Displaying publications 41 - 60 of 2505 in total

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  1. Khorramian K, Maleki S, Shariati M, Ramli Sulong NH
    PLoS One, 2015;10(12):e0144288.
    PMID: 26642193 DOI: 10.1371/journal.pone.0144288
    According to recent researches, angle shear connectors are appropriate to transfer longitudinal shear forces across the steel-concrete interface. Angle steel profile has been used in different positions as L-shaped or C-shaped shear connectors. The application of angle shear connectors in tilted positions is of interest in this study. This study investigates the behaviour of tilted-shaped angle shear connectors under monotonic loading using experimental push out tests. Eight push-out specimens are tested to investigate the effects of different angle parameters on the ultimate load capacity of connectors. Two different tilted angles of 112.5 and 135 degrees between the angle leg and steel beam are considered. In addition, angle sizes and lengths are varied. Two different failure modes were observed consisting of concrete crushing-splitting and connector fracture. By increasing the size of connector, the maximum load increased for most cases. In general, the 135 degrees tilted angle shear connectors have a higher strength and stiffness than the 112.5 degrees type.
  2. Mahmoodian R, Yahya R, Dabbagh A, Hamdi M, Hassan MA
    PLoS One, 2015;10(12):e0144632.
    PMID: 26641651 DOI: 10.1371/journal.pone.0144632
    A novel method is proposed to study the behavior and phase formation of a Si+C compacted pellet under centrifugal acceleration in a hybrid reaction. Si+C as elemental mixture in the form of a pellet is embedded in a centrifugal tube. The pellet assembly and tube are exposed to the sudden thermal energy of a thermite reaction resulted in a hybrid reaction. The hybrid reaction of thermite and Si+C produced unique phases. X-ray diffraction pattern (XRD) as well as microstructural and elemental analyses are then investigated. XRD pattern showed formation of materials with possible electronic and magnetic properties. The cooling rate and the molten particle viscosity mathematical model of the process are meant to assist in understanding the physical and chemical phenomena took place during and after reaction. The results analysis revealed that up to 85% of materials converted into secondary products as ceramics-matrix composite.
  3. Dawaki S, Al-Mekhlafi HM, Ithoi I, Ibrahim J, Abdulsalam AM, Ahmed A, et al.
    PLoS One, 2015;10(11):e0143667.
    PMID: 26606264 DOI: 10.1371/journal.pone.0143667
    Schistosomiasis is one of the most common neglected tropical diseases, especially in the developing countries in Africa, Asia and South America, with Nigeria having the greatest number of cases of schistosomiasis worldwide. This community-based study aims to evaluate the knowledge, attitude and practices (KAP) regarding schistosomiasis among rural Hausa communities in Kano State, Nigeria.
  4. Yap HY, Chooi YH, Fung SY, Ng ST, Tan CS, Tan NH
    PLoS One, 2015;10(11):e0143549.
    PMID: 26606395 DOI: 10.1371/journal.pone.0143549
    Lignosus rhinocerotis (Cooke) Ryvarden (tiger milk mushroom) has long been known for its nutritional and medicinal benefits among the local communities in Southeast Asia. However, the molecular and genetic basis of its medicinal and nutraceutical properties at transcriptional level have not been investigated. In this study, the transcriptome of L. rhinocerotis sclerotium, the part with medicinal value, was analyzed using high-throughput Illumina HiSeqTM platform with good sequencing quality and alignment results. A total of 3,673, 117, and 59,649 events of alternative splicing, novel transcripts, and SNP variation were found to enrich its current genome database. A large number of transcripts were expressed and involved in the processing of gene information and carbohydrate metabolism. A few highly expressed genes encoding the cysteine-rich cerato-platanin, hydrophobins, and sugar-binding lectins were identified and their possible roles in L. rhinocerotis were discussed. Genes encoding enzymes involved in the biosynthesis of glucans, six gene clusters encoding four terpene synthases and one each of non-ribosomal peptide synthetase and polyketide synthase, and 109 transcribed cytochrome P450 sequences were also identified in the transcriptome. The data from this study forms a valuable foundation for future research in the exploitation of this mushroom in pharmacological and industrial applications.
  5. Mariapun S, Li J, Yip CH, Taib NA, Teo SH
    PLoS One, 2015;10(2):e0117568.
