Serco

Serco Group plc is a British company with headquarters based in Hook, Hampshire, England. Serco manages over 500 contracts worldwide. The company employs over 50,000 people. Serco operates in the following sectors of public service provision: Health, Transport, Justice, Immigration, Defence, and Citizens Services. Serco primarily derives income as a contractor from the provision of government services.
It is listed on the London Stock Exchange and is a constituent of the FTSE 250 Index. The majority of Serco's turnover is generated from UK operations, but the company also operates in Continental Europe, the Middle East, the Asia Pacific region and North America.
In July 2019, a fine of £19.2m was imposed on Serco for fraud and false accounting over its electronic tagging service for the Ministry of Justice. The company was also ordered to pay the Serious Fraud Office's investigative costs of £3.7 million. The company has also been accused of an extensive cover-up over sexual abuse of immigrants at Yarl's Wood Immigration Removal Centre in Bedfordshire, and, together with its consortium partners, failing to develop a strategy for managing Higher Active radioactive Waste at the Atomic Weapons Establishment.
History.
Serco was founded in 1929 as RCA Services Limited, a United Kingdom division of the Radio Corporation of America and initially provided services to the cinema industry. Following the takeover of RCA by General Electric in late 1985, RCA Services Limited was bought out by its local management. It changed its name to Serco in 1987 and has been a London Stock Exchange listed company since 1988.
On 29 December 2008, Serco acquired SI International.
In November 2014 its share price, which stood at 674p before the taxpayer scandal broke in 2013 collapsed to 218.7p, after four profit warnings. The new chief executive Rupert Soames sold off "scores of divisions". He said the company was suffering from ministers’ improved ability at driving a bargain, and claimed that “the Government has got much more adept at writing contracts and transferring risk to the private sector”. On 17 November 2014, it was announced that Alastair Lyons would resign from his position as chairman of Serco. Lyons referred to “operational mis-steps” for which he took “ultimate responsibility”, but said he had not been forced out. Serco made a loss of £991 million in 2014, reducing to a loss of £69.4 million in 2015.
Sir Roy Gardner was appointed as Non-Executive Chairman on 28 May 2015: he is also a senior adviser to Credit Suisse Group AG. In September 2017, Serco announced that it would be combining its UK and Europe operations.
UK operations.
Border security.
Serco operates the National Border Targeting Centre for UK Visas and Immigration and provides the carrier gateway—the interface between carriers and the agency.
Work and pensions.
Serco is contracted to the Department for Work and Pensions (DWP) to provide telephone advice on behalf of DWP to recipients of Support for Mortgage Interest (SMI), which ends in April 2018.
Transport.
In London, Serco operates the London Cycle Hire Scheme for Transport for London and operated the Docklands Light Railway from 1997 until 2014.
Serco has operated a number of train operating companies. It has a 50% shareholding in Serco-Abellio that has a concession to operate the Merseyrail franchise in Liverpool until 2028, and previously operated the Northern Rail franchise from December 2004 until March 2016. Serco has a contract in its own right to operate the Caledonian Sleeper between London and Scotland until 2030.
In 1997 Serco purchased the Railtest business as part of the privatisation of British Rail. Included in the sale was a management contract for the Old Dalby Test Track. From 1997 until 2004, Serco operated the National Rail Enquiry Service under contract to the Association of Train Operating Companies. It maintains Network Rail's fleet of infrastructure and maintenance trains at the Railway Technical Centre.
In Scotland, Serco has operated the NorthLink Ferries ferry service since July 2012. In September 2018 it commenced operating a bicycle-sharing system under contract to Transport for Edinburgh.
Serco's Home Affairs division operates speed camera systems throughout the UK and, until November 2013, designed, wrote and tested the software that controls the matrix message signs, signals, emergency roadside telephones (SOS) and traffic monitoring on England's motorway network including, until 2011, the National Traffic Control Centre.
Science.
Serco managed the UK's National Physical Laboratory until 2015 and also provides IT Services, Industrial Support and Cryogenic Operations Support and Maintenance at CERN. Serco also was part of a consortium running the National Nuclear Laboratory under contract, until October 2013.
Prisons and justice.
In Britain Serco supplies electronic tagging devices for offenders and asylum seekers. Serco, as well as its rival G4S, was accused of overcharging the Ministry of Justice on its contract to tag offenders. The firm issued a profit warning for 2014 as a result of the costs of becoming embroiled in an electronic tagging scandal. Serco repaid £68.5 million to the government for its overcharging on the contract. In May 2014 a Survation poll for campaign group We Own It, found that 63% of respondents thought Serco should be banned from bidding for any new public contracts after the firm was investigated for overcharging on government contracts.
It runs four prisons, a Young Offenders Institution and a Secure Training Centre. It has also operated two Immigration Removal Centres since 2007. Serco is also responsible for the contracted-out court escort services in the south-east area (formerly a role undertaken by HM Prison Service).
In September 2013, Serco was accused of an extensive cover-up over sexual abuse at Yarl's Wood Immigration Removal Centre in Bedfordshire, England In August 2014, Serco was criticised for using immigrant detainees as cheap labour, with some being paid as little as £1 per hour. The decision to give the firm a new £70 million eight-year contract to run Yarl's Wood has been criticised. Natasha Walter, of Women for Refugee Women, said
"Serco is clearly unfit to manage a centre where vulnerable women are held and it is unacceptable the government continues to entrust Serco with the safety of women who are survivors of sexual violence."
A fine of £19.2m was imposed on Serco following the delayed legal action that began in 2013, for fraud and false accounting over its electronic tagging service for the Ministry of Justice. Serco was also ordered to pay the full amount of the Serious Fraud Office's investigative costs (£3.7m). In his judgment, Mr Justice Davis said: “SGL (Serco Geografix Ltd) engaged in quite deliberate fraud against the Ministry of Justice in relation to the provision of services vital to the criminal justice system."
Housing.
In Glasgow, in August 2018, it was disclosed that Serco had been planning to evict asylum seekers before their appeal procedure was completed. Lawyers questioned whether this was legal under Scottish law. Two asylum seekers started hunger striking. Serco confirmed that it was serving a notice of eviction on many tenants causing alarm and lawyers challenged one asylum seeker's eviction at the Scottish Court of Session. Councillor Jennifer Layden, equalities and human rights convener for Glasgow, said, "The lock change announcement by the Home Office and Serco has caused widespread fear and alarm among asylum seekers in Glasgow. There is confusion and panic among the community – some of whom have limited English and who may not be affected by Serco’s announcement. Both Serco and the Home Office have a responsibility to put this vulnerable group at ease".
In January 2019, it was reported that Serco had lost the contract to provide housing to asylum seekers in Glasgow.
A Freedom of Information request by the Scottish Refugee Council showed that Serco had been charged nearly £3m by the Home Office for repeatedly breaching its contract to house asylum seekers in Glasgow and Northern Ireland.
Defence.
Serco held defence contracts in 2004, including the UK Government's contract for the maintenance of the Ballistic Missile Early Warning System at RAF Fylingdales; contracts are also held for the operation and maintenance of RAF Brize Norton, RAF Halton, RAF Northolt and RNAS Culdrose in the UK and RAF Ascension Island in the mid-Atlantic. Serco also provides support services to garrisons in Australia. Serco also manages many aspects of operations at the Defence Academy of the United Kingdom in Shrivenham. Serco is one of three partners in the consortium which manages the Atomic Weapons Establishment: in July 2015 the Office for Nuclear Regulation issued an improvement notice to the consortium demanding that it demonstrate that it has a long-term strategy for managing Higher Active radioactive Waste in order to reduce the risk to the public and its employees.
Serco also has a 15-year contract worth £400 million to provide facilities management services to the Defence Science and Technology Laboratory (Dstl).
Serco is a major subcontractor to Airbus Defence and Space on the Skynet military communications satellites PFI contract.
"Serco Marine Services" is responsible for fleet support at the three main UK naval bases, HMNB Portsmouth, HMNB Devonport and HMNB Clyde.
Aviation.
Serco provides air traffic control services at international airports in the United Arab Emirates and at some smaller airports in the United States and Canada. Starting in 2004 Serco had a £5m a year contract from the US government to manage airports in Iraq for 18 months. Serco also operate Scatsta Airport in Shetland. In June 2010 Serco signed a £4 million contract to operate all air traffic control services for Coventry Airport.
Health.
Serco provide facilities management services at the Norfolk and Norwich University Hospital, Leicester Royal Infirmary, and Wishaw General Hospital.
The company had the contract for out-of-hours GP services in Cornwall from which it withdrew in December 2013 after the company left the county short of doctors. The company also said it would stop running Braintree hospital in Essex as it pulled out of managing GP services and large hospitals.
In health services, Serco's failures include the poor handling of pathology labs and fatal errors in patient records. At St Thomas' Hospital, the increase in the number of clinical incidents arising from Serco non-clinical management has resulted in patients receiving incorrect and infected blood, as well as patients suffering kidney damage due to Serco providing incorrect data used for medical calculations. A Serco employee later revealed that the company had falsified 252 reports to the National Health Service regarding Serco health services in Cornwall.
It emerged in November 2013, Serco, which won a contract for Suffolk Community Healthcare in 2012, had 72 vacancies after earlier cutting 137 posts. Problems identified by Ipswich and East Suffolk Clinical Commissioning Group include “staff capacity, skill mix, workload, succession planning and morale, training, communication, mobile working, care co-ordination centre processes, incidents and near miss incidents”.
In April 2014 Serco revealed that it would lose almost £18 million on three of its NHS contracts. The firm has made provisions for losses in its Braintree and Cornwall contracts, which were cancelled early. It has also made provisions for losses in its contract for services in Suffolk. The company claims it will take longer to deliver the operational efficiencies it hoped for, despite saying in May 2013 that it expected to make a profit on the three-year, £140 million contract for community services. It said that staff had not recorded activity accurately on the Electronic health record and that activity had increased significantly during the course of the contract.
In August 2014 it was reported that the company had decided to withdraw from the clinical health services market in the UK after a review of the cost of delivering “improved service levels” and meeting the performance requirements of several existing contracts.
On 24 October 2017, it was reported that Serco was preparing to buy healthcare contracts from facilities management business Carillion. The deal included 15 contracts, with annual revenues of approximately £90m, for which Serco would pay £47.7m, with Carillion losing £1bn from the value of its order book.
In May 2020, Serco accidentally shared the personal email addresses of nearly 300 trainee COVID-19 contact tracers.
Education.
Serco held a ten-year contract with Bradford City Council between 2001 and 2011 to manage and operate the local education authority, providing education support services to the city's schools. This period was marked with "real problems" according to senior council officials and was taken back in house by the local authority after this period. Serco similarly manages and operates Walsall and Stoke-on-Trent local education authorities. Serco is one of Ofsted's three Regional Inspection Service Providers, responsible for school inspections in the English Midlands.
Leisure.
Serco Leisure Operating Ltd works with clients throughout the UK, running gyms, swimming pools, cycle hire schemes and National Sports Centres.
Information technology.
Serco administered the publicly funded UK Business Link website from 2005 until its closure in 2012. It won a five-year tender in 2007 to run the IT Infrastructure for the London Borough of Southwark.
Waste and recycling services.
Serco also operates recycling and waste collection services for local councils.
Outside the UK.
Drivers' licensing.
Serco, through a purpose-made division Serco DES, holds a ten-year, $114 million contract with the Ministry of Transportation of Ontario to operate the Ontario's DriveTest driver examination centres. These tests include vision, road, and knowledge tests for all persons seeking to become a licensed automobile driver in the province.
Parking meter servicing.
Serco has a contract with the City of Chicago, Illinois, to enforce parking meter regulations.
Health in the United States.
In July 2013 Serco was awarded a $1.25 billion contract to manage the implementation of the Patient Protection and Affordable Care Act, which makes Serco one of the most highly paid government contractors in the US.
Patent classification.
Serco does the classification for all incoming US patents.
Prisons and justice.
Serco runs partly privatised Hünfeld Prison in Hesse, Germany.
, Serco operates Acacia Prison in Western Australia, Australia's largest prison facility, as well as the Adelaide Remand Centre in South Australia.
It ran the Borallon Correctional Centre in Queensland for 22 years between 1990 and 2012, and Wandoo Reintegration Facility in Western Australia from 2012 to 2018.
It has also had the national contract for various immigration detention centres since 2009, including Christmas Island and the Villawood detention centre in Sydney. The Union of Christmas Island Workers highlighted the systemic failure by Serco to manage the Christmas Island Immigration Reception and Processing Centre. The centre detained a large number of refugees at its peak around 2013, including 1,000 children. Under Serco, there was an increase of deaths in custody and self-harm in the years leading up to 2013, as well as a deterioration of facilities, leading to the decline of the physical and the mental health of detainees and of staff. Ombudsman Allan Asher said "In the first week of June when I visited Christmas Island, more than 30 incidents of self-harm by detainees held there were reported". Serco, in a staged memo leaked to "The Australian", blamed the detainees for "creating a culture of self-harm", in order to use it as a "bargaining tool". The former manager of the detention centre stated the centre was grossly understaffed.
In Auckland, New Zealand, Serco operated the Mount Eden remand prison and in March 2012 was awarded a contract to build and operate a 960-bed prison at Wiri. Serco was heavily criticized for the existence of 'fight clubs' within Mount Eden prison that were not investigated until after they became public knowledge on 16 July 2015 when footage emerged online and was reported by TVNZ. On 24 July 2015, Serco's contract to run the Mount Eden prison was revoked and operation was given back to the New Zealand Department of Corrections. Serco was ordered to pay $8 million to the New Zealand government as a result of problems at Mount Eden Prison while it was under Serco's management. The New Zealand government did not accept that this was a failure of governmental contracting and oversight. It brought in correctional officers from afar to provide adequate staffing at Mount Eden, and by December 2016 had spent NZ$2 million housing up to 40 of them in Auckland hotels.
Transport.
Australia.
From 1996 until 2005, Serco operated TransAdelaide bus services in Adelaide. In November 1995 Serco commenced a contract to provide transport information services for Transperth and in May 1996, a contract to maintain all of its bus stations.
From 1997 until 2015, Serco owned Great Southern Rail that operated "The Ghan, Indian Pacific" and "The Overland" passenger trains. In March 2015, the business was sold to Allegro Funds.
In Sydney, Serco has operated transport information services for Transport for NSW since 1 July 2010.
Denmark.
Serco formerly operated the Copenhagen Metro in Copenhagen, Denmark, with Ansaldo STS, until it sold its share with effect on 1 January 2008.
Hong Kong.
Hong Kong's Cross-Harbour Tunnel operations has been contracted out to Serco since 2010.
Middle East.
Serco operated the Dubai Metro until 2021, and continues to operate the Dubai Tram and the Palm Jumeirah Monorail in Dubai.
Sweden.
Serco secured an eight-year contract in 2013 with its Swedish joint venture partner Strömma Tourism & Maritime to operate four Djurgården ferries on behalf of Stockholm County Council and public ferry company Waxholms Ångfartygs.
Offshore holdings in Mauritius.
The 2017 Paradise Papers revealed that Appleby carried out a risk assessment of Serco and noted it had a "history of problems, failures, fatal errors and overcharging" and had faced allegations of fraud and cover-ups.


