Stereoscopic motion

Stereoscopic motion, as introduced by Béla Julesz in his book "Foundations of Cyclopean Perception" of 1971, is a translational motion of figure boundaries defined by changes in binocular disparity over time in a real-life 3D scene, a 3D film or other stereoscopic scene. This translational motion gives rise to a mental representation of three dimensional motion created in the brain on the basis of the binocular motion stimuli. Whereas the motion stimuli as presented to the eyes have a different direction for each eye, the stereoscopic motion is perceived as yet another direction on the basis of the views of both eyes taken together. Stereoscopic motion, as it is perceived by the brain, is also referred to as "cyclopean motion", and the processing of visual input that takes place in the visual system relating to stereoscopic motion is called "stereoscopic motion processing".
Provided the binocular motion stimuli correspond to a physical object moving in 3D space, the stereoscopic motion closely represents its actual motion. Alternatively, the images with the binocular motion stimuli can be artificially created, for instance using dynamic random dot stereograms.
Cyclopean (stereoscopic) motion and cyclopean images are aspects of so-called "cyclopean vision" – named after the mythical giant Cyclops who had only one eye – involving a mental representation of objects in space as if they were perceived in full depth and from a position of a "cyclopean eye" situated approximately between the two eyes.
By definition, individuals who have only monocular vision do not perform stereoscopic motion processing. They rely instead on monocular depth cues to perceive motion in space ("see also:" kinetic depth effect).
Sensing and processing.
Stereoscopic motion is sensed in a way that cannot be explained by feature tracking or by inferring the motion from memory of position and time, and it appears to involve specific low-level motion sensing. Purely binocular motion stimuli appear to influence also stereoblind persons as far as their sensation of self-motion is concerned. Using dynamic random dot stereograms presented using a virtual reality head-mounted display, it was demonstrated from subjects' performance on real-world tasks of ball catching and obstacle avoidance that stereoscopic motion can derive from purely binocular stimuli, that is, without requiring any first-order motion perception. In other words, motion can be derived without using retinal flow, instead using optical flow understood in a more abstract sense.
It has been shown that also the adaptation to moving disparity information induces a motion aftereffect. This effect is called the "stereoscopic motion aftereffect" to distinguish it from the more well-known luminance motion aftereffect.
How the brain combines different cues, including stereo cues, motion cues (both temporal changes in disparity and monocular velocity ratios), vergence angle and monocular cues for sensing motion in depth and 3D object position is an area of active research in vision science and neighboring disciplines.


Current of injury

The current of injury – also known as the "demarcation current" or "hermann's demarcation current" – is the electric current from the central part of the body to an injured nerve or muscle, or to another injured excitable tissue. The injured tissue has a negative voltage compared to the central part of the body.
History.
The concept originates from the research of Carlo Matteucci and Emil du Bois-Reymond in the mid-19th century. It has later occasionally been used in physiology textbooks, but is now mostly used in connection with heart damages (as listed in e.g. the index of Guyton's "Textbook of Medical Physiology"). Such manifestations in the heart may be seen in the electrocardiogram as Osborn waves.
It has been found by Elmer J. Lund that establishing an artificial electrical field causing a current mimicking the current of injury could facilitate regeneration. This potential for a regeneration therapy was further studied by Robert O. Becker, who described this work in his book "The Body Electric". He found that the current of injury runs through the perineurium – through the myelin sheaths of the peripheral nerves.


Duygu Asena

Duygu Asena (April 19, 1946 – July 30, 2006) was a Turkish journalist, best-selling author and activist for women’s rights.
Legacy.
Since 2007 PEN Turkey has been presenting an award entitled Duygu Asena Women’s Rights Award. A Google Doodle commemorated Asena’s 73rd birth anniversary on 19 April 2019.


Jinnat Ali

Jinnat Ali (1996 – 28 April 2020) was a Bangladeshi citizen, and the tallest person from Bangladesh.
Biography.
Jinnat Ali was born in 1996 in Barabili, in the village of Gorjania union under Ramu Upazila of Cox's Bazar, Bangladesh, to farmer Amir Hamza and Shahampura Begum. Ali was the second of the three sons of his parents. He lived with his parents, a sister, and two brothers. Family sources stated Ali's body suddenly started to grow abnormally in childhood. His body continued to grow at the age of 23. Ali's height was predicted to keep increasing, and therefore he had to eat at least a kilogram of food every day to keep a sufficient muscle mass and healthy weight. According to Md Farid Uddin, the doctor of BSMMU, Ali suffered from acromegalic gigantism — a condition caused by a tumor on his pituitary gland which caused his body to produce too much growth hormone.
Personal life.
Ali's height was increasing unnaturally due to a hormonal imbalance, and medical treatments were unable to solve the ongoing condition and its complications. In 2018, physicians treating Ali informed him he was suffering from a brain tumor when Ali was admitted at Bangabandhu Sheikh Mujib Medical University (BSMMU) in 2018. Subsequently, Bangladesh Prime Minister Sheikh Hasina gifted Ali and his family a house to make Ali's life and the life of his family more comfortable under the circumstances, after Ali met with the Prime Minister in 2018.
Treatment and death.
Ali underwent treatment for his hormonal imbalance at Bangabandhu Sheikh Mujib Medical University in Dhaka. However, Jinnat Ali died April 28, 2020, while on life support in the neurosurgery department of Chittagong Medical College Hospital due to a brain tumor and other complications.


Biochanin A

Biochanin A is an "O"-methylated isoflavone. It is a natural organic compound in the class of phytochemicals known as flavonoids. Biochanin A can be found in red clover in soy, in alfalfa sprouts, in peanuts, in chickpea ("Cicer arietinum") and in other legumes.
Biochanin A is classified as a phytoestrogen and has putative benefits in dietary cancer prophylaxis. It has also been found to be a weak inhibitor of fatty acid amide hydrolase "in vitro".
Biochanin A can block the vasoconstriction in a dose-dependent manner due to the inhibition of L-type calcium channels. Such vasodilatory effect, in micromolar concentrations, is of potential clinical interest for the management of cardiovascular pathologies.
Metabolism.
The enzyme biochanin-A reductase uses dihydrobiochanin A and NADP+ to produce biochanin A, NADPH, and H+. The enzyme isoflavone-7-O-beta-glucoside 6"-O-malonyltransferase uses malonyl-CoA and biochanin A 7-O-β--glucoside to produce CoA and biochanin A 7-O-(6-O-malonyl-β--glucoside).


Posterior thoracic nucleus

The posterior thoracic nucleus, (Clarke's column, column of Clarke, dorsal nucleus, nucleus dorsalis of Clarke) is a group of interneurons found in the medial part of lamina VII, also known as the intermediate zone, of the spinal cord. It is mainly located from the cervical vertebra C7 to lumbar L3-L4 levels and is an important structure for proprioception of the lower limb.
Anatomy.
It occupies the medial part of the base of the posterior grey column and appears on the transverse section as a well-defined oval area.
It begins caudally at the level of the second or third lumbar nerve, and reaches its maximum size opposite the twelfth thoracic nerve. Above the level of the eight thoracic nerve its size diminishes, and the column ends opposite the last cervical or first thoracic nerve.
It is represented, however, in the other regions by scattered cells, which become aggregated to form a cervical nucleus opposite the third cervical nerve, and a sacral nucleus in the middle and lower part of the sacral region.
Nerve cells in the posterior thoracic nucleus are most abundant between the lower thoracic and upper lumbar segments. Cell bodies are of medium size and oval- or pyriform-shape. These cells characteristically present coarse Nissl granules and have characteristic eccentric nuclei.
Axonal projections from neurons in this nucleus give rise to the dorsal spinocerebellar tract which ascends ipsilaterally through the spinal cord and ends as mossy fibers in the ipsilateral cerebellar cortex after passing through the inferior cerebellar peduncle.
Axons originating from the posterior thoracic nucleus which ascend contralaterally through the lateral funiculus of the spinal cord are named ventral spinocerebellar tract which cross over again within the white matter of the cerebellum, to ultimately end on its ipsilateral side.
Function.
The posterior thoracic nucleus is a major relay center for unconscious proprioception. Sensory information from muscle spindles and tendon organs is carried by axons of larger neurons in dorsal root ganglia, which synapse onto neurons in the spinal cord including the posterior thoracic nucleus. From here information continues rostrally until it reaches the cerebellar cortex. This relay pathway is generally known as the dorsal spinocerebellar tract.
Diseases.
It has been observed that in Friedreich's ataxia there is evident degeneration of the posterior thoracic nucleus as well as other proprioceptive spinal tracts. These patients might present with ataxia, dysarthria, muscle weakness or paralysis and skeletal defects.
Eponym.
Clarke's column is named for Jacob Augustus Lockhart Clarke.


