To the University of London Graduates' Committee.

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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

Dust in the Ionized Medium of the Galaxy: GHRS Measurements of Al III and S III

We present interstellar absorption line measurements of the ions S III and Al III towards six stars using archival Goddard High Resolution Spectrograph data. The ions Al III and S III trace heavily depleted and non-depleted elements, respectively, in ionized gas. We use the photoionization code CLOUDY to derive the ionization correction relating N(Al III)/N(S III) to the gas-phase abundance [Al/S]_i in the ionized gas. For spectral types considered here, the corrections are small and independent of the assumed ionization parameter. Using the results of these photoionization models, we find [Al/S]_i = -1.0 in the ionized gas towards three disk stars. These values of [Al/S]_i (=[Al/H]_i) imply that Al-bearing grains are present in the ionized nebulae around these stars. If the WIM of the Galaxy is photoionized by OB stars, our data for two halo stars imply [Al/S]_i = -0.4 to -0.5 in the WIM and thus the presence of dust grains containing Al in this important phase of the ISM. While photoionization appears to be the most likely origin of the ionization for Al III and S III, we cannot rule out confusion from the presence of hot, collisionally ionized gas along two sightlines. We find that [Al/S]_i in the ionized gas along the six sightlines is anti-correlated with the electron density and average sightline neutral density. The degree of grain destruction in the ionized medium of the Galaxy is not much higher than in the warm neutral medium. The existence of grains in the ionized regions studied here has important implications for the thermal balance of these regions. (Abstract Abridged)Comment: 30 pages including 8 embedded tables and 8 embedded figures. Accepted for publication in the Astrophysical Journa

Extremely metal-poor Lyman limit system at z = 2.917 toward the quasar HE 0940-1050

We report on detailed Monte Carlo inversion analysis of the Lyman limit system observed at z = 2.917 in the VLT/UVES spectrum of the quasar HE 0940-1050. Metal absorption lines of carbon and silicon in three ionization stages and numerous atomic hydrogen lines have been analyzed simultaneously. It is found that in order to match the observations, the shape of the ultraviolet background ionizing spectrum of Haardt & Madau (1996) should be modified: a spectrum with a higher intensity of the emission feature at 3 Ryd is required. It is also found that synthetic galactic spectra (or different mixtures of them with power law spectra) cannot reproduce the observations, indicating that the stellar contribution to the ionizing background is negligible at z ~= 3. For the first time a very low carbon abundance of [C/H] = -2.93+/-0.13 and the abundance ratio [Si/C] = 0.35+/-0.15 are directly measured in the Lyman limit system with N(H I) = 3.2 10^{17} cm^{-2}. If the absorber at z = 2.917 provides an example of a pristine gas enriched by the nucleosynthetic products of early generations of stars, then the measured value of [Si/C] seems to indicate that the initial mass functions for these stellar populations are constrained to intermediate masses, M_up <= 25M_solar.Comment: 7 pages, 4 figures, A&A in pres

The Sumatra subduction zone: A case for a locked fault zone extending into the mantle

A current view is that the portion of the subduction interface that remains locked in the time interval between large interplate earthquakes, hereinafter referred to as the locked fault zone (LFZ), does not extend into the mantle because serpentinization of the mantle wedge would favor stable aseismic sliding. Here, we test this view in the case of the Sumatra subduction zone where the downdip end of the LFZ can be well constrained from the pattern and rate of uplift deduced from coral growth and from GPS measurements of horizontal deformation. These geodetic data are modeled from a creeping dislocation embedded in an elastic half-space and indicate that the LFZ extends 132 ± 10/7 km from the trench, to a depth between 35 and 57 km. By combining this information with the geometry of the plate interface as constrained from two-dimensional gravimetric modeling and seismicity, we show that the LFZ extends below the forearc Moho, which is estimated to lie at a depth of ~30 km, at a horizontal distance of 110 km from the trench. So, in this particular island arc setting, the LFZ most probably extends into the mantle, implying that either the mantle is not serpentinized, or that the presence of serpentine does not necessarily imply stable sliding. From thermal modeling, the temperature at the downdip end of the LFZ is estimated to be 260 ± 100°C. This temperature seems too low for thermally activated ductile flow, so that aseismic slip is most probably due to pressure and/or temperature induced steady state brittle sliding, possibly favored by fluids released from the subducting slab

The first super-Earth Detection from the High Cadence and High Radial Velocity Precision Dharma Planet Survey

