Do not attempt resuscitation decisions in a cancer centre: addressing difficult ethical and communication issues

Talking to patients about ‘Do Not Attempt Resuscitation’ decisions is difficult for many doctors. Communication about ‘Do Not Attempt Resuscitation’ decisions should occur as part of a wider discussion of treatment goals at an earlier stage in the patient's illness. A doctor should not initiate any treatment, including cardio-pulmonary resuscitation if he/she does not believe it will benefit the patient. An ethical framework is offered which may be of practical help in clarifying decision-making

Radio emission from Supernova Remnants

The explosion of a supernova releases almost instantaneously about 10^51 ergs of mechanic energy, changing irreversibly the physical and chemical properties of large regions in the galaxies. The stellar ejecta, the nebula resulting from the powerful shock waves, and sometimes a compact stellar remnant, constitute a supernova remnant (SNR). They can radiate their energy across the whole electromagnetic spectrum, but the great majority are radio sources. Almost 70 years after the first detection of radio emission coming from a SNR, great progress has been achieved in the comprehension of their physical characteristics and evolution. We review the present knowledge of different aspects of radio remnants, focusing on sources of the Milky Way and the Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief overview of theoretical background, analyze morphology and polarization properties, and review and critical discuss different methods applied to determine the radio spectrum and distances. The consequences of the interaction between the SNR shocks and the surrounding medium are examined, including the question of whether SNRs can trigger the formation of new stars. Cases of multispectral comparison are presented. A section is devoted to reviewing recent results of radio SNRs in the Magellanic Clouds, with particular emphasis on the radio properties of SN 1987A, an ideal laboratory to investigate dynamical evolution of an SNR in near real time. The review concludes with a summary of issues on radio SNRs that deserve further study, and analyzing the prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure

A Genotype-First Approach for the Molecular and Clinical Characterization of Uncommon De Novo Microdeletion of 20q13.33

Background: Subtelomeric deletions of the long arm of chromosome 20 are rare, with only 11 described in the literature. Clinical features of individuals with these microdeletions include severe limb malformations, skeletal abnormalities, growth retardation, developmental and speech delay, mental retardation, seizures and mild, non-specific dysmorphic features. Methodology/Principal Findings: We characterized microdeletions at 20q13.33 in six individuals referred for genetic evaluation of developmental delay, mental retardation, and/or congenital anomalies. A comparison to previously reported cases of 20q13.33 microdeletion shows phenotypic overlap, with clinical features that include mental retardation, developmental delay, speech and language deficits, seizures, and behavior problems such as autistic spectrum disorder. There does not appear to be a clinically recognizable constellation of dysmorphic features among individuals with subtelomeric 20q microdeletions. Conclusions/Significance: Based on genotype-phenotype correlation among individuals in this and previous studies, we discuss several possible candidate genes for specific clinical features, including ARFGAP1, CHRNA4 and KCNQ2 and neurodevelopmental deficits. Deletion of this region may play an important role in cognitive development

From 2D to 3D: novel nanostructured scaffolds to investigate signalling in reconstructed neuronal networks

To recreate in vitro 3D neuronal circuits will ultimately increase the relevance of results from cultured to whole-brain networks and will promote enabling technologies for neuro-engineering applications. Here we fabricate novel elastomeric scaffolds able to instruct 3D growth of living primary neurons. Such systems allow investigating the emerging activity, in terms of calcium signals, of small clusters of neurons as a function of the interplay between the 2D or 3D architectures and network dynamics. We report the ability of 3D geometry to improve functional organization and synchronization in small neuronal assemblies. We propose a mathematical modelling of network dynamics that supports such a result. Entrapping carbon nanotubes in the scaffolds remarkably boosted synaptic activity, thus allowing for the first time to exploit nanomaterial/cell interfacing in 3D growth support. Our 3D system represents a simple and reliable construct, able to improve the complexity of current tissue culture models

Topoisomerase IIα Binding Domains of Adenomatous Polyposis Coli Influence Cell Cycle Progression and Aneuploidy

Truncating mutations in the tumor suppressor gene APC (Adenomatous Polyposis Coli) are thought to initiate the majority of colorectal cancers. The 15- and 20-amino acid repeat regions of APC bind beta-catenin and have been widely studied for their role in the negative regulation of canonical Wnt signaling. However, functions of APC in other important cellular processes, such as cell cycle control or aneuploidy, are only beginning to be studied. Our previous investigation implicated the 15-amino acid repeat region of APC (M2-APC) in the regulation of the G2/M cell cycle transition through interaction with topoisomerase IIalpha (topo IIalpha).We now demonstrate that the 20-amino acid repeat region of APC (M3-APC) also interacts with topo IIalpha in colonic epithelial cells. Expression of M3-APC in cells with full-length endogenous APC causes cell accumulation in G2. However, cells with a mutated topo IIalpha isoform and lacking topo IIbeta did not arrest, suggesting that the cellular consequence of M2- or M3-APC expression depends on functional topoisomerase II. Both purified recombinant M2- and M3-APC significantly enhanced the activity of topo IIalpha. Of note, although M3-APC can bind beta-catenin, the G2 arrest did not correlate with beta-catenin expression or activity, similar to what was seen with M2-APC. More importantly, expression of either M2- or M3-APC also led to increased aneuploidy in cells with full-length endogenous APC but not in cells with truncated endogenous APC that includes the M2-APC region.Together, our data establish that the 20-amino acid repeat region of APC interacts with topo IIalpha to enhance its activity in vitro, and leads to G2 cell cycle accumulation and aneuploidy when expressed in cells containing full-length APC. These findings provide an additional explanation for the aneuploidy associated with many colon cancers that possess truncated APC

