Roles In Interpretation: How to Share Your Literary Analysis with an Audience (PDF)

The transmission soil transmitted helminths (STH) occurs via ingestion of or contact with infective stages present in soil contaminated with human faeces. It follows therefore that efforts to reduce faecal contamination of the environment should help to reduce risk of parasite exposure and improvements in water, sanitation and hygiene (WASH) are seen as essential for the long-term, sustainable control of STH. However, the link between WASH and STH is not always supported by the available evidence from randomised controlled trials, which report mixed effects of WASH intervention on infection risk. This review critically summarises the available trial evidence and offers an interpretation of the observed heterogeneity in findings. The review also discusses the implications of findings for control programmes and highlights three main issues which merit further consideration: intervention design, exposure assessment, and intervention fidelity assessment.

Hippo signaling exerts a critical role in modulating cell proliferation and has been demonstrated to contribute to the progression of various diseases including cancer. The Hippo signaling pathway is primarily composed of mammalian Ste20-like kinases 1/2 (MST1/2) and large tumor suppressor 1/2 (LATS1/2), yes association protein (YAP) and/or its paralog TAZ (which is also known as WW domain containing transcription regulator 1 (WWTR1) [1]. Following the activation of the Hippo pathway, MST1/2 is phosphorylated and activates LATS1/2, which can then phosphorylate YAP/TAZ, resulting in the inhibition of activity of YAP/TAZ. LATS kinases and its mammalian homologs MST1 and MST2 are activated by Hippo (Fig. 1) [1]. There are multiple functions of Hippo kinase activity associated with the activation of Hippo, including the promotion of MOB-Hippo or MOB-LATS binding, and the activation of LATS [2]. MOB proteins have diverse range of roles in the activity of LATS. The ability of MOB proteins to interact with Hippo and LATS kinases can result in the phosphorylation of LATS, and their associations with LATS induce a necessary conformational change [3]. SAV was observed to link Hippo and Warts by acting as a scaffolding protein. In addition, SAV1 can inhibit the recruitment of SLMAP and maintain the activation of MST1/2 [4]. It has previously been reported that MST1/2 kinases can interact with the adaptor protein SAV and with phosphorylated LATS1/2 kinase. The phosphorylation of LATS promotes their cytoplasmic localization in YAP proteins (Ser 127 of human YAP1, Ser 89 of human TAZ) by creating a binding site on 14-3-3 proteins [2]. In addition, previous studies have demonstrated that the expression of YAP/TAZ is unusually excessive in tumors, enhances the occurrence of tumors and is thought to be a cancer gene for a large number of solid cancers [5, 6].

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Recent observations have indicated that the overexpression of YAP1 dissociates K-Ras4B inhibition. Therefore, the transcriptional activation of YAP1 and β-catenin as a survival rescue strategy of K-Ras4B-inhibited cells [32, 33] has further become a key concern, as it can negate the effects of K-Ras4B therapeutics. YAP1 and β-catenin transcriptional regulators serve a role in the targeting of K-Ras4B and can induce resistance by controlling the progression of cells from the G1 phase to S phase in the cell cycle. The role of ERK corresponds to that of YAP1 and PI3Kα. ERK and YAP can produce consequences similar to those of PI3K and β-catenin, which is why K-Ras4B drug resistance is caused by the expropriation of YAP and β-catenin [32,33,34]. The emerging picture from relevant experimental and clinical data suggests that oncogenic KRAS, YAP1 and β -catenin serve similar roles in cell cycle control in tumor initiation [34].

Despite the use of valid assessment instruments to quantify results across all studies, measurements were likewise heterogeneous, hindering a holistic interpretation of effects. For example, studies used different versions of established measurements, e.g. of the Stroop task, which could be delivered as an audio-verbal, as well as visual-verbal or visual-manual task. In general, assessment instruments varied between written or computerised measurements to the active conduction of specific functions, which increased difficulty of comparing assessment structures.

We found that general cognitive-motor interventions improve global cognition and executive functions. All but one study found improvement of at least one specific function. Of note, type of exercise, dose, intervention settings and outcomes differed across trials which allowed for fractional interpretation of the given results only.

