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

Thymidine Phosphorylase/β-tubulin III expressions predict the response in Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel

<p>Abstract</p> <p>Background</p> <p>To assess the role of Thymidine Phosphorylase and β-tubulin III in clinical outcome of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel.</p> <p>Methods</p> <p>The clinical data and tumor biopsies prior treatment from 33 advanced gastric cancer patients receiving capecitabine plus paclitaxel (cohort 1, experimental group) and 18 patients receiving capecitabine plus cisplatin (cohort 2, control group) in Beijing Cancer Hospital from July 2003 to December 2008 were retrospectively collected and analyzed for Thymidine Phosphorylase and β-tubulin III expressions by immunohistochemistry. The relationships between expressions of biomarkers and response or survival were determined by statistical analysis.</p> <p>Results</p> <p>The median age of 51 patients was 57 years (range, 27-75) with male 34 and female 17, and the response rate, median progression-free survival and overall survival were 43.1%, 120d and 265d. Among cohort 1, the response rate, median progression-free survival and overall survival in β-tubulin III positive (n = 22) and negative patients (n = 11) were 36.4%/72.7% (positive vs negative, <it>P </it>= 0.049), 86d/237d (<it>P </it>= 0.046) and 201d/388d (<it>P </it>= 0.029), respectively; the response rate (87.5% vs 14.3%, <it>P </it>= 0.01) and median progression-free survival (251d vs 84d, <it>P </it>= 0.003) in Thymidine Phosphorylase positive & β-tubulin III negative patients (n = 8) were also significantly higher than those in Thymidine Phosphorylase negative & β-tubulin III positive patients (n = 7). There was no correlation between β-tubulin III expression and response or survival among cohort 2 (n = 18).</p> <p>Conclusions</p> <p>In Chinese advanced gastric cancer, Thymidine Phosphorylase positive & β-tubulin III negative might predict response and prognosis to capecitabine plus paclitaxel chemotherapy. Further prospective evaluation in large samples should be performed to confirm these preliminary findings.</p

Integration of Consonant and Pitch Processing as Revealed by the Absence of Additivity in Mismatch Negativity

Consonants, unlike vowels, are thought to be speech specific and therefore no interactions would be expected between consonants and pitch, a basic element for musical tones. The present study used an electrophysiological approach to investigate whether, contrary to this view, there is integrative processing of consonants and pitch by measuring additivity of changes in the mismatch negativity (MMN) of evoked potentials. The MMN is elicited by discriminable variations occurring in a sequence of repetitive, homogeneous sounds. In the experiment, event-related potentials (ERPs) were recorded while participants heard frequently sung consonant-vowel syllables and rare stimuli deviating in either consonant identity only, pitch only, or in both dimensions. Every type of deviation elicited a reliable MMN. As expected, the two single-deviant MMNs had similar amplitudes, but that of the double-deviant MMN was also not significantly different from them. This absence of additivity in the double-deviant MMN suggests that consonant and pitch variations are processed, at least at a pre-attentive level, in an integrated rather than independent way. Domain-specificity of consonants may depend on higher-level processes in the hierarchy of speech perception

Prostate-specific Antigen Decline After 4 Weeks of Treatment with Abiraterone Acetate and Overall Survival in Patients with Metastatic Castration-resistant Prostate Cancer.

Background The availability of multiple new treatments for metastatic castration-resistant prostate cancer (mCRPC) mandates earlier treatment switches in the absence of a response. A decline in prostate-specific antigen (PSA) is widely used to monitor treatment response, but is not validated as an intermediate endpoint for overall survival (OS).Objective To evaluate the association between early PSA decline and OS following abiraterone acetate (AA) treatment.Design, setting, and participants We identified mCRPC patients treated with AA before or after docetaxel at the Royal Marsden NHS Foundation Trust between 2006 and 2014. Early PSA decline was defined as a 30% decrease in PSA at 4 wk relative to baseline, and early PSA rise as a 25% increase.Outcome measurements and statistical analysis Association with OS was analyzed using multivariate Cox regression and log-rank analyses. Spearman's rho correlation coefficient (r) was calculated to evaluate the association between PSA changes at 4 wk and 12 wk.Results and limitations There were 274 patients eligible for this analysis. A 30% PSA decline at 4 wk was associated with longer OS (25.8 vs 15.1 mo; hazard ratio [HR] 0.47, p<0.001), and a 25% PSA rise at 4 wk with shorter OS (15.1 vs 23.8 mo; HR 1.7, p=0.001) in both univariate and multivariable models. The percentage PSA decline at 4 wk was significantly correlated with the percentage PSA change at 12 wk (r=0.82; p<0.001). Patients achieving a 30% PSA decline at 4 wk were 11.7 times more likely to achieve a 50% PSA decrease at 12 wk (sensitivity 90.9%, specificity 79.4%). Limitations include the retrospective design of this analysis.Conclusions Patients not achieving 30% PSA decline after 4 wk of AA have a lower likelihood of achieving PSA response at 12 wk and significantly inferior OS. Prospective multicentre validation studies are needed to confirm these findings.Patient summary Prostate-specific antigen (PSA) is commonly used to evaluate response to treatment in metastatic castration-resistant prostate cancer. Expert recommendations discourage reliance on PSA changes earlier than 12 wk after treatment initiation. Our data suggest that early PSA changes are associated with survival in patients receiving abiraterone acetate

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