Human disease modifier gene

A human disease modifier gene is a modifier gene that alters expression of a human gene at another locus that in turn causes a genetic disease. Whereas medical genetics has tended to distinguish between monogenic traits, governed by simple, Mendelian inheritance, and quantitative traits, with cumulative, multifactorial causes, increasing evidence suggests that human diseases exist on a continuous spectrum between the two.
In the context of human disease, the terms 'modifier gene' and 'oligogene' have similar meanings, and characterization of a particular locus depends on characterization of the phenotype (effects) that it causes or modifies. The term 'modifier gene' may be taken to mean a gene in which genetic variation modifies the effects of mutation at a major locus, but has no effect on the normal condition, a condition not necessarily met for oligogenic interactions. The study of diseases that arise from interactions amongst genes is important for understanding the genetic basis of disease. For these purposes, the study of both modifier genes and oligogenes are useful.
Theoretical origins.
Early theories that established the likely existence of modifier genes, and gene interactions as determinants of phenotypic variation, originated form theories of evolution, notably the evolution of the condition of allelic dominance. While many insightful early theorists contributed to current understanding of modifier genes, emphasized here are the theories of Ronald A. Fisher, Sewall Wright, and John B. S. Haldane. Fisher and Wright proposed somewhat opposing theories of the evolution of dominance in 1928 and 1931 respectively. Both sought to explain the observation that overwhelmingly, wild-type alleles were dominant to a majority of deleterious mutations. Their theories on the evolution of dominance had far-reaching implications for the fields of evolution, population and quantitative genetics, and biochemistry, and laid the early foundation of current understanding of human disease modifier genes.
Fisher theorized that, since negative selective pressures are strongest against dominant, deleterious mutations, de novo mutations that arise are initially codominant, but evolve recessivity through the accumulation of modifier alleles at other loci that attenuate disadvantageous phenotypes. He cited breeding experiments in nasturtium and "Drosophila", in which a distinct, mutant phenotype is lost with successive outcrossings, and recovered with inbreeding of offspring. By outcrossing, he argued, the breeder selects for modifying factors that attenuate the mutant phenotype, and by inbreeding and limiting the gene pool of modifiers, the dominance of the mutation is recovered. Importantly, Fisher argues that, "even in small isolated stocks, a sufficient variety of modifying factors" exists to observe this evolution of dominance in an observable succession of generations.
Wright challenged Fisher's theory and proposed that dominance of wild-type alleles evolves not by selection of modifiers, but by selection for physiological margins in biochemical pathways, that often allows them to function even with the occurrence of mutations, for instance in component enzymes. He argued that the effects of competition and genetic drift on populations, limited in genetic diversity, would overwhelm weak selection pressure acting on modifier alleles with nominal phenotypic consequences.
Ultimately, Wright's explanation of the evolution of dominance garnered most support, from experimental biochemists and geneticists, and later theorists, but it was Fisher's theory that first introduced the concept of modifier genes.
For the field of modifier genes, the most important responses to Fisher's theory came from Haldane. Haldane showed that, contrary to Fisher's argument, despite a decreased intensity of selection for dominance in self-fertilized populations, dominance is often more common in inbred than in outbred plant species. In 1941, Haldane applied the genetic model of modifier genes, which originated from theories of on the evolution of dominance, to phenotypic disease variation in humans. He analyzed data collected by Julia Bell on the heritability of several human diseases with quantitative phenotypes, specifically variation in age of onset. From this data, Haldane concluded that no single factor could be proven responsible for the observed phenotypic variation, in what were considered to be simple, monogenic diseases. He proposed a very simple theory, yet one that is operative in the study of oligogenic and complex human genetic disorders today. Haldane proposed that there exist three possible sources of observed phenotypic variation in monogenic traits:
Model diseases.
Haldane provided a fundamental, theoretical basis for the existence of modifier genes. Emerging experimental evidence has substantiated the likely existence and importance of modifier genes of human genetic disease, and a few diseases serve as models for the course of this emerging evidence.
Phenylketonuria.
Characterization of the metabolic disorder, phenylketonuria (PKU) represents a progression from an initial biochemical discovery that informed genetic studies and led to an understanding that genetic heterogeneity within a major locus, and in addition to it, was responsible for variation in clinical phenotypes. In 1953, G. A. Jervis identified a defect in the hepatic enzyme phenylalanine hydroxylase (PAH) as a cause of PKU. This led to the understanding that aberrant phenylalanine metabolism was responsible for the observed phenotype and to the development of diagnostics measuring blood or urine phenylalanine levels. Importantly, the development of clinical diagnostics facilitated better characterization of phenotypic variation, eliciting theories that genetic variation may underlie these observations. In 1983, Woo et al. mapped and cloned that PAH gene confirming theorized allelic heterogeneity. Importantly, phenotypic heterogeneity unexplained by allelic heterogeneity in the PAH gene was observed over time and new mutations in tetrahydrobiopterin recycling were characterized such as by Blau et al. in 1993.
Cystic fibrosis.
Research on cystic fibrosis (CF) exhibits a progression from genetic to molecular characterization of the major locus, CFTR. In 1985, the gene was mapped by linkage analysis by Tsui et al., and in 1989, the gene was cloned by Riordan et al. When analyses of allelic variation in CFTR did not suffice to yield dependable genotype-phenotype correlations or explain the total phenotypic heterogeneity in CF, the existence of modifier loci was suspected and association studies, such as by Zielenski et al. in 1999, have identified and characterized these loci.
Application to genetic disease.
Characterization of human disease modifier genes and oligogenic inheritance holds promise for understanding the abundance of phenotypic variation in human disease, which poses great challenge for therapies that are individually effective. Characterization of these phenotypes and the genes responsible for them, has relied on a combination of molecular techniques typically used to characterizing simple, monogenic disease, and statistical methods, typically used to characterize complex traits.
Understanding the mechanism of disease modifier genes and oligogenic inheritance may provide unique insights into the functions of gene-gene interactions that underlie human disease. Currently, techniques for molecular characterization of disease mechanisms are established for many monogenic diseases, but these studies do not improve understanding of genetic interactions and their phenotypic implications. Methodology for studying complex traits are primarily statistical, and involve large human populations in which genetic modifiers cannot be experimentally manipulated. Thus, in human populations the roles of genetic modifiers are often established by statistical implications, without evidence for causation or opportunity for functional characterization. The study of human disease modifiers and oligogenic disease is a hybrid field that can yield unique and comprehensive insight into complex mechanistic causes of human disease, necessary for the development of effective therapeutics
Characterizing complex multi-gene interactions responsible for disease- and further, developing effective therapeutics- is exceedingly difficult, and the molecular mechanisms of few oligogenic diseases have been elucidated. Retinitis pigmentosa is one disease for which genes responsible for phenotypic variation are identified and the molecular mechanisms by which they interact characterized. Mutations in the human RDS gene have been found, which reduce the formation of functional Rds-Rds protein homodimers, and with digenic inheritance of mutation in ROM1, prevent tetramerization of Rds-Rds and Rom1-Rom1 homodimers. In the double mutant condition, dosage of functional tetrameric complex is sufficiently reduced to cause RP.
Short of the challenge of thoroughly understanding of the molecular basis of complex disease, studying modifier genes and oligogenes can improve clinical diagnoses and prognoses, by combinatorially improving the accuracy genotype-phenotype correlations and shifting from clinical reliance on epidemiological data to patient-specific genetic and biological data. Ultimately, developing therapeutics for human disease informed by an understanding of its molecular mechanisms is challenging. In the case where multi-gene interactions give rise to disease, a series of thorough methodological steps must be taken to determine these mechanisms.
For the common case in which a major locus is causally associated with disease, but there exists considerable, unexplained phenotypic variation, this process of discovery typically begins with establishing heritability of the disease phenotype, and the reasonable likelihood that modifier genes contribute to the observed phenotypic variation. The process proceeds with the identification of modifier loci and functional determination of the mechanisms of their interactions with other disease-causing genes, and culminates with the discovery and development of effective therapeutics for disease, informed by mechanistic understanding of the functions of modifier genes. For skilled researchers using modern techniques, each step in this process of curing human genetic disease by studying modifier gene interactions poses great challenges.
Characterizing modifier gene interactions may not be the easiest approach to curing disease. This is certainly true in the case that modifier genes do not exist or functionally contribute to the disease phenotype of interest. Thus, the first step of establishing the likelihood that modifier genes indeed exist and contribute to observed variation is crucial to this described research process. This is typically done by eliminating other sources of heterogeneity as likely causes of the phenotypic variation in the disease of interest. Recalling Haldane's model, these sources of are generally classified as 1) genetic variation in the major locus 2) other sources of genetic heterogeneity, which include but are not limited to modifier genes, and 3) environmental influences.