Medical uses of bicalutamide

The medical uses of bicalutamide, a nonsteroidal antiandrogen (NSAA), include the treatment of androgen-dependent conditions and hormone therapy to block the effects of androgens. Such indications include the treatment of prostate cancer in men, skin and hair conditions such as acne, seborrhea, hirsutism, and pattern hair loss in women, high testosterone levels in women, hormone therapy in transgender women, as a puberty blocker to prevent puberty in transgender girls and to treat early puberty in boys, and the treatment of long-lasting erections in men. It may also have some value in the treatment of paraphilias and hypersexuality in men.
Prostate cancer.
Bicalutamide is used primarily in the treatment of early and advanced prostate cancer. It is approved at a dosage of 50 mg/day as a combination therapy with a gonadotropin-releasing hormone analogue (GnRH analogue) or orchiectomy (that is, surgical or medical castration) in the treatment of stage D2 metastatic prostate cancer (mPC), and as a monotherapy at a dosage of 150 mg/day for the treatment of stage C or D1 locally advanced prostate cancer (LAPC). Although effective in and , bicalutamide is no longer indicated for the treatment of localized prostate cancer (LPC) due to negative findings in the Early Prostate Cancer (EPC) trial. Prior to the introduction of the newer enzalutamide in 2012, bicalutamide was considered to be the standard-of-care antiandrogen in the treatment of prostate cancer, and still remains widely used for this indication. Compared to earlier antiandrogens like the steroidal antiandrogen (SAA) cyproterone acetate (CPA) and the flutamide and nilutamide, bicalutamide shows an improved profile of effectiveness, tolerability, and safety, and for this reason has largely replaced them in the treatment of prostate cancer.
In the early 1940s, it was discovered that growth of prostate cancer in men regressed with surgical castration or high-dose estrogen therapy, which produced very low levels of circulating testosterone, and accelerated with the administration of exogenous testosterone. It has since been elucidated that androgens like testosterone and dihydrotestosterone (DHT) function as trophic factors for the prostate gland, stimulating cell division and proliferation and producing tissue growth and glandular enlargement, which, in the context of prostate cancer, results in stimulation of tumors and a considerable acceleration of disease progression. As a result of these discoveries, androgen deprivation therapy (ADT), via a variety of modalities including surgical castration, high-dose estrogens, , analogues, , and androgen biosynthesis inhibitors (e.g., abiraterone acetate), has become the mainstay of treatment for prostate cancer. Although can shrink or stabilize prostate tumors and hence significantly slow the course of prostate cancer and prolong life, it is not generally curative. While effective in slowing the progression of the disease initially, most advanced prostate cancer patients eventually become resistant to and prostate cancer growth starts to accelerate again, in part due to progressive mutations in the androgen receptor (AR) that result in the transformation of drugs like bicalutamide from antagonists to agonists.
A few observations form the basis of the reasoning behind combined androgen blockade (CAB), in which castration and an are combined. It has been found that very low levels of androgens, as in castration, are able to significantly stimulate growth of prostate cancer cells and accelerate disease progression. Although castration ceases production of androgens by the gonads and reduces circulating testosterone levels by about 95%, low levels of androgens continue to be produced by the adrenal glands, and this accounts for the residual levels of circulating testosterone. Moreover, it has been found that prostate gland levels of , which is the major androgen in the prostate, remain at 40 to 50% of their initial values following castration. This has been determined to be due to uptake of circulating weak adrenal androgens like dehydroepiandrosterone (DHEA) and androstenedione (A4) by the prostate and their "de novo" transformation into testosterone and . As such, a considerable amount of androgen signaling continues within the prostate gland even with castration.
In the past, surgical adrenalectomy and early androgen biosynthesis inhibitors like ketoconazole and aminoglutethimide were successfully employed in the treatment of castration-resistant prostate cancer. However, adrenalectomy is an invasive procedure with high morbidity, ketoconazole and aminoglutethimide have relatively high toxicity, and both treatment modalities require supplementation with corticosteroids, making them in many ways unideal. The development of with like bicalutamide and enzalutamide and with newer and more tolerable androgen biosynthesis inhibitors like abiraterone acetate has since allowed for non-invasive, convenient, and well-tolerated therapies that have replaced the earlier modalities.
Subsequent clinical research has found that monotherapy with higher dosages of than those used in is roughly equivalent to castration in extending life in men with prostate cancer. Moreover, monotherapy is overall better tolerated and associated with greater quality of life than is castration, which is thought to be related to the fact that testosterone levels do not decrease with monotherapy and hence by extension that levels of biologically active and beneficial metabolites of testosterone such as estrogens and neurosteroids are preserved. For these reasons, monotherapy has become an important alternative to castration and in the treatment of prostate cancer.
Bicalutamide may be used to reduce the effects of the testosterone flare at the initiation of agonist therapy.
The combination of bicalutamide with an estrogen such as ethinylestradiol sulfonate has been used as a form of and as an alternative to the combination of bicalutamide with surgical or medical castration.
Skin and hair conditions.
Androgens like testosterone and play a critical role in the pathogenesis of a number of dermatological conditions including acne, seborrhea, hirsutism (excessive facial/body hair growth in women), and pattern hair loss (androgenic alopecia). In demonstration of this, women with complete androgen insensitivity syndrome (CAIS) do not produce sebum or develop acne and have little to no body, pubic, or axillary hair. Moreover, men with congenital 5α-reductase type II deficiency, 5α-reductase being an enzyme that greatly potentiates the androgenic effects of testosterone in the skin, have little to no acne, scanty facial hair, reduced body hair, and reportedly no incidence of male pattern hair loss. Conversely, hyperandrogenism in women, for instance due to polycystic ovary syndrome (PCOS) or congenital adrenal hyperplasia (CAH), is commonly associated with acne and hirsutism as well as virilization (masculinization) in general. In accordance with the preceding, antiandrogens have been found to be highly effective in the treatment of the aforementioned androgen-dependent skin and hair conditions.
Low-dose bicalutamide has been found to be effective in the treatment of hirsutism in women in clinical studies. In one of the studies, the medication was well tolerated, all of the patients experienced a visible decrease in hair density, and a highly significant clinical improvement was observed with the Ferriman–Gallwey score decreasing by 41.2% at 3 months and by 61.6% at 6 months (from 22.0 ± 5.1 to 8.6 ± 3.5). According to a 2013 review, "Low dose bicalutamide (25 mg/day) was shown to be effective in the treatment of hirsutism related to and . It does not have any significant side effects [or lead] to irregular periods." In 2017, the combination of bicalutamide with a combined birth control pill was evaluated in a phase III clinical trial for the treatment of severe hirsutism in women with , and was found to be significantly more effective than a combined birth control pill alone. In addition, bicalutamide was shown to be safe and to produce no side effects, except for a significant increase in total cholesterol and low-density lipoprotein levels. A 2019 study reported bicalutamide to be effective in the treatment of scalp hair loss in women.
In addition to hirsutism, bicalutamide can be used in the treatment of acne in women. Flutamide has generally been found to reduce symptoms of acne by 80 or 90% even at low doses, with several studies showing complete acne clearance. In one study, it decreased acne scores by 80% within 3 months, whereas the spironolactone decreased symptoms by only 40% in the same time period. Bicalutamide has an antiandrogenic efficacy that is comparable to or greater than that of flutamide, and would be expected to produce similar therapeutic benefits. Other androgen-dependent skin and hair conditions, such as seborrhea and pattern hair loss, may also be treated by bicalutamide. In addition to acne, flutamide has been found to produce an 80% or greater decrease in scores of seborrhea and androgen-dependent scalp hair loss. Moreover, in combination with a combined birth control pill, flutamide treatment resulted in an increase in cosmetically acceptable scalp hair density in almost all women suffering from pattern hair loss in one small study. Bicalutamide is an appealing alternative to flutamide for the treatment of androgen-dependent skin and hair conditions in women because flutamide has a considerable risk of serious liver toxicity, which bicalutamide does not share.
Antiandrogens like flutamide and bicalutamide are male-specific teratogens which can feminize male fetuses due to their antiandrogen effects. For this reason, they are not recommended by the Food and Drug Administration for use in women. Because of this risk, it is strongly recommended that antiandrogens only be used to treat women who are of reproductive age in conjunction with adequate contraception. Birth control pills, which contain an estrogen and a progestin, are typically used for this purpose. Moreover, birth control pills themselves are functional antiandrogens and are independently effective in the treatment of androgen-dependent skin and hair conditions; hence, they can significantly augment the effectiveness of antiandrogens in the treatment of such conditions.
Transgender hormone therapy.
Bicalutamide is used as an antiandrogen in feminizing hormone therapy for transgender women and as a puberty blocker in adolescent transgender girls. It can be used in transgender females both in combination with an estrogen and alone. The medication directly blocks the effects of androgens like testosterone and dihydrotestosterone in the body, and, when used by itself, also induces a significant increase in estradiol levels. As a result, bicalutamide causes demasculinization, and can additionally promote feminization, even without concomitant use of an estrogen. This is analogous to what occurs in women with a defective due to complete androgen insensitivity syndrome. Demasculinizing and feminizing effects of bicalutamide in those assigned male at birth include breast development, reduced male-pattern hair, decreased muscle mass, feminine changes in fat distribution, decreased sex drive, and reduced spontaneous erections. Dosages of bicalutamide of 25 to 50 mg/day have been employed and recommended for use in transgender females. However, lower doses of bicalutamide may also be effective for such purposes.
Unlike various other antiandrogens, bicalutamide when used as a monotherapy significantly increases testosterone and estradiol levels in individuals assigned male at birth, and hence can have indirect estrogenic effects in transgender women. This is desirable in transgender women, as it can help promote feminization. However, bicalutamide does not increase sex hormone levels if combined with adequate doses of an antigonadotropin such as a analogue, estrogen, or progestogen, due to the negative feedback effects of these medications on sex-hormone production. Because bicalutamide does not lower androgen levels, it may be a particularly favorable antiandrogen for transgender women who wish to help preserve sex drive, sexual function, and/or fertility, as antiandrogens that strongly suppress levels of testosterone and its metabolites, such as and modulators, can greatly disrupt these functions. Although bicalutamide has the potential to increase testosterone levels, there is no effect of this testosterone due to the blockade of the by bicalutamide.
Neyman et al. (2017, 2019) studied bicalutamide as a puberty blocker in adolescent transgender girls. It was assessed both alone and in combination with an estrogen. The patients were 14 transgender girls with a mean age of 15.8 years (range 12 to 18.4 years) who were treated with 50 mg/day bicalutamide between 2013 and 2017, of whom 7 returned for follow-up. In addition to showing effectiveness as an antiandrogen in the individuals, bicalutamide monotherapy increased estradiol levels and promoted feminization as a secondary effect. This included breast development to Tanner stage 2 and 3 in 86% of the patients after an average of 5.7 months of treatment, with the seventh girl showing Tanner stage 3 breast development at her second follow-up at 12.5 months. Testosterone levels were 524 to 619 ng/dL and estradiol levels were 26 to 61 pg/mL in the patients. Liver function tests were performed and were unremarkable. Although analogues are the first-line treatment to prevent puberty in transgender adolescents, they are very expensive and are often denied by medical insurance. According to the researchers, bicalutamide represents a potential alternative to analogues as a puberty blocker in transgender girls.
