scholarly journals Towards better hypothesis tests in oxytocin research: Evaluating the validity of auxiliary assumptions

2021 ◽  
Author(s):  
Daniel S Quintana
Keyword(s):  
Experimental Design ◽  
Hypothesis Testing ◽  
Small Sample ◽  
Social Cues ◽  
The Body ◽  
Theoretical Frameworks ◽  
Small Sample Sizes ◽  
The Brain ◽  
Behavior And Cognition

Various factors have been attributed to the inconsistent reproducibility of human oxytocin research in the cognitive and behavioral sciences. These factors include small sample sizes, a lack of pre-registered studies, and the absence of overarching theoretical frameworks that can account for oxytocin’s effects over a broad range of contexts. While there have been efforts to remedy these issues, there has been very little systematic scrutiny of the role of auxiliary assumptions, which are claims that are not central for testing a hypothesis but nonetheless critical for testing theories. For instance, the hypothesis that oxytocin increases the salience of social cues is predicated on the assumption that intranasally administered oxytocin increases oxytocin levels in the brain. Without robust auxiliary assumptions, it is unclear whether a hypothesis testing failure is due to an incorrect hypothesis or weak auxiliary assumptions. Consequently, weak auxiliary assumptions can be blamed for hypothesis failure, thereby safeguarding theories from falsification. In this article, I will evaluate the body of evidence for key auxiliary assumptions in human behavioral oxytocin research in terms of theory, experimental design, and statistical inference, and highlight assumptions that require stronger evidence. Strong auxiliary assumptions will leave hypotheses vulnerable for falsification, which will improve hypothesis testing and consequently advance our understanding of oxytocin’s role in behavior and cognition.

scholarly journals Millimeter (MM) wave and microwave frequency radiation produce deeply penetrating effects: the biology and the physics

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Martin L. Pall
Keyword(s):  
Magnetic Fields ◽  
Electric Fields ◽  
Cardiac Activity ◽  
Maximum Level ◽  
Voltage Sensor ◽  
The Body ◽  
Time Varying ◽  
The Brain ◽  
Mm Waves

Abstract Millimeter wave (MM-wave) electromagnetic fields (EMFs) are predicted to not produce penetrating effects in the body. The electric but not magnetic part of MM-EMFs are almost completely absorbed within the outer 1 mm of the body. Rodents are reported to have penetrating MM-wave impacts on the brain, the myocardium, liver, kidney and bone marrow. MM-waves produce electromagnetic sensitivity-like changes in rodent, frog and skate tissues. In humans, MM-waves have penetrating effects including impacts on the brain, producing EEG changes and other neurological/neuropsychiatric changes, increases in apparent electromagnetic hypersensitivity and produce changes on ulcers and cardiac activity. This review focuses on several issues required to understand penetrating effects of MM-waves and microwaves: 1. Electronically generated EMFs are coherent, producing much higher electrical and magnetic forces then do natural incoherent EMFs. 2. The fixed relationship between electrical and magnetic fields found in EMFs in a vacuum or highly permeable medium such as air, predicted by Maxwell’s equations, breaks down in other materials. Specifically, MM-wave electrical fields are almost completely absorbed in the outer 1 mm of the body due to the high dielectric constant of biological aqueous phases. However, the magnetic fields are very highly penetrating. 3. Time-varying magnetic fields have central roles in producing highly penetrating effects. The primary mechanism of EMF action is voltage-gated calcium channel (VGCC) activation with the EMFs acting via their forces on the voltage sensor, rather than by depolarization of the plasma membrane. Two distinct mechanisms, an indirect and a direct mechanism, are consistent with and predicted by the physics, to explain penetrating MM-wave VGCC activation via the voltage sensor. Time-varying coherent magnetic fields, as predicted by the Maxwell–Faraday version of Faraday’s law of induction, can put forces on ions dissolved in aqueous phases deep within the body, regenerating coherent electric fields which activate the VGCC voltage sensor. In addition, time-varying magnetic fields can directly put forces on the 20 charges in the VGCC voltage sensor. There are three very important findings here which are rarely recognized in the EMF scientific literature: coherence of electronically generated EMFs; the key role of time-varying magnetic fields in generating highly penetrating effects; the key role of both modulating and pure EMF pulses in greatly increasing very short term high level time-variation of magnetic and electric fields. It is probable that genuine safety guidelines must keep nanosecond timescale-variation of coherent electric and magnetic fields below some maximum level in order to produce genuine safety. These findings have important implications with regard to 5G radiation.

