where does facial recognition occur in the brain

There are several parts of the brain that play a role in face perception. Rossion, Hanseeuw, and Dricot[30] used BOLD fMRI mapping to identify activation in the brain when subjects viewed both cars and faces. The majority of BOLD fMRI studies use blood oxygen level dependent (BOLD) contrast to determine which areas of the brain are activated by various cognitive functions.[31] They found that the occipital face area, located in the occipital lobe, the fusiform face area, the superior temporal sulcus, the amygdala, and the anterior/inferior cortex of the temporal lobe, all played roles in contrasting the faces from the cars, with the initial face perception beginning in the area and occipital face areas. This entire region links to form a network that acts to distinguish faces. The processing of faces in the brain is known as a "sum of parts" perception.[32] However, the individual parts of the face must be processed first in order to put all of the pieces together. In early processing, the occipital face area contributes to face perception by recognizing the eyes, nose, and mouth as individual pieces.[33] Furthermore, Arcurio, Gold, and James[34] used BOLD fMRI mapping to determine the patterns of activation in the brain when parts of the face were presented in combination and when they were presented singly. The occipital face area is activated by the visual perception of single features of the face, for example, the nose and mouth, and preferred combination of two-eyes over other combinations. This research supports that the occipital face area recognizes the parts of the face at the early stages of recognition. On the contrary, the fusiform face area shows no preference for single features, because the fusiform face area is responsible for "holistic/configural" information,[35] meaning that it puts all of the processed pieces of the face together in later processing. This theory is supported by the work of Gold et al.[32] who found that regardless of the orientation of a face, subjects were impacted by the configuration of the individual facial features. Subjects were also impacted by the coding of the relationships between those features. This shows that processing is done by a summation of the parts in the later stages of recognition.

Face perception

Face perception is an individual's understanding and interpretation of the face, particularly the human face, especially in relation to the associated information processing in the brain.

The proportions and expressions of the human face are important to identify origin, emotional tendencies, health qualities, and some social information. From birth, faces are important in the individual's social interaction. Face perceptions are very complex as the recognition of facial expressions involves extensive and diverse areas in the brain. Sometimes, damaged parts of the brain can cause specific impairments in understanding faces or prosopagnosia.

From birth, infants possess rudimentary facial processing capacities and show heightened interest in faces.[1][2] For example, newborns (1-3 days) have been shown to be able to recognize faces even when they are rotated up to 45 degrees.[3] However, interest in faces is not continuously present in infancy and shows increases and decreases over time as the child grows older. Specifically, while newborns show a preference for faces, this behavior is reduced between one- to four months of age.[4]Around three months of age, a preference for faces re-emerges and interest in faces seems to peak late during the first year but then declines again slowly over the next two years of life[5]. The re-emergence of a preference for faces at three months of age may be influenced by the child's own motor abilities and experiences.[6][7]  Infants as young as two days of age are capable of mimicking the facial expressions of an adult, displaying their capacity to note details like mouth and eye shape as well as to move their own muscles in a way that produces similar patterns in their faces.[8][9] However, despite this ability, newborns are not yet aware of the emotional content encoded within facial expressions. Five-month-olds, when presented with an image of a person making a fearful expression and a person making a happy expression, pay the same amount of attention to and exhibit similar event-related potentials (ERPs) for both. However, when seven-month-olds are given the same treatment, they focus more on the fearful face, and their event-related potential for the scared face shows a stronger initial negative central component than that for the happy face. This result indicates an increased attentional and cognitive focus toward fear that reflects the threat-salient nature of the emotion.[10] In addition, infants' negative central components were not different for new faces that varied in the intensity of an emotional expression but portrayed the same emotion as a face they had been habituated to but were stronger for different-emotion faces, showing that seven-month-olds regarded happy and sad faces as distinct emotive categories.[11]  While seven-month-olds have been found to focus more on fearful faces, another study by Jessen, Altvater-Mackensen, and Grossmann found that "happy expressions elicit enhanced sympathetic arousal in infants" both when facial expressions were presented subliminally and when they were presented supraliminally, or in a way that the infants were consciously aware of the stimulus.[12]  These results show that conscious awareness of a stimulus is not connected to an infant's reaction to that stimulus.[12]

The recognition of faces is an important neurological mechanism that individuals in society use every day. Jeffrey and Rhodes[13] write that faces "convey a wealth of information that we use to guide our social interactions".[14] Emotions play a large role in our social interactions. The perception of a positive or negative emotion on a face affects the way that an individual perceives and processes that face. For example, a face that is perceived to have a negative emotion is processed in a less holistic manner than a face displaying a positive emotion.[15]  The ability of face recognition is apparent even in early childhood. The neurological mechanisms responsible for face recognition are present by age five. Research shows that the way children process faces is similar to that of adults, but adults process faces more efficiently. The reason for this may be because of advancements in memory and cognitive functioning that occur with age.[14]

Infants are able to comprehend facial expressions as social cues representing the feelings of other people before they are a year old. At seven months, the object of an observed face's apparent emotional reaction is relevant in processing the face. Infants at this age show greater negative central components to angry faces that are looking directly at them than elsewhere, although the direction of fearful faces' gaze produces no difference. In addition, two ERP components in the posterior part of the brain are differently aroused by the two negative expressions tested. These results indicate that infants at this age can at least partially understand the higher level of threat from anger directed at them as compared to anger directed elsewhere.[16] By at least seven months of age, infants are also able to use facial expressions to understand others' behavior. Seven-month-olds will look to facial cues to understand the motives of other people in ambiguous situations, as shown by a study in which they watched an experimenter's face longer if she took a toy from them and maintained a neutral expression than if she made a happy expression.[17] Interest in the social world is increased by interaction with the physical environment. Training three-month-old infants to reach for objects with Velcro-covered "sticky mitts" increases the amount of attention that they pay to faces as compared to passively moving objects through their hands and non-trained control groups.[18]

In following with the notion that seven-month-olds have categorical understandings of emotion, they are also capable of associating emotional prosodies with corresponding facial expressions. When presented with a happy or angry face, shortly followed by an emotionally neutral word read in a happy or angry tone, their ERPs follow different patterns. Happy faces followed by angry vocal tones produce more changes than the other incongruous pairing, while there was no such difference between happy and angry congruous pairings, with the greater reaction implying that infants held greater expectations of a happy vocal tone after seeing a happy face than an angry tone following an angry face. Considering an infant's relative immobility and thus their decreased capacity to elicit negative reactions from their parents, this result implies that experience has a role in building comprehension of facial expressions.[19]

Several other studies indicate that early perceptual experience is crucial to the development of capacities characteristic of adult visual perception, including the ability to identify familiar people and to recognize and comprehend facial expressions.[20] The capacity to discern between faces, much like language, appears to have a broad potential in early life that is whittled down to kinds of faces that are experienced in early life.[20] Infants can discern between macaque faces at six months of age, but, without continued exposure, cannot at nine months of age. Being shown photographs of macaques during this three-month period gave nine-month-olds the ability to reliably distinguish between unfamiliar macaque faces.[21]

The neural substrates of face perception in infants are likely similar to those of adults, but the limits of imaging technology that are feasible for use with infants currently prevent very specific localization of function as well as specific information from subcortical areas[22] like the amygdala, which is active in the perception of facial expression in adults.[20] In a study on healthy adults, it was shown that faces are likely to be processed, in part, via a retinotectal (subcortical) pathway.[23]

However, there is activity near the fusiform gyrus,[22] as well as in occipital areas.[16] when infants are exposed to faces, and it varies depending on factors including facial expression and eye gaze direction.[11][16]

Recognizing and perceiving faces are vital abilities needed to coexist in society.  Faces can tell things such as identity, mood, age, sex, race, and the direction that someone is looking.[24][25][26] Studies based on neuropsychology, behavior, electrophysiology, and neuro-imaging have supported the notion of a specialized mechanism for perceiving faces.[26] Prosopagnosia patients demonstrate neuropsychological support for a specialized face perception mechanism as these people, due to brain damage, have deficits in facial perception, but their cognitive perception of objects remains intact. The face inversion effect provides behavioral support of a specialized mechanism as people tend to have greater deficits in task performance when prompted to react to an inverted face than to an inverted object.  Electrophysiological support comes from the finding that the N170 and M170 responses tend to be face-specific.  Neuro-imaging studies such as PET and fMRI studies have shown support for a specialized facial processing mechanism as they have identified regions of the fusiform gyrus that have higher activation during face perception tasks than other visual perception tasks.[26] Theories about the processes involved in adult face perception have largely come from two sources: research on normal adult face perception and the study of impairments in face perception that are caused by brain injury or neurological illness. Novel optical illusions such as the Flashed Face Distortion Effect, in which scientific phenomenology outpaces neurological theory, also provide areas for research.

One of the most widely accepted theories of face perception argues that understanding faces involves several stages:[27] from basic perceptual manipulations on the sensory information to derive details about the person (such as age, gender or attractiveness), to being able to recall meaningful details such as their name and any relevant past experiences of the individual.

