Dimension Distortion by Sobolev Mappings in Foliated Metric Spaces

We quantify the extent to which a supercritical Sobolev mapping can increase the dimension of subsets of its domain, in the setting of metric measure spaces supporting a Poincaré inequality. We show that the set of mappings that distort the dimensions of sets by the maximum possible amount is a prevalent subset of the relevant function space. For foliations of a metric space X defined by a David–Semmes regular mapping Π : X → W, we quantitatively estimate, in terms of Hausdorff dimension in W, the size of the set of leaves of the foliation that are mapped onto sets of higher dimension. We discuss key examples of such foliations, including foliations of the Heisenberg group by left and right cosets of horizontal subgroups.

Doxycycline for osteoarthritis of the knee or hip

BACKGROUND: Osteoarthritis is a chronic joint disease that involves degeneration of articular cartilage. Pre-clinical data suggest that doxycycline might act as a disease-modifying agent for the treatment of osteoarthritis, with the potential to slow cartilage degeneration. OBJECTIVES: To examine the effects of doxycycline compared with placebo or no intervention on pain and function in patients with osteoarthritis of the hip or knee. SEARCH STRATEGY: We searched CENTRAL ( The Cochrane Library 2008, issue 3), MEDLINE, EMBASE and CINAHL up to 28 July 2008, checked conference proceedings, reference lists, and contacted authors. SELECTION CRITERIA: We included studies if they were randomised or quasi-randomised controlled trials that compared doxycycline at any dosage and any formulation with placebo or no intervention in patients with osteoarthritis of the knee or hip. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate. We contacted investigators to obtain missing outcome information. We calculated differences in means at follow-up between experimental and control groups for continuous outcomes and risk ratios for binary outcomes. MAIN RESULTS: We found one randomised controlled trial that compared doxycycline with placebo in 431 obese women. After 30 months of treatment, clinical outcomes were similar between the two treatment groups, with a mean difference of -0.20 cm (95% confidence interval (CI) -0.77 to 0.37 cm) on a visual analogue scale from 0 to 10 cm for pain and -1.10 units (95% CI -3.86 to 1.66) for function on the WOMAC disability subscale, which ranges from 17 to 85. These differences correspond to clinically irrelevant effect sizes of -0.08 and -0.09 standard deviation units for pain and function, respectively. The difference in changes in minimum joint space narrowing was in favour of doxycycline (-0.15 mm, 95% CI -0.28 to -0.02 mm), which corresponds to a small effect size of -0.23 standard deviation units. More patients withdrew from the doxycycline group compared with placebo due to adverse events (risk ratio 1.69, 95% CI 1.03 to 2.75). AUTHORS' CONCLUSIONS: The symptomatic benefit of doxycycline is minimal to non-existent. The small benefit in terms of joint space narrowing is of questionable clinical relevance and outweighed by safety problems. Doxycycline should not be recommended for the treatment of osteoarthritis of the knee or hip.

Mitochondrial translation factors of Trypanosoma brucei: elongation factor-Tu has a unique subdomain that is essential for its function

Mitochondrial translation in the parasitic protozoan Trypanosoma brucei relies on imported eukaryotic-type tRNAs as well as on bacterial-type ribosomes that have the shortest known rRNAs. Here we have identified the mitochondrial translation elongation factors EF-Tu, EF-Ts, EF-G1 and release factor RF1 of trypanosomatids and show that their ablation impairs growth and oxidative phosphorylation. In vivo labelling experiments and a SILAC-based analysis of the global proteomic changes induced by EF-Tu RNAi directly link EF-Tu to mitochondrial translation. Moreover, EF-Tu RNAi reveals downregulation of many nuclear encoded subunits of cytochrome oxidase as well as of components of the bc1-complex, whereas most cytosolic ribosomal proteins were upregulated. Interestingly, T. brucei EF-Tu has a 30-amino-acid-long, highly charged subdomain, which is unique to trypanosomatids. A combination of RNAi and complementation experiments shows that this subdomain is essential for EF-Tu function, but that it can be replaced by a similar sequence found in eukaryotic EF-1a, the cytosolic counterpart of EF-Tu. A recent cryo-electron microscopy study revealed that trypanosomatid mitochondrial ribosomes have a unique intersubunit space that likely harbours the EF-Tu binding site. These findings suggest that the trypanosomatid-specific EF-Tu subdomain serves as an adaption for binding to these unusual mitochondrial ribosomes.

