Setting an Optimal α That Minimizes Errors in Null Hypothesis Significance Tests

Null hypothesis significance testing has been under attack in recent years, partly owing to the arbitrary nature of setting α (the decision-making threshold and probability of Type I error) at a constant value, usually 0.05. If the goal of null hypothesis testing is to present conclusions in which we have the highest possible confidence, then the only logical decision-making threshold is the value that minimizes the probability (or occasionally, cost) of making errors. Setting α to minimize the combination of Type I and Type II error at a critical effect size can easily be accomplished for traditional statistical tests by calculating the α associated with the minimum average of α and β at the critical effect size. This technique also has the flexibility to incorporate prior probabilities of null and alternate hypotheses and/or relative costs of Type I and Type II errors, if known. Using an optimal α results in stronger scientific inferences because it estimates and minimizes both Type I errors and relevant Type II errors for a test. It also results in greater transparency concerning assumptions about relevant effect size(s) and the relative costs of Type I and II errors. By contrast, the use of α = 0.05 results in arbitrary decisions about what effect sizes will likely be considered significant, if real, and results in arbitrary amounts of Type II error for meaningful potential effect sizes. We cannot identify a rationale for continuing to arbitrarily use α = 0.05 for null hypothesis significance tests in any field, when it is possible to determine an optimal α

The Early Positive Approaches to Support (E-PAtS) study: study protocol for a feasibility cluster randomised controlled trial of a group programme (E-PAtS) for family caregivers of young children with intellectual disability

Background: Children with intellectual disability have an IQ < 70, associated deficits in adaptive skills and are at increased risk of having clinically concerning levels of behaviour problems. In addition, parents of children with intellectual disability are likely to report high levels of mental health and other psychological problems. The Early Positive Approaches to Support (E-PAtS) programme for family caregivers of young children (5 years and under) with intellectual and developmental disabilities is a group-based intervention which aims to enhance parental psychosocial wellbeing and service access and support positive development for children. The aim of this study is to assess the feasibility of delivering E-PAtS to family caregivers of children with intellectual disability by community parenting support service provider organisations. The study will inform a potential, definitive RCT of the effectiveness and cost-effectiveness of E-PAtS. Methods: This study is a feasibility cluster randomised controlled trial, with embedded process evaluation. Up to 2 family caregivers will be recruited from 64 families with a child (18 months to 5 years) with intellectual disability at research sites in the UK. Participating families will be allocated to intervention: control on a 1:1 basis; intervention families will be offered the E-PAtS programme immediately, continuing to receive usual practice, and control participants will be offered the opportunity to attend the E-PAtS programme at the end of the follow-up period and will continue to receive usual practice. Data will be collected at baseline, 3 months post-randomisation and 12 months post-randomisation. The primary aim is to assess feasibility via the assessment of: recruitment of service provider organisations; participant recruitment; randomisation; retention; intervention adherence; intervention fidelity and the views of participants, intervention facilitators and service provider organisations regarding intervention delivery and study processes. The secondary aim is preliminary evaluation of a range of established outcome measures for individual family members, subsystem relationships and overall family functioning, plus additional health economic outcomes for inclusion in a future definitive trial. Discussion: The results of this study will inform a potential future definitive trial, to evaluate the effectiveness and cost-effectiveness of the E-PAtS intervention to improve parental psychosocial wellbeing. Such a trial would have significant scientific impact internationally in the intellectual disability field

A probabilistic interpretation of PID controllers using active inference

In the past few decades, probabilistic interpretations of brain functions have become widespread in cognitive science and neuroscience. The Bayesian brain hypothesis, predictive coding, the free energy principle and active inference are increasingly popular theories of cognitive functions that claim to unify understandings of life and cognition within general mathematical frameworks derived from information and control theory, statistical physics and machine learning. The connections between information and control theory have been discussed since the 1950’s by scientists like Shannon and Kalman and have recently risen to prominence in modern stochastic optimal control theory. However, the implications of the confluence of these two theoretical frameworks for the biological sciences have been slow to emerge. Here we argue that if the active inference proposal is to be taken as a general process theory for biological systems, we need to consider how existing control theoretical approaches to biological systems relate to it. In this work we will focus on PID (Proportional-Integral-Derivative) controllers, one of the most common types of regulators employed in engineering and more recently used to explain behaviour in biological systems, e.g. chemotaxis in bacteria and amoebae or robust adaptation in biochemical networks. Using active inference, we derive a probabilistic interpretation of PID controllers, showing how they can fit a more general theory of life and cognition under the principle of (variational) free energy minimisation under simple linear generative models.most common types of regulators employed in engineering and more recently used to explain behaviour in biological systems, e.g. chemotaxis in bacteria and amoebae or robust adaptation in biochemical networks. Using active inference, we derive a probabilistic interpretation of PID controllers, showing how they can fit a more general theory of life and cognition under the principle of (variational) free energy minimisation under simple linear generative models

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Genome sequence analyses of two isolates from the recent Escherichia coli outbreak in Germany reveal the emergence of a new pathotype: Entero-Aggregative-Haemorrhagic Escherichia coli (EAHEC)

