Explore the vast range of titles available.

PIM and PI3K/mTOR pathways are often dysregulated in prostate cancer, and may lead to decreased survival, increased metastasis and invasion. The pathways are heavily interconnected and act on a variety of common effectors that can lead to the development of resistance to drug inhibitors. Most current treatments exhibit issues with toxicity and resistance. We investigated the novel multikinase PIM/PI3K/mTOR inhibitor, AUM302, versus a combination of the PIM inhibitor, AZD-1208, and the PI3K/mTOR inhibitor BEZ235 (Dactolisib) to determine their impact on mRNA and phosphoprotein expression, as well as their functional efficacy. We have determined that around 20% of prostate cancer patients overexpress the direct targets of these drugs, and this cohort are more likely to have a high Gleason grade tumour (≥ Gleason 8). A co-targeted inhibition approach offered broader inhibition of genes and phosphoproteins in the PI3K/mTOR pathway, when compared to single kinase inhibition. The preclinical inhibitor AUM302, used at a lower dose, elicited a comparable or superior functional outcome compared with combined AZD-1208 + BEZ235, which have been investigated in clinical trials, and could help to reduce treatment toxicity in future trials. We believe that a co-targeting approach is a viable therapeutic strategy that should be developed further in pre-clinical studies.

Social networks are becoming very prominent in educational discourse. The discourse centers on the role of social media and its utility in the teaching and learning environment. Several arguments have been made to support its use because they are highly collaborative, easily accessible, and provide opportunities to embed a variety of Web 2.0 tools such as blogs, wikis, and online chats. However, there is a dearth in research on teacher use of educational social networking sites (SNS) in Trinidad and Tobago. The purpose of this study was to explore how 35 secondary school teachers in Trinidad and Tobago participated in an educational online social networking site. This study utilized a mixed methods exploratory approach and allowed for the use of online data capture together with questionnaires and interviews. Combined data analysis revealed five different levels of site participation, with most teachers adopting the role of content consumer rather than of content producer. Barriers to participation were time, motivation, technology, and usability. The designed social networking site allowed teachers to make public their discourse on their practice while connecting with colleagues from other schools. The study was qualitative dominant, with the mixed methods research approach allowing for deeper exploration of teachers’ participation on this social networking website, and was justified by the newness and transient nature of data from social networking websites.

Prostate-cancer biopsy directed at areas of MRI abnormality was compared with standard transrectal ultrasonographic biopsy for diagnostic specificity and sensitivity. MRI-targeted biopsy identified more high-risk cancers and fewer clinically insignificant tumors.

Background: Transrectal prostate biopsy has limited diagnostic accuracy. Prostate Imaging Compared to Transperineal Ultrasound-guided biopsy for significant prostate cancer Risk Evaluation (PICTURE) was a paired-cohort confirmatory study designed to assess diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) in men requiring a repeat biopsy. Methods: All underwent 3 T mpMRI and transperineal template prostate mapping biopsies (TTPM biopsies). Multiparametric MRI was reported using Likert scores and radiologists were blinded to initial biopsies. Men were blinded to mpMRI results. Clinically significant prostate cancer was defined as Gleason ⩾4+3 and/or cancer core length ⩾6 mm. Results: Two hundred and forty-nine had both tests with mean (s.d.) age was 62 (7) years, median (IQR) PSA 6.8 ng ml (4.98–9.50), median (IQR) number of previous biopsies 1 (1–2) and mean (s.d.) gland size 37 ml (15.5). On TTPM biopsies, 103 (41%) had clinically significant prostate cancer. Two hundred and fourteen (86%) had a positive prostate mpMRI using Likert score ⩾3; sensitivity was 97.1% (95% confidence interval (CI): 92–99), specificity 21.9% (15.5–29.5), negative predictive value (NPV) 91.4% (76.9–98.1) and positive predictive value (PPV) 46.7% (35.2–47.8). One hundred and twenty-nine (51.8%) had a positive mpMRI using Likert score ⩾4; sensitivity was 80.6% (71.6–87.7), specificity 68.5% (60.3–75.9), NPV 83.3% (75.4–89.5) and PPV 64.3% (55.4–72.6). Conclusions: In men advised to have a repeat prostate biopsy, prostate mpMRI could be used to safely avoid a repeat biopsy with high sensitivity for clinically significant cancers. However, such a strategy can miss some significant cancers and overdiagnose insignificant cancers depending on the mpMRI score threshold used to define which men should be biopsied.

