Left-right patterning is set up early in development, at embryonic day 8.5 in the mouse. Cilia are present on the cells of a transient structure, termed the node, the location where L/R symmetry is ...broken. In this pit-like structure, motile cilia generate a leftwards flow of extracellular fluid, which is translated into a left-specific signal by immotile cilia on crown cells at the edge of the node. How exactly this flow is translated remains unknown, with one hypothesis proposing that nodal vesicular parcels (NVPs) within the node transport signalling molecules to the left side. FGF signalling was first implicated in L/R patterning when an Fgf8 mutant mouse was shown to exhibit situs defects. The precise role of FGFs in L/R patterning is unclear, but they have been proposed to regulate NVP release. Other hypotheses include them functioning in the regulation of node cilia length, and in the formation and maintenance of the node structure. These hypotheses are explored in this thesis, through the re-assessment of the Fgf8 mouse mutant and through the use of FGF signalling receptor inhibitors in embryo culture. My findings confirm a role for FGF signalling in L/R determination, and support a role for FGF signalling in specifying, maintaining and/or patterning the cells that make up the embryonic node. My data also casts doubt on the evidence previously used to argue for the existence of NVPs. Analysis of the location of FGFRs in the embryo and within cells shows the presence of FGFR2 in the node cilia, but whether ciliary localisation of FGFRs is important in L/R patterning remains unclear. I present evidence that the major mechanism by which FGF signalling affects L/R determination is through the formation/patterning of the node. However, I also present evidence for a lesser role FGFs may play in controlling mammalian cilia length. Intriguingly, my data also indicates a strong influence of genetic background on the Fgf8 mutants.
Early life stress (ELS) is one of the biggest known risk factors for the development of a range of psychiatric disorders including depression. Events exceeding a child's ability to cope lead to ...elevated glucocorticoid concentrations which cause abnormal brain development with regions involved in reward circuitry such as the hippocampus, amygdala and prefrontal cortex being most impacted. Impairments of reward learning (RL) have been reported to act as an intermediate phenotype in the aetiology of depression. This thesis therefore investigates the hypothesis that ELS predisposes to depression through reprogramming of brain regions associated with reward which causes reward processing deficits that in turn lead to the development of depression. Reward learning was initially attempted to be assessed in a mouse model of ELS using a modified version of the affective bias test. ELS mice showed no differences in RL compared to controls, however there was evidence for a lack of an affective phenotype in the mouse model. A translational reward learning assay, the probabilistic reversal learning task (PRLT), was therefore validated in a cohort of rats for use in future ELS studies. This task was initially sensitive to manipulations of serotonin but showed non-specific impairments following a range of other manipulations including ketamine and amphetamine administration. Task sensitivity also decreased over time suggesting a window of opportunity for successful use. Next the electrophysiological consequences of ELS were assessed in the hippocampus of rats. Maternally separated rats showed increased NMDA but not AMPA receptor function but no changes in basal transmission. Finally reward learning was assessed in a cohort of humans with high levels of ELS. ELS was associated with decreased positive feedback sensitivity and reduced initial learning in the PRLT. The results from this thesis suggest that the proposed hypothesis is plausible, however further work is needed to both confirm this and translate findings into patient benefit.
