Oxaliplatin/capecitabine versus oxaliplatin/infusional 5-FU in advanced colorectal cancer: The MRC COIN Trial.

Background:

COIN compared first-line continuous chemotherapy with the same chemotherapy given intermittently or with cetuximab in advanced colorectal cancer (aCRC).


Methods:

Choice between oxaliplatin/capecitabine (OxCap) and oxaliplatin/leucovorin (LV)/infusional 5-FU (OxFU) was by physician and patient choice and switching regimen was allowed. We compared OxCap with OxFU and OxCap+cetuximab with OxFU+cetuximab retrospectively in patients and examined efficacy, toxicity profiles and the effect of mild renal impairment.


Results:

In total, 64% of 2397 patients received OxCap(±cetuximab). Overall survival, progression free survival and overall response rate were similar between OxCap and OxFU but rate of radical surgeries was higher for OxFU. Progression free survival was longer for OxFU+cetuximab compared with OxCap+cetuximab but other efficacy measures were similar. Oxaliplatin/LV/infusional 5-FU (±cetuximab) was associated with more mucositis and infection whereas OxCap(±cetuximab) caused more gastrointestinal toxicities and palmar-plantar erythema. In total, 118 patients switched regimen, mainly due to toxicity; only 16% came off their second regimen due to intolerance. Patients with creatinine clearance (CrCl) 50–80?ml?min-1 on OxCap(±cetuximab) or OxFU+cetuximab had more dose modifications than those with better renal function.


Conclusions:

Overall, OxFU and OxCap are equally effective in treating aCRC. However, the toxicity profiles differ and switching from one regimen to the other for poor tolerance is a reasonable option. Patients with CrCl 50–80?ml?min-1 on both regimens require close toxicity monitoring.

The machinist landscape:Land Art Generator Initiative (Competition)

THE MACHINIST LANDSCAPE: AN ENTROPIC GRID OF VARIANCE
‘By drawing a diagram, a ground plan of a house, a street plan to the location of a site, or a topographic map, one draws a “logical two dimensional picture”. A “logical picture” differs from a natural or realistic picture in that it rarely looks like the thing it stands for.’
A Provisional Theory of Non-Sites, Robert Smithson (1968)

Between design and ground there are variances, deviations and gaps. These exist as physical interstices between what is conceptualised and what is realised; and they reveal moments in the design process that resist the reconciliation of people and their environment (McHarg 1963). The Machinist Landscape interrogates the significance of these variances through the contrasting processes of coppice and photovoltaic energy. It builds on the potential of these gaps, and in doing so proposes that these spaces of variance can reveal the complexity of relationships between consumption and remediation, design and nature.
Fresh Kills Park, and in particular the draft master plan (2006), offers a framework to explore this artificial construct. Central to the Machinist Landscape is the analysis of the landfill gas collection system, planned on a notional 200ft grid. Variations are revealed between this diagrammatic grid measure and that which has been constructed on the site. These variances between the abstract and the real offer the Machinist Landscape a powerful space of enquiry. Are these gaps a result of unexpected conditions below ground, topographic nuances or natural phenomena? Does this space of difference, between what is planned and what is constructed, have the potential to redefine the dynamic processes and relations with the land?
The Machinist Landscape is structured through this space of variance with an ‘entropic grid’, the under-storey of which hosts a carefully managed system of short-rotation coppice (SRC). The coppice, a medieval practice related to energy, product, and space, operates on theoretical and programmatic levels. It is planted along a structure of linear bunds, stabilized through coppice pole retaining structures and enriched with nutrients from coppice produced bio-char. Above the coppice is built an upper-storey of photovoltaic (PV); its structures fabricated from the coppiced timber and the PV produced with graphene from coppice charcoal processes.

