A case of TDP-43 type C pathology presenting as nonfluent variant primary progressive aphasia

We report a case of rapidly progressive nonfluent variant PPA (nfvPPA), age at onset 77 years old and disease duration 3.3 years, who came to post mortem and was found to have TDP-43 type C pathology, an unusual finding for nfvPPA. All prior TDP-43 type C cases from the UCL FTD cohort (n=25) had a semantic variant PPA (svPPA) phenotype, with all having a younger age at onset and longer disease duration than the nfvPPA case. Volumetric analysis of MRI from the nfvPPA case, twelve of the svPPA cases and ten age-matched controls was performed. Whilst left frontal and insular volumes were lower in the nfvPPA case compared with svPPA, cortical and medial temporal lobe volumes were lower (particularly on the right) in the svPPA group compared with the nfvPPA patient. Such anatomical involvement is likely to be consistent with the presence of a nonfluent aphasia (left frontal lobe and insula), and only mild semantic deficit early in the illness (left but not right temporal lobe). Such unique cases add to the heterogeneity of the FTD spectrum

Searching for an anchor in an unpredictable world: A computational model of obsessive compulsive disorder

In this article, we develop a computational model of obsessive–compulsive disorder (OCD). We propose that OCD is characterized by a difficulty in relying on past events to predict the consequences of patients’ own actions and the unfolding of possible events. Clinically, this corresponds both to patients’ difficulty in trusting their own actions (and therefore repeating them), and to their common preoccupation with unlikely chains of events. Critically, we develop this idea on the basis of the well-developed framework of the Bayesian brain, where this impairment is formalized as excessive uncertainty regarding state transitions. We illustrate the validity of this idea using quantitative simulations and use these to form specific empirical predictions. These predictions are evaluated in relation to existing evidence, and are used to delineate directions for future research. We show how seemingly unrelated findings and phenomena in OCD can be explained by the model, including a persistent experience that actions were not adequately performed and a tendency to repeat actions; excessive information gathering (i.e., checking); indecisiveness and pathological doubt; overreliance on habits at the expense of goal-directed behavior; and overresponsiveness to sensory stimuli, thoughts, and feedback. We discuss the relationship and interaction between our model and other prominent models of OCD, including models focusing on harm-avoidance, not-just-right experiences, or impairments in goal-directed behavior. Finally, we outline potential clinical implications and suggest lines for future research

World citation and collaboration networks: uncovering the role of geography in science

Modern information and communication technologies, especially the Internet, have diminished the role of spatial distances and territorial boundaries on the access and transmissibility of information. This has enabled scientists for closer collaboration and internationalization. Nevertheless, geography remains an important factor affecting the dynamics of science. Here we present a systematic analysis of citation and collaboration networks between cities and countries, by assigning papers to the geographic locations of their authors' affiliations. The citation flows as well as the collaboration strengths between cities decrease with the distance between them and follow gravity laws. In addition, the total research impact of a country grows linearly with the amount of national funding for research & development. However, the average impact reveals a peculiar threshold effect: the scientific output of a country may reach an impact larger than the world average only if the country invests more than about 100,000 USD per researcher annually.Comment: Published version. 9 pages, 5 figures + Appendix, The world citation and collaboration networks at both city and country level are available at http://becs.aalto.fi/~rajkp/datasets.htm

Analyticity, Unitarity and One-loop Graviton Corrections to Compton Scattering

We compute spin-flip cross section for graviton photoproduction on a spin-1/2 target of finite mass. Using this tree-level result, we find one-loop graviton correction to the spin-flip low-energy forward Compton scattering amplitude by using Gerasimov-Drell-Hearn sum rule. We show that this result agrees with the corresponding perturbative computations, implying the validity of the sum rule at one-loop level, contrary to the previous claims. We discuss possible effects from the black hole production and string Regge trajectory exchange at very high energies. These effects seem to soften the UV divergence present at one-loop graviton level. Finally, we discuss the relation of these observations with the models that involve extra dimensions.Comment: 15 pages, 3 figure

Interactive effects of elevated CO <inf>2</inf> and drought on nocturnal water fluxes in Eucalyptus saligna

Nocturnal water flux has been observed in trees under a variety of environmental conditions and can be a significant contributor to diel canopy water flux. Elevated atmospheric CO 2 (elevated [CO 2]) can have an important effect on day-time plant water fluxes, but it is not known whether it also affects nocturnal water fluxes. We examined the effects of elevated [CO 2] on nocturnal water flux of field-grown Eucalyptus saligna trees using sap flux through the tree stem expressed on a sapwood area (J s) and leaf area (E t) basis. After 19 months growth under well-watered conditions, drought was imposed by withholding water for 5 months in the summer, ending with a rain event that restored soil moisture. Reductions in J s and E t were observed during the severe drought period in the dry treatment under elevated [CO 2], but not during moderate- and post-drought periods. Elevated [CO 2] affected night-time sap flux density which included the stem recharge period, called 'total night flux' (19:00 to 05:00, J s,r), but not during the post-recharge period, which primarily consisted of canopy transpiration (23:00 to 05:00, J s,c). Elevated [CO 2] wet (EW) trees exhibited higher J s,r than ambient [CO 2] wet trees (AW) indicating greater water flux in elevated [CO 2] under well-watered conditions. However, under drought conditions, elevated [CO 2] dry (ED) trees exhibited significantly lower J s,r than ambient [CO 2] dry trees (AD), indicating less water flux during stem recharge under elevated [CO 2]. J s,c did not differ between ambient and elevated [CO 2]. Vapour pressure deficit (D) was clearly the major influence on night-time sap flux. D was positively correlated with J s,r and had its greatest impact on J s,r at high D in ambient [CO 2]. Our results suggest that elevated [CO 2] may reduce night-time water flux in E. saligna when soil water content is low and D is high. While elevated [CO 2] affected J s,r, it did not affect day-time water flux in wet soil, suggesting that the responses of J s,r to environmental factors cannot be directly inferred from day-time patterns. Changes in J s,r are likely to influence pre-dawn leaf water potential, and plant responses to water stress. Nocturnal fluxes are clearly important for predicting effects of climate change on forest physiology and hydrology. © 2011 The Author. Published by Oxford University Press. A ll rights reserved

