Ground-glass opacity

Ground-glass opacity (GGO) is a finding seen on chest x-ray (radiograph) or computed tomography (CT) imaging of the lungs. It is typically defined as an area of hazy opacification (x-ray) or increased attenuation (CT) due to air displacement by fluid, airway collapse, fibrosis, or a neoplastic process. When a substance other than air fills an area of the lung it increases that area's density. On both x-ray and CT, this appears more grey or hazy as opposed to the normally dark-appearing lungs. Although it can sometimes be seen in normal lungs, common pathologic causes include infections, interstitial lung disease, and pulmonary edema.
Definition.
In both CT and chest radiographs, normal lungs appear dark due to the relative lower density of air compared to the surrounding tissues. When air is replaced by another substance (e.g fluid or fibrosis), the density of the area increases, causing the tissue to appear lighter or more grey.
Ground-glass opacity is most often used to describe findings in high-resolution CT imaging of the thorax, although it is also used when describing chest radiographs. In CT, the term refers to one or multiple areas of increased attenuation (density) "without" concealment of the pulmonary vasculature. This appears more grey, as opposed to the normally dark-appearing (air-filled) lung on CT imaging. In chest radiographs, the term refers to one or multiple areas in which the normally darker-appearing (air-filled) lung appears more opaque, hazy, or cloudy. Ground-glass opacity is in contrast to consolidation, in which the pulmonary vascular markings are obscured. GGO can be used to describe both focal and diffuse areas of increased density. Subtypes of GGOs include diffuse, nodular, centrilobular, mosaic, crazy paving, halo sign, and reversed halo sign.
Causes.
The differential diagnosis for ground-glass opacities is broad. General etiologies include infections, interstitial lung diseases, pulmonary edema, pulmonary hemorrhage, and neoplasm. A correlation of imaging with a patient's clinical features is useful in narrowing the diagnosis. GGOs can be seen in normal lungs. Upon expiration there is less air in the lungs, leading to a relative increase in density of the tissue, and thus increased attenuation on CT. Furthermore, when a patient lays supine for a CT scan, the posterior lungs are in a dependent position, causing partial collapse of the posterior alveoli. This leads to an increase in density of the tissue, resulting increased attenuation and a possible ground-glass appearance on CT.
Infectious causes.
In the setting of pneumonia, the presence of GGO (as opposed to consolidation) is a useful diagnostic clue. Most bacterial infections lead to lobar consolidation, while atypical pneumonias may cause GGOs. It is important to note that while many of the pulmonary infections listed below may lead to GGOs, this does not occur in every case.
Patterns.
There are seven general patterns of ground-glass opacities. When combined with a patient's clinical signs and symptoms, the GGO pattern seen on imaging is useful in narrowing the differential diagnosis. It is important to note that while some disease processes present as only one pattern, many can present with a mixture of GGO patterns.
Diffuse.
The diffuse pattern typically refers to GGOs in multiple lobes of one or both lungs. Broadly, a diffuse pattern of GGO can be caused by displacement of air with fluid, inflammatory debris, or fibrosis. Cardiogenic pulmonary edema and ARDS are common causes of a fluid-filled lung. Diffuse alveolar hemorrhage is a rarer cause of diffuse GGO seen in some types of vasculitis, autoimmune conditions, and bleeding disorders.
Inflammation and fibrosis can also cause diffuse GGOs. Pneumocystis pneumonia, an infection typically seen in immunocompromised (e.g. patients with AIDS) or immunosuppressed individuals, is a classic cause of diffuse GGOs. Many viral pneumonias and idiopathic interstitial pneumonias can also lead to a diffuse GGO pattern. Radiation pneumonitis, a side effect of pulmonary radiation therapy, can lead to pulmonary fibrosis and diffuse GGOs.
Nodular.
There are numerous potential causes of nodular GGOs which can be broadly separated into benign and malignant conditions. Benign conditions potentially leading to the formation of nodular GGOs include aspergillosis, acute eosinophilic pneumonia, focal interstitial fibrosis, granulomatosis with polyangiitis, IgA vasculitis, organizing pneumonia, pulmonary contusion, pulmonary cryptococcus, and thoracic endometriosis. Focal interstitial fibrosis presents a unique challenge when differentiating from malignant nodular GGOs on CT imaging. It is typically persistent over long-term imaging follow-up and shares a similar appearance to malignant nodular GGOs.
Pre-malignant or malignant causes of nodular GGOs include adenocarcinoma, adenocarcinoma in situ, and atypical adenomatous hyperplasia (AAH). One large review study found that 80% of nodular GGOs which were present on repeated CT imaging represented either pre-malignant or malignant growths. Differentiating between pre-malignancy and malignancy on the basis of CT alone can pose a challenge to radiologists; however, there are several features that that are indicative of pre-malignant nodules. AAH is a pre-malignant cause of nodular GGO and is more commonly associated with lower attenuation on CT and smaller nodule size (<10 mm) compared to adenocarcinoma. In addition, AAH often lacks the solid features and spiculated appearance that are often associated with malignant growths. In contrast, as adenocarcinoma becomes invasive it will more often cause retraction of adjacent pleura and may show an increase in vascular markings. Nodules >15 mm almost always represent an invasive adenocarcinoma.
Centrilobular.
Centrilobular GGOs refer to opacities occurring within one or multiple secondary lobules of the lung, which consist of a respiratory bronchiole, small pulmonary artery, and the surrounding tissue. A defining feature of these GGOs is the lack of involvement of the interlobular septum. Potential causes of centrilobular GGOs include pulmonary calcifications from metastatic disease, some types of idiopathic interstitial pneumonias, hypersensitivity pneumonitis, aspiration pneumonitis, cholesterol granulomas, and pulmonary capillary hemangiomastosis.
Mosaic.
A mosaic pattern of GGO refers to multiple irregular areas of both increased attenuation and decreased attenuation on CT. It is often the result of occlusion of small pulmonary arteries or obstruction of small airways leading to air trapping. Sarcoidosis is an additional cause of a mosaic GGOs due to the formation of granulomas in interstitial areas. This may coexist with granulomatosis with polyangiitis, leading to diffuse areas of increased attenuation with ground-glass appearance.
Crazy paving.
The crazy paving pattern may occur when there is both interlobular and intralobular widening. This sometimes resembles a road paved with irregular bricks or tiles. It is typically diffuse, involving larger areas of one or multiple lobes. There are a variety of potential causes, including Pneumocystis pneumonia, late-stage adenocarcinoma, pulmonary edema, some types of idiopathic interstitial pneumonias, diffuse alveolar hemorrhage, sarcoidosis, and pulmonary alveolar proteinosis. COVID-19 has also been shown to occasionally cause GGOs with a crazy paving pattern.
Halo sign.
A halo sign refers to a GGO that fills the area around a consolidation or nodule. This is a most commonly seen in various types of pulmonary infections, including CMV pneumonia, tuberculosis, nocardia infection, some fungal pneumonias, and septic emboli. Schistosomiasis, a parasitic infection, also commonly presents with the halo sign. Important non-infectious causes include granulomatosis with polyangiitis, metastatic disease with pulmonary hemorrhage, and some types of idiopathic interstitial pneumonias.
Reversed halo sign.
A reversed halo sign is a central ground-glass opacity surrounded by denser consolidation. According to published criteria, the consolidation should form more than three-fourths of a circle and be at least 2 mm thick. It is often suggestive of organizing pneumonia, but is only seen in about 20% of individuals with this condition. It can also be present in lung infarction where the halo consists of hemorrhage, as well as in infectious diseases such as paracoccidioidomycosis, tuberculosis, and aspergillosis, as well as in granulomatosis with polyangiitis, lymphomatoid granulomatosis, and sarcoidosis.
COVID-19.
Ground-glass opacity is among the most common imaging findings in patients with confirmed COVID-19. One systematic review found that among patients with COVID-19 and abnormal lung findings on CT, greater than 80% had GGOs, with greater than 50% having mixed GGOs and consolidation. GGOs with mixed consolidation has most often been found in elderly populations.
Several studies have described a pattern among initial, intermediate, and hospital discharge imaging findings in the disease course of COVID-19. Most commonly, initial CT imaging reveals bilateral GGOs at the periphery of the lungs. During initial stages, this is most often found in the lower lobes, although involvement of the upper lobes and right middle lobe has also been reported early in the disease course. This is in contrast to the two similar coronaviruses, SARS and MERS, which more commonly involve only one lung on initial imaging. As the COVID-19 infection progresses, GGOs typically become more diffuse and often progress to consolidation. This is sometimes accompanied by the development of a crazy paving pattern and interlobular septal thickening. In many cases the most severe pulmonary CT abnormalities occurred within 2 weeks after symptoms began. At this point, many individuals begin showing resolution of consolidation and GGOs as symptoms improve. However, some patients have worsening symptoms and imaging findings, with further increase in septal thickening, GGOs, and consolidation. These patients may develop lung "white-out" with progression to acute respiratory distress syndrome (ARDS) requiring treatment escalation.
Preliminary reports have shown many patients have residual GGOs at time of discharge from the hospital. Due to the novelty of COVID-19, large studies investigating the long-term pulmonary CT changes have yet to be completed. However, long-term pulmonary changes have been seen in patients after recovery from SARS and MERS, suggesting the possibility of similar long-term complications in patients who have recovered from acute COVID-19 infection.
History.
The first usage of "ground-glass opacity" by a major radiological society occurred in a 1984 publication of the "American Journal of Roentgenology." It was published as part of a glossary of recommended nomenclature from the Fleischner Society, a group of thoracic imaging radiologists. The original published definition read as: "Any extended, finely granular pattern of pulmonary opacity within which normal anatomic details are partly obscured; from a fancied resemblance to etched or abraded glass." It was again included in an updated glossary by the Fleischner Society in 2008 with a more detailed definition.


