Participants identified human factors as having priority for developing and sustaining a collaborative research network. In particular, leadership, a shared vision and a communication plan that includes social media were identified as crucial for sustaining an imaging network in health research. It is important to develop metrics that map relationships between network members and the role that communication tools can contribute to this process.
This study confirms that human factors remain significant across a range of collaborative endeavours. The use of focus group discussions, interviews, and literature and website reviews means we can now strongly recommend the primacy of human factors. More work is needed to identify how the network operates and what specific indicators or metrics help build the capacity of clinicians and scientists to participate in translational research.
The Human Factor Graham Greene Epub Download
This study identified a number of key human and technical factors that are vital to support the formation of research networks. Human factors include the value of face to face interaction, having clear aims, a vision and influential leadership, the important role of social media and technology in supporting networks, the value of having seed funding as a means of promoting collaboration, and having a broad engagement strategy across participants and organisations. Technical factors include security issues, the propriety nature of some data, the importance of a document sharing function, and using an online portal to describe and promote imaging equipment and resources.
These findings are consistent with other evaluations of collaborative networks. Williams et al. [6] identified a number of similar human factors impacting on the development of collaborative networks in the context of establishing trust amongst participants. The emphasis placed on face to face contact to build relationships identified in this study supports this focus on building trust amongst participants as a necessary precursor to the development of collaboration. In this study, effective leadership, a communication plan and a shared vision were identified as key enabling factors for collaborative research endeavours. It is important, therefore, that due consideration is given to strategies for strengthening connections and relationships between network participants. For example, network meetings could be organised to bring together champions and researchers, along with service users and funding providers to look critically at the scope of imaging research. This would require administrative support and project oversight that is often overlooked in funding allocations. Research that extends to service delivery and implementation is more challenging and requires particular support, but Thyer [21] notes that interdisciplinary evidence-based practice guidelines are one effective way of enabling stronger links in implementation research.
Overall, findings from this study highlight the important role of human factors in promoting knowledge translation in collaborative health research that can be readily translated into clinical practice. The CPC offers a rich environment for studying a variety of questions about chronic disease from a range of disciplinary approaches. In addition, because many network members are now co-located, there is an opportunity for ongoing evaluation of exchange activities and discipline linkages that may help to foster translational research to improve outcomes for people with complex and chronic disease. Furthermore, the CPC is well placed to support implementation studies that aim to identify key enabling factors for knowledge translation. This is important because the increasingly competitive nature of health research funding in Australia means that evaluation and implementation scientists face significant hurdles to fund their research, which relies on complex methods and is not always amenable to randomised controlled trials.
Although the current study focused on improving a local network and the findings are not necessarily generalizable, it does provide a more nuanced understanding of the challenges and human factors that enable the development of a collaborative research network in imaging and highlights the need for metrics to capture the relationships and collaborations between network members. Nevertheless, there are ongoing questions about how to sustain the network management and test frameworks for knowledge translation across the relevant policy, practice and research domains. By combining focus group discussions and interviews with a survey and literature and website reviews, we can now strongly recommend the need to address human issues when building a collaborative network. The findings from this study will inform the development of evaluation metrics, including processes for engagement and mapping relationships that will be applied in future multi-disciplinary implementation studies.
There is wide acknowledgement that creating multi-disciplinary and inter-professional links across networks is important but challenging. Few collaborative research networks have rigorously scoped the context and processes that need to be addressed to initiate and sustain their collaborative research endeavours. The current scoping study used multi-methods to synthesise broad knowledge about how to develop and support a multi-disciplinary imaging research network in the CPC. In particular, it included consultation with key stakeholders, focus group discussions and interviews, which are often omitted from scoping studies. The study has the potential to inform ongoing evaluation of the network, which is essential for identifying how knowledge is translated and the impacts on clinical practice and policy. Relationships and human factors are important enabling factors and future research efforts should be directed to the validation of frameworks that incorporate metrics for key stakeholder engagement and metrics for capturing changing patterns of relationships between network users.
Seasonal changes in human reproduction have been observed in many studies [1,2,3]. There is a seasonal pattern in the rate of natural conception in women [4,5,6]. In warm areas, a peak in natural conception was observed during winter [7], whereas, in cold areas, the peak was observed during summer [8]. The seasonal patterns in human reproduction are consistent with the meteorological change. However, the sole effect of the meteorological change on human reproduction may be masked by other factors, such as food availability, seasonal movement, social-cultural factors, and other such factors [2].
Non-human primates (NHPs) have been vital for medical research due to their close evolutionary relationship, similar behavioral and physiological characteristics to humans. Two of the most commonly used NHPs are Cynomolgus macaque (Macaca fascicularis) and African green monkey (Chlorocebus Sabaeus), which can both be used in studies of neuroscience, infectious diseases and drug safety testing [6,7,8,9,10]. Differences also exist between these two species. For example, AGM has been known to be resistant to simian immunodeficiency virus which can be used as a model organism for HIV research [11, 12]. Also, AGM develops spontaneous hypertension with pathophysiological changes that mimic those of patients with essential hypertension [13, 14]. Research has also shown that genetic factors influence the atherogenic response of lipoproteins to dietary fat and cholesterol in nonhuman primates which reflects different capacities in lipid metabolism between AGM and CM [15].
