Virus quantification

Virus quantification involves counting the number of viruses in a specific volume to determine the virus concentration. It is utilized in both research and development (R&D) in commercial and academic laboratories as well as production situations where the quantity of virus at various steps is an important variable. For example, the production of viral vaccines, recombinant proteins using viral vectors and viral antigens all require virus quantification to continually adapt and monitor the process in order to optimize production yields and respond to ever changing demands and applications. Examples of specific instances where known viruses need to be quantified include clone screening, multiplicity of infection (MOI) optimization and adaptation of methods to cell culture. This page discusses various techniques currently used to quantify viruses in liquid samples. These methods are separated into two categories, traditional vs. modern methods. Traditional methods are industry-standard methods that have been used for decades but are generally slow and labor-intensive. Modern methods are relatively new commercially available products and kits that greatly reduce quantification time. This is not meant to be an exhaustive review of all potential methods, but rather a representative cross-section of traditional methods and new, commercially available methods. While other published methods may exist for virus quantification, non-commercial methods are not discussed here.
Traditional methods.
Plaque assay.
Plaque-based assays are the standard method used to determine virus concentration in terms of infectious dose. Viral plaque assays determine the number of plaque forming units (pfu) in a virus sample, which is one measure of virus quantity. This assay is based on a microbiological method conducted in petri dishes or multi-well plates. Specifically, a confluent monolayer of host cells is infected with the virus at varying dilutions and covered with a semi-solid medium, such as agar or carboxymethyl cellulose, to prevent the virus infection from spreading indiscriminately. A viral plaque is formed when a virus infects a cell within the fixed cell monolayer. The virus infected cell will lyse and spread the infection to adjacent cells where the infection-to-lysis cycle is repeated. The infected cell area will create a plaque (an area of infection surrounded by uninfected cells) which can be seen with an optical microscope or visually (pouring off the overlay medium and adding a crystal violet solution for 15 minutes until it has colored the cytoplasm, gently removing the excess with water will show uncolored the location of dead cells). Plaque formation can take 3–14 days, depending on the virus being analyzed. Plaques are generally counted manually and the results, in combination with the dilution factor used to prepare the plate, are used to calculate the number of plaque forming units per sample unit volume (pfu/mL). The pfu/mL result represents the number of infective particles within the sample and is based on the assumption that each plaque formed is representative of one infective virus particle.
Focus forming assay (FFA).
The focus forming assay (FFA) is a variation of the plaque assay, but instead of relying on cell lysis in order to detect plaque formation, the FFA employs immunostaining techniques using fluorescently labeled antibodies specific for a viral antigen to detect infected host cells and infectious virus particles before an actual plaque is formed. The FFA is particularly useful for quantifying classes of viruses that do not lyse the cell membranes, as these viruses would not be amenable to the plaque assay. Like the plaque assay, host cell monolayers are infected with various dilutions of the virus sample and allowed to incubate for a relatively brief incubation period (e.g., 24–72 hours) under a semisolid overlay medium that restricts the spread of infectious virus, creating localized clusters (foci) of infected cells. Plates are subsequently probed with fluorescently labeled antibodies against a viral antigen, and fluorescence microscopy is used to count and quantify the number of foci. The FFA method typically yields results in less time than plaque or fifty-percent-tissue-culture-infective-dose (TCID50) assays, but it can be more expensive in terms of required reagents and equipment. Assay completion time is also dependent on the size of area that the user is counting. A larger area will require more time but can provide a more accurate representation of the sample. Results of the FFA are expressed as focus forming units per milliliter, or FFU/mL.
Endpoint dilution assay.
Fifty-percent tissue culture infective dose (TCID50) is the measure of infectious virus titer. This endpoint dilution assay quantifies the amount of virus required to kill 50% of infected hosts or to produce a cytopathic effect in 50% of inoculated tissue culture cells. This assay may be more common in clinical research applications where the lethal dose of virus must be determined or if the virus does not form plaques. When used in the context of tissue culture, host cells are plated and serial dilutions of the virus are added. After incubation, the percentage of cell death (i.e. infected cells) is manually observed and recorded for each virus dilution, and results are used to mathematically calculate a TCID50 result. Due to distinct differences in assay methods and principles, TCID50 and pfu/mL or other infectivity assay results are not equivalent. This method can take up to a week due to cell infectivity time.
Two methods commonly used to calculate TCID50 (can also be used to calculate other types of 50% endpoint such EC50, IC50, and LD50) are:
The "theoretical" relationship between TCID50 and PFU is approximately 0.69 PFU = 1 TCID50 based on the Poisson distribution, a probability distribution which describes how many random events (virus particles) occurring at a known average rate (virus titer) are likely to occur in a fixed space (the amount of virus medium in a well). However it must be emphasized that in practice, this relationship may not hold even for the same virus + cell combination, as the two types of assay are set up differently and virus infectivity is very sensitive to various factors such as cell age, overlay media, etc.
But the following reference defines the relationship differently:
Assuming that the same cell system is used, that the virus forms plaques on those cells, and that no procedures are added which would inhibit plaque formation, 1 ml of virus stock would be expected to have about half of the number of plaque forming units (PFUs) as TCID50. This is only an estimate but is based on the rationale that the limiting dilution which would infect 50% of the cell layers challenged would often be expected to initially produce a single plaque in the cell layers which become infected. In some instances, two or more plaques might by chance form, and thus the actual number of PFUs should be determined experimentally.
Mathematically, the expected PFUs would be somewhat greater than one-half the TCID50, since the negative tubes in the TCID50 represent zero plaque forming units and the positive tubes each represent one or more plaque forming units. A more precise estimate is obtained by applying the Poisson distribution. Where P(o) is the proportion of negative tubes and m is the mean number of infectious units per volume (PFU/ml), P(o) = e(-m). For any titer expressed as a TCID50, P(o) = 0.5. Thus e(-m) = 0.5 and m = -ln 0.5 which is ~ 0.7.
Therefore, one could multiply the TCID50 titer (per ml) by 0.7 to predict the mean number of PFU/ml. When actually applying such calculations, remember the calculated mean will only be valid if the changes in protocol required to visualize plaques do not alter the expression of infectious virus as compared with expression under conditions employed for TCID50.
Thus as a working estimate, one can assume material with a TCID50 of 1 × 105 TCID50/ml will produce 0.7 × 105 PFUs/ml.
Protein assays.
There are several variations of protein-based virus quantification assays. In general, these methods quantify either the amount of all protein or the amount of a specific virus protein in the sample rather than the number of infected cells or virus particles. Quantification most commonly relies on fluorescence detection. Some assay variations quantify protein directly in a sample while other variations require host cell infection and incubation to allow virus growth prior to protein quantification. The variation used depends primarily on the amount of protein (i.e. virus) in the initial sample and the sensitivity of the assay itself. If incubation and virus growth are required, cell and/or virus lysis/digestion are often conducted prior to analysis. Most protein-based methods are relatively fast and sensitive but require quality standards for accurate calibration, and quantify protein, not actual virus particle concentrations. Below are specific examples of widely used protein-based assays.
Hemagglutination assay.
The hemagglutination assay (HA) is a common non-fluorescence protein quantification assay specific for influenza. It relies on the fact that hemagglutinin, a surface protein of influenza viruses, agglutinates red blood cells (i.e. causes red blood cells to clump together). In this assay, dilutions of an influenza sample are incubated with a 1% erythrocyte solution for one hour and the virus dilution at which agglutination first occurs is visually determined. The assay produces a result of hemagglutination units (HAU), with typical pfu to HAU ratios in the 106 range. This assay takes ~1–2 hours to complete and results can differ widely based on the technical expertise of the operator.
The hemagglutination inhibition assay is a common variation of the HA assay used to measure flu-specific antibody levels in blood serum. In this variation, serum antibodies to the influenza virus will interfere with the virus attachment to red blood cells. Therefore, hemagglutination is inhibited when antibodies are present at a sufficient concentration.
Bicinchoninic acid assay.
The bicinchoninic acid assay (BCA) is based on a simple colorimetric measurement and is the most common protein quantification assay. BCA is similar to the Lowry or Bradford protein assays and was first made commercially available by Pierce, which is now owned by Thermo Fisher Scientific. In the BCA assay, a protein's peptide bonds quantitatively reduce Cu2+ to Cu1+, which produces a light blue color. BCA chelates Cu1+ at a 2:1 ratio resulting in a more intensely colored species that absorbs at 562 nm. Absorbance of a sample at 562 nm is used to determine the bulk protein concentration in the sample. Assay results are compared with known standard curves after analysis with a spectrophotometer or plate reader. Total assay time is 30 minutes to one hour. While this assay is ubiquitous and fast, it lacks specificity since it counts all protein, the virus preparation to be quantified must contain very low levels host cell proteins.
Single radial immunodiffusion assay.
Single radial immunodiffusion assay (SRID), also known as the Mancini method, is a protein assay that detects the amount of specific viral antigen by immunodiffusion in a semi-solid medium (e.g. agar). The medium contains antiserum specific to the antigen of interest and the antigen is placed in the center of the disc. As the antigen diffuses into the medium it creates a precipitate ring that grows until equilibrium is reached. Assay time can range from 10 hours to days depending on equilibration time of the antigen and antibody. The zone diameter from the ring is linearly related to the log of protein concentration and is compared to zone diameters for known protein standards for quantification. There are kits and serums commercially available for this assay (e.g. The Binding Site Inc.).
Transmission electron microscopy (TEM).
TEM is a specialized type of microscopy that utilizes a beam of electrons focused with a magnetic field to image a sample. TEM provides imaging with 1000x greater spatial resolution than a light microscope (resolution down to 0.2 nm). An ultrathin, negatively stained sample is required. Sample preparations involve depositing specimens onto a coated TEM grid and negative staining with an electron-opaque liquid. Tissue embedded samples can also be examined if thinly sectioned. Sample preparations vary depending on protocol and user but generally require hours to complete. TEM images can show individual virus particles and quantitative image analysis can be used to determine virus concentrations. These high resolution images also provide particle morphology information that most other methods cannot. Quantitative TEM results will often be greater than results from other assays as all particles, regardless of infectivity, are quantified in the reported virus-like particles per mL (vlp/mL) result. Quantitative TEM generally works well for virus concentrations greater than 106 particles/mL. Because of high instrument cost and the amount of space and support facilities needed, TEM equipment is available in a limited number of facilities.
Modern methods.
Tunable resistive pulse sensing (TRPS).
Tunable resistive pulse sensing (TRPS) is a method that allows high-throughput single particle measurements of individual virus particles, as they are driven through a size-tunable nanopore, one at a time. The technique has the advantage of simultaneously determining the size and concentration, of virus particles in solution with high resolution. This can be used in assessing sample stability and the contribution of aggregates, as well as total viral particle concentration (vp/mL).
TRPS-based measurement occurs in an ionic buffer, and no pre-staining of samples is required prior to analysis, thus the technique is more rapid than those which require pre-treatment with fluorescent dyes, with a total preparation and measurement time of less than 10 minutes per sample. TRPS-bases virus analysis is commercially available through qViro-X systems, which have the ability to be decontaminated chemically by autoclaving after measurement has occurred.
Flow cytometry.
While most flow cytometers do not have sufficient sensitivity, there are a few commercially available flow cytometers that can be used for virus quantification. A virus counter quantifies the number of intact virus particles in a sample using fluorescence to detect colocalized proteins and nucleic acids. Samples are stained with two dyes, one specific for proteins and one specific for nucleic acids, and analyzed as they flow through a laser beam. The quantity of particles producing simultaneous events on each of the two distinct fluorescence channels is determined, along with the measured sample flow rate, to calculate a concentration of virus particles (vp/mL). The results are generally similar in absolute quantity to a TEM result. The assay has a linear working range of 105–109 vp/mL and an analysis time of ~10 min with a short sample preparation time.
Single Virus Inductively Coupled Plasma Mass Spectroscopy (SV ICP-MS).
This technique is similar to Single Particle Inductively Coupled Plasma Mass Spectroscopy (SP ICP-MS)discovered by Degueldre and Favarger (2003) and adapted later for other nanoparticles e.g. gold colloids, see Degueldre et al (2006). The SP ICP-MS was adapted for the analysis of Single Virus Inductively Coupled Plasma Mass Spectroscopy (SV ICPMS) in a comprehensive study i.e. Degueldre (2021). This study suggests to adapting this method for single viruses (SV) identification and counting. With high resolution multi-channel sector field (MC SF) ICP-MS records in SV detection mode, the counting of master and key ions can allow analysis and identification of single viruses. The counting of 2-500 virial units can be performed in 20 s. Analyses are proposed to be carried out in Ar torch for master ions: 12C+, 13C+, 14N+, 15N+, and key ions 31P+, 32S+, 33S+ and 34S+. All interferences are discussed in detail. The use of high resolution MC ICP-MS is recommended while options with anaerobic/aerobic atmospheres are explored to upgrade the analysis when using quadrupole ICP-MS. Application for two virus types (SARS-COV2 and bacteriophage T5) is investigated using time scan and fixed mass analysis for the selected virus ions allowing characterisation of the species using the N/C, P/C and S/C molar ratio's and quantification of their number concentration.
Quantitative polymerase chain reaction (qPCR).
Quantitative PCR utilizes polymerase chain reaction chemistry to amplify viral DNA or RNA to produce high enough concentrations for detection and quantification by fluorescence. In general, quantification by qPCR relies on serial dilutions of standards of known concentration being analyzed in parallel with the unknown samples for calibration and reference. Quantitative detection can be achieved using a wide variety of fluorescence detection strategies, including sequence specific probes or non-specific fluorescent dyes such as SYBR Green. Sequence specific probes, such as TaqMan (developed by Applied Biosystems), Molecular Beacons, or Scorpion, bind only to the DNA of the appropriate sequence produced during the reaction. SYBR Green dye binds to all double-stranded DNA produced during the reaction. While SYBR Green is easy to use, its lack of specificity and lower sensitivity lead most labs to use probe-based qPCR detection schemes. There are many variations of qPCR including the comparative threshold method, which allows relative quantification through comparison of Ct values (PCR cycles that show statistically significant increases in the product) from multiple samples that include an internal standard. PCR amplifies all target nucleic acid, including ones originating from intact infectious viral particles, from defective viral particles as well as free nucleic acid in solution. Because of this, qPCR results (expressed in terms of genome copies/mL) are likely to be higher in quantity than TEM results. For viral quantification, the ratio of whole virions to copies of nucleic acid is seldom one to one. This is because during viral replication, the nucleic acid and viral proteins are not always produced in 1:1 ratio and viral assembly process results in complete virions as well as empty capsids and/or excess free viral genomes. In the example of foot-and-mouth disease virus, the ratio of whole virions to RNA copies within an actively replicating host cell is approximately 1:1000. Products for qPCR-based virus titration are available commercially through numerous companies (e.g. Invitrogen, Roche or Qiagen). Advantages of titration by qPCR include quick turnaround time (1–4 hours) and sensitivity (can detect much lower concentration of viruses than other methods).
Enzyme-linked immunosorbent assay (ELISA).
ELISA is a more modern variation of a protein assay that utilizes a specific antibody linked to an enzyme to detect the presence of an unknown amount of antigen (i.e. virus) in a sample. The antibody-antigen binding event is detected and/or quantified through the enzyme's ability to convert a reagent to a detectable signal that can be used to calculate the concentration of the antigen in the sample. Horseradish peroxidase (HRP) is a common enzyme utilized in ELISA schemes due to its ability to amplify signal and increase assay sensitivity. There are many variations, or types of ELISA assays but they can generally be classified as either indirect, competitive, sandwich or reverse. ELISA kits are commercially available from numerous companies and quantification generally occurs via chromogenic reporters or fluorescence (e.g. Invitrogen, Santa Cruz Biotechnology Inc.). This technique is much less labor-intensive than the traditional methods and can take anywhere from 4 to 24 hours based on antibody incubation time.


