Emotional dysregulation

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Emotional_dysregulation 

Emotional dysregulation is characterized by an inability to flexibly respond to and manage emotional states, resulting in intense and prolonged emotional reactions that deviate from social norms, given the nature of the environmental stimuli encountered. Such reactions not only deviate from accepted social norms but also surpass what is informally deemed appropriate or proportional to the encountered stimuli.

It is often linked to physical factors such as brain injury, psychological factors such as adverse childhood experiences, and ongoing maltreatment including child abuse, neglect, or institutional abuse.

Emotional dysregulation may be present in people with psychiatric and neurodevelopmental disorders such as attention deficit hyperactivity disorder, autism spectrum disorder, bipolar disorder, borderline personality disorder, complex post-traumatic stress disorder, and fetal alcohol spectrum disorders. The dysregulation of emotions is also present in individuals with mood disorders and anxiety disorders. In such cases as borderline personality disorder and complex post-traumatic stress disorder, hypersensitivity to emotional stimuli causes a slower return to a normal emotional state and may reflect deficits in prefrontal regulatory regions. Damage to the frontal cortices of the brain can cause deficits in behavior that can severely impact an individual's ability to manage their daily life. As such, the period after a traumatic brain injury, such as a frontal lobe disorder, can be marked by emotional dysregulation. This is also true of neurodegenerative diseases.

Possible manifestations of emotion dysregulation include extreme tearfulness, angry outbursts or behavioral outbursts such as destroying or throwing objects, aggression towards self or others, and threats to kill oneself. Emotion dysregulation can lead to behavioral problems and can interfere with a person's social interactions and relationships at home, in school, or at their place of employment.

Etymology

The word dysregulation is a neologism created by combining the prefix dys- to regulation. According to Webster's Dictionary, dys- has various roots and is of Greek origin. With Latin and Greek roots, it is akin to Old English tō-, te- 'apart' and Sanskrit dus- 'bad, difficult'. It is frequently confused with the spelling disregulation, with the prefix dis meaning 'the opposite of' or 'absence of'; while disregulation refers to the removal or absence of regulation, dysregulation refers to ways of regulating that are inappropriate or ineffective.

Child psychopathology

There are links between child emotional dysregulation and later psychopathology. For instance, ADHD symptoms are associated with problems with emotional regulation, motivation, and arousal. One study found a connection between emotional dysregulation at 5 and 10 months, and parent-reported problems with anger and distress at 18 months. Low levels of emotional regulation behaviors at 5 months were also related to non-compliant behaviors at 30 months. While links have been found between emotional dysregulation and child psychopathology, the mechanisms behind how early emotional dysregulation and later psychopathology are related are not yet clear.

Symptoms

Smoking, self-harm, eating disorders, and addiction have all been associated with emotional dysregulation. Somatoform disorders may be caused by a decreased ability to regulate and experience emotions or an inability to express emotions in a positive way. Individuals who have difficulty regulating emotions are at risk for eating disorders and substance abuse, as they may use food or substances as a way to regulate their emotions. Emotional dysregulation is also found in people who have an increased risk of developing a mental disorder, particularly an affective disorder such as depression or bipolar disorder.

Childhood

Dysregulation is more prevalent in children, and is generally seen to decrease as children develop. During early childhood, emotional dysregulation or reactivity is considered to be situational rather than indicative of emotional disorders. It is important to consider parental mood disorders as genetic and environmental determinants. Children of parents with symptoms of depression are less likely to learn strategies for regulating their emotions and are at risk of inheriting a mood disorder. When parents have difficulty regulating their emotions, they often cannot teach their children to regulate properly. The role of parents in a child's development is acknowledged by attachment theory, which argues that the characteristics of the caregiver-child relationship impact future relationships. Current research indicates that parent-child relationships characterized by less affection and greater hostility may result in children developing emotional regulation problems. If the child's emotional needs are ignored or rejected, they may experience greater difficulty dealing with emotions in the future. Moreover, conflict between parents is linked to increased emotional reactivity or dysregulation in children. Other factors involved include the quality of relationship with peers, the child's temperament, and social or cognitive understanding. Additionally, loss or grief can contribute to emotional dysregulation.

Research has shown that failures in emotional regulation may be related to the display of acting out, externalizing disorders, or behavior problems. When presented with challenging tasks, children who were found to have defects in emotional regulation (high-risk) spent less time attending to tasks and more time throwing tantrums or fretting than children without emotional regulation problems (low-risk). High-risk children had difficulty with self-regulation, had difficulty complying with requests from caregivers and were more defiant. Emotional dysregulation has also been associated with childhood social withdrawal.

Internalizing behaviors

Emotional dysregulation in children can be associated with internalizing behaviors including:

• exhibiting emotions too intense for a situation;
• difficulty calming down when upset;
• difficulty decreasing negative emotions;
• being less able to calm themselves;
• difficulty understanding emotional experiences;
• becoming avoidant or aggressive when dealing with negative emotions; and
• experiencing more negative emotions.

