How to teach fully illiterate adults to read.

About 750 million adults (15%) worldwide lack any literacy skills, most because they lack adequate learning opportunities (UNESCO, 2016). In this chapter, we discuss how to teach to read to such people. We first examine scientific evidence suggesting that literacy acquisition does not radically differ as a function of age of acquisition. We then discuss the data relevant for designing effective methods aimed at teaching literacy to fully illiterate adults. We argue that the available adult data confirm those relative to teaching methods and learning processes that have been gathered on literacy acquisition by children. On the basis of those works we propose principles that should underlie any method aiming at rapidly developing basic literacy skills. Lastly, we present evidence (Kolinsky, Leite, Carvalho, Franco, & Morais, submitted) suggesting that implementing these principles does indeed allow teaching illiterate adults to decode words and pseudo-words in a very short period of time

A phase I dose-escalation study of enzalutamide in combination with the AKT inhibitor AZD5363 (capivasertib) in patients with metastatic castration-resistant prostate cancer.

Background Activation of the PI3K/AKT/mTOR pathway through loss of phosphatase and tensin homolog (PTEN) occurs in approximately 50% of patients with metastatic castration-resistant prostate cancer (mCRPC). Recent evidence suggests that combined inhibition of the androgen receptor (AR) and AKT may be beneficial in mCRPC with PTEN loss.Patients and methods mCRPC patients who previously failed abiraterone and/or enzalutamide, received escalating doses of AZD5363 (capivasertib) starting at 320 mg twice daily (b.i.d.) given 4 days on and 3 days off, in combination with enzalutamide 160 mg daily. The co-primary endpoints were safety/tolerability and determining the maximum tolerated dose and recommended phase II dose; pharmacokinetics, antitumour activity, and exploratory biomarker analysis were also evaluated.Results Sixteen patients were enrolled, 15 received study treatment and 13 were assessable for dose-limiting toxicities (DLTs). Patients were treated at 320, 400, and 480 mg b.i.d. dose levels of capivasertib. The recommended phase II dose identified for capivasertib was 400 mg b.i.d. with 1/6 patients experiencing a DLT (maculopapular rash) at this level. The most common grade ≥3 adverse events were hyperglycemia (26.7%) and rash (20%). Concomitant administration of enzalutamide significantly decreased plasma exposure of capivasertib, though this did not appear to impact pharmacodynamics. Three patients met the criteria for response (defined as prostate-specific antigen decline ≥50%, circulating tumour cell conversion, and/or radiological response). Responses were seen in patients with PTEN loss or activating mutations in AKT, low or absent AR-V7 expression, as well as those with an increase in phosphorylated extracellular signal-regulated kinase (pERK) in post-exposure samples.Conclusions The combination of capivasertib and enzalutamide is tolerable and has antitumour activity, with all responding patients harbouring aberrations in the PI3K/AKT/mTOR pathway.Clinical trial number NCT02525068

Effect on Overall Survival of Locoregional Treatment in a Cohort of De Novo Metastatic Prostate Cancer Patients: A Single Institution Retrospective Analysis From the Royal Marsden Hospital.

Background The optimal management of the primary tumor in metastatic at diagnosis (M1) prostate cancer (PCa) patients is not yet established. We retrospectively evaluated the effect of locoregional treatment (LRT) on overall survival (OS) hypothesizing that this could improve outcome through better local disease control and the induction of an antitumor immune response (abscopal effect).Patients and methods M1 at diagnosis PCa patients referred to the Prostate Targeted Therapy Group at the Royal Marsden between June 2003 and December 2013 were identified. LRT was defined as either surgery, radiotherapy (RT) or transurethral prostatectomy (TURP) administered to the primary tumor at any time point from diagnosis to death. Kaplan-Meier analyses generated OS data. The association between LRT and OS was evaluated in univariate (UV) and multivariate (MV) Cox regression models.Results Overall 300 patients were identified; 192 patients (64%) experienced local symptoms at some point during their disease course; 72 patients received LRT (56.9% TURP, 52.7% RT). None of the patients were treated with prostatectomy. LRT was more frequently performed in patients with low volume disease (35.4% vs. 16.2%; P < .001), lower prostate-specific antigen (PSA) level at diagnosis (median PSA: 75 vs. 184 ng/mL; P = .005) and local symptoms (34.2% vs. 4.8%; P < .001). LRT was associated in UV and MV analysis with longer OS (62.1 vs. 55.8 months; hazard ratio [HR], 0.74; P = .044), which remained significant for RT (69.4 vs. 55.1 months; HR, 0.54; P = .002) but not for TURP. RT was associated with better OS independent of disease volume at diagnosis.Conclusion These data support the conduct of randomized phase III trials to evaluate the benefit of local control in patients with M1 disease at diagnosis

