Precise knowledge of the positions of aircraft would permit a reduction in the normal procedural separation standards, which in turn promised considerable increases in the efficiency of the airways system. Meta-Analysis of Observational Studies". The Russian population in Kazakhstan was ,, or
However, the delayed response between when patients first begin SSRI treatment to when they see effects has led scientists to believe that other molecules are involved in the efficacy of these drugs. The study showed decreased levels of interleukin IL -6 , a cytokine that has proinflammatory effects, in patients taking SSRIs compared to non-medicated patients. Macrophages are a subset of immune cells responsible for host defense in the innate immune system.
Macrophages can release cytokines and other chemicals to cause an inflammatory response. Peripheral inflammation can induce an inflammatory response in microglia and can cause neuroinflammation. SSRIs inhibit proinflammatory cytokine production which leads to less activation of microglia and peripheral macrophages. SSRIs not only inhibit the production of these proinflammatory cytokines, they also have been shown to upregulate anti-inflammatory cytokines such as IL Taken together, this reduces the overall inflammatory immune response.
In addition to affecting cytokine production, there is evidence that treatment with SSRIs has effects on the proliferation and viability of immune system cells involved in both innate and adaptive immunity. Evidence shows that SSRIs can inhibit proliferation in T-cells , which are important cells for adaptive immunity and can induce inflammation. SSRIs can also induce apoptosis , programmed cell death, in T-cells.
The full mechanism of action for the anti-inflammatory effects of SSRIs is not fully known. However, there is evidence for various pathways to have a hand in the mechanism. One such possible mechanism is the increased levels of cyclic adenosine monophosphate cAMP as a result of interference with activation of protein kinase A PKA , a cAMP dependent protein.
Other possible pathways include interference with calcium ion channels, or inducing cell death pathways like MAPK. The anti-inflammatory effects of SSRIs have prompted studies of the efficacy of SSRIs in the treatment of autoimmune diseases such as multiple sclerosis , RA, inflammatory bowel diseases , and septic shock.
These studies have been performed in animal models but have shown consistent immune regulatory effects. Fluoxetine , an SSRI, has also shown efficacy in animal models of graft vs. The effectiveness of this has been hypothesized to be at least in part due to the anti-inflammatory effects of SSRIs.
Large bodies of research are devoted to using genetic markers to predict whether patients will respond to SSRIs or have side effects that will cause their discontinuation, although these tests are not yet ready for widespread clinical use. SSRIs are described as ' selective ' because they affect only the reuptake pumps responsible for serotonin, as opposed to earlier antidepressants, which affect other monoamine neurotransmitters as well, and as a result, SSRIs have fewer side effects.
There appears to be no significant difference in effectiveness between SSRIs and tricyclic antidepressants , which were the most commonly used class of antidepressants before the development of SSRIs. Further, they have fewer and milder side effects.
Tricyclic antidepressants also have a higher risk of serious cardiovascular side effects, which SSRIs lack. BDNF enhances the growth and survival of cortical neurons and synapses. Fluoxetine was introduced in and was the first major SSRI to be marketed. A study examining publication of results from FDA-evaluated antidepressants concluded that those with favorable results were much more likely to be published than those with negative results.
David Healy has argued that warning signs were available for many years prior to regulatory authorities moving to put warnings on antidepressant labels that they might cause suicidal thoughts. From Wikipedia, the free encyclopedia. For other uses, see SSRI disambiguation. Serotonin , the neurotransmitter that is involved in the mechanism of action of SSRIs. Development and discovery of SSRI drugs. Biopsychiatry controversy and Biological psychiatry.
Mood Disorders and Suicide". An Integrative Approach Fifth ed. Past, Present and Future. The New York Times. Retrieved 13 July Journal of Clinical Psychopharmacology. A systematic review with meta-analysis and Trial Sequential Analysis". Advances in Psychiatric Treatment NICE clinical guidelines 90 and Archived from the original PDF on September 28, The International Journal of Neuropsychopharmacology.
