Hypothesis testing in multivariate normal models with block circular covariance structures.

In this article, we address the problem of simultaneous testing hypothesis about mean and covariance matrix for repeated measures data when both the mean vector and covariance matrix are patterned. In particular, tests about the mean vector under block circular and doubly exchangeable covariance structures have been considered. The null distributions are established for the corresponding likelihood ratio test statistics, and expressions for the exact or near-exact probability density and cumulative distribution functions are obtained. The application of the results is illustrated by both a simulation study and a real-life data example.

Fear inoculation among snake experts.

BACKGROUND: Fear acquisition of certain stimuli, such as snakes, is thought to be rapid, resistant to extinction, and easily transferable onto other similar objects. It has been hypothesized that due to increased survival chances, preparedness to instantly acquire fear towards evolutionary threats has been hardwired into neural pathways of the primate brain. Here, we compare participants' fear of snakes according to experience; from those who often deal with snakes and even suffer snakebites to those unfamiliar with snakes. METHODS: The Snake Questionnaire-12 (SNAQ-12) and Specific Phobia Questionnaire (SPQ) were administered to three groups of participants with a different level of experience with snakes and snakebites: 1) snake experts, 2) firefighters, and 3) college students. RESULTS: This study shows that individuals more experienced with snakes demonstrate lower fear. Moreover, participants who have suffered a snakebite (either venomous or not) score lower on fear of snakes (SNAQ-12), but not of all other potentially phobic stimuli (SPQ). CONCLUSIONS: Our results suggest that a harmless benign exposure might immunize people to highly biologically prepared fears of evolutionary threats, such as snakes.

Interval estimation of small tail probabilities - applications in food safety.

Often in food safety and bio-surveillance it is desirable to estimate the probability that a contaminant or a function thereof exceeds an unsafe high threshold. The probability or chance in question is very small. To estimate such a probability, we need information about large values. In many cases, the data do not contain information about exceedingly large contamination levels, which ostensibly renders the problem insolvable. A solution is suggested whereby more information about small tail probabilities are obtained by combining the real data with computer-generated data repeatedly. This method provides short yet reliable interval estimates based on moderately large samples. An illustration is provided in terms of lead exposure data. Copyright © 2016 John Wiley & Sons, Ltd.

The Influence of the Diameter of Orthodontic Mini-Implants on Primary Stability: Bending Tests-An In Vitro Study.

Orthodontic Mini-Implants have a high success rate, but it is crucial to assess the load that they bear in order to maintain their primary stability. Increasing the diameter can improve this stability, but there are limitations due to the proximity of the tooth roots. To avoid damage, smaller diameters are used, which can decrease resistance and cause permanent deformations. OBJECTIVE: The objective of this study is to evaluate the influence of the diameter of Mini-Implants through bending force tests, taking into account primary stability after one and two insertions. METHODS: Here, 40 Ti6AI4V alloy Mini-Implants of two different brands and diameters were divided into eight groups, half of which received one insertion in the artificial bone, and the rest received two. All were subjected to a constant bending force using an INSTRON-Electropuls E10000LT (Norwood, MA, USA) until fracture. RESULTS: The smaller-diameter Mini-Implants were less resistant to fracture, but both were able to withstand the necessary loads produced by orthodontic movements. As for the inserts, there were no statistically significant differences. CONCLUSIONS: There is an advantage to using 1.6 mm Mini-Implants over 2.0 mm ones, as a smaller diameter does not lead to fracture due to the forces used in orthodontic treatment. Having one or two inserts did not have a statistically significant effect.

A network approach to emotion regulation and symptom activation in depression and anxiety.