Studies assessing bicalutamide as an antiandrogen in transgender women are quite limited at present. In any case, bicalutamide is clinically effective as an antiandrogen in women with hirsutism due to hyperandrogenism (including in a phase III trial) and in boys with precocious puberty, and demasculinization and feminization are well-documented effects of bicalutamide in men treated with it for prostate cancer. In addition, nilutamide, a closely related antiandrogen with the same mechanism of action as bicalutamide, has been evaluated in transgender women in at least five small clinical studies. It was given at a high dosage of 300 mg/day, the same dosage at which it has been used as a monotherapy in the treatment of prostate cancer. The corresponding monotherapy dosage of bicalutamide in the treatment of prostate cancer is 150 mg/day. Flutamide has also been employed as an antiandrogen in transgender women, with at least two treatment centers reporting its frequent use.
In the clinical studies of nilutamide for transgender hormone therapy, the medication, given alone and not in combination with an estrogen, induced observable signs of clinical feminization in young transgender women (ages 19 to 33 years) within 8 weeks. These changes included breast development, decreased male-pattern hair, decreased spontaneous erections and sex drive, and positive psychological and emotional changes. Signs of breast development, such as increased nipple sensitivity, were, along with decreased male-pattern hair, the earliest indications of feminization, and occurred in all subjects within 6 weeks. Nilutamide by itself more than doubled luteinizing hormone (LH) and testosterone levels and tripled estradiol levels. The addition of 100 μg/day oral ethinylestradiol to nilutamide therapy after 8 weeks abolished the increase in , testosterone, and estradiol levels and dramatically suppressed testosterone levels, into the female/castrate range. On the basis of these results, both nilutamide alone, and particularly the combination of nilutamide and an estrogen, were regarded as effective in terms of producing antiandrogenic effects and feminization in transgender women.
Although nilutamide has been found to be effective for transgender hormone therapy, the use of nilutamide in the treatment of prostate cancer and particularly for other indications that are of a less clinically serious nature is now discouraged due to the unique adverse effects of the medication, most importantly a high incidence of interstitial pneumonitis. This is an adverse effect that can progress to pulmonary fibrosis and can potentially be fatal. Flutamide is also no longer recommended due to excessive risk of hepatotoxicity and liver failure in men with prostate cancer. For these reason, newer and safer like bicalutamide have largely replaced flutamide and nilutamide, and are now used for relevant indications instead. As selective antagonists, flutamide, nilutamide, and bicalutamide have the same mechanism of action, and bicalutamide has similar or greater efficacy to flutamide and nilutamide as an antiandrogen.
Bicalutamide is known to have a small risk of elevated liver enzymes and hepatotoxicity at dosages of 50 mg/day and above. As a result, it is recommended that liver function tests (LFTs) periodically be performed. One recommended procedure is to check LFTs at baseline, at one month, at two months, and then every 6 months thereafter, for lifetime. The risk of elevated liver enzymes and liver failure with bicalutamide appears to be much smaller than with , which is the most widely used antiandrogen in transgender women in Europe and elsewhere in the world. In the United States, one of the only countries where has not been approved for medical use, the relatively weak and non-selective antiandrogen spironolactone is commonly used in transgender women instead. Bicalutamide is a favorable alternative option to these antiandrogens in transgender females. It is much more potent than and spironolactone as an antagonist. However, is a more potent antiandrogen than bicalutamide in the context of male levels of testosterone, due to its additional action of substantially suppressing testosterone levels at low doses. In transgender women who do not achieve their desired results or are unable to tolerate the side effects of other antiandrogens, clinicians sometimes introduce or switch to bicalutamide.
Male early puberty.
Bicalutamide is used in combination with an aromatase inhibitor such as anastrozole or letrozole in the treatment of peripheral precocious puberty in young boys. The combination has specifically been used to treat male peripheral precocious puberty due to familial male-limited precocious puberty (FMPP, otherwise known as testotoxicosis) and, to a lesser extent, McCune–Albright syndrome. Whereas antigonadotropic medications such as modulators and progestogens like cyproterone acetate and medroxyprogesterone acetate are normally used to treat central precocious puberty, these medications are less or not at all effective in peripheral precocious puberty, as this type of precocious puberty is independent of gonadotropin secretion. Instead, androgens and estrogens must be more directly inhibited in peripheral precocious puberty via the use of sex-hormone receptor antagonists and synthesis inhibitors. A dosage of bicalutamide of 2 mg/kg (or about 40 to 60 mg in boys that are 20 to 30 kg or 45 to 65 lbs) once daily is recommended for use in male peripheral precocious puberty. Bicalutamide is used to block the actions of androgens in the condition, while the aromatase inhibitor is used to decrease levels of estrogens. The goal of treatment is to prevent further development of secondary sexual characteristics, and particularly to slow the rate of growth and improve final adult height.
Due to the rare nature of peripheral precocious puberty, medications used in the treatment of the condition have only been studied limitedly in small numbers of patients. The largest and sole study employing bicalutamide, an industry-sponsored, phase II, multicenter, international, open-label, single-arm clinical trial known as the icalutamide and nastrozole of estotoxicosis (BATT) study, assessed the combination of 12.5 to 100 mg/day bicalutamide and 0.5 to 1 mg/day anastrozole over a period of 12 months in 14 young boys with . The mean age of the boys was 4 ± 2 years, with a range of 2 to 9 years of age. At baseline, the boys weighed 23 ± 6 kg (52 ± 12 lbs) on average, with a range 17 to 35 kg (37 to 77 lbs). Mean total levels of testosterone in the boys were 277 ± 208 ng/dL at baseline and increased to 523 ± 258 ng/dL at 6 months and 427 ± 243 ng/dL at 12 months. Mean total levels of estradiol in the boys were 3.8 pg/mL at baseline and were relatively unchanged at 6 and 12 months (2.5 pg/mL and 3.5 pg/mL, respectively). The dosage of bicalutamide was initiated at 12.5 mg/day and was then increased, with adjustment as necessary to maintain trough circulating ("R")-bicalutamide concentrations within a target range of 5 to 15 μg/mL. This range is similar to ("R")-bicalutamide levels achieved with approximately 30 to 100 mg/day bicalutamide in adult men with prostate cancer. The mean final dosage of bicalutamide in the boys at 12 months was 60 ± 29 mg/day, with 86% of the boys on either 50 or 100 mg/day bicalutamide. Levels of ("R")-bicalutamide were proportional to dosage and did not appear to be related to the age or weight of the boys.
In the trial, growth velocity was decreased, bone age advancement was slowed, aggressiveness was decreased, and masculinization, measured via Tanner staging of pubic hair and genitals, did not appear to further progress. However, the decrease in growth rate was modest and fell just short of reaching statistical significance ("p" = 0.053). Conversely, although the decrease in rate of bone maturation was described as modest similarly, the ratio of bone age to chronological age was significantly reduced ("p" < 0.0001). Linear growth and skeletal maturation during normal puberty is mainly due to estradiol and not testosterone in both boys and girls, and hence inhibition of these processes with the combination of bicalutamide and anastrozole in precocious puberty would in theory be mostly dependent on the aromatase inhibitor rather than on bicalutamide. Testicular volume increased mildly over the year that the boys were observed. A New Drug Application of bicalutamide for in the United States was submitted on the basis of the trial data. However, the application was not approved by the Food and Drug Administration, which cited insufficient evidence of effectiveness. Although indication of bicalutamide for the use was not granted, the bicalutamide medication label was updated to include the findings of the study. In terms of side effects, the combination of bicalutamide and anastrozole in the study was described as well tolerated with no safety concerns. However, gynecomastia, attributed to bicalutamide, was observed in almost half of the boys. In addition, one case of mildly elevated liver enzymes (1 of 14; 7%), possibly related to bicalutamide, was observed but resolved spontaneously without discontinuation of therapy.
Additional research is necessary to more clearly determine the true effectiveness and safety of bicalutamide and anastrozole in the treatment of . No long-term results for the study have been published as of yet, but a 5-year follow-up of two of the boys in the study was published and reported continued effectiveness. It is intended that the study will continue until all of the boys reach adult final height, with an additional publication planned in the future. In addition to the study, a variety of case reports and series of bicalutamide in combination with an aromatase inhibitor in male peripheral precocious puberty have been published. These case reports have described similar results as those of the study.
Alternatives to bicalutamide in the treatment of male peripheral precocious puberty include spironolactone, cyproterone acetate, and ketoconazole. Bicalutamide with anastrozole is considered to be superior to the combination of spironolactone and testolactone in peripheral precocious puberty, with greater efficacy and fewer side effects. This corresponds to the fact that bicalutamide is a much more potent and selective antiandrogen than spironolactone. Additionally, dosing is easier with bicalutamide, as it requires administration only once daily as opposed to twice daily at 12-hour intervals with spironolactone. For these reasons, bicalutamide has replaced spironolactone in the treatment of the condition. For comparison to bicalutamide, a higher dosage of spironolactone of 5 mg/kg (or about 100 to 150 mg in boys that are 20 to 30 kg or 45 to 65 lbs) once daily is recommended for use in male peripheral precocious puberty.
Long-lasting erections.
Antiandrogens can considerably relieve and prevent priapism (potentially painful penile erections that last more than four hours) via direct blockade of penile . In accordance, bicalutamide, at low dosages (50 mg every other day or as little as once or twice weekly), has been found in a series of case reports to completely resolve recurrent priapism in men without producing significant side effects, and is used for this indication off-label. In the reported cases, libido, rigid erections, the potential for sexual intercourse, orgasm, and subjective ejaculatory volume have all remained intact or unchanged, and gynecomastia has not developed when bicalutamide is administered at a total dosage of 25 mg/day or less. Some gynecomastia and breast tenderness developed in one patient treated with 50 mg/day, but significantly improved upon the dosage being halved. The observed tolerability profile of bicalutamide in these subjects has been regarded as significantly more favorable than that of analogues and estrogens (which are also used in the treatment of this condition). However, although successful and well tolerated, very few cases have been reported. Despite the apparent efficacy of bicalutamide for priapism, a small clinical study found that bicalutamide monotherapy at a dosage of 50 mg/day had no effect on nocturnal erections in men with prostate cancer.
Sexual deviance.
The antigonadotropic antiandrogens , medroxyprogesterone acetate (MPA), and analogues have all been widely used to treat paraphilias (e.g., pedophilia) and hypersexuality in men. They suppress androgen levels to castrate or near-castrate levels and are highly effective in reducing sexual urges, arousal, and behaviors. In addition, they are used to treat sex offenders as a means of chemical castration for the purpose of reducing the likelihood of recidivism.
Although they have not been studied in the treatment of paraphilias and hypersexuality, like flutamide and bicalutamide have been suggested as potential medications for these indications and may have superior tolerability and safety relative to antigonadotropic antiandrogens. As an example, because do not reduce estrogen levels, unlike antigonadotropic antiandrogens, they preserve bone mineral density (BMD) and have little or no risk of osteoporosis and associated bone fractures. However, due to unopposed estrogen signaling, a substantial incidence of gynecomastia is associated with . In addition to potential monotherapy use, have been advocated for temporarily suppressing sex drive during the start of agonist treatment via prevention of the increased androgen signaling associated with the initial testosterone flare.
Though treatment of paraphilias and hypersexuality with selective antagonists is a seemingly sound strategy, this may not be true in practice. Surprisingly, little or no sexual dysfunction, including loss of sex drive and decreased sexual activity, has been observed in clinical studies of monotherapy. The explanation for this is that do not lower androgen levels, and metabolites of testosterone like estrogens and neurosteroids may be of critical importance for maintenance of sex drive and function in males. In accordance, testosterone is locally aromatized into estradiol widely throughout the brain and estradiol appears to be the mediator of many of the central actions of testosterone. For these reasons, unlike antigonadotropic antiandrogens, monotherapy may have limited usefulness in the management of paraphilias and hypersexuality. The addition of to antigonadotropic antiandrogens like analogues may have some usefulness however, particularly in severe cases. In any case, insufficient evidence is available at this time, and further research is thus warranted.