Establishing residual heritability.
Crucial to the efficient study of the molecular basis of human genetic disease via genetic modifiers is first establishing that clinical variation in the phenotype cannot be otherwise explained by factors such as major locus heterogeneity or environmental influences. Methods of establishing disease heritability attributable to modifier genes can be categorized into familial studies and whole-population studies.
Familial studies of phenotypic variation and heritability to establish the existence of modifier loci found themselves on fundamental principles. If heterogeneity in modifier loci underlies observed phenotypic variation, then, on the whole, the more similar their genetic backgrounds, the more similar will be their phenotypes. Thus, interfamilial phenotypic variation will be greater than intrafamilial variation. Researchers use sibling and twin studies, for instance, to estimate heritability of a phenotype, controlling for sources of variation such as major locus heterogeneity and environmental influence. In one such example, Vanscoy et al. compare lung function between monozygotic and dizygotic twin pairs, as well as siblings with cystic fibrosis (CF). By comparing phenotype correlations between relatives, they estimate, using several models, heritability factors of lung function all greater than 0.5, after correcting for variation in major locus (CFTR) genotype and other sources of variation, and this significant proportion of sources of variation invites further study to characterize these factors.
Whole-population approaches are another important method of demonstrating the probability of modifier gene interactions. These approaches typically involve more complex statistical modeling, but ultimately serve the same purpose of family studies, by controlling for sources of phenotypic variance in disease populations to estimate the degree of residual heritability attributable to modifier loci. Wexler et al. use these methods in a sample of about 4,000 Huntington's disease (HD) patients from one of the world's best characterized populations in Venezuela to estimate that about 40% of residual variation in age of onset is attributable to unidentified genetic loci, aside from the HD locus.
Identifying modifier loci.
Perhaps most obviously important to understanding the roles of modifier loci in causing human genetic disease is identifying them. The size and complexity of the human genome make this a challenging task. Methods of identifying modifier loci can be categorized into three major approaches: genotype-phenotype correlations, linkage and association studies, and experimental phenotypic analyses in animal models.
Commonly, speculation of the responsibility of modifier loci for phenotypic variation of human disease arises from observations of genotype-phenotype correlations that deviate from simple, Mendelian inheritance of mutations at a single locus. Bardet–Biedl syndrome (BBS) provides one such example. BBS is a genetically-heterogeneous disorder with at least 6 known causative loci. It was initially thought that recessive inheritance of mutations at any one of these loci caused the disease, but once the first BBS gene, BBS6, was cloned, mutational and haplotype analysis revealed that some mutations did not conform to the expected monogenic, recessive transmission. Katsanis, et al. were the first to demonstrate the phenomenon of 'triallelic' inheritance, a form of digenic inheritance, of BBS, which initially seemed to be transmitted in a recessive manner. With genotyping of 163 BBS pedigrees, they demonstrated that manifestation of the disease likely requires the presence of three mutant alleles, including those in BBS2, BBS6, and possibly in other loci and they identified a digenic mechanism of inheritance in what was previously considered to be a simple, Mendelian disorder.
Genetic linkage analysis and association studies are widely used methods of identifying modifier loci. The advent of new genetic markers and automated genotyping methods have led to great diversity in applications of these studies. Common methodologies used to identify human disease modifier loci include linkage analysis in families, candidate association studies, and whole-genome association studies.
In an example of a familial linkage study, genotyping and linkage analysis conducted in a population of 197 sibpairs and their parents identified a single modifier gene responsible for meconium ileus, an intestinal obstruction phenotype detected in a subset of CF patients. Their study provides an example of the utility and feasibility of linkage analysis in identifying modifier loci, by simple genotyping and linkage analysis, especially where phenotypes under study are binary, and a subset of candidate markers can be tested.
Associations studies, genome-wide or biologically-informed candidate approaches, can also reveal modifier loci. To identify genes responsible for disease, association studies commonly compare case and control populations with and without phenotypic indications of the disease of interest respectively. To identify modifier loci of diseases of interest, for which causative major loci are commonly established, researchers consider a population composed only of individuals affected by the disease. Distribution of marker genotype is compared in patients with and without 'modified' phenotypes of interest to detect markers in linkage disequilibrium with potential modifier loci. Association studies for detecting markers linked to modifier loci require large populations and dense maps of genomic markers, especially to detect markers of subtle effect on phenotypes for which quantification or dichotomization may be challenging. Since these types of association studies are constrained to populations of patients affected by a disease, a primary challenge is collecting a sizable population that will lend the study sufficient statistical power. While, genome-wide approaches to association studies are systematic and comprehensive, candidate approaches spare the researcher some of the rigor of statistical analyses, for instance reducing the need for multiple testing corrections, but require informed selection of candidates.
Milet et al. conducted a candidate association study for modifiers of genetic hemochromatosis (GH), to explain its variable penetrance. Where most cases of GH are caused by mutations in the HFE gene, they focus on genes in two candidate pathways, those involved in non-HFE GH and those involved in expression of the iron storage hormone hepcidin, and find evidence that several common SNPs in these candidates modify serum ferritin levels. The identified modifier loci have established roles in iron metabolism and, with very simple interpretation, their results suggest future avenues for functional study, a corollary of their informed, candidate approach.
Corvol et al. conducted a whole-genome association study to identify modifiers of CF lung disease, identifying five associated loci. Their methods exemplify the large sample size required to conduct a statistically powerful analysis capable of identifying loci of relatively small effects. To obtain a large population, of 6,365 patients, they combine data on new and previously reported subjects and use linear mixed models that allow for the inclusion of affected siblings. The Genetic Modifiers of Huntington's Disease (GeM-HD) Consortium conducted a similar genome-wide association study, the first to demonstrate modifier loci modulating age of onset phenotype in Huntington's disease (HD). Their analyses were conducted on a population of 1,089 individuals affected by HD, genetic samples for which were collected over a period of almost 30 years.
Genotype-phenotype correlations, and linkage and association analyses in humans can effectively identify modifier genes with statistical support, but do not establish functional or causative effects of modifier genes. While genetic backgrounds cannot be experimentally manipulated in human populations, transgenic expression of modifier genes in animal models has been effectively used to show that variation in specific loci can cause phenotypic variation. For example, Ikeda et al. established that moth1 is a modifier gene of the tub gene, mutations in which cause obesity, retinal degeneration and hearing loss in tubby mice. In the wild-type form, the protein Mtap1a, encoded by neuronally-expressed moth1, is protective against hearing loss. Ikeda et al. showed, by transgenic expression in mice, that sequence polymorphisms in Mtap1a are crucial in causing the hearing-loss phenotype associated with tub gene mutation.
Unexplained heritability.
Unexplained variation in human disease phenotype is a complex issue, and with established methodologies of identifying and characterizing modifier genes, it is tempting to pursue them as explanation, with the potential to lead to a better understanding of the biological mechanisms of disease, such as by characterized interactions between gene products.
But identifying new modifier loci is challenging, and becomes more so, as those variants most easily detectable by current methods are increasingly identified and characterized. Still, for a majority human genetic diseases, less than 20% of heritability is explained by known variants. Some argue that unexplained heritability may be due to many rare variants, which typical association studies are not designed to detect, or structural genetic variation. Though the challenging identification of new genetic variants may not be the most efficient approach to developing mechanistically-informed drugs, it may lead to the development of more safe, individualized, and effective interventional strategies, risk-assessments and prognoses.
Zuk et al. argue that biomedical research should focus on interacting molecular mechanisms of genetic variants already discovered. They argue that genetic interactions are common. Widely used estimates of narrow-sense heritability, the ratio of additive genetic variance (calculated from measured effects of known variants) to total phenotypic variance (inferred from population data) assume additive effects in the heritability effects of variants. For most human traits, this fraction remains below 0.2. They argue that the assumption that heritability effects are additive overestimates heritability attributable to all genetic variation underlying disease, and thus underestimates the fraction of heritability attributable to already-discovered ones. Thus, they argue, research should focus on the molecular bases of already-discovered variants, as estimates of discovered sources of heritability are flawed, and there is insufficient evidence that undiscovered genetic modifiers exist. Furthermore, "the proportion of phenotypic variance explained by a variant in the human population is a notoriously poor predictor of the importance of the gene for biology or medicine," and effective therapeutics may target products of genes that explain very little of the clinically-observed variation in phenotype.