Archives of General Psychiatry. Annals of Internal Medicine. The Cochrane Database of Systematic Reviews. The Cochrane Database of Systematic Reviews 2: Core interventions in the treatment of obsessive-compulsive disorder and body dysmorphic disorder" PDF. The Cochrane Database of Systematic Reviews 3: Archived from the original on April 13, Department of Health and Human Services. Archived from the original on The Urologic Clinics of North America.
Journal of the American Pharmacists Association. The Journal of Clinical Psychiatry. The Open Psychology Journal. Neurology of Sexual and Bladder Disorders. Handbook of Clinical Neurology. Diagnostic and Statistical Manual of Mental Disorders 5th ed. The American Journal of Psychiatry. A Potentially Avoidable Therapeutic Challenge". Current Women's Health Reports. Meta-Analysis of Observational Studies".
British Journal of Clinical Pharmacology. New England Journal of Medicine. Archives of Family Medicine. QT interval prolongation—new maximum daily dose restrictions including in elderly patients , contraindications, and warnings. Expert Opinion on Drug Safety. The Maudsley prescribing guidelines in psychiatry. Over one million political prisoners from various parts of the Soviet Union passed through the Karaganda Corrective Labor Camp KarLag between and , with an unknown number of deaths.
The influx of immigrants , mostly Russians , skewed the ethnic mixture and enabled non-Kazakhs to outnumber natives. As a result, the use of the Kazakh language declined, but has started to experience a revival since independence, both as a result of its resurging popularity in law and business and the growing proportion of Kazakhs. Kazakh independence has caused many of these newcomers to emigrate. Following the dismissal of Dinmukhamed Konayev , the First Secretary of the Communist Party of Kazakhstan by the last Soviet leader, Mikhail Gorbachev , the riots broke out for four days between December 16 to December 19, known as Jeltoqsan by student demonstrators in Brezhnev Square in the capital city, Alma-Ata.
Approximately civilians were killed in the uprising. The events were then spilled over to Shymkent , Pavlodar , Karaganda and Taldykorgan. On March 25, , Kazakhstan held its first elections with Nursultan Nazarbayev , the chairman of the Supreme Soviet elected as its first president.
Later that year on October 25, it then declared sovereignty. The republic participated in a referendum to preserve the union in a different entity with It did not happen when hardline communists in Moscow took control of the government in August. Nazarbayev then condemned the failed coup. It became independent on December 16 the fifth anniversary of Jeltosqan , becoming the last republic to secede from the USSR.
Its capital was the site of the Alma-Ata Protocol on December 21, that dissolved the Soviet Union and formed the Commonwealth of Independent States in its place which Kazakhstan joined. The Soviet Union officially ceased to exist as a sovereign state on December 26, and Kazakhstan became an internationally recognized independent state.
On January 28, , the new Constitution of Kazakhstan was officially adopted. According to the census, the earliest census taken in the region, Kazakhs constituted The Russian population in Kazakhstan was ,, or Ethnic Composition of Kazakhstan census data . A mode-C interrogation produces an pulse response pulse D1 is not used , indicating aircraft altitude as indicated by its altimeter in foot increments. Mode B gave a similar response to mode A and was at one time used in Australia.
Mode D has never been used operationally. The new mode, Mode S, has different interrogation characteristics. It comprises pulses P1 and P2 from the antenna main beam to ensure that Mode-A and Mode-C transponders do not reply, followed by a long phase-modulated pulse. The ground antenna is highly directional but cannot be designed without sidelobes. Aircraft could also detect interrogations coming from these sidelobes and reply appropriately.
However these replies can not be differentiated from the intended replies from the main beam and can give rise to a false aircraft indication at an erroneous bearing. To overcome this problem the ground antenna is provided with a second, mainly omni-directional, beam with a gain which exceeds that of the sidelobes but not that of the main beam.