Egg jelly

Egg jelly(extracellular layer", "jelly coat) is a gelatinous layer that surrounds the oocytes of many organisms and releases species-specific chemoattractants that activate and guide sperm to the oocyte. The release of chemoattractants is species dependent. For example, sperm in "Lytechinus variegatus,"the green sea urchin, are not chemotactically attracted to the jelly or the egg. The egg jelly is located immediately surrounding the vitelline envelope and consists primarily of a network of short peptides and sulfated fucan glycoproteins. These short peptides diffuse into the surrounding area and stimulate respiration and movement of the sperm to the egg. An example of such a peptide is resact, which has been studied as the primary means of attracting and orientating sperm to the eggs in sea urchins. The sulfated fucan glycoproteins play an important role in binding to sperm receptors and triggering the acrosomal reaction.
Many other functions for the egg jelly have been proposed including sperm agglomeration, protection from mechanical stress and polyspermy, and increasing the size of the egg to improve its chances of colliding with sperm. For echinoderms the jelly coat can increase the diameter of the egg by more than 100%, making it efficient in enhancing fertilization. In female "P. shqipericus," the Albanian water frog, the jelly coat cause sperm to become motile and move faster. For this species of frog, the sperm must interact with the jelly coat for the egg to be successfully fertilized.
Unlike the egg cell, jelly coats do not provide the embryo nutrients. In addition to the sea urchin, egg jelly appears in many species including invertebrates and mammals. Egg jelly can vary in composition and complexity from the relatively homogenous single layer sea urchin egg to the three layer egg jelly in starfish.
There is an increasing concern in how ocean acidification will affect the fertilization of eggs. In "H. tuberculate," low pH can damage the eggs chemical influence on sperm mobility and velocity.


Florida Dental Association

The Florida Dental Association (also abbreviated as FDA) is an organization of dentists in Florida, United States, and it was established in 1884. Currently, there are approximately 7,000 members in the FDA.


Antoine de La Garanderie

Antoine de La Garanderie (22 March 1920 – 27 June 2010) was a French educator and philosopher.


Robert G. Bernreuter

Robert Gibbon Bernreuter (1901–1995) was an American psychologist. In 1931 he developed the Bernreuter Personality Inventory.
He was born in 1901 in Tampico, Illinois.
He received his Ph.D. from Stanford University in 1931, for his thesis he developed the Bernreuter Personality Inventory. He worked at Pennsylvania State University from 1931 to his retirement in 1966.
He married Shirley Buell (1902-2005) of Howard, Pennsylvania in 1931.


Matthew Giobbi

Matthew Tyler Giobbi (born 1974) is an author and educator in the fields of music, science criticism, philosophy, media theory, psychoanalysis and psychology. He has written "A Postcognitive Negation".


