flanking sequence around candidate and non-candidate genes. We used summary statistics publicly available from the discovery stage of the genome-wide meta-analysis for BMI performed by the genetic investigation of anthropometric traits consortium in 123 564 individuals. Hypergeometric, rank tail-strength and gene-set enrichment analysis tests were used to test for the enrichment of association in candidate compared with non-candidate genes. The hypergeometric test of enrichment was not significant at the 5% P-value quantile (P = 0.35), but was nominally significant at the 25% quantile (P = 0.015). The rank tail-strength and gene-set enrichment tests were nominally significant for the full set of genes and borderline significant for the subset without SNPs at P < 10(-7). Taken together, the observed evidence for enrichment suggests that the candidate gene approach retains some value. However, the degree of enrichment is small despite the extensive number of candidate genes and the large sample size. Studies that focus on candidate genes have only slightly increased chances of detecting associations, and are likely to miss many true effects in non-candidate genes, at least for obesity-related traits.

Mechanisms of protease-activated receptor 2-evoked hyperexcitability of nociceptive neurons innervating the mouse colon

Agonists of protease-activated receptor 2 (PAR(2)) evoke hyperexcitability of dorsal root ganglia (DRG) neurons by unknown mechanisms. We examined the cellular mechanisms underlying PAR(2)-evoked hyperexcitability of mouse colonic DRG neurons to determine their potential role in pain syndromes such as visceral hyperalgesia. Colonic DRG neurons were identified by injecting Fast Blue and DiI retrograde tracers into the mouse colon. Using immunofluorescence, we found that DiI-labelled neurons contained PAR(2) immunoreactivity, confirming the presence of receptors on colonic neurons. Whole-cell current-clamp recordings of acutely dissociated neurons demonstrated that PAR(2) activation with a brief application (3 min) of PAR(2) agonists, SLIGRL-NH(2) and trypsin, evoked sustained depolarizations (up to 60 min) which were associated with increased input resistance and a marked reduction in rheobase (50% at 30 min). In voltage clamp, SLIGRL-NH(2) markedly suppressed delayed rectifier I(K) currents (55% at 10 min), but had no effect on the transient I(A) current or TTX-resistant Na(+) currents. In whole-cell current-clamp recordings, the sustained excitability evoked by PAR(2) activation was blocked by the PKC inhibitor, calphostin, and the ERK(1/2) inhibitor PD98059. Studies of ERK(1/2) phosphorylation using confocal microscopy demonstrated that SLIGRL-NH(2) increased levels of immunoreactive pERK(1/2) in DRG neurons, particularly in proximity to the plasma membrane. Thus, activation of PAR(2) receptors on colonic nociceptive neurons causes sustained hyperexcitability that is related, at least in part, to suppression of delayed rectifier I(K) currents. Both PKC and ERK(1/2) mediate the PAR(2)-induced hyperexcitability. These studies describe a novel mechanism of sensitization of colonic nociceptive neurons that may be implicated in conditions of visceral hyperalgesia such as irritable bowel syndrome.

Suck the living labour

The project, commissioned by Ort, Birmingham, explores geriatric vampirism. Austerity measures have indebted the young and the old through the privatisation of education and health. These age groups have been thrown into a relationship of mutual dependency and conflicting interests. As well as a new film, the exhibition featured six videos that have been outsourced using the services of sellers on the website Fiverr, ‘a place for people to share things they're willing to do for $5’. Interrogating the means of production and the meaning of work under post-Fordism, the Suck the Living Labour extends Marx’s metaphor, comparing Capital to a vampiric force that thirsts for infinite surplus.

Contribution of the geriatrician to the management of cancer in older patients

With an increasingly aged population, many patients will present with cancer in their 80s and 90s. Although some may be very fit, frail individuals will require the input of geriatricians to aid in the assessment of co-existing morbidity, in an attempt to assess those most likely to benefit from active treatment of their cancer, and those in whom the ‘giants of geriatric medicine’ require special consideration before undergoing definitive cancer therapy. The role of the geriatrician in assessment and management of such patients, together with communication and end of life care, may be more important in ensuring a good quality of life, than the cancer therapy itself. Whilst numbers of geriatricians will not be adequate to care for all elderly patients with cancer, a variety of assessment scales will help target financial and manpower resources to those most at risk.

Varieties of semantic ‘access’ deficit in Wernicke’s aphasia and semantic aphasia

Comprehension deficits are common in stroke aphasia, including in cases with (i) semantic aphasia (SA), characterised by poor executive control of semantic processing across verbal and nonverbal modalities, and (ii) Wernicke’s aphasia (WA), associated with poor auditory-verbal comprehension and repetition, plus fluent speech with jargon. However, the varieties of these comprehension problems, and their underlying causes, are not well-understood. Both patient groups exhibit some type of semantic ‘access’ deficit, as opposed to the ‘storage’ deficits observed in semantic dementia. Nevertheless, existing descriptions suggest these patients might have different varieties of ‘access’ impairment – related to difficulty resolving competition (in SA) vs. initial activation of concepts from sensory inputs (in WA). We used a case-series design to compare WA and SA patients on Warrington’s paradigmatic assessment of semantic ‘access’ deficits. In these verbal and non-verbal matching tasks, a small set of semantically-related items are repeatedly presented over several cycles so that the target on one trial becomes a distractor on another (building up interference and eliciting semantic ‘blocking’ effects). WA and SA patients were distinguished according to lesion location in the temporal cortex, but in each group, some individuals had additional prefrontal damage. Both of these aspects of lesion variability – one that mapped onto classical ‘syndromes’ and one that did not – predicted aspects of the semantic ‘access’ deficit. Both SA and WA cases showed multimodal semantic impairment, although as expected the WA group showed greater deficits on auditory-verbal than picture judgements. Distribution of damage in the temporal lobe was crucial for predicting the initially beneficial effects of stimulus repetition: WA cases showed initial improvement with repetition of words and pictures, while in SA, semantic access was initially good but declined in the face of competition from previous targets. Prefrontal damage predicted the harmful effects of repetition: the ability to re-select both word and picture targets in the face of mounting competition was linked to left prefrontal damage in both groups. Therefore, SA and WA patients have partially distinct impairment of semantic ‘access’ but, across these syndromes, prefrontal lesions produce declining comprehension with repetition in both verbal and non-verbal tasks.