Semantic variant primary progressive aphasia: Practical recommendations for treatment from 20 years of behavioural research

People with semantic variant primary progressive aphasia (svPPA) present with a char-acteristic progressive breakdown of semantic knowledge. There are currently no pharmacological interventions to cure or slow svPPA, but promising behavioural approaches are increasingly reported. This article offers an overview of the last two decades of research into interventions to support language in people with svPPA including recommendations for clinical practice and future research based on the best available evidence. We offer a lay summary in English, Spanish and French for education and dissemination purposes. This paper discusses the implications of right-versus left-predominant atrophy in svPPA, which naming therapies offer the best outcomes and how to capitalise on preserved long-term memory systems. Current knowledge regarding the maintenance and generalisation of language therapy gains is described in detail along with the development of compensatory approaches and educational and support group programmes. It is concluded that there is evidence to support an integrative framework of treatment and care as best practice for svPPA. Such an approach should combine rehabilitation interventions addressing the language impairment, compensatory approaches to support activities of daily living and provision of education and support within the context of dementia

The Star Cluster Population of M51: II. Age distribution and relations among the derived parameters

We use archival {\it Hubble Space Telescope} observations of broad-band images from the ultraviolet (F255W-filter) through the near infrared (NICMOS F160W-filter) to study the star cluster population of the interacting spiral galaxy M51. We obtain age, mass, extinction, and effective radius estimates for 1152 star clusters in a region of $\sim 7.3 \times 8.1$ kpc centered on the nucleus and extending into the outer spiral arms. In this paper we present the data set and exploit it to determine the age distribution and relationships among the fundamental parameters (i.e. age, mass, effective radius). Using this dataset we find: {\it i}) that the cluster formation rate seems to have had a large increase $\sim$ 50-70 Myr ago, which is coincident with the suggested {\it second passage} of its companion, NGC 5195, {\it ii}) a large number of extremely young ($<$ 10 Myr) star clusters, which we interpret as a population of unbound clusters of which a large majority will disrupt within the next $\sim$10 Myr, and {\it iii)} that the distribution of cluster sizescan be well approximated by a power-law with exponent, $-\eta = -2.2 \pm 0.2$, which is very similar to that of Galactic globular clusters, indicating that cluster disruption is largely independent of cluster radius. In addition, we have used this dataset to search for correlations among the derived parameters. In particular, we do not find any strong trends between the age and mass, mass and effective radius, nor between the galactocentric distance and effective radius. There is, however, a strong correlation between the age of a cluster and its extinction, with younger clusters being more heavily reddened than older clusters.Comment: 21 pages, 20 figures, accepted A&

The Abundances of Nitrogen and Oxygen in Damped Lyman Alpha Systems

We take a fresh look at the abundance of nitrogen in DLAs with oxygen abundances between 1/10 and 1/100 of solar. This is a metallicity regime poorly sampled in the local universe and where QSO absorbers may hold clues to both the nucleosynthetic origin of N and the chemical evolution of high redshift galaxies. We combine new VLT UVES observations with others from the literature to form a sample of 10 DLAs in which the abundances of N and of one of the two alpha-capture elements O or S have been measured. We confirm earlier reports that the (N/O) ratio exhibits a larger range of values than other ratios of heavy elements in DLAs; however, all 10 DLAs fall in the region of the (N/O) vs. (O/H) plot delimited by the primary and secondary levels of nitrogen production. Our results provide empirical evidence in support of the proposal that intermediate mass stars (with masses less than 7 solar masses) are the main source of primary nitrogen, so that its release into the ISM lags behind that of oxygen, which is produced by Type II SNae. A high proportion (40%) of the DLAs in our sample have apparently not yet attained the full primary level of N enrichment; this finding may be an indication that the metallicity regime we are studying preferentially picks out galaxies which have only recently condensed out of the IGM and begun forming stars. Alternatively, the delay in the release of N following an episode of star formation may increase with decreasing metallicity, if stars of progressively lower masses than 4 solar masses can synthesize N in their hotter interiors.Comment: 17 pages, LaTeX, 7 Postscript Figures. Accepted for publication in Astronomy & Astrophysic

Distinct Abundance Patterns in Multiple Damped Ly-alpha Galaxies: Evidence for Truncated Star Formation?