Determinants of Habitat Selection by Hatchling Australian Freshwater Crocodiles

Animals almost always use habitats non-randomly, but the costs and benefits of using specific habitat types remain unknown for many types of organisms. In a large lake in northwestern Australia (Lake Argyle), most hatchling (<12-month-old) freshwater crocodiles (Crocodylus johnstoni) are found in floating vegetation mats or grassy banks rather than the more widely available open banks. Mean body sizes of young crocodiles did not differ among the three habitat types. We tested four potential explanations for non-random habitat selection: proximity to nesting sites, thermal conditions, food availability, and exposure to predation. The three alternative habitat types did not differ in proximity to nesting sites, or in thermal conditions. Habitats with higher food availability harboured more hatchlings, and feeding rates (obtained by stomach-flushing of recently-captured crocodiles) were highest in such areas. Predation risk may also differ among habitats: we were twice as likely to capture a crocodile after seeing it in open-bank sites than in the other two habitat types. Thus, habitat selection of hatchling crocodiles in this system may be driven both by prey availability and by predation risk

The Effect of Structural Complexity, Prey Density, and “Predator-Free Space” on Prey Survivorship at Created Oyster Reef Mesocosms

Interactions between predators and their prey are influenced by the habitat they occupy. Using created oyster (Crassostrea virginica) reef mesocosms, we conducted a series of laboratory experiments that created structure and manipulated complexity as well as prey density and “predator-free space” to examine the relationship between structural complexity and prey survivorship. Specifically, volume and spatial arrangement of oysters as well as prey density were manipulated, and the survivorship of prey (grass shrimp, Palaemonetes pugio) in the presence of a predator (wild red drum, Sciaenops ocellatus) was quantified. We found that the presence of structure increased prey survivorship, and that increasing complexity of this structure further increased survivorship, but only to a point. This agrees with the theory that structural complexity may influence predator-prey dynamics, but that a threshold exists with diminishing returns. These results held true even when prey density was scaled to structural complexity, or the amount of “predator-free space” was manipulated within our created reef mesocosms. The presence of structure and its complexity (oyster shell volume) were more important in facilitating prey survivorship than perceived refugia or density-dependent prey effects. A more accurate indicator of refugia might require “predator-free space” measures that also account for the available area within the structure itself (i.e., volume) and not just on the surface of a structure. Creating experiments that better mimic natural conditions and test a wider range of “predator-free space” are suggested to better understand the role of structural complexity in oyster reefs and other complex habitats

Deducing the source and composition of rare earth mineralising fluids in carbonatites: insights from isotopic (C, O, 87Sr/86Sr) data from Kangankunde, Malawi

This is the final version of the article. Available from Springer Verlag via the DOI in this record.Carbonatites host some of the largest and highest grade rare earth element (REE) deposits but the composition and source of their REE-mineralising fluids remains enigmatic. Using C, O and 87Sr/86Sr isotope data together with major and trace element compositions for the REE-rich Kangankunde carbonatite (Malawi), we show that the commonly observed, dark brown, Fe-rich carbonatite that hosts REE minerals in many carbonatites is decoupled from the REE mineral assemblage. REE-rich ferroan dolomite carbonatites, containing 8–15 wt% REE2O3, comprise assemblages of monazite-(Ce), strontianite and baryte forming hexagonal pseudomorphs after probable burbankite. The 87Sr/86Sr values (0.70302–0.70307) affirm a carbonatitic origin for these pseudomorph-forming fluids. Carbon and oxygen isotope ratios of strontianite, representing the REE mineral assemblage, indicate equilibrium between these assemblages and a carbonatite-derived, deuteric fluid between 250 and 400 °C (δ18O + 3 to + 5‰VSMOW and δ13C − 3.5 to − 3.2‰VPDB). In contrast, dolomite in the same samples has similar δ13C values but much higher δ18O, corresponding to increasing degrees of exchange with low-temperature fluids (< 125 °C), causing exsolution of Fe oxides resulting in the dark colour of these rocks. REE-rich quartz rocks, which occur outside of the intrusion, have similar δ18O and 87Sr/86Sr to those of the main complex, indicating both are carbonatite-derived and, locally, REE mineralisation can extend up to 1.5 km away from the intrusion. Early, REE-poor apatite-bearing dolomite carbonatite (beforsite: δ18O + 7.7 to + 10.3‰ and δ13C −5.2 to −6.0‰; 87Sr/86Sr 0.70296–0.70298) is not directly linked with the REE mineralisation.This project was funded by the UK Natural Environment Research Council (NERC) SoS RARE project (NE/M011429/1) and by NIGL (NERC Isotope Geoscience Laboratory) Project number 20135

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700