Background: Emotions can be regulated through several regulatory strategies that are involved in the development of psychopathological symptoms. Despite the well-established association between psychopathology and emotion dysregulation, little is known about the relationship between individual symptoms of depression and anxiety and emotion regulation strategies (ERS), as well as between ERS themselves. Method: We conducted a cross-sectional study and examined the interactions between six ERS (reappraisal, engagement, rumination, suppression, arousal control, and distraction) and assessed their distinctive association with the activation of specific symptoms of depression and anxiety in a community sample of 376 adults (80.4% female; Mage = 32.70; SDage = 11.80). The Regulation Emotion Systems Survey (RESS) was used to measure ERS. The Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) were used to assess psychological symptoms. An exploratory graph analysis was performed to examine the structural properties of the network of interactions between these behaviors. Additionally, to test the association of ERS with the activation of the depression symptoms network, an expected symptoms activity (ESA) was conducted. Results: Six communities were found that correspond to the six ERS. Rumination and suppression have a significant association with symptom activation (particularly low self-esteem), whereas reappraisal reduces symptomatic activation. The effect of arousal control, engagement, and distraction appears to depend on the remaining ERS rather than having much influence on their own. Conclusion: This study provides insight into how ERS interact with each other and with individual symptoms of depression and anxiety. Understanding the effects of these interactions on symptom activation and comorbidity can improve our understanding of psychopathology.

Real-time 3D tracking of swimming microbes using digital holographic microscopy and deep learning.

The three-dimensional swimming tracks of motile microorganisms can be used to identify their species, which holds promise for the rapid identification of bacterial pathogens. The tracks also provide detailed information on the cells' responses to external stimuli such as chemical gradients and physical objects. Digital holographic microscopy (DHM) is a well-established, but computationally intensive method for obtaining three-dimensional cell tracks from video microscopy data. We demonstrate that a common neural network (NN) accelerates the analysis of holographic data by an order of magnitude, enabling its use on single-board computers and in real time. We establish a heuristic relationship between the distance of a cell from the focal plane and the size of the bounding box assigned to it by the NN, allowing us to rapidly localise cells in three dimensions as they swim. This technique opens the possibility of providing real-time feedback in experiments, for example by monitoring and adapting the supply of nutrients to a microbial bioreactor in response to changes in the swimming phenotype of microbes, or for rapid identification of bacterial pathogens in drinking water or clinical samples.

p300/CBP-associated factor selectively regulates the extinction of conditioned fear.

It is well established that the activity of chromatin-modifying enzymes is crucial for regulating gene expression associated with hippocampal-dependent memories. However, very little is known about how these epigenetic mechanisms influence the formation of cortically dependent memory, particularly when there is competition between opposing memory traces, such as that which occurs during the acquisition and extinction of conditioned fear. Here we demonstrate, in C57BL/6 mice, that the activity of p300/CBP-associated factor (PCAF) within the infralimbic prefrontal cortex is required for long-term potentiation and is necessary for the formation of memory associated with fear extinction, but not for fear acquisition. Further, systemic administration of the PCAF activator SPV106 enhances memory for fear extinction and prevents fear renewal. The selective influence of PCAF on fear extinction is mediated, in part, by a transient recruitment of the repressive transcription factor ATF4 to the promoter of the immediate early gene zif268, which competitively inhibits its expression. Thus, within the context of fear extinction, PCAF functions as a transcriptional coactivator, which may facilitate the formation of memory for fear extinction by interfering with reconsolidation of the original memory trace.

Numerical Simulations of the Low-Velocity Impact Response of Semicylindrical Woven Composite Shells.

This paper presents an efficient and reliable approach to study the low-velocity impact response of woven composite shells using 3D finite element models that account for the physical intralaminar and interlaminar progressive damage. The authors' previous work on the experimental assessment of the effect of thickness on the impact response of semicylindrical composite laminated shells served as the basis for this paper. Therefore, the finite element models were put to the test in comparison to the experimental findings. A good agreement was obtained between the numerical predictions and experimental data for the load and energy histories as well as for the maximum impact load, maximum displacement, and contact time. The use of the mass-scaling technique was successfully implemented, reducing considerably the computing cost of the solutions. The maximum load, maximum displacement, and contact time are negligibly affected by the choice of finite element mesh discretization. However, it has an impact on the initiation and progression of interlaminar damage. Therefore, to accurately compute delamination, its correct definition is of upmost importance. The validation of these finite element models opens the possibility for further numerical studies on of woven composite shells and enables shortening the time and expenses associated with the experimental testing.