Externalizing behaviors

Emotional dysregulation in children can be associated with externalizing behaviors including:

• exhibiting more extreme emotions;
• difficulty identifying emotional cues;
• difficulty recognizing their own emotions;
• focusing on the negative;
• difficulty controlling their attention;
• being impulsive;
• difficulty decreasing their negative emotions; and
• difficulty calming down when upset.

Adolescence

In adolescents, emotional dysregulation is a risk factor for many mental health disorders including depressive disorders, anxiety disorders, post-traumatic stress disorder, bipolar disorder, borderline personality disorder, substance use disorder, alcohol use disorder, eating disorders, oppositional defiant disorder, and disruptive mood dysregulation disorder. Dysregulation is also associated with self-injury, suicidal ideation, suicide attempts, and risky sexual behavior. Emotional dysregulation is not a diagnosis, but an indicator of an emotional or behavioral problem that may need intervention.

Attachment theory and the idea of an insecure attachment are implicated in emotional dysregulation. Greater attachment security correlates with less emotional dysregulation in daughters. Moreover, it has been observed that more female teens struggle with emotional dysregulation than males. Professional treatment, such as therapy or admittance into a psychiatric facility, is recommended.

Adulthood

Emotional dysregulation tends to present as emotional responses that may seem excessive compared to the situation. Individuals with emotional dysregulation may have difficulty calming down, avoiding difficult feelings, or focusing on the negative.^[37] On average, women tend to score higher on scales of emotional reactivity than men.^[40][41][42] A study at University College Dublin found that dysregulation correlates to negative feelings about one's ability to cope with emotions and rumination in adults. They also found dysregulation to be common in a sample of individuals not affected by mental disorders.

Part of emotional dysregulation, which is a core characteristic in borderline personality disorder, is affective instability, which manifests as rapid and frequent shifts in mood of high affect intensity and rapid onset of emotions, often triggered by environmental stimuli. The return to a stable emotional state is notably delayed, exacerbating the challenge of achieving emotional equilibrium. This instability is further intensified by an acute sensitivity to psychosocial cues, leading to significant challenges in managing emotions effectively.

Effect on relationships

Established relationships

Relationships are generally linked to better well-being, but dissatisfaction in relationships can lead to increased divorce, worsened health, and potential violence. Emotional dysregulation plays a role in relationship quality and overall satisfaction. It can be difficult for emotionally dysregulated individuals to maintain healthy relationships. People who struggle with emotional dysregulation often externalize, internalize, or dissociate when exposed to stressors. These behaviors are attempts to regulate emotions but often are ineffective in addressing stress in relationships. This commonly presents itself as intense anxiety around relationships, poor ability to set and sustain boundaries, frequent and damaging arguments, preoccupation with loneliness, worries about losing a relationship, and jealous or idealizing feelings towards others. These feelings may be accompanied by support-seeking behaviors such as clinging, smothering, or seeking to control.

The counterpart of emotional dysregulation, emotional regulation, strengthens relationships. The ability to regulate negative emotions in particular is linked to positive coping and thus higher relationship satisfaction. Emotional regulation and communication skills are linked to secure attachment, which has been related to higher partner support as well as openness in discussing negative experiences and resolving conflict. On the other hand, emotional dysregulation has a negative impact on relationships. Multiple studies note the effects of emotion dysregulation on relationship quality. One study found that relationship satisfaction is lower in couples that lack impulse control or regulatory strategies. Another study found that both husbands' and wives' emotional reactivity was negatively linked with marriage quality as well as perceptions of partner responsiveness. The literature concludes that dysregulation increases instances of perceived criticism, contributes to physical and psychological violence, and worsens depression, anxiety, and sexual difficulties. Dysregulation has also been observed to lower empathy and decrease relationship satisfaction, quality, and intimacy.

Sexual health

Research conflicts on whether higher levels of emotional reactivity are linked to increases or decreases in sexual desire. Moreover, this effect could differ between men and women based on observed differences in emotional reactivity between genders. Some research posits that higher emotional reactivity in women is linked to greater sexual attraction in their male partners. However, difficulties in regulating emotions have been linked to poorer sexual health, both in terms of ability and overall satisfaction.

Emotional dysregulation plays a role in nonconsensual and violent sexual encounters. Emotional regulation skills prevent verbal coercion by regulating feelings of sexual attraction in men. Consequently, a lack of emotional regulation skills can cause both internalizing and externalizing behaviors in a sexual context. This may mean violence, which can serve as a strategy for regulating emotion. In a non-violent context, insecurely attached individuals may seek to satisfy their need for connection or to resolve relational issues with sex. Communication can also be hindered, as emotional dysregulation has been linked to an inability to express oneself in sexual situations. This can lead to victimization as well as further sexual difficulties. Thus, the ability to both recognize emotions and express negative emotions are important for communication and social adjustment, including within sexual contexts.

Mediating effects

While personal characteristics and experiences can contribute to externalizing and internalizing behaviors as listed above, emotional regulation has an interpersonal aspect. Couples who effectively co-regulate have higher emotional satisfaction and stability. Openly discussing emotions in the relationship can help to validate feelings of insecurity and encourage closeness. For partners who struggle with emotional dysregulation, there are available treatments. Couples' therapy has shown itself to be an effective method of improving relationship satisfaction and quality by positively affecting the process of emotional regulation in relationships.