Alan Reay

Lieutenant General Sir Hubert Alan John Reay, KBE, FRCP, CStJ (19 March 1925 – 4 February 2012) was a senior British Army officer. He served as Director General Army Medical Services between 1981 and 1984.
Early life.
Reay was born on 19 March 1925 in Hednesford, Staffordshire. His father, a chaplain, had been awarded the Military Cross during World War I. He was educated at Lancing College, then an all-boys public school in the village of Lancing, West Sussex. He studied medicine at the University of Edinburgh, graduating in 1948 with Bachelor of Medicine, Bachelor of Surgery (MB ChB) degrees.
Military career.
On 23 October 1949, as part of national service, Reay was commissioned into the Royal Army Medical Corps with the rank of lieutenant. He was promoted to captain on 23 October 1950. On 23 November 1949, he transferred from the National Service List to the regular army on a short service commission. His first posting was as a Regimental Medical Officer attached to 1st Battalion, The Devonshire Regiment in the Federation of Malaya during the Malayan Emergency. By April 1952, he was a temporary major. He transferred to a regular commission on 26 November 1952 in the rank of captain. He was promoted to substantive major on 23 October 1957. He was promoted to lieutenant colonel on 23 October 1962.
He was promoted to colonel on 23 October 1972. He was promoted to brigadier on 14 July 1976. On 4 July 1977, he was appointed Commandant and Postgraduate Dean of the Royal Army Medical College and was granted the local rank of major general. He was promoted to substantive major general on 1 August 1977. In 1979, he was appointed Director of Medical Services BAOR. He was promoted to lieutenant general on 7 April 1981 with seniority from 7 November 1980. He served as Director General Army Medical Services from 1981 to 1984.
He retired from the British Army on 25 February 1985.
Later life.
Reay served as chairman of Lambeth health care NHS trust between 1992 and 1997.
He died on 4 February 2012, aged 86. His funeral was held at St Mary's Church, Barnes, London on 24 February. He was buried at East Sheen Cemetery.
Personal life.
In 1960, Reay married Ferelith Deane. Together they had three sons and two daughters. One of their sons predeceased him. Lady Reay died on 16 December 2016.
Honours and decorations.
On 4 April 1952, it was gazetted that Reay had been Mentioned in Despatches "in recognition of gallant and distinguished services in Malaya, during the period 1st July to 31st December, 1951".
He was appointed Officer of the Venerable Order of Saint John (OStJ) in December 1980, and promoted to Commander of the Venerable Order of Saint John (CStJ) in May 1981. In the 1981 Queen's Birthday Honours, he was appointed Knight Commander of the Order of the British Empire (KBE).
Having been appointed Honorary Physician to the Queen (QHP) on 3 January 1976, he was succeeded in the appointment on 25 February 1985. On 5 May 1986, he was appointed Honorary Colonel of the 217 (London) General Hospital Royal Army Medical Corps (Volunteers), a Territorial Army unit. His tenure expired on 19 March 1990.


Ophthalmology (journal)

Ophthalmology is a peer-reviewed medical journal of the American Academy of Ophthalmology, published by Elsevier.
Topics include new diagnostic and surgical techniques, treatment methods, instrument updates, the latest drug findings, results of clinical trials, and research findings. Ophthalmology also publishes major reviews of specific topics by acknowledged authorities.
Editors.
Editor-in-Chief
Family of Journals.
On June 6, 2016 The American Academy of Ophthalmology announced plans to launch "Ophthalmology Retina" as an extension of the journal "Ophthalmology". This new journal was planned in response to the growing volume of research within the retina subspecialty of ophthalmology, and will be a print and online publication.


James A. Schlipmann Melanoma Cancer Foundation

The James A. Schlipmann Melanoma Cancer Foundation was a US-based non-profit organization with a mission to fund clinical trials and research studies, and to advance education, awareness, screenings and treatment to eventually eradicate melanoma. The organization was founded December 15, 2002.
In 2007 the foundation awarded $160,000 in grants to fight melanoma. Grants were awarded to Dr. Rick Kefford of the Sydney Melanoma Unit, the University of Texas Southwestern Melanoma Center, and efforts to develop resources and educational materials directed toward melanoma patients and caregivers. Since its inception, the foundation has awarded $445,000 in grants.
According to an announcement posted on the foundation's home page, the James A. Schlipmann Melanoma Cancer Foundation merged with the Charlie Guild Foundation in 2009 to create the AIM at Melanoma Foundation.


Robert F. Bales

Robert Freed Bales (March 9, 1916 – June 16, 2004) was an American social psychologist. He specialized in small group interpersonal interaction and developed the SYMLOG (SYstematic MultiLevel Observation of Groups) method of group observation.
Biography.
Bales was born in Ellington, Missouri on March 9, 1916. He received a B.A. and M.S. in sociology from the University of Oregon. In 1945 he received a Ph.D. in sociology from Harvard University. Bales then became a professor at Harvard, working in the university's Laboratory of Human Relations. In 1950, Bales published a book titled Interaction Process Analysis: A Method for the Study of Small Groups in which he described in great detail his musings of human interaction within small groups.
Bales died in San Diego, California on June 16, 2004 at the age of 88.
Interaction Process Analysis.
The goal of this method was to capture direct face-to-face interaction as they takes place, then to analyze the interactions into useful information. In order to capture an interaction, Bales’ method utilized observers. The observer's job is to interpret and categorize the observed behavior. This is not without error as the observer must infer intent and meaning of the observable action. The observer is supposed to be well trained on the variables they are categorizing and they should be able to do it effortlessly; however, human raters bring with them their own preconceived schemas and heuristics. Human raters are subject to subconscious biases and fallacies. To circumvent this pitfall, Bales’ method makes use of multiple observers and an inter-rater reliability is then derived from both rater's produced data. Bales’ method was formed under two assumptions. The first assumption is that the observer must assume that all small groups are similar in that any given group contains a variety of people, or follows a normal distribution of variance. These group members share task problems that materialize in relation to their situational context, but also socio-emotional problems that materialize in the interaction with other members of their group. The second assumption is that each individual's behavior can affect those problems.
Observers must categorize each individual's behavior continuously, capturing behavior as a sequence of events through time. The unit of measure is the smallest discriminable segment of verbal or nonverbal behavior the observer can differentiate and classify. He referred to the content of these categories to be “process content” as opposed to the topical content. Bales claimed process content, which later became known as group process, was at the core of small groups; what remained when situational variance was stripped away.
SYMLOG.
The use of SYMLOG and the certification of SYMLOG consultants is now maintained by the SYMLOG Consulting Group, whose formation Bales supported. In 2016 the group honoured the centenary of Bales' birth by publishing excerpts from a video interview which he gave in 1996.


Adam Opalski

Adam Opalski (26 November 1897 – 3 November 1963) was a Polish neurologist and neuropathologist .
He was born in Olkusz and described a specific type of characteristically altered glial cells (currently referred to as Opalski cells), developing in the brain in Wilson’s disease. He died in Warsaw.


George Aghajanian

George K. Aghajanian is an Emeritus Foundations Fund Professor at the Yale School of Medicine, New Haven, Connecticut, in the Department of Psychiatry. He has been a pioneer in the area of neuropharmacology. He has also served as a member of NARSAD Scientific Advisory Board.
Early life and education.
George Aghajanian was born on 14 April 1932 in Beirut, Lebanon. He received his B.A. from Cornell University, followed by his Doctor of Medicine at Yale University.
Research and career.
Aghajanian did his research on the actions of LSD by which it produces hallucinations in the brain, and he has also uncovered the therapeutic mechanism of atypical antipsychotic drugs. He also found that application of serotonin (5-HT) produces an increase in the frequency and amplitude of spontaneous excitatory postsynaptic potentials in layer V pyramidal cells of the neocortex and transitional cortex by whole-cell recording in rat brain slices. He did research on the structure and mechanism of psychotropic drugs and neurotransmitters.
He was a medical officer in the United States Army in the starting days of his career. He served different positions at the Yale School of Medicine, including Assistant Professor of Psychiatry, Professor of Psychiatry and Pharmacology, Foundations Fund Professor of research in Psychiatry.
Awards and honors.
Aghajanian received the CINP Pioneer Award from the International College of Neuropsychopharmacology. He also received the Lieber Prize for research on schizophrenia. Additional awards include the Daniel H. Efron Research Award and the Julius Axelrod Mentorship Award from the American College of Neuropsychopharmacology, the Scheele Award from the Swedish Academy of Pharmacy, and the Heffter Award from the Heffter Research Institute, and election to the National Academy of Medicine.


Copper beaten skull

Copper beaten skull is a phenomenon wherein intense intracranial pressure disfigures the internal surface of the skull. The name comes from the fact that the inner skull has the appearance of having been beaten with a ball-peen hammer, such as is often used by coppersmiths. The condition is most common in children with hydrocephalus and is due to abnormal collagen development and ossification.


Dadang Hawari

Dadang Hawari (16 June 1940 – 3 December 2020) was an Indonesian psychiatrist.
Biography.
He was well known for his ability to combine a medical approach with a religious approach within an Islamic framework.
He died on 3 December 2020 due to COVID-19 during the COVID-19 pandemic in Indonesia.


Per Brinck

Per Simon Valdemar Brinck (4 September 1919 – 6 October 2013) was a Swedish zoologist.
He began his career as a veterinarian, but wrote a thesis on "Plecoptera" and later became a worldwide authority on "Gyrinidae". He travelled extensively to Africa and Southeast Asia, among others co-publishing the fifteen-volume "South African Animal Life" between 1955 and 1973. He served as a professor of zoology at the Lund University from 1958 to 1986. Brinck edited the journal "Oikos" from 1965 to 1989, and since 2007 the journal has given out the Per Brinck Oikos Award.
Brinck was a fellow of the Royal Swedish Academy of Sciences from 1974 and of the Norwegian Academy of Science and Letters. He also was a Honorary Member of the British Ecological Society.
The genera "Perbrinckia" and "Perbrinckiella" have been named after him.