Accessory cuneate nucleus

The accessory cuneate nucleus is located lateral to the cuneate nucleus in the medulla oblongata at the level of the sensory decussation (the crossing fibers of the posterior column/medial lemniscus tract).
It receives sensory input about position and movement (proprioception) from the upper limb by way of cervical spinal nerves and transmits that information to the cerebellum.
These fibers are called cuneocerebellar (cuneate nucleus → cerebellum) fibers.
In this function, the accessory cuneate nucleus is the upper extremity equivalent of Clarke's column, also called the nucleus thoracicus, which is the source of spinocerebellar connections for proprioception from the lower limb.


LY-2452473

LY-2452473 (TT-701) is a drug which acts as a selective androgen receptor modulator (SARM). It has been investigated for the treatment of erectile dysfunction and symptoms associated with benign prostate hyperplasia.


Nisoldipine

Nisoldipine is a pharmaceutical drug used for the treatment of chronic angina pectoris and hypertension. It is a calcium channel blocker of the dihydropyridine class. It is sold in the United States under the proprietary name Sular. Nisoldipine has tropism for cardiac blood vessels.
It was patented in 1975 and approved for medical use in 1990.
Contraindications.
Nisoldipine is contraindicated in people with cardiogenic shock, unstable angina, myocardial infarction, and during pregnancy and lactation.
Adverse effects.
Common side effects are headache, confusion, fast heartbeat, and edema. Hypersensitivity reactions are rare and include angioedema.
Interactions.
The substance is metabolized by the liver enzyme CYP3A4. Consequently, CYP3A4 inducers such as rifampicin or carbamazepine could reduce the effectiveness of nisoldipine, while CYP3A4 inhibitors such as ketoconazole increase the amount of nisoldipine in the body more than 20-fold. Grapefruit juice also increases nisoldipine concentrations by inhibiting CYP3A4.
Pharmacology.
Mechanism of action.
Nisoldipine is a calcium channel blocker that selectively inhibits L-type calcium channels.


Tetrahydropapaveroline

Tetrahydropapaveroline (norlaudanosoline) is a benzyltetrahydroisoquinoline alkaloid.
It can be formed in trace amounts in the brain by a condensation reaction of dopamine and dopaldehyde (a metabolite of dopamine).
It inhibits dopamine uptake within the cerebral cortex.


