directional hypothesis
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Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 382
Author(s):  
Corina-Marcela Rus ◽  
Sebastiano Di Bucchianico ◽  
Claudia Cozma ◽  
Ralf Zimmerman ◽  
Peter Bauer

Lysosomal storage diseases (LSDs) are a heterogeneous group of inherited metabolic diseases caused by mutations in genes encoding for proteins involved in the lysosomal degradation of macromolecules. They occur in approximately 1 in 5000 live births and pose a lifelong risk. Therefore, to achieve the maximum benefit from LSDs therapies, a fast and early diagnosis of the disease is required. In this framework, biomarker discovery is a significant factor in disease diagnosis and in predicting its outcomes. On the other hand, the dried blood spot (DBS)based metabolomics platform can open up new pathways for studying non-directional hypothesis approaches to biomarker discovery. This study aims to increase the efficiency of the developed methods for biomarker development in the context of rare diseases, with an improved impact on the reliability of the detected compounds. Thereby, we conducted two independent experiments and integrated them into the screening of the human blood metabolome: (1) comparison of EDTA blood and filter cards in terms of their suitability for metabolomics studies; (2) optimization of the extraction method: a side-by-side comparison of a series of buffers to the best utility to the disease of interest. The findings were compared to previous studies across parameters such as metabolite coverage, sample type suitability, and stability. The results indicate that measurements of metabolites are susceptible to differences in pre-analytical conditions and extraction solvents. This proposed approach can increase the positive rate of the future development of biomarkers. Altogether, the procedure can be easily adapted and applied to other studies, where the limited number of samples is a common barrier.


2017 ◽  
Author(s):  
Gabriel Guerrer

Motivated by a series of reported experiments and their controversial results, the present work investigated if volunteers could causally affect an optical double-slit system by mental efforts alone. The participants' task in the experimental sessions alternated between intending an increase in the (real-time feedback-informed) amount of light diffracted through a specific single slit versus relaxing their intentional effort. In total, 240 sessions contributed by 171 volunteers were recorded. The first 160 sessions were collected in an exploratory mode, and those data revealed statistically significant differences between the intention and relax conditions. The analysis method and variables of interest derived from the exploratory sessions were then pre-registered for the subsequent 80 formal sessions. The formal experiments, based on a directional hypothesis, were not statistically significant. A post hoc meta-analysis based on a bi-directional hypothesis, and applied to the same data, resulted in a 2.75 sigma outcome ($p=6.02\times10^{-3}; \, es=0.31 \pm 0.22$ 95\% CI). Directional and bi-directional analyses applied to an equal number of control sessions, all conducted without observers present, resulted in uniformly non-significant outcomes. Analysis of environmental factors did not reveal any artifactual sources that might have produced the significant bi-directional effect. While the pre-registered analysis did not support the existence of the investigated phenomenon, the post hoc findings warrant further investigation to formally test the bi-directional hypothesis.


2013 ◽  
Vol 10 (4) ◽  
pp. 523-532 ◽  
Author(s):  
Irini Anastasiadi ◽  
George Tzetzis

Background:The Children’s Assessment of Participation and Enjoyment (CAPE) and the Preferences for Activities of Children (PAC) are 2 measures of children’s participation in various activities. The purpose of this study was the validation of the Greek version of “CAPE & PAC.”Methods:The questionnaires were translated and pilot tested on a sample of 25 individuals. The reliability and validity of the questionnaires were tested on 302 individuals (253 typical population, 49 disabled), 6−21 years of age. The construct validity of the instruments was examined the directional hypothesis by comparing known groups with existing differences. An exploratory factor analysis was conducted to determine the validity of the typology of activities. The reliability was examined by checking the internal consistency of the instruments.Results:The comparison between divergent groups confirmed the predicted differences of the mean scores and the validity of the instruments. Seven factors (categories of activities) emerged from the factor analysis. The acceptable range of Cronbach alpha for the PAC scale indicated high consistency.Conclusion:This study provides evidence that partially support the validity and reliability of “CAPE & PAC” instruments to use in Greek population. Further investigation is recommended for both clinical and research purposes.


2006 ◽  
Vol 24 (5) ◽  
pp. 727-735 ◽  
Author(s):  
Michael I. Koukourakis ◽  
Søren M. Bentzen ◽  
Alexandra Giatromanolaki ◽  
George D. Wilson ◽  
Frances M. Daley ◽  
...  

Purpose Randomized controlled trials have generally shown a benefit from accelerated radiotherapy in head and neck squamous cell carcinoma (HNSCC). However, the large randomized United Kingdom trial CHART (Continuous Hyperfractionated Accelerated Radiotherapy) failed to show a benefit of strongly accelerated over standard radiotherapy (RT) in 918 patients with HNSCC. In this study, we investigated the impact of tumor hypoxia on the outcome of HNSCC patients in the CHART trial. There are two distinct hypoxia inducible factors (HIFs) that control different gene response pathways and we assessed them both with endogenous markers of hypoxia, hypoxia inducible factor HIF-2 alpha (HIF-2) and carbonic anhydrase CA9, an indicator of HIF-1 alpha (HIF-1) function. Methods Tissue from pre-RT biopsies performed in 198 of 918 patients recruited was analyzed for the immunohistochemical expression of HIF-2 and CA9. Results A significant association of high HIF2 and of high CA9 reactivity with poor locoregional control (P < .0001 and P = .0002, respectively) and poor survival (P = .0004 and 0.002, respectively) was noted. In multivariate analysis, HIF-2 and CA9 maintained their independent prognostic significance. Coexpression of both pathways had an additive effect, supporting their independent role. The uni-directional hypothesis, that a benefit from randomization to CHART should be seen in the nonhypoxic tumors, was supported by the data (one-tailed P = .04). Conclusion Expression of endogenous markers of hypoxia for the HIF-1 and HIF-2 pathway is strongly associated with radiotherapy failure. Using immunohistochemical methods it is possible to identify subgroups of HNSCC patients who are highly curable with radiotherapy, or who are excellent candidates for clinical trials on hypoxia-targeting drugs in two distinct pathways.


Curationis ◽  
1991 ◽  
Vol 14 (2) ◽  
Author(s):  
M.C. Herselman ◽  
M.E. Muller ◽  
M.C. Van Huyssteen

In this study two decentralised organisational designs in nursing management were investigated The purpose of the study was to investigate the effect of two different designs, namely the territorial and matrix designs, on the attitudes and perceptions of nurses towards their work. An explorative descriptive multi-phase study was conducted. The attitudes and perceptions of nurses were assessed by means of the Michigan Organisational Assessment Scale, during the territorial design and after changing to a matrix design. An analysis of the data showed a positive and statistically significant change in attitudes and perceptions in the matrix design, and therefore the directional hypothesis was accepted. Recommendations include further refinement of the matrix design, as well as training and accompaniment of nurse managers to implement the principles.


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