Noah Lewis

Noah Lewis (September 3, 1891 – February 7, 1961) was an American jug band and country blues musician, generally known for playing the harmonica.
Life and career.
Lewis was born in Henning, Tennessee, and learned to play the harmonica as a child. He moved to Memphis, Tennessee, in his early teens, where he met Gus Cannon near Ripley in 1910. By that time he was already a respected original stylist on the harmonica, noted for his liquid tone and breath control, which allowed him to generate enormous volume from the instrument. By then he was also noted for his ability to play two harmonicas at once – one with his mouth and one with his nose, a trick he probably taught to Big Walter Horton, who recorded briefly as a teenager with the Memphis Jug Band some 20 years later. Lewis' ability to generate volume led to him playing in string bands and brass marching bands around Henning and on the streets of Memphis.
At their meeting in 1907, Lewis introduced Cannon to the 13-year-old guitarist and singer Ashley Thompson, with whom Lewis had been playing in the streets of Ripley and Memphis for some time, and the three of them worked together over the next 20 years whenever Cannon was in Memphis and not away working medicine and tent shows. When Will Shade's Memphis Jugband recorded and became popular in the late 1920s, Cannon added a coal-oil can on a rack round his neck and renamed the trio (Cannon, Lewis and Thompson) Cannon's Jug Stompers. It was this lineup that made the Jug Busters' first recordings, for Victor Records, in Memphis on January 30, 1928. The songs from that session included "Minglewood Blues", "Springdale Blues", "Big Railroad Blues" and "Madison Street Rag". By the time of the band's next recording, on September 5, 1928, Cannon had replaced Thompson with Elijah Avery on banjo and guitar. By the time of the band's third recording session, four days later, Avery had in turn been replaced with an old friend of Cannon's from the medicine and tent show circuit, the six-string banjo player and guitarist Hosea Woods. The band's lineup remained unchanged from then on. With the Jug Stompers, Lewis sang lead vocal and played a melancholy harmonica solo on "Viola Lee Blues".
Lewis recorded four solo tracks and another four sides with the Noah Lewis Jug Band, consisting of Lewis, Sleepy John Estes (guitar) and Yank Rachell (mandolin), in 1930.
His songs "New, New Minglewood Blues", "Viola Lee Blues", and "Big Railroad Blues" were in the repertoire of the Grateful Dead.
Death.
Lewis died in poverty, of gangrene brought on by frostbite, in Ripley, Tennessee, in 1961. He is buried in the Moorer (aka Marrows) Cemetery, 5 miles southwest of his birthplace, Henning.


R. Ananthanarayan

R. Ananthanarayan Ph.D. (born Trivandrum, Kerala - died 1998) was an Indian microbiologist. He graduated from Madras Medical College in 1941 and joined the Army Medical Corps during the Second World War. He joined Stanley Medical College, Madras in 1946 and developed an interest in influenza. He obtained his Ph.D. from the London School of Hygiene & Tropical Medicine in 1953 with a thesis on "The Fabric of the Influenza virus". He became professor of bacteriology at Trivandrum Medical College. He was a member of the team set up to monitor the Asian Flu Pandemic in 1957–58. He served as principal of Calicut Medical College from 1961 to 1967 and subsequently of Kottayam Medical College. After retirement in 1969, he was professor of microbiology at Mahadevappa Rampure Medical College, Kalburgi. Ananthanarayan was president of the Indian Association of Pathologists and Microbiologists (1976) and the Kerala State branch of the Indian Medical Association. His work on "A. Asia 57" was recognized by the World Health Organization. He wrote a "Textbook of Microbiology" in collaboration with C. K. Jayaram Panicker, of which ten editions have been published.


George Woodson

Dr. Georgina "George" Woodson is a fictional character from the BBC soap opera "Doctors", portrayed by Stirling Gallacher. She first appeared during the episode broadcast on 7 January 2003, and departed on 27 March 2009. George is introduced alongside husband Ronnie Woodson (Seán Gleeson), and together the pair have a daughter, Bracken (Jessica Gallagher).
Development.
Shortly after joining the cast, Gallacher fell pregnant. The producers decided against writing in her pregnancy, as they felt that George and her husband Ronnie Woodson (Seán Gleeson) were not ready for it. The couple were seen discussing the issue of having children, but the storyline led to the revelation that Ronnie is "frightened" about having a child. Gallacher explained, "When a child of one of the other characters is snatched, Ronnie thinks its too great a responsibility to take on and he cant cope with all the worry." The producer informed Gallacher that they would film around her bump and she expected to be hiding behind filing cabinets and carrying large bags.
In 2008, the script writers plotted a love triangle storyline for Georgie, Ronnie and Dr Nick West (Michael McKell) that tested the Woodson's marriage. Series producer Peter Lloyd told Kris Green of Digital Spy that things would "quiet down" for the couple, as he was keen not to exhaust them and Gleeson was planning to direct future episodes. Lloyd also said that he wanted the characters to be seen having fun, as they both turned 40 and continued to repair their marriage.
Gallacher decided to leave "Doctors" in 2009 to pursue other roles. Her departure aired alongside Gleeson's.
Storylines.
George is married to Ronnie Woodson (Seán Gleeson) whom she met at university. Ronnie does not want children, but George stopped taking the pill, so they had a baby called Bracken. In March 2009, Ronnie tells George about a job he has been offered in Shanghai; Ronnie declines the offer but George convinces him to accept it. However, just before their departure they learn that George is pregnant. This leads to a fight between the pair as George wants to remain in Letherbridge, but Ronnie wants to leave. Eventually, George relents and leaves with her husband and daughter, Bracken, with the staff at The Mill throwing a surprise leaving party beforehand. Julia Parsons (Diane Keen) gives Georgina a DVD to remember them all by, which includes a message from Bermuda from former colleague Vivien March (Anita Carey). When leaving, George says goodbye to everybody, and George and Julia agree they would stay in touch.
Reception.
In 2007, Gallacher and Gleeson won Best On-Screen Partnership at the British Soap Awards. The following year, their character's car crash and the aftermath was nominated for Spectacular Scene of the Year and Best Storyline. Gallacher also received a nomination for Best Actress.
"The Guardian"'s Gareth McLean made a case for "Doctors" replacing "Neighbours" on the BBC schedule because it "features the sterling Stirling Gallacher, who any sane primetime soap producer would be madly courting to join their cast."


William Canfield

"For the actor who appears in American silent films see William Canfield (actor)"
William Canfield is a glycobiologist, chief scientific officer and founder of an Oklahoma City-based biotechnology company, Novazyme, which was acquired by Genzyme in August 2001 and developed, among other things, an enzyme that can stabilize (but not cure) Pompe disease, based on Canfield's ongoing research since 1998. Canfield subsequently left Genzyme and established, with his partner in the Novazyme operation, John Crowley, another research laboratory (Cytovance Biologics), which he still heads. He saved Cytovance from bankruptcy by forming an investor group and raising $9 million after Crowley suddenly left the lab in 2005 to become the chief executive officer at Amicus Therapeutics in New Jersey
Biography.
Canfield obtained a B.S. in Chemistry from the University of Puget Sound followed by a Ph.D. in Biochemistry and Molecular Biology and an M.D. from the School of Medicine at the University of Washington. Canfield currently holds a faculty position in medical glycobiology at the University of Oklahoma Health Sciences Center. John Crowley took over a position as a CEO in Novazyme after leaving Bristol-Myers Squibb in March 2000 and together with at Duke University pushed for expedited approval by the U.S. Food and Drug Administration (FDA) of a new drug compound, NZ-1001 under orphan drug designation for the treatment of Glycogen storage disease type II in October 2005. The FDA stated: “We have determined that Novazyme’s recombinant human highly phosphorylated acid alpha-glucosidase (rhHPGAA) qualifies for orphan designation for enzyme replacement therapy in patients with all subtypes of glycogen storage disease type II (Pompe's disease).” Subsequent research at Genzyme on NZ-1001 along with three other potential compounds brought approval of the first enzyme replacement therapy for Pompe's disease - Alglucosidase alfa (Myozyme or Lumizyme, Genzyme Inc) in 2006.
Popular culture.
William Canfield's work with Pompe Disease was fictionalized and made the subject of a 2010 movie "Extraordinary Measures" in which he is called Dr. Robert Stonehill and played by Harrison Ford.