British Neuroscience Association

The British Neuroscience Association (BNA) is a scientific society with around 2,000 members. Established on the 23rd of February 1968 as the Brain Research Association, it was subsequently relaunched as the British Neuroscience Association in 1997.
The BNA is the largest UK organisation of its kind, supporting and promoting neuroscience and neuroscientists.
Charitable objects.
It is a registered charity (number 1103852), with charitable objects as follows:
"‘To preserve and protect health and advance public education in neurosciences related to health and disease (in particular but not exclusively) by:’"
The BNA is a member of the International Brain Research Organisation (IBRO), the Federation of European Neuroscience Societies (FENS) and the Royal Society of Biology (RSB).
Publications.
The BNA publishes a peer-reviewed scientific journal, "Brain and Neuroscience Advances" which is edited by Jeffrey W. Dalley (Cambridge University). It also publishes the "BNA Bulletin" membership magazine.
Events.
The headline event of the BNA is the biennial 'Festival of Neuroscience'. The Festivals are unique in bringing together multiple people and organisations with a shared interested in neuroscience - societies, charities, companies, scientists, clinicians and members of the public too.


Projection areas

Projection areas are areas in the four lobes (frontal, parietal, temporal, occipital) of the brain where sensory processing occurs.


(S,S)-Tetrahydrochrysene

("S","S")-Tetrahydrochrysene (("S","S")-THC) is a steroid-like nonsteroidal estrogen and agonist of both the estrogen receptors, ERα and ERβ. It is an enantiomer of ("R","R")-tetrahydrochrysene (("R","R")-THC), which, in contrast, is an ERβ silent antagonist and ERα agonist with 10-fold selectivity (i.e., affinity) for the ERβ over the ERα and with 20-fold greater affinity for the ERβ relative to that of ("S","S")-THC.


Flicker fusion threshold

The flicker fusion threshold, or flicker fusion rate, is a concept in the psychophysics of vision. It is defined as the frequency at which an intermittent light stimulus appears to be completely steady to the average human observer. Flicker fusion threshold is related to persistence of vision. Although flicker can be detected for many waveforms representing time-variant fluctuations of intensity, it is conventionally, and most easily, studied in terms of sinusoidal modulation of intensity. There are seven parameters that determine the ability to detect the flicker:
Explanation.
As long as the modulation frequency is kept above the fusion threshold, the perceived intensity can be changed by changing the relative periods of light and darkness. One can prolong the dark periods and thus darken the image; therefore the effective and average brightness are equal. This is known as the Talbot-Plateau law. Like all psychophysical thresholds, the flicker fusion threshold is a statistical rather than an absolute quantity. There is a range of frequencies within which flicker sometimes will be seen and sometimes will not be seen, and the threshold is the frequency at which flicker is detected on 50% of trials.
Different points in the visual system have very different critical flicker fusion rate (CFF) sensitivities; the overall threshold frequency for perception cannot exceed the slowest of these for a given modulation amplitude. Each cell type integrates signals differently. For example, rod photoreceptor cells, which are exquisitely sensitive and capable of single-photon detection, are very sluggish, with time constants in mammals of about 200 ms. Cones, in contrast, while having much lower intensity sensitivity, have much better time resolution than rods do. For both rod- and cone-mediated vision, the fusion frequency increases as a function of illumination intensity, until it reaches a plateau corresponding to the maximal time resolution for each type of vision. The maximal fusion frequency for rod-mediated vision reaches a plateau at about 15 hertz (Hz), whereas cones reach a plateau, observable only at very high illumination intensities, of about 60 Hz.
In addition to increasing with average illumination intensity, the fusion frequency also increases with the extent of modulation (the maximal relative decrease in light intensity presented); for each frequency and average illumination, there is a characteristic modulation threshold, below which the flicker cannot be detected, and for each modulation depth and average illumination, there is a characteristic frequency threshold. These values vary with the wavelength of illumination, because of the wavelength dependence of photoreceptor sensitivity, and they vary with the position of the illumination within the retina, because of the concentration of cones in central regions including the fovea and the macula, and the dominance of rods in the peripheral regions of the retina.
Technological considerations.
Display frame rate.
Flicker fusion is important in all technologies for presenting moving images, nearly all of which depend on presenting a rapid succession of static images (e.g. the frames in a cinema film, TV show, or a digital video file). If the frame rate falls below the flicker fusion threshold for the given viewing conditions, flicker will be apparent to the observer, and movements of objects on the film will appear jerky. For the purposes of presenting moving images, the human flicker fusion threshold is usually taken between 60 and 90 Hz, though in certain cases it can be higher by an order of magnitude. In practice, movies are recorded at 24 frames per second and displayed by repeating each frame two or three times for a flicker of 48 or 72 Hz. Standard-definition television operates at 25 or 30 frames per second, or sometimes at 50 or 60 (half-)frames per second through interlacing. High-definition video is displayed at 24, 25, 30, 60 frames per second or higher.
The flicker fusion threshold does not prevent indirect detection of a high frame rate, such as the phantom array effect or wagon-wheel effect, as human-visible side effects of a finite frame rate were still seen on an experimental 480 Hz display.
Display refresh rate.
Cathode ray tube (CRT) displays usually by default operated at a vertical scan rate of 60 Hz, which often resulted in noticeable flicker. Many systems allowed increasing the rate to higher values such as 72, 75 or 100 Hz to avoid this problem. Most people do not detect flicker above 400 Hz.
Other display technologies do not flicker noticeably, so the frame rate is less important. Liquid-crystal display (LCD) flat panels do not "seem" to flicker at all, as the backlight of the screen operates at a very high frequency of nearly 200 Hz, and each pixel is changed on a scan rather than briefly turning on and then off as in CRT displays. However, the nature of the back-lighting used can induce flicker Light-emitting diodes (LEDs) cannot be easily dimmed, and therefore use pulse-width modulation to create the illusion of dimming, and the frequency used can be perceived as flicker by sensitive users.
Lighting.
Flicker is also important in the field of domestic (alternating current) lighting, where noticeable flicker can be caused by varying electrical loads, and hence can be very disturbing to electric utility customers. Most electricity providers have maximum flicker limits that they try to meet for domestic customers.
Fluorescent lamps using conventional magnetic ballasts flicker at twice the supply frequency. Electronic ballasts do not produce light flicker since the phosphor persistence is longer than a half cycle of the higher operation frequency of 20 kHz. The 100–120 Hz flicker produced by magnetic ballasts is associated with headaches and eyestrain.
Individuals with high critical flicker fusion threshold are particularly affected by light from fluorescent fixtures that have magnetic ballasts: their EEG alpha waves are markedly attenuated and they perform office tasks with greater speed and decreased accuracy. The problems are not observed with electronic ballasts. Ordinary people have better reading performance using high-frequency (20–60 kHz) electronic ballasts than magnetic ballasts, although the effect was small except at high contrast ratio.
The flicker of fluorescent lamps, even with magnetic ballasts, is so rapid that it is unlikely to present a hazard to individuals with epilepsy. Early studies suspected a relationship between the flickering of fluorescent lamps with magnetic ballasts and repetitive movement in autistic children. However, these studies had interpretive problems and have not been replicated.
LED lamps generally do not benefit from flicker attenuation through phosphor persistence, the notable exception being white LEDs. Flicker at frequencies as high as 2000 Hz (2 kHz) can be perceived by humans during saccades and frequencies above 3000 Hz (3 kHz) have been recommended to avoid human biological effects.
Visual phenomena.
In some cases, it is possible to see flicker at rates beyond 2000 Hz (2 kHz) in the case of high-speed eye movements (saccades) or object motion, via the "phantom array" effect. Fast-moving flickering objects zooming across view (either by object motion, or by eye motion such as rolling eyes), can cause a dotted or multicolored blur instead of a continuous blur, as if they were multiple objects. Stroboscopes are sometimes used to induce this effect intentionally.
Some special effects, such as certain kinds of electronic glowsticks commonly seen at outdoor events, have the appearance of a solid color when motionless but produce a multicolored or dotted blur when waved about in motion. These are typically LED-based glow sticks. The variation of the duty cycle upon the LED(s), results in usage of less power while by the properties of flicker fusion having the direct effect of varying the brightness. When moved, if the frequency of duty cycle of the driven LED(s) is below the flicker fusion threshold timing differences between the on/off state of the LED(s) becomes evident, and the color(s) appear as evenly spaced points in the peripheral vision.
A related phenomenon is the DLP rainbow effect, where different colors are displayed in different places on the screen for the same object due to fast motion.
Flicker.
Flicker is the perception of visual fluctuations in intensity and unsteadiness in the presence of a light stimulus, that is seen by a static observer within a static environment. Flicker that is visible to the human eye will operate at a frequency of up to 80 Hz.
Stroboscopic effect.
The stroboscopic effect is sometimes used to "stop motion" or to study small differences in repetitive motions. The stroboscopic effect refers to the phenomenon that occurs when there is a change in perception of motion, caused by a light stimulus that is seen by a static observer within a dynamic environment. The stroboscopic effect will typically occur within a frequency range between 80 and 2000 Hz, though can go well beyond to 10,000 Hz for a percentage of population.
Phantom array.
Phantom array, also known as the ghosting effect, occurs when there is a change in perception of shapes and spatial positions of objects. The phenomenon is caused by a light stimulus in combination with rapid eye movements (saccades) of an observer in a static environment. Similar to the stroboscopic effect, the phantom effect will also occur at similar frequency ranges. The mouse arrow is a common example of the phantom array effect.
Non-human species.
The flicker fusion threshold also varies between species. Pigeons have been shown to have higher threshold than humans (100 Hz vs. 75 Hz), and the same is probably true for all birds, particularly birds of prey. Many mammals have a higher proportion of rods in their retina than humans do, and it is likely that they would also have higher flicker fusion thresholds. This has been confirmed in dogs.
Research also shows that size and metabolic rate are two factors that come into play: small animals with high metabolic rate tend to have high flicker fusion thresholds.


