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One fundamental question is what makes two brain states similar. For example, what makes the activity in visual cortex elicited from viewing a robin similar to a sparrow? One common assumption in fMRI analysis is that neural similarity is described by Pearson correlation. However, there are a host of other possibilities, including Minkowski and Mahalanobis measures, with each differing in its mathematical, theoretical, and neural computational assumptions. Moreover, the operable measures may vary across brain regions and tasks. Here, we evaluated which of several competing similarity measures best captured neural similarity. Our technique uses a decoding approach to assess the information present in a brain region, and the similarity measures that best correspond to the classifier's confusion matrix are preferred. Across two published fMRI datasets, we found the preferred neural similarity measures were common across brain regions but differed across tasks. Moreover, Pearson correlation was consistently surpassed by alternatives.

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This paper improves the understanding of the use of eye-tracking tools in the pilot selection process. Research of eye movement and attention distribution of candidate pilots may provide the capability for visual behavior prediction in more demanding flight training phases. The research included psychological testing, flight screening of subjects and their achievements in a flight simulator in combination with an eye-tracking device. Participants were divided into three categories: high performance, average performance, and low performance and separately regarded through psychological testing results and flight screening results. An eye-tracking device tracked visual behavior of subjects through the scope and speed of visual perception. The number of fixations and revisits recorded during the simulated visual flight conditions measured the difference in visual response between subjects. Comparison of results showed a positive correlation with psychological test results. Correlation with flight screening selection was not confirmed. We used the new network-based approach with three target importance measures to overcome the shortcomings of traditional eye movement metrics. The results of the adopted network approach presented in the form of graphs and analysis of normalized importance measures showed that it was possible to extract specific saccade strategy for each participant. Discovered differences between them positively detected week ones. In this way, Eye-tracking tools can potentially improve the pilot selection process and complement other tests and assessment methods.

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IgA-expressing antibody secreting cells that are formed in the gut travel to the brain to diminish inflammation during multiple sclerosis exacerbations.

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Improving the charge carrier mobility of solution-processable organic semiconductors is critical for the development of advanced organic thin-film transistors and their application in the emerging sector of printed electronics. Here, a simple method is reported for enhancing the hole mobility in a wide range of organic semiconductors, including small-molecules, polymers, and small-molecule:polymer blends, with the latter systems exhibiting the highest mobility. The method is simple and relies on admixing of the molecular Lewis acid B(C6F5)3 in the semiconductor formulation prior to solution deposition. Two prototypical semiconductors where B(C6F5)3 is shown to have a remarkable impact are the blends of 2,8-difluoro-5,11-bis(triethylsilylethynyl)anthradithiophene:poly(triarylamine) (diF-TESADT:PTAA) and 2,7-dioctyl[1]-benzothieno[3,2-b][1]benzothiophene:poly(indacenodithiophene-co-benzothiadiazole) (C8-BTBT:C16-IDTBT), for which hole mobilities of 8 and 11 cm2 V-1 s-1, respectively, are obtained. Doping of the 6,13-bis(triisopropylsilylethynyl)pentacene:PTAA blend with B(C6F5)3 is also shown to increase the maximum hole mobility to 3.7 cm2 V-1 s-1. Analysis of the single and multicomponent materials reveals that B(C6F5)3 plays a dual role, first acting as an efficient p-dopant, and secondly as a microstructure modifier. Semiconductors that undergo simultaneous p-doping and dopant-induced long-range crystallization are found to consistently outperform transistors based on the pristine materials. Our work underscores Lewis acid doping as a generic strategy towards high performance printed organic microelectronics.

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Thin-film transistors made of solution-processed metal oxide semiconductors hold great promise for application in the emerging sector of large-area electronics. However, further advancement of the technology is hindered by limitations associated with the extrinsic electron transport properties of the often defect-prone oxides. We overcome this limitation by replacing the single-layer semiconductor channel with a low-dimensional, solution-grown In2O3/ZnO heterojunction. We find that In2O3/ZnO transistors exhibit band-like electron transport, with mobility values significantly higher than single-layer In2O3 and ZnO devices by a factor of 2 to 100. This marked improvement is shown to originate from the presence of free electrons confined on the plane of the atomically sharp heterointerface induced by the large conduction band offset between In2O3 and ZnO. Our finding underscores engineering of solution-grown metal oxide heterointerfaces as an alternative strategy to thin-film transistor development and has the potential for widespread technological applications.