Protective factors

Early experiences with caregivers can lead to differences in emotional regulation. The responsiveness of a caregiver to an infant's signals can help an infant regulate their emotional systems. Caregiver interaction styles that overwhelm a child or that are unpredictable may undermine emotional regulation development. Effective strategies involve working with a child to support developing self-control, such as modeling a desired behavior rather than demanding it.

The richness of an environment that a child is exposed to helps the development of emotional regulation. An environment must provide appropriate levels of freedom and constraint. The environment must allow opportunities for a child to practice self-regulation. An environment with opportunities to practice social skills without overstimulation or excessive frustration helps a child develop self-regulation skills.

Substance use

Several variables have been explored to explain the connection between emotional dysregulation and substance use in young adults, such as child maltreatment, cortisol levels, family environment, and symptoms of depression and anxiety. Vilhena-Churchill and Goldstein (2014) explored the association between childhood maltreatment and emotional dysregulation. More severe childhood maltreatment was found to be associated with an increase in difficulty regulating emotion, which in turn was associated with a greater likelihood of coping by using marijuana. Kliewer et al. (2016) performed a study on the relationship between negative family emotional climate, emotional dysregulation, blunted anticipatory cortisol, and substance use in adolescents. Increased negative family emotional climate was found to be associated with high levels of emotional dysregulation, which was then associated with increased substance use. Girls were seen to have blunted anticipatory cortisol levels, which was also associated with an increase in substance use. Childhood events and family climate with emotional dysregulation are both factors seemingly linked to substance use. Prosek, Giordano, Woehler, Price, and McCullough (2018) explored the relationship between mental health and emotional regulation in collegiate illicit substance users. Illicit drug users reported higher levels of depression and anxiety symptoms. Emotional dysregulation was more prominent in illicit drug users in the sense that they had less clarity and were less aware of their emotions when the emotions were occurring.

Treatment

See also: Management of borderline personality disorder and Management of attention deficit hyperactivity disorder

Many people experience dysregulation and can struggle at times with uncontrollable emotions. Thus, potential underlying issues are important to consider in determining severity. As the ability to appropriately express and regulate emotions is related to better relationships and mental health, parental support can help regulate the emotions of children struggling with emotional dysregulation. Training to help parents address this issue focuses on predictability and consistency. These tenets are thought to provide comfort by creating a sense of familiarity and thus safety.

While cognitive behavioral therapy (CBT) is the most widely prescribed treatment for such psychiatric disorders, a commonly prescribed psychotherapeutic treatment for emotional dysregulation is dialectical behavioral therapy (DBT), a psychotherapy which promotes the use of mindfulness, a concept called dialectics, and emphasis on the importance of validation and maintaining healthy behavioral habits.

When diagnosed as being part of ADHD, norepinephrine and dopamine reuptake inhibitors such as methylphenidate (Ritalin) and atomoxetine are often used. A few studies have also showed promise in terms of non-pharmacological treatments for people with ADHD and emotional problems, although the research is limited and requires additional inquiry.

Eye Movement Desensitization and Reprocessing (EMDR) can help recovery from emotional dysregulation in cases where the dysregulation is a symptom of prior trauma. Outside of therapy, there are helpful strategies to help individuals recognize how they are feeling and put space between an event and their response. These include mindfulness, affirmations, and gratitude journaling. Hypnosis may also help to improve emotional regulation. Movement such as yoga and aerobic exercise can also be therapeutic by aiding with regulation and the ability to understand how one's mind influences behavior.

Molecular diagnostics

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Molecular_diagnostics 

Specialist using "QIAsymphony", an automation platform for molecular diagnostic tests

Molecular diagnostics is a collection of techniques used to analyze biological markers in the genome and proteome, and how their cells express their genes as proteins, applying molecular biology to medical testing. In medicine the technique is used to diagnose and monitor disease, detect risk, and decide which therapies will work best for individual patients, and in agricultural biosecurity similarly to monitor crop- and livestock disease, estimate risk, and decide what quarantine measures must be taken.

By analysing the specifics of the patient and their disease, molecular diagnostics offers the prospect of personalised medicine. These tests are useful in a range of medical specialties, including infectious disease, oncology, human leucocyte antigen typing (which investigates and predicts immune function), coagulation, and pharmacogenomics—the genetic prediction of which drugs will work best. They overlap with clinical chemistry (medical tests on bodily fluids).

History

Molecular diagnostics uses techniques such as mass spectrometry and gene chips to capture the expression patterns of genes and proteins

The field of molecular biology grew in the late twentieth century, as did its clinical application. In 1980, Yuet Wai Kan et al. suggested a prenatal genetic test for Thalassemia that did not rely upon DNA sequencing—then in its infancy—but on restriction enzymes that cut DNA where they recognised specific short sequences, creating different lengths of DNA strand depending on which allele (genetic variation) the fetus possessed. In the 1980s, the phrase was used in the names of companies such as Molecular Diagnostics Incorporated and Bethseda Research Laboratories Molecular Diagnostics.