Grey component replacement

Within the CMY color space used in color printing, a range of colors can be achieved by combining the three primary colors. This combination can be thought of as a hue component (which will require a maximum of two primary colors) and a grey component (a mixture of all three, in an appropriate quantity to give the required saturation). If the grey component is replaced by black ink, the same color is being achieved by using two primaries and black. The substitution of black for the grey component is described as grey component replacement (GCR).
In GCR, contrary to under color removal (UCR), the CMY values that add to grey all along the tone scale can be replaced with black ink. UCR only adds black to the CMY equivalent of what would have printed as a grey or near-grey.


Metaculus

Metaculus is an American reputation-based, massive online prediction solicitation and aggregation engine. One of the focuses of Metaculus is predicting the timing, nature and impact of scientific and technological advances and breakthroughs.
Reward system.
Three types of predictions can be made: probability predictions to binary questions that resolve as either 'yes' or 'no', numerical-range predictions, and date-range predictions. Users can contribute to the community prediction for any given question, leave comments and discuss prediction strategies with other users. Users can suggest new questions which, after moderation, will be opened to the community.
Users can earn points for successful predictions (or lose points for unsuccessful predictions), and track their own predictive progress. The scoring awards points both for being right and for being more right than the community.
In January 2020, Metaculus introduced the Bentham Prize, which awards bi-weekly monetary prizes of $300, $200 and $100 to the first, second and third most valuable user contributions. The following month, Metaculus introduced the Li Wenliang prize, which awards a number of different monetary prizes to questions, forecasts and analyses related to the COVID-19 outbreak.
History.
Data scientist Max Wainwright and physicists Greg Laughlin and Anthony Aguirre launched the site in 2015.
In June 2017, the Metaculus prediction was launched, which is a system for aggregating user's predictions. The Metaculus prediction, on average, outperforms the median of the community's predictions when evaluated using the Brier or Log scoring rules.


Sensory cortex

The sensory cortex can refer informally to the primary somatosensory cortex, or it can be used as a term for the primary and secondary cortices of the different senses (two cortices each, on left and right hemisphere): the visual cortex on the occipital lobes, the auditory cortex on the temporal lobes, the primary olfactory cortex on the uncus of the piriform region of the temporal lobes, the gustatory cortex on the insular lobe (also referred to as the insular cortex), and the primary somatosensory cortex on the anterior parietal lobes. Just posterior to the primary somatosensory cortex lies the somatosensory association cortex, which integrates sensory information from the primary somatosensory cortex (temperature, pressure, etc.) to construct an understanding of the object being felt. Inferior to the frontal lobes are found the olfactory bulbs, which receive sensory input from the olfactory nerves and route those signals throughout the brain. Not all olfactory information is routed to the olfactory cortex: some neural fibers are routed to the supraorbital region of the frontal lobe, while others are routed directly to limbic structures. The direct limbic connection makes the olfactory sense unique.
The brain cortical regions are related to the auditory, visual, olfactory, and somatosensory (touch, proprioception) sensations, which are located lateral to the lateral fissure and posterior to the central sulcus, that is, more toward the back of the brain. The cortical region related to gustatory sensation is located anterior to the central sulcus.
Note that the central sulcus (sometimes referred to as the central fissure) divides the primary motor cortex (on the precentral gyrus of the posterior frontal lobe) from the primary somatosensory cortex (on the postcentral gyrus of the anterior parietal lobe).
The sensory cortex is involved in somatic sensation, visual stimuli, and movement planning.


Internal capsule

The internal capsule is a white matter structure situated in the inferomedial part of each cerebral hemisphere of the brain. It carries information past the basal ganglia, separating the caudate nucleus and the thalamus from the putamen and the globus pallidus. The internal capsule contains both ascending and descending axons, going to and coming from the cerebral cortex. It also separates the caudate nucleus and the putamen in the dorsal striatum, a brain region involved in motor and reward pathways.
The corticospinal tract constitutes a large part of the internal capsule, carrying motor information from the primary motor cortex to the lower motor neurons in the spinal cord.
Above the basal ganglia the corticospinal tract is a part of the corona radiata, below the basal ganglia the tract is called cerebral crus (a part of the cerebral peduncle) and below the pons it is referred to as the corticospinal tract.
Structure.
The internal capsule consists of three parts and is V-shaped when cut horizontally, in a transverse plane.
Genu.
The "genu" is the flexure of the internal capsule. It is formed by fibers from the corticonuclear tracts. The fibers in this region are named the geniculate fibers; they originate in the motor part of the cerebral cortex and after passing downward through the base of the cerebral peduncle with the cerebrospinal fibers, undergo decussation and end in the motor nuclei of the cranial nerves of the opposite side. It contains the corticobulbar tract, which carries upper motor neurons from the motor cortex to cranial nerve nuclei that mainly govern motion of striated muscle in the head and face.
Anterior limb.
The "anterior limb" of internal capsule (or frontal part) contains:
Posterior limb.
The "posterior limb" of internal capsule (or occipital part) is the portion of the internal capsule posterior to the genu.
The anterior two-thirds of the occipital part of the internal capsule contains fibers of the corticospinal tract, which arise in the motor area of the cerebral cortex and, passing downward through the middle three-fifths of the base of the cerebral peduncle, are continued into the pyramids of the medulla oblongata.
The posterior third of the occipital part contains:
Blood supply.
The superior parts of both the "anterior and posterior limbs" and the "genu" of the internal capsule are supplied by the lenticulostriate arteries, which are branches of the M1 segment of the middle cerebral artery.
The inferior half of the "anterior limb" is supplied via the recurrent artery of Heubner, which is a branch of the anterior cerebral artery.
The inferior half of the "posterior limb" is supplied by the anterior choroidal artery, which is a branch of the internal carotid artery.
In summary, the blood supply of the internal capsule is
As in many parts of the body, some degree of variation in the blood supply exists. For example, thalamoperforator arteries, which are branches of the basilar artery, occasionally supply the inferior half of the posterior limb.
Function.
The internal capsule provides passage to ascending and descending fibres running to and from the cerebral cortex.
Working anterior to posterior:
Other fibers within the internal capsule
Clinical significance.
The lenticulostriate arteries supply a substantial amount of the internal capsule. These small vessels are particularly vulnerable to narrowing in the setting of chronic hypertension and can result in small, punctate infarctions or intraparenchymal haemorrhage due to vessel rupture.
Lesions of the genu of the internal capsule affect fibers of the corticobulbar tract.
The primary motor cortex sends its axons through the posterior limb of the internal capsule. Lesions, therefore, result in a contralateral hemiparesis or hemiplegia. While symptoms of weakness due to an isolated lesion of the posterior limb can initially be severe, recovery of motor function is sometimes possible due to spinal projections of premotor cortical regions that are contained more rostrally in the internal capsule.