This model (developed by psychologists Vicki Bruce and Andrew Young) argues that face perception might involve several independent sub-processes working in unison.
A "view centered description" is derived from the perceptual input. Simple physical aspects of the face are used to work out age, gender or basic facial expressions. Most analysis at this stage is on feature-by-feature basis. That initial information is used to create a structural model of the face, which allows it to be compared to other faces in memory, and across views. After several exposures to a face this structural code allows us to recognize that face in different contexts.[28] This explains why the same person seen from a novel angle can still be recognized. This structural encoding can be seen to be specific for upright faces as demonstrated by the Thatcher effect. The structurally encoded representation is transferred to notional "face recognition units" that are used with "personal identity nodes" to identify a person through information from semantic memory. The natural ability to produce someone's name when presented with their face has been shown in experimental research to be damaged in some cases of brain injury, suggesting that naming may be a separate process from the memory of other information about a person.

The study of prosopagnosia (an impairment in recognizing faces which is usually caused by brain injury) has been particularly helpful in understanding how normal face perception might work. Individuals with prosopagnosia may differ in their abilities to understand faces, and it has been the investigation of these differences which has suggested that several stage theories might be correct.

Face perception is an ability that involves many areas of the brain; however, some areas have been shown to be particularly important. Brain imaging studies typically show a great deal of activity in an area of the temporal lobe known as the fusiform gyrus, an area also known to cause prosopagnosia when damaged (particularly when damage occurs on both sides). This evidence has led to a particular interest in this area and it is sometimes referred to as the fusiform face area (FFA) for that reason.[29]

Facial perception has well identified, neuroanatomical correlates in the brain. During the perception of faces, major activations occur in the extrastriate areas bilaterally, particularly in the fusiform face area, the occipital face area (OFA), and the superior temporal sulcus (fSTS).[36][37] Perceiving an inverted human face involves increased activity in the inferior temporal cortex, while perceiving a misaligned face involves increased activity in the occipital cortex.  However, none of these results were found when perceiving a dog face, suggesting that this process may be specific to perception of human faces.[38]

The fusiform face area is located in the lateral fusiform gyrus. It is thought that this area is involved in holistic processing of faces and it is sensitive to the presence of facial parts as well as the configuration of these parts. The fusiform face area is also necessary for successful face detection and identification. This is supported by fMRI activation and studies on prosopagnosia, which involves lesions in the fusiform face area.[36][37][39]

The OFA is located in the inferior occipital gyrus.[37] Similar to the FFA, this area is also active during successful face detection and identification, a finding that is supported by fMRI activation.[36] The OFA is involved and necessary in the analysis of facial parts but not in the spacing or configuration of facial parts. This suggests that the OFA may be involved in a facial processing step that occurs prior to the FFA processing.[36]

The fSTS is involved in recognition of facial parts and is not sensitive to the configuration of these parts. It is also thought that this area is involved in gaze perception.[40] The fSTS has demonstrated increased activation when attending to gaze direction.[36] Recent studies have tried to delineate whether fSTS area lights up while people use gaze of others in order to establish joint attention and not fSTS but another area (the gaze following patch which is still close to fSTS but not overlapping) was found to be the core of the gaze processing system in humans.[41]

Bilateral activation is generally shown in all of these specialized facial areas.[42][43][44][45][46][47] However, there are some studies that include increased activation in one side over the other. For instance McCarthy (1997) has shown that the right fusiform gyrus is more important for facial processing in complex situations.[39]

Gorno-Tempini and Price have shown that the fusiform gyri are preferentially responsive to faces, whereas the parahippocampal/lingual gyri are responsive to buildings.[48]

It is important to note that while certain areas respond selectively to faces, facial processing involves many neural networks. These networks include visual and emotional processing systems as well. Emotional face processing research has demonstrated that there are some of the other functions at work. While looking at faces displaying emotions (especially those with fear facial expressions) compared to neutral faces there is increased activity in the right fusiform gyrus. This increased activity also correlates with increased amygdala activity in the same situations.[49] The emotional processing effects observed in the fusiform gyrus are decreased in patients with amygdala lesions.[49] This demonstrates possible connections between the amygdala and facial processing areas.[49]

Another aspect that affects both the fusiform gyrus and the amygdala activation is the familiarity of faces. Having multiple regions that can be activated by similar face components indicates that facial processing is a complex process.[49] Platek and Kemp (2009) further showed increased brain activation in precuneus and cuneus when differentiation of two faces are easy (e.g., kin and familiar non-kin faces) and the role of posterior medial substrates for visual processing of faces with familiar features (e.g., faces that are averaged with the face of a sibling).[50]

Ishai and colleagues have proposed the object form topology hypothesis, which posits that there is a topological organization of neural substrates for object and facial processing.[51] However, Gauthier disagrees and suggests that the category-specific and process-map models could accommodate most other proposed models for the neural underpinnings of facial processing.[52]

Most neuroanatomical substrates for facial processing are perfused by the middle cerebral artery (MCA). Therefore, facial processing has been studied using measurements of mean cerebral blood flow velocity in the middle cerebral arteries bilaterally. During facial recognition tasks, greater changes in the right middle cerebral artery (RMCA) than the left (LMCA) have been observed.[53][54] It has been demonstrated that men were right lateralized and women left lateralized during facial processing tasks.[55]

Just as memory and cognitive function separate the abilities of children and adults to recognize faces, the familiarity of a face may also play a role in the perception of faces.[32] Zheng, Mondloch, and Segalowitz recorded event-related potentials in the brain to determine the timing of recognition of faces in the brain.[56] The results of the study showed that familiar faces are indicated and recognized by a stronger N250,[56] a specific wavelength response that plays a role in the visual memory of faces.[57] Similarly, Moulson et al.[58] found that all faces elicit the N170 response in the brain.

Using fMRI with single-unit electrophysiological recordings, Doris Tsao's group revealed[59] a code that brain uses to process faces in macaques. The brain conceptually needs only ~50 neurons to encode any human face, with facial features projected on individual axes (neurons) in a 50-dimensional "Face Space".

The mechanisms underlying gender-related differences in facial processing have not been studied extensively.

Studies using electrophysiological techniques have demonstrated gender-related differences during a face recognition memory (FRM) task and a facial affect identification task (FAIT). The male subjects used a right, while the female subjects used a left, hemisphere neural activation system in the processing of faces and facial affect.[60] Moreover, in facial perception there was no association to estimated intelligence, suggesting that face recognition performance in women is unrelated to several basic cognitive processes.[61] Gender-related differences[62] may suggest a role for sex hormones. In females there may be variability for psychological functions[63] related to differences in hormonal levels during different phases of the menstrual cycle.[64]

Data obtained in norm and in pathology support asymmetric face processing.[65][66][67] Gorno-Tempini and others in 2001, suggested that the left inferior frontal cortex and the bilateral occipitotemporal junction respond equally to all face conditions. Some neuroscientists contend that both the left inferior frontal cortex (Brodmann area 47) and the occipitotemporal junction are implicated in facial memory.[68][69][70] The right inferior temporal/fusiform gyrus responds selectively to faces but not to non-faces. The right temporal pole is activated during the discrimination of familiar faces and scenes from unfamiliar ones.[71] Right asymmetry in the mid temporal lobe for faces has also been shown using 133-Xenon measured cerebral blood flow (CBF).[72] Other investigators have observed right lateralization for facial recognition in previous electrophysiological and imaging studies.[73]

The implication of the observation of asymmetry for facial perception would be that different hemispheric strategies would be implemented. The right hemisphere would be expected to employ a holistic strategy, and the left an analytic strategy.[74][75][76][77] In 2007, Philip Njemanze, using a novel functional transcranial Doppler (fTCD) technique called functional transcranial Doppler spectroscopy (fTCDS), demonstrated that men were right lateralized for object and facial perception, while women were left lateralized for facial tasks but showed a right tendency or no lateralization for object perception.[78] Njemanze demonstrated using fTCDS, summation of responses related to facial stimulus complexity, which could be presumed as evidence for topological organization of these cortical areas in men. It may suggest that the latter extends from the area implicated in object perception to a much greater area involved in facial perception.

This agrees with the object form topology hypothesis proposed by Ishai and colleagues in 1999. However, the relatedness of object and facial perception was process-based, and appears to be associated with their common holistic processing strategy in the right hemisphere. Moreover, when the same men were presented with facial paradigm requiring analytic processing, the left hemisphere was activated. This agrees with the suggestion made by Gauthier in 2000, that the extrastriate cortex contains areas that are best suited for different computations, and described as the process-map model. Therefore, the proposed models are not mutually exclusive, and this underscores the fact that facial processing does not impose any new constraints on the brain other than those used for other stimuli.

It may be suggested that each stimulus was mapped by category into face or non-face, and by process into holistic or analytic. Therefore, a unified category-specific process-mapping system was implemented for either right or left cognitive styles. Njemanze in 2007, concluded that, for facial perception, men used a category-specific process-mapping system for right cognitive style, but women used same for the left.

Cognitive neuroscientists Isabel Gauthier and Michael Tarr are two of the major proponents of the view that face recognition involves expert discrimination of similar objects (See the Perceptual Expertise Network). Other scientists, in particular Nancy Kanwisher and her colleagues, argue that face recognition involves processes that are face-specific and that are not recruited by expert discriminations in other object classes (see the domain specificity).

Studies by Gauthier have shown that an area of the brain known as the fusiform gyrus (sometimes called the fusiform face area because it is active during face recognition) is also active when study participants are asked to discriminate between different types of birds and cars,[79] and even when participants become expert at distinguishing computer generated nonsense shapes known as greebles.[80] This suggests that the fusiform gyrus may have a general role in the recognition of similar visual objects. Yaoda Xu, then a post doctoral fellow with Nancy Kanwisher, replicated the car and bird expertise study using an improved fMRI design that was less susceptible to attentional accounts.