Coxa vara

Coxa vara is a deformity of the hip, whereby the angle between the head and the shaft of the femur is reduced to less than 120 degrees. This results in the leg being shortened and the development of a limp. It may be congenital and is commonly caused by injury, such as a fracture. It can also occur when the bone tissue in the neck of the femur is softer than normal, causing it to bend under the weight of the body. This may either be congenital or the result of a bone disorder. The most common cause of coxa vara is either congenital or developmental. Other common causes include metabolic bone diseases (e.g. Paget's disease of bone), post-Perthes deformity, osteomyelitis, and post traumatic (due to improper healing of a fracture between the greater and lesser trochanter). Shepherd's Crook deformity is a severe form of coxa vara where the proximal femur is severely deformed with a reduction in the neck shaft angle beyond 90 degrees. It is most commonly a sequela of osteogenesis imperfecta, Pagets disease, osteomyelitis, tumour and tumour-like conditions (e.g. fibrous dysplasia).
Coxa vara can happen in cleidocranial dysostosis.
Anatomy.
In early skeletal development, a common physis serves the greater trochanter and the capital femoral epiphysis. This physis divides as growth continues in a balance that favors the capital epiphysis and creates a normal neck shaft angle (angle between the femoral shaft and the neck). The corresponding angle at maturity is 135 ± 7 degrees. Another angle used for the measurement of coxa vara is the cervicofemoral angle which is approximately 35 degrees at infancy and increases to 45 degrees after maturity.
Types.
Developmental.
Clinical feature: presents after the child has started walking but before six years of age. Usually associated with a painless hip due to mild abductor weakness and mild limb length discrepancy.
If there is a bilateral involvement the child might have a waddling gait or trendelenburg gait with an increased lumbar lordosis. The greater trochanter is usually prominent on palpation and is more proximal. Restricted abduction and internal rotation.
X-ray: decreased neck shaft angle, increased cervicofemoral angle, vertical physis, shortened femoral neck decrease in femoral anteversion. HE angle (Hilgenriener epiphyseal angle- angle subtended between a horizontal line connecting the triradiate cartilage and the epiphysis); normal angle is <30 degrees.
Treatment:
HE angle of 45–60 degrees: observation and periodic follow up.
Indication for surgery: HE angle more than 60 degrees, progressive deformity, neckshaft angle <90 degrees, development of Trendelenburg gait
Surgery: subtrochanteric valgus osteotomy with adequate internal rotation of distal fragment to correct anteversion;
common complication is recurrence. If HE angle is reduced to 38 degrees, less evidence of recurrence;
post operative spica cast is used for a period of 6–8 weeks.
Coxa vara is also seen in Niemann–Pick disease.
Congenital.
Presence at birth is extremely rare and associated with other congenital anomalies such as proximal femoral focal deficiency, fibular hemimelia or anomalies in other part of the body such as cleidocranial dyastosis. The femoral deformity is present in the subtrochantric area where the bone is bent. The cortices are thickened and may be associated with overlying skin dimples. External rotation of the femur with valgus deformity of knee may be noted. This condition does not resolve and requires surgical management. Surgical management includes valgus osteotomy to improve hip biomechanics and length and rotational osteotomy to correct retroversion and lengthening.