The Dharma Planet Survey (DPS) aims to monitor about 150 nearby very bright FGKM dwarfs (within 50 pc) during 2016$-$2020 for low-mass planet detection and characterization using the TOU very high resolution optical spectrograph (R$\approx$100,000, 380-900nm). TOU was initially mounted to the 2-m Automatic Spectroscopic Telescope at Fairborn Observatory in 2013-2015 to conduct a pilot survey, then moved to the dedicated 50-inch automatic telescope on Mt. Lemmon in 2016 to launch the survey. Here we report the first planet detection from DPS, a super-Earth candidate orbiting a bright K dwarf star, HD 26965. It is the second brightest star ($V=4.4$ mag) on the sky with a super-Earth candidate. The planet candidate has a mass of 8.47$\pm0.47M_{\rm Earth}$, period of $42.38\pm0.01$ d, and eccentricity of $0.04^{+0.05}_{-0.03}$. This RV signal was independently detected by Diaz et al. (2018), but they could not confirm if the signal is from a planet or from stellar activity. The orbital period of the planet is close to the rotation period of the star (39$-$44.5 d) measured from stellar activity indicators. Our high precision photometric campaign and line bisector analysis of this star do not find any significant variations at the orbital period. Stellar RV jitters modeled from star spots and convection inhibition are also not strong enough to explain the RV signal detected. After further comparing RV data from the star's active magnetic phase and quiet magnetic phase, we conclude that the RV signal is due to planetary-reflex motion and not stellar activity.Comment: 13 pages, 17 figures, Accepted for publication in MNRA

Evolutions in care, unmet needs, and research priorities in heart failure

The current treatment landscape for heart failure is predominantly stratified using ejection fraction. Established drug combinations and devices such as cardiac resynchronisation therapy are available for heart failure with reduced ejection fraction (HFrEF), but medical options for heart failure with preserved ejection fraction (HFpEF) have, until recently, been lacking.A major advance in recent years has been the discovery of effective therapies for HFpEF, including sodium-glucose co-transporter 2 (SGLT2) inhibitors and perhaps also the mineralocorticoid receptor antagonist, spironolactone. For patients with atrial fibrillation and heart failure, the benefit of rhythm control with either radiofrequency ablation or medical therapy is uncertain. Targeted therapies for the small proportion of patients with transthyretin cardiac amyloidosis are available, while antifibrotics seem promising for a larger proportion of patients.For patients with HFrEF, additional treatment options have emerged in the past 10 years. The angiotensin receptor–neprilysin inhibitor (ARNI) combination sacubitril–valsartan and SGLT-2 inhibitors reduce mortality and improve life expectancy in symptomatic patients with HFrEF and at least mildly elevated plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP). The oral soluble guanylate cyclase stimulator vericiguat and cardiac myosin activator omecamtiv mecarbil are not yet licensed in the UK but may provide further treatment options, perhaps in more select groups of patients.Whether all patients with a prior diagnosis of HFrEF who are now in heart failure remission should continue all therapies at maximum tolerated dose indefinitely remains a dilemma. Individualised de-escalation of therapy remains controversial due to the risk of relapse but is occasionally trialled, particularly in patients with a triggering factor such as pregnancy. The ultimate aim is a personalised treatment plan—based on disease phenotype and trajectory—that minimises the risk of relapse and maximises the individual’s quality of life

Evolutions in care, unmet needs, and research priorities in heart failure

The current treatment landscape for heart failure is predominantly stratified using ejection fraction. Established drug combinations and devices such as cardiac resynchronisation therapy are available for heart failure with reduced ejection fraction (HFrEF), but medical options for heart failure with preserved ejection fraction (HFpEF) have, until recently, been lacking.A major advance in recent years has been the discovery of effective therapies for HFpEF, including sodium-glucose co-transporter 2 (SGLT2) inhibitors and perhaps also the mineralocorticoid receptor antagonist, spironolactone. For patients with atrial fibrillation and heart failure, the benefit of rhythm control with either radiofrequency ablation or medical therapy is uncertain. Targeted therapies for the small proportion of patients with transthyretin cardiac amyloidosis are available, while antifibrotics seem promising for a larger proportion of patients.For patients with HFrEF, additional treatment options have emerged in the past 10 years. The angiotensin receptor–neprilysin inhibitor (ARNI) combination sacubitril–valsartan and SGLT-2 inhibitors reduce mortality and improve life expectancy in symptomatic patients with HFrEF and at least mildly elevated plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP). The oral soluble guanylate cyclase stimulator vericiguat and cardiac myosin activator omecamtiv mecarbil are not yet licensed in the UK but may provide further treatment options, perhaps in more select groups of patients.Whether all patients with a prior diagnosis of HFrEF who are now in heart failure remission should continue all therapies at maximum tolerated dose indefinitely remains a dilemma. Individualised de-escalation of therapy remains controversial due to the risk of relapse but is occasionally trialled, particularly in patients with a triggering factor such as pregnancy. The ultimate aim is a personalised treatment plan—based on disease phenotype and trajectory—that minimises the risk of relapse and maximises the individual’s quality of life