The activity found by Gauthier when participants viewed non-face objects was not as strong as when participants were viewing faces, however this could be because we have much more expertise for faces than for most other objects. Furthermore, not all findings of this research have been successfully replicated, for example, other research groups using different study designs have found that the fusiform gyrus is specific to faces and other nearby regions deal with non-face objects.[81]

However, these failures to replicate are difficult to interpret, because studies vary on too many aspects of the method. It has been argued that some studies test experts with objects that are slightly outside of their domain of expertise. More to the point, failures to replicate are null effects and can occur for many different reasons. In contrast, each replication adds a great deal of weight to a particular argument. With regard to "face specific" effects in neuroimaging, there are now multiple replications with Greebles, with birds and cars,[82] and two unpublished studies with chess experts.[83][84]

Although it is sometimes found that expertise recruits the FFA (e.g. as hypothesized by a proponent of this view in the preceding paragraph), a more common and less controversial finding is that expertise leads to focal category-selectivity in the fusiform gyrusâ€”a pattern similar in terms of antecedent factors and neural specificity to that seen for faces. As such, it remains an open question as to whether face recognition and expert-level object recognition recruit similar neural mechanisms across different subregions of the fusiform or whether the two domains literally share the same neural substrates. Moreover, at least one study argues that the issue as to whether expertise-predicated category-selective areas overlap with the FFA is nonsensical in that multiple measurements of the FFA within an individual person often overlap no more with each other than do measurements of FFA and expertise-predicated regions.[85] At the same time, numerous studies have failed to replicate them altogether.[citation needed] For example, four published fMRI studies have asked whether expertise has any specific connection to the FFA in particular, by testing for expertise effects in both the FFA and a nearby but not face-selective region called LOC (Rhodes et al., JOCN 2004; Op de Beeck et al., JN 2006; Moore et al., JN 2006; Yue et al. VR 2006). In all four studies, expertise effects are significantly stronger in the LOC than in the FFA, and indeed expertise effects were only borderline significant in the FFA in two of the studies, while the effects were robust and significant in the LOC in all four studies.[citation needed]

Therefore, it is still not clear in exactly which situations the fusiform gyrus becomes active, although it is certain that face recognition relies heavily on this area and damage to it can lead to severe face recognition impairment.

Studies regarding face perception have also looked specifically at self-face perception.  One study found that the perception/recognition of one's own face was unaffected by changing contexts, while the perception/recognition of familiar and unfamiliar faces was adversely affected.[86] Another study that focused on older adults found that they had self-face advantage in configural processing but not featural processing.[87]

During face perception, neural networks make connections with the brain to recall memories.[88] According to the Seminal Model of face perception, there are three stages of face processing including recognition of the face, the recall of memories and information that are linked with that face, and finally name recall.[27][88] There are, however, exceptions to this order. For example, names are recalled faster than semantic information in cases of highly familiar stimuli.[89] While the face is powerful identifier of individuals, the voice also helps in the recognition of people and is an identifier for important information.[90][91]

Research has been conducted to see if faces or voices make it easier to identify individuals and recall semantic memory and episodic memory.[92] These experiments look at all three stages of face processing. The experiment method was to show two groups celebrity and familiar faces or voices with a between-group design and ask the participants to recall information about them.[92] The participants are first asked if the stimulus is familiar. If they answer yes then they are asked to information (semantic memory) and memories they have of the person (episodic memory) that fits the face or voice presented. These experiments all demonstrate the strong phenomenon of the face advantage and how it persists through different follow-up studies with different experimental controls and variables.[92]

After the first experiments on the advantage of faces over voices in memory recall, errors and gaps were found in the methods used.[92] For one, there was not a clear face advantage for the recognition stage of face processing. Participants showed a familiarity-only response to voices more often than faces.[93] In other words, when voices were recognized (about 60-70% of the time) they were much harder to recall biographical information but very good at being recognized.[92] The results were looked at as remember versus know judgements. A lot more remember results (or familiarity) occurred with voices, and more know (or memory recall) responses happened with faces.[91] This phenomenon persists through experiments dealing with criminal line-ups in prisons. Witnesses are more likely to say that a suspect's voice sounded familiar than his/her face even though they cannot remember anything about the suspect.[94] This discrepancy is due to a larger amount of guesswork and false alarms that occur with voices.[91]

To give faces a similar ambiguity to that of voices, the face stimuli were blurred in the follow-up experiment[93]  This experiment followed the same procedures as the first, presenting two groups with sets of stimuli made up of half celebrity faces and half unfamiliar faces.[92] The only difference was that the face stimuli were blurred so that detailed features could not be seen.  Participants were then asked to say if they recognized the person, if they could recall specific biographical information about them, and finally if they knew the person's name. The results were completely different from those of the original experiment, supporting the view that there were problems in the first experiment's methods.[92] According to the results of the followup, the same amount of information and memory could be recalled through voices and faces, dismantling the face advantage. However, these results are flawed and premature because other methodological issues in the experiment still needed to be fixed.[92]

The process of controlling the content of speech extract has proven to be more difficult than the elimination of non facial cues in photographs.[92]  Thus the findings of experiments that did not control this factor lead to misleading conclusions regarding the voice recognition over the face recognition.[92]  For example, in an experiment it was found that 40% of the time participants could easily pair the celebrity-voice with their occupation just by guessing.[93] In order to eliminate these errors, experimenters removed parts of the voice samples that could possibly give clues to the identity of the target, such as catchphrases.[95]   Even after controlling the voice samples as well as the face samples (using blurred faces), studies have shown that semantic information can be more accessible to retrieve when individuals are recognizing faces than voices.[96]

Another technique to control the content of the speech extracts is to present the faces and voices of personally familiar individuals, like the participant's teachers or neighbors, instead of the faces and voices of celebrities.[92]  In this way alike words are used for the speech extracts.[92]  For example, the familiar targets are asked to read exactly the same scripted speech for their voice extracts. The results showed again that semantic information is easier to retrieve when individuals are recognizing faces than voices.[92]

Another factor that has to be controlled in order for the results to be reliable is the frequency of exposure.[92]  If we take the example of celebrities, people are exposed to celebrities' faces more often than their voices because of the mass media.[92]  Through magazines, newspapers and the Internet, individuals are exposed to celebrities' faces without their voices on an everyday basis rather than their voices without their faces.[92] Thus, someone could argue that for all of the experiments that were done until now the findings were a result of the frequency of exposure to the faces of celebrities rather than their voices.[97]

To overcome this problem researchers decided to use personally familiar individuals as stimuli instead of celebrities.[92]  Personally familiar individuals, such as participant's teachers, are for the most part heard as well as seen.[98]  Studies that used this type of control also demonstrated the face advantage.[98]  Students were able to retrieve semantic information more readily when recognizing their teachers faces (both normal and blurred)rather their voices.[96]

However, researchers over the years have found an even more effective way to control not only the frequency of exposure but also the content of the speech extracts, the associative learning paradigm.[92]  Participants are asked to link semantic information as well as names with pre-experimentally unknown voices and faces.[99][100]  In a current experiment that used this paradigm, a name and a profession were given together with, accordingly, a voice, a face or both to three participant groups.[99]  The associations described above were repeated four times.[99]  The next step was a cued recall task in which every stimulus that was learned in the previous phase was introduced and participants were asked to tell the profession and the name for every stimulus.[99][101]  Again, the results showed that semantic information can be more accessible to retrieve when individuals are recognizing faces than voices even when the frequency of exposure was controlled.[92][99]

Episodic memory is our ability to remember specific, previously experienced events.[102] In recognition of faces as it pertains to episodic memory, there has been shown to be activation in the left lateral prefrontal cortex, parietal lobe, and the left medial frontal/anterior cingulate cortex.[103][104] It was also found that a left lateralization during episodic memory retrieval in the parietal cortex correlated strongly with success in retrieval.[103] This may possibly be due to the hypothesis that the link between face recognition and episodic memory were stronger than those of voice and episodic memory.[93] This hypothesis can also be supported by the existence of specialized face recognition devices thought to be located in the temporal lobes.[103][105] There is also evidence of the existence of two separate neural systems for face recognition: one for familiar faces and another for newly learned faces.[103] One explanation for this link between face recognition and episodic memory is that since face recognition is a major part of human existence, the brain creates a link between the two in order to be better able to communicate with others.[106]

Differences in own- versus other-race face recognition and perceptual discrimination was first researched in 1914.[107] Humans tend to perceive people of other races than their own to all look alike:

Other things being equal, individuals of a given race are distinguishable from each other in proportion to our familiarity, to our contact with the race as whole. Thus, to the uninitiated American all Asiatics look alike, while to the Asiatics, all White men look alike.[107]

This phenomenon is known mainly as the cross-race effect, but is also called the own-race effect, other-race effect, own race bias or interracial-face-recognition-deficit.[108]