In addition to highlighting possible peripheral vascular and inflammatory alterations during LOAD progression, our plasma and CSF analysis suggests possible mechanisms contributing to such dysregulations. Peripheral insulin resistance, inflammatory and lipid/fatty acid metabolism alterations, supported by the observed high proinsulin, IP-10, hFABP and Apo A abnormalities, were some of the main pathological mechanisms suggested by the proteomics findings. Some of these have been previously associated with vascular/metabolic integrity and neurodegenerative progression3,31,34,35. Potentially, they might be reflecting the cascade of multifactorial pathological events conducive to LOAD. However, as discussed below, we should be cautious about the interpretation of these findings, since our analysis does not reveal direct causal relationships among the considered biomarkers, and consequently, neither among their corresponding biological factors.

In line with previous models of LOAD progression9,10,11,12,13, a strong assumption in our study is that the analysed biomarkers precisely reflect specific pathophysiological processes. Qualitative and data-driven models depend on how realistically the available observations represent the underlying biological processes. Although grey matter density and atrophy measurements, obtained with structural MRI techniques, are commonly used to characterize structural brain properties, results and interpretations depend on how accurately the used MRI techniques reflect the real tissue properties and also under which spatial scales these measurements are precise. Similarly, current ASL and PET techniques still offer a limited characterization of the vascular and metabolic/Aβ brain properties. Consequently, it is important to exert caution about the observed biomarkers ordering with disease progression. Although the obtained abnormality trajectories may be reflecting a tentative ordering in which pathophysiological events occur, our results should be interpreted more in terms of biomarker sensitivity to disease progression than in terms of causal pathologic interactions conducive of LOAD. In addition, here structural alterations were only evaluated in the grey matter, ignoring possible alterations within the white matter and in its associated structural connectivity patterns. This will be the main focus of a separate study, for which we are combining structural T1 atrophy and diffusion-weighted connectivity measurements58,59. Another potential limitation of our study is that all evaluations were performed within a linear regression framework. This could mean that the obtained results are mainly reflecting the linear tendencies in the analysed biomarkers. The alternative use of non-linear modelling techniques (for example, radial basis and kernel functions) may provide a solution to overcome this particular limitation. Similarly, the assumption of an explicit analytic expression associated with each biomarker (for example, equation 3, Methods section) is a limitation in line with some previous data-driven models13,14,17. An event-based perspective11,12 presents the advantage of not assuming any a priori biomarkers shape. However, the latest models demand a high computational cost to test exhaustively all the possible combinations in events ordering, which can make it difficult to apply such perspectives to a high number of multifactorial biomarkers. Finally, and similarly to the previous models9,10,11,12,13,14, here we are not addressing the issue that initial small changes/alterations in specific biological factors could potentially cause large alterations in other interconnected factors. This traditional limitation suggests the need to study disease progression not only in terms of alteration levels of specific biomarkers, but also through the analysis of the multifactorial causal pathological interactions that take place at the different spatiotemporal scales. Causal analyses could potentially lead us to a more integrative understanding of neurodegenerative progression, and will form the central purpose of our future research.

Y.I.-M. conceived and designed the experiment. ADNI acquired the data. Y.I.-M. implemented the programming codes, analysed the data and wrote the main manuscript. R.C.S. and P.J.T. provided feedback on the data analysis and the manuscript preparation/writing. Y.I.-M. and J.M.M.-P. prepared the figures. A.C.E. supervised the project. All authors contributed to constructive discussions regarding the interpretation of the results.

With respect to these different aspects, roles can be allotted to a traditional or an egalitarian point of view. The former implies that the private sphere, for example, is assigned to women, and they are restricted to complying with their family responsibilities. In contrast, egalitarian attitudes are demonstrated, for example, when someone believes that men and women should share equally the responsibility for family tasks and that women as well as men should participate in paid work. The distinction between traditional and egalitarian roles can be made regarding the different aspects of gender roles: role ascription, role conflict, and role segregation. Figure 1 presents an outline of the concept of gender role attitudes.

Another development that also facilitates a more egalitarian opinion regarding gender roles is increasing secularization. With a shift away from church membership, and its related traditional thinking, towards more individualistic religious beliefs, a shift toward less traditional gender role attitudes also can be observed. 2ff7e9595c