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Different from Cauchy elastic materials, generalized continua, and in particular constrained Cosserat materials, can be designed to possess extreme (near a failure of ellipticity) orthotropy properties and in this way to model folding in a three-dimensional solid. Following this approach, folding, which is a narrow zone of highly localized bending, spontaneously emerges as a deformation pattern occurring in a strongly anisotropic solid. How this peculiar pattern interacts with wave propagation in the time-harmonic domain is revealed through the derivation of an antiplane, infinite-body Green's function, which opens the way to integral techniques for anisotropic constrained Cosserat continua. Viewed as a perturbing agent, the Green's function shows that folding, emerging near a steadily pulsating source in the limit of failure of ellipticity, is transformed into a disturbance with wavefronts parallel to the folding itself. The results of the presented study introduce the possibility of exploiting constrained Cosserat solids for propagating waves in materials displaying origami patterns of deformation.This article is part of the themed issue 'Patterning through instabilities in complex media: theory and applications.'

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IMPORTANCE: Myasthenia gravis (MG), an autoimmune disorder of neuromuscular transmission, is treated by an array of immunotherapeutics, many of which are nonspecific. Even with current therapies, a subset of patients has medically refractory MG. The benefits of B-cell-targeted therapy with rituximab have been observed in MG; however, the duration of these benefits after treatment is unclear. OBJECTIVE: To evaluate the durability of response to rituximab in the treatment of acetylcholine receptor autoantibody-positive (AChR+) generalized MG. DESIGN, SETTING AND PARTICIPANTS: This retrospective case series study included 16 patients with AChR+ MG referred to an MG clinic from January 1, 2007, to December 31, 2015. The patients were treated with rituximab and followed up for 18 to 84 months after treatment. MAIN OUTCOMES AND MEASURES: Assessment of long-term clinical response, durability of response and/or relapse rate, AChR autoantibody levels, adverse effects, and inflammatory markers. RESULTS: In the 16 patients (6 men and 10 women; median age, 42 [range, 18-69] years), clinical improvement was observed in parallel with complete withdrawal or reduction of other immunotherapies, with all patients achieving complete stable remission, pharmacologic remission, or minimal manifestations based on the Myasthenia Gravis Foundation of America postintervention status criteria. Nine patients (56%) had a relapse during a mean follow-up of 36 (range, 24-47) months. Seven patients (44%) remained relapse free with a mean follow-up of 47 (range, 18-81) months since the last rituximab treatment. All values were normalized to a pretreatment anti-AChR antibody level of 100% and the mean levels after each rituximab cycle were calculated. A 33% decrease was seen after cycle 1 of rituximab treatment (100% vs 67%; P = .004); 20% after cycle 2 (compared with cycle 1) (67% vs 47%; P = .008); and 17% after cycle 3 (compared with cycle 2) (47% vs 30%; P = .02). However, the serum cytokine levels measured were found to be unchanged. CONCLUSIONS AND RELEVANCE: Rituximab therapy appears to be an effective option in patients with refractory AChR+ MG, who were observed to have a durable response after treatment. Identification of markers of disease relapse and sustained remission are critical next steps in the development of pathophysiology-relevant, evidence-based practice parameters for rituximab in the treatment of MG.

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A ternary organic semiconducting blend composed of a small-molecule, a conjugated polymer, and a molecular p-dopant is developed and used in solution-processed organic transistors with hole mobility exceeding 13 cm(2) V(-1) s(-1) (see the Figure). It is shown that key to this development is the incorporation of the p-dopant and the formation of a vertically phase-separated film microstructure.