Sopite syndrome

The sopite syndrome (; Latin: sopire, "to lay to rest, to put to sleep") is a neurological disorder that relates symptoms of fatigue, drowsiness, and mood changes to prolonged periods of motion. The sopite syndrome has been attributed to motion-induced drowsiness such as that experienced by a baby when rocked. Researchers Graybiel and Knepton at the Naval Aerospace Medical Research Laboratory first used the term "the sopite syndrome", in 1976, to refer to the sometimes sole manifestation of motion sickness, though other researchers have referred to it as "Sopite syndrome."
Signs and symptoms.
Several symptoms are associated with the sopite syndrome. Typical responses include:
The sopite syndrome is distinguished from other manifestations of motion sickness (i.e. nausea, dizziness, etc.) in that it may occur before other symptoms of motion sickness or in their absence. The sopite syndrome may persist even after an individual has adapted to the other symptoms associated with motion-induced sickness.
Severity.
The effects of the sopite syndrome may range from minor physical inconveniences to hazardous conditions. People who operate automobiles, airplanes, etc., may experience impaired motor function due to the motions of the vehicle. These impairments often result in a decreased attention span; those who consider themselves well-rested may still succumb to drowsiness at inopportune moments. The sopite syndrome may therefore contribute to motor vehicle accidents in which automobile operators fall asleep at the wheel. However, the sopite syndrome itself does not directly result in death.
A subject experiencing the sopite syndrome on a frequent basis may increase the number of hours spent sleeping by fifty percent. A study of motion sickness occurrences in workers on an offshore oil vessel showed a large majority of participants experienced mild symptoms of fatigue. Many participants also experienced severe sleep disturbances. These symptoms were associated with impaired task performance.
Causes.
The sopite syndrome has been associated with visually-induced and vestibular motion sickness. Other factors associated with drowsiness such as darkness or physical fatigue may intensify the effects of motion-induced sleepiness. The sopite syndrome may occur with little motional stimulus (though the greatest effects tend to be observed in subjects who have been exposed for longer periods of time), and often persists for a time after the motional stimulus has ceased.
Susceptibility.
A study of certain aspects of motion sickness among medical transport attendants showed that the onset of the sopite syndrome is likely to occur independently of the mode of transportation; little difference was observed in the frequency of sopite symptoms for ground transport compared to air transport. Also, the length of time exposed to vehicular motion did not appear to affect the occurrence (or lack thereof) or severity of the sopite syndrome. No difference was observed in the incidence of the sopite syndrome for men versus women.
The sopite syndrome is likely a cumulative disorder. For instance, when a subject has the flu, a hangover may exacerbate the symptoms of the illness. A subject normally resistant to motion sickness may experience symptoms of motion sickness when also experiencing flu-like (or hangover-like) symptoms.
Mechanism.
The exact mechanism for the induction of the sopite syndrome is still unknown; however, a leading theory asserts that the sopite syndrome (and perhaps motion sickness in general) is somehow related to the reticular formation, an area of the brainstem associated with arousal. A study of motion-induced effects on the P50 potential (a measure of arousal) showed that subjects exposed to motion environments experience decreased sensory gating, which involves the filtering of information in the brain. In the case of Space Motion Sickness, the unweighting of otolith organs can lead to a sensory mismatch between the visual, vestibular, and somatosensory systems. Motion studies in which the subjects lacked vestibular systems did not experience symptoms of the sopite syndrome or other manifestations of motion sickness.
Vestibular system.
The role of the vestibular system in the inducement of the sopite syndrome or related symptoms may be difficult to ascertain. Researchers must compare the results of test subjects experiencing a motion environment to a control environment lacking motion. Experimental subjects who suffered increased fatigue in a rotating environment apparently recovered from this side effect when the same environment ceased motion. In similar studies, control subjects lacking vestibular function did not experience the motion-induced drowsiness associated with the sopite syndrome, while subjects with normal-functioning vestibular systems did experience increased fatigue in the rotating environments.
Visual stimulus.
The relation of the visual-vestibular stimulus to the sopite syndrome may be observed when comparing airline cockpit crew with cabin crew. While the former typically experience more confined conditions, the airline cabin crew tend to experience more symptoms associated with sopite syndrome; this effect may be attributed to the lack of visual validation and increased movement of the cabin crew.
Biochemicals.
Certain hormones or biochemicals likely affect the pathways associated with motion sickness in general and the sopite syndrome in particular. Studies reported by Kennedy, Drexler and Kennedy (2010) have investigated the role of cortisol and melatonin (a hormone associated with the maintenance of circadian rhythms) in motion-induced drowsiness. Subjects were exposed to vection-producing environments (virtual reality, for example) and symptoms were evaluated using a "Simulator Sickness Questionnaire". Sopite symptoms were also measured using a developed scale. The levels of endogenous cortisol and melatonin were then compared with levels before the subjects were tested in the vection environments. Most subjects showed increased levels of endogenous cortisol and melatonin post-vection. Melatonin may therefore be involved in the drowsy state associated with the sopite syndrome.
Noradrenergic pathways.
The inhibition of noradrenergic pathways has also been associated with symptoms of the sopite syndrome. Studies have shown that animals exposed to motion environments commonly exhibit drowsiness and disinclination for activity. These animals show slowed electroencephalography waves, which are involved in the firing of neurons in the brain. The locus coeruleuses of these animals are apparently deactivated. The sopite syndrome is therefore linked to inhibition of the locus coeruleus-noradrenergic pathways. As such, noradrenaline releasers may be useful in counteracting these symptoms.
Diagnosis.
Classification.
The sopite syndrome is classified as a symptom-complex centered on drowsiness. It may be distinguished from ordinary fatigue. Researchers have previously studied this effect through the use of rotating rooms. When subjects who had previously shown minimal susceptibility to general motion sickness and fatigue (in this particular case, four military officers) were recruited to live in a rotating room for several days, they exhibited several signs of drowsiness, such as yawning and frequent napping. Despite numerous activities designed to promote awareness and excitability, the subjects showed decreased motivation to socialize or perform physical activities. Many of these symptoms could be attributed to the vestibular stimulation of the rotating rooms.
Management.
Many drugs taken to relieve typical symptoms of motion sickness (including nausea, dizziness, etc.) contain compounds that may exacerbate drowsiness. Antihistamines are commonly used to treat motion sickness; however, side effects include drowsiness and impaired cognitive abilities. Anticholinergics such as scopolamine have also proved effective against motion sickness, but may induce drowsiness. These treatments may be combined with stimulants to counteract typical motion-induced nausea and dizziness while also preventing sedation.
However, many stimulants possess addictive properties, which result in a high potential for substance abuse. Some stimulants also tend to interfere with normal sleep patterns. Modafinil has been studied as a possible treatment for the sopite syndrome that does not appear to have the same side effects of normal stimulants. Modafinil appears to be effective when taken in combination with anticholinergics such as scopolamine, but studies of Modafinil-only treatments for motion sickness remain inconclusive.
Research.
The sopite syndrome may be difficult to test due to the nature of the symptoms. Indicators such as drowsiness, mood changes, and apathy must be observed and graded objectively. Therefore, many of the results obtained from studies of the sopite syndrome are not sufficiently repeatable for the purposes of scientific writing.
Questionnaires.
A typical method for determining the effects of the sopite syndrome is through the use of one or several questionnaires. The available questionnaires for motion sickness and sopite syndrome are described by Lawson. Two such questionnaires widely used to evaluate motion sickness are the Pensacola Diagnostic Index and the Motion Sickness Questionnaire. These questionnaires are limited, however, in that they group symptoms of drowsiness with other non-sopite related effects, such as nausea and dizziness. Motion sickness is measured based on the cumulative ratings of all these symptoms without distinguishing different levels for each effect.
A Motion Sickness Assessment Questionnaire has been developed to test the multiple dimensions of motion sickness more thoroughly; this survey defines motion sickness as gastrointestinal (involving nausea), peripheral (referring to thermoregulatory effects such as clamminess and sweating), central (involving symptoms such as dizziness and lightheadedness), and sopite-related. This questionnaire may more accurately determine how subjects experience sopite symptoms relative to other motion sickness effects. Another questionnaire designed to measure sleepiness is the Epworth Sleepiness Scale.
Optokinetic drum.
An optokinetic drum may be used to study visually induced sopite effects. The optokinetic drum is a rotating instrument in which test subjects are seated facing the wall of the drum. The interior surface of the drum is normally striped; thus, as the drum rotates, the subject's eyes are subject to a moving visual field while the subject remains stationary. The speed of the drum and the duration of the test may be varied. Control groups are placed in a drum without stripes or rotation. After exposure to the rotating drum, subjects are surveyed to determine their susceptibility to motion sickness. A study in which the optokinetic drum was used to test the symptoms of the sopite syndrome showed increased mood changes in response to the visual cues, though these effects were compounded by other environmental factors such as boredom and lack of activity.


Gordon McVie

John Gordon McVie (13 January 1945 – 20 January 2021) was an international authority on the treatment and research of cancer. He wrote over 350 peer-reviewed articles, editorials and books. McVie was born in Glasgow, Scotland and died of non-Hodgkin lymphona and COVID-19 in Bristol, England.
He served on several committees including the American Association for Cancer Research and the American Society of Clinical Oncology, and the boards of the National Cancer Institutes of France, Italy and the Netherlands. In the UK, he served on the boards of cancer institutes including the Beatson Institute for Cancer Research, the Institute for Cancer Research, and the Christie Hospital.
He was a visiting professor, King's College London, Senior Clinical Research Consultant at the Italian Institute for Molecular Oncology (IFOM) Milan, and Non Executive Director at Ellipses Pharma Ltd, UK Chair of ORIL, Australia and Chair of the European Alliance for Personalised Medicine.
He contributed several substantial additions to the field of cancer care including establishing localised, more pin-point, administration of chemotherapy, and encouraging the use of chemotherapy for the treatment of lung cancer throughout the EU. He also emphasised the importance of adjusting a patient's management according to their ethnicity.
Education.
McVie obtained his degrees in science and medicine at the University of Edinburgh in 1969, and became a lecturer in Therapeutics and Materia Medica, University of Edinburgh.
History.
In 1970, McVie took an MRC research fellowship at Edinburg University, Department of Therapeutics, investigating Hodgkin lymphoma. In 1975 McVie became the Foundation Senior Lecturer at the Cancer Research Campaign Oncology Unit (currently Beatson West of Scotland Cancer Centre) at the University of Glasgow. Under Gordon Hamilton-Fairley and Sir Kenneth Calman, he trained in the United States, spending sabbaticals at the NCI, Bethesda, Paris, Sydney, Australia and Amsterdam.
In 1979, McVie became the Clinical Research Director at the Netherlands Cancer Institute, and Consultant in Medical Oncology at the Antoni van Leewenhoek hospital in Amsterdam. He developed a drug development laboratory, and a clinical research unit, for Phase 1 and 2 drugs, plus establishing intraperitoneal therapy in ovarian cancer and limb perfusion in localised sarcoma and melanoma.
At the European Organisation for Research and Treatment of Cancer (EORTC) he started the lung cancer group and researched standard chemotherapy / irradiation regimes which were adopted for small and non small cell lung cancer, mesothelioma and thymoma. As Chair of the Pharmacology and Metabolism Group he developed a platform for young investigators to present new molecules and their pharmacology. He was elected President of EORTC and initiated the present Drug Development Group in Brussels, and with NCI support, the European New Drug Development Network and the joint EORTC, NCI, CRC Formulation Committee for anti cancer molecules.
In 1989 McVie became the Scientific Director then Director General of the Cancer Research Campaign. During this time over 60 new drugs were taken from laboratory to clinical trial, and carboplatin, temozolomide, olaparib and abiraterone, all important “breakthrough” anticancer drugs, emerged. In the UK he was one of the architects of the Cancer Trials Networks in Scotland, Wales, and England, and was a founding member of the National Cancer Research Institute, UK.
Having overseen a doubling of Cancer Research Campaign charitable income, he led the merger with ICRF to found Cancer Research UK (CRUK), the largest cancer charity in Europe.
In 2002 McVie became joint CEO of Cancer Research UK with Sir Paul Nurse, where he continued to support new molecule testing and support start-up companies.
Then in 2003 McVie founded a new endeavour, Cancer Intelligence, then with the late Umberto Veronesi - a free online global cancer journal ecancer.org, which was published for eleven years in Zurich, then moved to become a UK charity.
In 2004 McVie became a Senior Consultant of Clinical Research at the European Institute of Oncology, Milan. He set up a clinical research unit to test new molecules and devices, and synergised the new institute with other leading cancer centres throughout the world.
In 2016 he joined the Italian Institute for Molecular Oncology in Milan.
Honours and distinctions.
1967Gunning Victoria Jubilee Prize in Pathology

1977Honeyman Gillespie Lecturer in Medicine

1978Visiting Fellow, University of Paris, Department of Medical Oncology

1979Visiting Fellow, Netherlands Cancer Institute, Amsterdam

1980Consultant, Carcinogenesis of Cytostatic Drugs, International Agency Research in Cancer, WHO, Lyon

1983Visiting Professor, University of Sydney, NSW Australia

1990–1996 Visiting Professor, British Postgraduate Medical Federation, London University

1990–1998 Chairman UICC Fellowships Program and Board member (Union Internationale Contre le Cancer/International Union Against Cancer)

1994–1997 President, European Organisation for Research and Treatment of Cancer

1994–2002 First European Editor of Journal of the National Cancer Institute, US

1995King of Jordan’s Medal for Excellence in Science

1996DSc (Hon) University of Abertay, Dundee

1996–2000 Visiting Professor, University of Glasgow

1997DSc (Hon) University of Nottingham

1998FMedSci (Fellow of the Academy of Medical Sciences)