CCM3 Loss-Induced Lymphatic Defect Is Mediated by the Augmented VEGFR3-ERK1/2 Signaling

2021 ◽  
Author(s):  
Lingfeng Qin ◽  
Haifeng Zhang ◽  
Busu Li ◽  
Quan Jiang ◽  
Francesc Lopez ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Fluorescein Isothiocyanate ◽  
The Body ◽  
Blue Dye ◽  
Transcriptional Level ◽  
Dependent Manner ◽  
Cavernous Malformations ◽  
Morphological Alterations ◽  
The Brain

Objective: Cerebral cavernous malformations (CCMs) can happen anywhere in the body, although they most commonly produce symptoms in the brain. The role of CCM genes in other vascular beds outside the brain and retina is not well-examined, although the 3 CCM-associated genes ( CCM1 , CCM2 , and CCM3 ) are ubiquitously expressed in all tissues. We aimed to determine the role of CCM gene in lymphatics. Approach and Results: Mice with an inducible pan–endothelial cell (EC) or lymphatic EC deletion of Ccm3 ( Pdcd10 ECKO or Pdcd10 LECKO ) exhibit dilated lymphatic capillaries and collecting vessels with abnormal valve structure. Morphological alterations were correlated with lymphatic dysfunction in Pdcd10 LECKO mice as determined by Evans blue dye and fluorescein isothiocyanate(FITC)-dextran transport assays. Pdcd10 LECKO lymphatics had increased VEGFR3 (vascular endothelial growth factor receptor-3)-ERK1/2 signaling with lymphatic hyperplasia. Mechanistic studies suggested that VEGFR3 is primarily regulated at a transcriptional level in Ccm3-deficient lymphatic ECs, in an NF-κB (nuclear factor κB)–dependent manner. CCM3 binds to importin alpha 2/KPNA2 (karyopherin subunit alpha 2), and a CCM3 deletion releases KPNA2 to activate NF-κB P65 by facilitating its nuclear translocation and P65-dependent VEGFR3 transcription. Moreover, increased VEGFR3 in lymphatic EC preferentially activates ERK1/2 signaling, which is critical for lymphatic EC proliferation. Importantly, inhibition of VEGFR3 or ERK1/2 rescued the lymphatic defects in structure and function. Conclusions: Our data demonstrate that CCM3 deletion augments the VEGFR3-ERK1/2 signaling in lymphatic EC that drives lymphatic hyperplasia and malformation and warrant further investigation on the potential clinical relevance of lymphatic dysfunction in patients with CCM.

scholarly journals Role of MicroRNAs in Parkinson’s Disease

2019 ◽  
Vol 20 (22) ◽  
pp. 5649 ◽  
Author(s):  
Suh Yee Goh ◽  
Yin Xia Chao ◽  
Shaikali Thameem Dheen ◽  
Eng-King Tan ◽  
Samuel Sam-Wah Tay
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Small Sample Size ◽  
Small Sample ◽  
Biological Molecules ◽  
Incomplete Penetrance ◽  
Cellular Functions ◽  
Druggable Targets ◽  
The Brain

Parkinson’s disease (PD) is a disabling neurodegenerative disease that manifests with resting tremor, bradykinesia, rigidity and postural instability. Since the discovery of microRNAs (miRNAs) in 1993, miRNAs have been shown to be important biological molecules involved in diverse processes to maintain normal cellular functions. Over the past decade, many studies have reported dysregulation of miRNA expressions in PD. Here, we identified 15 miRNAs from 34 reported screening studies that demonstrated dysregulation in the brain and/or neuronal models, cerebrospinal fluid (CSF) and blood. Specific miRNAs-of-interest that have been implicated in PD pathogenesis include miR-30, miR-29, let-7, miR-485 and miR-26. However, there are several challenges and limitations in drawing definitive conclusions due to the small sample size in clinical studies, varied laboratory techniques and methodologies and their incomplete penetrance of the blood–brain barrier. Developing an optimal delivery system and unravelling druggable targets of miRNAs in both experimental and human models and clinical validation of the results may pave way for novel therapeutics in PD.

scholarly journals Radiomics for the Diagnosis and Differentiation of Pancreatic Cystic Lesions