An ethologically based view into human fear.

The quality of the defensive response to a threat depends on the elements that trigger the fear response. The current classification system of phobias does not account for this. Here, we analyze the fear-eliciting elements and discern the different types of fears that originate from them. We propose Pain, Disgust, Vasovagal response, Visual-vestibular and postural interactions, Movement and Speed, Distance and Size, Low and mid-level visual features, Smell, and Territory and social status. We subdivide phobias according to the fear-eliciting elements most frequently triggered by them and their impact on behavior. We discuss the implications of a clinical conceptualization of phobias in humans by reconsidering the current nosology. This conceptualization will facilitate finding etiological factors in defensive behavior expression, fine-tuning exposure techniques, and challenging preconceived notions of preparedness. This approach to phobias leads to surprising discoveries and shows how specific responses bear little relation to the interpretation we might later give to them. Dividing fears into their potentially fear-eliciting elements can also help in applying the research principles formulated by the Research Domain Criteria initiative.

The role of self-reported fear and disgust in the activation of behavioral harm avoidance related to medical settings.

Introduction: Although adaptive defense mechanisms are useful in helping us avoid getting injured, they are also triggered by medical interventions and procedures, when avoidance is harmful. A body of previous results showed that both fear and disgust play a pivotal role in medical avoidance. However, the underlying mechanisms are not fully understood. Thus, the aim of the current study was to examine the effects of experience, perceived control, and pain on medical avoidance with disgust and fear as mediating factors from an evolutionary perspective. Methods: We assessed participants' knowledge of and experience with medical procedures, former negative medical experiences, and health-related information; their life history strategy variation; pain-related fear and anxiety of medical procedures; perceived control over emotional reactions and extreme threats; disgust sensitivity; blood-injury-injection phobia and medical treatment avoidance. Results: We found that more knowledge, experience, and a slower life strategy were linked to a greater level of perceived control and attenuated emotional reactions. Further, better ability to control affective and stress reactions to negative experiences was linked to reduced disgust and fear of pain, and thus might mitigate the level of perceived threat, and diminish fear and disgust reactions. Discussion: More knowledge and experiences, better perceived control together with reduced disgust and fear of pain can decrease the probability of avoiding medical situations. Implications to treatment are discussed. Results support the importance of targeting these contextual factors in prevention to increase the likelihood of people attending regular screenings or seeking medical care when needed.

Key factors behind various specific phobia subtypes.

While it has been suggested that more than a quarter of the whole population is at risk of developing some form of specific phobia (SP) during their lives, we still know little about the various risk and protective factors and underlying mechanisms. Moreover, although SPs are distinct mental disorder categories, most studies do not distinguish between them, or stress their differences. Thus, our study was manifold. We examined the psychometric properties of the Specific Phobia Questionnaire (SPQ) and assessed whether it can be used for screening in the general population in a large sample (N = 685). Then, using general linear modeling on a second sample (N = 432), we tested how potential socio-demographic, cognitive emotion regulatory, and personality variables were associated with the five SP subtypes. Our results show that the SPQ is a reliable screening tool. More importantly, we identified transdiagnostic (e.g., younger age, female gender, rumination, catastrophizing, positive refocusing) as well as phobia-specific factors that may contribute to the development and maintenance of SPs. Our results support previous claims that phobias are more different than previously thought, and, consequently, should be separately studied, instead of collapsing into one category. Our findings could be pertinent for both prevention and intervention strategies.

Nanodroplet vaporization with pulsed-laser excitation repeatedly amplifies photoacoustic signals at low vaporization thresholds.