1999DSc (Hon) University of Portsmouth

2000Semmelweis Medal for Excellence in Science, Budapest

2000Medal of the National Scientific Research Fund of Belgium

2001Silver Medal, Royal Scottish Society of Arts

2001Medal of the National Cancer Society of Greece

2001FRCSE (Hon) (Fellow of the Royal College of Surgeons), Ed

2002DSc (Hon) Napier University, Edinburgh

2003–2006 Visiting Professor in Cancer Medicine, University of Cardiff

2005DSc (Hon) University of Ghent, Belgium

2004Fellow of the European Academy of Cancer Sciences

2005MD (Hon), University of Bath

2017Fellow of the Association of Cancer Physicians, UK


John Maurice Hardman Campbell

John Maurice Hardman Campbell (1891–1973) was a British physician, cardiologist, and medical journal editor.
Biography.
After education at Winchester College, J. Maurice Campbell studied at New College, Oxford, where he graduated with a first-class honours degree in physiology. He was awarded a senior demyship at Magdalen College, Oxford and entered in 1914 Guy's Hospital Medical School, where he graduated in 1916 BM BCh (Oxon.). He joined in 1916 the RAMC, served with the rank of captain in Mesopotamia and North Persia, and was twice mentioned in despatches. In June 1919 he was awarded the OBE for his services with a field ambulance.
In 1920 Campbell returned to Guy's Hospital as a medical registrar. He graduated DM in 1921 and qualified MRCP in 1921. He spent three years (from 1923 to 1925) in the department of physiology working with E. P. Poulton on oxygen therapy and with Marcus Pembrey. Campbell held from 1923 to 1927 a Beit memorial research fellowship, in 1925 resumed clinical work as a medical registrar, and in 1926 became an assistant physician at Guy's Hospital. He was elected FRCP in 1929.
At the National Heart Hospital he began working in 1926 with the cardiologist John Parkinson and in 1930 became there a consultant physician. During WWII Campbell was superintendent of the Emergency Medical Service Hospital, Orpington. At Guy's Hospital he was promoted in 1945 to general physician, and in 1948 became a cardiologist and head of the newly-founded cardiac department.
The Worshipful Company of Clothworkers sponsored a visitor exchange of senior staff members between Guy's Hospital and the Johns Hopkins Hospital. Under this sponsorship Campbell invited in 1947 Alfred Blalock to Guy's Hospital to perform the first "blue baby operation" in the UK. Campbell identified a number of patients with cyanotic heart disease as possible candidates for surgery.
Campbell delivered in 1946 the Lumleian Lectures. In 1958 he retired from active clinical practice but continued to write papers and attend medical conferences. He was president from 1956 to 1960 of the British Cardiac Society and was the chair of the British Heart Foundation upon its inception in 1961. The Royal College of Physicians award him the Moxon medal in 1966.
Campbell published in 1935 a book entitled "Sherlock Holmes and Doctor Watson: A Medical Digression" and was an active member of the Sherlock Holmes Society of London. In the autumn of 1972 he made a lecture tour of American medical centres.
J. Maurice Campbell's father was the mathematician John Edward Campbell. On 28 August 1924 in Nefyn, Caernarfonshire, Maurice Campbell married Ethel Mary Chrimes, a nurse at Guy's Hospital. He was survived by his widow, two sons and three daughters.


Independent sector treatment centre

Independent sector treatment centres (ISTCs) are private-sector owned treatment centres contracted within the English National Health Service to treat NHS patients free at the point of use. They are sometimes referred to as 'surgicentres' or ‘specialist hospitals’. ISTCs are often co-located with NHS hospitals. They perform common elective (i.e. non-emergency) surgery and diagnostic procedures and tests. Typically they undertake 'bulk' surgery such as hip replacements, cataract operations or MRI scans rather than more complex operations such as neurosurgery.
The NHS Plan 2000 originally conceived of opening eight treatment centres by 2005, but by August 2005 at least 25 had been opened, with more being planned. 46 NHS treatment centres opened between 2003 and 2009, treating approximately 300,000 patients a year with high rate of patient satisfaction (>94%).
Contracts.
Wave I ISTCs worked on pre-arranged central government bulk contracts nominally at or below the national tariff on which NHS hospitals can charge commissioning NHS primary care trusts. These contracts included a profit margin. Additional costs associated with the programme, up to a ceiling of 25% over and above the NHS Equivalent Cost, were paid for by central Government. Treatments were paid for in advance by central government whether or not the numbers paid for were taken up and regardless of success rates. The rationale was that the waiting times for patients are cut by separating routine elective surgery and tests from emergency work.
Referral rates varied across the country, with some ISTCs performing as much 115% of their contracted volumes but with the average referral rate around 85%. Pressure was put on local GPs to refer patients to the centres, rather than to NHS hospitals, because the primary care trusts had to pay for activity whether or not it was used. According to the NHS Partners Network, which represents private providers working within the health service, GP referral rates were rising in 2009 as patients report positive experiences back to their GPs.
In 2009 a "British Medical Journal" paper concluded that up to £927m of the £1.5bn first wave of ISTC contracts "may have been paid to ISTCs for patients who did not receive treatment". This was based on a Scottish example and does not in fact reflect the experience of the English ISTC program, where referrals have been more in line with the expectations of the original contracts and continue to grow.
Debate.
The Department of Health claims stated that by concentrating on a set type of procedures they are able to streamline the patient care pathway, resulting in an improved patient experience and help the NHS to quickly meet waiting time targets; however, the majority of independent research conducted to date has contradicted these claims.
A critique of this development is that more difficult and expensive work is left for NHS hospitals to do, increasing their marginal costs and making them appear less 'efficient'. An article by Angus Wallace in the British Medical Journal (BMJ vol 332 11 March 2006) suggested that treatments may be proportionally less successful in ISTCs due to the employment of inexperienced or less fully trained staff with less backup than the NHS facilities. This could result in the NHS having to fund difficult revision operations (insofar as they can be so revised) and would defeat the object of the exercise. However, a subsequent study conducted by the researchers from London School of Hygiene & Tropical Medicine and the Royal College of Surgeons of England confirmed the high quality of care, concluding that "patients undergoing cataract surgery or hip replacements in ISTCs achieved a slightly greater improvement … than those treated in NHS facilities" and "Patients treated in ISTCs were less likely to report post-operative problems than those treated in NHS facilities…"(BMC Health Services Research 2008. 8:78). ISTC contracts typically exclude referrals of older, fatter and sicker patients, so comparisons with results in NHS hospitals who deal with these more difficult patients is difficult.
In the 2008 Healthcare Commission 2008 NHS Inpatient Survey, ISTCs scored highly on a number of measures, including overall quality of care.
A British Medical Journal study in 2011 concluded: " Patients undergoing surgery in ISTCs were slightly healthier and had less severe conditions than those undergoing surgery in NHS providers. Some outcomes were better in ISTCs, but differences were small compared with the impact ISTCs could have on the provision of elective services.". Their findings supported the idea that separating elective surgical care from emergency services could improve the quality of care.
Providers.
The NHS Plan 2000 originally conceived of opening eight treatment centres by 2005, but by August 2005 at least 25 had been opened, with more being planned. A second Wave of ISTCs was completed in 2009 and those marked the end of the centrally planned centres. It was then for local PCTs to make decisions on how best to work with their local ISTCs after the initial five-year contracts have expired. This list of providers was current in 2006. Some of the centres subsequently changed hands.


Cecilia Mettler

Cecilia Charlotte Asper Mettler (October 26, 1909 – December 1, 1943) was a medical historian. She was one of the first full-time, and the first female, professors of the history of medicine in the United States.
Biography.
Mettler was born on October 26, 1909 in Weehawken, New Jersey. Her father, William Charles Asper, was a lawyer. She learned Latin at the Convent of St. Elizabeth, where she received her A.B. in 1931. She studied further at Cornell University where she received her Ph.D. in 1938. During this time she familiarized herself with medicine at the Washington University School of Nursing and at the University of Georgia School of Medicine, where her husband, Fred Mettler, worked. In 1939, she was named assistant professor of medical history at the University of Georgia School of Medicine. In 1941, they moved to New York City, where she held a position as an associate in neurology, Columbia University College of Physicians and Surgeons.
She noted that medical history is typically taught either by delivering chronological lectures or by focusing on a specific topic, and proposed to correlate medical history teaching with the teaching of the medical curriculum. Her major work, "The History of Medicine", reflected that approach. It was completed after nine years of work just a few days before her death, and published posthumously.
Mettler died on December 1, 1943, three days after the birth of her daughter.


School of Medicine, Siam University

School of Medicine, Siam University is the second private university in Thailand to be assessed for quality by the Medical Council of Thailand in 2013.
History.
The School of Medicine, Siam University, is the second private medical school in Thailand. It was established in 2013 by a group of doctors. Its first semester began in August, 2013 under the guidance of Asst. Prof. Dr. Chookiet Asawanich, Dean of Medical Faculty, with advisers such as Dr. Amorn Lelarasamee and Dr. Chaleum Warawit.
On 17 February 2013, Police General Hospital agreed to be the main site of clinical practice for the new medical program. The agreement ceased in November 2015 and was clinical teaching was undertaken in Phra Nang Klao Hospital from January 2016 onwards.