Immunodominance

Immunodominance is the immunological phenomenon in which immune responses are mounted against only a few of the antigenic peptides out of the many produced. That is, despite multiple allelic variations of MHC molecules and multiple peptides presented on antigen presenting cells, the immune response is skewed to only specific combinations of the two. Immunodominance is evident for both antibody-mediated immunity and cell-mediated immunity. Epitopes that are not targeted or targeted to a lower degree during an immune response are known as subdominant epitopes. The impact of immunodominance is immunodomination, where immunodominant epitopes will curtail immune responses against non-dominant epitopes.
Antigen-presenting cells such as dendritic cells, can have up to six different types of MHC molecules for antigen presentation. There is a potential for generation of hundreds to thousands of different peptides from the proteins of pathogens. Yet, the effector cell population that is reactive against the pathogen is dominated by cells that recognize only a certain class of MHC bound to only certain pathogen-derived peptides presented by that MHC class.
Antigens from a particular pathogen can be of variable immunogenicity, with the antigen that stimulates the strongest response being the immunodominant one. The different levels of immunogenicity amongst antigens forms what is known as dominance hierarchy.
Mechanism.
CTL Immunodominance.
The mechanisms of immunodominance are very poorly understood. What determines cytotoxic T lymphocyte (CTL) immunodominance can be a number of factors, many of which are debated. Of these, one in particular focuses on the timing of CTL clonal expansion. The dominant CTLs that arise were activated sooner so therefore proliferate faster than subdominant CTLs that were activated later, thus resulting in a greater number of CTLs for that immunodominant epitope. This can be in concordance with an additional theory which states that immunodominance may be dependent on the affinity of the T-cell receptor (TCR) to the immunodominant epitope. That is, T cells with a TCR that has high affinity for its antigen are most likely to be immunodominant. High affinity of the peptide to the TCR contributes to the T cell’s survival and proliferation, allowing for more clonal selection of the immunodominant T cells over the subdominant T cells. Immunodominant T cells also curtail subdominant T cells by outcompeting them for cytokine sources from antigen-presenting cells. This leads to a greater expansion of the T cells that recognize a high affinity epitope and is favoured since these cells are likely to clear the infection much more quickly and effectively than their subdominant counterparts. It is important to note, however, that immunodominance is a relative term. If subdominant epitopes are introduced without the dominant epitope, the immune response will be focused to that subdominant epitope. Meanwhile, if the dominant epitope is introduced with the subdominant epitope, the immune response will be directed against the dominant epitope while silencing the response against the subdominant epitope.
Antibody Immunodominance.
The mechanism of immunodominance in B cell activation focuses on the affinity of epitope binding to the B-cell receptor (BCR). If an epitope binds very strongly to a B cell BCR, it will then subsequently bind with high affinity to the resultant antibodies produced by that B cell upon activation. These antibodies then out-compete the BCR for the epitope, and thus that B cell lineage will be unavailable for subsequent stimulation. On the opposite end of the scale where BCRs have low affinity for the epitopes, these B cells are outcompeted for stimulation by B cells with BCRs that have higher affinities for their respective epitopes. Insufficient T cell stimulation by these B cells also leads to suppression of these B cells by the T cells. The immunodominant epitope will be a BCR that has a particular ‘goldilocks’ amount of affinity for its epitope determined by equilibrium binding affinity. This leads to initial IgM response directed at the strongly binding epitope, and the subsequent IgG response focused on the immunodominant epitope. That is, those within the ‘goldilocks zone’ for affinity will be available for subsequent T helper stimulation, allowing for class switching, affinity maturation and thus, resulting in immunodominance to that particular epitope.
Implications.
 Having the immune response focused on a specific immunodominant epitope is useful because it allows the strongest immune response against a certain pathogen to dominate, thus eliminating the pathogen fast and effectively. However, it can also cause a hindrance because of potential pathogen escape. In the case of HIV, immunodominance can be unfavourable because of the high mutation rate of HIV. The immunodominant epitope can be mutated in the virus, thus allowing HIV to avoid the adaptive immune response when reintroduced from latency. This is why the disease perpetuates, as the virus mutates to avoid the antibodies and T cells specific for the immunodominant epitope that is no longer expressed by the virus.
 Immunodominance can also have implications in cancer immunotherapy. Similar to HIV-escape, cancer can escape the immune system’s detection by antigenic variation. As the immunodominant epitope is mutated and/or lost in the cancer, the immune response no longer has
 Immunodominance also has implications in vaccine development. Immunodominant epitopes vary from person to person. This phenomenon is due to the variability of HLA types, which make up the MHC molecules that present the immunodominant epitopes. Therefore, people with different alleles may respond to different epitopes of the same pathogen. With vaccine development particularly for subunit-based and recombinant vaccines, this may lead to some individuals which have different HLA haplotype to not respond while others do.


American College of Medical Practice Executives

The American College of Medical Practice Executives (ACMPE), established in 1956, supports and promotes the personal and professional growth of leaders to advance the medical practice management profession and is the certification and standard-setting body of the Medical Group Management Association (MGMA). Both are headquartered in Englewood, Colo. Nearly 6,000 members strong, ACMPE developed the standard-setting Body of Knowledge for Medical Practice Management. It grants nationally recognized certification and fellowship designations to the most accomplished medical practice executives and leaders in the profession.
Members of the ACMPE may obtain recognition for their knowledge and experience by becoming Certified Medical Practice Executives (CMPE) or a Fellow of the American College of Medical Practice Executives (FACMPE). Certification (CMPE) requires candidates who have the requisite two years of relevant experience to demonstrate their proficiency through objective and essay examinations and presentations that include content from the Body of Knowledge for Medical Practice Management. Fellowship (FACMPE) requires the submission of a professional paper or series of case studies by members who have already earned the CMPE designation. Both the CMPE and FACMPE status require the maintenance of continuing education credit hours.
MGMA.
The Medical Group Management Association defines and advances the medical practice management profession and advocates on its behalf. Its resources help the American College of Medical Practice Executives support and promote the professional growth of leaders.


Samuel Guze

Samuel Barry Guze (October 18, 1923 – July 19, 2000) was an American psychiatrist, medical educator, and researcher. He was an influential psychiatrist and worked at the Washington University School of Medicine in St. Louis for most of his career.
Along with Eli Robins, George Winokur and others, Guze advanced psychiatry by establishing criteria for diagnosis. A short paper by Guze and Robins contained a discussion of validity from a medical perspective. and came up with five phases of research that demonstrated that a diagnostic concept represented a disease. These five phases were: clinical description, laboratory studies, delimitation from other disorders, follow-up studies and family studies. While previously two psychiatrists might interview the same patient and propose differing diagnoses, the Guze system lead to great leaps in diagnostic "reliability", that is, different physicians would agree more often on what the diagnosis really was. Following publication of what came to be known as the Feighner Criteria, in 1980 he helped compile Diagnostic and Statistical Manual for Mental Disorders (3rd edition). The diagnostic reliability is still an essential component to modern versions of the Manual.
He was also among the first psychiatrists to study twins as a way to investigate the role of heredity in mental illness and contributed to the knowledge of genetic vulnerability to alcoholism and schizophrenia.
Papers.
Feighner, JP, Robins, E, Guze, SB, Woodruff, RA Jr, Winokur, G, Munoz, R. Diagnostic criteria for use in psychiatric research. Arch Gen Psychiatry 1972; 26:57-63
Robins, E and Guze, SB. Establishment of diagnostic validity in psychiatric illness: its application to schizophrenia. Am J Psychiatry 1970; 126:983-987


Great scapular notch

The great scapular notch (or "spinoglenoid notch") is a notch which serves to connect the supraspinous fossa and infraspinous fossa. It lies immediately medial to the attachment of the acromion to the lateral angle of the scapular spine.
The Suprascapular artery and suprascapular nerve pass around the great scapular notch anteroposteriorly.
Supraspinatus and infraspinatus are both supplied by the suprascapular nerve, which originates from the superior trunk of the brachial plexus (roots C5-C6).


Murad Alam

Physician, scientist, and author. Is a frequently cited expert in the area of cosmetic dermatology, and noted for his research in areas of cosmetic repair and barbed suture use. His work has also extended to serving on expert panels such as those dedicated to merkel cell cancer and guidelines of care. He is the current president of the Blade and Light Society for dermatologic surgeons and serves as the Chief of the Section of Cutaneous and Aesthetic Surgery at Northwestern University's Feinberg School of Medicine. Serves as a regular figure, in local and national news outlets, on discussions of skin care and skin cancer. He is an outspoken advocate of skin health.
Alam has both an undergraduate and MD degree from Yale University. He did his medical residency at Columbia University.


Pityriasis lichenoides chronica

Pityriasis lichenoides chronica (PLC) is an uncommon, idiopathic, acquired dermatosis, characterized by evolving groups of erythematous, scaly papules that may persist for months.
Symptoms and signs.
Although other forms of the disease occur at younger ages, some individuals start having long term symptoms at thirty years of age. This disease also affects adolescents and young adults. This also affects the immune system which therefore results in rashes. The symptoms rarely affect the face or scalp, but occurs at other sites of the body. The duration may last for months or even several years. For instance, new crops of lesions appear every few weeks.
Causes.
Pityriasis lichenoides chronica is probably caused by a hypersensitivity reaction to infectious agents such as the Epstein–Barr virus. Other infectious agents include the adenovirus and Parvovirus B19.
Treatment.
There is no standard treatment for PLC. Treatments may include ultraviolet phototherapy, topical steroids, sun exposure, oral antibiotics, corticosteroid creams and ointments to treat rash and itching.One study identified the enzyme bromelain as an effective therapeutic option for PLC.