During the 1990s, the identification of newly discovered genes and new techniques for DNA sequencing led to the appearance of a distinct field of molecular and genomic laboratory medicine; in 1995, the Association for Molecular Pathology (AMP) was formed to give it structure. In 1999, the AMP co-founded The Journal of Medical Diagnostics. Informa Healthcare launched Expert Reviews in Medical Diagnostics in 2001. From 2002 onwards, the HapMap Project aggregated information on the one-letter genetic differences that recur in the human population—the single nucleotide polymorphisms—and their relationship with disease. In 2012, molecular diagnostic techniques for Thalassemia use genetic hybridization tests to identify the specific single nucleotide polymorphism causing an individual's disease.

As the commercial application of molecular diagnostics has become more important, so has the debate about patenting of the genetic discoveries at its heart. In 1998, the European Union's Directive 98/44/ECclarified that patents on DNA sequences were allowable. In 2010 in the US, AMP sued Myriad Genetics to challenge the latter's patents regarding two genes, BRCA1, BRCA2, which are associated with breast cancer. In 2013, the U.S. Supreme Court partially agreed, ruling that a naturally occurring gene sequence could not be patented.

Techniques

The Affymetrix 5.0, a microarray chip

Development from research tools

The industrialisation of molecular biology assay tools has made it practical to use them in clinics. Miniaturisation into a single handheld device can bring medical diagnostics into the clinic and into the office or home. The clinical laboratory requires high standards of reliability; diagnostics may require accreditation or fall under medical device regulations. As of 2011, some US clinical laboratories nevertheless used assays sold for "research use only".

Laboratory processes need to adhere to regulations, such as the Clinical Laboratory Improvement Amendments, Health Insurance Portability and Accountability Act, Good Laboratory Practice, and Food and Drug Administration specifications in the United States. Laboratory Information Management Systems help by tracking these processes. Regulation applies to both staff and supplies. As of 2012, twelve US states require molecular pathologists to be licensed; several boards such as the American Board of Medical Genetics and the American Board of Pathology certify technologists, supervisors, and laboratory directors.

Automation and sample barcoding maximise throughput and reduce the possibility of error or contamination during manual handling and results reporting. Single devices to do the assay from beginning to end are now available.

Assays

Main articles: Assay and Biological assay

Molecular diagnostics uses in vitro biological assays such as PCR-ELISA or Fluorescence in situ hybridization. The assay detects a molecule, often in low concentrations, that is a marker of disease or risk in a sample taken from a patient. Preservation of the sample before analysis is critical. Manual handling should be minimised. The fragile RNA molecule poses certain challenges. As part of the cellular process of expressing genes as proteins, it offers a measure of gene expression but it is vulnerable to hydrolysis and breakdown by ever-present RNAse enzymes. Samples can be snap-frozen in liquid nitrogen or incubated in preservation agents.

Because molecular diagnostics methods can detect sensitive markers, these tests are less intrusive than a traditional biopsy. For example, because cell-free nucleic acids exist in human plasma, a simple blood sample can be enough to sample genetic information from tumours, transplants or an unborn fetus. Many, but not all, molecular diagnostics methods based on nucleic acids detection use polymerase chain reaction (PCR) to vastly increase the number of nucleic acid molecules, thereby amplifying the target sequence(s) in the patient sample. PCR is a method that a template DNA is amplified using synthetic primers, a DNA polymerase, and dNTPs. The mixture is cycled between at least 2 temperatures: a high temperature for denaturing double-stranded DNA into single-stranded molecules and a low temperature for the primer to hybridize to the template and for the polymerase to extend the primer. Each temperature cycle theoretically doubles the quantity of target sequence. Detection of sequence variations using PCR typically involves the design and use oligonucleotide reagents that amplify the variant of interest more efficiently than wildtype sequence. PCR is currently the most widely used method for detection of DNA sequences. The detection of the marker might use real time PCR, direct sequencing, microarray chips—prefabricated chips that test many markers at once, or MALDI-TOF The same principle applies to the proteome and the genome. High-throughput protein arrays can use complementary DNA or antibodies to bind and hence can detect many different proteins in parallel. Molecular diagnostic tests vary widely in sensitivity, turn around time, cost, coverage and regulatory approval. They also vary in the level of validation applied in the laboratories using them. Hence, robust local validation in accordance with the regulatory requirements and use of appropriate controls is required especially where the result may be used to inform a patient treatment decision.

Benefits

A microarray chip contains complementary DNA (cDNA) to many sequences of interest. The cDNA fluoresces when it hybridises with a matching DNA fragment in the sample.

Prenatal

See also: Category:Tests during pregnancy

Conventional prenatal tests for chromosomal abnormalities such as Down syndrome rely on analysing the number and appearance of the chromosomes—the karyotype. Molecular diagnostics tests such as microarray comparative genomic hybridisation test a sample of DNA instead, and because of cell-free DNA in plasma, could be less invasive, but as of 2013 it is still an adjunct to the conventional tests.