Paul Fraisse

Paul Fraisse (20 March 1911 – 12 October 1996) was a French psychologist.


Elias Traboulsi

Elias I. Traboulsi (born May 19, 1957) is a physician in the fields of ophthalmic genetics and pediatric ophthalmology.
Early life.
Elias Traboulsi was born May 19, 1957 in Beirut, Lebanon, to Iskandar and Renée Traboulsi. Dr. Traboulsi earned a bachelor's degree in Science in 1977 and a Doctorate in Medicine in 1982 at the American University of Beirut.
Professional career.
Traboulsi completed a residency in ophthalmology at the American University of Beirut Medical Center in 1985. He then moved to the United States, to complete a fellowship in ophthalmic genetics at the Wilmer Ophthalmological Institute of Johns Hopkins Hospital, Baltimore, Maryland. Traboulsi continued his training with a residency in ophthalmology at Georgetown University Medical Center and a fellowship in pediatric ophthalmology and strabismus at Children's National Medical Center, both in Washington, DC.
Positions.
Following a year as chief resident in ophthalmology at Georgetown University Medical Center, Traboulsi joined the faculty at The Johns Hopkins Hospital, where he served as Associate Professor of Ophthalmology from 1990 to 1997. He additionally was named as Chairman of the Department of Ophthalmology at Johns Hopkins Bayview Medical Center 1995–1997.
In 1997, Traboulsi left Johns Hopkins to join the faculty at, Cleveland Clinic, Cleveland, Ohio, as Head of the Department of Pediatric Ophthalmology and Strabismus and Director of the Center for Genetic Eye Diseases, where he has worked since. He was Director of the Cole Eye Institute fellowship program in Pediatric Ophthalmology and Strabismus 1997–2009, and has been the Cole Eye Institute Residency Program Director since 2001. He was appointed Director of the Graduate Medical Education and Vice-Chairman of the Cleveland Clinic Education Institute in 2005.
Traboulsi has also been a Professor of Ophthalmology at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University since 2006.
Additional positions include:
Awards.
His honors include:
Scientific contributions and professional legacy.
Traboulsi has authored the books Genetic Diseases of the Eye (Oxford Press, First Ed. 1999) and A Compendium of Inherited Disorders and the Eye (Oxford Press, 2005). He has worked as principal investigator on a number of studies focused on determination and description of the molecular genetics and clinical manifestations of ocular disorders.