Space, diffusion and mobility

Given its origins in traditional dialectology, and given advances in our understanding of the social embedding of language variation, it is paradoxical that space should be one of the categories that has received least attention of all in variationist sociolinguistics. Until recently, space has largely been treated as an empty stage on which sociolinguistic processes are enacted. It has been unexamined, untheorized, and its role in shaping and being shaped by variation and change untested. One function of this chapter, therefore, is to assert that space makes a difference, and to begin, in a very hesitant way, to map out what a geographically informed variation analysis might need to address. It also examines variationist interactions with the related concept of mobility. It might be reasonable to think that human geographers would provide some clues on how to proceed. As we will see, they have engaged in a great deal of soul searching about the goals of their discipline, its very existence as a separate field of enquiry, and the directions it should take. Indeed there are remarkable parallels between the recent history of human geographic thought, and interest in language variation across space. Although space has been undertheorized in variation studies, a number of researchers, from the traditional dialectologists through to those interested in the dialectology of mobility and contact, have, of course, been actively engaged in research on geographical variation and language use. Their work will be contextualized here to highlight both the parallels with theory-building in human geography, but also some of the criticisms of earlier approaches which have fed through to human geography, but remain largely unquestioned in variationist practice. The chapter therefore presents a brief theoretical background to space and mobility, before exemplifying these concepts in variationist research through an examination of, for example, the spatial diffusion of linguistic innovations, the spatial configuration of linguistic boundaries and initial steps to examine the consequences of mobility for variationist research.

The free escape continuum of diffuse ions upstream of the Earth's quasi-parallel bow shock

The Earth's bow shock is very efficient in accelerating ions out of the incident solar wind distribution to high energies (≈ 200 keV/e). Fluxes of energetic ions accelerated at the quasi-parallel bow shock, also known as diffuse ions, are best represented by exponential spectra in energy/charge, which require additional assumptions to be incorporated into these model spectra. One of these assumptions is a so-called "free escape boundary" along the interplanetary magnetic field into the upstream direction. Locations along the IBEX orbit are ideally suited for in situ measurements to investigate the existence of an upstream free escape boundary for bow shock accelerated ions. In this study we use 2 years of ion measurements from the background monitor on the IBEX spacecraft, supported by ACE solar wind observations. The IBEX Background Monitor is sensitive to protons > 14 keV, which includes the energy of the maximum flux for diffuse ions. With increasing distance from the bow shock along the interplanetary magnetic field, the count rates for diffuse ions stay constant for ions streaming away from the bow shock, while count rates for diffuse ions streaming toward the shock gradually decrease from a maximum value to ~1/e at distances of about 10 RE to 14 RE. These observations of a gradual decrease support the transition to a free escape continuum for ions of energy >14 keV at distances from 10 RE to 14 RE from the bow shock.

Test Facility to Study Surface-Interaction Processes for Particle Detection in Space

The Imager for Low Energetic Neutral Atoms test facility at the University of Bern was developed to investigate, characterize, and quantify physical processes on surfaces that are used to ionize neutral atoms before their analysis in neutral particle-sensing instruments designed for space research. The facility has contributed valuable knowledge of the interaction of ions with surfaces (e.g., fraction of ions scattered from surfaces and angular scattering distribution) and employs a novel measurement principle for the determination of secondary electron emission yields as a function of energy, angle of incidence, particle species, and sample surface for low particle energies. Only because of this test facility it was possible to successfully apply surface-science processes for the new detection technique for low-energetic neutral particles with energies below about 1 keV used in space applications. All successfully flown spectrometers for the detection of low-energetic neutrals based on the particle–surface interaction process use surfaces evaluated, tested, and calibrated in this facility. Many instruments placed on different spacecraft (e.g., Imager for Magnetopause-to-Aurora Global Exploration, Chandrayaan-1, Interstellar Boundary Explorer, etc.) have successfully used this technique.