AmmTX3

AmmTX3, produced by "Androctonus mauretanicus", is a scorpion toxin of the α-KTX15 subfamily. The toxin is known for its ability to act as a specific Kv4 channel blocker, and thereby reducing the A-type potassium current through this channel.
Etymology and source.
AmmTX3 (α-KTX15.3) is a peptide that can be isolated from the venom of "Androctonus mauretanicus". "Androctonus mauretanicus" is a fat-tailed scorpion with its origins in North Africa.
Chemistry.
AmmTX3 has a molecular mass of 3823.5 Da and consists of a single chain of 37 amino acid residues. These residues are cross-linked by three disulfide bridges. The toxin contains the dyad characteristic (K27 and Y36) that is found in pore-blocking potassium channel-specific toxins, and is therefore likely to act as a pore blocker.
AmmTX3 is a member of the α-KTX15 subfamily. This subfamily currently exists of six very homologous peptides, originating from scorpion venom: Aa1, AaTX1, AaTX2, AmmTX3, BmTx3 and Discrepin. Toxins of the α-KTX15 subfamily all seem to have an effect on the A-type potassium current.
Target.
AmmTX3 is a specific pore blocker of Kv4.2 and Kv4.3 channels of mice. This high-affinity blockade depends on the expression of dipeptidyl peptidase-like proteins (DPP) DPP6 and DPP10, which are proteins that co-assemble with the alpha-subunits of Kv4 channels. Besides its potent ability to block Kv4 channel, AmmTx3 also has a small blocking effect on hERG channels without alteration of the gating kinetics.
Mode of action.
By blocking specifically the Kv4 channels, AmmTX3 reduces the A-type potassium current through these channels almost completely. A-type potassium currents can be generated by Kv1.4, Kv3.3, Kv3.4, all members of Kv4 and Erg3 channels. The influence of AmmTX3 on the overall A-type potassium currents hence depends on the specific channel types that mediate this current in the cell. For example, in the solitary nucleus, the A-type potassium current is Kv4-mediated. Therefore, presence of AmmTX3 in the solitary nucleus cells blocks the A-type potassium current almost completely. Similar effects have been found in the hippocampus, substantia nigra, and cerebellum granule cells of rats and mice.
While AmmTX3 nearly completely blocks the transient component of the A-type potassium current in cerebellar granular neurons at 0.5 μM, the sustained component of the current, which is thought to be Kv3.1 mediated, seems unaffected, in contrast to Aa1 and BmTX3.
AmmTX3 is predominantly used in research setting, where it is often injected into specific brain areas to learn more about the role of Kv4 channels in those areas. For example, AmmTX3 possibly impairs the consolidation of spatial information and learning strategy through Kv4 channel inhibition, as found within rats in a radial-maze task. AmmTX3 also increases spontaneous pacemaking frequency in substantia nigra pars compacta dopaminergic neurons
Toxicity.
The Ki of AmmTX3 was found to be approximately 131 nM when tested on striatal neurons in cell culture. AmmTX3 has a small blocking effect on hERG channels with an IC50 of 7.9 ± 1.4 μM.


Birth Control Glasses


Sabine Chaouche

Sabine Chaouche is a French scholar who specializes in theatre and social and economic history.
Biography.
She studied at the University of Oxford (New College), where she completed a DPhil in Social and Economic History (2017) and at the Université de Paris-Sorbonne where she completed a PhD in Literature and Theatre (1999) and an Habilitation à Diriger des Recherches (2005). As a Reader, she taught French literature and theatre in Oxford. Her books on acting and declamation in the seventeenth and eighteenth centuries have become reference works. In recent years, she examined staging, the philosophy of performance and the economy of entertainments. She has edited almost all the theories on "actio" and baroque acting from the 1650s to the 1800s and is regarded by Konrad Schoell as "one of the most important representatives of current research into the history of the French theatre of the 17th and 18th centuries". Her multidisciplinary area of expertise includes the history of consumption and trade in nineteenth-century Europe, as well as Oxford students' daily life in the Victorian and Edwardian eras.
She is a Fellow of the Royal Historical Society and a member of the Peer Review College of the Arts and Humanities Research Council in the UK.
She is the director of the journal "European Drama and Performance Studies" published by Éditions Classiques Garnier and the director of the e-magazine "The Frenchmag."


Subthreshold membrane potential oscillations

Subthreshold membrane potential oscillations are membrane oscillations that do not directly trigger an action potential since they do not reach the necessary threshold for firing. However, they may facilitate sensory signal processing.
Neurons produce action potentials when their membrane potential increases past a critical threshold. In order for neurons to reach threshold for action potential to fire, enough sodium (Na+) ions must enter the cell through voltage gated sodium channels through membrane and depolarize the cell. The threshold is reached to overcome the electrochemical equilibrium within a neuron, where there is a balance between potassium ions (K+) moving down their concentration gradient (inside the cell to outside), and the electrical gradient that prevents K+ from moving down its own gradient. Once the threshold value is reached, an action potential is produced, causing a rapid increase of Na+ enters the cell with more Na+ channels along the membrane opening, resulting in a rapid depolarization of the cell. Once the cell has been depolarized, voltage-gated sodium channels close, causing potassium channels to open; K+ ions then proceed to move against their concentration gradient out of the cell.
However, if the voltage is below the threshold, the neuron does not fire, but the membrane potential still fluctuates due to postsynaptic potentials and intrinsic electrical properties of neurons. Therefore, these subthreshold membrane potential oscillations do not trigger action potentials, since the firing of an action potential is an "all-or-nothing" response, and these oscillations do not allow for the depolarization of the neuron to reach the threshold needed, which is typically around -55 mV; an "all-or-nothing" response refers to the ability of a neuron to fire an action potential only after reaching the exact threshold. For example, "figure 1" depicts the localized nature and the graded potential nature of these subthreshold membrane potential oscillations, also giving a visual representation of their placement on an action potential graph, comparing subthreshold oscillations versus a fire above the threshold. In some types of neurons, the membrane potential can oscillate at specific frequencies. These oscillations can produce firing by joining with depolarizations. Although subthreshold oscillations do not directly result in neuronal firing, they may facilitate synchronous activity of neighboring neurons. It may also facilitate computation, particularly processing of sensory signals. All in all, although the subthreshold membrane potential oscillations do not produce action potentials by themselves, through summation, they are able to still impact action potential outcomes.
Overview.
Neurons display, beyond synaptic and action potentials, rhythmic subthreshold membrane potential oscillations (a particular type of neural oscillations). These oscillations, which resembled sinusoidal wave forms, were originally discovered in the mammalian inferior olive nucleus cells. The functional relevance of subthreshold oscillations concerns the nature of the intrinsic electrical properties of neurons; that is, the electrical responsiveness are not derived from interactions with other cells. These properties define the dynamic phenotype independently from form or connectivity. Subthreshold oscillation frequency can vary, from few Hz to over 40 Hz, and their dynamic properties have been studied in detail in relation to neuronal activity coherence and timing in CNS, in particular with respect to the 10 Hz physiological tremor that controls motor execution, Theta rhythm in the entorhinal cortex, and gamma band activity in cortical inhibitory interneurons and in thalamus neurons. They have also been described and studied in layers V of the entorhinal cortex, the inferior olive in vivo, the olfactory bulb and the dorsal cochlear nucleus. These neurons have been a major input into the cerebellum, as well, and have been found to contribute to the overall generation of movement patterns. The dynamic aspects of such oscillations have been defined using mathematical modeling.
Based on the analysis done by Bohemer et al., the hypothalamic supraoptic nucleus (SON) contains two major populations of magnocellular neurosecretory neurons which produces and secretes vasopressin and oxytocin, respectively. The study examined electrophysiological properties and ionic bases of subthreshold oscillation of the membrane potential in 104 magnocellular neurons of rats, using intracellular recording techniques. The study found that SMOP that occurred in all neurons examined were voltage-dependent; oscillation was not a result of excitatory or inhibitory activity and neither was it from an electric coupling. This suggests that the subthreshold oscillation of the membrane potential may be crucial for inter-neuronal synchronization of discharge and for the amplification of synaptic events.
Neurons of a subpopulation of supraoptic neurosecretory cells are able to generate phasic bursts of action potentials. In the neurons examined in this experiment, action potentials are succeeded by a depolarizing after-potential. Another article investigated the effect of GABAergic input, an example of an inhibitor, to the model of the fast-spiking neuron. They suggested that inhibitory input will be able to induce a stuttering episode in these cells.
GABA, an important neurotransmitter, is involved with modulating synaptic firing within the brain. It's been found that inhibitory neurons, including GABA, depolarize synchronously with excitatory neurons. However, they exhibit varying activities during different brain states. This inhibitor is critical for sustaining subthreshold membrane potential oscillations and for excitatory synaptic impulses. Maintaining the equilibrium of GABA presence in the synapse (release and reuptake of GABA) is necessary for these rhythmic subthreshold membrane potential oscillations to occur.
In addition to neurons firing action potentials, they can also perform synchronized spiking or bursts. Subthreshold membrane potential oscillations do not create an action potential; however, neurons do experience bursting when they group together and create a synchronized potential by firing all at once, which is usually the result of these subthreshold potentials.
Several studies have used various techniques to study the frequency of subthreshold oscillations at a different membrane potential. For example, a study examined the frequencies of SMPO in different anatomical positions on the dorsoventral axis of a rat medial entorhinal cortex. They used whole-cell patch recording in vivo and biophysical modeling in compartmental simulations of entorhinal stellate cells to examine the properties (SMPO), at different membrane potentials of the entorhinal cortex layer II stellate cells. This technique incorporates electrical stimulation of polar molecules in cell membrane. The study found that Dorsal cells are likely to show a positive slope of peak frequency with depolarization, whereas ventral cells tend to show a negative slope of peak frequency with depolarization. These findings illustrate that there are high frequencies of SMPO in dorsal cells and low frequencies in the ventral cells. A similar study that did whole-cell recordings of olivary neurons in vivo to investigate the relationship between subthreshold activities and spiking behavior in an intact brain illustrates that the majority of neurons displayed subthreshold oscillation activities. Which means that the inferior olive of mammals’ brain exhibits relatively stable frequencies settings of oscillations. As a result, this might be used to generate and rest temporal firing patterns in an electrically coupled ensemble.
Sensory Circuits.
Subthreshold membrane potential oscillations play an important role in the development of the sensory systems, including, but not being limited to the visual system and the olfactory system.
In the visual system, through the help of electroencephalogram or EEG readings, the subthreshold membrane potential oscillations help equip the cortex for not only processing visual stimulation, but also neuronal plasticity. These oscillations are present even before birth and also before a newborn opens its eyes, as they are forms of maturation and preparation of the human sensory cortex, which is a part of the cerebral cortex that is responsible for processing and encoding sensory information. This subthreshold activity is responsible for shaping circuits for maturation and are especially distinct in the retina, in the form of retinal waves.
In the olfactory system, responsible for sense of smell, according to the study, subthreshold membrane potential oscillations present in mitral cells, which are neurons in the olfactory system, are said to influence the timing of the spikes of action potentials, which in turn allows for the synchronization of multiple mitral cells. The study also mentions how this oscillatory activity is thought to also impact excitatory postsynaptic potentials in the way that they act as refinement tools to this post neural activity.


