The management of the painful bipartite patella: a systematic review

Purpose: This study aimed to identify the most effective method for the treatment of the symptomatic bipartite patella. Methods: A systematic review of the literature was completed, and all studies assessing the management of a bipartite patella were included. Owing to the paucity of randomised controlled trials, a narrative review of 22 studies was completed. A range of treatments were assessed: conservative measures, open and arthroscopic fixation or excision and soft tissue release and excision. Results: All of the methods provided results ranging from good to excellent, with acceptable complication rates. Conclusions: This is a poorly answered treatment question. No firm guidance can be given as to the most appropriate method of treating the symptomatic bipartite patella. This study suggests that there are a number of effective treatments with acceptable complication rates and it may be that treatments that conserve the patella are more appropriate for larger fragments

Holocene dynamics of the Southern Hemisphere westerly winds and possible links to CO2 outgassing

The Southern Hemisphere westerly winds (SHW) play an important role in regulating the capacity of the Southern Ocean carbon sink. They modulate upwelling of carbon-rich deep water and, with sea ice, determine the ocean surface area available for air–sea gas exchange. Some models indicate that the current strengthening and poleward shift of these winds will weaken the carbon sink. If correct, centennial- to millennial-scale reconstructions of the SHW intensity should be linked with past changes in atmospheric CO2, temperature and sea ice. Here we present a 12,300-year reconstruction of wind strength based on three independent proxies that track inputs of sea-salt aerosols and minerogenic particles accumulating in lake sediments on sub-Antarctic Macquarie Island. Between about 12.1 thousand years ago (ka) and 11.2 ka, and since about 7 ka, the wind intensities were above their long-term mean and corresponded with increasing atmospheric CO2. Conversely, from about 11.2 to 7.2 ka, the wind intensities were below their long-term mean and corresponded with decreasing atmospheric CO2. These observations are consistent with model inferences of enhanced SHW contributing to the long-term outgassing of CO2 from the Southern Ocean

Antarctic last interglacial isotope peak in response to sea ice retreat not ice-sheet collapse

Several studies have suggested that sea-level rise during the last interglacial implies retreat of the West Antarctic Ice Sheet (WAIS). The prevalent hypothesis is that the retreat coincided with the peak Antarctic temperature and stable water isotope values from 128,000 years ago (128 ka); very early in the last interglacial. Here, by analysing climate model simulations of last interglacial WAIS loss featuring water isotopes, we show instead that the isotopic response to WAIS loss is in opposition to the isotopic evidence at 128 ka. Instead, a reduction in winter sea ice area of 65±7% fully explains the 128 ka ice core evidence. Our finding of a marked retreat of the sea ice at 128 ka demonstrates the sensitivity of Antarctic sea ice extent to climate warming

Millennial changes in North American wildfire and soil activity over the last glacial cycle

Climate changes in the North Atlantic region during the last glacial cycle were dominated by the slow waxing and waning of the North American ice sheet as well as by intermittent Dansgaard-­‐Oeschger (DO) events. However prior to the last deglaciation, little is known about the response of North American vegetation to such rapid climate changes and especially about the response of biomass burning, an important factor for regional changes in radiative forcing. Here we use continuous, high-­‐resolution ammonium (NH4+) records derived from the NGRIP and GRIP ice cores to document both North American NH4+ background emissions from soils and wildfire frequency over the last 110,000 yr. Soil emissions increased on orbital timescales with warmer climate, related to the northward expansion of vegetation due to reduced ice-­‐covered areas. During Marine Isotope Stage (MIS) 3 DO warm events, a higher fire recurrence rate is recorded, while NH4+ soil emissions rose only slowly during longer interstadial warm periods, in line with slow ice sheet shrinkage and delayed ecosystem changes. Our results indicate that sudden warming events had little impact on NH4+ soil emissions and NH4+ aerosol transport to Greenland during the glacial but triggered a significant increase in the frequency of fire occurrence.This paper has greatly benefitted from the Sir Nicholas Shackleton fellowship, Clare Hall, University of Cambridge, U.K., awarded to HF in 2014. The Division for Climate and Environmental Physics, Physics Institute, University of Bern acknowledges the long-­‐term financial support of ice core research by the Swiss National Science Foundation (SNSF) and the Oeschger Centre for Climate Change Research. EW is supported by a Royal Society professorship. NGRIP is directed and organized by the Department of Geophysics at the Niels Bohr Institute for Astronomy, Physics and Geophysics, University of Copenhagen. It is supported by funding agencies in Denmark (SNF), Belgium (FNRS-­‐CFB), France (IPEV and INSU/CNRS), Germany (AWI), Iceland (RannIs), Japan (MEXT), Sweden (SPRS), Switzerland (SNSF) and the USA (NSF, Office of Polar Programs).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ngeo249