Studies of the Precipitation Pattern of Paclitaxel in Intravenous Infusions and Rat Plasma Using Laser Nephelometry

Cremophor EL (CrEL) is commonly used to solubilize paclitaxel (Ptx); a widely established anticancer agent used against many types of cancer. Using laser-based microplate nephelometry, in this work we assessed the precipitation kinetics of Ptx in CrEL-containing formulations upon dilutions with different infusion media or upon introduction into rat plasma. The precipitation profile of Ptx was assessed for a Taxol-like formulation and compared with a preparation with reduced CrEL content. These two formulations were diluted at various ratios in compatible infusion media and with or without rat plasma. The percentages of Ptx precipitated in dilution media and protein-binding in plasma were quantified using HPLC. The findings of turbidity measurements were in good agreement with HPLC. Despite the presence of albumin, it was possible to assess turbidity within infusion solutions and predict Ptx precipitation. Upon addition to plasma, no precipitation in Taxol-like formulation occurred after 2 h. In contrast, precipitation occurred immediately in CrEL-reduced formulation. It is possible that the high percentage of protein-bound Ptx in plasma (98.5–99.2%) has inhibited drug precipitation. Turbidity measurements using laser nephelometry can provide a rapid screening tool when developing intravenous formulations for poorly soluble drugs, such as Ptx and assess its stability upon dilution in animal plasma

The Mitochondrial Genome of the Legume Vigna radiata and the Analysis of Recombination across Short Mitochondrial Repeats

The mitochondrial genomes of seed plants are exceptionally fluid in size, structure, and sequence content, with the accumulation and activity of repetitive sequences underlying much of this variation. We report the first fully sequenced mitochondrial genome of a legume, Vigna radiata (mung bean), and show that despite its unexceptional size (401,262 nt), the genome is unusually depauperate in repetitive DNA and "promiscuous" sequences from the chloroplast and nuclear genomes. Although Vigna lacks the large, recombinationally active repeats typical of most other seed plants, a PCR survey of its modest repertoire of short (38–297 nt) repeats nevertheless revealed evidence for recombination across all of them. A set of novel control assays showed, however, that these results could instead reflect, in part or entirely, artifacts of PCR-mediated recombination. Consequently, we recommend that other methods, especially high-depth genome sequencing, be used instead of PCR to infer patterns of plant mitochondrial recombination. The average-sized but repeat- and feature-poor mitochondrial genome of Vigna makes it ever more difficult to generalize about the factors shaping the size and sequence content of plant mitochondrial genomes

Redefining the phenotype of ALSP and AARS2 mutation-related leukodystrophy

OBJECTIVE: To provide an overview of the phenotype of 2 clinically, radiologically, and pathologically similar leukodystrophies, adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and alanyl-transfer RNA synthetase 2 mutation-related leukodystrophy (AARS2-L), and highlight key differentiating features. METHODS: ALSP and AARS2-L cases were identified from the adult-onset leukodystrophy database at our institution. In addition, cases with imaging findings were identified from a literature review. The phenotypic features were determined by combining published cases with those from our database. RESULTS: A combined total of 74 cases of ALSP and 10 cases of AARS2-L with neuroimaging data were identified. The mean age at onset was 42 years in ALSP and 26 years in AARS2-L. Cognitive and motor symptoms were the most common symptoms overall in both. Ovarian failure was exclusive to AARS2-L, present in all known female cases. Both ALSP and AARS2-L showed a confluent, asymmetric, predominantly frontoparietal, periventricular pattern of white matter disease with subcortical U-fiber sparing; pyramidal tract and corpus callosum involvement; and diffusion changes in the white matter which we have termed "deep white matter diffusion dots." Central atrophy and corpus callosal thinning were prominent in ALSP and disproportionately mild in AARS2-L when present. ALSP also occasionally showed ventricular abnormalities and calcifications in the frontal periventricular white matter, features not seen in AARS2-L. AARS2-L demonstrates white matter rarefaction which suppresses on fluid-attenuated inversion recovery MRI sequences, a feature not seen in ALSP. CONCLUSIONS: ALSP and AARS2-L share similar clinical, imaging, and pathologic characteristics with key differentiating features that we have highlighted

'Surely the most natural scenario in the world’: Representations of ‘Family’ in BBC Pre-school Television

Historically, the majority of work on British children’s television has adopted either an institutional or an audience focus, with the texts themselves often overlooked. This neglect has meant that questions of representation in British children’s television – including issues such as family, gender, class or ethnicity - have been infrequently analysed in the UK context. In this article, we adopt a primarily qualitative methodology and analyse the various textual manifestations of ‘family’, group, or community as represented in a selected number of BBC pre-school programmes. In doing so, we question the (limited amount of) international work that has examined representations of the family in children’s television, and argue that nuclear family structures do not predominate in this sphere