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Folding is a process in which bending is localized at sharp edges separated by almost undeformed elements. This process is rarely encountered in Nature, although some exceptions can be found in unusual layered rock formations (called 'chevrons') and seashell patterns (for instance Lopha cristagalli). In mechanics, the bending of a three-dimensional elastic solid is common (for example, in bulk wave propagation), but folding is usually not achieved. In this article, the route leading to folding is shown for an elastic solid obeying the couple-stress theory with an extreme anisotropy. This result is obtained with a perturbation technique, which involves the derivation of new two-dimensional Green's functions for applied concentrated force and moment. While the former perturbation reveals folding, the latter shows that a material in an extreme anisotropic state is also prone to a faulting instability, in which a displacement step of finite size emerges. Another failure mechanism, namely the formation of dilation/compaction bands, is also highlighted. Finally, a geophysical application to the mechanics of chevron formation shows how the proposed approach may explain the formation of natural structures.

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The use of ultrasonic spray pyrolysis is demonstrated for the growth of polycrystalline, highly uniform indium oxide films at temperatures in the range of 200-300 °C in air using an aqueous In(NO3)3 precursor solution. Electrical characterization of as-deposited films by field-effect measurements reveals a strong dependence of the electron mobility on deposition temperature. Transistors fabricated at ∼250 °C exhibit optimum performance with maximum electron mobility values in the range of 15-20 cm(2) V (-1) s(-1) and current on/off ratio in excess of 10(6). Structural and compositional analysis of as-grown films by means of X-ray diffraction, diffuse scattering, and X-ray photoelectron spectroscopy reveal that layers deposited at 250 °C are denser and contain a reduced amount of hydroxyl groups as compared to films grown at either lower or higher temperatures. Microstructural analysis of semiconducting films deposited at 250 °C by high resolution cross-sectional transmission electron microscopy reveals that as-grown layers are extremely thin (∼7 nm) and composed of laterally large (30-60 nm) highly crystalline In2O3 domains. These unique characteristics of the In2O3 films are believed to be responsible for the high electron mobilities obtained from transistors fabricated at 250 °C. Our work demonstrates the ability to grow high quality low-dimensional In2O3 films and devices via ultrasonic spray pyrolysis over large area substrates while at the same time it provides guidelines for further material and device improvements.

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Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial protein frataxin. We previously generated BAC-based transgenic mice containing an FXN-EGFP genomic reporter construct in which the EGFP gene is fused in-frame immediately following the final codon of exon 5a of the human FXN gene. These transgenic mice were mated with mice heterozygous for a knockout mutation of the murine Fxn gene, to generate mice homozygous for the Fxn knockout mutation and hemizygous or homozygous for the human transgene. Rescue of the embryonic lethality that is associated with homozygosity for the Fxn knockout mutation was observed. Rescue mice displayed normal behavioral and histological parameters with normal viability, fertility and life span and without any signs of aberrant phenotype. Immunoblotting demonstrated the production of full-length frataxin-EGFP fusion protein that appears to act as a bifunctional hybrid protein. This study shows frataxin replacement may be a viable therapeutic option. Further, these mice should provide a useful resource for the study of human FXN gene expression, frataxin function, the evaluation of pharmacologic inducers of FXN expression in a whole-animal model and provide a useful source of cells for stem cell transplantation studies.