    PMID: 25659139 DOI: 10.1371/journal.pone.0117568
    BACKGROUND: Mammographic density is a strong risk factor for breast cancer and is highly variable, but, to date, few studies have examined density in Asian women, particularly those in low and middle-income Asian countries where genetic and lifestyle determinants may be significantly different.
    METHODS: A total of 1,240 women who attended an opportunistic mammogram screening programme were eligible for analysis. Mammographic density was estimated using a fully-automated thresholding method and differences across ethnic groups were examined using linear regression in 205 randomly selected Chinese women, 138 Malay and 199 Indian women.
    RESULTS: Percent density was significantly higher in Chinese women (28.5%; 95% CI 27.0%, 30.0%) compared to Malay (24.2%; 95% CI 22.5%, 26.0%) and Indian (24.3%; 95% CI 22.8%, 25.7%) women (p<0.001), after adjustment for age, BMI, menopausal status, parity and age at first full term pregnancy. Correspondingly, adjusted nondense area was significantly lower in Chinese (72.2cm2; 95% CI 67.9cm2, 76.5cm2) women compared to Malay (92.1cm2; 95% CI 86.9cm2, 97.2cm2) and Indian (97.7cm2; 95% CI 93.4cm2, 101.9cm2) women (p<0.001), but dense area did not differ across the three ethnic groups.
    CONCLUSIONS: Our study shows that higher percent density and lower nondense area reflect the higher incidence of breast cancer in Chinese compared to Malay and Indian women in Malaysia. Known lifestyle determinants of mammographic density do not fully account for the ethnic variations observed in mammographic density in this Asian cohort.
  6. Sekizuka T, Kai M, Nakanaga K, Nakata N, Kazumi Y, Maeda S, et al.
    PLoS One, 2014;9(12):e114848.
    PMID: 25503461 DOI: 10.1371/journal.pone.0114848
    Mycobacterium abscessus group subsp., such as M. massiliense, M. abscessus sensu stricto and M. bolletii, are an environmental organism found in soil, water and other ecological niches, and have been isolated from respiratory tract infection, skin and soft tissue infection, postoperative infection of cosmetic surgery. To determine the unique genetic feature of M. massiliense, we sequenced the complete genome of M. massiliense type strain JCM 15300 (corresponding to CCUG 48898). Comparative genomic analysis was performed among Mycobacterium spp. and among M. abscessus group subspp., showing that additional ß-oxidation-related genes and, notably, the mammalian cell entry (mce) operon were located on a genomic island, M. massiliense Genomic Island 1 (MmGI-1), in M. massiliense. In addition, putative anaerobic respiration system-related genes and additional mycolic acid cyclopropane synthetase-related genes were found uniquely in M. massiliense. Japanese isolates of M. massiliense also frequently possess the MmGI-1 (14/44, approximately 32%) and three unique conserved regions (26/44; approximately 60%, 34/44; approximately 77% and 40/44; approximately 91%), as well as isolates of other countries (Malaysia, France, United Kingdom and United States). The well-conserved genomic island MmGI-1 may play an important role in high growth potential with additional lipid metabolism, extra factors for survival in the environment or synthesis of complex membrane-associated lipids. ORFs on MmGI-1 showed similarities to ORFs of phylogenetically distant M. avium complex (MAC), suggesting that horizontal gene transfer or genetic recombination events might have occurred within MmGI-1 among M. massiliense and MAC.
  7. Ismail F, Couvin D, Farakhin I, Abdul Rahman Z, Rastogi N, Suraiya S
    PLoS One, 2014;9(12):e114832.
    PMID: 25502956 DOI: 10.1371/journal.pone.0114832
    Tuberculosis (TB) still constitutes a major public health problem in Malaysia. The identification and genotyping based characterization of Mycobacterium tuberculosis complex (MTBC) isolates causing the disease is important to determine the effectiveness of the control and surveillance programs.
  8. Salari N, Shohaimi S, Najafi F, Nallappan M, Karishnarajah I
    PLoS One, 2014;9(11):e112987.
