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Drosophila germ-band extension is thought to rely mainly on cell intercalation events. Quantitative analysis of cell shape changes and movements show that extrinsic tensile forces generated by the invaginating mesoderm drive cell shape changes to participate in this elongation. Drosophila germ-band extension ( GBE ) is an example of the convergence and extension movements that elongate and narrow embryonic tissues. To understand the collective cell behaviours underlying tissue morphogenesis, we have continuously quantified cell intercalation and cell shape change during GBE . We show that the fast, early phase of GBE depends on cell shape change in addition to cell intercalation. In antero-posterior patterning mutants such as those for the gap gene Krüppel , defective polarized cell intercalation is compensated for by an increase in antero-posterior cell elongation, such that the initial rate of extension remains the same. Spatio-temporal patterns of cell behaviours indicate that an antero-posterior tensile force deforms the germ band, causing the cells to change shape passively. The rate of antero-posterior cell elongation is reduced in twist mutant embryos, which lack mesoderm. We propose that cell shape change contributing to germ-band extension is a passive response to mechanical forces caused by the invaginating mesoderm.

Aims Mutation detection accuracy has been described extensively; however, it is surprising that pre-PCR processing of formalin-fixed paraffin-embedded (FFPE) samples has not been systematically assessed in clinical context. We designed a RING trial to (i) investigate pre-PCR variability, (ii) correlate pre-PCR variation with EGFR/BRAF mutation testing accuracy and (iii) investigate causes for observed variation. Methods 13 molecular pathology laboratories were recruited. 104 blinded FFPE curls including engineered FFPE curls, cell-negative FFPE curls and control FFPE tissue samples were distributed to participants for pre-PCR processing and mutation detection. Follow-up analysis was performed to assess sample purity, DNA integrity and DNA quantitation. Results Rate of mutation detection failure was 11.9%. Of these failures, 80% were attributed to pre-PCR error. Significant differences in DNA yields across all samples were seen using analysis of variance (p<0.0001), and yield variation from engineered samples was not significant (p=0.3782). Two laboratories failed DNA extraction from samples that may be attributed to operator error. DNA extraction protocols themselves were not found to contribute significant variation. 10/13 labs reported yields averaging 235.8 ng (95% CI 90.7 to 380.9) from cell-negative samples, which was attributed to issues with spectrophotometry. DNA measurements using Qubit Fluorometry demonstrated a median fivefold overestimation of DNA quantity by Nanodrop Spectrophotometry. DNA integrity and PCR inhibition were factors not found to contribute significant variation. Conclusions In this study, we provide evidence demonstrating that variation in pre-PCR steps is prevalent and may detrimentally affect the patient's ability to receive critical therapy. We provide recommendations for preanalytical workflow optimisation that may reduce errors in down-stream sequencing and for next-generation sequencing library generation.

Harold Macmillan's 'Wind of Change' speech, delivered to the South African parliament in Cape Town at the end of a landmark six-week African tour, presaged the end of the British Empire in Africa. This book, the first to focus on Macmillan's 'Wind of Change', comprises a series of essays by leading historians in the field.

This is a study of the evolving relationship between the British colonial state and the copper mining industry in Northern Rhodesia, from the early stages of development to decolonization, encompassing depression, wartime mobilization and fundamental changes in the nature and context of colonial rule.

Osteochondral lesions (OCL) are common among young patients and often require surgical interventions since cartilage has a poor capacity for self-repair. Bone marrow stimulation (BMS) has been used clinically for decades to treat OCLs, however a persisting challenge with BMS and other cartilage repair strategies is the inferior quality of the resulting fibrocartilaginous repair tissue. Lubrication-based therapies have the potential to improve the quality of cartilage repair tissue as joint lubrication is linked to local cartilage tissue strains and subsequent cellular responses including death and apoptosis. Recently, a full length recombinant human lubricin (rhLubricin) was developed and has been shown to lower friction in cartilage. This study investigated the effect of a single delayed injection of rhLubricin on cartilage repair in an rabbit OCL model using gross macroscopic evaluation, surface profilometry, histology, and tribology. Moderate improvement in macroscopic scores for cartilage repair were observed. Notably, quantitative analysis of Safranin-O histology showed that rhLubricin treated joints had significantly higher glycosaminoglycan content compared to saline treated joints, and there were no differences in repair integration between groups. Furthermore, rhLubricin treated joints had significantly lower friction coefficients tested across three sliding speeds compared to saline treated joints (rhLubricin: 0.15 ± 0.03 at 0.1 mm/s to 0.12 ± 0.03 at 10 mm/s, Saline: 0.22 ± 0.06 at 0.1 mm/s to 0.19 ± 0.05 at 10 mm/s). Overall, a single delayed injection of rhLubricin improved the quality and lubricating ability of the repair cartilage tissue without inhibiting repair tissue integration.