Diagnostics ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 505
Author(s):  
Jorge D. Machicado ◽  
Eugene J. Koay ◽  
Somashekar G. Krishna
Keyword(s):  
Predictive Accuracy ◽  
Quantitative Imaging ◽  
Standard Of Care ◽  
Small Sample ◽  
Cystic Lesions ◽  
Current Standard ◽  
Cross Sectional ◽  
Small Sample Sizes ◽  
Insight Into

Radiomics, also known as quantitative imaging or texture analysis, involves extracting a large number of features traditionally unmeasured in conventional radiological cross-sectional images and converting them into mathematical models. This review describes this approach and its use in the evaluation of pancreatic cystic lesions (PCLs). This discipline has the potential of more accurately assessing, classifying, risk stratifying, and guiding the management of PCLs. Existing studies have provided important insight into the role of radiomics in managing PCLs. Although these studies are limited by the use of retrospective design, single center data, and small sample sizes, radiomic features in combination with clinical data appear to be superior to the current standard of care in differentiating cyst type and in identifying mucinous PCLs with high-grade dysplasia. Combining radiomic features with other novel endoscopic diagnostics, including cyst fluid molecular analysis and confocal endomicroscopy, can potentially optimize the predictive accuracy of these models. There is a need for multicenter prospective studies to elucidate the role of radiomics in the management of PCLs.

scholarly journals Concentrations of the Selected Biomarkers of Endothelial Dysfunction in Response to Antiepileptic Drugs: A Literature Review

2019 ◽  
Vol 25 ◽  
pp. 107602961985942 ◽  
Author(s):  
Beata Sarecka-Hujar ◽  
Izabela Szołtysek-Bołdys ◽  
Ilona Kopyta ◽  
Barbara Dolińska ◽  
Andrzej Sobczak
Keyword(s):  
Risk Factors ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Literature Review ◽  
Antiepileptic Drug ◽  
Asymmetric Dimethylarginine ◽  
The Body ◽  
Biochemical Processes ◽  
The Brain

Epilepsy is a disease arising from morphological and metabolic changes in the brain. Approximately 60% of patients with seizures can be controlled with 1 antiepileptic drug (AED), while in others, polytherapy is required. The AED treatment affects a number of biochemical processes in the body, including increasing the risk of cardiovascular diseases (CVDs). It is indicated that the duration of AED therapy with some AEDs significantly accelerates the process of atherosclerosis. Most of AEDs increase levels of homocysteine (HCys) as well as may affect concentrations of new, nonclassical risk factors for atherosclerosis, that is, asymmetric dimethylarginine (ADMA) and homoarginine (hArg). Because of the role of these parameters in the pathogenesis of CVD, knowledge of HCys, ADMA, and hArg concentrations in patients with epilepsia treated with AED, both pediatric and adult, appears to be of significant importance.

scholarly journals What Role Does the Prefrontal Cortex Play in the Processing of Negative and Positive Stimuli in Adolescent Depression?

2019 ◽  
Vol 9 (5) ◽  
pp. 104 ◽  
Author(s):  
Siyabend Kaya ◽  
Ciara McCabe
Keyword(s):  
Prefrontal Cortex ◽  
Adolescent Depression ◽  
Region Of Interest ◽  
Small Sample ◽  
Symptoms Of Depression ◽  
Small Sample Sizes ◽  
Positive Stimuli ◽  
Larger Sample ◽  
Negative Stimuli

This perspective describes the contribution of the prefrontal cortex to the symptoms of depression in adolescents and specifically the processing of positive and negative information. We also discuss how the prefrontal cortex (PFC) activity and connectivity during tasks and at rest might be a biomarker for risk for depression onset in adolescents. We include some of our recent work examining not only the anticipation and consummation of positive and negative stimuli, but also effort to gain positive and avoid negative stimuli in adolescents with depression. We find, using region of interest analyses, that the PFC is blunted in those with depression compared to controls across the different phases but in a larger sample the PFC is blunted in the anticipatory phase of the study only. Taken together, in adolescents with depression there is evidence for dysfunctional PFC activity across different studies and tasks. However, the data are limited with small sample sizes and inconsistent findings. Larger longitudinal studies with more detailed assessments of symptoms across the spectrum are needed to further evaluate the role of the PFC in adolescent depression.