    PMID: 25419659 DOI: 10.1371/journal.pone.0112987
    Among numerous artificial intelligence approaches, k-Nearest Neighbor algorithms, genetic algorithms, and artificial neural networks are considered as the most common and effective methods in classification problems in numerous studies. In the present study, the results of the implementation of a novel hybrid feature selection-classification model using the above mentioned methods are presented. The purpose is benefitting from the synergies obtained from combining these technologies for the development of classification models. Such a combination creates an opportunity to invest in the strength of each algorithm, and is an approach to make up for their deficiencies. To develop proposed model, with the aim of obtaining the best array of features, first, feature ranking techniques such as the Fisher's discriminant ratio and class separability criteria were used to prioritize features. Second, the obtained results that included arrays of the top-ranked features were used as the initial population of a genetic algorithm to produce optimum arrays of features. Third, using a modified k-Nearest Neighbor method as well as an improved method of backpropagation neural networks, the classification process was advanced based on optimum arrays of the features selected by genetic algorithms. The performance of the proposed model was compared with thirteen well-known classification models based on seven datasets. Furthermore, the statistical analysis was performed using the Friedman test followed by post-hoc tests. The experimental findings indicated that the novel proposed hybrid model resulted in significantly better classification performance compared with all 13 classification methods. Finally, the performance results of the proposed model was benchmarked against the best ones reported as the state-of-the-art classifiers in terms of classification accuracy for the same data sets. The substantial findings of the comprehensive comparative study revealed that performance of the proposed model in terms of classification accuracy is desirable, promising, and competitive to the existing state-of-the-art classification models.
  9. Haridan US, Mokhtar U, Machado LR, Abdul Aziz AT, Shueb RH, Zaid M, et al.
    PLoS One, 2015;10(1):e0116791.
    PMID: 25594501 DOI: 10.1371/journal.pone.0116791
    The FCGR3 locus encoding the low affinity activating receptor FcγRIII, plays a vital role in immunity triggered by cellular effector and regulatory functions. Copy number of the genes FCGR3A and FCGR3B has previously been reported to affect susceptibility to several autoimmune diseases and chronic inflammatory conditions. However, such genetic association studies often yield inconsistent results; hence require assays that are robust with low error rate. We investigated the accuracy and efficiency in estimating FCGR3 CNV by comparing Sequenom MassARRAY and paralogue ratio test-restriction enzyme digest variant ratio (PRT-REDVR). In addition, since many genetic association studies of FCGR3B CNV were carried out using real-time quantitative PCR, we have also included the evaluation of that method's performance in estimating the multi-allelic CNV of FCGR3B. The qPCR assay exhibited a considerably broader distribution of signal intensity, potentially introducing error in estimation of copy number and higher false positive rates. Both Sequenom and PRT-REDVR showed lesser systematic bias, but Sequenom skewed towards copy number normal (CN = 2). The discrepancy between Sequenom and PRT-REDVR might be attributed either to batch effects noise in individual measurements. Our study suggests that PRT-REDVR is more robust and accurate in genotyping the CNV of FCGR3, but highlights the needs of multiple independent assays for extensive validation when performing a genetic association study with multi-allelic CNVs.
  10. Talei D, Valdiani A, Rafii MY, Maziah M
    PLoS One, 2014;9(11):e112907.
    PMID: 25423252 DOI: 10.1371/journal.pone.0112907
    Separation of proteins based on the physicochemical properties with different molecular weight and isoelectric points would be more accurate. In the current research, the 45-day-old seedlings were treated with 0 (control) and 12 dS m(-1) of sodium chloride in the hydroponic system. After 15 days of salt exposure, the total protein of the fresh leaves and roots was extracted and analyzed using two-dimensional electrophoresis system (2-DE). The analysis led to the detection of 32 induced proteins (19 proteins in leaf and 13 proteins in the root) as well as 12 upregulated proteins (four proteins in leaf and eight proteins in the root) in the salt-treated plants. Of the 44 detected proteins, 12 were sequenced, and three of them matched with superoxide dismutase, ascorbate peroxidase and ribulose-1, 5-bisphosphate oxygenase whereas the rest remained unknown. The three known proteins associate with plants response to environmental stresses and could represent the general stress proteins in the present study too. In addition, the proteomic feedback of different accessions of A. paniculata to salt stress can potentially be used to breed salt-tolerant varieties of the herb.
  11. Rodrigues AS, Brooks TM, Butchart SH, Chanson J, Cox N, Hoffmann M, et al.
    PLoS One, 2014;9(11):e113934.