Focal hyperhidrosis

Focal hyperhidrosis, also known as primary hyperhidrosis, is a disease characterized by an excessive sweating localized in certain body regions (particularly palms, feet and underarms). Recent studies have shown that this condition, affecting between 1% and 3% of the general population, seems to have a genetic origin.
Focal hyperhidrosis is sometimes referred to as "The Silent Handicap", as it has a significant impact on the quality of life, affecting the individual socially, psychologically, emotionally and professionally.
Genetics.
In 2006, researchers uncovered that primary palmar hyperhidrosis, referring to excess sweating on the palms of the hands and feet, maps to the gene locus 14q11.2-q13.
After this discovery, further research was conducted to examine if primary focal hyperhidrosis maps back to the same locus. In addition, researchers wanted to see if other previously unknown genes were responsible for different phenotypes among individuals with hyperhidrosis.
Based on previous research using mice and rats, researchers looked towards the role of aquaporin 5 (AQP5), a water channel protein, in human individuals with primary focal hyperhidrosis. AQP5 has been identified as a candidate gene in many hyperhidrosis studies. Using a family that had members with primary focal hyperhidrosis, researchers found that there was no connection between primary focal hyperhidrosis and AQP5. There was also no significant connection between the gene 14q11.2-q13 locus, which was linked to primary palmar hyperhidrosis, and primary focal hyperhidrosis in this family. Due to the inconclusive findings in the study, the question as to what are the genes and proteins that play a significant role in primary focal hyperhidrosis still remains.
The expression of the AQP5 protein and AQP5 mRNA was significantly higher in a patient group in comparison to the control group. In 2011, using a control group (individuals without primary focal hyperhidrosis) and a patient group (individuals with primary focal hyperhidrosis) researchers found that there was no difference between the number of sweat coils in the axillary sweat glands. This indicates that there is nothing morphologically different between individuals with and without primary focal hyperhidrosis. The discrepancies between the studies above call on further studies to confirm or deny the role of AQP5, and the role of other proteins, in hyperhidrosis.
Beyond looking at the genes and individual proteins that play a role in primary focal hyperhidrosis, researchers have looked at the patterns of heredity for this trait. In a 2003 study, using multiple families, researchers found that primary focal hyperhidrosis was not a sex-linked gene, since male-to-male transmission was seen in multiple families. Instead evidence supported an autosomal dominant pattern of inheritance with an incomplete disease penetrance. 21 patients in this study reported a positive family history of hyperhidrosis (62%). Researchers were able to uncover this by creating pedigrees of all the participants in the study. Not every member of the pedigree exhibited forms of hyperhidrosis, which allowed the researchers to track the patterns of inheritance. The findings in this study indicated that primary focal hyperhidrosis is typically an hereditary disorder.
Diagnosis.
Typical regions of excessive sweating include the hand palms, underarms, the sole of the foot, and sometimes groin, face, and scalp. Indeed, profuse sweating is present mostly in the underarms, followed by the feet, palms and facial region. Sweating patterns of focal hyperhidrosis are typically bilateral or symmetric and rarely occur in just one palm or one underarm. Night sweats or sweating while sleeping is also rare. The onset of focal hyperhidrosis is usually before the age of 25 years. This is in contrast to generalized hyperhidrosis which tends to occur in an older age group.
Evidence demonstrates that a positive family history is also present (see the "Genetics" part).
Treatments.
The Canadian Hyperhidrosis Advisory Committee has published a comprehensive set of guidelines which outlines key aspects of treatment related to this condition. Topical hyperhidrosis gels containing aluminum chloride hexahydrate are usually first choice treatments for this condition. Topical agents for Focal hyperhidrosis therapy include Formaldehyde lotion, topical anticholinergics... These agents reduce perspiration by denaturing keratin, in turn occluding the pores of the sweat glands. They have a short-lasting effect. Contact sensitization is increased, especially with formalin.
In addition to topical antiperspirants (whose main active ingredients usually are aluminum or zirconium salts) treatment options include: iontophoresis (hands, feet), onabotulinumtoxinA (Botox) injections (underarms, hands, feet, and other localized areas), electromagnetic/microwave energy thermolysis of underarm sweat glands (miraDry), laser-assisted removal of the sweat glands (underarms), other local procedures such as liposuction and curettage of the sweat glands (underarms), medications of the anticholinergic type that are taken by mouth, and sympathectomy surgery for sweating of the hands or head that can't be controlled by other means.


Ian Rusted

Ian Edwin Lawman Hollands Rusted (July 12, 1921 – July 14, 2007) was a Canadian doctor in Newfoundland and Labrador.
The son of Reverend Canon Ernest E. Rusted and Faith Hollands Rusted, he was born in Upper Island Cove, Newfoundland and attended school in Carbonear and St. John's. Rusted earned a pre-med degree from Memorial University College in 1940 and continued his studies at Trinity College, Toronto and Dalhousie University. He interned at Victoria General Hospital in Halifax and went on to earn a BSc from McGill University in 1949. He was awarded a fellowship in medicine by the Mayo Foundation and continued post-graduate studies at the Mayo Clinic from 1949 to 1952. In 1952, he became a fellow in the Royal College of Physicians of Canada. Later that year, he returned to Newfoundland, where he specialized in internal medicine. From 1952 to 1967, he served as medical consultant to the Newfoundland Department of Health. He was director of Medical Education, director of the Memorial University Research Unit and chairman of the Department of Medicine at St. John's General Hospital, also practising privately.
Rusted was able to persuade the federal and provincial governments to create a faculty of Medicine at Memorial University in 1967 and he served as its first dean and as professor of medicine. He stepped down as dean in 1974, when he was named vice-president of Health Sciences. He retired from that position in 1988.
In 1949, Rusted married Ellen Marie Hansen and they had two sons.
He was named an Officer in the Order of Canada in 1985. In 2013, he was inducted into the Canadian Medical Hall of Fame.
His older brother Nigel was also a physician.