In 1990, Mullen reported finding evidence that the other-race effect is larger among White subjects than among African American subjects, whereas Brigham and Williamson (1979, cited in Shepherd, 1981) obtained the opposite pattern.[109] However, it should be noted that it is difficult to measure the true influence of the cross-race effect. D. Stephen Lindsay and colleagues note that results in these studies could be due to intrinsic difficulty in recognizing the faces presented, an actual difference in the size of cross-race effect between the two test groups, or some combination of these two factors.[109] Shepherd reviewed studies that found better performance on both African American[110] and White faces,[111] and yet Shepherd also reviewed other studies in which no difference was found.[112] Overall, Shepherd reported a reliable positive correlation between the size of the effect and the amount of interaction subjects had with members of the other race. This correlation reflects the fact that African American subjects, who performed equally well on faces of both races in Shepherd's study, almost always responded with the highest possible self-rating of amount of interaction with white people (M = 4.75; 5 being the most interaction with people of that race, 1 being the least), whereas their white counterparts both displayed a larger other-race effect and reported less other-race interaction (M = 2.13). This difference in rating was found statistically reliable, Â£(30) = 7.86, p <.01.[109]

The cross-race effect seems to appear in humans around 6 months of age.[113] Cross-race effects can be changed from early childhood through adulthood through interaction with people of other races.[114] Other-race experience in own- versus other-race face processing is a major influence on the cross-race effect (O'Toole et al., 1991; Slone et al., 2000; Walker & Tanaka, 2003). In a series of studies, Walker and colleagues revealed that participants with greater other-race experience were consistently more accurate at discriminating between other-race faces than were participants with less other-race experience (Walker & Tanaka, 2003; Walker & Hewstone, 2006a,b; 2007). Many current models of the cross-race effect assume that holistic face processing mechanisms are more fully engaged when viewing own-race faces compared to other-race faces.[115]

The own-race effect appears to be related to increased ability to extract information about the spatial relationships between different facial features.[116] Daniel T. Levin writes that a deficit occurs when viewing people of another race because visual information specifying race takes up mental attention at the expense of individuating information when recognizing faces of other races.[117] Further research using perceptual tasks could shed light on the specific cognitive processes involved in the other-race effect.[109] Bernstein et al. (2007) demonstrate that the own-race effect likely extends beyond racial membership into in-group versus out-group concepts. It was shown that categorizing somebody by the university he or she attends results in similar results compared to studies about the own-race effect.[118] Hugenberg, Miller, and Claypool (2007) shed light on overcoming the own-race effect. They performed a study in which they introduced people to the concept of the own-race effect before presenting them faces and found that if people were made aware of the own-race effect prior to the experiment, the test subjects showed significantly less if any own-race effect.[119]

Studies on adults have also shown sex differences in face recognition. Men tend to recognize fewer faces of women than women do, whereas there are no sex differences with regard to male faces.[120]

Autism spectrum disorder (ASD) is a comprehensive neural developmental disorder that produces many deficits including social, communicative,[121] and perceptual deficits.[122] Of specific interest, individuals with autism exhibit difficulties in various aspects of facial perception, including facial identity recognition and recognition of emotional expressions.[123][124] These deficits are suspected to be a product of abnormalities occurring in both the early and late stages of facial processing.[125]

People with ASD process face and non-face stimuli with the same speed.[125][126] In typically developing individuals, there is a preference for face processing, thus resulting in a faster processing speed in comparison to non-face stimuli.[125][126] These individuals primarily utilize holistic processing when perceiving faces.[122] Contrastingly, individuals with ASD employ part-based processing or bottom-up processing, focusing on individual features rather than the face as a whole.[127][128] When focusing on the individual parts of the face, persons with ASD direct their gaze primarily to the lower half of the face, specifically the mouth, varying from the eye trained gaze of typically developing people.[127][128][129][130][131]  This deviation from holistic face processing does not employ the use of facial prototypes, which are templates stored in memory that make for easy retrieval.[124][132]

Additionally, individuals with ASD display difficulty with recognition memory, specifically memory that aids in identifying faces. The memory deficit is selective for faces and does not extend to other objects or visual inputs.[124] Some evidence lends support to the theory that these face-memory deficits are products of interference between connections of face processing regions.[124]

The atypical facial processing style of people with ASD often manifests in constrained social ability, due to decreased eye contact, joint attention, interpretation of emotional expression, and communicative skills.[133] These deficiencies can be seen in infants as young as 9 months; specifically in terms of poor eye contact and difficulties engaging in joint attention.[125]  Some experts have even used the term 'face avoidance' to describe the phenomena where infants who are later diagnosed with ASD preferentially attend to non-face objects over faces.[121] Furthermore, some have proposed that the demonstrated impairment in children with ASD's ability to grasp emotional content of faces is not a reflection of the incapacity to process emotional information, but rather, the result of a general inattentiveness to facial expression.[121] The constraints of these processes that are essential to the development of communicative and social-cognitive abilities are viewed to be the cause of impaired social engagement and responsivity.[134] Furthermore, research suggests that there exists a link between decreased face processing abilities in individuals with ASD and later deficits in Theory of Mind; for example, while typically developing individuals are able to relate others' emotional expressions to their actions, individuals with ASD do not demonstrate this skill to the same extent.[135]

There is some contention about this causation however, resembling the chicken or the egg dispute. Others theorize that social impairment leads to perceptual problems rather than vice versa.[127] In this perspective, a biological lack of social interest inherent to ASD inhibits developments of facial recognition and perception processes due to underutilization.[127] Continued research is necessary to determine which theory is best supported.

Many of the obstacles that individuals with ASD face in terms of facial processing may be derived from abnormalities in the fusiform face area and amygdala, which have been shown to be important in face perception as discussed above. Typically, the fusiform face area in individuals with ASD has reduced volume compared to normally developed persons.[136] This volume reduction has been attributed to deviant amygdala activity that does not flag faces as emotionally salient and thus decreases activation levels of the fusiform face area. This hypoactivity in the fusiform face area has been found in several studies.[127]

Studies are not conclusive as to which brain areas people with ASD use instead. One study found that, when looking at faces, people with ASD exhibit activity in brain regions normally active when typically developing individuals perceive objects.[127] Another study found that during facial perception, people with ASD use different neural systems, with each one of them using their own unique neural circuitry.[136]

As ASD individuals age, scores on behavioral tests assessing ability to perform face-emotion recognition increase to levels similar to controls.[125][137] Yet, it is apparent that the recognition mechanisms of these individuals are still atypical, though often effective.[137] In terms of face identity-recognition, compensation can take many forms including a more pattern-based strategy which was first seen in face inversion tasks.[130] Alternatively, evidence suggests that older individuals compensate by using mimicry of other's facial expressions and rely on their motor feedback of facial muscles for face emotion-recognition.[138] These strategies help overcome the obstacles individuals with ASD face in interacting within social contexts.

Attention, perception, memory, learning, processing, reasoning, and problem solving are known to be affected in individuals with schizophrenia.[139] Schizophrenia has been linked to impaired face and emotion perception.[139][3][140][86] People with schizophrenia demonstrate worse accuracy and slower response time in face perception tasks in which they are asked to match faces, remember faces, and recognize which emotions are present in a face.[86] People with schizophrenia have more difficulty matching upright faces than they do with inverted faces.[139] A reduction in configural processing, using the distance between features of an item for recognition or identification (e.g. features on a face such as eyes or nose), has also been linked to schizophrenia.[86] Schizophrenia patients are able to easily identify a "happy" affect but struggle to identify faces as "sad" or "fearful".[140] Impairments in face and emotion perception are linked to impairments in social skills, due to the individual's inability to distinguish facial emotions.[140][86]People with schizophrenia tend to demonstrate a reduced N170 response, atypical face scanning patterns, and a configural processing dysfunction.[141] The severity of schizophrenia symptoms has been found to correlate with the severity of impairment in face perception.[86]

Individuals with diagnosed schizophrenia and antisocial personality disorder have been found to have even more impairment in face and emotion perception than individuals with just schizophrenia. These individuals struggle to identify anger, surprise, and disgust. There is a link between aggression and emotion perception difficulties for people with this dual diagnosis.[140]

Data from magnetic resonance imaging and functional magnetic resonance imaging has shown that a smaller volume of the fusiform gyrus is linked to greater impairments in face perception.[3]

There is a positive correlation between self-face recognition and other-face recognition difficulties in individuals with schizophrenia.  The degree of schizotypy has also been shown to correlate with self-face difficulties, unusual perception difficulties, and other face recognition difficulties.[142] Schizophrenia patients report more feelings of strangeness when looking in a mirror than do normal controls. Hallucinations, somatic concerns, and depression have all been found to be associated with self-face perception difficulties.[143]

Neurobiologist Jenny Morton and her team have been able to teach sheep to choose a familiar face over unfamiliar one when presented with two photographs, which has led to the discovery that sheep can recognise human faces.[144][145] Archerfish (distant relatives of humans) were able to differentiate between forty-four different human faces, which supports the theory that there is no need for a neocortex or a history of discerning human faces in order to do so.[146] Pigeons were found to use the same parts of the brain as humans do to distinguish between happy and neutral faces or male and female faces.[146]

A great deal of effort has been put into developing software that can recognize human faces. Much of the work has been done by a branch of artificial intelligence known as computer vision which uses findings from the psychology of face perception to inform software design. Recent breakthroughs using noninvasive functional transcranial Doppler spectroscopy as demonstrated by Njemanze, 2007, to locate specific responses to facial stimuli have led to improved systems for facial recognition. The new system uses input responses called cortical long-term potentiation (CLTP) derived from Fourier analysis of mean blood flow velocity to trigger target face search from a computerized face database system.[147][148] Such a system provides for brain-machine interface for facial recognition, and the method has been referred to as cognitive biometrics.