    PMID: 25426636 DOI: 10.1371/journal.pone.0113934
    The world's governments have committed to preventing the extinction of threatened species and improving their conservation status by 2020. However, biodiversity is not evenly distributed across space, and neither are the drivers of its decline, and so different regions face very different challenges. Here, we quantify the contribution of regions and countries towards recent global trends in vertebrate conservation status (as measured by the Red List Index), to guide action towards the 2020 target. We found that>50% of the global deterioration in the conservation status of birds, mammals and amphibians is concentrated in <1% of the surface area, 39/1098 ecoregions (4%) and eight/195 countries (4%) - Australia, China, Colombia, Ecuador, Indonesia, Malaysia, Mexico, and the United States. These countries hold a third of global diversity in these vertebrate groups, partially explaining why they concentrate most of the losses. Yet, other megadiverse countries - most notably Brazil (responsible for 10% of species but just 1% of deterioration), plus India and Madagascar - performed better in conserving their share of global vertebrate diversity. Very few countries, mostly island nations (e.g. Cook Islands, Fiji, Mauritius, Seychelles, and Tonga), have achieved net improvements. Per capita wealth does not explain these patterns, with two of the richest countries - United States and Australia - fairing conspicuously poorly. Different countries were affected by different combinations of threats. Reducing global rates of biodiversity loss will require investment in the regions and countries with the highest responsibility for the world's biodiversity, focusing on conserving those species and areas most in peril and on reducing the drivers with the highest impacts.
  12. Khosravi Y, Dieye Y, Loke MF, Goh KL, Vadivelu J
    PLoS One, 2014;9(11):e112214.
    PMID: 25386948 DOI: 10.1371/journal.pone.0112214
    Helicobacter pylori (H. pylori) is a major gastric pathogen that has been associated with humans for more than 60,000 years. H. pylori causes different gastric diseases including dyspepsia, ulcers and gastric cancers. Disease development depends on several factors including the infecting H. pylori strain, environmental and host factors. Another factor that might influence H. pylori colonization and diseases is the gastric microbiota that was overlooked for long because of the belief that human stomach was a hostile environment that cannot support microbial life. Once established, H. pylori mainly resides in the gastric mucosa and interacts with the resident bacteria. How these interactions impact on H. pylori-caused diseases has been poorly studied in human. In this study, we analyzed the interactions between H. pylori and two bacteria, Streptococcus mitis and Lactobacillus fermentum that are present in the stomach of both healthy and gastric disease human patients. We have found that S. mitis produced and released one or more diffusible factors that induce growth inhibition and coccoid conversion of H. pylori cells. In contrast, both H. pylori and L. fermentum secreted factors that promote survival of S. mitis during the stationary phase of growth. Using a metabolomics approach, we identified compounds that might be responsible for the conversion of H. pylori from spiral to coccoid cells. This study provide evidences that gastric bacteria influences H. pylori physiology and therefore possibly the diseases this bacterium causes.
  13. Gul T, Islam S, Shah RA, Khan I, Khalid A, Shafie S
    PLoS One, 2014;9(11):e103843.
    PMID: 25383797 DOI: 10.1371/journal.pone.0103843
    This article aims to study the thin film layer flowing on a vertical oscillating belt. The flow is considered to satisfy the constitutive equation of unsteady second grade fluid. The governing equation for velocity and temperature fields with subjected initial and boundary conditions are solved by two analytical techniques namely Adomian Decomposition Method (ADM) and Optimal Homotopy Asymptotic Method (OHAM). The comparisons of ADM and OHAM solutions for velocity and temperature fields are shown numerically and graphically for both the lift and drainage problems. It is found that both these solutions are identical. In order to understand the physical behavior of the embedded parameters such as Stock number, frequency parameter, magnetic parameter, Brinkman number and Prandtl number, the analytical results are plotted graphically and discussed.
  14. Nathan AM, Rani F, Lee RJ, Zaki R, Westerhout C, Sam IC, et al.
    PLoS One, 2014;9(10):e111162.
    PMID: 25360811 DOI: 10.1371/journal.pone.0111162
    Lower respiratory tract infections (LRTIs) are an important cause of morbidity and mortality, especially in low income countries. The aim of this study was to determine risk factors of life-threatening LRTIs in hospitalised children in Malaysia.