Objectives To investigate changes in the Apparent Diffusion Coefficient (ADC) using diffusion-weighted imaging (DWI) in men on active surveillance for prostate cancer taking dutasteride 0.5 mg or placebo . Methods We analysed 37 men, randomised to 6 months of daily dutasteride (n = 18) or placebo (n = 19), undergoing 3T multi-parametric Magnetic Resonance Imaging (mpMRI) scans at baseline and 6 months. Images were reviewed blind to treatment allocation and clinical information. Mean ADC of peripheral (PZ) and transition (TZ) zones, and MR-suspicious lesions were compared between groups over 6 months. Conspicuity was defined as the PZ divided by tumour ADC, and its change over 6 months was assessed. Results A decrease in mean conspicuity in the dutasteride group (but not the controls) was seen over 6 months (1.54 vs 1.38; p = 0.025). Absolute changes in ADC and conspicuity were significantly different between placebo and dutasteride groups at 6 months: (-0.03 vs 0.08, p = 0.033) and (0.11 vs –0.16, p = 0.012), as were percentage changes in the same parameters: (-2.27% vs 8.56% p = 0.048) and (9.25% vs -9.89% p = 0.013). Conclusions Dutasteride was associated with increased tumour ADC and reduced conspicuity . A lower threshold for triggering biopsy might be considered in men on dutasteride undergoing mpMRI for prostate cancer. Key points • Dutasteride increases ADC and reduces conspicuity in small mpMRI - visible prostate cancers . • Knowledge of dutasteride exposure is important in the interpretation of prostate mpMRI . • A lower threshold for triggering biopsy may be appropriate on dutasteride .

Introduction Focal therapy has increasingly become an accepted treatment option for patients with localised prostate cancer. Most follow-up protocols use a mixture of protocol biopsies or “for cause” biopsies triggered by a rising PSA. In this paper, we discuss the histological outcomes from these biopsies and their use in guiding subsequent management and trial development. Methods We conducted a literature search and reviewed the post-treatment biopsy results from studies on focal HIFU and focal cryotherapy. We subsequently reviewed the results of three recently published consensus statements released discussing many of the issues concerning focal therapy. Results Research suggests that 1 in 5 of all post-treatment biopsies after focal therapy are positive. However, the majority of these seemed to be from the untreated portion of the gland or met criteria for clinically insignificant disease. The histological outcomes from focal therapy are promising and confirm its effectiveness in the short to medium term. Furthermore re-treatment is possible whilst maintaining a low-side-effect profile. Conclusion Debate is ongoing about the clinical significance of various levels of residual disease after focal therapy and the exact threshold at which to call failure within a patient who has had focal therapy.

Background Bladder cancer (BC) is one of the most common cancers in the western world and ranks as the most expensive to manage, due to the need for cystoscopic examination. BC shows frequent changes in DNA methylation, and several studies have shown the potential utility of urinary biomarkers by detecting epigenetic alterations in voided urine. The aim of this study is to develop a targeted bisulfite next-generation sequencing assay to diagnose BC from urine with high sensitivity and specificity. Results We defined a 150 CpG loci biomarker panel from a cohort of 86 muscle-invasive bladder cancers and 30 normal urothelium. Based on this panel, we developed the UroMark assay, a next-generation bisulphite sequencing assay and analysis pipeline for the detection of bladder cancer from urinary sediment DNA. The 150 loci UroMark assay was validated in an independent cohort ( n  = 274, non-cancer ( n  = 167) and bladder cancer ( n  = 107)) voided urine samples with an AUC of 97%. The UroMark classifier sensitivity of 98%, specificity of 97% and NPV of 97% for the detection of primary BC was compared to non-BC urine. Conclusions Epigenetic urinary biomarkers for detection of BC have the potential to revolutionise the management of this disease. In this proof of concept study, we show the development and utility of a novel high-throughput, next-generation sequencing-based biomarker for the detection of BC-specific epigenetic alterations in urine.