Forest self-reliance Measurements taken by aircraft flying over the Amazon rain forest reveal unexpectedly high concentrations of hydroxyl radicals in the lower atmosphere. Hydroxyl is the primary atmospheric oxidant, and it was conventional wisdom that large forest emissions of hydrocarbons strongly reduce the atmospheric oxidation capacity. The new data suggest that this is not the case, and that the pristine forest can 'manage' its atmospheric sustainability remarkably well. A possible mechanism is suggested: hydroxyl radicals may be recycling via the natural oxidation of volatile organic compounds, mainly isoprene. In the absence of external influences, the forest seems able to maintain a benign atmosphere. But where deforestation and anthropogenic emissions of NO intervene, photochemical air pollution remains likely. Aircraft measurements of atmospheric trace gases performed over the pristine Amazon forest find unexpectedly high hydroxyl radical concentrations. On the basis of a model study and the results of laboratory experiments, it is proposed that natural volatile organic compounds oxidation, notably of isoprene, recycles hydroxyl radical efficiently through reactions of organic peroxy radicals, which may be able to explain the high hydroxyl radical levels observed. Terrestrial vegetation, especially tropical rain forest, releases vast quantities of volatile organic compounds (VOCs) to the atmosphere 1 , 2 , 3 , which are removed by oxidation reactions and deposition of reaction products 4 , 5 , 6 . The oxidation is mainly initiated by hydroxyl radicals (OH), primarily formed through the photodissociation of ozone 4 . Previously it was thought that, in unpolluted air, biogenic VOCs deplete OH and reduce the atmospheric oxidation capacity 5 , 6 , 7 , 8 , 9 , 10 . Conversely, in polluted air VOC oxidation leads to noxious oxidant build-up by the catalytic action of nitrogen oxides 5 , 6 , 7 , 8 , 9 , 10 (NO x = NO + NO 2 ). Here we report aircraft measurements of atmospheric trace gases performed over the pristine Amazon forest. Our data reveal unexpectedly high OH concentrations. We propose that natural VOC oxidation, notably of isoprene, recycles OH efficiently in low-NO x air through reactions of organic peroxy radicals. Computations with an atmospheric chemistry model and the results of laboratory experiments suggest that an OH recycling efficiency of 40–80 per cent in isoprene oxidation may be able to explain the high OH levels we observed in the field. Although further laboratory studies are necessary to explore the chemical mechanism responsible for OH recycling in more detail, our results demonstrate that the biosphere maintains a remarkable balance with the atmospheric environment.

Cancer survival is a key measure of the effectiveness of health-care systems. Persistent regional and international differences in survival represent many avoidable deaths. Differences in survival have prompted or guided cancer control strategies. This is the first study in a programme to investigate international survival disparities, with the aim of informing health policy to raise standards and reduce inequalities in survival. Data from population-based cancer registries in 12 jurisdictions in six countries were provided for 2·4 million adults diagnosed with primary colorectal, lung, breast (women), or ovarian cancer during 1995–2007, with follow-up to Dec 31, 2007. Data quality control and analyses were done centrally with a common protocol, overseen by external experts. We estimated 1-year and 5-year relative survival, constructing 252 complete life tables to control for background mortality by age, sex, and calendar year. We report age-specific and age-standardised relative survival at 1 and 5 years, and 5-year survival conditional on survival to the first anniversary of diagnosis. We also examined incidence and mortality trends during 1985–2005. Relative survival improved during 1995–2007 for all four cancers in all jurisdictions. Survival was persistently higher in Australia, Canada, and Sweden, intermediate in Norway, and lower in Denmark, England, Northern Ireland, and Wales, particularly in the first year after diagnosis and for patients aged 65 years and older. International differences narrowed at all ages for breast cancer, from about 9% to 5% at 1 year and from about 14% to 8% at 5 years, but less or not at all for the other cancers. For colorectal cancer, the international range narrowed only for patients aged 65 years and older, by 2–6% at 1 year and by 2–3% at 5 years. Up-to-date survival trends show increases but persistent differences between countries. Trends in cancer incidence and mortality are broadly consistent with these trends in survival. Data quality and changes in classification are not likely explanations. The patterns are consistent with later diagnosis or differences in treatment, particularly in Denmark and the UK, and in patients aged 65 years and older. Department of Health, England; and Cancer Research UK.

The effects of acidic deposition in the northeastern US include the acidification of soil and water, which stresses terrestrial and aquatic biota. Driscoll et al examine the ecological effects of acidic deposition in New England and New York and explore the relationship between emissions reductions and ecosystem recovery.