Abstract only Introduction A “reproducibility crisis” has afflicted the recent medical literature, affecting 75‐89% of major reported findings. An important cause of the inability to replicate ...results is hypothesizing after the results are known (HARKing): presenting a post hoc hypothesis according with findings as if it were a confirmed a priori hypothesis. Meeting abstract instructions may affect the frequency of HARKing. Methods We tested the hypothesis that, compared with abstract instructions NOT indicating a "hypothesis" should be stated, instructions indicating THAT a "hypothesis" should be stated would increase the proportion of abstracts judged by field content experts to exhibit HARKing. Hypothesis pre‐registered at AsPredicted.org (#5019). We analyzed randomly sampled abstracts from 4 International Stroke Conference (ISC) meeting years with highly forceful (2015), moderately forceful (2017), and non‐forceful (2013 and 2022) requirements for statement of a “hypothesis” in abstract preparation instructions, regardless of whether a hypothesis statement was appropriate (confirmatory science) or inappropriate (exploratory science). Results The 163 abstracts (39 to 43 in each meeting year) equally sampled the 14‐17 ISC topic categories. Explicit “hypothesis” statements were more common in the highly and moderately forceful instruction years (30% and 27%) than in the non‐forceful instruction years (9% and 13%) (p = 0.006). Among the total 32 hypothesis statements, 81% were deemed falsifiable, and 19% non‐falsifiable. None (0%) of hypotheses were stated as pre‐registered prior to study conduct. Overall, 59% (19/32) of the hypothesis statements were adjudicated by two independent content experts as likely to be hypothesizing after the results were known (HARKing). HARKing was more common in the highly and moderately forceful instruction years (20% and 15%) than the non‐forceful instruction years (9% and 3%) (p = 0.03). Conclusion Abstract preparation instructions requiring the use of a hypothesis statement promoted hypothesizing after the results are known, with HARKing present in 1 out of every 5 meeting abstracts. To improve reproducibility of neurovascular research studies, appropriate meeting abstract preparation instructions are desirable, recommending hypothesis statements only for the small proportion of stroke studies that are of confirmatory, rather than exploratory, design.
La presente investigación trata de explorar la validez de algunas de las principales hipótesis deducidas de la Teoría de las Estrategias Sexuales de Buss, en una muestra representativa de la ...población española. Dichas hipótesis hacen referencia a «estrategias» (no necesariamente conscientes ni planeadas) diferentes entre hombres y mujeres a la hora de involucrarse en una relación sexual a corto plazo (coloquialmente «ligar») o a largo plazo («relación amorosa»). Los datos se obtuvieron mediante autoinforme, sobre una muestra representativa de la población española (n= 1.949). Casi todos los resultados obtenidos confirman las hipótesis planteadas, lo cual supone un cierto apoyo empírico a la teoría de la que han sido deducidas, dentro del enfoque evolucionista de la Psicología Social. En cualquier caso, se argumenta que la mayor parte de las diferencias constatadas son también explicables desde los enfoques de la socialización diferencial (la «doble moral» y la construcción social del rol de género y de la identidad sexual), y se comenta la perfecta compatibilidad de ambos enfoques. Analysis of Sexual Strategies Theory in the Spanish population.The aim of this study was to test some of the main hypotheses derived from Buss’ Sexual Strategies Theory on a representative Spanish sample. These hypotheses refer to the different strategies men and woman seem to adopt when they want to engage in a short-term sexual relationship (fling), or in a long-term one (loving relationship). (The technical term «strategies», unlike its equivalent in everyday language, is not meant to imply something necessarily planned or conscious). Data was obtained by self-report from a representative sample of 1949 Spanish people. Almost all the results verify the working hypotheses, conferring some empirical support on the theory from which they were deduced, within an evolutionary Social Psychology paradigm. In any case, it is argued that socialization approaches («double moral» and the social construction of gender role and sexual identity) can also explain most of the differences obtained, in perfect compatibility with biological perspectives.
Background: Appendicular lean mass (ALM), which is a surrogate measure of appendicular skeletal muscle mass, can be easily measured by a dual-energy X-ray absorptiometry (DXA) scanner. The amount of ...muscle a child has is the main determinant of their strength, however other developmental factors may change the relationship between strength and muscle mass. The current study tested the hypothesis that strength increases as a function of age in children and adolescents independently of ALM; and that even after controlling for lean mass and age, males have greater strength than females. Methods: The hypothesis was tested by measuring strength (peak torque) in a racially and ethnically diverse sample of 190 children and adolescents in the ShapeUp! Kids study (age, X ± SD; 11.59 ± 3.36 yrs). Peak Torque measurements were taken on a Biodex System 4, and ALM was evaluated with Hologic Discovery A DXA system. Stepwise multiple regression models were developed with strength as the dependent variable and ALM, age, and gender as covariates. Results: The developed model including strength as the dependent variable and age, gender, and ALM as covariates showed a combined R2 of 0.77 with girls separately, R2, 0.65 and boys R2, 0.83. Using strength as the dependent variable, age, gender, and ALM were all significant (p < 0.05) covariates. Similar trends were observed when age was replaced with Tanner Stage; strength/ALM increased with Tanner Stage. Conclusions: Strength in children and adolescents is strongly related to ALM, a surrogate measure of muscle mass. After controlling for ALM, age and gender were additional strength determinants, suggesting that strength is determined by mechanisms beyond that accounted solely be muscle mass. Our results also suggest that even after controlling for lean mass and age, that boys are stronger than girls.