ObjectivesTo evaluate the feasibility of a novel multiparametric MRI (mpMRI) and cognitive fusion transperineal targeted biopsy (MRTB) led prostate cancer (PCa) diagnostic service with regard to cancer detection and reducing time to diagnosis and treatment.DesignConsecutive men being investigated for possible PCa under the UK 2-week wait guidelines.SettingTertiary referral centre for PCa in the UK.ParticipantsMen referred with a raised prostate-specific antigen (PSA) or abnormal digital rectal examination between February 2015 and March 2016 under the UK 2-week rule guideline.InterventionsAn mpMRI was performed prior to patients attending clinic, on the same day. If required, MRTB was offered. Results were available within 48 hours and discussed at a specialist multidisciplinary team meeting. Patients returned for counselling within 7 daysPrimary and secondary outcome measuresOutcome measures in this regard included the time to diagnosis and treatment of patients referred with a suspicion of PCa. Quality control outcome measures included clinically significant and total cancer detection rates.Results112 men were referred to the service. 111 (99.1%) underwent mpMRI. Median PSA was 9.4 ng/mL (IQR 5.6–21.0). 87 patients had a target on mpMRI with 25 scoring Likert 3/5 for likelihood of disease, 26 4/5 and 36 5/5.57 (51%) patients received a local anaesthetic, Magnetic resonance imaging targeted biopsy (MRTB). Cancer was detected in 45 (79%). 43 (96%) had University College London definition 2 disease or greater. The times to diagnosis and treatment were a median of 8 and 20 days, respectively.ConclusionsThis approach greatly reduces the time to diagnosis and treatment. Detection rates of significant cancer are high. Similar services may be valuable to patients with a potential diagnosis of PCa.

Historically, youth development discourse in the Commonwealth Caribbean straddles two distinctive perspectives. On the one hand, there is the deficit perspective which describes young people as wards in need of welfare. On the other hand, there is the positive youth development perspective which speaks to the empowerment of young people to perform their role as change agents and strategic partners in development. Both perspectives have informed the Commonwealth Caribbean youth development agenda. In this paper, we trace the origins and manifestations of the two perspectives on the Commonwealth Caribbean youth development landscape from post-Emancipation to present. We conclude with the recommendation for a paradigm shift in youth development strategies, and we proffer proposals to facilitate the transition. Históricamente, el discurso relativo al desarrollo juvenil en la Mancomunidad del Caribe se plantea desde dos perspectivas distintas. Por un lado, la perspectiva es una de déficit que representa los jóvenes como pupilos que requieren asistencia social; y por otro lado, hay la perspectiva del desarrollo positivo de los jóvenes que presenta el empoderamiento juvenil para desempeñar su papel como agentes de cambio y socios estratégicos en el desarrollo. Ambas perspectivas informan la agenda sobre el desarrollo de jóvenes de la Mancomunidad del Caribe. En este articulo, trazamos los orígenes y las manifestaciones de las dos perspectivas sobre el panorama del desarrollo juvenil en la Mancomunidad del Caribe desde la época de pos-emancipación hasta el presente. Concluimos recomendando un cambio de paradigma en las estrategias de desarrollo juvenil, y presentamos propuestas para facilitar la transición. Historiquement, le discours sur le développement des jeunes dans les Caraïbes du Commonwealth est à cheval sur deux perspectives distinctes. D'une part, il y a la perspective de déficit qui décrit les jeunes comme des pupilles qui ont besoin de la protection. D'autre part, il ya le point de vue du développement positif des jeunes qui parle de l'autonomisation des jeunes pour jouer leur rôle d'agents de changement et de partenaires stratégiques dans le développement. Les deux points de vue ont informé le programme de développement de la jeunesse des Caraïbes du Commonwealth. Dans cet article, nous traçons les origines et les manifestations des deux perspectives sur le paysage du développement des jeunes dans les Caraïbes du Commonwealth depuis la période postémancipation jusqu'au présent. Nous concluons avec la recommandation pour un changement de paradigme au niveau des stratégies de développement des jeunes, et nous offrons des propositions visant à faciliter cette transition.

Historically, youth development discourse in the Commonwealth Caribbean straddles two distinctive perspectives. On the one hand, there is the deficit perspective which describes young people as wards in need of welfare. On the other hand, there is the positive youth development perspective which speaks to the empowerment of young people to perform their role as change agents and strategic partners in development. Both perspectives have informed the Commonwealth Caribbean youth development agenda. In this paper, we trace the origins and manifestations of the two perspectives on the Commonwealth Caribbean youth development landscape from post-Emancipation to present. We conclude with the recommendation for a paradigm shift in youth development strategies, and we proffer proposals to facilitate the transition.