Penalized Binary Regression for Gene Expression Profiling

2004 ◽  
Vol 43 (05) ◽  
pp. 439-444 ◽  
Author(s):  
Michae Schimek
Keyword(s):  
Microarray Analysis ◽  
Predictive Performance ◽  
Small Sample ◽  
Probit Regression ◽  
Binary Regression ◽  
Data Set ◽  
Small Sample Sizes ◽  
Bayesian Probit Regression

Summary Objectives: A typical bioinformatics task in microarray analysis is the classification of biological samples into two alternative categories. A procedure is needed which, based on the expression levels measured, allows us to compute the probability that a new sample belongs to a certain class. Methods: For the purpose of classification the statistical approach of binary regression is considered. High-dimensionality and at the same time small sample sizes make it a challenging task. Standard logit or probit regression fails because of condition problems and poor predictive performance. The concepts of frequentist and of Bayesian penalization for binary regression are introduced. A Bayesian interpretation of the penalized log-likelihood is given. Finally the role of cross-validation for regularization and feature selection is discussed. Results: Penalization makes classical binary regression a suitable tool for microarray analysis. We illustrate penalized logit and Bayesian probit regression on a well-known data set and compare the obtained results, also with respect to published results from decision trees. Conclusions: The frequentist and the Bayesian penalization concept work equally well on the example data, however some method-specific differences can be made out. Moreover the Bayesian approach yields a quantification (posterior probabilities) of the bias due to the constraining assumptions.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Epigenetic modifications and gestational diabetes: a systematic review of published literature

2017 ◽  
Vol 176 (5) ◽  
pp. R247-R267 ◽  
Author(s):  
Gunn-Helen Moen ◽  
Christine Sommer ◽  
Rashmi B Prasad ◽  
Line Sletner ◽  
Leif Groop ◽  
...  
Keyword(s):  
Systematic Review ◽  
Gestational Diabetes ◽  
Current Knowledge ◽  
Epigenetic Modifications ◽  
Research Literature ◽  
Small Sample ◽  
Epigenetic Alterations ◽  
Search Terms ◽  
Small Sample Sizes

ObjectiveTo summarize the current knowledge on epigenetic alterations in mother and offspring subjected to gestational diabetes (GDM) and indicate future topics for research.DesignSystematic review.MethodsWe performed extensive searches in PubMed, EMBASE and Google scholar, using a combination of the search terms: GDM, gestational diabetes, epigenetic(s), methylation, histone modification, histone methylation, histone acetylation, microRNA and miRNA. Studies that compared women diagnosed with GDM and healthy controls were included. Two authors independently scanned the abstracts, and all included papers were read by at least two authors. The searches were completed on October 31st, 2016.ResultsWe identified 236 articles, of which 43 were considered relevant for this systematic review. Studies published showed that epigenetic alterations could be found in both mothers with GDM and their offspring. However, differences in methodology, diagnostic criteria for GDM and populations studied, together with a limited number of published studies and small sample sizes, preclude clear conclusions about the role of epigenetic modifications in transmitting risk from GDM mothers to their offspring.ConclusionThe current research literature suggests that GDM may have impact on epigenetic modifications in the mother and offspring. However, larger studies that include multiple cohorts of GDM patients and their offspring are needed.

scholarly journals Co-occuring Toxoplasma Infection and Psychotic Symptoms : Case Report

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Carla R Marchira ◽  
Andrian F Kusumadewi ◽  
Patricia Wulandari
Keyword(s):  
Life Support ◽  
The United States ◽  
The Body ◽  
Psychotic Symptoms ◽  
Toxoplasma Infection ◽  
Case Presentation ◽  
The Family ◽  
Brain Neurotransmitter ◽  
The Brain

Abstract   Introduction Schizophrenia is a neuropsychiatric disease that is global and is experienced by 1% of the population in the United States and Europe. This study raises awareness of the role of infectious agents in the initiation of psychotic symptoms in schizophrenia. Case Presentation A 20-year-old man is taken by the family to the emergency department because he has decreased consciousness, and the body suddenly stiffens. Patients begin to experience changes in behavior in the form of difficulty sleeping, when invited to talk quietly, laughing alone and whispering without the other person. TORCH examination found an increase in anti-toxoplasma IgM and IgG. This patient is then given basic life support in the form of ABC (airway, breathing, circulation support) and seizure management. Also given risperidone 2 mg / 12 hours, pyrimethamine 1-II (1x200 mg), pyrimethamine day III-XXI (1x 25 mg), intravenous Cefotaxim 2g / 8 hours, Clindamycin 500 mg / 8 hours. The patient experienced improvement after the second week of treatment. Conclusion Toxoplasmosis causes lesions in the brain that cause changes in brain neurotransmitter pathways, which lead to changes in patient behavior.

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