  15. Yap HJ, Taha Z, Dawal SZ, Chang SW
    PLoS One, 2014;9(10):e109692.
    PMID: 25360663 DOI: 10.1371/journal.pone.0109692
    Traditional robotic work cell design and programming are considered inefficient and outdated in current industrial and market demands. In this research, virtual reality (VR) technology is used to improve human-robot interface, whereby complicated commands or programming knowledge is not required. The proposed solution, known as VR-based Programming of a Robotic Work Cell (VR-Rocell), consists of two sub-programmes, which are VR-Robotic Work Cell Layout (VR-RoWL) and VR-based Robot Teaching System (VR-RoT). VR-RoWL is developed to assign the layout design for an industrial robotic work cell, whereby VR-RoT is developed to overcome safety issues and lack of trained personnel in robot programming. Simple and user-friendly interfaces are designed for inexperienced users to generate robot commands without damaging the robot or interrupting the production line. The user is able to attempt numerous times to attain an optimum solution. A case study is conducted in the Robotics Laboratory to assemble an electronics casing and it is found that the output models are compatible with commercial software without loss of information. Furthermore, the generated KUKA commands are workable when loaded into a commercial simulator. The operation of the actual robotic work cell shows that the errors may be due to the dynamics of the KUKA robot rather than the accuracy of the generated programme. Therefore, it is concluded that the virtual reality based solution approach can be implemented in an industrial robotic work cell.
  16. Seiffert J, Hussain F, Wiegman C, Li F, Bey L, Baker W, et al.
    PLoS One, 2015;10(3):e0119726.
    PMID: 25747867 DOI: 10.1371/journal.pone.0119726
    Particle size and surface chemistry are potential determinants of silver nanoparticle (AgNP) respiratory toxicity that may also depend on the lung inflammatory state. We compared the effects of intratracheally-administered AgNPs (20 nm and 110 nm; polyvinylpyrrolidone (PVP) and citrate-capped; 0.1 mg/Kg) in Brown-Norway (BN) and Sprague-Dawley (SD) rats. In BN rats, there was both a neutrophilic and eosinophilic response, while in SD rats, there was a neutrophilic response at day 1, greatest for the 20 nm citrate-capped AgNPs. Eosinophilic cationic protein was increased in bronchoalveolar lavage (BAL) in BN and SD rats on day 1. BAL protein and malondialdehyde levels were increased in BN rats at 1 and 7 days, and BAL KC, CCL11 and IL-13 levels at day 1, with increased expression of CCL11 in lung tissue. Pulmonary resistance increased and compliance decreased at day 1, with persistence at day 7. The 20 nm, but not the 110 nm, AgNPs increased bronchial hyperresponsiveness on day 1, which continued at day 7 for the citrate-capped AgNPs only. The 20 nm versus the 110 nm size were more proinflammatory in terms of neutrophil influx, but there was little difference between the citrate-capped versus the PVP-capped AgNPs. AgNPs can induce pulmonary eosinophilic and neutrophilic inflammation with bronchial hyperresponsiveness, features characteristic of asthma.
  17. Vanderelst D, Peremans H, Razak NA, Verstraelen E, Dimitriadis G, Dimitriadis G
    PLoS One, 2015;10(3):e0118545.
    PMID: 25739038 DOI: 10.1371/journal.pone.0118545
    At first sight, echolocating bats face a difficult trade-off. As flying animals, they would benefit from a streamlined geometric shape to reduce aerodynamic drag and increase flight efficiency. However, as echolocating animals, their pinnae generate the acoustic cues necessary for navigation and foraging. Moreover, species emitting sound through their nostrils often feature elaborate noseleaves that help in focussing the emitted echolocation pulses. Both pinnae and noseleaves reduce the streamlined character of a bat's morphology. It is generally assumed that by compromising the streamlined charactered of the geometry, the head morphology generates substantial drag, thereby reducing flight efficiency. In contrast, it has also been suggested that the pinnae of bats generate lift forces counteracting the detrimental effect of the increased drag. However, very little data exist on the aerodynamic properties of bat pinnae and noseleaves. In this work, the aerodynamic forces generated by the heads of seven species of bats, including noseleaved bats, are measured by testing detailed 3D models in a wind tunnel. Models of Myotis daubentonii, Macrophyllum macrophyllum, Micronycteris microtis, Eptesicus fuscus, Rhinolophus formosae, Rhinolophus rouxi and Phyllostomus discolor are tested. The results confirm that non-streamlined facial morphologies yield considerable drag forces but also generate substantial lift. The net effect is a slight increase in the lift-to-drag ratio. Therefore, there is no evidence of high aerodynamic costs associated with the morphology of bat heads.