Treatment

Main article: Pharmacogenomics

Some of a patient's single nucleotide polymorphisms—slight differences in their DNA—can help predict how quickly they will metabolise particular drugs; this is called pharmacogenomics. For example, the enzyme CYP2C19 metabolises several drugs, such as the anti-clotting agent Clopidogrel, into their active forms. Some patients possess polymorphisms in specific places on the 2C19 gene that make poor metabolisers of those drugs; physicians can test for these polymorphisms and find out whether the drugs will be fully effective for that patient. Advances in molecular biology have helped show that some syndromes that were previously classed as a single disease are actually multiple subtypes with entirely different causes and treatments. Molecular diagnostics can help diagnose the subtype—for example of infections and cancers—or the genetic analysis of a disease with an inherited component, such as Silver-Russell syndrome.

Infectious disease

See also: Pathogenomics

Molecular diagnostics are used to identify infectious diseases such as chlamydia, influenza virus and tuberculosis; or specific strains such as H1N1 virus or SARS-CoV-2. Genetic identification can be swift; for example a loop-mediated isothermal amplification test diagnoses the malaria parasite and is rugged enough for developing countries. But despite these advances in genome analysis, in 2013 infections are still more often identified by other means—their proteome, bacteriophage, or chromatographic profile. Molecular diagnostics are also used to understand the specific strain of the pathogen—for example by detecting which drug resistance genes it possesses—and hence which therapies to avoid. In addition, assays based on metagenomic next generation sequencing can be implemented to identify pathogenic organisms without bias.

Disease risk management

See also: Screening (medicine) and Genetic testing

A patient's genome may include an inherited or random mutation which affects the probability of developing a disease in the future. For example, Lynch syndrome is a genetic disease that predisposes patients to colorectal and other cancers; early detection can lead to close monitoring that improves the patient's chances of a good outcome. Cardiovascular risk is indicated by biological markers and screening can measure the risk that a child will be born with a genetic disease such as Cystic fibrosis. Genetic testing is ethically complex: patients may not want the stress of knowing their risk. In countries without universal healthcare, a known risk may raise insurance premiums.

Cancer

See also: Tumor metabolome

Cancer is a change in the cellular processes that cause a tumour to grow out of control. Cancerous cells sometimes have mutations in oncogenes, such as KRAS and CTNNB1 (β-catenin). Analysing the molecular signature of cancerous cells—the DNA and its levels of expression via messenger RNA—enables physicians to characterise the cancer and to choose the best therapy for their patients. As of 2010, assays that incorporate an array of antibodies against specific protein marker molecules are an emerging technology; there are hopes for these multiplex assays that could measure many markers at once. Other potential future biomarkers include micro RNA molecules, which cancerous cells express more of than healthy ones.

Cancer is a disease with excessive molecular causes and constant evolution. There's also heterogeneity of disease even in an individual. Molecular studies of cancer have proved the significance of driver mutations in the growth and metastasis of tumors. Many technologies for detection of sequence variations have been developed for cancer research. These technologies generally can be grouped into three approaches: polymerase chain reaction (PCR), hybridization, and next-generation sequencing (NGS). Currently, a lot of PCR and hybridization assays have been approved by FDA as in vitro diagnostics. NGS assays, however, are still at an early stage in clinical diagnostics.

To do the molecular diagnostic test for cancer, one of the significant issue is the DNA sequence variation detection. Tumor biopsy samples used for diagnostics always contain as little as 5% of the target variant as compared to wildtype sequence. Also, for noninvasive applications from peripheral blood or urine, the DNA test must be specific enough to detect mutations at variant allele frequencies of less than 0.1%.

Currently, by optimizing the traditional PCR, there's a new invention, amplification-refractory mutation system (ARMS) is a method for detecting DNA sequence variants in cancer. The principle behind ARMS is that the enzymatic extension activity of DNA polymerases is highly sensitive to mismatches near the 3' end of primer. Many different companies have developed diagnostics tests based on ARMS PCR primers. For instance, Qiagen therascreen, Roche cobas and Biomerieux THxID have developed FDA approved PCR tests for detecting lung, colon cancer and metastatic melanoma mutations in the KRAS, EGFR and BRAF genes. Their IVD kits were basically validated on genomic DNA extracted from FFPE tissue.

There are also microarrays that utilize hybridization mechanism to diagnose cancer. More than a million of different probes can be synthesized on an array with Affymetrix's Genechip technology with a detection limit of one to ten copies of mRNA per well. Optimized microarrays are typically considered to produce repeatable relative quantitation of different targets. Currently, FDA have already approved a number of diagnostics assays utilizing microarrays: Agendia's MammaPrint assays can inform the breast cancer recurrence risk by profiling the expression of 70 genes related to breast cancer; Autogenomics INFNITI CYP2C19 assay can profile genetic polymorphisms, whose impacts on therapeutic response to antidepressants are great; and Affymetrix's CytoScan Dx can evaluate intellectual disabilities and congenital disorders by analyzing chromosomal mutation.