Characterization of granite matrix porosity and pore-space geometry by in situ and laboratory methods

Most available studies of interconnected matrix porosity of crystalline rocks are based on laboratory investigations; that is, work on samples that have undergone stress relaxation and were affected by drilling and sample preparation. The extrapolation of the results to in situ conditions is therefore associated with considerable uncertainty, and this was the motivation to conduct the ‘in situ Connected Porosity’ experiment at the Grimsel Test Site (Central Swiss Alps). An acrylic resin doped with fluorescent agents was used to impregnate the microporous granitic matrix in situ around an injection borehole, and samples were obtained by overcoring. The 3-D structure of the porespace, represented by microcracks, was studied by U-stage fluorescence microscopy. Petrophysical methods, including the determination of porosity, permeability and P -wave velocity, were also applied. Investigations were conducted both on samples that were impregnated in situ and on non-impregnated samples, so that natural features could be distinguished from artefacts. The investigated deformed granites display complex microcrack populations representing a polyphase deformation at varying conditions. The crack population is dominated by open cleavage cracks in mica and grain boundary cracks. The porosity of non-impregnated samples lies slightly above 1 per cent, which is 2–2.5 times higher than the in situ porosity obtained for impregnated samples. Measurements of seismic velocities (Vp ) on spherical rock samples as a function of confining pressure, spatial direction and water saturation for both non-impregnated and impregnated samples provide further constraints on the distinction between natural and induced crack types. The main conclusions are that (1) an interconnected network of microcracks exists in the whole granitic matrix, irrespective of the distance to ductile and brittle shear zones, and (2) conventional laboratory methods overestimate the matrix porosity. Calculations of contaminant transport through fractured media often rely on matrix diffusion as a retardation mechanism.

A new Bayesian approach to the reconstruction of spectral functions

We present a novel approach for the reconstruction of spectra from Euclidean correlator data that makes close contact to modern Bayesian concepts. It is based upon an axiomatically justified dimensionless prior distribution, which in the case of constant prior function m(ω) only imprints smoothness on the reconstructed spectrum. In addition we are able to analytically integrate out the only relevant overall hyper-parameter α in the prior, removing the necessity for Gaussian approximations found e.g. in the Maximum Entropy Method. Using a quasi-Newton minimizer and high-precision arithmetic, we are then able to find the unique global extremum of P[ρ|D] in the full Nω » Nτ dimensional search space. The method actually yields gradually improving reconstruction results if the quality of the supplied input data increases, without introducing artificial peak structures, often encountered in the MEM. To support these statements we present mock data analyses for the case of zero width delta peaks and more realistic scenarios, based on the perturbative Euclidean Wilson Loop as well as the Wilson Line correlator in Coulomb gauge.

The Beach in Anglophone Literatures and Cultures: Reading Littoral Space

From early colonial encounters to the ecological disasters of the twenty-first century, the performativity of contact has been a crucial element in the political significance of the beach. Conceptualising the beach as a creative trope and as a socio-cultural site, as well as an aesthetically productive topography, this collection examines its multiplicity of meanings and functions as a natural environment engendering both desire and fear in the human imagination from the Victorian period to the present. The contributors examine literature, film, and art, in addition to moments of encounter and environmental crisis, to highlight the beach as a social space inspiring particular codes of behaviour and specific discourses, as a geographical frontier between land and water, as an historical site of contact and conflict, and as a vacationscape promising regeneration and withdrawal from everyday life. The diversity of the beach is reflected in the geographical range, with essays on locales and texts from Britain, Ireland, the Caribbean, South Africa, the United States, Polynesia, and New Zealand. Focusing on the changed function of the beach as a result of processes of industrialisation and the rise of a modern leisure and health culture, this interdisciplinary volume theorises the beach as a demarcater of the precarious boundary between land and the sea, as well as between nature and culture.

Intra-articular corticosteroid for knee osteoarthritis.

