A hierarchical systems formulation of the rural development process in developing countries

A very urgent and significant set of problems facing developing countries arises in the area of rural development. The reasons for this are that the majority of the populations of these countries lives in the rural areas and the fact that the level of production in the rural areas has a major effect on the overall economy of the developing countries. In this paper hierarchical systems theory is applied to rural development. The latter is complex in the sense that it is multidimensional, highly interacting and stochastic in nature, whilst reliable causal explanations of its socio-economic aspects in particular are commonly not availables Here a multilevel/hierarchical formulation of the rural development system is presented and analysed to provide an improved conceptual framework for the design, phasing and inter-connection of component management procedures which together comprise an effective rural development planning and control system. This analysis has been applied to design an initial set of procedures which have been introduced and tested in six rural areas of Kenya. These provide at the first level a short cycle of one month for plan implementation and at the second level a medium cycle of one year for plan reformulation. These and further procedural components are being considered for replication in all rural areas of Kenya as an integral part of the introduction of district level development plans in the context of the third five year plan (1974-79). Although the main benefits arising from the application of systems analysis to date have been at the level of procedural and institutional innovation,the multilevel/hierarchical formulation described in this paper now lays a foundation for a more quantitative approach based on systematic assembly of data describing the operation of the rural development system. ventually, simulation studies using sophisticated planning models will enable a more efficient selection between alternative rural development strategies, projects and programmes

Integrated genomic approaches identify major pathways and upstream regulators in late onset Alzheimer's disease.

Previous studies have evaluated gene expression in Alzheimer's disease (AD) brains to identify mechanistic processes, but have been limited by the size of the datasets studied. Here we have implemented a novel meta-analysis approach to identify differentially expressed genes (DEGs) in published datasets comprising 450 late onset AD (LOAD) brains and 212 controls. We found 3124 DEGs, many of which were highly correlated with Braak stage and cerebral atrophy. Pathway Analysis revealed the most perturbed pathways to be (a) nitric oxide and reactive oxygen species in macrophages (NOROS), (b) NFkB and (c) mitochondrial dysfunction. NOROS was also up-regulated, and mitochondrial dysfunction down-regulated, in healthy ageing subjects. Upstream regulator analysis predicted the TLR4 ligands, STAT3 and NFKBIA, for activated pathways and RICTOR for mitochondrial genes. Protein-protein interaction network analysis emphasised the role of NFKB; identified a key interaction of CLU with complement; and linked TYROBP, TREM2 and DOK3 to modulation of LPS signalling through TLR4 and to phosphatidylinositol metabolism. We suggest that NEUROD6, ZCCHC17, PPEF1 and MANBAL are potentially implicated in LOAD, with predicted links to calcium signalling and protein mannosylation. Our study demonstrates a highly injurious combination of TLR4-mediated NFKB signalling, NOROS inflammatory pathway activation, and mitochondrial dysfunction in LOAD

Discovery of Novel Biomarkers for Alzheimer's Disease from Blood

Blood-based biomarkers for Alzheimer’s disease would be very valuable because blood is a more accessible biofluid and is suitable for repeated sampling. However, currently there are no robust and reliable blood-based biomarkers for practical diagnosis. In this study we used a knowledge-based protein feature pool and two novel support vector machine embedded feature selection methods to find panels consisting of two and three biomarkers. We validated these biomarker sets using another serum cohort and an RNA profile cohort from the brain. Our panels included the proteins ECH1, NHLRC2, HOXB7, FN1, ERBB2, and SLC6A13 and demonstrated promising sensitivity (&gt;87%), specificity (&gt;91%), and accuracy (&gt;89%).</jats:p

Изменение психических состояний педагогов в процессе профессиональной деятельности с учетом стажа деятельности

It is relatively unknown how different dietary components, in partnership, regulate gene expression linked to colon pathology. It has been suggested that the combination of various bioactive components present in a plant-based diet is crucial for their potential anticancer activities. This study employed a combinatorial chemopreventive strategy to investigate the impact of selenium and/or isothiocyanates on DNA methylation processes in colorectal carcinoma cell lines