The genome sequences of two Escherichia coli O104:H4 strains derived from two different patients of the 2011 German E. coli outbreak were determined. The two analyzed strains were designated E. coli GOS1 and GOS2 (German outbreak strain). Both isolates comprise one chromosome of approximately 5.31 Mbp and two putative plasmids. Comparisons of the 5,217 (GOS1) and 5,224 (GOS2) predicted protein-encoding genes with various E. coli strains, and a multilocus sequence typing analysis revealed that the isolates were most similar to the entero-aggregative E. coli (EAEC) strain 55989. In addition, one of the putative plasmids of the outbreak strain is similar to pAA-type plasmids of EAEC strains, which contain aggregative adhesion fimbrial operons. The second putative plasmid harbors genes for extended-spectrum β-lactamases. This type of plasmid is widely distributed in pathogenic E. coli strains. A significant difference of the E. coli GOS1 and GOS2 genomes to those of EAEC strains is the presence of a prophage encoding the Shiga toxin, which is characteristic for enterohemorrhagic E. coli (EHEC) strains. The unique combination of genomic features of the German outbreak strain, containing characteristics from pathotypes EAEC and EHEC, suggested that it represents a new pathotype Entero-Aggregative-Haemorrhagic Escherichiacoli (EAHEC)

Does home neighbourhood supportiveness influence the location more than volume of adolescent's physical activity? An observational study using Global Positioning Systems

Background: Environmental characteristics of home neighbourhoods are hypothesised to be associated with residents’ physical activity levels, yet many studies report only weak or equivocal associations. We theorise that this may be because neighbourhood characteristics influence the location of activity more than the volume. Using a sample of UK adolescents, we examine the role of home neighbourhood supportiveness for physical activity, both in terms of volume of activity undertaken and a measure of proximity to home at which activity takes place. Methods: Data were analysed from 967 adolescents living in and around the city of Bristol, UK. Each participant wore an accelerometer and a GPS device for seven days during school term time. These data were integrated into a Geographical Information System containing information on the participants’ home neighbourhoods and measures of environmental supportiveness. We then identified the amount of out-of-school activity of different intensities that adolescents undertook inside their home neighbourhood and examined how this related to home neighbourhood supportiveness. Results: We found that living in a less supportive neighbourhood did not negatively impact the volume of physical activity that adolescents undertook. Indeed these participants recorded similar amounts of activity (e.g. 20.5 mins per day of moderate activity at weekends) as those in more supportive neighbourhoods (18.6 mins per day). However, the amount of activity adolescents undertook inside their home neighbourhood did differ according to supportiveness; those living in less supportive locations had lower odds of recording activity inside their home neighbourhood. This was observed across all intensities of activity including sedentary, light, moderate, and vigorous. Conclusions: Our findings suggest that the supportiveness of the neighbourhood around home may have a greater influence on the location of physical activity than the volume undertaken. This finding is at odds with the premise of the socio-ecological models of physical activity that have driven this research field for the last two decades, and has implications for future research, as by simply measuring volumes of activity we may be underestimating the impact of the environment on physical activity behaviours

A latent trait look at pretest-posttest validation of criterion-referenced test items

Since Cox and Vargas (1966) introduced their pretest-posttest validity index for criterion-referenced test items, a great number of additions and modifications have followed. All are based on the idea of gain scoring; that is, they are computed from the differences between proportions of pretest and posttest item responses. Although the method is simple and generally considered as the prototype of criterion-referenced item analysis, it has many and serious disadvantages. Some of these go back to the fact that it leads to indices based on a dual test administration- and population-dependent item p values. Others have to do with the global information about the discriminating power that these indices provide, the implicit weighting they suppose, and the meaningless maximization of posttest scores they lead to. Analyzing the pretest-posttest method from a latent trait point of view, it is proposed to replace indices like Cox and Vargas’ Dpp by an evaluation of the item information function for the mastery score. An empirical study was conducted to compare the differences in item selection between both methods

Association between neighborhood safety and overweight status among urban adolescents

<p>Abstract</p> <p>Background</p> <p>Neighborhood safety may be an important social environmental determinant of overweight. We examined the relationship between perceived neighborhood safety and overweight status, and assessed the validity of reported neighborhood safety among a representative community sample of urban adolescents (who were racially and ethnically diverse).</p> <p>Methods</p> <p>Data come from the 2006 Boston Youth Survey, a cross-sectional study in which public high school students in Boston, MA completed a pencil-and-paper survey. The study used a two-stage, stratified sampling design whereby schools and then 9^th–12^thgrade classrooms within schools were selected (the analytic sample included 1,140 students). Students reported their perceptions of neighborhood safety and several associated dimensions. With self-reported height and weight data, we computed body mass index (BMI, kg/m²) for the adolescents based on CDC growth charts. Chi-square statistics and corresponding <it>p</it>-values were computed to compare perceived neighborhood safety by the several associated dimensions. Prevalence ratios (PRs) and 95% confidence intervals (CI) were calculated to examine the association between perceived neighborhood safety and the prevalence of overweight status controlling for relevant covariates and school site.</p> <p>Results</p> <p>More than one-third (35.6%) of students said they always felt safe in their neighborhood, 43.9% said they sometimes felt safe, 11.6% rarely felt safe, and 8.9% never felt safe. Those students who reported that they rarely or never feel safe in their neighborhoods were more likely than those who said they always or sometimes feel safe to believe that gang violence was a serious problem in their neighborhood or school (68.0% vs. 44.1%, <it>p </it>< 0.001), and to have seen someone in their neighborhood assaulted with a weapon (other than a firearm) in the past 12 months (17.8% vs. 11.3%, <it>p </it>= 0.025). In the fully adjusted model (including grade and school) stratified by race/ethnicity, we found a statistically significant association between feeling unsafe in one's own neighborhood and overweight status among those in the Other race/ethnicity group [(PR = 1.56, (95% CI: 1.02, 2.40)].</p> <p>Conclusion</p> <p>Data suggest that perception of neighborhood safety may be associated with overweight status among urban adolescents in certain racial/ethnic groups. Policies and programs to address neighborhood safety may also be preventive for adolescent overweight.</p