Nanodroplets' explosive vaporization triggered by absorption of laser pulses produces very large volume changes. These volume changes are two orders of magnitude higher than those of thermoelastic expansion generated by equivalent laser pulses, and should generate correspondingly higher photoacoustic waves (PAW). The generation of intense PAWs is desirable in photoacoustic tomography (PAT) to increase sensitivity. The biocompatibility and simplicity of nanodroplets obtained by sonication of perfluoropentane (PFP) in an aqueous solution of bovine serum albumin (BSA) containing a dye make them particularly appealing for use as contrast agents in clinical applications of PAT. Their usefulness depends on stability and reproducible vaporization of nanodroplets (liquid PFP inside) to microbubbles (gaseous PFP inside), and reversible condensation to nanodroplets. This work incorporates porphyrins with fluorinated chains and BSA labelled with fluorescent probes in PFP nanodroplets to investigate the structure and properties of such nanodroplets. Droplets prepared with average diameters in the 400-1000 nm range vaporize when exposed to nanosecond laser pulses with fluences above 3 mJ cm-2 and resist coalescence. The fluorinated chains are likely responsible for the low vaporization threshold, ∼2.5 mJ cm-2, which was obtained from the laser fluence dependence of the photoacoustic wave amplitudes. Only ca. 10% of the droplets incorporate fluorinated porphyrins. Nevertheless, PAWs generated with nanodroplets are ten times higher than those generated by aqueous BSA solutions containing an equivalent amount of porphyrin. Remarkably, successive laser pulses result in similar amplification, indicating that the microbubbles revert back to nanodroplets at a rate faster than the laser repetition rate (10 Hz). PFP nanodroplets are promising contrast agents for PAT and their performance increases with properly designed dyes.

Paradoxical enhancement of fear extinction memory and synaptic plasticity by inhibition of the histone acetyltransferase p300.

It is well established that the coordinated regulation of activity-dependent gene expression by the histone acetyltransferase (HAT) family of transcriptional coactivators is crucial for the formation of contextual fear and spatial memory, and for hippocampal synaptic plasticity. However, no studies have examined the role of this epigenetic mechanism within the infralimbic prefrontal cortex (ILPFC), an area of the brain that is essential for the formation and consolidation of fear extinction memory. Here we report that a postextinction training infusion of a combined p300/CBP inhibitor (Lys-CoA-Tat), directly into the ILPFC, enhances fear extinction memory in mice. Our results also demonstrate that the HAT p300 is highly expressed within pyramidal neurons of the ILPFC and that the small-molecule p300-specific inhibitor (C646) infused into the ILPFC immediately after weak extinction training enhances the consolidation of fear extinction memory. C646 infused 6 h after extinction had no effect on fear extinction memory, nor did an immediate postextinction training infusion into the prelimbic prefrontal cortex. Consistent with the behavioral findings, inhibition of p300 activity within the ILPFC facilitated long-term potentiation (LTP) under stimulation conditions that do not evoke long-lasting LTP. These data suggest that one function of p300 activity within the ILPFC is to constrain synaptic plasticity, and that a reduction in the function of this HAT is required for the formation of fear extinction memory.

Moderate physical training attenuates muscle-specific effects on fibre type composition in adult rats submitted to a perinatal maternal low-protein diet.

AIM: To verify whether moderate physical training affects the muscle fibre composition of adult rats subjected to a low protein diet during the perinatal period. METHODS: Male Wistar rats were divided into two groups according to their mother's diet during gestation and lactation: control (17% casein, C) and low-protein (8% casein, LP). On postnatal day 60, half of each group was submitted to moderate physical training (8 weeks, 5 days/week(-1), 60 min/day(-1), at 70% of VO(2max), T) or not. After the physical training period, soleus and extensor digitorum longus (EDL) muscles were removed. Myofibrillar ATPase staining was used to classify muscle fibres as type I, IIa, IIb, and intermediate. RESULTS: In the EDL muscle, LP rats showed no changes in the fibre type proportion. Both the C + T and LP + T groups showed a higher percentage of fibres of type IIa, and a lower proportion of fibres of type IIb. In the soleus muscle, LP animals showed a reduction in the proportion of fibre types I and intermediate. C + T rats showed an increase in the fibre type I and IIa. In the LP + T rats, the proportions of the fibre types remained similar to control rats. CONCLUSIONS: Moderate physical training acts as a positive environmental stimulus that reverts the effects of a perinatal low-protein diet on the proportion of fibre types in skeletal muscle.