In the future, the diagnostic tools for cancer will likely to focus on the Next Generation Sequencing (NGS). By utilizing DNA and RNA sequencing to do cancer diagnostics, technology in the field of molecular diagnostics tools will develop better. Although NGS throughput and price have dramatically been reduced over the past 10 years by roughly 100-fold, we remain at least 6 orders of magnitude away from performing deep sequencing at a whole genome level. Currently, Ion Torrent developed some NGS panels based on translational AmpliSeq, for example, the Oncomine Comprehensive Assay. They are focusing on utilizing deep sequencing of cancer-related genes to detect rare sequence variants.

Molecular diagnostics tool can be used for cancer risk assessment. For example, the BRCA1/2 test by Myriad Genetics assesses women for lifetime risk of breast cancer. Also, some cancers are not always employed with clear symptoms. It is useful to analyze people when they do not show obvious symptoms and thus can detect cancer at early stages. For example, the ColoGuard test may be used to screen people over 55 years old for colorectal cancer. Cancer is a longtime-scale disease with various progression steps, molecular diagnostics tools can be used for prognosis of cancer progression. For example, the OncoType Dx test by Genomic Health can estimate risk of breast cancer. Their technology can inform patients to seek chemotherapy when necessary by examining the RNA expression levels in breast cancer biopsy tissue.

With rising government support in DNA molecular diagnostics, it is expected that an increasing number of clinical DNA detection assays for cancers will become available soon. Currently, research in cancer diagnostics are developing fast with goals for lower cost, less time consumption and simpler methods for doctors and patients.

Allergy

Molecular diagnostics is increasingly used in allergology, especially for food and respiratory allergy. Conventional diagnosis is based on clinical history, skin-prick testing and measurement of serum allergen-specific IgE to whole allergen extracts. Molecular-based allergy diagnostics, also called component-resolved diagnostics, measures IgE to individual allergen molecules rather than only to extracts. This can help distinguish genuine sensitization from cross-reactivity, refine assessment of clinical risk in some allergies, and support decisions about allergen immunotherapy. Multiplex platforms, such as Allergy Explorer (ALEX), can test IgE reactivity to many allergen extracts and molecular components in a single assay. Precision allergy molecular diagnosis (PAMD®) is a broader diagnostic approach using molecular IgE profiles to guide prognosis, risk assessment and personalized management, although results must be interpreted together with the patient’s clinical history.

 

Greatness

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Greatness

Monument of Peter the Great in Saint Petersburg

Coronation of the Hero of Virtue (c. 1612–1614) by Peter Paul Rubens

Great Wall of China

Greatness is a concept of a state of exceptional superiority affecting a person or object in a particular place or area. Greatness can also be attributed to individuals who possess a natural ability to be better than all others. An example of an expression of the concept in a qualified sense would be "Hector is the definition of greatness" or "Napoleon was one of the greatest wartime leaders". In the unqualified sense it might be stated "George Washington achieved greatness within his own lifetime", thus implying that "greatness" is a definite and identifiable quality. Application of the terms "great" and "greatness" is dependent on the perspective and subjective judgements of those who apply them. Whereas in some cases the perceived greatness of a person, place or object might be agreed upon by many, this is not necessarily the case, and the perception of greatness may be both fiercely contested and highly idiosyncratic.

Historically, in Europe, rulers were sometimes given the attribute "the Great", as in Alexander the Great, Frederick the Great, Alfred the Great and Catherine the Great. Starting with the Roman consul and general Pompey, the Latin equivalent Magnus was also used, as in Pompeius Magnus, Albertus Magnus, and Carolus Magnus. The English language uses the Latin term magnum opus, (literally "great work") to describe certain works of art and literature.

Since the publication of Francis Galton's Hereditary Genius in 1869, and especially with the accelerated development of intelligence tests in the early 1900s, there has been a vast amount of social scientific research published relative to the question of greatness. Much of this research does not actually use the term great in describing itself, preferring terms such as eminence, genius, exceptional achievement, etc. Historically the major intellectual battles over this topic have focused around the questions of nature versus nurture or person versus context. Today the importance of both dimensions is accepted by all, but disagreements over the relative importance of each are still reflected in variations in research emphases.

"Jesus teaches about greatness" (Matthew 18) by Julius Schnorr von Karolsfeld, 1860

Genetic approaches

Early scientific research on greatness had a strong genetic emphasis and focused on intelligence as the driving force behind the concept.

Hereditary Genius – Galton (1869)

The earliest such research, Hereditary Genius, by Francis Galton (1869), argued that people vary hugely in "natural ability" which is allegedly inherited biologically. Those at the very top end of the range, i.e., geniuses, become according to Galton the "eminent" achievers of their generation. To prove this thesis Galton collected data showing that genius clusters in what he termed "Notable Family Lines", such as those of Bernoulli, Cassini, Darwin, Herschel, and Jussieu in science, or Bach in music.

Galton then calculated the odds of eminent people having eminent relations, taking into account the closeness of the biological connection (e.g., son vs grandson), and the magnitude of achievement of the eminent parent. His findings were as anticipated: the more famous the parent (i.e., the greater level of presumed "natural ability"), the greater likelihood there would be illustrious relatives; and the closer the blood tie, the greater those odds.

