103 research outputs found

    Smash and DASH with Cas9

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    Agroforestry Systems for Soil Health Improvement and Maintenance

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    Agroforestry integrates woody perennials with arable crops, livestock, or fodder in the same piece of land, promoting the more efficient utilization of resources as compared to monocropping via the structural and functional diversification of components. This integration of trees provides various soil-related ecological services such as fertility enhancements and improvements in soil physical, biological, and chemical properties, along with food, wood, and fodder. By providing a particular habitat, refugia for epigenic organisms, microclimate heterogeneity, buffering action, soil moisture, and humidity, agroforestry can enhance biodiversity more than monocropping. Various studies confirmed the internal restoration potential of agroforestry. Agroforestry reduces runoff, intercepts rainfall, and binds soil particles together, helping in erosion control. This trade-off between various non-cash ecological services and crop production is not a serious constraint in the integration of trees on the farmland and also provides other important co-benefits for practitioners. Tree-based systems increase livelihoods, yields, and resilience in agriculture, thereby ensuring nutrition and food security. Agroforestry can be a cost-effective and climate-smart farming practice, which will help to cope with the climate-related extremities of dryland areas cultivated by smallholders through diversifying food, improving and protecting soil, and reducing wind erosion. This review highlighted the role of agroforestry in soil improvements, microclimate amelioration, and improvements in productivity through agroforestry, particularly in semi-arid and degraded areas under careful consideration of management practices

    Genomic evaluation of multiparametric magnetic resonance imaging-visible and -nonvisible lesions in clinically localised prostate cancer

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    Background: The prostate cancer (PCa) diagnostic pathway is undergoing a radical change with the introduction of multiparametric magnetic resonance imaging (mpMRI), genomic testing, and different prostate biopsy techniques. It has been proposed that these tests should be used in a sequential manner to optimise risk stratification. Objective: To characterise the genomic, epigenomic, and transcriptomic features of mpMRI-visible and -nonvisible PCa in clinically localised disease. Design, setting, and participants: Multicore analysis of fresh prostate tissue sampled immediately after radical prostatectomy was performed for intermediate- to high-risk PCa. Intervention: Low-pass whole-genome, exome, methylation, and transcriptome profiling of patient tissue cores taken from microscopically benign and cancerous areas in the same prostate. Circulating free and germline DNA was assessed from the blood of five patients. Outcome measurement and statistical analysis: Correlations between preoperative mpMRI and genomic characteristics of tumour and benign prostate samples were assessed. Gene profiles for individual tumour cores were correlated with existing genomic classifiers currently used for prognostication. Results and limitations: A total of 43 prostate cores (22 tumour and 21 benign) were profiled from six whole prostate glands. Of the 22 tumour cores, 16 were tumours visible and six were tumours nonvisible on mpMRI. Intratumour genomic, epigenomic, and transcriptomic heterogeneity was found within mpMRI-visible lesions. This could potentially lead to misclassification of patients using signatures based on copy number or RNA expression. Moreover, three of the six cores obtained from mpMRI-nonvisible tumours harboured one or more genetic alterations commonly observed in metastatic castration-resistant PCa. No circulating free DNA alterations were found. Limitations include the small cohort size and lack of follow-up. Conclusions: Our study supports the continued use of systematic prostate sampling in addition to mpMRI, as avoidance of systematic biopsies in patients with negative mpMRI may mean that clinically significant tumours harbouring genetic alterations commonly seen in metastatic PCa are missed. Furthermore, there is inconsistency in individual genomics when genomic classifiers are applied. Patient summary: Our study shows that tumour heterogeneity within prostate tumours visible on multiparametric magnetic resonance imaging (mpMRI) can lead to misclassification of patients if only one core is used for genomic analysis. In addition, some cancers that were missed by mpMRI had genomic aberrations that are commonly seen in advanced metastatic prostate cancer. Avoiding biopsies in mpMRI-negative cases may mean that such potentially lethal cancers are missed

    Post-primary education in West Ham, 1918-39.

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    This thesis is concerned with post-primary education in West Ham 1918-39, with particular reference to secondary education. The realities of local educational experience are set against a background of educational acts an economies. The economic difficulties of the 1920s and the Depression of the 1930s were keenly felt in West Ham despite the efforts of the predominantly Labour council to mitigate poverty. A gap sometimes existed between the educational opportunities Labour councillors wished to provide and those they were able to provide. Generally a pragmatic approach was taken and certainly a secondary education was not seen as essential for all. Chapter One outlines West Ham's pre-1918 history and growth with reference to local politics and immigrant and religious groupings. West Ham's interwar history is told in greater detail. Chapter Two relates the difficulties encountered by the West Ham Education Committee in its decision to establish compulsory continuation schools, not least from the parents of West Ham. West Ham was one of the few areas in the country which succeeded in implementing compulsory continuation education albeit for a limited period. A section on technical education is also included in this chapter, although detailed treatment is hampered by a scarcity of records. Chapter Three examines West Ham's secondary school scholarships in the context of the national situation. West Ham's higher elementary/central school scholarships are subjected to the same scrutiny. Each of West Ham's secondary schools shared a broadly similar curriculum and ethos. Chapter Four highlights these similarities but also points out differences. Of the five interwar secondary schools, two catered for girls, one for boys and two were mixed. Two of the secondary schools were Catholic institutions, although both accepted non-Catholic pupils. Three of the schools were aided and two municipal. A section is included on West Ham's higher elementary/central schools but records are less full than those for the secondary schools. Chapter Five compares and contrasts West Ham's interwar secondary school system with that in East Ham, its sister borough. Chapter Six discusses both the economic and cultural factors underlying local attitudes to post-compulsory schooling. The main conclusions drawn relate to these attitudes which militated against any easy acceptance of such education as necessarily beneficial

    Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial

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    BACKGROUND: STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL). METHODS AND FINDINGS: Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively. CONCLUSIONS: Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC. TRIAL REGISTRATION: ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544
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