Super-natural fears.

Supernatural fears, although common, are not as well-understood as natural fears and phobias (e.g., social, blood, and animal phobias) which are prepared by evolution, such that they are easily acquired through direct experience and relatively immune to cognitive mediation. In contrast, supernatural fears do not involve direct experience but seem to be related to sensory or cognitive biases in the interpretation of stimuli as well as culturally driven cognitions and beliefs. In this multidisciplinary synthesis and collaborative review, we claim that supernatural beliefs are "super natural." That is, they occur spontaneously and are easy to acquire, possibly because such beliefs rest on intuitive concepts such as mind-body dualism and animism, and may inspire fear in believers as well as non-believers. As suggested by psychological and neuroscientific evidence, they tap into an evolutionarily prepared fear of potential impending dangers or unknown objects and have their roots in "prepared fears" as well as "cognitively prepared beliefs," making fear of supernatural agents a fruitful research avenue for social, anthropological, and psychological inquires.

"Finding an Emotional Face" Revisited: Differences in Own-Age Bias and the Happiness Superiority Effect in Children and Young Adults.

People seem to differ in their visual search performance involving emotionally expressive faces when these expressions are seen on faces of others close to their age (peers) compared to faces of non-peers, known as the own-age bias (OAB). This study sought to compare search advantages in angry and happy faces detected on faces of adults and children on a pool of children (N = 77, mean age = 5.57) and adults (N = 68, mean age = 21.48). The goals of this study were to (1) examine the developmental trajectory of expression recognition and (2) examine the development of an OAB. Participants were asked to find a target face displaying an emotional expression among eight neutral faces. Results showed that children and adults found happy faces significantly faster than angry and fearful faces regardless of it being present on the faces of peers or non-peers. Adults responded faster to the faces of peers regardless of the expression. Furthermore, while children detected angry faces significantly faster compared to fearful ones, we found no such difference in adults. In contrast, adults detected all expressions significantly faster when they appeared on the faces of other adults compared to the faces of children. In sum, we found evidence for development in detecting facial expressions and also an age-dependent increase in OAB. We suggest that the happy face could have an advantage in visual processing due to its importance in social situations and its overall higher frequency compared to other emotional expressions. Although we only found some evidence on the OAB, using peer or non-peer faces should be a theoretical consideration of future research because the same emotion displayed on non-peers' compared to peers' faces may have different implications and meanings to the perceiver.

Towards Customized Footwear with Improved Comfort.

A methodology enabling the customization of shoes for comfort improvement is proposed and assessed. For this aim, 3D printed graded density inserts were placed in one of the critical plantar pressure zones of conventional insoles, the heel. A semi-automated routine was developed to design the 3D inserts ready for printing, which comprises three main stages: (i) the definition of the number of areas with different mesh density, (ii) the generation of 2D components with continuous graded mesh density, and (iii) the generation of a 3D component having the same 2D base mesh. The adequacy of the mesh densities used in the inserts was previously assessed through compression tests, using uniform mesh density samples. Slippers with different pairs of inserts embedded in their insoles were mechanically characterized, and their comfort was qualitatively assessed by a panel of users. All users found a particular pair, or a set, of prototype slippers more comfortable than the original ones, taken as reference, but their preferences were not consensual. This emphasizes the need for shoe customization, and the usefulness of the proposed methodology to achieve such a goal.