A large body of research has shown that engaging in self-explanation improves learning across a range of tasks. It has been proposed that the act of explaining draws attention and cognitive resources ...towards evidence that supports good explanations—information that is broad, abstract, and consistent with prior knowledge—which in turn aids discovery and promotes generalization. However, it remains unclear whether explanation impacts the learning process via improved hypothesis generation, increasing the probability that the most generalizable hypotheses are considered in the first place, or hypothesis evaluation, the appraisal of such hypotheses in light of observed evidence. In two experiments with adults, we address this question by separating hypothesis generation and evaluation in a novel category learning task and quantifying the effect of explaining on each process independently. We find that explanation supports learners' generation of broad and abstract hypotheses but does not impact their evaluation of them. These results provide a more precise account of the process by which explanation impacts learning and offer additional support for the claim that hypothesis generation and evaluation play distinct roles in problem solving.
What do the leaders of the Municipal Health Service (SMS) report and say about the systematic monitoring and evaluation of their own government management? The purpose of this paper is to provide ...input for the formulation of plausible hypotheses about such institutional processes and practices based on information produced in an exploratory study. This is a multiple case study with quantitative and qualitative analysis of answers to a semi-structured questionnaire given to government officials of a systematic sample of 577 Municipal Health Services (10.4% of the total in Brazil). They were selected and stratified by proportional distribution among states and by the population size of municipalities. In general, it shows that approximately half of the respondents use information from Health Monitoring Evaluations to orient decision-making, planning and other management approaches. This proportion tends to decrease in cities with smaller populations. There are specific and significant gaps in financial, personnel and crisis management. The evidence from the hypotheses highlights the fact that these processes are still at an early stage.
Reply Gaucher, David; Gaudric, Alain
American journal of ophthalmology,
09/2008, Volume:
146, Issue:
3
Journal Article
Peer reviewed
...these cases of severe hypotonia are usually associated with choroidal folds and optic disc edema,1 which was not the case in our patients. ...no objective element in our observations supported the ...hypothesis of hypotonia.
We tested the hypothesis that underrepresented students in active-learning classrooms experience narrower achievement gaps than underrepresented students in traditional lecturing classrooms, averaged ...across all science, technology, engineering, and mathematics (STEM) fields and courses. We conducted a comprehensive search for both published and unpublished studies that compared the performance of underrepresented students to their overrepresented classmates in active-learning and traditional-lecturing treatments. This search resulted in data on student examination scores from 15 studies (9,238 total students) and data on student failure rates from 26 studies (44,606 total students). Bayesian regression analyses showed that on average, active learning reduced achievement gaps in examination scores by 33% and narrowed gaps in passing rates by 45%. The reported proportion of time that students spend on in-class activities was important, as only classes that implemented high-intensity active learning narrowed achievement gaps. Sensitivity analyses showed that the conclusions are robust to sampling bias and other issues. To explain the extensive variation in efficacy observed among studies, we propose the heads-and-hearts hypothesis, which holds that meaningful reductions in achievement gaps only occur when course designs combine deliberate practice with inclusive teaching. Our results support calls to replace traditional lecturing with evidence-based, active-learning course designs across the STEM disciplines and suggest that innovations in instructional strategies can increase equity in higher education.
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