  18. Johnston SC, Briese T, Bell TM, Pratt WD, Shamblin JD, Esham HL, et al.
    PLoS One, 2015;10(2):e0117817.
    PMID: 25706617 DOI: 10.1371/journal.pone.0117817
    Henipaviruses are implicated in severe and frequently fatal pneumonia and encephalitis in humans. There are no approved vaccines or treatments available for human use, and testing of candidates requires the use of well-characterized animal models that mimic human disease. We performed a comprehensive and statistically-powered evaluation of the African green monkey model to define parameters critical to disease progression and the extent to which they correlate with human disease. African green monkeys were inoculated by the intratracheal route with 2.5 × 10(4) plaque forming units of the Malaysia strain of Nipah virus. Physiological data captured using telemetry implants and assessed in conjunction with clinical pathology were consistent with shock, and histopathology confirmed widespread tissue involvement associated with systemic vasculitis in animals that succumbed to acute disease. In addition, relapse encephalitis was identified in 100% of animals that survived beyond the acute disease phase. Our data suggest that disease progression in the African green monkey is comparable to the variable outcome of Nipah virus infection in humans.
  19. Choi JR, Pingguan-Murphy B, Wan Abas WA, Yong KW, Poon CT, Noor Azmi MA, et al.
    PLoS One, 2015;10(1):e0115034.
    PMID: 25615717 DOI: 10.1371/journal.pone.0115034
    Adipose tissue-derived stromal cells (ASCs) natively reside in a relatively low-oxygen tension (i.e., hypoxic) microenvironment in human body. Low oxygen tension (i.e., in situ normoxia), has been known to enhance the growth and survival rate of ASCs, which, however, may lead to the risk of tumourigenesis. Here, we investigated the tumourigenic potential of ASCs under their physiological condition to ensure their safe use in regenerative therapy. Human ASCs isolated from subcutaneous fat were cultured in atmospheric O2 concentration (21% O2) or in situ normoxia (2% O2). We found that ASCs retained their surface markers, tri-lineage differentiation potential, and self-renewal properties under in situ normoxia without altering their morphology. In situ normoxia displayed a higher proliferation and viability of ASCs with less DNA damage as compared to atmospheric O2 concentration. Moreover, low oxygen tension significantly up-regulated VEGF and bFGF mRNA expression and protein secretion while reducing the expression level of tumour suppressor genes p16, p21, p53, and pRb. However, there were no significant differences in ASCs telomere length and their relative telomerase activity when cultured at different oxygen concentrations. Collectively, even with high proliferation and survival rate, ASCs have a low tendency of developing tumour under in situ normoxia. These results suggest 2% O2 as an ideal culture condition for expanding ASCs efficiently while maintaining their characteristics.
  20. Albert JA, Beare D, Schwarz AM, Albert S, Warren R, Teri J, et al.
    PLoS One, 2014;9(12):e115386.
    PMID: 25513808 DOI: 10.1371/journal.pone.0115386
    Fish aggregating devices, or FADs, are used widely in developing countries to concentrate pelagic fish, making them easier to catch. Nearshore FADs anchored close to the coast allow access for rural communities, but despite their popularity among policy makers, there is a dearth of empirical analysis of their contributions to the supply of fish and to fisheries management. In this paper we demonstrate that nearshore FADs increased the supply of fish to four communities in Solomon Islands. Estimated total annual fish catch ranged from 4300 to 12,000 kg across the study villages, with nearshore FADs contributing up to 45% of the catch. While it is clear that FADs increased the supply of fish, FAD catch rates were not consistently higher than other fishing grounds. Villages with limited access to diverse or productive fishing grounds seemingly utilized FADs to better effect. Villagers believed FADs increased household income and nutrition, as well as providing a source of fish for community events. FADs were also perceived to increase intra-household conflict and reduce fishers' participation in community activities. FADs need to be placed within a broader rural development context and treated as another component in the diversified livelihoods of rural people; as with other livelihood options they bring trade-offs and risks.
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