Another application is the estimation of human age from face images. As an important hint for human communication, facial images contain lots of useful information including gender, expression, age, etc. Unfortunately, compared with other cognition problems, age estimation from facial images is still very challenging. This is mainly because the aging process is influenced not only by a person's genes but also many external factors. Physical condition, living style etc. may accelerate or slow the aging process. Besides, since the aging process is slow and with long duration, collecting sufficient data for training is fairly demanding work.[149]

While it has been widely recognized that many cognitive abilities, such as general intelligence, have genetic bases, evidence for the genetic basis of facial recognition abilities specifically is fairly recent. Some of the earliest published research on the relationship between facial recognition and genetics focused on the genetic bases of facial recognition in the context of genetic disorders which impair facial recognition abilities, such as Turner syndrome. In a study by Lawrence, K. et al. in 2003[87] the authors found significantly poorer facial recognition abilities in individuals with Turner syndrome, a genetic disorder which results in impaired amygdala functioning, suggesting that amygdala functioning may impact face perception.[87] Evidence for the genetic basis of facial recognition abilities in the general population, however, comes from studies on face perception in twin participants by Wilmer, J. B. et al. in 2009,[150] in which the facial recognition scores on the Cambridge Face Memory test were twice as similar for monozygotic twins in comparison to dizygotic twins.[150] This finding was supported by a twin study on the genetic bases of facial recognition by Zhu, Q. et al. in (2009) which found a similar difference in facial recognition scores when comparing monozygotic and dizygotic twins[151] and Shakeshaft, N. G. & Plomin, R. (2015),[152] which determined the heritability of facial recognition to be approximately 61%, using a similar set of twin studies.[152] There was also no significant relationship identified between facial recognition scores and measures of any other cognitive abilities,[150] most notably the lack of a correlation with general object recognition abilities. This suggests that facial recognition abilities are not only heritable, but that their genetic basis is independent from the bases of other cognitive abilities and are specialized for face perception.[150] Research by Cattaneo, Z. et al. (2016)[153] and suggest that the more extreme examples of facial recognition abilities, specifically hereditary prosopagnosics, are also highly genetically correlated.[153] For hereditary prosopagnosics, an autosomal dominant model of inheritance has been proposed by Kennerknecht, I. et al. (2006).[154] Research by Cattaneo, Z. et al. (2016)[153] also correlated the probability of hereditary prosopagnosia with the presence of single nucleotide polymorphisms[153] along the Oxytocin receptor gene (OXTR), specifically at nucleotides rs2254298 and rs53576 on OXTR intron three,[153] suggesting that these alleles may serve a critical role in normal face perception. Mutation from the wild type allele at these loci has also been found to result in other disorders in which social and facial recognition deficits are common,[153] such as autism spectrum disorder, which may imply that the genetic bases for general facial recognition are complex and polygenic.[153] This relationship between the OXTR gene and facial recognition abilities is also supported by studies of individuals who do not suffer from hereditary prosopagnosia by Melchers, M. et al. (2013)[155] and Westberg, L. et al. (2016)[156] which correlated general facial recognition abilities with different polymorphisms of the OXTR gene, specifically rs7632287[156] and rs2268498.[155] Further research is needed to confirm the specific mechanisms of these genetic components on face perception; however, current evidence does suggest that facial recognition abilities are highly linked to genetic, rather than environmental, bases.


what is the symbol of subset in math

Some authors use the symbols ⊂ and ⊃ to indicate subset and superset respectively; that is, with the same meaning and instead of the symbols, ⊆ and ⊇.[2] So for example, for these authors, it is true of every set A that A ⊂ A.

Subset

In mathematics, a set A is a subset of a set B, or equivalently B is a superset of A, if A is "contained" inside B, that is, all elements of A are also elements of B. A and B may coincide. The relationship of one set being a subset of another is called inclusion or sometimes containment. A is a subset of B may also be expressed as B includes A; or A is included in B.

The subset relation defines a partial order on sets.

The algebra of subsets forms a Boolean algebra in which the subset relation is called inclusion.

If A and B are sets and every element of A is also an element of B, then:

If A is a subset of B, but A is not equal to B (i.e. there exists at least one element of B which is not an element of A), then

For any set S, the inclusion relation ⊆ is a partial order on the set

P

(
S
)

{\displaystyle {\mathcal {P}}(S)}

 of all subsets of S (the power set of S) defined by

A
≤
B

⟺

A
⊆
B

{\displaystyle A\leq B\iff A\subseteq B}

. We may also partially order

P

(
S
)

{\displaystyle {\mathcal {P}}(S)}

 by reverse set inclusion by defining

A
≤
B

⟺

B
⊆
A
.

{\displaystyle A\leq B\iff B\subseteq A.}

When quantified, A ⊆ B is represented as: ∀x{x∈A → x∈B}.[1]

Other authors prefer to use the symbols ⊂ and ⊃ to indicate proper subset and proper superset respectively; that is, with the same meaning and instead of the symbols, ⊊ and ⊋.[3] This usage makes ⊆ and ⊂ analogous to the inequality symbols ≤ and <. For example, if x ≤ y then x may or may not equal y, but if x < y, then x definitely does not equal y, and is less than y. Similarly, using the convention that ⊂ is proper subset, if A ⊆ B, then A may or may not equal B, but if A ⊂ B, then A definitely does not equal B.

Another example in an Euler diagram:

A is a proper subset of B

C is a subset but not a proper subset of B

Inclusion is the canonical partial order in the sense that every partially ordered set (X,

⪯

{\displaystyle \preceq }

) is isomorphic to some collection of sets ordered by inclusion. The ordinal numbers are a simple example—if each ordinal n is identified with the set [n] of all ordinals less than or equal to n, then a ≤ b if and only if [a] ⊆ [b].

For the power set

P

(
S
)

{\displaystyle {\mathcal {P}}(S)}

 of a set S, the inclusion partial order is (up to an order isomorphism) the Cartesian product of k = |S| (the cardinality of S) copies of the partial order on {0,1} for which 0 < 1. This can be illustrated by enumerating S = {s1, s2, …, sk} and associating with each subset T ⊆ S (which is to say with each element of 2S) the k-tuple from {0,1}k of which the ith coordinate is 1 if and only if si is a member of T.


when did a bad moms christmas cone out

A Bad Moms Christmas is a 2017 American Christmas comedy film written and directed by Jon Lucas and Scott Moore. It is a sequel to the 2016 film Bad Moms. The plot follows the three moms from the first film (Mila Kunis, Kristen Bell, and Kathryn Hahn) dealing with their own mothers (Christine Baranski, Cheryl Hines, and Susan Sarandon) visiting during the Christmas holiday.

A Bad Moms Christmas

Principal photography on the film began in Atlanta, Georgia in May 2017, and the film was released by STXfilms in the United States on November 1, 2017. It received mixed reviews, with criticism aimed at the thin story and raunchy jokes, and has grossed $122 million worldwide.[3]

Amy is now in a happy relationship with Jessie and is looking forward to having a simple Christmas. Her plans are derailed when her overly critical mother, Ruth, texts her to say she is coming for Christmas.

Meanwhile, Kiki is still overworked with her four kids but now her husband Kent is much more helpful. Kiki is surprised when her mother Sandy shows up three days earlier than expected and is planning to spend the next three weeks with Kiki. Sandyâ€™s love for Kiki is overwhelming, and smothering Kiki.

When Carla gets home, her mother, Isis, has arrived on a bus telling her she intends to spend time with her for the first time in years. Surprised by this turn of events Carla is excited to spend time with her. Eventually, Amy, Kiki and Carla go to the mall where they express their misery over the holidays. But while commiserating about the pressures of the holidays they make a pact to “take Christmas back”. Ruth tries to create a spectacle out of Christmas, rather than keeping it simple like Amy wanted. In an effort to temper down those plans Amy takes the family to Sky Zone to meet up with Kiki and Carla and their families. Ruth, Sandy and Isis all meet and chat while their daughters have fun with their kids.

At work, Carla meets an erotic dancer named Ty, who says he is competing in a Sexy Santa competition and he asks Carla to be his date, which she enthusiastically accepts. Kiki continues to have issues with her motherâ€™s overbearing ways and decides to bring Sandy to Dr. Karl to discuss these issues. This leads to a breakdown in communication leading to Kiki scolding Sandy and causing her to leave the session. Amy and Kiki join Carla as they attend the Sexy Santa show. All the ladies in the room are impressed with Ty's dancing. To everyone's surprise, Isis gets up on the bar and starts dancing with Ty. Carla runs up to get Ty back, leading to a fight. When Carla brings Isis home, Isis tells her she needs money for a new investment, but Carla knows she's just going to gamble it all away and then disappear from Carla's life like it's been for years. Nonetheless, Carla relents and loans Isis the money.

On Christmas Eve, Sandy tells Kiki that she put up a cash offer for the house next door so that she can live right next to Kiki. Finally, Kiki lashes out and tells Sandy she cannot live next door and that she wants some space. Sandy leaves the room crying.

Amy gets angry with Ruth when she discovers Ruth has invited a bunch of strangers over to her home to throw an elaborate Christmas party. Exactly what Amy did not want. Amy loses her temper and demands everyone leave her home and tells Ruth to leave and get out of her life forever. The kids, Jane and Dylan, witness this outburst and become upset with Amy. Meanwhile, Carla finds a note from Isis indicating she has just taken off with the money she lent her and Kiki is all alone as well.