Child and adolescent psychiatry

Child and adolescent psychiatry (or pediatric psychiatry) is a branch of psychiatry that focuses on the diagnosis, treatment, and prevention of mental disorders in children, adolescents, and their families. It investigates the biopsychosocial factors that influence the development and course of psychiatric disorders and treatment responses to various interventions. Child and adolescent psychiatrists primarily use psychotherapy and/or medication to treat mental disorders in the pediatric population.
History.
When psychiatrists and pediatricians first began to recognize and discuss childhood psychiatric disorders in the 19th century, they were largely influenced by literary works of the Victorian era. Authors like the Brontë sisters, George Eliot, and Charles Dickens, introduced new ways of thinking about the child mind and the potential influence early childhood experiences could have on child development and the subsequent adult mind. When the "Journal of Psychological Medicine and Mental Pathology", the first psychiatric journal in English, was published in 1848, child psychiatry didn't exist as its own field yet. However, some of the earliest works on the possibility of nervous disorders and "insanity" in children were published in the Journal and several medical writers directly referenced works such as "Jane Eyre" (1847), "Wuthering Heights" (1847), "Dombey and Son" (1848), and "David Copperfield" (1850), to illustrate this new conceptualization of the child mind. Until that time, it was generally accepted that children were free from nervous disorders and the "passions" that affected the adult mind.
As early as 1899, the term "child psychiatry" (in French) was used as a subtitle in Manheimer's monograph "Les Troubles Mentaux de l'Enfance". However, the Swiss psychiatrist Moritz Tramer (1882–1963) was probably the first to define the parameters of child psychiatry in terms of diagnosis, treatment, and prognosis within the discipline of medicine, in 1933. In 1934, Tramer founded the "Zeitschrift für Kinderpsychiatrie (Journal of Child Psychiatry)", which later became "Acta Paedopsychiatria". The first academic child psychiatry department in the world was founded in 1930 by Leo Kanner (1894–1981), an Austrian émigré and medical graduate of the University of Berlin, under the direction of Adolf Meyer at the Johns Hopkins Hospital in Baltimore. Kanner was the very "first" physician to be identified as a child psychiatrist in the US and his textbook, "Child Psychiatry" (1935), is credited with introducing both the specialty and the term to the anglophone academic community. In 1936, Kanner established the first formal elective course in child psychiatry at the Johns Hopkins Hospital. In 1944 he provided the first clinical description of early infantile autism, otherwise known as Kanner Syndrome.
Maria Montessori together with and Clodomiro Bonfigli, two distinguished child psychiatrists, created in 1901 in Italy the "Lega Nazionale per la Protezione del Fanciullo" (National League for the Protection of Children). She gradually developed her own pedagogic method, initially based on the "intuition that the question of the 'mentally deficient' was more pedagogic than medical". In 1909, Jane Addams and her female colleagues established the Juvenile Psychopathic Institute (JPI) in Chicago, later renamed as the Institute for Juvenile Research (IJR), the world's first child guidance clinic. Neurologist William Healy, M.D., its first director, was charged with not only studying the delinquent's biological aspects of brain functioning and IQ, but also the delinquent's social factors, attitudes, and motivations, thus it was the birthplace of American child psychiatry.
From its establishment in February 1923, the Maudsley Hospital, a South London-based postgraduate teaching and research psychiatric hospital, contained a small children's department. Similar overall early developments took place in many other countries during the late 1920s and 1930s. In the United States, child and adolescent psychiatry was established as a recognized medical speciality in 1953 with the founding of the American Academy of Child Psychiatry, but was not established as a legitimate, board-certifiable medical speciality until 1959.
The use of medication in the treatment of children also began in the 1930s, when Charles Bradley opened a neuropsychiatric unit and was the first to use amphetamine for brain-damaged and hyperactive children. But it was not until the 1960s that the first NIH grant to study paediatric psychopharmacology was awarded. It went to one of Kanner's students, Leon Eisenberg, the second director of the division.
The discipline has relatively flourished since the 1980s, in large part, because of contributions made in the 1970s, even if the outcomes for patients have been disappointing at times. It was a decade during which child psychiatry witnessed a major evolution as a result of the work carried out by, Eva Frommer, Douglas Haldane, Michael Rutter, Robin Skynner and Sula Wolff, among others. The first comprehensive population survey of 9- to 11-year-olds, carried out in London and the Isle of Wight, which appeared in 1970, addressed questions that have continued to be of importance for child psychiatry; for example, rates of psychiatric disorders, the role of intellectual development and physical impairment, and specific concern for potential social influences on children's adjustment. This work was influential, especially since the investigators demonstrated specific continuities of psychopathology over time, and the influence of social and contextual factors in children's mental health, in their subsequent re-evaluation of the original cohort of children. These studies described the prevalence of ADHD (relatively low as compared to the US), identified the onset and prevalence of depression in mid-adolescence and the frequent co-morbidity with conduct disorder, and explored the relationship between various mental disorders and scholastic achievement.
It was paralleled similarly by work on the epidemiology of autism that was to enormously increase the number of children diagnosed with autism in future years. Although attention had been given in the 1960s and '70s to the classification of childhood psychiatric disorders, and some issues had then been delineated, such as the distinction between neurotic and conduct disorders, the nomenclature did not parallel the growing clinical knowledge. It was claimed that this situation was altered in the late 1970s with the development of the DSM-III system of classification, although research has shown that this system of classification has problems of validity and reliability. Since then, the DSM-IV and DSM-IVR have altered some of the parsing of psychiatric disorders into "childhood" and "adult" disorders, on the basis that while many psychiatric disorders are not diagnosed until adulthood, they may present in childhood or adolescence (DSM-IV).. The American Psychiatric Association's DSM is now on its fifth edition (DSM-5).
People in the field are sometimes referred to as "neurodevelopmentalists". As of 2005 there was debate in the field as to whether "neurodevelopmentalist" should be made a new speciality.
In terms of patient outcomes, there is evidence that, in the United Kingdom at least on the 70th anniversary of the NHS, mental health remains a medical "Cinderella" (low priority) and the more so Child and Adolescent Health services which have been through repeated reorganisations and underinvestment all of which leads to disruption and loss of adequate provision.
"Modern neuroscience, genetics, epigenetics, and public health research has presented
the tantalizing possibility that it can now be said with relative certainty that
much (certainly not all) is understood about why some children struggle and others
soar. Although it is an oversimplification, it can now be suggested that it is possible
to understand how environmental factors, both negative and positive, influence the
genome or epigenome, which in turn influence the structure and function of the brain
and thus human thoughts, actions, and behaviors."
Classification of disorders.
"Not an exhaustive list"
Developmental disorders
Disorders of attention and behaviour
Psychotic disorders
Mood disorders
Anxiety disorders
Eating disorders
Gender identity disorder
Disorders are often "comorbid". For example, an adolescent can be diagnosed with both major depressive disorder and generalized anxiety disorder. The incidence of psychiatric comorbidities during adolescence may vary by race, ethnicity and socioeconomic status, among other variables.
Clinical practice.
Assessment.
The psychiatric assessment of a child or adolescent starts with obtaining a psychiatric history by interviewing the young person and his/her parents or caregivers. The assessment includes a detailed exploration of the current concerns about the child's emotional or behavioral problems, the child's physical health and development, history of parental care (including possible abuse and neglect), family relationships and history of parental mental illness. It is regarded as desirable to obtain information from multiple sources (for example both parents, or a parent and a grandparent) as informants may give widely differing accounts of the child's problems. Collateral information is usually obtained from the child's school with regards to academic performance, peer relationships, and behavior in the school environment.
Psychiatric assessment always includes a mental state examination of the child or adolescent which consists of a careful behavioral observation and a first-hand account of the young person's subjective experiences. The assessment also includes an observation of the interactions within the family, especially the interactions between the child and his/her parents.
The assessment may be supplemented by the use of behavior or symptom rating scales such as the Achenbach Child Behavior Checklist or CBCL, the Behavioral Assessment System for Children or BASC, Connors Rating Scales (used for diagnosis of ADHD), Millon Adolescent Clinical Inventory or MACI, and the Strengths and Difficulties Questionnaire or SDQ. These instruments bring a degree of objectivity and consistency to the clinical assessment. More specialized psychometric testing may be carried out by a psychologist, for example using the Wechsler Intelligence Scale for Children, to detect intellectual impairment or other cognitive problems which may be contributing to the child's difficulties.
Diagnosis and formulation.
The child and adolescent psychiatrist makes a diagnosis based on the pattern of behavior and emotional symptoms, using a standardized set of diagnostic criteria such as the Diagnostic and Statistical Manual (DSM-IV-TR) or the International Classification of Diseases (ICD-10). While the DSM system is widely used, it may not adequately take into account social, cultural and contextual factors and it has been suggested that an individualized clinical formulation may be more useful. A case formulation is standard practice for child and adolescent psychiatrists and can be defined as a process of integrating and summarizing all the relevant factors implicated in the development of the patient's problem, including biological, psychological, social and cultural perspectives (the "biopsychosocial model"). The applicability of DSM diagnoses have also been questioned with regard to the assessment of very young children: it is argued that very young children are developing too rapidly to be adequately described by a fixed diagnosis, and furthermore that a diagnosis unhelpfully locates the problem within the child when the parent-child relationship is a more appropriate focus of assessment.
The child and adolescent psychiatrist then designs a treatment plan which considers all the components and discusses these recommendations with the child or adolescent and family.
Treatment.
Treatment will usually involve one or more of the following elements: behavior therapy, cognitive-behavior therapy, problem-solving therapies, psychodynamic therapy, parent training programs, family therapy, and/or the use of medication. The intervention can also include consultation with pediatricians, primary care physicians or professionals from schools, juvenile courts, social agencies or other community organizations.
In a review of existing meta-analyses and disorders on the four most frequent childhood and adolescent psychiatric disorders (anxiety disorder, depression, ADHD, conduct disorder), only for ADHD was the use of medication (stimulants) considered to be the most efficacious treatment option available. For the remaining three disorders, psychotherapy is recommended as the most effective treatment of choice. A combination of psychological and pharmacological treatments is an important option in ADHD and depressive disorders. Treatments for ADHD and anxiety disorders produce higher effect-sizes than do interventions for depressive and conduct disorders.
Training.
In the United States, Child and adolescent psychiatric training requires 4 years of medical school, at least 4 years of approved residency training in medicine, neurology, and general psychiatry with adults, and 2 years of additional specialized training in psychiatric work with children, adolescents, and their families in an accredited residency in child and adolescent psychiatry. Child and adolescent sub-speciality training is similar in other Western countries (such as the UK, New Zealand, and Australia), in that trainees must generally demonstrate competency in general adult psychiatry prior to commencing sub-speciality training.
Certification and continuing education.
In the US, having completed the child and adolescent psychiatry residency, the child and adolescent psychiatrist is eligible to take the additional certification examination in the subspecialty of child and adolescent psychiatry from the American Board of Psychiatry and Neurology (ABPN) or the American Osteopathic Board of Neurology and Psychiatry (AOBNP). Although the ABPN and AOBNP examinations are not required for practice, they are a further assurance that the child and adolescent psychiatrist with these certifications can be expected to diagnose and treat all psychiatric conditions in patients of any age competently. Training requirements are listed on the web site of The American Academy of Child & Adolescent Psychiatry.
Shortage of child and adolescent psychiatrists in the United States.
The demand for child and adolescent psychiatrists continues to far outstrip the supply worldwide. There is also a severe maldistribution of child and adolescent psychiatrists, especially in rural and poor, urban areas where access is significantly reduced. As of 2016, there are 7991 child and adolescent psychiatrists in the United States. A report by the US Bureau of Health Professions (2000) projected a need by the year 2020 for 12,624 child and adolescent psychiatrists, but a supply of only 8,312. In its 1998 report, the Center for Mental Health Services estimated that 9-13% of 9- to 17-year-olds had serious emotional disturbances, and 5-9% had extreme functional impairments. In 1999, however, the Surgeon General reported that "there is a dearth of child psychiatrists." Only 20% of emotionally disturbed children and adolescents received "any" mental health treatment, a small percentage of which was performed by child and adolescent psychiatrists. Furthermore, the US Bureau of Health Professions projects that the demand for child and adolescent psychiatry services will increase by 100% between 1995 and 2020.
Cross-cultural considerations.
Steady growth in migration of immigrants to higher-income regions and countries has contributed to the growth and interest in cross-cultural psychiatry. Families of immigrants whose child has a psychiatric illness must come to understand the disorder while navigating an unfamiliar health care system.
Criticisms.
Subjective diagnoses.
One criticism against psychiatry is that psychiatric diagnoses lack "objectivity", particularly when compared with diagnosis in other medical specialties. However, for several major psychiatric disorders interrater reliability, which shows the degree to which psychiatrists agree on the diagnosis, is generally similar to those in other medical specialties. In 2013, Allen Frances said that "psychiatric diagnosis still relies exclusively on fallible subjective judgments rather than objective biological tests".
Traditional deficit and disease models of child psychiatry have been criticized as rooted in the medical model which conceptualizes adjustment problems in terms of disease states. It is said by these critics that these normative models explicitly characterize problematic behavior as representing a disorder within the child or young person and these commentators assert that the role of environmental influences on behavior has become increasingly neglected, leading to a decrease in the popularity of, for example, family therapy. There are criticisms of the medical model approach from within and without the psychiatric profession (see references): it is said to neglect the role of environmental, family, and cultural influences, to discount the psychological meaning of behavior and symptoms, to promote a view of the "patient" as dependent and needing to be cured or cared for and therefore undermines a sense of personal responsibility for conduct and behavior, to promote a normative conception based on adaptation to the norms of society (the ill person must adapt to society), and to be based on the shaky foundations of reliance on a classificatory system that has been shown to have problems of validity and reliability (Boorse, 1976; Jensen, 2003; Sadler et al. 1994; Timimi, 2006).
Prescription of psychotropic medications.
Since the late 1990s, use of psychiatric medication has become increasingly common for children and adolescents. In 2004 the U.S. Food and Drug Administration (FDA) issued the Black Box Warning on antidepressant prescriptions to alert patients of a research link between use of medication and apparent increased risk of suicidal thoughts, hostility, and agitation in pediatric patients. The most common diagnoses for which children receive psychiatric medication are ADHD, ODD, and conduct disorder.
Some research suggests that children and adolescents are sometimes given antipsychotic drugs as a first-line treatment for mental health problems or behavioral issues other than a psychotic disorder, which is not the ideal treatment approach for these drugs. In the United States, the usage of these drugs in young people has greatly increased since 2000, especially among children from low-income families. More research is needed to specifically assess the efficacy and tolerability of antipsychotic medications in pediatric populations. Because of the risk of weight gain, metabolic syndrome, and cardiovascular changes with antipsychotic use, the use of the drugs in pediatric populations is highly scrutinized and their use recommended only in combination with effective parent-training interventions.
Electroconvulsive therapy.
In 1947, child neuropsychiatrist Lauretta Bender published a study on 98 children aged between four and eleven years old who had been treated in the previous five years with intensive courses of electroconvulsive therapy (ECT). These children received ECT daily for a typical course of approximately twenty treatments. This formed part of an experimental trend amongst a cadre of psychiatrists to explore the therapeutic impact of intensive regimes of ECT, which is also known as either regressive ECT or annihilation therapy. In the 1950s Bender abandoned ECT as a therapeutic practice for the treatment of children. In the same decade the results of her published work on the use of ECT in children was discredited after a study showing that the condition of the children so treated had either not improved or deteriorated. Commenting on his experience as part of Bender's therapeutic program, Ted Chabasinski said that, "It really made a mess of me ... I went from being a shy kid who read a lot to a terrified kid who cried all the time." Following his treatment, he spent ten years as an inmate of Rockland State Hospital, a psychiatric facility now known as the Rockland Psychiatric Center.


Roger L. Greene

Roger L. Greene is a professor at Palo Alto University. He received the Bruno Klopfer Award in 2010.
He worked on self-report measures of personality, particularly the Minnesota Multiphasic Personality Inventory.