Early Mental Traits of 300 Geniuses – Cox (1926)

Catharine Cox's book on The Early Mental Traits of Three Hundred Geniuses (1926), was similar to Galton's in its orientation. Using the method that her mentor, Stanford Psychology Professor Lewis Terman, had developed for differentiating children in terms of intelligence, Cox coded records of childhood and adolescent achievements of 301 historic eminent leaders and creators to estimate what their IQs would have been on the basis of intellectual level of such achievements relative to the age at which they were accomplished. For example, John Stuart Mill reportedly studied Greek at 3, read Plato at 7, and learned calculus at 11. As such, what he was doing at 5, the average person couldn't do until 9 years, 6 months of age, giving Mill an estimated IQ of 190.

Cox found that the perceived eminence of those with the highest IQs was higher than that of those attaining lower IQ estimates, and that those with higher IQs also exhibited more versatility in their achievements. For example, da Vinci, Michelangelo, Descartes, Benjamin Franklin, Goethe, and others with IQs in the mid 160s or above were superior in their versatility to those attaining lower scores, such as George Washington, Palestrina, or Philip Sheridan.

The work of both Cox and Galton has been criticized for failing to take sufficient account of the role of nurture, or more specifically socio-economic and educational advantage, in the achievements of these historical greats.

Cultural approach

There was one major anthropological study of genius, and it was triggered specifically by the author's contentions with Galton's work.

Configurations of Cultural Growth – Kroeber (1944)

Alfred Kroeber's Configurations of Cultural Growth (1944) looked at many of the same historic greats as did Galton and Cox, but from a completely different orientation. As a cultural anthropologist, Kroeber maintained that, in Simonton's words, "culture takes primacy over the individual in any account of human (behavior), and that historic geniuses are no exception..."

To prove his thesis, Kroeber collected "long lists of notable figures from several nationalities and historic eras", and then grouped them within a field and a shared cultural context, e.g., "Configuration for American Literature". Then within these groupings he listed his notables in "strict chronological order", identifying the most eminent figures by using capital letters for their surnames (e.g. EMERSON, LONGFELLOW, POE, WHITMAN, etc. in above configuration).

Kroeber found that genius never appeared in isolation, but rather, in Simonton's words, that "one genius cluster(ed) with others of greater and lesser fame in adjacent generations". He also found that there were historical "crests" and "troughs" in every field. These fluctuations in the appearance of genius were much too rapid to be explained by the simple mechanism of genetic inheritance along family lines.

Kroeber argued, in Simonton's words, that his "configurations" were due to "emulations": "Geniuses cluster in history because the key figures of one generation emulate those in the immediately preceding generations... (until) it attains a high point of perfection that stymies further growth". At this point the "tradition degenerates into empty imitation, as most creative minds move on to greener pastures".

Recent research is consistent with these explanations; but many aspects of the developmental process from birth to the attainment of greatness remain unaccounted for by Kroeber's anthropological approach.

Developmental approaches

Retrospective studies, involving extensive interviews with individuals who have attained eminence, or at least exceptional levels of achievement, have added much to our understanding of the developmental process. Two studies in particular stand out.

Scientific Elite – Zuckerman (1977)

Harriet Zuckerman's Scientific Elite: Nobel Laureates in the United States, is based on many sources of research evidence, including a series of forty-one extended interviews with American winners of the Nobel Prize for science.

Zuckerman reported her results around two main topics: How the Prize is Awarded, and Career Development of the Scientific Elite. Her findings on the first topic are briefly overviewed in the Wikipedia article regarding the Nobel Prize

In relation to the question of the career development of the scientific elite Zuckerman uses the phrase "accumulation of advantage" to describe her findings. In her words: "Scientists who show promise early in their careers (are) given greater opportunities in the way of research training and facilities. To the extent that these scientists are as competent as the rest or more so, they ultimately will do far better in terms of both role performance and reward... rewards (which) can be transformed into resources for further work... (and hence over time) scientists who are initially advantaged gain even greater opportunities for further achievement and rewards."

To see if 'accumulation of advantage' was operating in the career development of the scientific elite, Zuckerman compared the careers of future laureates with those of "members of the United States National Academy of Sciences and the scientific rank and file" along a number of dimensions including socioeconomic origins, status of undergraduate and graduate education, the process of moving into the scientific elite, and first jobs and professorships.

She also interviewed forty-one Nobel laureates extensively about their "apprenticeships" to "master" scientists while they were doing their doctoral research, and other aspects of their career development related to the above topics.

Zuckerman concluded that evidence of "accumulative of advantage" was clearly present over the course of development, with result that her research "... cast(s) considerable doubt on the conclusion that marked differences in performance between the ultra-elite and other scientists reflect equally marked differences in their initial capacities to do scientific work".