Ruth goes to church for Midnight Mass and is surprisingly joined by Sandy and Isis. All the ladies criticize each other for their efforts as mothers, with each of them realizing their flaws. Amyâ€™s father goes to her to talk about Ruth and the horrible fight they had, but acknowledging that while Ruth can be difficult to deal with, she has always been insecure over her work as a mom toward Amy, always worried whether or not she was doing a good job as a mother, but she always had the right intentions and loved Amy unconditionally. Amy goes to the church to try and repair her relationship with her mother. They apologize to each other and express their love. Once the clock strikes midnight, Amy and Ruth rush home to fix Christmas.

On Christmas morning, Jane and Dylan go downstairs to see that Ruth has returned, the relationship has been repaired and the house looking wonderful with decorations and gifts. Kiki makes up with Sandy, who tells her she put the neighboring house on the market and admits that she's just always felt lonely on Christmas since Kiki's father died. Carla is then visited by Isis, who is serious about turning her life around and has a new job at Sky Zone.

All the families get together and Ruth, Sandy and Isis announce that they have become friends and are now planning to take a trip to Las Vegas.

In December 2016, it was announced that A Bad Moms Christmas would be released on November 3, 2017, and that it would be Christmas-themed, with Bell, Hahn, and Kunis returning to reprise their roles.[4][5] The release date was subsequently moved up two days to November 1, 2017.[6] In April 2017, Justin Hartley joined the cast of the film,[7] and in May 2017, Susan Sarandon, Christine Baranski, and Cheryl Hines joined as the mothers' mothers, alongside Wanda Sykes and Jay Hernandez reprising their roles from the first film.[8]

Principal photography on the film began in Atlanta, Georgia on May 1, 2017.[9][10]

A Bad Moms Christmas was released on Wednesday, November 1, 2017. It was originally scheduled for November 3, 2017, but was pushed up two days to avoid direct competition with Thor: Ragnarok.[11]

As of December 17, 2017[update], A Bad Moms Christmas has grossed $70.7 million in the United States and Canada, and $51.3 million in other territories, for a worldwide total of $122 million, against a production budget of $28 million.[2]

In North America, the film was projected to gross around $25 million from 3,615 theaters in its first five days (including $17 million over the weekend).[12] It took in $2.7 million on its first day,[13] and $17 million over the weekend, for a five-day total of $21.6 million, finishing second at the box office behind Thor: Ragnarok.[14]

On review aggregator Rotten Tomatoes, the film has an approval rating of 28%, based on 103 reviews, and an average rating of 4.4/10. The site's critical consensus reads, "Featuring twice the moms but roughly half the laughs, A Bad Moms Christmas is a slapdash holiday sequel that falls short of the original with a disappointing dearth of good cheer."[15] On Metacritic, which assigns a normalized rating to reviews, the film has a weighted average score of 42 out of 100, based on 30 critics, indicating "mixed or average reviews".[16] Audiences polled by CinemaScore gave the film an average grade of "B" on an A+ to F scale, down from the "A" earned by the first film.[13]

Owen Gleiberman of Variety gave the film a mixed review, writing, "A Bad Moms Christmas should appeal to the same—dare I say it?—demo that Bad Moms did, even though it’s not nearly as wild a comedy. It has one halfway original idea, which is that when you’re a mom yourself, the ability of your own mom to drive you nuts is heightened to the third power, because you’re competing on levels that are almost primal."[17] Pete Hammond of Deadline.com gave the film a positive review, calling it a "good time movie" and writing: "...it goes way over the top, but I have to confess I laughed—a lot—and that’s obviously the point even if this is not critic’s fodder or meant to be. Subtle this is not, but A Bad Moms Christmas is the perfect tonic to lift your spirits and forget your troubles in these dark times."[18]


what is the disease that turns muscle into bone

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare connective tissue disease. The disease is caused by a mutation of the body's repair mechanism, which causes fibrous tissue (including muscle, tendon, and ligament) to be ossified spontaneously or when damaged. In many cases, injuries can cause joints to become permanently frozen in place. Surgical removal of the extra bone growths has been shown to cause the body to "repair" the affected area with even more bone.

Fibrodysplasia ossificans progressiva

For unknown reasons, children born with FOP have deformed big toes, possibly missing a joint or simply presenting with a notable lump at the minor joint. The first "flare-up" that leads to the formation of FOP bones usually occurs before the age of 10. The bone growth progresses from the top downward, just as bones grow in fetuses. A child with FOP will typically develop bones starting at the neck, then on the shoulders, arms, chest area and finally on the feet.

Specifically, ossification is typically first seen in the dorsal, axial, cranial and proximal regions of the body. Later the disease progresses in the ventral, appendicular, caudal and distal regions of the body.[1] However, it does not necessarily occur in this order due to injury-caused flare-ups. Often, the tumor-like lumps that characterize the disease appear suddenly. This condition causes loss of mobility to affected joints, including inability to fully open the mouth limiting speech and eating. Extra bone formation around the rib cage restricts the expansion of lungs and diaphragm causing breathing complications.

Since the disease is so rare, the symptoms are often misdiagnosed as cancer or fibrosis. This leads physicians to order biopsies, which can exacerbate the growth of these lumps.[2] However, those born with FOP tend to have malformed toes or thumbs which help distinguish this disorder from other skeletal problems.[3]

The median age of survival is 40 years with proper management. However, delayed diagnosis, trauma and infections can decrease life expectancy.[4]

FOP is caused by an autosomal dominant allele on chromosome 2q23-24.[5] The allele has variable expressivity, but complete penetrance. Most cases are caused by spontaneous mutation in the gametes; most people with FOP cannot or choose not to have children. A similar but less catastrophic disease is fibrous dysplasia, which is caused by a post-zygotic mutation.

A mutation in the gene ACVR1 (also known as activin-like kinase 2 (ALK2)) is responsible for the disease.[6] ACVR1 encodes activin receptor type-1, a BMP type-1 receptor. The mutation causes substitution of codon 206 from arginine to histidine in the ACVR1 protein.[7][8] This substitution causes abnormal activation of ACVR1, leading to the transformation of connective tissue and muscle tissue into a secondary skeleton. This causes endothelial cells to transform to mesenchymal stem cells and then to bone.[9]

FOP is an autosomal dominant disorder. Thus, children of an affected heterozygous parent and a homozygous recessive parent have a 50% chance of being affected. Two affected individuals can produce unaffected children. The homozygous dominant phenotype is more severe than the heterozygous phenotype.[10]

The gene that causes ossification is normally deactivated after a fetus's bones are formed in the womb, but in patients with FOP, the gene keeps working. Aberrant bone formation in patients with FOP occurs when injured connective tissue or muscle cells at the sites of injury or growth incorrectly express an enzyme for bone repair during apoptosis (self-regulated cell death), resulting in lymphocytes containing excess bone morphogenetic protein 4 (BMP4) provided during the immune system response. The bone that results occurs independently of the normal skeleton, forming its own discrete skeletal elements. These elements, however, can fuse with normal skeletal bone.[11] Interestingly, the diaphragm, tongue, and extra-ocular muscles are spared in this process, as well as cardiac and smooth muscle.[1] Since the incorrect enzyme remains unresolved within the immune response, the body continues providing the incorrect BMP4-containing lymphocytes. BMP4 is a product that contributes to the development of the skeleton in the normal embryo.[12]

DNA sequencing electropherograms of a typical FOP patient can differ when being compared to two other patients. The ACVR1 gene encodes a bone morphogenic protein (BMP) receptor; this gene is mutated in FOP. This protein is responsible for growth and development of bone and muscles. Scientists theorize that a mutation in the ACVR1 changes the shape of the receptor and disrupts certain mechanisms that control the receptor's activity. There is a certain molecule, otherwise known as a ligand, that binds at the site to cause this reaction to activate with which it forms a complex. Due to the mutation, however, the bind site is modified and no longer stops the reaction.[13] The end result is an overgrowth of bone and cartilage and fusion of joints.[14]

Most of the cases of FOP were results of a new gene mutation: these people had no history of this particular disorder in their family. There are some cases which have shown people inheriting the mutation from one affected parent.[14]

Outbreaks may be measurable clinically by elevated levels of alkaline phosphatase and bone-specific alkaline phosphatase.[15]

There is no cure or approved treatment for FOP.[16] Attempts to surgically remove the bone result in explosive bone growth.[17] While under anesthesia, people with FOP may encounter difficulties with intubation, restrictive pulmonary disease, and changes in the electrical conduction system of the heart.[18] Activities that increase the risk of falling or soft tissue injury should be avoided, as even minor trauma may provoke heterotopic bone formation.[19]

As of 2017, approximately 800 cases of FOP have been confirmed worldwide making FOP one of the rarest diseases known.[16] The estimated incidence of FOP is 0.5 cases per million people and affects all races.[16]

Medical reports describing individuals affected by FOP date back as far as the seventeenth century.[16] FOP was originally called myositis ossificans progressiva and was thought to be caused by muscular inflammation (myositis) that caused bone formation.[16] The disease was renamed by Victor A. McKusick in 1970 following the discovery that soft tissue other than muscles (e.g., ligaments) were also affected by the disease process.[16]

The best known FOP case is that of Harry Eastlack (1933â€“1973). His condition began to develop at the age of ten, and by the time of his death from pneumonia in November 1973, six days before his 40th birthday, his body had completely ossified, leaving him able to move only his lips. Eastlack only lived to meet one other person with his same disease.