(abridged) Following our previous work on metal abundances of a double damped Ly-alpha system with a line-of-sight separation ~2000 km/s (Ellison & Lopez 2001), we present VLT UVES abundances of 3 new systems spanning a total of \~6000 km/s at z~2.5 toward the southern QSO CTQ247. These abundances are supplemented with echelle observations of another `double' damped Ly-alpha system in the literature. We propose a definition in terms of velocity shift of the sub-class 'multiple damped Ly-alpha system', which is motivated by its possible connection with large-scale structure. We find that the abundance ratio alpha/Fe is systematically low in multiple systems compared with single systems, and with a small scatter. The same behavior is found in 2 more single DLA systems taken from the literature that show evidence of belonging to a galaxy group. After a careful investigation of possible sources of systematic errors, we conclude that the low alpha/Fe ratios in multiple DLAs have a nucleosynthetic origin. We suggest that they could be explained by reduced star formation in multiple damped Ly-alpha systems, possibly due to environmental effects.Comment: in press at A&

“We have been magnified for years - now you are under the microscope!": Co-researchers with learning disabilities created an online survey to challenge public understanding of learning disabilities

Public attitudes towards learning disabilities (LDs) are generally reported as positive, inclusive and empathetic. However, these findings do not reflect the lived experiences of people with LDs. To shed light on this disparity, a team of co-researchers with LDs created the first online survey to challenge public understanding of LDs, asking questions in ways that are important to them and represent how they see themselves. Here, we describe and evaluate the process of creating an accessible survey platform and an online survey in a research team consisting of academic and non-academic professionals with and without LDs or autism. Through this inclusive research process, the co-designed survey met the expectations of the co-researchers and was well-received by the initial survey respondents. We reflect on the co-researchers’ perspectives following the study completion, and consider the difficulties and advantages we encountered deploying such approaches and their potential implications on future survey data analysis

The Connection between a Lyman Limit System, a very strong OVI Absorber, and Galaxies at z~0.203

With a column density log N(OVI) = 14.95+/-0.05, the OVI absorber at z_abs~0.2028 observed toward the QSO PKS0312-77 (z_em=0.223) is the strongest yet detected at z<0.5. At nearly identical redshift (z_abs=0.2026), we also identify a Lyman limit system (LLS, log N(HI)=18.22). Combining FUV and NUV spectra of PKS0312-77 with optical observations of galaxies in the surrounding field (15'x32'), we present an analysis of these absorbers and their connection to galaxies. The observed OI/HI ratio and photoionization modelling of other low ions indicate the metallicity of the LLS is [Z/H]_LLS=-0.6 and that the LLS is nearly 100% photoionized. In contrast, the OVI-bearing gas is collisionally ionized at T~(3-10)x10^5 K as derived from the high-ion ratios and profile broadenings. Our galaxy survey reveals 13 (0.3<L/L*<1.6) galaxies at \rho<2 h^{-1}_{70} Mpc and |\delta v|<1100 km/s from the LLS. A probable origin for the LLS is debris from a galaxy merger, which led to a 0.7L* galaxy ([Z/H]_gal=+0.15) at\rho~38 h^{-1}_{70} kpc. Outflow from this galaxy may also be responsible for the supersolar ([Z/H]_abs=+0.15), fully ionized absorber at z_abs=0.2018 (-190 km/s from the LLS). The hot OVI absorber likely probes coronal gas about the 0.7 L* galaxy and/or (~0.1 keV) intragroup gas of a spiral-rich system. The association of other strong OVI absorbers with LLS suggests they trace galactic and not intergalactic structures.Comment: Accepted for publication in the Ap

Petrophysical, Geochemical, and Hydrological Evidence for Extensive Fracture-Mediated Fluid and Heat Transport in the Alpine Fault's Hanging-Wall Damage Zone