BACKGROUND Knee osteoarthritis is a leading cause of chronic pain, disability, and decreased quality of life. Despite the long-standing use of intra-articular corticosteroids, there is an ongoing debate about their benefits and safety. This is an update of a Cochrane review first published in 2005. OBJECTIVES To determine the benefits and harms of intra-articular corticosteroids compared with sham or no intervention in people with knee osteoarthritis in terms of pain, physical function, quality of life, and safety. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE (from inception to 3 February 2015), checked trial registers, conference proceedings, reference lists, and contacted authors. SELECTION CRITERIA We included randomised or quasi-randomised controlled trials that compared intra-articular corticosteroids with sham injection or no treatment in people with knee osteoarthritis. We applied no language restrictions. DATA COLLECTION AND ANALYSIS We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain, function, quality of life, joint space narrowing, and risk ratios (RRs) for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis. MAIN RESULTS We identified 27 trials (13 new studies) with 1767 participants in this update. We graded the quality of the evidence as 'low' for all outcomes because treatment effect estimates were inconsistent with great variation across trials, pooled estimates were imprecise and did not rule out relevant or irrelevant clinical effects, and because most trials had a high or unclear risk of bias. Intra-articular corticosteroids appeared to be more beneficial in pain reduction than control interventions (SMD -0.40, 95% CI -0.58 to -0.22), which corresponds to a difference in pain scores of 1.0 cm on a 10-cm visual analogue scale between corticosteroids and sham injection and translates into a number needed to treat for an additional beneficial outcome (NNTB) of 8 (95% CI 6 to 13). An I(2) statistic of 68% indicated considerable between-trial heterogeneity. A visual inspection of the funnel plot suggested some asymmetry (asymmetry coefficient -1.21, 95%CI -3.58 to 1.17). When stratifying results according to length of follow-up, benefits were moderate at 1 to 2 weeks after end of treatment (SMD -0.48, 95% CI -0.70 to -0.27), small to moderate at 4 to 6 weeks (SMD -0.41, 95% CI -0.61 to -0.21), small at 13 weeks (SMD -0.22, 95% CI -0.44 to 0.00), and no evidence of an effect at 26 weeks (SMD -0.07, 95% CI -0.25 to 0.11). An I(2) statistic of ≥ 63% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.001), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.43). There was evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.05) or at least 100 participants per group (P=0.013), in trials that used concomittant viscosupplementation (P=0.08), and in trials that used concomitant joint lavage (P≤0.001).Corticosteroids appeared to be more effective in function improvement than control interventions (SMD -0.33, 95% CI -0.56 to -0.09), which corresponds to a difference in functions scores of -0.7 units on standardised Western Ontario and McMaster Universities Arthritis Index (WOMAC) disability scale ranging from 0 to 10 and translates into a NNTB of 10 (95% CI 7 to 33). An I(2) statistic of 69% indicated a moderate to large degree of between-trial heterogeneity. A visual inspection of the funnel plot suggested asymmetry (asymmetry coefficient -4.07, 95% CI -8.08 to -0.05). When stratifying results according to length of follow-up, benefits were small to moderate at 1 to 2 weeks after end of treatment (SMD -0.43, 95% CI -0.72 to -0.14), small to moderate at 4 to 6 weeks (SMD -0.36, 95% CI -0.63 to -0.09), and no evidence of an effect at 13 weeks (SMD -0.13, 95% CI -0.37 to 0.10) or at 26 weeks (SMD 0.06, 95% CI -0.16 to 0.28). An I(2) statistic of ≥ 62% indicated a moderate to large degree of between-trial heterogeneity up to 13 weeks after end of treatment (P for heterogeneity≤0.004), and an I(2) of 0% indicated low heterogeneity at 26 weeks (P=0.52). We found evidence of lower treatment effects in trials that randomised on average at least 50 participants per group (P=0.023), in unpublished trials (P=0.023), in trials that used non-intervention controls (P=0.031), and in trials that used concomitant viscosupplementation (P=0.06).Participants on corticosteroids were 11% less likely to experience adverse events, but confidence intervals included the null effect (RR 0.89, 95% CI 0.64 to 1.23, I(2)=0%). Participants on corticosteroids were 67% less likely to withdraw because of adverse events, but confidence intervals were wide and included the null effect (RR 0.33, 95% CI 0.05 to 2.07, I(2)=0%). Participants on corticosteroids were 27% less likely to experience any serious adverse event, but confidence intervals were wide and included the null effect (RR 0.63, 95% CI 0.15 to 2.67, I(2)=0%).We found no evidence of an effect of corticosteroids on quality of life compared to control (SMD -0.01, 95% CI -0.30 to 0.28, I(2)=0%). There was also no evidence of an effect of corticosteroids on joint space narrowing compared to control interventions (SMD -0.02, 95% CI -0.49 to 0.46). AUTHORS' CONCLUSIONS Whether there are clinically important benefits of intra-articular corticosteroids after one to six weeks remains unclear in view of the overall quality of the evidence, considerable heterogeneity between trials, and evidence of small-study effects. A single trial included in this review described adequate measures to minimise biases and did not find any benefit of intra-articular corticosteroids.In this update of the systematic review and meta-analysis, we found most of the identified trials that compared intra-articular corticosteroids with sham or non-intervention control small and hampered by low methodological quality. An analysis of multiple time points suggested that effects decrease over time, and our analysis provided no evidence that an effect remains six months after a corticosteroid injection.