Beth Sullivan

Beth Sullivan (born August 29, 1949 in Burbank, California) is an American film and television writer and producer, best known as the creator and executive producer of the CBS series "Dr. Quinn, Medicine Woman".
Career.
Sullivan created and served as the sole executive producer of "Dr. Quinn, Medicine Woman" (a co-production of The Sullivan Company and CBS Entertainment Productions). In doing so, she was the first woman to succeed in a singular capacity in the traditionally male arena of one-hour drama "showrunners." The series received numerous Emmy and People’s Choice Award nominations and won several of each, plus a Golden Globe Award. In addition, the show attained widespread community acknowledgment, receiving the Heroes Memorial Foundation of the United States of America Founder’s Award for honorable recognition of Native Americans, the Genesis Award for spotlighting animal issues, the Family Film Award for promoting family values, the Environmental Media Award for raising environmental awareness, as well as a citation from the Library of Congress for the promotion of literacy.
Prior to "Dr. Quinn," Sullivan created and served as co-executive producer of the Emmy and Golden Globe Award-winning one-hour drama series "The Trials of Rosie O'Neill." She was a Senior TV Story Analyst, TV Division for Twentieth Century Fox and was named developer of programming in 1978.
Sullivan brought her interest in drama to prime time made-for-television movies, as well. In the 1989-90 season, two of Sullivan’s telefilms, both of which dealt with social issues, aired on NBC and CBS in November sweeps. Most notably, "" dramatized the landmark federal lawsuit that resulted in legislation to strengthen police responsibility toward battered wives. It earned both critical acclaim and the highest movie rating of the season. In addition, it received a special commendation from the Los Angeles County Board of Supervisors for its use as a training instrument for law enforcement officers. Sullivan was also honored for her work by the Los Angeles County Domestic Violence Council.
After "Dr. Quinn, Medicine Woman", Sullivan created and executive produced the one-hour drama series "Ponderosa" for NBC/PAX from January 2000 until May 2002, when she was catastrophically injured in a car crash. She was then in long-term recovery for many years, while also caring for her twins, Tess and Jack, who were only six at the time of her traumatic injury. They're now in college, and Beth has recently resumed her writing and producing career.
Sullivan is a past member of the Writers Guild of America - West Board of Directors and a former Trustee of the Guild Foundation. She is a graduate of the UCLA School of Theater, Film and Television and a former development and production executive in the television division of 20th Century Fox Studio. Sullivan has lectured in the UCLA Writers Program and taught at the American Film Institute.
For her contributions to the television industry, Sullivan received one of its highest honors, the Genii Award from the American Women in Radio and Television—now called Alliance for Women in Media—organization. As well, she has received top honors from the Women’s American Medical Association, the National Organization of the Daughters of the American Revolution, the YWCA USA, Catholics In the Media, Big Brothers Big Sisters of America and an Emmy citation from the Academy of Television Arts & Sciences for her contributions to the medium.


Maximilian Stoll

Maximilian Stoll (October 12, 1742 – May 25, 1787) was an Austrian physician who was a native of Erzingen, Baden-Württemberg.
Stoll originally trained as a theologian, with his interests later turning to medicine, and in 1776 attained a professorship at the University of Vienna. Soon afterwards, he succeeded Anton de Haen (1704–1776) at the Vienna clinic. In Vienna he worked closely with Leopold Auenbrugger (1722–1809) and Anton von Störck (1731–1803). One of Stoll's better known students was phrenologist Franz Joseph Gall (1758–1828).
Stoll is remembered for his epidemiological and systematic approach to medicine. He stressed the importance of knowing the clinical details of a patient's history, and installed a practice of keeping daily progress records of patients. He also developed a system of classifying diseases that was similar to the nosology of Thomas Sydenham (1624–1689). Stoll was one of the first practitioners of Auenbrugger's percussion methodology. In 1777 he is credited with providing the first description of gall bladder cancer.
Stoll was a popular lecturer, and is considered an important figure in the "Old Vienna School" of medicine, a group that included Auenbrugger, Störck, Gerard van Swieten (1700–1772), et al.


Eugene Floyd DuBois

Eugene Floyd DuBois (June 4, 1882 – February 12, 1959) was an American physician and teacher, remembered for his work on the physiology of fever and heat production. His grandmother Mary Ann Delafield DuBois founded a hospital in New York City in 1854.
He graduated in 1906 from the Columbia College of Physicians and Surgeons. He and Rebeckah Rutter were married in 1910. While also teaching at Cornell Medical College, he was medical director of the Russell Sage Institute of Pathology from 1911 until he retired.
During World War II, DuBois was a captain in the United States Naval Reserve, where he taught gas warfare training and defense, aviation medicine, and deep diving and submarine ventilation. Before the advent of nuclear powered submarines, DuBois spent 96 hours submerged, the record for the time.
DuBois mapped out basal metabolism for aging men, which he published in 1916. The Aub-DuBois table is still in use today.
He was most proud of the concept, worked out with David P. Barr, that the body can give off as much heat with a cool skin as with warm skin.
DuBois thought his "chief contribution was popularizing the simple, fundamental principles of metabolism in disease so that they eventually found their way into the textbooks and habits of thought."


Richard Clark (dermatologist)

Richard A.F. Clark is a dermatologist and biomedical engineer currently at the State University of New York at Stony Brook in Stony Brook, New York. Clark co-edited, with Peter M. Henson, of "The Molecular and Cellular Biology of Wound Repair" (Plenum Press, 1988) and is a contributor to wound repair, dermatology, and angiogenesis research. In addition, he is also a member of the board of directors of the Society for Investigative Dermatology.
Clark graduated from the Massachusetts Institute of Technology and has worked at the Massachusetts General Hospital. He was previously professor at Harvard University. He is now a professor at State University of New York at Stony Brook.


Pierre Barbet (physician)

Pierre Barbet (1884–1961) was a French physician, and the chief surgeon at Saint Joseph's Hospital in Paris.
By performing various experiments, Barbet introduced a set of theories on the crucifixion of Jesus.
In 1950 he wrote a long study called "A Doctor at Calvary" which was later published as a book. Barbet stated that his experience as a battlefield surgeon during World War I led him to conclude that the image on the Shroud of Turin was authentic, anatomically correct and consistent with crucifixion.


Stewart Cameron (nephrologist)

Professor John Stewart Cameron (born 1934), known as Stewart, is a British nephrologist.
Cameron undertook his medical training at Guy's Hospital and spent the large part of his career there and at King's College Medical School, into which it was merged. He eventually became professor of renal medicine.
While at Cornell University in 1962, he became interested in dialysis. He has also worked on kidney transplantation, and has written on the history of nephrology. He was president of the European Society of Paediatric Nephrology from 1975–98, the European Renal Association - European Dialysis and Transplant Association (ERA/EDTA) from 1984–87, the UK Renal Association from 1992–95, and the International Society of Nephrology (ISN) from 1993–1995. He retired from active clinical practice in 1996. He gave the Lumleian Lectures in 1997.
He was made a Commander of the Order of the British Empire (CBE) in the 1998 New Year Honours, "For services to Nephrology", and has been elected a Fellow of the Royal College of Physicians (FRCP). He was awarded the Jean Hamburger Award of the ISN in 2003, and the David M. Hume Award of the National Kidney Foundation (NKF) in 2004.


Akio Suzuki

 was a Japanese doctor, medical scientist, educator and president of Tokyo Medical and Dental University (TMDU). He was best known as an expert on heart surgery.
Early life.
Suzuki earned his medical degree from TMDU in 1956. His training continued as a surgical intern in Tokyo at the U.S. Army Hospital. He was a surgical resident at Albany Medical School in New York.
Career.
In 1950, his medical career began as a staff surgeon at St Vincent's Hospital in Cleveland, Ohio. His academic career began in 1971 as an associate professor at the medical school of the University of Mississippi. When he returned to Japan in 1974, he was a professor of chest surgery at Juntendo University.
In 1983, he joined the faculty of TMDU. He was named president of TMDU in 1995.
Legacy.
Akio Suzuki Memorial Hall at TMDU is named after the doctor's honor.


Edwin Hurry Fenwick

Edwin Hurry Fenwick (1856–1944), British urologist, early adopter of cystoscopic and x-ray technologies. It was largely through the efforts of Fenwick that urology was shaped into a specialty in Great Britain, recognized by the Royal Society of Medicine.
He is depicted by David Troughton in the BBC serial Casualty 1909, during his tenure at the London Hospital.
His name is engraved on the St Peter's Medal.


Frederick Bogue Noyes

Frederick Bogue Noyes (1872–1961) was an American dentist. His dental career began before the age of ten when he worked as an assistant to his dentist father. Noyes began dental practice before entering dental school (legal at the time), and while a student at Northwestern University Dental School, organized the first course on dental pathology in the United States, and began a long association providing illustrations for the texts of G. V. Black.
In 1908, he started a new career as an orthodontist after studying with Edward Angle. Noyes joined the University of Illinois at Chicago College of Dentistry as professor and head of the Department of Dental Histology in 1913 and became dean of the College in 1924. He was known for his willingness to experiment with change and innovation in the curriculum. Noyes served as dean of the College until 1940.


Central tolerance

Central tolerance, also known as negative selection, is the process of eliminating any "developing" T or B lymphocytes that are reactive to self. Through elimination of autoreactive lymphocytes, tolerance ensures that the immune system does not attack self peptides. Lymphocyte maturation (and central tolerance) occurs in primary lymphoid organs such as the bone marrow and the thymus. In mammals, B cells mature in the bone marrow and T cells mature in the thymus.
Central tolerance is not perfect, so peripheral tolerance exists as a secondary mechanism to ensure that T and B cells are not self-reactive once they leave primary lymphoid organs. Peripheral tolerance is distinct from central tolerance in that it occurs once developing immune cells exit primary lymphoid organs (the thymus and bone-marrow), prior to their export into the periphery.
Function of central tolerance.
Central tolerance is essential to proper immune cell functioning because it helps ensure that mature B cells and T cells do not recognize self-antigens as foreign microbes. More specifically, central tolerance is necessary because T cell receptors (TCRs) and B cell receptors (BCRs) are made by cells through random somatic rearrangement. This process, known as V(D)J recombination, is important because it increases the receptor diversity which increases the likelihood that B cells and T cells will have receptors for novel antigens. Junctional diversity occurs during recombination and serves to further increase the diversity of BCRs and TCRs. The production of random TCRs and BCRs is an important method of defense against microbes due to their high mutation rate. This process also plays an important role in promoting the survival of a species because there will be a variety of receptor rearrangement within a species meaning that there is a very high chance of at least one member of the species having receptors for a novel antigen.
While the process of somatic recombination is essential to a successful immune defense, it can lead to autoreactivity. For example, lack of functional RAG1/2, enzymes necessary for somatic recombination, has been linked to development of immune cytopenias in which antibodies are produced against the patient's blood cells. Due to the nature of a random receptor recombination, there will be some BCRs and TCRs produced that recognize self antigens as foreign. This is problematic since these B and T cells would, if activated, mount an immune system attack against self if not killed or inactivated by central tolerance mechanisms. Therefore, without central tolerance, the immune system could attack self, which is not sustainable and could result in an autoimmune disorder.
Mechanisms of central tolerance.
The end result of tolerance is a population of lymphocytes that are not reactive to self-antigens but may be able to recognize foreign, non-self antigens depending on the randomly arranged receptor. Importantly, lymphocytes can only develop tolerance towards antigens that are present in the bone marrow (for B cells) and thymus (for T cells).
B cell tolerance.
Immature B cells in the bone marrow undergo negative selection when they bind self peptides.
Properly functioning B cell receptors recognize non-self antigen or pathogen associated molecular proteins (PAMPs).
Main outcomes of autoreactivity of BCRs
T cell tolerance.
T cell central tolerance occurs in the thymus. T cells undergo positive and negative selection.
T cell receptors must have the ability to recognize self major histocompatibility complex (MHC) molecules with bound non-self peptide.
Steps of T cell tolerance
Regulatory T cells are another type of T cell that mature in the thymus. Selection of T reg cells occurs in the thymic medulla and is accompanied by the transcription of Foxp3. T reg cells are important for regulating autoimmunity by suppressing the immune system when it should not be active.
Genetic diseases caused by defects in central tolerance.
Genetic defects in central tolerance can lead to autoimmunity.
History of central tolerance.
The first use of central tolerance was by Ray Owen in 1945 when he noticed that dizygotic twin cattle did not produce antibodies when one of the twins was injected with the others blood. His findings were confirmed by later experiments by Hasek and Billingham. The results were explained by Buret's clonal selection hypothesis. Burnet and Medawar won the Nobel Prize in 1960 for their work in explaining how immune tolerance worked.