Mandatory reporting in the United States

In many parts of the world, mandated reporters are people who have regular contact with vulnerable people such as children, disabled persons, and senior citizens, and are therefore legally required to ensure a report is made when abuse is observed or suspected. Specific details vary across jurisdictions—the abuse that must be reported may include neglect, or financial, physical, sexual, or other types of abuse. Mandated reporters may include paid or unpaid people who have assumed full or intermittent responsibility for the care of a child, dependent adult, or elder.
History.
In 1962, United States doctors C. Henry Kempe and Brandt Steele published "The Battered Child Syndrome," which helped doctors identify child abuse, its effects, and the need to report serious physical abuse to legal authorities. Its publication changed the prevalent views in the United States, where child abuse was previously seen as uncommon, and not a regular issue. In 1974, the United States Congress passed the Child Abuse Prevention and Treatment Act (CAPTA), which provides funds to states for development of Child Protective Services (CPS) and hotlines to prevent serious injuries to children. These laws and the media and advocacy coverage and research brought about a gradual change in societal expectations on reporting in the United States and, at different rates, in other western nations.
Originally created to respond to physical abuse, reporting systems in various countries began to expand to address sexual and emotional abuse, neglect, and exposure to domestic abuse. This expansion was accompanied by broader requirements for reporting abuse: previously reports were only submitted when an incident caused serious physical injury, but as the definitions changed, more minor physical injuries and developmental and psychological trauma began to be included as well.
As of 2013, there had been a huge increase of reporting over the decades with enormous numbers of unsubstantiated cases. Referrals increase each year, but the actual substantiated cases remain low and are approximately the same or decline each year.
Media and commentators often take the number of referrals to be synonymous with the number of cases of actual child maltreatment, which makes the problem appear larger than it actually is.
Statistics.
Nationwide, there was a 2348% increase in hotline calls from 150,000 in 1963 to 3.3 million in 2009. In 2011, there were 3.4 million calls.
From 1992 to 2009 in the US, substantiated cases of sexual abuse declined 62%, physical abuse decreased 56% and neglect 10%. About 1% of the child population are substantiated victims of abuse.
There are approximately 3.6 million calls each year nationwide: 9,000/day, 63,000/week, affecting on average 1 out of 10 U.S. families with children under the age of 18 each year (there are 32.2 million such families). From 1998 to 2011 there were a total of 43 million hotline calls. Of those substantiated, over half are minor situations and many are situations where the worker thinks something may happen in the future.
Each year, approximately 85% of hotline calls either do not warrant investigation or are not substantiated. Approximately 78% of all investigations are unsubstantiated and approximately 22% are substantiated, with around 9% where "alternative responses" are offered in some states, which have a focus on working with the family to address issues rather than confirming maltreatment.
Criteria.
In the United States, the Centers for Disease Control and Prevention (CDC) and the Department for Children and Families (DCF) define child maltreatment as any act or series of acts of commission or omission by a parent or other caregiver that results in harm, potential for harm, or threat of harm to a child.
There are four major categories of child abuse: neglect, physical abuse, psychological or emotional abuse, and sexual abuse. Neglect may include abandonment, denial of proper care and attention physically, emotionally, or morally, or living under conditions, circumstances or associations injurious to well-being.
Typically, minimum requirements for what must be reported include:
Typically, reporters are encouraged to report their suspicions and not to investigate or wait for absolute proof, which can lead to further harm directed at the suspected victim, and allow for perpetrators to prepare their defence through intimidation. The investigation of the abuse is then left to professionals.
Some jurisdictions allow clear protections for reports made in good faith, protecting the disclosure of the reporter's name.
Innocence should be presumed unless and until evidence establishing guilt is obtained and it must be remembered that only suspicions are being reported.
Some states require reporting of additional categories of mistreatment. For example, Kentucky requires all citizens to report not only suspected abuse and neglect, but also specifically requires reporting of suspected trafficking or female genital mutilation of children.
Mandated professions.
States frequently amend their laws, but as of 2019, all States, the District of Columbia, American Samoa, Guam, the Northern Mariana Islands, Puerto Rico, and the U.S. Virgin Islands have statutes identifying persons who are required to report suspected child maltreatment to an appropriate agency.
Approximately 48 States, the District of Columbia, American Samoa, Guam, the Northern Mariana Islands, Puerto Rico, and the Virgin Islands designate professions whose members are mandated by law to report child maltreatment. Mandated professions may include, but are not limited to the following:
, any person who suspects child abuse or neglect is required to report suspected abuse or neglect regardless of profession in 18 States and Puerto Rico. In all other States, territories, and the District of Columbia, any person is permitted to report. These voluntary reporters of abuse are often referred to as "permissive reporters."
Anonymity and immunity.
Mandated reporters are usually required to give their name when they make a report, but may request anonymity to protect their privacy. A mandated reporter who knowingly makes a false report will ordinarily have their identity disclosed to the appropriate law enforcement agency, and their identity may be disclosed to the alleged perpetrator of the reported abuse or neglect.
A mandated reporter may be subject to penalties, though immunity from civil or criminal liability is granted to reporters who report in good faith. Immunity is also granted to reporters who, in good faith, have not reported. However, failure to report suspected abuse or neglect could result in fines or other sanctions, such as participation in a training program. Failure to act may result in even stiffer penalties, such as civil litigation or criminal prosecution with the prospect of potential imprisonment.
Clergy–penitent privilege and other exemptions.
Conflicts between a mandated reporter's duties and some privileged communication statutes are common but, in general, attorney–client privileges and clergy–penitent privileges are usually exempt from mandatory reporting. In some states in the US, Psychiatrist and PhD. psychologists are also exempt from mandatory reporting.
"Clergy–penitent privilege" is privileged communication that protects communication between a member of the clergy and a communicant, who shares information in confidence. When applied, neither the minister nor the "penitent" can be forced to testify in court, by deposition, or other legal proceedings, about the contents of the communication. Most US states provide the privilege, typically in rules of evidence or civil procedure, and the confidentiality privilege has also been extended to non-Catholic clergy and non-Sacramental counseling.
Investigation of reports.
Each year in the US approximately 2 million allegations are investigated, affecting 1 out of 16 families in the US with children under 18.
Law enforcement or public health agencies are responsible for immediately evaluating all reports of abuse. Referrals in most states are screened to determine which are investigated – many clearly do not constitute abuse or neglect, or provide insufficient information to conduct an investigation. Rates of screening vary considerably between states – some investigate all reports, others screen out between 5% to 78% in this manner.
When reports contain sufficient information to warrant an investigation, authorities must make efforts within a reasonable time frame to begin (and conclude) an effective investigation, particularly when there is an imminent risk of physical harm or another emergency. Agencies should coordinate activities to minimize impacts upon the (possible) victim. In the US in 1985 the Children Advocacy Center model was founded, including "Multi-Discipline Teams" (law enforcement, child protection, prosecution, mental health) to interview, treat, manage and prosecute child abuse cases.
Consent to interview(s) of the (possible) victim often must be obtained from guardians, unless there is reason to believe such person is the alleged perpetrator. In cases where serious abuse or neglect is substantiated, local law enforcement, prosecutors or other public offices must be notified, and a copy of the investigation report must be sent.
US school districts adopted policies, following the 9th Circuit's ruling in Greene v. Camreta, requiring police or state case workers to produce a warrant, court order, parental permission or exigent circumstances prior to interviewing a student on school grounds as part of a sexual abuse investigation.
Substantiation by maltreatment type.
Total U.S. maltreatment substantiation annual rate is less than 1% of U.S. child population (9.3 per 1000 non-duplicates).
Of those:
The % of US children affected annually by substantiated neglect, physical and sexual abuse:
Appeals/expunction.
An attempt to appeal a decision is administrative, involving a review within the CPS agency, by CPS staff. CAPTA requires that states have procedures for expunging records. Procedures for doing so vary and may not be adhered. Ten states do not have provisions.
Arkansas, a CAPTA compliant state and a leader in addressing problems with the Child Maltreatment Registry has laws and procedures to remove one's name from the Central Abuse Registry after one year. (see Arkansas Department of Human Services Policy and Procedure Manual).
Child removals as a result of mandatory reporting.
CPS can take a child into protective custody with assistance from the police. Each day in the US approximately 700 children are removed from their parents to protect them from alleged abuse or neglect. In 2001, one US child every 5 minutes (approximately 100,000 children) was removed from their family who was later determined not to be maltreated.
Due to the human impact of removal, the law in the US requires it to be used sparingly. The U.S. Supreme Court has held that the Fourteenth Amendment to the U.S. Constitution provides a fundamental right to family integrity, requiring the state to provide notice and a hearing before forcibly separating a parent and child- with the exception of occasions when a child's life or health is in danger. Most removals are done on an emergency basis, bypassing the courts but requiring a post removal hearing.
Consequences/effects of investigations on children and their families.
Critics of investigations into reports of child abuse state that
Training.
Training is typically offered wherever mandated reporting laws are enforced, entailing matters such as recognition of abuse and neglect, what must be reported, how to report it, anonymity, immunity and penalties.
Training programs often use educational materials that use pat phrases and ambiguous indicators: e.g. defining emotional abuse to include the failure to provide a child with "adequate love" or reporting children who are withdrawn or shy as well as children who are friendly to strangers, despite the fact that only a small minority of children who exhibit such behaviors have been abused.
Training is available through a variety of sources. Many local child protective service organizations conduct classroom training. Training is also available through video and web-based courses.
Criticism.
Critics state that mandatory reporting may make the public more vigilant or overload the child welfare system which may increase tax dollars and needlessly separate children from their parents. It is predicted that expanding the list of mandated reporters or creating tougher penalties for failure to report will increase the number of unfounded reports. Mandatory reporting is also criticized because it jeopardizes the ability of people, including abused people, to seek medical treatment or maintain a therapeutic relationship, for fear of being reported. It has also been criticized for disproportionately affecting African-American families.
Critics also state that much that is now defined as child abuse and neglect (due to vague and broad laws) does not merit governmental interference. Unsubstantiated rates are enormous and go beyond anything reasonably needed and should concern everyone. Emotions about child abuse and sensational media coverage has led to an overreaction by some professionals and citizens, who report many cases that do not amount to child abuse. Eagerness to protect children cannot be allowed to overcome commitment to fairness and due process.
A further criticism is that mandatory reporting laws have had unintended consequences. Individuals, including juveniles, who have never been convicted of anything may be placed on child abuse registries for decades, limiting educational and employment opportunities due to background checks. Unnecessary reporting by professionals (under threat of prosecution) discourages fellow citizens from taking positive neighborhood action with families in trouble, as they may consider that their responsibilities have been met when they call in an anonymous hotline.
Better publicized and widely known use of statistics may have important implications for public policy. This would reduce hysteria about child abuse, which would lower rhetoric and high rates of unfounded reporting. This would reduce the burden on child protection agencies and would be fairer to the children and parents involved.


Tina Cooper

Christine Elizabeth "Tina" Cooper (21 July 1918 – 1 September 1986) was an English paediatrician and an expert on child abuse. She worked at Newcastle General Hospital for the majority of her career and received an OBE in 1967 for her services to children's health in Sierra Leone, which included establishing a national immunisation programme.
Early life.
Tina Cooper was born on 21 July 1918 in Watford. Her father, William Francis Cooper, was an analytical chemist and general practitioner. Her mother, Christine Maud Jones, died from influenza when Tina was six months old; her father remarried to Eileen Hall in 1920. The family moved to Surrey in 1924. Cooper attended numerous schools including Surbiton High School (1927–30), St John's School for Girls in Bexhill-on-Sea (1930–35), and Beau Soleil, a finishing school near Lausanne, Switzerland (1935–36). After spending two years training as a nursery nurse in Highgate, London, she decided to pursue a career in medicine to contribute further to children's welfare. She was admitted in 1939 to Girton College, Cambridge, for undergraduate studies, and completed her clinical training at the Royal Free Hospital School of Medicine, graduating as MB BCh in 1945.
Career.
Cooper began her medical career at London's Royal Free Hospital as a house physician, a house officer in obstetrics, and first assistant in the paediatric department. She received a diploma in child health in 1948 and moved to Newcastle the following year to join James Calvert Spence as a paediatric registrar at Newcastle General Hospital. She was appointed consultant in 1952, and held the role until her retirement in 1983. From 1964, she spent two years in Sierra Leone advising the government on child health policy, which included establishing a national immunisation programme against measles and other childhood infections. She was awarded an OBE in 1967 for her services to children's health in Sierra Leone, and elected Fellow of the Royal College of Physicians in the same year.
Cooper was interested in a family-oriented approach to paediatrics, believing that children's health relied strongly upon environmental and parental influences. On this basis, she studied fostered and adopted children, becoming an advisor to the Northern Counties Adoption Society and serving on the council of the Association of British Adoption and Fostering Agencies. In the 1960s, she turned her focus to abused children, embracing the ideas of C. Henry Kempe, an American who argued that child abuse was more prevalent than previously thought. While most British specialists refuted Kempe's research, according to the "Oxford Dictionary of National Biography", Cooper was "one of the first child specialists in Britain to recognise the prevalence, and the physical, psychological, and sexual nature, of child abuse". In 1979 she co-founded the British Association for the Study and Prevention of Child Abuse and Neglect (now the Association of Child Protection Professionals), subsequently serving as its president. She was also a member of an early research group on child abuse that influenced national government policy in the 1970s.
Death.
Cooper retired in 1983 and died from cancer on 1 September 1986 in Gosforth, Newcastle.