Constanza (physician)


Sarah Potts (Shortland Street)

Dr. Sarah Marjorie Potts is a fictional character on the New Zealand soap opera "Shortland Street", who was portrayed by Amanda Billing from her first appearance in September 2004 until the character's on-screen death in August 2014.
Arriving as a love interest for established character, Craig (Renato Bartolomei), Sarah became the centre of a high-profile storyline when it was revealed her young brother Daniel (Jarred Blakiston) was in fact her illegitimate son. Sarah and Craig's romance carried on for four years and climaxed in what has been described as ""Shortland Street's" steamiest ever scene." Sarah's romance storyline's again took a high-profile role with her pairing to TK Samuels (Benjamin Mitchell) in 2006. Over the next 8 years the two were involved in a "will they-won't they" situation that involved the two getting married, divorced, having a child, and engaged for a second time. Public interest was high for the romance and boosted the show some of its highest ever ratings; the Prime Minister Helen Clark also expressed her interest in whether the two would end up together. In 2008 the character was diagnosed with multiple sclerosis in a storyline producers intended to use to explore the long-term effects of the illness and help educate New Zealanders.
The character of Sarah has seen high acclaim for the show and Billing's acting. She has been nominated and won multiple awards including a nomination in the "New Zealand Television Awards" for "Best Actress". The characters diagnosis with multiple sclerosis has seen huge acclaim, with sufferers and health advocates praising the show for bringing the illness to such a high-profile programme.
Creation and casting.
Amanda Billing previously auditioned for the roles of lesbian nurse Maia Jeffries and the ill fated Avril Luchich before she was offered the role of Sarah in early 2004. Sarah made her debut on 14 September 2004. The character was described as "a good looking, vivacious and driven woman in her early 30s" and was "liked, easy-going and good-humoured". In the casting of Sarah, it was suggested that producers were carrying on the tradition of placing talented unknowns in starring roles. Sarah was written off the show in late 2010 when Billing took a four-month break to star in a play. Her exit storyline was purposefully ambiguous so that the audience was not aware Sarah would return. Billing struggled to keep the secret from the public and was hugely relieved when Sarah returned onscreen in March 2011.
In late 2013 producers decided to retire the character of Sarah. They decided it was best to kill her off as then the character of TK Samuels could develop further romantic connections without fans opposing to it due to Sarah still being alive. Billing was informed in March 2014. She described the writing off process as one that had a lot of "stuff that plays into it" and noted some of it she understood, whilst a lot of it she did not. She hoped that Sarah would get a "dramatic" write-off that would involve a lot of location shooting. One of Sarah's final scenes that saw her say goodbye to her toddler daughter Tillie (Leila Eketone) proved difficult to film due to the cast and crew crying; a scene Billing described filming as "deliciously painful". Billing finished filming in July and was celebrated with a large cast party. The publicity department worked hard to ensure the departure would not be leaked to the press following previous leaks on the departures of Teuila Blakely (Vasa Levi) and Beth Allen (Brooke Freeman), something Billing found hard to keep a secret. The character was killed off during scenes airing on 18 August 2014.
Storylines.
Sarah arrived to Shortland Street and won a job working in ED under Craig Valentine (Renato Bartolomei). They dated but broke up when it was scandalously revealed that Sarah's brother Daniel (Jarred Blakiston), was in fact her son. Despite being attracted to Craig, she married Andrew Solomon (Paolo Rotondo) but their marriage was annulled after Andrew left Sarah to be with his ex-girlfriend and children. Sarah briefly dated a schoolboy and later conman Hamish (Phil Brown). She continually found herself attracted to Craig and started to date him before the two broke up due to his anger problems. They made up and dated again but broke up when Craig cheated on Sarah with Huia (Nicola Kawana), impregnating her. Huia's cousin TK Samuels (Benjamin Mitchell) comforted her through the ordeal and when Craig readmitted his love, Sarah was faced with a tough decision between Craig and TK. Sarah finally made a decision and in December 2006 asked TK to marry her. The couple married in mid-2007 and later decided to have kids. However, in 2008 after being diagnosed with Multiple sclerosis the couple suffered a shock when they learnt Sarah's baby would be born with a deathly illness and it was terminated. In 2009 Brooke Freeman (Beth Allen) manipulated Sarah into thinking TK was unhappy and the two separated. She rebounded to Maxwell Avia (Robbie Magasiva) but the two broke up in 2010 and Sarah had a one-night stand with TK shortly before leaving to work in America.
Sarah made a surprise return to Shortland Street in March 2011 and announced she was pregnant with TK's child, a girl. Sarah planned to get back with TK and clashed with his new fiance Roimata Ngatai (Shavaughn Ruarkere). In July 2011 Sarah gave birth to daughter, Matilda Mareikura "Tillie" Potts (Nathan Anderson) after leaving TK's wedding. Sarah began to date Daniel's (Ido Drent) carer Zac Smith (Mike Edward) and accepted more administrative positions at the hospital. However, after 8 months of dating, Sarah discovered Zac had been having a long-term affair behind her back with her friend Vasa Levi and they broke up. In 2013 Sarah lost her job to her friend Harper Whitley (Ria Vandervis) and ended up reconciling with TK after nearly 4 years apart. Their relationship was put to the test when Sarah accidentally reversed over Tillie in her truck, but the two remained together. In mid 2014 Sarah began researching a killer virus and ultimately ended up getting engaged to TK once again. However, in August, upon finally discovering the illness' cure, Sarah's MS relapsed and she contracted it herself and died after a tearful farewell to TK and Tillie.
Character development.
Relationships.
Craig Valentine.
The character of Sarah was originally written into the show as a potential love interest for established character, Craig Valentine (Renato Bartolomei). Sarah's first scene involved her crashing into Craig's car, driven by his son Jake Valentine (Calum Gittins). Upon learning Sarah was trying for a job in his department, Craig opposed to her job application, nonetheless, CEO Andrew Solomon (Paolo Rotondo) hired her. Throughout Sarah's early scenes, she often interacted with Craig and a sense of chemistry and potential romance was established between them. Billing offered an opinion as to why the two had such good chemistry saying; "I think you can find someone physically attractive but hate their guts, someone can irritate you heaps but you still find them a lovable rogue. The two characters are a lot alike, and that's why they spar. They're both headstrong and think that they're right more often than not." Following the two characters first kiss, the cast and crew reportedly fell quiet in awe. Billing agreed saying: "We have monitors through the whole building and everyone was going, 'Bloody hell!' Their chemistry is quite extraordinary," The two broke up due to Sarah's son Daniel (Jarred Blakiston) and Sarah became engaged to Andrew but after believing he had died in a plane crash, Sarah realized she was in love with Craig. Nonetheless when she found out Andrew had survived, she committed to marry him. Billing believed Sarah was: "being a chicken ... She does love Andrew and she does have feelings for him but it's not really what she wants in her heart of hearts. There's a real risk that she is making a mistake, she will regret it and they will break up." Bartolomei believed Craig would still love Sarah even if she were married, "from Craig's point of view, he really loves (Sarah), whether he can have her or not. I think his love for her is so great that he would love her even if she married Andrew and lives happily ever after." Even Rotondo believed Craig was a better suit, "Andrew hasn't been set up as the ideal guy for her so definitely I think she should be with Craig." Despite this, Sarah and Andrew married.
In 2006 Sarah and Craig finally got together in what has been described as "Shortland Street's Steamiest ever scene." However, the two constantly argued and Craig cheated on Sarah with Huia Samuels (Nicola Kawana), impregnating her. Bartolomei believed Sarah would be devastated when she found out about the child and stated: "He would be aware that it was going to be very difficult for Sarah but he would tell her what he was going to do and hope that it was going to work out. I think he will stand back and let things play their natural course, if that meant Sarah was no longer in his world... then so be it. I think he will stand back and say, 'well Sarah, how are you going to behave in this situation? If you are going to behave stupidly then let's call it quits'." The two stayed together following the revelation of the baby but Huia ended up dying in an explosion whilst pregnant and Sarah broke it off once again. At the end of the year, Craig admitted his love before a short holiday but Sarah had a difficult time deciding between him and TK Samuels (Benjamin Mitchell). Billing described the conundrum, saying: "Sarah is nervous about Craig’s return because she knows that he will be coming back to a situation that will be very different from the one that he left. In a lot of ways Sarah and Craig are still the hero couple but she is scared of him being angry and is worried that she is going to lose him."< Despite Billing labelling the couple as having; "dynamic that is high voltage", she also believed; "They’re not very good at being a couple together because they haven’t figured out how to work as a team." Sarah ended up choosing TK over him. On her wedding day to TK in 2007, Sarah decided to call off the marriage, fearing she still loved Craig. She visited Craig but he insisted on driving her to the wedding himself. Sarah came back from her honeymoon early to help Craig, causing a feud with Craig's girlfriend Alice Piper (Toni Potter). In 2008 Craig diagnosed Sarah with multiple sclerosis. Upon resigning, Bartolomei commented on Craig's relationship with Sarah, stating: "Craig and Sarah are your classic unrequited love story. That does get revisited but not in a stereotypical way. There is a great deal of resolution at the end for everyone concerned." On screen Craig resigned from Shortland Street and admitted he would always love Sarah before the two shared a moment. He was murdered later that evening. Sarah sung an emotional song at his service, highlighting his personality and kindness. Billing believed that for several years, Craig was Sarah's one true love and was touched when she saw a hashtag '#ReunitedwithCraig' on Twitter concerning Sarah's death in 2014.
TK Samuels.
With TK Samuels (Benjamin Mitchell) arriving in early 2006, Sarah found herself annoyed and conflicted with the newby immature doctor. However, TK took a shine to Sarah and did all he could to impress her. Having found boyfriend, Craig (Renato Bartolomei) cheating on her with TK's cousin Huia (Nicola Kawana), Sarah used TK as a shoulder to cry on and the two soon got together. Billing explained Sarah's conflict between Craig and TK, stating: "TK really loves Sarah and he is very patient and understanding with her where Craig isn’t. He accepts that she is difficult whereas Craig isn’t very patient with her and doesn’t understand her well at all." As 2006 ended, Sarah found herself torn between Craig and TK, eventually choosing and proposing to TK. Mitchell believed that TK was the love of Sarah's life, and stating that neither Andrew Solomon (Paolo Rotondo) or Craig; "Were the right one for Sarah; TK is the one." Mitchell also believed that TK was alright with Craig's attendance at the wedding, stating: "He was invited by Sarah, and he thinks it’s fair for Craig to attend the wedding. TK still has respect for Craig." Shortly into the relationship, Sarah began to lose trust in TK when she saw him sharing a drink with his ex lover Holly Makatea, Billing explained: "Sarah doesn’t know anything about their relationship. She has heard the name Holly mentioned before but she only knows her in passing as a social worker up on Q Road. TK has never told her about any previous relationship." Billing also stated: "The last thing Sarah expects to see is her boyfriend with a young gorgeous Maori Woman like Holly. She can tell they have a close connection and that makes her feel immediately uncomfortable and a little bit insecure." Sarah proposed to TK, feeling bad about her judgmental nature towards Holly but he declined as he feared Holly had given him HIV, Sarah promised to love him nonetheless and they got engaged. Tests later declared TK free of HIV. TK and Sarah wed in mid-2007, with Sarah initially cautious as she believed she may still love Craig. Sarah clashed with TK's family and Billing believed the arrival of TK's nephews to the house only further drove a wedge between her and the Samuels, stating: "Sarah is aware that when she went to the tangi she made some enemies, even though she was just trying to be straight up. She has been on the marae before, but she found that quite an alienating experience and she is prepared to feel that way again. She is definitely feeling apprehensive because they decided not to invite a lot of the whanau to the wedding and she realises she might get some flack for that. But she realises going to the Marae is important for TK’s sake and her relationship’s sake, and it is important she doesn’t make any more enemies. She is determined to put on a brave face and be nice and show she is capable of integrating into the family."