Cell morphology governs directional control in swimming bacteria

The ability to rapidly detect and track nutrient gradients is key to the ecological success of motile bacteria in aquatic systems. Consequently, bacteria have evolved a number of chemotactic strategies that consist of sequences of straight runs and reorientations. Theoretically, both phases are affected by fluid drag and Brownian motion, which are themselves governed by cell geometry. Here, we experimentally explore the effect of cell length on control of swimming direction. We subjected Escherichia coli to an antibiotic to obtain motile cells of different lengths, and characterized their swimming patterns in a homogeneous medium. As cells elongated, angles between runs became smaller, forcing a change from a run-and-tumble to a run-and-stop/reverse pattern. Our results show that changes in the motility pattern of microorganisms can be induced by simple morphological variation, and raise the possibility that changes in swimming pattern may be triggered by both morphological plasticity and selection on morphology

The Extracellular Matrix Component Psl Provides Fast-Acting Antibiotic Defense in Pseudomonas aeruginosa Biofilms

Bacteria within biofilms secrete and surround themselves with an extracellular matrix, which serves as a first line of defense against antibiotic attack. Polysaccharides constitute major elements of the biofilm matrix and are implied in surface adhesion and biofilm organization, but their contributions to the resistance properties of biofilms remain largely elusive. Using a combination of static and continuous-flow biofilm experiments we show that Psl, one major polysaccharide in the Pseudomonas aeruginosa biofilm matrix, provides a generic first line of defense toward antibiotics with diverse biochemical properties during the initial stages of biofilm development. Furthermore, we show with mixed-strain experiments that antibiotic-sensitive “non-producing” cells lacking Psl can gain tolerance by integrating into Psl-containing biofilms. However, non-producers dilute the protective capacity of the matrix and hence, excessive incorporation can result in the collapse of resistance of the entire community. Our data also reveal that Psl mediated protection is extendible to E. coli and S. aureus in co-culture biofilms. Together, our study shows that Psl represents a critical first bottleneck to the antibiotic attack of a biofilm community early in biofilm development.National Institutes of Health (U.S.). National Institute of Environmental Health Sciences (Training Grant in Toxicology 5 T32 ES7020-37

MAP4K3 Is a Component of the TORC1 Signalling Complex that Modulates Cell Growth and Viability in Drosophila melanogaster

Background: MAP4K3 is a conserved Ser/Thr kinase that has being found in connection with several signalling pathways, including the Imd, EGFR, TORC1 and JNK modules, in different organisms and experimental assays. We have analyzed the consequences of changing the levels of MAP4K3 expression in the development of the Drosophila wing, a convenient model system to characterize gene function during epithelial development. Methodology and Principal Findings: Using loss-of-function mutants and over-expression conditions we find that MAP4K3 activity affects cell growth and viability in the Drosophila wing. These requirements are related to the modulation of the TORC1 and JNK signalling pathways, and are best detected when the larvae grow in a medium with low protein concentration (TORC1) or are exposed to irradiation (JNK). We also show that MAP4K3 display strong genetic interactions with different components of the InR/Tor signalling pathway, and can interact directly with the GTPases RagA and RagC and with the multi-domain kinase Tor. Conclusions and Significance: We suggest that MAP4K3 has two independent functions during wing development, one related to the activation of the JNK pathway in response to stress and other in the assembling or activation of the TORC1 complex, being critical to modulate cellular responses to changes in nutrient availability

Continued Neurogenesis in Adult Drosophila as a Mechanism for Recruiting Environmental Cue-Dependent Variants