Fault rock assemblages reflect interaction between deformation, stress, temperature, fluid, and chemical regimes on distinct spatial and temporal scales at various positions in the crust. Here we interpret measurements made in the hanging-wall of the Alpine Fault during the second stage of the Deep Fault Drilling Project (DFDP-2). We present observational evidence for extensive fracturing and high hanging-wall hydraulic conductivity (∼10−9 to 10−7 m/s, corresponding to permeability of ∼10−16 to 10−14 m2) extending several hundred meters from the fault's principal slip zone. Mud losses, gas chemistry anomalies, and petrophysical data indicate that a subset of fractures intersected by the borehole are capable of transmitting fluid volumes of several cubic meters on time scales of hours. DFDP-2 observations and other data suggest that this hydrogeologically active portion of the fault zone in the hanging-wall is several kilometers wide in the uppermost crust. This finding is consistent with numerical models of earthquake rupture and off-fault damage. We conclude that the mechanically and hydrogeologically active part of the Alpine Fault is a more dynamic and extensive feature than commonly described in models based on exhumed faults. We propose that the hydrogeologically active damage zone of the Alpine Fault and other large active faults in areas of high topographic relief can be subdivided into an inner zone in which damage is controlled principally by earthquake rupture processes and an outer zone in which damage reflects coseismic shaking, strain accumulation and release on interseismic timescales, and inherited fracturing related to exhumation

Speech production deficits in early readers: predictors of risk

Speech problems and reading disorders are linked, suggesting that speech problems may potentially be an early marker of later difficulty in associating graphemes with phonemes. Current norms suggest that complete mastery of the production of the consonant phonemes in English occurs in most children at around 6–7 years. Many children enter formal schooling (kindergarten) around 5 years of age with near-adult levels of speech production. Given that previous research has shown that speech production abilities and phonological awareness skills are linked in preschool children, we set out to examine whether this pattern also holds for children just beginning to learn to read, as suggested by the critical age hypothesis. In the present study, using a diverse sample, we explored whether expressive phonological skills in 92 5-year-old children at the beginning and end of kindergarten were associated with early reading skills. Speech errors were coded according to whether they were developmentally appropriate, position within the syllable, manner of production of the target sounds, and whether the error involved a substitution, omission, or addition of a speech sound. At the beginning of the school year, children with significant early reading deficits on a predictively normed test (DIBELS) made more speech errors than children who were at grade level. Most of these errors were typical of kindergarten children (e.g., substitutions involving fricatives), but reading-delayed children made more of these errors than children who entered kindergarten with grade level skills. The reading-delayed children also made more atypical errors, consistent with our previous findings about preschoolers. Children who made no speech errors at the beginning of kindergarten had superior early reading abilities, and improvements in speech errors over the course of the year were significantly correlated with year-end reading skills. The role of expressive vocabulary and working memory were also explored, and appear to account for some of these findings

Metabolic Network Topology Reveals Transcriptional Regulatory Signatures of Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) is a disorder characterized by both insulin resistance and impaired insulin secretion. Recent transcriptomics studies related to T2DM have revealed changes in expression of a large number of metabolic genes in a variety of tissues. Identification of the molecular mechanisms underlying these transcriptional changes and their impact on the cellular metabolic phenotype is a challenging task due to the complexity of transcriptional regulation and the highly interconnected nature of the metabolic network. In this study we integrate skeletal muscle gene expression datasets with human metabolic network reconstructions to identify key metabolic regulatory features of T2DM. These features include reporter metabolites—metabolites with significant collective transcriptional response in the associated enzyme-coding genes, and transcription factors with significant enrichment of binding sites in the promoter regions of these genes. In addition to metabolites from TCA cycle, oxidative phosphorylation, and lipid metabolism (known to be associated with T2DM), we identified several reporter metabolites representing novel biomarker candidates. For example, the highly connected metabolites NAD+/NADH and ATP/ADP were also identified as reporter metabolites that are potentially contributing to the widespread gene expression changes observed in T2DM. An algorithm based on the analysis of the promoter regions of the genes associated with reporter metabolites revealed a transcription factor regulatory network connecting several parts of metabolism. The identified transcription factors include members of the CREB, NRF1 and PPAR family, among others, and represent regulatory targets for further experimental analysis. Overall, our results provide a holistic picture of key metabolic and regulatory nodes potentially involved in the pathogenesis of T2DM

Lattice QCD and Particle Physics

Contribution from the USQCD Collaboration to the Proceedings of the US Community Study on the Future of Particle Physics (Snowmass 2021).Comment: 27 pp. main text, 4 pp. appendices, 30 pp. reference