The two decided to start a family in late 2007; however, TK soon voted against it and Sarah feared she had made a mistake marrying TK. However, the two soon made up and decided to try for a family again. The couple found themselves pregnant, but the baby would have been born ill, so the pregnancy was terminated. Sarah broke up with TK when Brooke Freeman (Beth Allen) purposely drove a wedge between the couple after falling madly in love with TK. Billing found the breakup uncomfortable to film, stating: "It has been very difficult to play, there are some days when I've thought she's just being a complete twit." She believed that Sarah found herself to be a "burden" to TK with her illness and it affected her "confidence and belief in herself". TK and Sarah set up a clinic in 2010 and Sarah later readmitted her love, causing a one-night stand before she left the country. Upon her unexpected arrival, Sarah announced she was pregnant with TK's child and she loved him. However, TK had moved on with Roimata (Shavaughn Ruakere) and despite feelings for Sarah, announced it was over forever. Billing sympathised with Sarah during the ordeal, "My heart breaks for Sarah Potts because her bubble is well and truly burst. She has a fantasy in her head and when she comes home it's not what she expects." Billing acknowledged that TK and Roimata have good chemistry but praised TK and Sarah's possible rekindling saying; "Roimata and TK make a really good couple but Sarah and TK were really good too and wouldn't it be great for them to be a family?" In October 2012, following the revelation that her boyfriend of 8 months, Zac Smith (Mike Edward) had been cheating on her, Sarah found herself attracted once again to TK, who offered her support.
In August 2013, Sarah moved in with TK so that they could look after Tillie together following his separation from Roimata. Sarah's hopes for romance reignited but Billing hoped that it was mutual. Mitchell was "shocked" when he read the storyline and hoped that their relationship "would be different" than before. Sarah struggled to tell TK her true feelings as Billing believed "it'll ruin the friendship that they have ... Sarah doesn't imagine he has romantic feelings for her." In September 2013, Sarah and TK finally reconciled. Sarah travelled to America for several months on a MS trial and in the interim, TK developed feelings for her friend Harper Whitley (Ria Vandervis) but stayed committed. However, Sarah's trial turned out not to have worked and TK ended up turning to violence, Mitchell believed that, "His violent reaction definitely doesn’t go unnoticed and it’s going to cause problems for him and his family." In early 2014 producers decided to kill off the character of Sarah as they didn't think fans would believe TK dating any other character with the possibility of Sarah returning. Billing believed the way the relationship was written in her final storyline was "sweet" and well "crafted", as she believed he was her true soul mate. The storyline saw Sarah fight to discover the cure of a killer illness much to the annoyance of TK, whom disagreed with her ambition. Mitchell believed that this, "pisses him off to tell the truth. She's a mother; she should be there spending time with her family. She's got MS herself and she's not really taking care of herself." Billing believed the storyline saw a development in the relationship, "Their relationship changes because of their involvement in this situation. That tenacity can be really annoying for (TK) but he knows that it results in good things for other people." The storyline saw the two become engaged once again. Sarah ended up finding a cure, only to succumb to the illness herself.
Multiple Sclerosis.
After suggesting her character have a sickness storyline, Billing was notified Sarah was to undergo a storyline where she is diagnosed with multiple sclerosis. Billing originally thought Sarah was to be killed off but realised it was to be a larger story arc, saying; "I thought they were trying to kill her off, but the idea is to show Sarah living with it". Producer Jason Daniel explained the situation; "As a continuing serial Shortland Street has the ability to explore situations and issues in considerable depth over long periods – and this is what we intend to do with Sarah's multiple sclerosis." In mid-2008, Sarah started to realise she was suffering from an illness which began to gradually affect her work. Ex-boyfriend Craig Valentine diagnosed Sarah with multiple sclerosis, a fact Sarah kept kidden from husband, TK. The illness starts to seriously affect Sarah's fast paced job as a consultant in the Emergency Department. Sarah later reveals to TK the truth about her illness and TK goes into overdrive, changing her meal plans and exercise routines. To accurately portray the symptoms of MS, Billing researched heavily, including using the internet, medical advisers and the advice of a friend with the illness. Sarah begun to attend MS support groups but struggled to come to terms with how sick she may become. Billing herself attended MS groups to research the role but found attendance a strange experience: "It was quite a bit different to be pretending to have MS in the midst of people who do have MS. I was intimidated by that, it was quite strange, really humbling." Despite finally being awarded head of ED, Sarah realised she had to resign as a result of her eventual inability to perform such a fast paced job. Billing commented on Sarah resigning, "Sarah has a hard time letting go. Emergency medicine is her number one love - it's her identity and the thought of not having that in her life is terrifying. But she knows her MS is getting worse and deep down she knows leaving ED is her only choice."
In late 2009 Sarah has a relapse in her MS symptoms, confirming her suspicion she will never heal and it will affect her chance of having children, causing her to leave TK. She has another relapse in mid-2010, cementing her relationship with Maxwell. Billing hoped the relapse was realistic saying; "Initially, I did a lot of reading, as well as speaking to a couple of people directly affected by MS. I also spoke to a psychologist about how the condition affects people's mental health and wellbeing. It's important to me that Sarah's experience looks real, so I always ask the medical advisor at Shortland Street for information about her symptoms." She also thoroughly enjoyed playing them, being quoted as saying; "Sarah's Multiple Sclerosis diagnosis has meant when she has a relapse, I'm telling the story of people living with the condition. It makes work less 'soapy' and more realistic, more meaningful." However, Billing found the remissions relaxing, stating; "When Sarah's in remission it's a relief, but I sometimes catch myself waiting for things to get hard again when she has a relapse. I always find her recurrences a bit stressful and not just form a technical view (i.e. wanting to make her condition looks authentic). I know it's acting, and it's not real, but when Sarah's having a recurrence I do feel a bit of what it must be like when something like MS changes you – and changes the way people relate to you." In November 2010 Sarah leaves Ferndale, having won a position in a MS research team in the United States. However, upon her return, she is finally pregnant. Once having given birth to daughter, Tillie in July 2011, Sarah has another relapse in her symptoms and begins to fear for her ability to mother Tillie. In September, Sarah's condition appears to be in remission but she suddenly has a severe attack, losing control of her speech, legs and arms, with Tillie unsupervised.
Reception.
Accolades.
Billing received a nomination in the New Zealand TV Guide "Best on the Box" awards 2011 for "Best Actress", losing out to Robyn Malcolm for her role in Outrageous Fortune. She received the same nomination the following year for her acting throughout 2011, for which she won. Billing was pleased with the win saying; "I was up against some amazingly talented ladies so I am incredibly surprised that I won! But it's lovely to know that people have been watching and that the character resonates with them." In 2012, the character was named as one of the standout characters of the show's first 20 years. Billing also received a nomination for "Best Actress" in the 2012 "New Zealand Television Awards". In 2013 Billing was again nominated for the "TV Guide Best on the Box Award" for "Best Actress", for which she won again. She stated, "I was very flattered and pleased to be considered'" and voiced her disbelief at beating co-star Shavaughn Ruakere (Roimata Samuels) following her sexual assault storyline. Billing also landed a nomination for "Sexiest Female". In the "Ferndale Talk Best of 2013 awards", Sarah was runner up for "Favourite Character" whilst Billing was also runner up for "Favourite Actress". Sarah and TK won "Favourite Couple" and Sarah also won the character whom fans most want to return due to her temporary absence. In 2014 Billing was nominated for the fourth time in the "TV Guide Best on the Box Award" for "Best Actress".
Impact.
The character has also received a lot of dislike with Billing stating the role takes a toll and; "one doesn’t like to play a character that people don’t have a lot of sympathy for. Shes a good doctor but she's a but useless in her private life." In November 2006, Fiona Rae of The Listener magazine, criticised the storyliners of the show, suggesting they had turned Sarah: "into a self-absorbed witch with a “b”. Fortunately for us, she does a mean drunk and gets to embarrass herself heaps." She was called "popular" by producer Jason Daniel in 2008. Billing herself reflected on the strong nature of her character, referring to her as "stroppy". One fan enjoyed the character to such an extent they made a false profile on social networking site, Myspace. They chose to create the page about Sarah as they liked the character and; "It's easy to create a page about a character with so many issues." During a speech at the show's 15th anniversary, the Prime Minister Helen Clark satirically suggested that the question of whether Sarah would marry TK was a major issue. The departure of Sarah alongside several other characters, saw what journalist Duncan Grieve described as a "disappointing" era of the show, where it entered a style of "regularity" and lacked "long-running and well-acted" characters and became a "blur". The "New Zealand Woman's Day" magazine listed Sarah as the best character of the soap's first 25 years.
The character's diagnosis with multiple sclerosis has also helped educate New Zealanders about the illness. Sufferers of multiple sclerosis praised the show, pleasing producer Jason Daniel who said; "The story has already examined the impact her diagnosis has on her personally and professionally. And in the future it will explore how she learns to live with her MS. I’m very pleased that the MS Society approves of our efforts so far, and I hope that audiences will continue to find Sarah's story inspiring and uplifting." Billing was pleased that fans of the show were so supportive of Sarah and TK and believed they saw their own families in the coupling, "I'm stoked that the audience is so supportive of them getting back together. Maybe it's because we all want Mum, Dad and the kids to be together." Billing believed that the love triangle between Sarah, TK and Roimata was relatable, "Everyone's had the experience of feeling that something's getting in the way."
Sarah and Andrew's (Paolo Rotondo) wedding was viewed by 676,400 people, landing more viewers than ratings juggernaut – "Desperate Housewives". In 2006 an episode focused solely on the character of Sarah and was told through flashback. Daniel ensured viewers that fans of the TK/Sarah/Craig love triangle would thoroughly enjoy the episode.The July 2011 90-minute episode which concluded with Sarah giving birth, received incredibly high ratings with an audience of 834,200. Billing offered an opinion on the reason as to why Sarah's storyline concerning her daughter was so well received, saying; "When theres children involved, and love and illness, it gets really hard and I think the audience loves that." Producer, Steven Zanoski suggested part of the reason for the episodes success was the song Billing released as part of the marketing towards the Winter Season. The song, a cover of Ever Fallen in Love (With Someone You Shouldn't've) by Pete Shelley, peaked at number 24 in the New Zealand chart. The birth scene was also named by Television New Zealand as one of the top moments of 2011, and was voted by fans as one of the show's most iconic moments. The episode was the second most watched episode in the shows first 25 years on screen.
The episode airing Sarah's death drew 564,210 viewers, making it the second most watched television show in New Zealand that night. The week following the episode saw an average of 614,000 viewers and became the most watched week of the year. Following the episodes airing, 1.2 million Facebook comments were posted mourning the character. This reached 1.6 million by the end of the week. "Television New Zealand" set up a "Sarah Potts Tribute" website that some commentators saw as a blur between fiction and reality. The hashtag '#RIPSarahPotts' became the number one topic trending in New Zealand on Twitter following the episode. The episode featuring Sarah's funeral was the 10th most watched episode of the show in its first 25 years.