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Piophila Fallén, 1810 is a genus of small flies composed of two species: Piophila casei (P. casei ) (Linnaeus, 1758), worldwide distributed, and Piophila megastigmata (P. megastigmata ) McAlpine, 1978, recently referred in the Palaearctic Region, from the Iberian Peninsula. Both species share ecological niche and are very interesting for forensic purposes, since they are present in carrion in advance stages of decay and have been found to be related to human corpses. The immature stages of P. megastigmata have ever been described, so this paper gives the ultrastructural morphologies of all preimaginal stages of P. megastigmata studied by light microscopy and scanning electron microscopy (SEM). Particular attention is given to pseudocephalon features­antenna, maxillary palps, facial mask, etc.­cephalopharyngeal skeleton, anterior and posterior spiracles, tegumentary sculpturing, and anal division among others. A comparative analysis of the main distinguishing features is made in order to understand how those features evolve along the developmental process, while larvae II and III are morphologically similar to each other, the larva I shows particular features. Larvae of all stages and pupae are easily distinguishable from other Diptera of forensic importance just based on the presence of trichoid sensilla associated to respiratory slits, instead of peristigmatig tufts, as well as on thewell-known disposition of anal papillae. The shapes of both dorsal edge at the basal part of mouthhook and dorsal bridge of cephalopharyngeal skeleton, and the tegumental ornamentationmay be considered as good features to distinguish the Piophila species, especially for P. megastigmata and P. casei . At the SEM level, shape, number, and arrangement of oral combs, oral ridges, sensilla of maxillary palpus, papillae of anterior spiracle, scales of spiracular field, and posterior spiracles represent good features to distinguish P. megastigmata from P. casei, but further studies will be necessary in West-Paleartic specimens of latter species. The key for identifying third instar larvae of forensically important Piophilidae in the Iberian Peninsula has been updated to include P. megastigmata.

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Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial protein frataxin. There is a correlation between expansion length, the amount of residual frataxin and the severity of disease. As the coding sequence is unaltered, pharmacological up-regulation of FXN expression may restore frataxin to therapeutic levels. To facilitate screening of compounds that modulate FXN expression in a physiologically relevant manner, we established a cellular genomic reporter assay consisting of a stable human cell line containing an FXN-EGFP fusion construct, in which the EGFP gene is fused in-frame with the entire normal human FXN gene present on a BAC clone. The cell line was used to establish a fluorometric cellular assay for use in high throughput screening (HTS) procedures. A small chemical library containing FDA-approved compounds and natural extracts was screened and analyzed. Compound hits identified by HTS were further evaluated by flow cytometry in the cellular genomic reporter assay. The effects on FXN mRNA and frataxin protein levels were measured in lymphoblast and fibroblast cell lines derived from individuals with FRDA and in a humanized GAA repeat expansion mouse model of FRDA. Compounds that were established to increase FXN gene expression and frataxin levels included several anti-cancer agents, the iron-chelator deferiprone and the phytoalexin resveratrol.

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Synovial sarcoma is a rare malignant soft-tissue tumor that most commonly occurs in the extremities of young adults. Primary pericardial synovial sarcoma is extremely rare. We report the case of a 37 year old male patient who presented with intermittent fever, nocturnal sweating and asthenia. Chest X-ray revealed an enlarged cardiac silhouette. Echocardiography identified pericardial effusion and a mass compressing the right ventricle. After percutaneous drainage of the effusion, the mass was not visible and deemed to have been septations of the effusion. Chest computed tomography (CT) did not show the mass visible on the X-ray. At one month follow-up, the pericardial mass was again visible on echocardiography and confirmed by magnetic resonance imaging (MRI). CT-guided biopsy showed malignant mesenchymal cells. Complete resection was attempted, but not possible due to diffuse infiltration of the epicardium. Histological examination of the resected tissue revealed an undifferentiated primary pericardial synovial sarcoma. The patient refused adjuvant treatment and died 15 days later. Surgical resection is considered the cornerstone of treatment of this rare type of malignant tumor of the young; our patient presented with a diffusely infiltrating tumor which could not be resected and required reoperation for tamponade and left pericardectomy. We question whether the choice to attempt resection was beneficial.