Moho depth across the Trans-European Suture Zone from P-and S-receiver functions

The Mohorovicic discontinuity, Moho for short, which marks the boundary between crust and mantle, is the main first-order structure within the lithosphere. Geodynamics and tectonic evolution determine its depth level and properties. Here, we present a map of the Moho in central Europe across the Teisseyre-Tornquist Zone, a region for which a number of previous studies are available. Our results are based on homogeneous and consistent processing of P- and S-receiver functions for the largest passive seismological data set in this region yet, consisting of more than 40 000 receiver functions from almost 500 station. Besides, we also provide new results for the crustal Vp/Vs ratio for the whole area. Our results are in good agreement with previous, more localized receiver function studies, as well as with the interpretation of seismic profiles, while at the same time resolving a higher level of detail than previous maps covering the area, for example regarding the Eifel Plume region, Rhine Graben and northern Alps. The close correspondence with the seismic data regarding crustal structure also increases confidence in use of the data in crustal corrections and the imaging of deeper structure, for which no independent seismic information is available. In addition to the pronounced, stepwise transition from crustal thicknesses of 30km in Phanerozoic Europe to more than 45 beneath the East European Craton, we can distinguish other terrane boundaries based on Moho depth as well as average crustal Vp/Vsratio and Moho phase amplitudes. The terranes with distinct crustal properties span a wide range of ages, from Palaeoproterozoic in Lithuania to Cenozoic in the Alps, reflecting the complex tectonic history of Europe. Crustal thickness and properties in the study area are also markedly influenced by tectonic overprinting, for example the formation of the Central European Basin System, and the European Cenozoic Rift System. In the areas affected by Cenozoic rifting and volcanism, thinning of the crust corresponds to lithospheric updoming reported in recent surface wave and S-receiver function studies, as expected for thermally induced deformation. The same correlation applies for crustal thickening, not only across the Trans-European Suture Zone, but also within the southern part of the Bohemian Massif. A high Poisson’s ratio of 0.27 is obtained for the craton, which is consistent with a thick mafic lower crust. In contrast, we typically find Poisson’s ratios around 0.25 for Phanerozoic Europe outside of deep sedimentary basins. Mapping of the thickness of the shallowest crustal layer, that is low-velocity sediments or weathered rock, indicates values in excess of 6km for the most pronounced basins in the study area, while thicknesses of less than 4km are found within the craton, central Germany and most of the Czech Republic.Peer reviewe

The Effect of Retirement on Cognition: Evidence from the Irish Marriage Bar

This study empirically investigates the relationship between retirement du- ration and cognition among older Irish women using microdata collected in the third wave of The Irish Longitudinal Study on Ageing. Ordinary least squares (OLS) regression estimates indicate that the longer an individual has been retired, the lower the cognitive functioning, with other factors thought to affect cognition held constant (e.g., age, education, and early-life socioeconomic conditions). However, retirement is potentially endogenous with respect to cognition because cognition may affect deci- sions relating to retiring. If so, the OLS estimates will be biased. To test for this possibility, instrumental variable (IV) estimation is used. This method requires an IV that is highly correlated with retirement duration but not correlated with cognition. The instrument used in this study is based on the so-called marriage bar, the legal require- ment that women leave paid employment upon getting married, which took effect in Ireland in the 1930s and was abolished only in the 1970s. The IV regression estimates, along with formal statistical tests, provide no evidence in support of the view that cognition affects retirement decisions. The finding of a small negative effect of retirement duration on cognition is robust to alternative empirical specifications. These findings are discussed in the wider context of the effects of work-like and work-related activities on cognition