A causal framework for cross-cultural generalizability

Behavioral researchers increasingly recognize the need for more diverse samples that capture the breadth of human experience. Current attempts to establish generalizability across populations focus on threats to validity, constraints on generalization, and the accumulation of large, cross-cultural data sets. But for continued progress, we also require a framework that lets us determine which inferences can be drawn and how to make informative cross-cultural comparisons. We describe a generative causal-modeling framework and outline simple graphical criteria to derive analytic strategies and implied generalizations. Using both simulated and real data, we demonstrate how to project and compare estimates across populations and further show how to formally represent measurement equivalence or inequivalence across societies. We conclude with a discussion of how a formal framework for generalizability can assist researchers in designing more informative cross-cultural studies and thus provides a more solid foundation for cumulative and generalizable behavioral research

Progressive Supranuclear Palsy and Corticobasal Degeneration: Pathophysiology and Treatment Options

There are currently no disease-modifying treatments for progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD), and no approved pharmacological or therapeutic treatments that are effective in controlling their symptoms. The use of most pharmacological treatment options are based on experience in other disorders or from non-randomized historical controls, case series, or expert opinion. Levodopa may provide some improvement in symptoms of Parkinsonism (specifically bradykinesia and rigidity) in PSP and CBD; however, evidence is conflicting and where present, benefits are often negligible and short lived. In fact, “poor” response to levodopa forms part of the NINDS-SPSP criteria for the diagnosis of PSP and consensus criteria for the diagnosis of CBD (Lang Mov Disord. 20 Suppl 1:S83–91, 2005; Litvan et al. Neurology. 48:119–25, 1997; Armstrong et al. Neurology. 80(5):496–503, 2013). There is some evidence that intrasalivery gland botulinum toxin is useful in managing problematic sialorrhea and that intramuscular botulinum toxin and baclofen are helpful in reducing dystonia, including blepharospasm. Benzodiazepines may also be useful in managing dystonia. Myoclonus may be managed using levetiracetam and benzodiazepines. Pharmacological agents licensed for Alzheimer’s disease (such as acetylcholinesterase inhibitors and N-Methyl-D-aspartate receptor antagonists) have been used off-label in PSP, CBD, and other tauopathies with the aim of improving cognition; however, there is limited evidence that they are effective and risk of adverse effects may outweigh benefits. The use of atypical antipsychotics for behavioural symptoms is not recommended in the elderly or those with demetia associated conditions and most antipsychotics will worsen Parkinsonism. Antidepressants may be useful for behavioral symptoms and depression but are often poorly tolerated due to adverse effects. In the absence of an effective drug treatment to target the underlying cause of CBD and PSP, management should focus on optimizing quality of life, relieving symptoms and assisting patients with their activities of daily living (ADL). Patients should be managed by a multidisciplinary team consisting of neurologists, physiotherapists (PT), occupational therapists (OT), speech and language therapists (SALT), dieticians, ophthalmologists, psychologists, and palliative care specialists

A novel A781V mutation in the CSF1R gene causes hereditary diffuse leucoencephalopathy with axonal spheroids

We report a family with a novel CSF1R mutation causing hereditary diffuse leucoencephalopathy with axonal spheroids. Family members presented with neuropsychiatric and behavioural symptoms, with subsequent development of motor symptoms and gait disturbance. MRI brain showed extensive white matter change with a frontal predominance and associated atrophy in two members of the family. Genetic testing revealed a novel mutation c.2342C>T (p.A781V) in the CSF1R gene in two brothers of the family. This report highlights the difficulties in diagnosing HDLS and discusses the indications for testing for mutations in the CSF1R gene

Identification of Quantitative Trait Loci Affecting Female Reproductive Traits in a Multigeneration Meishan-White Composite Swine Population