Michael Palmer (novelist)

Michael Stephen Palmer, M.D. (October 9, 1942 – October 30, 2013), was an American physician and author. His novels are often referred to as medical thrillers. Some of his novels have made "The New York Times" Best Seller list and have been translated into 35 languages. One, "Extreme Measures" (1991), was adopted into a 1996 film of the same name starring Hugh Grant, Sarah Jessica Parker, and Gene Hackman.
Biography.
Michael Stephen Palmer was born in Springfield, Massachusetts on October 9, 1942 to Milton and May Palmer. He grew up with two younger sisters, Donna and Susan. Palmer graduated from Wesleyan University in 1964 with a pre-med major, and with "sort of a Russian minor". He then went to Case Western Reserve University for medical school. Palmer trained in internal medicine at Boston City Hospital and Massachusetts General Hospital.
Palmer once claimed he never wanted to be a writer. He did not think he had much "flair" for it, even though he read in his spare time. In 1978, he read Robin Cook's medical thriller "Coma" (1977). Palmer thought if Cook, also a Wesleyan graduate could write a novel, then he could too. When not writing, he worked part-time at Massachusetts Medical Society. Before he began work on his first published novel, "The Sisterhood", about euthanasia, Palmer was practicing treatment of drug addiction.
"Side Effects" (1985), his second published work, was about the testing of unapproved drugs on a patient in Nazi Germany, but his most famous novel proved to be "Extreme Measures" (1991), in which a promising young doctor is threatened by a hospital elite after discovering the body's criminal acts. A selection of his other books include: "Natural Causes" (1994), about a holistic doctor who prescribes medicine that actually kills patients; "Miracle Cure" (1998), about a drug for heart disease that actually is very dangerous because of its side effects; and "Extreme Measures" (1991) on which the eponymous 1996 thriller film starring Hugh Grant, Sarah Jessica Parker, and Gene Hackman is based.
Palmer married Judith Grass and Noelle Shaughnessy with both marriages ending in divorce. He had three sons—Matthew, Daniel, and Luke.
On October 29, 2013, Palmer unexpectedly suffered a heart attack and stroke, dying the next day in New York City. In Palmer's memory, a tribute trail was named in his honor at Red Run Stream Valley Trail in November 2013.


Pseudoainhum


United Examining Board

The United Examining Board was formed in 1993 to administer non-university qualifying examinations in medicine and surgery. The diplomas offered by the United Examining Board were registerable with the General Medical Council in order to register as a medical practitioner in the United Kingdom, and an individual who had passed the examination could become a Pre-registration house officer.
The qualifications offered by the United Examining Board were either the
or the
These examinations were usually taken either by partly trained refugee doctors, or by doctors who had been trained at an overseas medical school not recognised by the World Health Organization, or by other overseas graduates who wished to transfer more easily from limited to full registration with the General Medical Council. They were also taken by students who had attended a UK medical school for one of two reasons; the first being those who had failed to obtain their primary medical qualification equivalent to a Bachelor of Medicine and Surgery; and the second being that students were allowed to sit these exams, or their precursors, before they were able to take the degrees from their own universities and so sitting this exam could mean earlier GMC registration and therefore enabled them to earn money sooner.
They were criticized as being a "backdoor into medicine".
The United Examining Board was dissolved in 2007.


GAZ-55

The GAZ-55 () was a Soviet military ambulance developed in the 1930s by Gorkovsky Avtomobilny Zavod (GAZ) and was used by the USSR during the Second World War. It was based on the GAZ-AA model. With only 9130 models ever being produced, the Red Army still relied heavily on standard trucks to transport their wounded. Production of this ambulance reportedly continued until 1946.
One GAZ-55 was captured by a unit of the "Luftwaffe".
In popular culture.
The GAZ-55 is featured in the 1941 Russian film 'Frontovye podrugi' (The Girl from Leningrad).
In video games.
The GAZ-55 is featured in the video game ".


Edward Atslowe

Edward Atslowe, M.D. (d. 1594), was a well-known physician in the reign of Elizabeth I of England.
Atslowe was educated at Winchester College and New College, Oxford. After being elected to a fellowship at his college he was created 'doctor of physic' at Oxford on 27 August 1566, and was one of the four doctors appointed by convocation to dispute before Queen Elizabeth when she was entertained at the university in September of that year. Shortly afterwards Atslowe settled in London and was admitted a fellow of the College of Physicians, and between 1569 and 1583 he filled successively most of the offices of distinction connected with the society. Among his patients Astlowe reckoned the chief noblemen of his time, and he was probably attached for some years as physician to the household of the Earl of Sussex.
But he did not wholly confine himself to the practice of medicine. If not a catholic himself, he strongly sympathised with the professors of that faith, and he proved himself an ardent supporter of Mary, Queen of Scots. As early as December 1570 he paid her a visit at Tutbury. For many years he is alleged to have aided the Earls of Arundel, Northumberland, and others, in a conspiracy to obtain assistance in her behalf from the continent, and in 1579 he was arrested on that charge, but released. In 1585 he was again sent to the Tower of London; but on being privately examined by the lord chancellor and other officials as to his relations with the papists he vehemently denied having had any treasonable 'intelligence' with any of them. A spy of the Queen of Scots wrote to her, however, in July of the same year: 'I heare that Dr. Atslowe was racked twice almost to the death in the Towre about the Earl of Arundell his matters and intentions to depart Englande, wherein he was betrayed'.
Atslowe was apparently released soon afterwards, as he attended a son of the Earl of Northumberland during a fatal illness in 1587.
His death occurred some seven years later; a private letter describes him as 'newly deade' on 2 May 1594. On 2 November 1573 Atslowe married Frances Wingfield at Stoke Newington, and upon her the Earl of Arundel settled an annuity after her husband's death.


CD8

CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). Along with the TCR, the CD8 co-receptor plays a role in T cell signaling and aiding with cytotoxic T cell antigen interactions.
Like the TCR, CD8 binds to a major histocompatibility complex (MHC) molecule, but is specific for the MHC class I protein.
There are two isoforms of the protein, alpha and beta, each encoded by a different gene. In humans, both genes are located on chromosome 2 in position 2p12.
Tissue distribution.
The CD8 co-receptor is predominantly expressed on the surface of cytotoxic T cells, but can also be found on natural killer cells, cortical thymocytes, and dendritic cells. The CD8 molecule is a marker for cytotoxic T cell population. It is expressed in T cell lymphoblastic lymphoma and hypo-pigmented mycosis fungoides.
Structure.
To function, CD8 forms a dimer, consisting of a pair of CD8 chains. The most common form of CD8 is composed of a CD8-α and CD8-β chain, both members of the immunoglobulin superfamily with an immunoglobulin variable (IgV)-like extracellular domain connected to the membrane by a thin stalk, and an intracellular tail. Less-common homodimers of the CD8-α chain are also expressed on some cells. The molecular weight of each CD8 chain is about 34 kDa. The structure of the CD8 molecule was determined by Leahy, D.J., Axel, R., and Hendrickson, W.A. by X-ray Diffraction at a 2.6A resolution. The structure was determined to have an immunoglobulin-like beta-sandwich folding and 114 amino acid residues. 2% of the protein is wound into α-helices and 46% into β-sheets, with the remaining 52% of the molecules remaining in the loop portions.
Function.
The extracellular IgV-like domain of CD8-α interacts with the α3 portion of the Class I MHC molecule. This affinity keeps the T cell receptor of the cytotoxic T cell and the target cell bound closely together during antigen-specific activation. Cytotoxic T cells with CD8 surface protein are called CD8+ T cells. The main recognition site is a flexible loop at the α3 domain of an MHC molecule. This was discovered by doing mutational analyses. The flexible α3 domain is located between residues 223 and 229 in the genome. In addition to aiding with cytotoxic T cell antigen interactions the CD8 co-receptor also plays a role in T cell signaling. The cytoplasmic tails of the CD8 co-receptor interact with Lck (lymphocyte-specific protein tyrosine kinase). Once the T cell receptor binds its specific antigen Lck phosphorylates the cytoplasmic CD3 and ζ-chains of the TCR complex which initiates a cascade of phosphorylation eventually leading to activation of transcription factors like NFAT, NF-κB, and AP-1 which affect the expression of certain genes.