An aircraft detecting P2 stronger than P1 therefore in the sidelobe and at the incorrect main lobe bearing , does not reply. Although 4, different identity codes available in a mode A reply may seem enough, once particular codes have been reserved for emergency and other purposes, the number is significantly reduced. Clearly the same mode A code should not be given to two aircraft at the same time as the controller on the ground could be given the wrong callsign with which to communicate with the aircraft.
The mode C reply provides height increments of feet, which was initially adequate for monitoring aircraft separated by at least feet. However, as airspace became increasingly congested, it became important to monitor whether aircraft were not moving out of their assigned flight level. A slight change of a few feet could cross a threshold and be indicated as the next increment up and a change of feet. Smaller increments were desirable. Several successive FRUIT replies could combine and appear to indicate an aircraft which does not exist.
As air transport expands and more aircraft occupy the airspace, the amount of FRUIT generated will also increase. FRUIT replies can overlap with wanted replies at a ground receiver, thus causing errors in extracting the included data. A solution is to increase the interrogation rate so as to receive more replies, in the hope that some would be clear of interference. The process is self-defeating as increasing the reply rate only increases the interference to other users and vice versa.
If two aircraft paths cross within about two miles slant range from the ground interrogator, their replies will overlap and the interference caused will make their detection difficult. Typically the controller will lose the longer range aircraft, just when the controller may be most interested in monitoring them closely.
While an aircraft is replying to one ground interrogation it is unable to respond to another interrogation, reducing detection efficiency. Accuracy can be improved by making many interrogations as the antenna beam scans an aircraft and a better estimate can be obtained by noting where the replies started and where stopped and taking the centre of the replies as the direction of the aircraft.
This is known as a sliding window process. The early system used an antenna known as a hogtrough. This has a large horizontal dimension to produce a narrow horizontal beam and a small vertical dimension to provide cover from close to the horizon to nearly overhead. There were two problems with this antenna.
First, nearly half the energy is directed at the ground where it is reflected back up, and interferes with, the upward energy causing deep nulls at certain elevation angles and loss of contact with aircraft. Second, if the surrounding ground is sloping, then the reflected energy is partly offset horizontally, distorting the beam shape and the indicated bearing of the aircraft.
This was particularly important in a monopulse system with its much improved bearing measurement accuracy. The deficiencies in modes A and C were recognised quite early in the use of SSR and in Ullyatt published a paper  and in an expanded paper,  which proposed improvements to SSR to address the problems.
The essence of the proposals was new interrogation and reply formats. Aircraft identity and altitude were to be included in the one reply so collation of the two data items would not be needed.
To protect against errors a simple parity system was proposed — see Secondary Surveillance Radar — Today and Tomorrow. The FAA were also considering similar problems but were assuming that a new pair of frequencies would be required. Monopulse, which means single pulse, had been used in military track-and-follow systems whereby the antenna was steered to follow a particular target by keeping the target in the centre of the beam.
Ullyatt proposed the use of a continuously rotating beam with bearing measurement made wherever the pulse may arrive in the beam. Further the proposed aircraft identity code also comprised 24 bits with 16 million permutations. This allowed each aircraft to be wired with its own unique address. Blocks of addresses are allocated to different countries  and further allocated to particular airlines so that knowledge of the address could identify a particular aircraft.
Functional Description gave details on the proposed new system. The only thing needed was an international name. Much had been made of the proposed new features but the existing ground SSR interrogators would still be used, albeit with modification, and the existing airbound transponders, again with modification.
The best way of showing that this was an evolution not a revolution was to still call it SSR but with a new mode letter. Mode S was the obvious choice, with the S standing for select. In ICAO issued an advisory circular, which described the new system.
The problem with the existing standard "hogtrough" antenna was caused by the energy radiated toward the ground, which was reflected up and interfered with the upwards directed energy. The answer was to shape the vertical beam. This necessitated a vertical array of dipoles suitably fed to produce the desired shape. A five-foot vertical dimension was found to be optimum and this has become the international standard.
The new Mode S system was intended to operate with just a single reply from an aircraft, a system known as monopulse. The accompanying diagram shows a conventional main or "sum" beam of an SSR antenna to which has been added a "difference" beam.