Hussein al Abri

Hussein al-Abri (Arabic:), an Omani writer of short stories and novels, born in 1972. He is a psychiatrist and works at the General psychiatric Hospital in Muscat. Abri has published 5 novels, short stories and numerous articles. He won the "Beirut 39" festival of Hay Festival Foundation in cooperation with the Lebanese Ministry of Culture 2009.
Education and career.
Hussein al-Abri was born in the state of Hamra in Oman. He began writing stories while he was at the university and publishing some articles and short stories in local and daily newspapers. In 2000, he published his first novel "Diazepam".
In his writings, Abri discusses social and political issues. In 2005, his second novel "Tingling" was banned for a while since he touched upon the Omani security services. Whereas, his third novel "Ship of Fools" which was published in 2015, tells about mentally ill patients and the obstacles the doctor faces in a hospital that does not care about public health.
Al Abri also translated into Arabic a philosophy book entitled "What Does It All Mean?" by Thomas Nigel. Later, he translated another book, with the contribution of Hamad Sinan Al-Ghaithi, entitled "Neanderthal Man: In Search of Lost Genomes" by Svante Paabo. In 2009, al Abri won the Hay Festival Beirut 39.


Eduardo Blanco Acevedo

Eduardo Blanco Acevedo (1884–1971) was a Uruguayan political figure and physician.
Background.
Son of Juan Carlos Blanco Fernández and Luisa Acevedo, his family was full of prominent personalities in the academic and political fields.
He was a distinguished Uruguayan political figure. He was long associated with the Colorado Party (Uruguay) party. He was father-in-law to President of Uruguay Gabriel Terra.
Political roles.
He served in the 1930s as President Gabriel Terra's public health minister.
He served as a Senator in the 1930s and 1940s. He served as the President of the Senate of Uruguay in 1950.
In the 1950s he served as minister for public instruction. From 1952 till 1955 he served at the Consejo Nacional de Gobierno.
Death.
He died in 1971.


Joseph Collins (neurologist)

Joseph Collins (1866–1950) was an American neurologist, born in Brookfield, Conn. He received the degree of M.D. from New York University in 1888, and after some years of private practice took up the specialty of neurology; in 1907, he was made a professor of that subject in the New York Post-Graduate Medical School. He was later a co-founder and visiting physician to the New York Neurological Institute.
Bibliography.
In addition to his attainment as a practitioner of medicine, Dr. Collins wrote books and other literature. He is notable as the man who first reviewed James Joyce's novel Ulysses for the New York Times. His major writings, medical and secular, are:


Samuel Bayard Woodward

Samuel Bayard Woodward (1787–1850) was an American psychiatrist who was the first superintendent of the Worcester Lunatic Asylum, and a co-founder and first president of the Association of Medical Superintendents of American Institutions for the Insane (later known as the American Psychiatric Association).


American Samoa Field Hockey Association

The American Samoa Field Hockey Association is the governing body of field hockey in American Samoa, Oceania. Its headquarters are in Pago Pago, American Samoa. It is affiliated to IHF International Hockey Federation and OCF Oceania Hockey Federation.
See also.
Oceania Hockey Federation


Scott Clinic

Scott Clinic is a medium secure psychiatric unit located on the outskirts of Rainhill, Merseyside, England. It originates from and lies on the site of the former Rainhill Hospital. The unit was named after the late Dr. Peter Scott and provides facilities for up to 50 patients on 5 wards. Ivy and Hawthorn are male admission ward. Myrtle is a male assertive rehabilitation/neurocognitive ward. Olive ward is pre-discharge and Poplar ward is the female ward.