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BACKGROUND: Friedreich ataxia (FRDA) is the most common form of hereditary ataxia characterized by the presence of a GAA trinucleotide repeat expansion within the first intron of the FXN gene. The expansion inhibits FXN gene expression resulting in an insufficiency of frataxin protein. METHODOLOGY/PRINCIPAL FINDING: In this study, computational analyses were performed on the 21.3 kb region upstream of exon 1 of the human FXN gene and orthologs from other species in order to identify conserved non-coding DNA sequences with potential regulatory functions. The conserved non-coding regions identified were individually analyzed in two complementing assay systems, a conventional luciferase reporter system and a novel Bacterial Artificial Chromosome (BAC)-based genomic reporter. The BAC system allows the evaluation of gene expression to be made in the context of its entire genomic locus and preserves the normal location and spacing of many regulatory elements which may be positioned over large distances from the initiation codon of the gene. CONCLUSIONS/SIGNIFICANCE: The two approaches were used to identify a region of 17 bp located approximately 4.9 kb upstream of the first exon of the FXN gene that plays an important role in FXN gene expression. Modulation of FXN gene expression was found to be mediated by the action of the Oct-1 transcription factor at this site. A better understanding of cis-acting regulatory elements that control FXN gene expression has the potential to develop new strategies for the upregulation of the FXN gene as a therapy for FRDA.

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This paper explores the potential of a computer-aided diagnosis system to discriminate the real benign microcalcifications among a specific subset of 109 patients with BIRADS 3 mammograms who had undergone biopsy, thus making it possible to downgrade them to BIRADS 2 category. The system detected and quantified critical features of microcalcifications and classified them on a risk percentage scale for malignancy. The system successfully detected all cancers. Nevertheless, it suggested biopsy for 11/15 atypical lesions. Finally, the system characterized as definitely benign (BIRADS 2) 29/88 benign lesions, previously assigned to BIRADS 3, and thus achieved a reduction of 33% in unnecessary biopsies.

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Hypothermia has been used for decades in cardiac surgery to limit the ischemic insult to the heart. With the diffusion of off-pump coronary artery surgery, the practice of arresting and cooling the heart has been abandoned. At University of Miami Miller School of Medicine, we tested a new warming device by performing a prospective study in which 50 patients were randomized to either the use of the Kimberly-Clark warming system or to standard methods of control of body temperature. The two groups were compared in terms of core body temperature (CBT), intra- and postoperative blood loss, blood products transfusions, extubation time, intensive care unit (ICU) and hospital length of stay and incidence of infections. Five patients in the control group and 0 patients in the study group dropped their CBT below 35 degrees C during the operation (P<0.01). Total blood loss, measured in terms of cell-saver and chest tube drainage, was 27 % and 14 % less for the study group (P<0.01). Hospital length of stay was 1.2 day less in the study group (P<0.01). The Kimberly-Clark Patient Warming System allowed for better control of core body temperature during off pump coronary artery bypass surgery compared to traditional techniques. This translated in less intra and postoperative blood loss and shorter hospital length of stay. Other advantages, such as decreased blood-products transfusions, decreased incidence of infections, decreased ICU length of stay and overall reduction of costs might be evident on larger study groups.

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BACKGROUND: Methylmalonic aciduria is an autosomal recessive inborn error of the propionate metabolic pathway. One form of this disorder is caused by mutations in methylmalonyl-coenzyme A mutase (MCM), resulting in reduced levels of enzyme activity. The pharmacological up-regulation of residual mutase activity is one approach to advance treatment strategies for individuals affected by this disorder. We describe the construction, characterization and use of a cellular genomic reporter assay for MCM expression that will potentially identify therapeutic pharmacological agents for methylmalonic aciduria treatment. METHODS: Homologous recombination was used to insert an enhanced green fluorescent protein (EGFP) cassette inframe before the last codon of exon 13 of the MCM gene (MUT) in a BAC clone. The construct was used to generate stable HeLa cell lines. EGFP expression was measured by flow cytometry and the real-time reverse transcriptase-polymerase chain reaction was used to quantify changes in MUT gene mRNA levels. RESULTS: The genomic reporter assay used to screen a selection of compounds. Cisplatin, zidovudine and adefovir were found to increase the levels of MCM mRNA and EGFP expression, providing support for the possible efficacy of these pharmacological compounds in treating methylmalonic aciduria. CONCLUSIONS: This assay has the potential of being used in high-throughput screening of chemical libraries for the identification of novel compounds that specifically modulate the expression of MCM.

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