Background The skills used by winged insects to explore their environment are strongly dependent upon the integration of neurosensory information comprising visual, acoustic and olfactory signals. The neuronal architecture of the wing contains a vast array of different sensors which might convey information to the brain in order to guide the trajectories during flight. In Drosophila, the wing sensory cells are either chemoreceptors or mechanoreceptors and some of these sensors have as yet unknown functions. The axons of these two functionally distinct types of neurons are entangled, generating a single nerve. This simple and accessible coincidental signaling circuitry in Drosophila constitutes an excellent model system to investigate the developmental variability in relation to natural behavioral polymorphisms. Methodology/Principal Findings A fluorescent marker was generated in neurons at all stages of the Drosophila life cycle using a highly efficient and controlled genetic recombination system that can be induced in dividing precursor cells (MARCM system, flybase web site). It allows fluorescent signals in axons only when the neuroblasts and/or neuronal cell precursors like SOP (sensory organ precursors) undergo division during the precedent steps. We first show that a robust neurogenesis continues in the wing after the adults emerge from the pupae followed by an extensive axonal growth. Arguments are presented to suggest that this wing neurogenesis in the newborn adult flies was influenced by genetic determinants such as the frequency dependent for gene and by environmental cues such as population density. Conclusions We demonstrate that the neuronal architecture in the adult Drosophila wing is unfinished when the flies emerge from their pupae. This unexpected developmental step might be crucial for generating non-heritable variants and phenotypic plasticity. This might therefore constitute an advantage in an unstable ecological system and explain much regarding the ability of Drosophila to robustly adapt to their environment

Emotional Engineers: Toward Morally Responsible Design

Engineers are normally seen as the archetype of people who make decisions in a rational and quantitative way. However, technological design is not value neutral. The way a technology is designed determines its possibilities, which can, for better or for worse, have consequences for human wellbeing. This leads various scholars to the claim that engineers should explicitly take into account ethical considerations. They are at the cradle of new technological developments and can thereby influence the possible risks and benefits more directly than anybody else. I have argued elsewhere that emotions are an indispensable source of ethical insight into ethical aspects of risk. In this paper I will argue that this means that engineers should also include emotional reflection into their work. This requires a new understanding of the competencies of engineers: they should not be unemotional calculators; quite the opposite, they should work to cultivate their moral emotions and sensitivity, in order to be engaged in morally responsible engineering

Disparate Impact of Butyroyloxymethyl Diethylphosphate (AN-7), a Histone Deacetylase Inhibitor, and Doxorubicin in Mice Bearing a Mammary Tumor

The histone deacetylase inhibitor (HDACI) butyroyloxymethyl diethylphosphate (AN-7) synergizes the cytotoxic effect of doxorubicin (Dox) and anti-HER2 on mammary carcinoma cells while protecting normal cells against their insults. This study investigated the concomitant changes occurring in heart tissue and tumors of mice bearing a subcutaneous 4T1 mammary tumor following treatment with AN-7, Dox, or their combination. Dox or AN-7 alone led to inhibition of both tumor growth and lung metastases, whereas their combination significantly increased their anticancer efficacy and attenuated Dox- toxicity. Molecular analysis revealed that treatment with Dox, AN-7, and to a greater degree, AN-7 together with Dox increased tumor levels of γH2AX, the marker for DNA double-strand breaks and decreased the expression of Rad51, a protein needed for DNA repair. These events culminated in increased apoptosis, manifested by the appearance of cytochrome-c in the cytosol. In the myocardium, Dox-induced cardiomyopathy was associated with an increase in γH2AX expression and a reduction in Rad51 and MRE11 expression and increased apoptosis. The addition of AN-7 to the Dox treatment protected the heart from Dox insults as was manifested by a decrease in γH2AX levels, an increase in Rad51 and MRE11 expression, and a diminution of cytochrome-c release. Tumor fibrosis was high in untreated mice but diminished in Dox- and AN-7-treated mice and was almost abrogated in AN-7+Dox-treated mice. By contrast, in the myocardium, Dox alone induced a dramatic increase in fibrosis, and AN7+Dox attenuated it. The high expression levels of c-Kit, Ki-67, c-Myc, lo-FGF, and VEGF in 4T1 tumors were significantly reduced by Dox or AN-7 and further attenuated by AN-7+Dox. In the myocardium, Dox suppressed these markers, whereas AN-7+Dox restored their expression. In conclusion, the combination of AN-7 and Dox results in two beneficial effects, improved anticancer efficacy and cardioprotection