Correcting errors in synthetic DNA through consensus shuffling

Although efficient methods exist to assemble synthetic oligonucleotides into genes and genomes, these suffer from the presence of 1–3 random errors/kb of DNA. Here, we introduce a new method termed consensus shuffling and demonstrate its use to significantly reduce random errors in synthetic DNA. In this method, errors are revealed as mismatches by re-hybridization of the population. The DNA is fragmented, and mismatched fragments are removed upon binding to an immobilized mismatch binding protein (MutS). PCR assembly of the remaining fragments yields a new population of full-length sequences enriched for the consensus sequence of the input population. We show that two iterations of consensus shuffling improved a population of synthetic green fluorescent protein (GFPuv) clones from ∼60 to >90% fluorescent, and decreased errors 3.5- to 4.3-fold to final values of ∼1 error per 3500 bp. In addition, two iterations of consensus shuffling corrected a population of GFPuv clones where all members were non-functional, to a population where 82% of clones were fluorescent. Consensus shuffling should facilitate the rapid and accurate synthesis of long DNA sequences

Bathing adaptations in the homes of older adults (BATH-OUT): protocol for a feasibility randomised controlled trial (RCT)

Introduction The Care Act 2014 has placed a responsibility on local authorities in England to provide services that prevent deterioration and minimise the use of other health and social care services. Housing adaptations have been identified as 1 of the 10 most promising prevention services for older adults, with bathing adaptations being the most requested. However, many local authorities have lengthy waiting times which may increase costs, reduce effectiveness and reduce the preventive effect. There is no robust evidence of the effect of these adaptations on: health, well-being and functional ability. Methods and analysis This is a feasibility randomised controlled trial (RCT) with nested qualitative interview study. The RCT will recruit between 40 and 60 people who have been referred for an accessible showering facility, and their carers, from 1 local authority in England. They will be randomised to either usual adaptations (∼3-month wait) or immediate adaptations (no wait). The primary outcome is the feasibility of conducting a powered study. The outcomes assessed will be: health and social care-related quality of life, independence in activities of daily living and bathing, falls and use of health and social care services. Outcomes will be assessed at 3 and 6 months. Preliminary health economic feasibility will be established. Ethics and dissemination Favourable ethical opinion was provided by the Social Care Research Ethics Committee (reference number 16/IEC08/0017). The results of this study will lay the foundations for a further powered study. This would investigate the effect of bathing adaptations on quality of life and whether increased waiting times are associated with poorer outcomes and increased costs. The results have further potential to inform trials of other housing or social care interventions using the novel waiting list control method. Dissemination will include peer-reviewed publications and presentations at national and international conferences. Trial registration number ISRCTN14876332; Pre-results

Nutritional factors and gender influence age-related DNA methylation in the human rectal mucosa

Aberrant methylation of CpG islands (CGI) occurs in many genes expressed in colonic epithelial cells, and may contribute to the dysregulation of signalling pathways associated with carcinogenesis. This cross-sectional study assessed the relative importance of age, nutritional exposures and other environmental factors in the development of CGI methylation. Rectal biopsies were obtained from 185 individuals (84 male, 101 female) shown to be free of colorectal disease, and for whom measurements of age, body size, nutritional status and blood cell counts were available. We used quantitative DNA methylation analysis combined with multivariate modelling to investigate the relationships between nutritional, anthropometric and metabolic factors and the CGI methylation of 11 genes, together with LINE-1 as an index of global DNA methylation. Age was a consistent predictor of CGI methylation for 9/11 genes but significant positive associations with folate status and negative associations with vitamin D and selenium status were also identified for several genes. There was evidence for positive associations with blood monocyte levels and anthropometric factors for some genes. In general, CGI methylation was higher in males than in females and differential effects of age and other factors on methylation in males and females were identified. In conclusion, levels of age-related CGI methylation in the healthy human rectal mucosa are influenced by gender, the availability of folate, vitamin D and selenium, and perhaps by factors related to systemic inflammatio

Systematic Analysis and Biomarker Study for Alzheimer's Disease.