A multigeneration crossbred Meishan- White composite resource population was used to identify quantitative trait loci (QTL) for age at first estrus (AP) and the components of litter size: ovulation rate (OR; number of ova released in an estrous period) and uterine capacity (UC). The population was established by reciprocally mating Meishan (ME) and White composite (WC) pigs. Resultant F1 females were mated to either ME or WC boars to produce backcross progeny (BC) of either ¾ WC ¼ ME or ¼ WC ¾ ME. To produce the next generation (F3) , ¾ WC ¼ ME animals were mated to ¼ WC ¾ ME animals yielding half-blood (½ WC ½ ME) progeny. A final generation (F4) was produced by inter se mating F3 animals. Measurements for AP and OR were recorded on 101 BC, 389 F3, and 110 F4 gilts, and UC data were from 101 BC and 110 F4 first parity litters. A genomic scan was conducted with markers (n = 157) spaced &#;20 cM apart. All parental, F1, BC, and F4 animals but only 84 F3 animals were genotyped and included in this study. The QTL analysis fitted a QTL at 1-cM intervals throughout the genome, and QTL effects were tested using approximate genome-wide significance levels. For OR, a significant (E[false positive] \u3c .05) QTL was detected on chromosome 8, suggestive (E[false positive] \u3c 1.0) QTL were detected on chromosomes 3 and 10, and two additional regions were detected that may possess a QTL (E[false positive] \u3c 2.0) on chromosomes 9 and 15. Two regions possessed suggestive evidence for QTL affecting AP on chromosomes 1 and 10, and one suggestive region on chromosome 8 was identified for UC. Further analyses of other populations of swine are necessary to determine the extent of allelic variation at the identified QTL

Automated profiling of spontaneous speech in primary progressive aphasia and behavioral-variant frontotemporal dementia: An approach based on usage-frequency

Language production provides important markers of neurological health. One feature of impairments of language and cognition, such as those that occur in stroke aphasia or Alzheimer's disease, is an overuse of high frequency, “familiar” expressions. We used computerized analysis to profile narrative speech samples from speakers with variants of frontotemporal dementia (FTD), including subtypes of primary progressive aphasia (PPA). Analysis was performed on language samples from 29 speakers with semantic variant PPA (svPPA), 25 speakers with logopenic variant PPA (lvPPA), 34 speakers with non-fluent variant PPA (nfvPPA), 14 speakers with behavioral variant FTD (bvFTD) and 20 older normal controls (NCs). We used frequency and collocation strength measures to determine use of familiar words and word combinations. We also computed word counts, content word ratio and a combination ratio, a measure of the degree to which the individual produces connected language. All dementia subtypes differed significantly from NCs. The most discriminating variables were word count, combination ratio, and content word ratio, each of which distinguished at least one dementia group from NCs. All participants with PPA, but not participants with bvFTD, produced significantly more frequent forms at the level of content words, word combinations, or both. Each dementia group differed from the others on at least one variable, and language production variables correlated with established behavioral measures of disease progression. A machine learning classifier, using narrative speech variables, achieved 90% accuracy when classifying samples as NC or dementia, and 59.4% accuracy when matching samples to their diagnostic group. Automated quantification of spontaneous speech in both language-led and non-language led dementias, is feasible. It allows extraction of syndromic profiles that complement those derived from standardized tests, warranting further evaluation as candidate biomarkers. Inclusion of frequency-based language variables benefits profiling and classification

Understanding adhesion at as-deposited interfaces from ab initio thermodynamics of deposition growth: thin-film alumina on titanium carbide

We investigate the chemical composition and adhesion of chemical vapour deposited thin-film alumina on TiC using and extending a recently proposed nonequilibrium method of ab initio thermodynamics of deposition growth (AIT-DG) [Rohrer J and Hyldgaard P 2010 Phys. Rev. B 82 045415]. A previous study of this system [Rohrer J, Ruberto C and Hyldgaard P 2010 J. Phys.: Condens. Matter 22 015004] found that use of equilibrium thermodynamics leads to predictions of a non-binding TiC/alumina interface, despite the industrial use as a wear-resistant coating. This discrepancy between equilibrium theory and experiment is resolved by the AIT-DG method which predicts interfaces with strong adhesion. The AIT-DG method combines density functional theory calculations, rate-equation modelling of the pressure evolution of the deposition environment and thermochemical data. The AIT-DG method was previously used to predict prevalent terminations of growing or as-deposited surfaces of binary materials. Here we extent the method to predict surface and interface compositions of growing or as-deposited thin films on a substrate and find that inclusion of the nonequilibrium deposition environment has important implications for the nature of buried interfaces.Comment: 8 pages, 6 figures, submitted to J. Phys.: Condens. Matte