A US government report on all forms of human trafficking estimates that around 43% of trafficking is undertaken to supply women and girls for forced commercial sex [60]. There are frequent accounts of Asian women recruited as maids, nannies, and factory workers in the Middle East being forced to sell sex on arrival at their destination[61].
One or more alternative mechanisms for the lengthening of telomeres other than telomerase were identified spanning from yeast to human normal cells and tumors. Two types of ALT mechanisms are known in yeast [22], a Rad51-dependent mechanism, mediated by homology recombination [23], and a Rad51-independent mechanism mediated by break-induced replication (BIR) [24]. In human, ALT activity has been detected also in non neoplastic somatic cells [13] and in embryonic cells [14], and recently also in canine sarcomas [25], indicating that this mechanism is conserved among mammalians. Cancers that have a mesenchymal origin are reported to activate ALT more frequently, while epithelial cancers rely on telomerase reactivation/re-expression [26, 27]. As mesenchymal stem cells are known to express minimal or no detectable amounts of telomerase [28], and harbor less frequent TERT mutations [29], this may predispose them to depend on ALT activation more frequently. ALT are characterized by telomere associated PML bodies (called APBs) containing HR proteins, sheltering factors and heterochromatin associated proteins such as HP1 [30, 31]. Moreover, a specific phosphorylated isoform of TRF1 has been found associated with and required for APBs formation [32, 33]. Therefore, chromatin modification appears to be one of the key factors determining the choice between TA and ALT. In this regard, the presence of one or more epigenetic repressors determining the TA to ALT switch has been known from years [34]. One of the best candidate for this function has been recently identified in the alpha thalassemia/mental retardation syndrome X-linked protein (ATRX), death-domain associated protein (DAXX) and Histone 3.3 complex [35,36,37]. Nevertheless, the role of ATRX/DAXX and H3.3 is not completely clarified. ATRX is a chromatin remodeling protein that presents a SWI/SNF2-type ATPase/helicase and a plant homeodomain-like zinc finger. ATRX/DAXX complex localizes mainly in the nucleus and is associated with PML nuclear bodies and other subnuclear domains [38]. Functional studies shows that loss of ATRX function is necessary but not sufficient for activation of ALT [39]. Mechanicistically, it has been demonstrated that ATRX can bind and suppress R-loops at transcribed telomeres, which are more frequent in ALT [40], bind to MRN complex and contribute to the replication fork restart [41]. Recent evidence shows that ATRX knock down suppresses the NHEJ in favor of HR, contributing to the increase of replication defects and genomic instability [42,43,44], thus suggesting a possible mechanism of induction of ALT activity by ATRX loss of function. The Homology Recombination dependent ALT pathway in human cancer is a RAD51 mediated processes, which is similar to the yeast Type I ALT and requires the integrity of the MRN (MRE11-RAD50-NBS1) recombination complex [45, 46] (Scheme 1). In agreement with an epigenetic control in the predisposition to acquire a TA or ALT phenotype, ALT cells are characterized by overall less H3K9 and H4K20 trimethylation as well as more H3 and H4 acetylation at subtelomeric and telomeric regions. The mechanisms leading to chromatin decompaction in ALT involve the regulation of the DNMT and HDAC enzymes, the CHK1 kinase, as well as other chromatin remodelling factors reviewed in [47]. Several HR proteins were already known to be targeted by miRNA (acknowledged in [47]), although only recently, a direct role of miRNA in the TA/ALT switch has been demonstrated [48]. The different chromatin organization at subtelomeric regions lead ALT telomeres to be hyper-transcribed into long ncRNA transcripts called telomeric repeat-containing RNA (TERRA) [49]. TERRA have been implicated in the regulation of telomerase, in the formation of heterochromatin at telomeres, and in telomere stability [50]. Recently, Graf and coauthors revealed differential regulation of TERRA according to the cell cycle and to telomere length, uncovering an elegant feedback loop for telomere length maintenance [51]. Moreover, TERRA was found to bind to extra-telomeric chromatin and to influences the transcription of nearby genes; additionally, TERRA was found associated with a proteome involved in diverse processes, including chromatin remodeling and transcription [52]. TERRA R-loops forming at telomeres in yeast and human cells predispose telomeres to double-strand breaks and homology-directed repair (HDR) [53]. In some cases, HDR can drive telomere elongation and allow cells to escape senescence [54, 55]. This has led to speculation that TERRA can trigger the initiating events leading to alternative lengthening of telomeres (ALT). 2ff7e9595c
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