Five Year Forward View

The Five Year Forward View was produced by NHS England in October 2014 under the leadership of Simon Stevens as a planning document.
Publication and reception.
It received praise for brevity, being only 39 pages, and lacking the illustrations which had graced its predecessors. Like the NHS Plan 2000 with which Stevens was also associated it was supported by the great and good of the NHS, but in this case it was regulators - Monitor, the Care Quality Commission and the like, rather than the Royal Colleges and Trades Unions of the earlier plan. This new national leadership of the NHS issues an unprecedented warning to politicians, none of whom are included in the endorsements, that it cannot continue at current funding levels, and additional resources worth more than 1.5 per cent a year in real terms will be required.
No more top-down reorganisation was proposed, but instead the development of new models to suit local needs, something quite radical for the NHS, which is accustomed to the imposition of uniformity regardless of local conditions. It seeks to break away from Enoch Powell’s 1962 Hospital Plan for England and Wales which established the district general hospital as the central pillar of British healthcare. Even more radical is the proposal to erode the distinction between hospital consultants and General practitioners, encouraging hospitals to employ GPs - a distinction which has lasted in the UK for more than a century - and permit the development of "Accountable Care Organisations" similar to those in Spain and parts of the USA. There is much stress on the fact that 70% of the NHS budget is spent on the management of the 15 million people with long term conditions. Two new models of care – multispecialty community providers, and primary and acute care systems – involve integrating primary care and hospital care in a single provider organisation.
The fact that the word “competition” does not appear once in the document was hailed by a victory by Labour.
Stevens said that the health service would have to break out of its “narrow confines” and promote healthy lifestyles. Employers are key to promoting better health in the population and there should be incentives to encourage participation in Weight Watchers-type schemes.
The plan includes a focus on the health of NHS staff, saying that three quarters of hospitals fail to make available nutritious food for nurses and other workers on night shifts. Stevens said NHS staff should set an example by leading healthier lifestyles as part of a drive to improve the health of the nation. He pledged to get junk food out of hospital canteens.
The plan also pays far more attention to the potential for technological innovation using the internet and mobile phone and apps than any previous NHS document. Technology, it envisages, will enable self-management, integration and patient centred care. This has already been done by the Modality Partnership which is given a favourable mention in the document. It already conducts 75 per cent of consultations remotely using phone or Skype. Patients have an electronic care plan they can manage themselves, and digital access to consultant advice.
According to Nick Timmins it is the first NHS document he could recall that said NHS structures did not have to be the same everywhere.
Next steps.
This document, published in March 2017, outlined progress since 2015 and priorities for the next two years. Containing the growth in A&E admissions and bed days is to be a priority. GP practices are to be organised into area hubs covering populations of up to 50,000. At least 150 new inpatient beds for children and young people with mental health problems are to be provided. There will be reforms to increase the number of nurses and reforms to enable more flexible working.
Finance.
Its claims that the NHS could deliver £22bn of annual savings in 5 years’ time, is the latest of a long line of reports to assert that there is scope for the NHS to make major savings, but the report does make it clear that more resources, an extra £8bn in Government funding by 2020 would be needed. It claimed that there would be a "radical upgrade in prevention and public health", but as Dr Sarah Wollaston pointed out in October 2016 there were reductions in other areas of health spending outside NHS England’s budget, in particular public health. Without improvements in social care she said the NHS could not be expected to deliver the Five Year Forward View.
NHS efficiency savings of 2% to 3% a year from 2015 to 2021 were supposed to save £22 billion a year. Between 2004 and 2014 NHS output increased considerably. Hospital admissions increased by 32%, outpatient attendances by 17%, primary care consultations by 25% and community care activity by 14%. Hospital death rates reduced, especially in stroke. At the same time there was an increase in wages of 24% and an increase of 10% in the number of staff and increases in the use of equipment and supplies. As a whole NHS output increased by 47% and inputs by 31%, an increase in productivity of 12.86% during the period, or 1.37% per year, considerably less than envisaged in the Five Year Forward View.
Vanguard areas.
29 areas were selected (from 269 applicants) to pilot new models for localised healthcare in March 2015. When insufficient transformation funding was allocated in September 2016 the plans were scaled down.
Proposals for companies to run primary and acute care systems or multispecialty community providers appear to have been prevented because they would be liable for VAT.
In the 12 months to September 2017, compared to the 2014-15 financial year, there was a reduction in the rate of hospital bed days per 1,000 population - for Primary and acute care systems 0.5%, for Multispecialty community providers 1.5%, and for the rest of England 1.3%. Both MCPs and PACS saw substantially slower growth in the rate of emergency admissions per 1,000 population than the rest of England. Growth for MCPs was 2.6% and for PACS the figure was 1.2%. In the rest of England it was 4.9%.
In order to ensure the knowledge from the new models of care was captured and shared throughout the health and care system, the national new care models programme established the FutureNHS collaboration platform, built on the Kahootz collaboration software.
An evaluation study of the platform estimated that it has saved the NHS £3.5 million within its first year in 2017.
Primary and acute care systems.
Integrated primary and acute care systems will bring together GPs, hospital, community and mental health services. Money will be directed from a joint budget to wherever patients are judged to need it most:
Multispecialty community providers.
Multispecialty community providers are supposed to bring specialist services, like chemotherapy and dialysis, out of the hospital and closer to people’s homes. They were described as a "political vanity project" in April 2017 by Dr Tom Coffey, who is NHS England London clinical director of emergency care. NHS England announced three potential routes for MCP contracts in July 2016:
By August 2017 some of these providers appeared to be merging into the proposed accountable care systems.
Approved proposals:
Enhanced health in social care.
Models of enhanced health in care homes will enable the NHS and councils to work together to provide more healthcare in care homes, and to provide better preventive services there:
Urgent and emergency care.
Development of the NHS 111 is a central issue for most of these projects. It's intended that it should meet all urgent clinical needs rather than just be a signposting service so that appointments could be made directly with GPs or rapid access mental health services.
A further wave of 8 new sites were announced in July 2015:
Sustainability and transformation plans.
In February 2016 NHS organisations in England, both Clinical Commissioning Groups and NHS trusts, were grouped into 44 footprints which were each required to produce joint plans with their local authorities for health and health service transformation for the period up to 2020. Each had a leader, some from the NHS and some from local authorities.
See Sustainability and transformation plan.


Sense (molecular biology)