Development of a novel experimental model to investigate radiobiological implications of respiratory motion in advanced radiotherapy

Respiratory motion introduces complex spatio-temporal variations in the dosimetry of radiotherapy. There is a paucity of literature investigating the radiobiological consequences of intrafraction motion and concerns regarding the impact of movement when applied to cancer cell lines in vitro exist. We have addressed this by developing a novel model which accurately replicates respiratory motion under experimental conditions to allow clinically relevant irradiation of cell lines. A bespoke phantom and motor driven moving platform was adapted to accommodate flasks containing medium and cells in order to replicate respiratory motion using varying frequencies and amplitude settings. To study this effect on cell survival in vitro, dose response curves were determined for human lung cancer cell lines H1299 and H460 exposed to a uniform 6 MV radiation field under moving or stationary conditions. Cell survival curves showed no significant difference between irradiation at different dose points for these cell lines in the presence or absence of motion. These data indicate that motion of unshielded cells in vitro does not affect cell survival in the presence of uniform irradiation. This model provides a novel research platform to investigate the radiobiological consequences of respiratory motion in radiotherapy.

The UK Renal Registry Advanced CKD Study: frequency of incorrect reporting of date of start of RRT

Background: A preliminary review of the UK Renal Registry (UKRR) pre-RRT study data revealed results suggesting that, for some patients, the date of start of renal replacement therapy (RRT), as reported to the UKRR, was incorrect and often significantly later than the true date of start. A more detailed study then aimed to validate a set of criteria to identify patients with an incorrect start date. Methods: Pre-RRT laboratory data were electronically extracted from 8,810 incident RRT patients from 9 UK renal centres. Any patient with a low urea (<15 mmol/L) at the start of RRT or with a substantial improvement in kidney function (either a fall in urea >10 mmol/L or rise in eGFR >2 ml/min/1.73 m) within the two months prior to RRT were considered to potentially have an incorrect date of start. In 4
selected centres, the electronic patient records of all patients flagged were reviewed to validate these criteria.
Results: Of 8,810 patients, 1,616 (18.3%) were flagged by the identification criteria as having a potentially incorrect date of start of RRT, although a single centre accounted for 41% of the total flagged cohort. Of these flagged patients, 61.7% had been assigned an incorrect date of start of haemodialysis (HD), 5.7% had evidence of acute RRT being given before the reported date of start of HD
and 9.2% had evidence of starting peritoneal dialysis exchanges prior to the reported date of start. Of
those flagged, 10.7% had a correct date of start of RRT.
Conclusions: Accurate reporting of RRT episodes is vital for the analysis of time dependent studies such as survival or time to transplantation. A proportion of patients starting RRT were assigned an incorrect start date. In order to improve the accuracy of this reporting the UK Renal Registry
must work with renal centres and clinical staff on improving data input for the start of RRT.

A biofuel strategy for Ireland with an emphasis on production of biomethane and minimization of land-take

Increasing energy consumption has exerted great pressure on natural resources; this has led to a move towards sustainable energy resources to improve security of supply and to reduce greenhouse gas emissions. However, the rush to the cure may have been made in haste. Biofuels in particular, have a bad press both in terms of competition with good agricultural land for food, and also in terms of the associated energy balance with the whole life cycle analysis of the biofuel system. The emphasis is now very much on sustainable biofuel production; biofuels from wastes and lignocellulosic material are now seen as good sustainable biofuels that affect significantly better greenhouse gas balances as compared with first generation biofuels. Ireland has a significant resource of organic waste that could be a potential source of energy through anaerobic digestion. Ireland has 8% of the cattle population of the EU with less than 1% of the human population; as a result 91% of agricultural land in Ireland is under grass. Residues such as slurries and slaughter waste together with energy crops such as grass have an excellent potential to produce biogas that may be upgraded to biomethane. This biomethane may be used as a natural gas substitute; bio-compressed natural gas may then be an avenue for a biofuel strategy. It is estimated that a maximum potential of 33% of natural gas may be substituted by 2020 with a practical obtainable level of 7.5% estimated. Together with biodiesel from residues the practical obtainable level of this strategy may effect greater than a 5% substitution by energy of transport. The residues considered in this strategy to produce biofuel (excluding grass) have the potential to save 93,000 ha of agricultural land (23% of Irish arable land) when compared to a rapeseed biodiesel strategy. © 2009 Elsevier Ltd. All rights reserved.