Approximating Nearest Neighbor Distances

Several researchers proposed using non-Euclidean metrics on point sets in Euclidean space for clustering noisy data. Almost always, a distance function is desired that recognizes the closeness of the points in the same cluster, even if the Euclidean cluster diameter is large. Therefore, it is preferred to assign smaller costs to the paths that stay close to the input points. In this paper, we consider the most natural metric with this property, which we call the nearest neighbor metric. Given a point set P and a path $\gamma$, our metric charges each point of $\gamma$ with its distance to P. The total charge along $\gamma$ determines its nearest neighbor length, which is formally defined as the integral of the distance to the input points along the curve. We describe a $(3+\varepsilon)$-approximation algorithm and a $(1+\varepsilon)$-approximation algorithm to compute the nearest neighbor metric. Both approximation algorithms work in near-linear time. The former uses shortest paths on a sparse graph using only the input points. The latter uses a sparse sample of the ambient space, to find good approximate geodesic paths.Comment: corrected author nam

Multi-Prover Commitments Against Non-Signaling Attacks

We reconsider the concept of multi-prover commitments, as introduced in the late eighties in the seminal work by Ben-Or et al. As was recently shown by Cr\'{e}peau et al., the security of known two-prover commitment schemes not only relies on the explicit assumption that the provers cannot communicate, but also depends on their information processing capabilities. For instance, there exist schemes that are secure against classical provers but insecure if the provers have quantum information processing capabilities, and there are schemes that resist such quantum attacks but become insecure when considering general so-called non-signaling provers, which are restricted solely by the requirement that no communication takes place. This poses the natural question whether there exists a two-prover commitment scheme that is secure under the sole assumption that no communication takes place; no such scheme is known. In this work, we give strong evidence for a negative answer: we show that any single-round two-prover commitment scheme can be broken by a non-signaling attack. Our negative result is as bad as it can get: for any candidate scheme that is (almost) perfectly hiding, there exists a strategy that allows the dishonest provers to open a commitment to an arbitrary bit (almost) as successfully as the honest provers can open an honestly prepared commitment, i.e., with probability (almost) 1 in case of a perfectly sound scheme. In the case of multi-round schemes, our impossibility result is restricted to perfectly hiding schemes. On the positive side, we show that the impossibility result can be circumvented by considering three provers instead: there exists a three-prover commitment scheme that is secure against arbitrary non-signaling attacks

Fly Photoreceptors Demonstrate Energy-Information Trade-Offs in Neural Coding

Trade-offs between energy consumption and neuronal performance must shape the design and evolution of nervous systems, but we lack empirical data showing how neuronal energy costs vary according to performance. Using intracellular recordings from the intact retinas of four flies, Drosophila melanogaster, D. virilis, Calliphora vicina, and Sarcophaga carnaria, we measured the rates at which homologous R1–6 photoreceptors of these species transmit information from the same stimuli and estimated the energy they consumed. In all species, both information rate and energy consumption increase with light intensity. Energy consumption rises from a baseline, the energy required to maintain the dark resting potential. This substantial fixed cost, ∼20% of a photoreceptor's maximum consumption, causes the unit cost of information (ATP molecules hydrolysed per bit) to fall as information rate increases. The highest information rates, achieved at bright daylight levels, differed according to species, from ∼200 bits s(−1) in D. melanogaster to ∼1,000 bits s(−1) in S. carnaria. Comparing species, the fixed cost, the total cost of signalling, and the unit cost (cost per bit) all increase with a photoreceptor's highest information rate to make information more expensive in higher performance cells. This law of diminishing returns promotes the evolution of economical structures by severely penalising overcapacity. Similar relationships could influence the function and design of many neurons because they are subject to similar biophysical constraints on information throughput

Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production

The epidemic of bovine spongiform encephalopathy (BSE) has led to a world-wide drop in the market for beef by-products, such as Meat-and-Bone Meal (MBM), a fat-containing but mainly proteinaceaous product traditionally used as an animal feed supplement. While normal rendering is insufficient, the production of biodiesel from MBM has been suggested to destroy infectivity from transmissible spongiform encephalopathies (TSEs). In addition to producing fuel, this method simultaneously generates a nutritious solid residue. In our study we produced biodiesel from MBM under defined conditions using a modified form of alkaline methanolysis. We evaluated the presence of prion in the three resulting phases of the biodiesel reaction (Biodiesel, Glycerol and Solid Residue) in vitro and in vivo. Analysis of the reaction products from 263K scrapie infected MBM led to no detectable immunoreactivity by Western Blot. Importantly, and in contrast to the biochemical results the solid MBM residue from the reaction retained infectivity when tested in an animal bioassay. Histochemical analysis of hamster brains inoculated with the solid residue showed typical spongiform degeneration and vacuolation. Re-inoculation of these brains into a new cohort of hamsters led to onset of clinical scrapie symptoms within 75 days, suggesting that the specific infectivity of the prion protein was not changed during the biodiesel process. The biodiesel reaction cannot be considered a viable prion decontamination method for MBM, although we observed increased survival time of hamsters and reduced infectivity greater than 6 log orders in the solid MBM residue. Furthermore, results from our study compare for the first time prion detection by Western Blot versus an infectivity bioassay for analysis of biodiesel reaction products. We could show that biochemical analysis alone is insufficient for detection of prion infectivity after a biodiesel process

Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes

<p>Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.</p> <p>Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.</p> <p>Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.</p&gt

Cross-sectional survey of users of internet depression communities

Background: Internet-based depression communities provide a forum for individuals to communicate and share information and ideas. There has been little research into the health status and other characteristics of users of these communities. Methods: Online cross-sectional survey of Internet depression communities to identify depressive morbidity among users of Internet depression communities in six European countries; to investigate whether users were in contact with health services and receiving treatment; and to identify user perceived effects of the communities. Results: Major depression was highly prevalent among respondents (varying by country from 40% to 64%). Forty-nine percent of users meeting criteria for major depression were not receiving treatment, and 35% had no consultation with health services in the previous year. Thirty-six percent of repeat community users who had consulted a health professional in the previous year felt that the Internet community had been an important factor in deciding to seek professional help. Conclusions: There are high levels of untreated and undiagnosed depression in users of Internet depression communities. This group represents a target for intervention. Internet communities can provide information and support for stigmatizing conditions that inhibit more traditional modes of information seeking

Large N Free Energy of 3d N=4 SCFTs and AdS/CFT

We provide a non-trivial check of the AdS_4/CFT_3 correspondence recently proposed in arXiv:1106.4253 by verifying the GKPW relation in the large N limit. The CFT free energy is obtained from the previous works (arXiv:1105.2551, arXiv:1105.4390) on the S^3 partition function for 3-dimensional N=4 SCFT T[SU(N)]. This is matched with the computation of the type IIB action on the corresponding gravity background. We unexpectedly find that the leading behavior of the free energy at large N is 1/2 N^2 ln N. We also extend our results to richer theories and argue that 1/2 N^2 ln N is the maximal free energy at large N in this class of gauge theories.Comment: 20 pages, 3 figure

Vedolizumab for Treating Moderately to Severely Active Crohn’s Disease After Prior Therapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost effectiveness of vedolizumab for the treatment of patients with moderate-to-severe, active Crohn’s disease. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned as the Evidence Review Group (ERG) and produced a critical review of the evidence of the clinical effectiveness and cost effectiveness of the technology, based upon the company’s submission to NICE. The GEMINI II and III trials formed the main supporting evidence for the intervention. Both studies were phase III, randomised, double-blind, placebo-controlled, multicentre trials designed to evaluate the efficacy and safety of vedolizumab. They included patients who were naïve to tumour necrosis factor alpha antagonist (anti-TNF-α) therapy and patients who had an inadequate response to, loss of response to or intolerance of immunomodulators or anti-TNF-α agents. GEMINI II was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment (dosing at weeks 0 and 2, with assessment at week 6) and maintenance treatment (during weeks 6–52). In contrast, GEMINI III was designed to evaluate the efficacy and safety of vedolizumab as an induction treatment only, with doses at weeks 0, 2 and 6, and assessment at weeks 6 and 10. In the absence of any direct head-to-head, randomised, controlled trials comparing vedolizumab with other relevant biologic therapies (adalimumab and infliximab) for the treatment of moderate-to-severe Crohn’s disease, the company conducted a network meta-analysis, which compared vedolizumab, adalimumab, infliximab and placebo for the outcomes of clinical response, enhanced clinical response, clinical remission and discontinuation due to adverse events. The company model estimated the incremental cost-effectiveness ratio (ICER) for vedolizumab compared with the standard of care (consisting of 5-aminosalicylic acids, corticosteroids and immunosuppressants) to be £21,620 per quality-adjusted life-year (QALY) gained within the anti-TNF-α-failure population (which included a confidential patient access scheme for vedolizumab). The ICERs were above £30,000 per QALY gained for the mixed intention-to-treat population (including both anti-TNF-α-naïve and anti-TNF-α-failure populations) and in patients who were anti-TNF-α naïve only. The ERG identified a number of limitations that were believed to limit the robustness of the results presented by the company. These limitations could not be addressed by the ERG without major restructuring of the economic model. Therefore, the ERG concluded that the results from the company’s model needed to be interpreted with caution and that it was unclear whether the ICERs would increase or decrease following amendment of the identified structural issues

What happens if you single out? An experiment

We present an experiment investigating the effects of singling out an individual on trust and trustworthiness. We find that (a) trustworthiness falls if there is a singled out subject; (b) non-singled out subjects discriminate against the singled out subject when they are not responsible of the distinct status of this person; (c) under a negative frame, the singled out subject returns significantly less; (d) under a positive frame, the singled out subject behaves bimodally, either selecting very low or very high return rates. Overall, singling out induces a negligible effect on trust but is potentially disruptive for trustworthiness