Eastlack donated his body to science. His skeleton is now at the Mütter Museum in Philadelphia, and has proven to be an invaluable source of information in the study of FOP.

Clinical trials of isotretinoin, etidronate with oral corticosteroids, and perhexiline maleate have failed to demonstrate effectiveness, though the variable course of the disease and small prevalence induces uncertainty.[15]

A handful of pharmaceutical companies focused on rare disease are currently in varying stages of investigation into different therapeutic approaches for FOP.

In August 2015, U.S. Food and Drug Administration (FDA) Office of Orphan Products Development granted La Jolla Pharmaceuticals orphan drug designation for two novel compounds for FOP. The compounds are small-molecule kinase inhibitors designed to selectively block ACVR1 (ALK2).[20]

In August 2015, Clementia Pharmaceuticals also began the enrollment of children (ages 6 and above) into its Phase II clinical trial investigating palovarotene for the treatment of FOP.[21] Preclinical studies demonstrated that palovarotene, a retinoic acid receptor gamma agonist, blocked abnormal bone formation in animal models via inhibition of secondary messenger systems in the BMP pathway.[22] Clementia licensed palovarotene from Roche Pharmaceuticals, which previously evaluated the compound in more than 800 individuals including healthy volunteers and patients with chronic obstructive pulmonary disease. Palovarotene received Fast Track designation from the U.S. Food and Drug Administration (FDA) and orphan designations for the treatment of FOP from both the FDA and the European Medicines Agency (EMA).[21]

In September 2015, Regeneron announced new insight into the mechanism of disease involving the activation of the ACVR1 receptor by activin A. In 2016, the company initiated a phase 1 study of its activin antibody, REGN 2477, in healthy volunteers; a phase 2 trial in FOP patients is planned for 2017.[23]

Another potential therapeutic approach involves allele-specific RNA interference that targets mutated mRNA for degradation while preserving normal ACVR1 gene expression.[24]

Further investigation into the mechanisms of heterotopic bone formation in FOP could aid in the development of treatments for other disorders involving extra-skeletal bone formation.


who made the song ride the white horse

"White Horse" is a 1983 song written by Tim Stahl and John Guldberg of the Danish duo Laid Back. The song was released as the B-side of their single "Sunshine Reggae" which became a major hit in several European countries. In the US, the A-side was mainly ignored and it was the B-side that became most successful. It was released as a single and went on to spend three weeks at number one on the Dance Charts.[4] The single also made the top five on the R&B singles chart and peaked at number 26 on the Billboard Hot 100.[5] Although being played in European clubs, it failed to chart there when re-released as an A-side.

White Horse (Laid Back song)

The song's lyrics, which refer to riding "the white horse" and "the white pony", have been interpreted as references to heroin and/or cocaine use. Rolling Stone described the song as "[p]erhaps the most unconvincing anti-drug song of all time".[6] An article in Miami New Times listed "White Horse" as one of the "top 10 cocaine songs" and stated, "It's often debated whether the white horse in this song refers to cocaine or heroin. Either way, Laid Back's 1982 single starts out persuading you not to ride the white horse but rather to ride the white pony, also a slang term for coke."[7] The book Totally Awesome 80s described "White Horse" as "a song with very few words that still managed to be about the joys of cocaine".[8]

Co-writer Tim Stahl referred to an alternative interpretation of the song when interviewed for the book Flashbacks to Happiness: Eighties Music Revisited (published by iUniverse), saying, "Another cute anecdote about the song was when we got a letter from a little girl in Jutland in 1983, thanking us for making a song for her white pony!"[9]


who won best actor academy award in 1969

Cliff Robertson's performance in Charly was met with a generally mixed reception from critics and audiences. When he won the Academy Award for Best Actor, it engendered some controversy: less than two weeks after the ceremony, TIME mentioned the Academy's generalized concerns over "excessive and vulgar solicitation of votes" and said "many members agreed that Robertson's award was based more on promotion than on performance."[2]

41st Academy Awards

The 41st Academy Awards were presented on April 14, 1969, at the Dorothy Chandler Pavilion, Los Angeles. It was the first Academy Awards ceremony to be staged at the Dorothy Chandler Pavilion. For the first time since the 11th Academy Awards, there was no host.

Oliver! became the first—and so far, the only—G-rated film to win the Academy Award for Best Picture. By contrast, the following year would see the only X-rated film to win Best Picture, Midnight Cowboy. Oliver! would also be the last British film to win Best Picture until Chariots of Fire in 1982 and the last movie musical to win until Chicago in 2003 (though others have been nominated between 1969 and 2003: Hello, Dolly!, Fiddler on the Roof, Cabaret, All That Jazz, Beauty and the Beast, and Moulin Rouge!).

The year was notable for the first—and so far, only—tie for Best Actress (or any female acting category). Katharine Hepburn in The Lion in Winter and Barbra Streisand in Funny Girl shared the award. Hepburn also became the second actress and third performer overall to win an acting Oscar two years in a row, after Luise Rainer in 1936 (The Great Ziegfeld) and 1937 (The Good Earth), and Spencer Tracy in 1937 (Captains Courageous) and 1938 (Boys Town). The previous year, Hepburn had won Best Actress for Guess Who's Coming to Dinner.

As the special effects director and designer for 2001: A Space Odyssey, Stanley Kubrick was the recipient of the Academy Award for Best Visual Effects this year. It was the only Oscar he would ever win.[1]

At the ceremony, Young Americans was announced as the Documentary Feature winner. On May 7, 1969, the film was disqualified because it had played in October 1967, thus making it ineligible for a 1968 award. Journey Into Self, the first runner-up, was awarded the Oscar on May 8, 1969.

Controversy was created on Oscar night when Johnny Carson and Buddy Hackett announced in a sketch on the evening's Tonight Show, which was recorded three hours before the awards ceremony, that Oliver! would be the winner for Best Picture and that Jack Albertson would win for Best Supporting Actor. Columnist Frances Drake claimed that most observers believed Carson and Hackett "were playing a huge practical joke or happened to make a lucky guess."[3] As Carson recalled it on the air years later, it created a huge controversy and people at Price Waterhouse were fired. Referring to it as "The Great Carson Hoax," PricewaterhouseCoopers stated in a 2004 press release that it was "later proven that Carson and Hackett made a few lucky guesses for their routine, dispelling rumors of a security breach and keeping the integrity of the balloting process intact."[4] The Academy later hired Carson five times to host the ceremony.

Winners are listed first, highlighted in boldface and indicated with a double dagger ().[5][6]

These films had multiple nominations:

The following films received multiple awards.


how many books are in the missing series by haddix

The Missing is a series of fictional young-adult novels written by Margaret Peterson Haddix. It tells the story of famous children from history stolen by futuristic time travelers from their place in time and accidentally sent to the 21st century as babies. They are then adopted by families in the 21st century. Because Jonah is one of the stolen children, he, along with his non-adopted sister Katherine, must help return the missing kids to their rightful places in history and fix time before it is destroyed. The first book in the series, Found, was published on April 22, 2008. The series continued with book titles Sent, Sabotaged, Torn, Caught, Risked (originally intended to be titled Kept), and Revealed. The eighth and final book, Redeemed, was released on September 8, 2015. There are also two ebook short stories, Sought (which takes place before Risked) and Rescued (which takes place between Risked and Revealed).[2] Haddix originally intended the series to consist of only seven books, however, she stated that she had trouble closing out the series in seven books; leading to her decision to write Redeemed.[3]

The Missing (novel series)

A thirteen-year-old boy named Jonah had always known that he was adopted and had never thought much of it until he began receiving strange letters sent to his house.[4][5] When Jonah's friend Chip, who received the same letters, learns that he is also adopted, Jonah, Chip and Jonah's sister, Katherine, set out to find out the truth about their origins. They end up in the middle of FBI investigation, people appearing and disappearing, and a strange tale from a woman named Angela DuPre, who saw a plane appear (and later disappear) from nowhere, and discovered 36 babies on board, minus pilot and copilot. The three come to realize that Jonah and Chip are important missing children from history who were transported to the 21st century by baby smuggling time travelers, whose names are Gary and Hodge. Later, they are unknowingly lured into a cave, known as a time hollow, with all but one of the other 36 missing children in an attempt by the smugglers to take them to the future. After they have defeated the smugglers, another time traveler from the future known to them as JB (Janitor Boy) decides to send Chip and another boy, Alex, back to the 1480s, where they were originally taken from. While trying to stop him, Jonah and Katherine are accidentally taken along for the trip as well, leaving it up to them to save their friends and return to the 21st century. This sets the plot and the title for the following book in the series, "Sent".

Found was released on April 22, 2008.[6] [7]

In this book, Jonah, Katherine, Chip, and Chip's real brother, Alex, have one warning of disaster before they are sent back to 15th century to the Tower of London, with the promise that they can return to their home in the 21st century if they can repair history. They quickly discover that Chip and Alex's true identities are Edward V (king of England) and Richard of Shrewsbury, Duke of York. But before Chip can enjoy being the King of England, they discover that they are virtually prisonersâ€”and that the boys' uncle, King Richard III, wants them dead. Jonah and Katherine must repair time and save Chip and Alex from their certain deaths before it is even possible that they can return home.[8][9]

After ending up in the Tower of London, the four discover Chip and Alex's true identities, but find them prisoners. They foil 2 men they suppose are murderers' attempt to kill Chip and Alex in the nick of time, but then must hide. The next day, they decide to do something and end up crossing the Thames to Westminster Abbey, where the boys' uncle, Richard of Gloucester, is being crowned King Richard III. After causing some distress, they visit the queen, their mother, in sanctuary at Westminster, intending to convince her of Chip and Alex's death, but instead Chip and Alex rejoin their tracers (which mark out the events of original time) and Jonah and Katherine are removed from time to a time hollow, where they and JB watch the next two years, from 1483 to 1485. Jonah and Katherine are sent to the Battle of Bosworth and accidentally convince Richard to give up his crown in favor of Edward (Chip), but he dies and Chip and Alex almost do, before Jonah and Katherine manage to convince them to come home. They return to the time cave, and then go home. JB soon shows up and explains the results and tells the four that he wants Jonah and Katherine to help the next missing child, Andrea Crowell, return to her place in history.