Developing Talent in Young People – Bloom (1985)

Benjamin Bloom and five colleagues conducted extensive interviews with 120 "young men and women (as well as their parents and influential teachers)... who had reached the highest levels of accomplishment" in six fields – Olympic sprint swimmers, Top 10 rated professional tennis players, concert pianists, accomplished sculptors, exceptional mathematicians, and outstanding research neurologists.

They report many findings relevant to the "talent development process", including:

• Development was tied throughout to the values, interests, resources, and personal investments of the family of origin. In most families "introduction to the field and initial... skill development occurred" because the "(p)arents (or other family members), in pursuing their own interests, created situations that intrigued, interested, or involved the child... The child's interest was rewarded or encouraged..." and the parents then provided other ways to extend this interest.
• The "work ethic" is central to talent development. It is developed by "the home environment" and "...directly related to learning and participation in the chosen talent field".
• "Each group of parents strongly encouraged their children's development in a particularly highly approved talent field (related to the parents' own "special interests") and gave much less support to other possible talent fields and activities."
• "Families and teachers were crucial at every point along the way to excellence... what families and teachers do at different times and how they do it clearly sets the stage for exceptional learning in each talent field".
• "Few... (of the) individuals (included in this study) were regarded as child prodigies"; and, as a result, this research "raises (serious) questions about earlier views of special gifts and innate abilities as necessary prerequisites of talent development".

Recent approaches

A 1995 book by Hans Eysenck argues that a "personality trait" called Psychoticism is central to becoming a creative genius; and a more recent book by Bill Dorris (2009) looks at the influence of "everything from genetics to cultural crises", including chance, over the course of development of those who attain greatness. See – Hans Eysenck, Genius: The Natural History of Creativity (1995), "construct(s)... a model of genius and creativity" whose "novelty lies in (its) attempt to make personality differences central to the argument".

In particular Eysenck is interested in a personality trait called "psychoticism ... chief among (whose) cognitive features is a tendency to over-inclusiveness, i.e., an inclination not to limit one's associations to relevant ideas, memories, images, etc."

He considers a massive range of experimental psychological research in order to establish the underlying genetic, neuro-chemical mechanisms which may be operating to influence levels of creativity associated with fluctuations in "the tendency towards over-inclusiveness indicative of psychoticism..."

Eysenck's assessment of his overall argument is as follows: "There is no hint that the theory is more than a suggestion of how many disparate facts and hypotheses can be pulled together into a causal chain, explaining... the apogee of human endeavour – genius. If the theory has one point in its favour it is that every step can be tested experimentally, and that many steps have already received positive support from such testing."

The Arrival of The Fittest

Bill Dorris's book, The Arrival of The Fittest: How The Great Become Great (2009), attempts to address a number of issues which remain unanswered on the subject. These include the role of chance over the course of development, the importance of the development of unique personal characteristics to achieving greatness, and the influence of changes in the wider worlds surrounding the person – from interpersonal to societal - on the course of an individual's development.

Dorris argues that those who attain 'greatness' are credited with solving a key generational problem in a field and/or society (e.g., Albert Einstein resolving the conflict between Isaac Newton and James Clerk Maxwell in physics at the outset of the 20th century; or Woody Guthrie providing a voice for the outcasts of the Great Depression of the 1930s).

Dorris's core argument is that those who become 'great' start out with sufficient genetic potential and then are able, over two or more decades, to obtain matches/fits with "the right kind of problems" to extend the development of these genetic biases into what Dorris terms, "key characteristics". These are the intellectual, personality, and self characteristics which eventually turn out to be required to solve a key generational problem in their field and/or society.

Dorris argues that there are four types of matching processes which occur over the course of such development. These refer to matches between the developmental needs of the person and the opportunities and resources essential to engaging in problem solving activities that stimulate further development of those aspects of intelligence, personality, and self which eventually become key characteristics.

Two of these matching processes are covered extensively in the existing research literature: continuous matching and cumulative matching.

The other two of the matching processes described by Dorris are completely new to this book: catalytic matching and chaotic matching.

Dorris's argument in relation to catalytic matching is that anyone who eventually becomes a 'great' will have experienced one or more sustained periods of exceptionally accelerated development of their key characteristics, accelerations which serve massively to differentiate them from their former peers in terms of both development and visibility within the field.

This acceleration occurs because the person becomes the focal point (star) of a self-reinforcing system of expertise and resources (catalytic system) which thrives off this person's accelerated development and visibility.

Dorris's argument in relation to chaotic matching is that access to the resources and learning opportunities essential to the development of key characteristics of an eventual 'great' often occurs not due to the efforts/planning of the individual, but simply due to chance events in the interpersonal, institutional or societal worlds around the person, who (unlike perhaps millions of equally capable peers) becomes the beneficiary of these chance events – events which Dorris argues can change a person's entire future in much the same way as a lottery jackpot or a Titanic ticket.

Dorris documents his theoretical arguments with extensive case studies of a wide range of individuals, including Einstein, Elvis, Monet, Mozart, da Vinci, Abraham Lincoln, Watson and Crick, basketball great Bill Russell, Louis Armstrong, Bill Gates, Alfred Hitchcock, Woody Guthrie, and Norma Jeane/Marilyn Monroe.