Institut Pasteur de Dalat

The Institut Pasteur de Dalat (English Dalat Pasteur Institute, Vietnamese "Công ty Vắc xin Pasteur Đà Lạt" ) is a vaccine research and production complex in Da Lat, Vietnam.
The institute in Dalat was one of the many Pasteur Institutes established outside France.
History.
French period.
The buildings were designed by the French architect and a Vietnamese colleague.
The Institute was established and first headed by Alexandre Yersin in 1936. At that time, the Institute manufactured vaccines against different strains of smallpox and rinderpest. The Institute in Dalat was one of four established by Yersin in Vietnam; the others being in Hanoi, Saigon and Nha Trang. In a report to the Grand Council of Economic and Financial Interests and to the Governing Council in 1937, the Institute reported producing over 3 000 000 vaccines, the majority of which were anti-cholera. Also produced were anti-plague, anti-typhoid, anti-staphylococcal, anti-gonococcal, anti-colibacillairy, anti-streptococcal and anti-meningococcal vaccines, along with tetra-vaccines and various Besredka filtrates. The Institute also kept a reserve of 1 000 000 cc of anti-cholera vaccine to be used in the event of a cholera epidemic. The Institute offered medical laboratory services, including microbiological examinations, pathological examinations and biological chemistry for the local populations of Dalat and the Upper Donnai regions. Their laboratories performed 1838 medical exams that year, helping to identify cases of dysentery, diphtheria, leprosy, malaria, typhoid fever and typhus. The Institute studied endemic diphtheria among the Europeans and Annamites of the Dalat region. It was also responsible for monitoring water purification for the city of Dalat.
A report published in a French magazine in September 1952 showed the Institute was still producing vaccines against contagious human diseases, such as cholera, typhoid fever, gonorrhea, cerebrospinal meningitis, colibacillosis and pneumonia. They studied human epidemiology and microbiology, biological chemistry and the monitoring of drinking water.
A new strain of "Penicillium" was isolated from hepatic lesions on a bamboo rat used for experimental infections at the Institute in 1956. "Penicillium marneffei" was named for Hubert Marneffei, Director of the Pasteur Institute of Vietnam.
The institute was still publishing articles in French as late as 1959.
French doctors ran the Institute until the 1960s. One of the last before the Communist victory, Jean Louis Colbert, worked at the Institute in Dalat from 1962 to 1968. He was responsible for the large scale production of vaccines for human use.
Vietnamese period.
The Dalat facility was taken over by the Vietnamese government in 1975. Even before the take-over, the Institute had one of the largest vaccine production facilities in Southeast Asia, shipping vaccines all over in Indochina. The institute was then run by the Ministry of Health until the south of Vietnam was fully integrated into the country in 1978, using the Institute for public health and disease prevention. In 2010, the Dalat Pasteur facility was incorporated as the Dalat Pasteur Vaccines Company Limited (DAVAC). "The company's primary mission is the production and sales of vaccines and biological products, relations with international organizations, institutes, companies at home and abroad in the fields of business, technology transfer and support, scientific research and staff training".
While now run by the Vietnamese government, the institute (along with the other Pasteur Institutes in Vietnam), seeks to establish a cooperation with the Institut Pasteur in France. One such declaration was issued in November 2010 at a conference in Haiphong, mentioning a cooperation that dates back 20 years.
Discoveries and production.
Working with scientists at the Pasteur Institute in Paris, scientists in Dalat discovered a new type of salmonella in 1956. The strain was called "S. dalat" (also and more commonly known as "Salmonella ball") and was isolated from fecal matter from a gecko captured in Phanrong.
The Dalat facility has experience in producing typhoid vaccines.
The facility was capable of producing 10 000 doses annually for this purpose, but production was discontinued due a lack of funding, an unsatisfactory vaccine production process and a lack of qualified staff. Since the start of production on the typhoid vaccine in 2008, the facility was not under full operation; producing only 0.3 million doses as of 2010.


Arturo Lussich

Arturo Lussich (Montevideo, 6 July 1872 - 22 May 1966) was a Uruguayan physician and politician.
He belonged to the National Party, for which he candidated several times. In 1916-1917 he was a member of the first National Council of Administration. In 1926 he presided over the Chamber of Deputies.


List of medical schools in Asia

The following is a list of medical schools (or universities with a medical school), in Asia.


Brian Jarman

Sir Brian Jarman (born 9 July 1933) is a retired English physician and academic. He was Professor of Primary Health Care from 1983−98 at Imperial College School of Medicine and President of the British Medical Association from 2003−4.
The Hospital Standardised Mortality Ratio (HSMR) methodology was developed by Jarman, director of the Dr Foster Unit at Imperial College, London. This method was applied by Dr Foster Intelligence.
Education.
Jarman was educated at Barking Abbey School.
Jarman originally trained in the natural sciences, graduating from St Catharine's College, Cambridge in 1954, and completing a PhD in Geophysics at Imperial College in 1960. After working for Shell for three years, Jarman switched to medicine, completing a medical degree at Imperial College in 1969. He was a Clinical Fellow at Harvard in 1970 and later occasional lecturer.


Coconut cadang-cadang viroid


Drona Prakash Rasali

Drona Prakash Rasali (, born in Humin, Palpa) was a Nepalese student who stood Board First position topping School Leaving Certificate (Nepal) i.e. national board examinations of Nepal, commonly abbreviated as SLC, held in 1972. He is the only one person so far from Dalit communities of Nepal, to obtain the most coveted rank in the history of SLC Board Examinations.
Community leadership.
Drona Prakash Rasali is featured in the list of prominent South Asian immigrants in Canada in Abdur Rahim's book, "Canadian Immigration and South Asian Immigrants"(page 437-438). He is an active member of Nepali Diaspora, who was elected as the Deputy Regional Coordinator for Americas (DRC) in the International Coordinating Council (ICC) of the global organization Non Resident Nepali Association (NRNA) for the period, 2009–2011. He ran and lost the election for the position of Regional Coordinator (RC) for Americas in the NRNA International Coordinating Council (ICC), 2011–2013. He has served as the Advisor to NRN-Canada National Coordinating Council since 2008 as well as the Advisor to the NRNA International Coordinating Council (ICC) for 2011–2013. He contributed significantly to the establishment of the Nepal Open University as one of the four leading task group members through the Open University of Nepal Initiative, a flagship project of Non-Resident Nepali Association.
He is the founding vice-president of Canada-Nepal Friendship and Cultural Society in Canada.
Professional background.
Drona Rasali carries a diverse professional background and is currently a Canadian public health professional who served as Provincial Chronic Disease Epidemiologist at the Saskatchewan Ministry of Health from 2005 to 2012, and is the Director, Population Health Surveillance & Epidemiology at the British Columbia Centre for Disease Control (BCCDC), Provincial Health Services Authority (PHSA) of British Columbia in Canada since 2012. He is veterinarian, with specializations received in health-related sciences including pathology, endocrinology, quantitative genetics, epidemiology and public health. He is a lifetime member of Nepal Veterinary Association and a registered veterinarian of Nepal Veterinary Council in Nepal, and was awarded the distinguished professional designation of a Fellow of American College of Epidemiology (FACE) in 2014, and currently holds the position Adjunct Professor at the School of Population and Public Health, University of British Columbia. He held the position of Adjunct Professor of Health Studies at the University of Regina in Canada (2009-2019). . His professional contributions span a wide range of scientific disciplines, including two notable international publications of scientific research to his credits:
1) World review of composite sheep breeds,
2) Establishing link between decreasing children's asthma disease incidence and declining antibiotic use in infants. Nepal Magazine featured him as a policy making personality, who played an important role in establishing Nepal Open University.
Drona Rasali served as the chair of Organizing Committee of Canadian Alliance for Regional Risk Factor Surveillance (CARRFS), a national network of public health professionals in Canada.


Meriandra dianthera

Meriandra dianthera, commonly known as Bengal sage and Bengal salvia (hi:कफ़ूर का पात), is a plant with a mint flavor that is cultivated for medical purposes.


Gamat

The word Gamat, the Malay word for sea cucumber, refers to medicinal remedies derived from several species of the Holothuroidea family.
Uses.
The golden sea cucumber ("Stichopus horrens") is commonly used. Tripang Emas is usually the dried, powdered bodies of sea cucumbers made into a lotion or other topical salve.
It is sometimes mixed into clay and applied to the face as a mask treatment, or put in tea and consumed for stomach complaints. Users believe that a solution of sea cucumbers can heal cuts, skin eruptions, and ulcers, and claim that it has a beneficial effect on the immune system.
Scarcity.
Sea cucumbers in the waters of Malaysia have been over-harvested to supply consumers of the folk remedy, and as a result the animal and its products are becoming scarce. Efforts to restock the fishery have not generally been successful. Recently, a sea cucumber aquaculture operation was opened on the shores of several Malaysian islands to increase the gamat supply.


Windber Research Institute

Windber Research Institute (WRI) is a private, non-profit biomedical research institute that is focused on women's health, cardiovascular disease and processes of aging, is located on Somerset Avenue in Windber, Pennsylvania. It opened in 2001.
The research of WRI is mainly divided into tissue banking, data warehousing of clinical, molecular (genomic and proteomic) and imaging data and data analysis and interpretation along with the biomedical informatics team.
Through an existing relationship with the Walter Reed Army Medical Center, in the Clinical Breast Care Program, WRI currently has greater than 14,000 highly annotated breast tissues, alone, with more than 500 data fields and single pathologist review on each patient, integrated with all the molecular and imaging data as well. Studies are ongoing regarding tumor heterogeneity, disease and patient stratification, environment and lifestyle risk factors, ethnicity, and biomarker development, all with a focus on addressing existing clinical problems.
In addition, WRI is examining the impact of lifestyle modification programs, using diet, stress management and exercise along with group support, to reduce cardiovascular risk factors, control obesity and impact diabetes. This is part of the Ornish Lifestyle Program that is offered at Windber.
Its diagnostic capabilities include digital and film mammography, 4-D ultrasound, 16-slice PET/CT and a 3T HD MRI which are integrated into the clinical data, molecular data and image repository.


Richard J. Allen (politician)

Richard J. Allen (born August 6, 1933) was a Republican member of both houses of the Michigan Legislature between 1969 and 1982.
Allen was elected to the Michigan House of Representatives in 1968 to succeed his father, Lester Allen. After serving two terms, Allen was defeated in the 1972 primary election. Two years later, he won election to the Michigan Senate, served two terms, and was defeated in the 1982 primary.
He was an unsuccessful candidate for Congress twice: in 1980, losing to Donald J. Albosta, and 1990, losing to Dave Camp in the primary. Allen was also a college professor, and a member of the Farm Bureau, Rotary, the Audubon Society, and the Sierra Club.
Allen was executive director of the Michigan State Fair from 1990 to 1993. He is also the namesake of the Dick Allen Lansing to Mackinaw Bike Tour (DALMAC).