In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context, sense may have slightly different meanings. For example, DNA is positive-sense if an RNA version of the same sequence is translated or translatable into protein, negative-sense if not.
DNA sense.
Because of the complementary nature of base-pairing between nucleic acid polymers, a double-stranded DNA molecule will be composed of two strands with sequences that are reverse complements of each other. To help molecular biologists specifically identify each strand individually, the two strands are usually differentiated as the "sense" strand and the "antisense" strand. An individual strand of DNA is referred to as positive-sense (also positive (+) or simply sense) if its nucleotide sequence corresponds directly to the sequence of an RNA transcript which is translated or translatable into a sequence of amino acids (provided that any thymine bases in the DNA sequence are replaced with uracil bases in the RNA sequence). The other strand of the double-stranded DNA molecule is referred to as negative-sense (also negative (-) or antisense), and is reverse complementary to both the positive-sense strand and the RNA transcript. It is actually the antisense strand that is used as the template from which RNA polymerases construct the RNA transcript, but the complementary base-pairing by which nucleic acid polymerization occurs means that the sequence of the RNA transcript will look identical to the sense strand, apart from the RNA transcript's use of uracil instead of thymine.
Sometimes the phrases coding strand and template strand are encountered in place of sense and antisense, respectively, and in the context of a double-stranded DNA molecule the usage of these terms is essentially equivalent. However, the coding/sense strand need not always contain a code that is used to make a protein; both protein-coding and non-coding RNAs may be transcribed.
The terms "sense" and "antisense" are relative only to the particular RNA transcript in question, and not to the DNA strand as a whole. In other words, either DNA strand can serve as the sense or antisense strand. Most organisms with sufficiently large genomes make use of both strands, with each strand functioning as the template strand for different RNA transcripts in different places along the same DNA molecule. In some cases, RNA transcripts can be transcribed in both directions (i.e. on either strand) from a common promoter region, or be transcribed from within introns on either strand (see "ambisense" below).
Antisense DNA.
The DNA sense strand looks like the messenger RNA (mRNA) transcript, and can therefore be used to read the expected codon sequence that will ultimately be used during translation (protein synthesis) to build an amino acid sequence and then a protein. For example, the sequence "ATG" within a DNA sense strand corresponds to an "AUG" codon in the mRNA, which codes for the amino acid methionine. However, the DNA sense strand itself is not used as the template for the mRNA; it is the DNA antisense strand which serves as the source for the protein code, because, with bases complementary to the DNA sense strand, it is used as a template for the mRNA. Since transcription results in an RNA product complementary to the DNA template strand, the mRNA is complementary to the DNA antisense strand.
Hence, a base triplet 3′-TAC-5′ in the DNA antisense strand (complementary to the 5′-ATG-3′ of the DNA sense strand) is used as the template which results in a 5′-AUG-3′ base triplet in the mRNA. The DNA sense strand will have the triplet ATG, which looks similar to the mRNA triplet AUG but will not be used to make methionine because it will not be directly used to make mRNA. The DNA sense strand is called a "sense" strand not because it will be used to make protein (it won't be), but because it has a sequence that corresponds directly to the RNA codon sequence. By this logic, the RNA transcript itself is sometimes described as "sense".
Example with double-stranded DNA.
Some regions within a double-stranded DNA molecule code for genes, which are usually instructions specifying the order in which amino acids are assembled to make proteins, as well as regulatory sequences, splicing sites, non-coding introns, and other gene products. For a cell to use this information, one strand of the DNA serves as a template for the synthesis of a complementary strand of RNA. The transcribed DNA strand is called the template strand, with antisense sequence, and the mRNA transcript produced from it is said to be sense sequence (the complement of antisense). The untranscribed DNA strand, complementary to the transcribed strand, is also said to have sense sequence; it has the same sense sequence as the mRNA transcript (though T bases in DNA are substituted with U bases in RNA).
The names assigned to each strand actually depend on which direction you are writing the sequence that contains the information for proteins (the "sense" information), not on which strand is depicted as "on the top" or "on the bottom" (which is arbitrary). The only biological information that is important for labeling strands is the relative locations of the terminal 5′ phosphate group and the terminal 3′ hydroxyl group (at the ends of the strand or sequence in question), because these ends determine the direction of transcription and translation. A sequence written 5′-CGCTAT-3′ is equivalent to a sequence written 3′-TATCGC-5′ as long as the 5′ and 3′ ends are noted. If the ends are not labeled, convention is to assume that both sequences are written in the 5′-to-3′ direction. The "Watson strand" refers to 5′-to-3′ top strand (5′→3′), whereas the "Crick strand" refers to the 5′-to-3′ bottom strand (3′←5′). Both Watson and Crick strands can be either sense or antisense strands depending on the specific gene product made from them.
For example, the notation "YEL021W", an alias of the URA3 gene used in the National Center for Biotechnology Information (NCBI) database, denotes that this gene is in the 21st open reading frame (ORF) from the centromere of the left arm (L) of Yeast (Y) chromosome number V (E), and that the expression coding strand is the Watson strand (W). "YKL074C" denotes the 74th ORF to the left of the centromere of chromosome XI and that the coding strand is the Crick strand (C). Another confusing term referring to "Plus" and "Minus" strand is also widely used. Whether the strand is sense (positive) or antisense (negative), the default query sequence in NCBI BLAST alignment is "Plus" strand.
Ambisense.
A single-stranded genome that is used in both positive-sense and negative-sense capacities is said to be ambisense. Some viruses have ambisense genomes. Bunyaviruses have three single-stranded RNA (ssRNA) fragments, some of them containing both positive-sense and negative-sense sections; arenaviruses are also ssRNA viruses with an ambisense genome, as they have three fragments that are mainly negative-sense except for part of the 5′ ends of the large and small segments of their genome.
Antisense RNA.
An RNA sequence that is complementary to an endogenous mRNA transcript is sometimes called "antisense RNA". In other words, it is a non-coding strand complementary to the coding sequence of RNA; this is similar to negative-sense viral RNA. When mRNA forms a duplex with a complementary antisense RNA sequence, translation is blocked. This process is related to RNA interference. Cells can produce antisense RNA molecules naturally, called microRNAs, which interact with complementary mRNA molecules and inhibit their expression. The concept has also been exploited as a molecular biology technique, by artificially introducing a transgene coding for antisense RNA in order to block the expression of a gene of interest. Radioactively or fluorescently labelled antisense RNA can be used to show the level of transcription of genes in various cell types.
Some alternative antisense structural types have been experimentally applied as antisense therapy. In the United States, the Food and Drug Administration (FDA) has approved the phosphorothioate antisense oligonucleotides fomivirsen (Vitravene) and mipomersen (Kynamro) for human therapeutic use.
RNA sense in viruses.
In virology, the term "sense" has a slightly different meaning. The genome of an RNA virus can be said to be either positive-sense, also known as a "plus-strand", or negative-sense, also known as a "minus-strand". In most cases, the terms "sense" and "strand" are used interchangeably, making terms such as "positive-strand" equivalent to "positive-sense", and "plus-strand" equivalent to "plus-sense". Whether a viral genome is positive-sense or negative-sense can be used as a basis for classifying viruses.
Positive-sense.
Positive-sense (5′-to-3′) viral RNA signifies that a particular viral RNA sequence may be directly translated into viral proteins (e.g., those needed for viral replication). Therefore, in positive-sense RNA viruses, the viral RNA genome can be considered viral mRNA, and can be immediately translated by the host cell. Unlike negative-sense RNA, positive-sense RNA is of the same sense as mRNA. Some viruses (e.g. Coronaviridae) have positive-sense genomes that can act as mRNA and be used directly to synthesize proteins without the help of a complementary RNA intermediate. Because of this, these viruses do not need to have an RNA polymerase packaged into the virion—the RNA polymerase will be one of the first proteins produced by the host cell, since it is needed in order for the virus's genome to be replicated.
Negative-sense.
Negative-sense (3′-to-5′) viral RNA is complementary to the viral mRNA, thus a positive-sense RNA must be produced by an RNA-dependent RNA polymerase from it prior to translation. Like DNA, negative-sense RNA has a nucleotide sequence complementary to the mRNA that it encodes; also like DNA, this RNA cannot be translated into protein directly. Instead, it must first be transcribed into a positive-sense RNA that acts as an mRNA. Some viruses (e.g. influenza viruses) have negative-sense genomes and so must carry an RNA polymerase inside the virion.
Antisense oligonucleotides.
Gene silencing can be achieved by introducing into cells a short "antisense oligonucleotide" that is complementary to an RNA target. This experiment was first done by Zamecnik and Stephenson in 1978 and continues to be a useful approach, both for laboratory experiments and potentially for clinical applications (antisense therapy). Several viruses, such as influenza viruses Respiratory syncytial virus (RSV) and SARS coronavirus (SARS-CoV), have been targeted using antisense oligonucleotides to inhibit their replication in host cells.
If the antisense oligonucleotide contains a stretch of DNA or a DNA mimic (phosphorothioate DNA, 2′F-ANA, or others) it can recruit RNase H to degrade the target RNA. This makes the mechanism of gene silencing catalytic. Double-stranded RNA can also act as a catalytic, enzyme-dependent antisense agent through the RNAi/siRNA pathway, involving target mRNA recognition through sense-antisense strand pairing followed by target mRNA degradation by the RNA-induced silencing complex (RISC). The R1 plasmid hok/sok system provides yet another example of an enzyme-dependent antisense regulation process through enzymatic degradation of the resulting RNA duplex.
Other antisense mechanisms are not enzyme-dependent, but involve steric blocking of their target RNA (e.g. to prevent translation or to induce alternative splicing). Steric blocking antisense mechanisms often use oligonucleotides that are heavily modified. Since there is no need for RNase H recognition, this can include chemistries such as 2′-O-alkyl, peptide nucleic acid (PNA), locked nucleic acid (LNA), and Morpholino oligomers.


Hammer toe

A hammer toe or contracted toe is a deformity of the muscles and ligaments of the proximal interphalangeal joint of the second, third, fourth, or fifth toe causing it to be bent, resembling a hammer. In the early stage a flexible hammertoe is movable at the joints; a rigid hammertoe joint cannot be moved and usually requires surgery.
Mallet toe is a similar condition affecting the distal interphalangeal joint.
Claw toe is another similar condition, with dorsiflexion of the proximal phalanx on the lesser metatarsophalangeal joint, combined with flexion of both the proximal and distal interphalangeal joints. Claw toe can affect the second, third, fourth, or fifth toes.
Risk factors.
Older people are more likely to develop hammer toes. Women are at higher risk, due to the construction of women's shoes. Injuries to the toes, and being born with a longer second toe, increase risk. Arthritis and diabetes may also increase the risk of foot deformities.
Causes.
Hammertoes and clawtoes have multiple causes. Hammer toe most frequently results from wearing poorly fitting shoes that can force the toe into a bent position, such as high heels or shoes that are too short or narrow for the foot. Having the toes bent for long periods of time can cause the muscles in them to shorten, resulting in the hammer toe deformity. This is often found in conjunction with bunions or other foot problems (e.g., a bunion can force the big toe to turn inward and push the other toes).
The toe muscles work in pairs; if the muscles pulling in one direction are much weaker than those pulling in the other direction, the imbalance can bend the toe. If the bend persists, then as the tendons and ligaments tighten (as they do if not stretched), the bend may become permanent. Ill-fitting shoes are especially likely to push the toes out of balance.
Toe deformities can also be caused by muscle, nerve, or joint damage, resulting from conditions such as osteoarthritis, rheumatoid arthritis, stroke, Charcot–Marie–Tooth disease, complex regional pain syndrome or diabetes. Hammer toe can also be found in Friedreich's ataxia (GAA trinucleotide repeat).
Treatment.
In many cases, conservative treatment consisting of physical therapy and new shoes with soft, spacious toe boxes is enough to resolve the condition, while in more severe or longstanding cases hammertoe surgery may be necessary to correct the deformity. The patient's doctor may also prescribe some toe exercises that can be done at home to stretch and strengthen the muscles. For example, the individual can gently stretch the toes manually, or use the toes to pick things up off the floor.


Swarming motility

Swarming motility is a rapid (2–10 μm/s) and coordinated translocation of a bacterial population across solid or semi-solid surfaces, and is an example of bacterial multicellularity and swarm behaviour. Swarming motility was first reported by Jorgen Henrichsen and has been mostly studied in genus "Serratia", "Salmonella", "Aeromonas", "Bacillus", "Yersinia", "Pseudomonas", "Proteus", "Vibrio" and "Escherichia".
This multicellular behavior has been mostly observed in controlled laboratory conditions and relies on two critical elements: 1) the nutrient composition and 2) viscosity of culture medium (i.e. % agar). One particular feature of this type of motility is the formation of dendritic fractal-like patterns formed by migrating swarms moving away from an initial location. Although the majority of species can produce tendrils when swarming, some species like "Proteus mirabilis" do form concentric circles motif instead of dendritic patterns.
Biosurfactant, quorum sensing and swarming.
In some species, swarming motility requires the self-production of biosurfactant to occur. Biosurfactant synthesis is usually under the control of an intercellular communication system called quorum sensing. Biosurfactant molecules are thought to act by lowering surface tension, thus permitting bacteria to move across a surface.
Cellular differentiation.
Swarming bacteria undergo morphological differentiation that distinguish them from their planktonic state. Cells localized at migration front are typically hyperelongated, hyperflagellated and grouped in multicellular raft structures.
Ecological significance.
The fundamental role of swarming motility remains unknown. However, it has been observed that active swarming bacteria of "Salmonella typhimurium" shows an elevated resistance to certain antibiotics compared to undifferentiated cells.