Deconstructing acrophobia: physiological and psychological precursors to developing a fear of heights.

BACKGROUND: Acrophobia is one of the most prevalent phobias, affecting as many as 1 in 20 individuals. Of course, heights often evoke fear in the general population too, and this suggests that acrophobia might actually represent the hypersensitive manifestation of an everyday, rational fear. In this study, we assessed the role of sensory and cognitive variables in acrophobia. METHODS: Forty-five participants (Mean age 25.07 years, 71% female) were assessed using a booklet with self-reports as well as several behavioral measures. The data analysis consisted in multivariate linear regression using fear of heights as the outcome variable. RESULTS: The regression analyses found that visual field dependence (measured with the rod and frame test), postural control (measured with the Sharpened Romberg Test), space and motion discomfort (measured with the Situational Characteristics Questionnaire), and bodily symptoms (measured with the Bodily Sensation Questionnaire) all serve as strong predictors for fear of heights (Adjusted r(2)=.697, P<.0001). Trait anxiety (measured with the State Trait Anxiety Inventory Form Y-2) was not related with fear of heights, suggesting that this higher order vulnerability factor is not necessary for explaining this particular specific phobia in a large number of individuals. CONCLUSION: The findings reveal that fear of heights is an expression of a largely sensory phenomena, which can produce strong feelings of discomfort and fear in the otherwise calm individuals. We propose a theory that embraces all these factors and provides new insight into the aetiology and treatment of this prevalent and debilitating fear.

Specific phobias in older adults: characteristics and differential diagnosis.

BACKGROUND: Differential diagnosis implies identifying shared and divergent characteristics between clinical states. Clinical work with older adults demands not only the knowledge of nosological features associated with differential diagnosis, but also recognition of idiosyncratic factors associated with this population. Several factors can interfere with an accurate diagnosis of specific phobia in older cohorts. The goal of this paper is to review criteria for specific phobia and its differential diagnosis with panic disorder, agoraphobia, post-traumatic stress disorder and obsessive compulsive disorder, while stressing the specific factors associated with aging. METHODS: A literature search regarding specific phobia in older adults was carried out using PubMed. Relevant articles were selected and scanned for further pertinent references. In addition, relevant references related to differential diagnosis and assessment were used. RESULTS: Etiologic factors, specificity of feared stimulus or situation, fear predictability and the nature of phobic situations are key points to be assessed when implementing a differential diagnosis of specific phobia. CONCLUSIONS: First, age-related sensory impairments are common and interfere both with information processing and communication. Second, medical illnesses create symptoms that might cause, interfere with, or mimic anxiety. Third, cohort effects might result in underreporting, through the inability to communicate or recognize anxiety symptoms, misattributing them to physical conditions. Finally, diagnostic criteria and screening instruments were usually developed using younger samples and are therefore not adapted to the functional and behavioral characteristics of older samples.

The face-in-the-crowd effect: when angry faces are just cross(es).

A common theme running through much of the visual recognition literature is that faces are special. Many studies now describe evidence for the idea that faces are processed in a dedicated center in cortex. Studies have also argued for the presence of evolutionarily expedient pathways dedicated to the processing of certain facial expressions. Evidence for this proposal comes largely from visual search tasks which have established that threatening expressions are more rapidly detected than other expressions: the 'face-in-the-crowd effect'. One open criticism of this effect is that it may be due to low-level visual artifacts, rather than biological preparedness. One attempt at controlling low-level differences has been to use schematic line-drawing versions of faces. This study aimed to discover if there might be alternative issues with schematic stimuli. The first study replicated the face-in-the-crowd threat advantage for schematic faces, but also measured a comparable effect using stimuli comprised of obliquely oriented lines. Similar results were achieved with these stimuli rotated, which had the effect of removing any residual resemblance to a face. The results suggest that low-level features probably underlie the face-in-the-crowd effect described for schematic face images, thereby undermining evidence for a search advantage for specific facial expressions.