Sent was released on August 25, 2009.[10] [11]

In this third volume of the series, Jonah and Katherine return Andrea, identified as the missing child Virginia Dare, to 1600, her correct time period from where she was kidnapped. During their time journey, the device used for their time travel, called an Elucidator, is lost, causing the children arrive not certain as to where or when they are. They discover that a man visited Andrea and wrongly convinced her to type in a code on the Elucidator which made it disappear, telling her it would take her back to the day her parents died, so she could rescue them. Eventually, they discover that they made it to Roanoke Island in 1600, and go to Croatoan Island. In the process, Andrea saves a man from drowning, who they discover is her grandfather, John White. Jonah, Katherine, and Andrea find that their attempt to fix time by sending Andrea back is being thwarted by a man who calls himself Second. Second is a projectionist that possibly messed up time forever.[12][13] Along the way they meet two of the other missing children, Brendan and Antonio, who were mysteriously sent back to their original time by Second. While on Croatoan Island, Andrea changes time itself and is reunited with her grandfather as Virginia Dare. It turns out Brendan and Antonio are adopted Native Americans who became excellent artists, and that Virginia Dare originally buried the bones on Croatoan Island, saving it from being a reminder of the plague that killed the Roanoke colonists and Croatoan Indians. Second appears and Jonah and Katherine are saved by JB, only to be hurled into another time (1611).

Sabotaged was released on August 24, 2010.[14] [15]

Jonah and Katherine land on the decks of Henry Hudson's ship, called the Discovery, moments before a mutiny in the early 17th century.[16] JB reveals that John Hudson, one of the kids stolen from history and Henry Hudson's son, is missing completely, and Jonah will have to play his part. Jonah and Katherine must survive being on the 17th century boat,[17] with unlikely help from two of the sailors. Hudson is trying to find the Northwest Passage that would connect Europe and Asia by way of the Americas. A mutiny takes place on the ship, the Discovery, soon after they arrive, and they, along with Hudson and his officers, are banished into the cold bay. But instead of the original version they remember, the boat returns for them, led by the first mate. When they find out that Second has disguised himself as Hudson's first mate and has murdered one of them, Jonah and Katherine have a harrowing time, and then relive the mutiny and banishment, except time splits, showing 1 version that they already lived (the return of the ship), and 1 that they live now (continued banishment, the original version). They escape the boat after a docking and manage to get into the Damaged Time of 1605. They save their friends Brendan, Antonio, Andrea, JB and John White when Jonah rescues everyone from the fire in the Indian village of 1605. It then turns out that Second sent John Hudson to 1605. John Hudson, called Dalton Sullivan in the 21st century, was already in 1605, living in England. JB then concludes that Second unraveled time from 1605 to 1611, made his own new, alternate universe and is sealing it off completely from others. JB then sends everyone to the 21st century, where they can live in peace, for a while.

Torn was released on August 23, 2011.[18] [19]

Jonah and Katherine are in school when time freezes. They are subsequently (accidentally) transported to Albert Einstein's time, where they must help to save his illegitimate daughter Lieserl,[20] who is known as Emily in the 21st century, and keep Einstein from discovering time travel instead of the theory of relativity, which would ruin history. Jonah and Katherine follow Mileva, Einstein's wife, in order to put Emily in her correct time, 1903. When they get to Mileva's parents' house, they discover that Lieserl is just a baby and close to death from scarlet fever. They witness Gary and Hodge kidnap Lieserl and Emily appear, and try to help by putting her in her tracer as Lieserl. However, during Jonah and Katherine's followings, Mileva discovers them,[21] steals their Elucidator, and communicates with them, causing a huge disturbance in time. When she tries to show Albert the 13-year-old Emily, time freezes in 1903 as well, but not Mileva, since she skipped time to when Albert arrived. They are all sent, along with Emily, to a place outside of time, called a time hollow. Mileva freezes everyone there using the Elucidator and then watches her whole life, Emily's life, and learns English to understand how time travel worked. Then she unfreezes only Jonah and allows him to come with her and save time. Jonah lets Mileva keep the Elucidator when she returns to her time, which allows her to later send her demented son, Tete Einstein, to the future as a baby, where he grows up to become JB.

Caught was released on September 3, 2012.[22] [23]

Right after Jonah, Katherine and Chip meet a girl named Daniella McCarthy, the four are kidnapped by a boy, Gavin Danes, and sent to 1918. It is revealed that Gavin and Daniella are Alexei and Anastasia Romanov, the youngest children of Czar Nicholas II. Everybody except Chip is arrested upon arrival, who rescues Jonah and Katherine and discovers that Yakov Yurovsky intends to kill the Romanovs. Yurovsky successfully lures the imperial family into the cellar and proceeds with the killings. Gary and Hodge, who tricked Gavin and escaped from time prison, try to send all of them, including Maria Romanova and Leonid Sednev, to the future as babies, but they escape, though significantly younger. They regain their ages. Jonah and Gavin are shot in the ensuing chaos, but JB appears and rescues Jonah and Katherine. Katherine later returns to save the others, including Maria and Leonid, but the four older Romanovs are killed. JB sends Jonah and Gavin to the future, where they are forced to stay while they recover from their injuries. It is shown that Angela is providing for Maria and Leonid's education and considering adopting them in the 21st century.

The book was released on September 4, 2013.[24][25] [26]

Charles Lindbergh appears in the Skidmores' home, grabs Katherine, and vanishes. Jonah finds out that Chip, Andrea, and all the other children from the plane have disappeared as well. Jonahâ€™s parents and all the other adults in his town have "un-aged" into 13-year-olds. Jonah is the only 'normal' person left, and must save everyone with the help of un-aged JB and Angela.[27][28]Jonah accidentally makes another dimension when he delivers what he thinks is himself as a baby, but is really his twin brother that he never knew about, to his parents, thinking that they and he are trapped in a doomed dimension anyway. Jonah discovers Gary and Hodge's plot: they convinced a grief-ridden Charles Lindbergh, reeling from the kidnapping of his son in 1932, that Jonah is his son and that he could have him back if he went to the night of the time crash and took the plane of babies to the future, cleaning up their mess and creating separate dimensions (and, in their plan, unaging Lindbergh himself as well). He convinces Lindbergh to return Katherine as well as to betray Gary and Hodge who are subsequently unaged into babies. Staying true to its name, Jonah's real identity as a missing child is finally "revealed" in this book; an orphanage baby from 1932 who was kidnapped to be passed off as Charles Lindbergh's son. Jonah finds out that the baby he saved was actually his twin (whom his parents named Jordan in the other dimension) and that though the dimensions were separate, they have now merged, meaning that Jordan and Jonah share a dimension, and contrary to Mom, Dad, and Katherine, have no memory of each other, since the others were in both dimensions. Jonah tries to take the first step in bringing the family, including Jordan, together afterward by having a big family hug.

Revealed was released on September 2, 2014.[29] [30]

Jordan Skidmore learns that he was an orphanage child from 1932 and that he now has a new twin brother named Jonah. Wanting to help his strangely unaged parents, he sends his entire family to the future.[31][32] Second traps his parents in a time hollow and Jonah, Jordan, and Katherine are forced to save a young version of Second, Kevin, from an accident in the past (falling from a fence at the airport the night of the time crash). They learn Second's story: having witnessed the appearance of the plane, he was kept on for the FBI investigation, but crippled from his accident, and Gary and Hodge, acting for Interchronological Rescue, hired him as a spy in the time agency for the company, taking him to the future and healing him, where he became JB's chief projectionist. The adult Second, frustrated with Jonah and Katherine, later traps them in a separate time hollow, leaving Jordan to save time by himself. In a time hollow, he watches the entire lives of his siblings and learns about their previous trips through time. Second reveals that he has been murdered and that he is only a hologram, and the fate of the alternate universe he created- destroyed, since he gave the secret of age-altering to everyone. After befriending Kevin, Jordan convinces him to help re-age the adults. In the process of doing so, Kevin himself is unaged into a baby. The two are captured by Curtis Rathbone, the CEO of the company that employed Gary and Hodge, who then reveals that he caused all the unaging. Jordan and Kevin are then joined by Jonah, Katherine, Chip, JB, Angela and his parents. Everybody is frozen by Mr. Rathbone but he is killed by Kevin's Elucidator. In the epilogue, Kevin is adopted by the Skidmore's, and babies Gary and Hodge by Hadley Correo and Angela, bringing them up to 4 adopted kids (including Maria and Leonid from Risked. JB reveals to them that the time agency is sealing off time travel to prevent any more near-disasters, but secretly gives them an emergency Elucidator.

Redeemed, was released on September 8, 2015.[33] [34]