Revealing the relationship between dysfunctional genes in blood and brain tissues from patients with Alzheimer's Disease (AD) will help us to understand the pathology of this disease. In this study, we conducted the first such large systematic analysis to identify differentially expressed genes (DEGs) in blood samples from 245 AD cases, 143 mild cognitive impairment (MCI) cases, and 182 healthy control subjects, and then compare these with DEGs in brain samples. We evaluated our findings using two independent AD blood datasets and performed a gene-based genome-wide association study to identify potential novel risk genes. We identified 789 and 998 DEGs common to both blood and brain of AD and MCI subjects respectively, over 77% of which had the same regulation directions across tissues and disease status, including the known ABCA7, and the novel TYK2 and TCIRG1. A machine learning classification model containing NDUFA1, MRPL51, and RPL36AL, implicating mitochondrial and ribosomal function, was discovered which discriminated between AD patients and controls with 85.9% of area under the curve and 78.1% accuracy (sensitivity = 77.6%, specificity = 78.9%). Moreover, our findings strongly suggest that mitochondrial dysfunction, NF-κB signalling and iNOS signalling are important dysregulated pathways in AD pathogenesis

Characterising a human endogenous retrovirus(HERV)-derived tumour-associated antigen: enriched RNA-Seq analysis of HERV-K(HML-2) in mantle cell lymphoma cell lines.

BACKGROUND: The cell-surface attachment protein (Env) of the HERV-K(HML-2) lineage of endogenous retroviruses is a potentially attractive tumour-associated antigen for anti-cancer immunotherapy. The human genome contains around 100 integrated copies (called proviruses or loci) of the HERV-K(HML-2) virus and we argue that it is important for therapy development to know which and how many of these contribute to protein expression, and how this varies across tissues. We measured relative provirus expression in HERV-K(HML-2), using enriched RNA-Seq analysis with both short- and long-read sequencing, in three Mantle Cell Lymphoma cell lines (JVM2, Granta519 and REC1). We also confirmed expression of the Env protein in two of our cell lines using Western blotting, and analysed provirus expression data from all other relevant published studies. RESULTS: Firstly, in both our and other reanalysed studies, approximately 10% of the transcripts mapping to HERV-K(HML-2) came from Env-encoding proviruses. Secondly, in one cell line the majority of the protein expression appears to come from one provirus (12q14.1). Thirdly, we find a strong tissue-specific pattern of provirus expression. CONCLUSIONS: A possible dependency of Env expression on a single provirus, combined with the earlier observation that this provirus is not present in all individuals and a general pattern of tissue-specific expression among proviruses, has serious implications for future HERV-K(HML-2)-targeted immunotherapy. Further research into HERV-K(HML-2) as a possible tumour-associated antigen in blood cancers requires a more targeted, proteome-based, screening protocol that will consider these polymorphisms within HERV-K(HML-2). We include a plan (and necessary alignments) for such work

Owner and veterinary surgeon perspectives on the roles of veterinary nurses and receptionists in relation to small animal preventative healthcare consultations in the United Kingdom

Veterinary receptionists and veterinary nurses rarely feature in published practice-based research, yet are integral to small animal veterinary practice in the United Kingdom (UK). The aim of this study was to investigate the perspectives of UK-based owners and veterinary surgeons about veterinary nurses and receptionists in relation to their role in preventative healthcare. Semi-structured telephone interviews were conducted with 15 dog and cat owners and 14 veterinary surgeons. Interview transcripts were thematically analysed. Reception staff were identified as having a range of important roles, from rapport building to providing healthcare information and advice. The perceived importance of those roles appeared to differ between owners and veterinary surgeons. Veterinary nurses were described as performing a diversity of roles in relation to preventative healthcare, both in the reception area and in the consulting room. Many owners, and some veterinary surgeons, expressed uncertainty about the remit and status of veterinary nurses in relation to providing veterinary advice. This study identifies for the first time the degree of responsibility for preventative healthcare given to veterinary receptionists and veterinary nurses in UK small animal practices. Further work is needed involving reception and nursing staff to fully appreciate and define their roles in small animal practice