Keep at bay! - Abnormal personal space regulation as marker of paranoia in schizophrenia.

BACKGROUND During threat, interpersonal distance is deliberately increased. Personal space regulation is related to amygdala function and altered in schizophrenia, but it remains unknown whether it is particularly associated with paranoid threat. METHODS We compared performance in two tests on personal space between 64 patients with schizophrenia spectrum disorders and 24 matched controls. Patients were stratified in those with paranoid threat, neutral affect or paranoid experience of power. In the stop-distance paradigm, participants indicated the minimum tolerable interpersonal distance. In the fixed-distance paradigm, they indicated the level of comfort at fixed interpersonal distances. RESULTS Paranoid threat increased interpersonal distance two-fold in the stop-distance paradigm, and reduced comfort ratings in the fixed-distance paradigm. In contrast, patients experiencing paranoid power had high comfort ratings at any distance. Patients with neutral affect did not differ from controls in the stop-distance paradigm. Differences between groups remained when controlling for gender and positive symptom severity. Among schizophrenia patients, the stop-distance paradigm detected paranoid threat with 93% sensitivity and 83% specificity. CONCLUSIONS Personal space regulation is not generally altered in schizophrenia. However, state paranoid experience has distinct contributions to personal space regulation. Subjects experiencing current paranoid threat share increased safety-seeking behavior.

Composition Space Analysis in the Development of Copper Molybdate Hybrids Decorated by a Bifunctional Pyrazolyl/1,2,4-Triazole Ligand

A bitopic ligand, 4-(3,5-dimethylpyrazol-4-yl)-1,2,4-triazole (Hpz-tr) (1), containing two different heterocyclic moieties was employed for the design of copper(II)–molybdate solids under hydrothermal conditions. In the multicomponent CuII/Hpz-tr/MoVI system, a diverse set of coordination hybrids, [Cu(Hpz-tr)2SO4]·3H2O (2), [Cu(Hpz-tr)Mo3O10] (3), [Cu4(OH)4(Hpz-tr)4Mo8O26]·6H2O (4), [Cu(Hpz-tr)2Mo4O13] (5), and [Mo2O6(Hpz-tr)]·H2O (6), was prepared and characterized. A systematic investigation of these systems in the form of a ternary crystallization diagram approach was utilized to show the influence of the molar ratios of starting reagents, the metal (CuII and MoVI) sources, the temperature, etc., on the reaction products outcome. Complexes 2–4 dominate throughout a wide crystallization range of the composition triangle, while the other two compounds 5 and 6 crystallize as minor phases in a narrow concentration range. In the crystal structures of 2–6, the organic ligand behaves as a short [N–N]-triazole linker between metal centers Cu···Cu in 2–4, Cu···Mo in 5, and Mo···Mo in 6, while the pyrazolyl function remains uncoordinated. This is the reason for the exceptional formation of low-dimensional coordination motifs: 1D for 2, 4, and 6 and 2D for 3 and 5. In all cases, the pyrazolyl group is involved in H bonding (H-donor/H-acceptor) and is responsible for π–π stacking, thus connecting the chain and layer structures in more complicated H-bonding architectures. These compounds possess moderate thermal stability up to 250–300 °C. The magnetic measurements were performed for 2–4, revealing in all three cases antiferromagnetic exchange interactions between neighboring CuII centers and long-range order with a net moment below Tc of 13 K for compound 4.