Neurula

A neurula is a vertebrate embryo at the early stage of development in which neurulation occurs. The neurula stage is preceded by the gastrula stage; consequentially, neurulation is preceded by gastrulation. Neurulation marks the beginning of the process of organogenesis.
Mice, chicks, and frogs are common experimental models for studying the neurula. Depending on the species, embryos reach the neurula stage at different time points and spend a varying amount of time in this stage. For oviparous organisms, incubation temperature also affects the length of neurulation. In addition to development of the neural tube, other processes occur in a neurula stage embryo depending on the species. For example, in reptiles, extra-embryonic membrane tissues become distinct from the embryo.
The neurula embryo has five regions of mesoderm that surround the neural tube. Anterior mesoderm develops into the head region, while posterior mesoderm develops into the trunk. Various molecules, including proteoglycans in the extracellular matrix, and genes, including Pax transcription factors, are essential for the development and closure of the neural tube in the neurula stage embryo.
Neurulation.
Neurulation is a process in vertebrate embryos at the neurula stage in which the neural tube is formed. There are two types of neurulation: primary and secondary neurulation. Primary neurulation refers to the formation and inward folding of the neural plate upon itself to form the neural tube. In secondary neurulation, the neural tube forms via the merging of cavities in the medullary cord. In amphibians and reptiles, primary neurulation forms the whole neural tube, and the neural tube closes simultaneously along its length. Contrarily, in fish, secondary neurulation forms the neural tube. Both primary and secondary neurulation occur in birds and mammals, although with slight differences. Primary neurulation occurs in the cranial and upper spinal regions, which gives rise to the brain and upper regions of the spinal cord. Secondary neurulation occurs in the lower sacral and caudal regions, resulting in the formation of the lower regions of the spinal cord. In birds, the neural tube closes anterior to posterior, while in mammals, the middle closes first, followed by the closure of both ends.
Developmental timing.
The point at which the embryo reaches the neurula stage differs among species, while for oviparous organisms, the length of neurulation is additionally affected by incubation temperature. In general, the lower the temperature, the greater the length of neurulation. Chick embryos reach the neurula stage on day 2 post-fertilization, and they undergo neurulation up to day 5. Reptiles, including crocodiles, lizards, and turtles, tend to spend a longer time in the neurula stage. A typical frog embryo, incubated at 18 °C, is an early stage neurula by 50 hours post-fertilization and a late stage neurula by 67 hours. The mouse embryo begins neurulation on day 7.5 of gestation and remains in the neurula stage until day 9.
Morphology.
The mesoderm of a vertebrate embryo in the neurula stage can be divided into five regions. Ventral to the neural tube is the chordamesoderm. Lateral to either side of the neural tube is the paraxial mesoderm, while the intermediate lateral region to the neural tube is the intermediate mesoderm. The fourth region is the lateral plate mesoderm, and the last region is the head mesenchym. Anterior portions of the mesoderm develop into rostral regions of an organism, such as the head, while posterior mesoderm develops into caudal regions, such as the trunk or tail. The paraxial mesoderm, also termed somitic mesoderm, develops into somites, blocks of tissue that occur in a segmental pattern. Somites, in turn, give rise to vertebrae, ribs, skeletal muscle, cartilage, tendons, and skin.
In "Xenopus laevis", the transition from the gastrula to the neurula involves morphological changes in two regions surrounding the blastopore: the dorsal involuting marginal zone (IMZ) and the overlying non-involuting marginal zone (NIMZ) of the gastrula. Following involution at the mid-gastrula stage, the IMZ undergoes convergent extension, in which the lateral regions narrow and move towards the midline and the anterior end lengthens. This has the effect of narrowing the blastopore. The NIMZ, which does not involute, simultaneously extends in the opposite direction and at a greater rate to cover regions no longer occupied by the IMZ. The convergent extension of the IMZ and NIMZ begins in the second half of gastrulation and continues into the late neurula stage. Eventually, deep tissue of the IMZ forms the central notochord and the surrounding paraxial mesoderm. By the early neurula stage, the notochord is clearly distinguished. Notochordal cells become arranged in a formation representing a stack of coins in a process termed circumferential intercalation. The superficial layer of the IMZ develops into the roof of the archenteron, or the primitive gut, while the underlying endoderm forms the archenteron floor. The NIMZ develops into a structure resembling the early neural tube. The outer ectodermal layer of the neurula is formed by uniform expansion of the cells at the animal pole, known as the animal cap. The ectoderm then differentiates into neural and epidermal tissue.
In reptilian embryos, beginning in the late-stage neurula and carrying over into the early stages of organogenesis, extra-embryonic membrane tissues comprising the yolk sac, chorion, and amnion become distinct from the tissues of the embryo. The mesoderm splits to create the extra-embryonic coelom, which consists of two layers. The vascularized mesoderm-endoderm inner layer, termed the splanchnopleure, develops into the yolk sac, while the nonvascularized ectoderm-mesoderm outer layer, termed the somatopleure, becomes the amnion and chorion. During organogenesis, these three extra-embryonic tissues become fully developed. Additionally, within the reptilian neurula, tissues of the brain begin to differentiate and the heart and blood vessels start to form.
Chemical composition.
Mouse neurula tissues divide rapidly, with an average cell cycle lasting 8–10 hours. Proteoglycans in the extracellular matrix (ECM) of neurula-stage cells play an important role in promoting functional cranial neurulation and neural fold elevation; hyaluronic acid (HA) is synthesized and becomes accumulated, while the cell maintains a low level of sulfated glycosaminoglycans (GAGs). HA is involved in creation of biconvex neural folds, while sulfated GAGs are critical in manipulating the neural groove into a V-shape, as well as in neural tube closure. The ECM does not play a major role in spinal neurulation due to the close-packed nature of the mesodermal cells in the spinal region, which allows little intercellular space. Additionally, actin-containing microfilaments are believed to be necessary in cranial neurulation. They may act as the mechanism for neural folding, or they may stabilize neural folds that have already formed; however, their exact role has not been determined. There is some evidence that growth factors, such as insulin or transferrin, also play a role in neurulation, but this link has not been well-studied.
Gene activation.
A variety of genes have been found to be expressed in the neurula stage embryo. Different genes are activated for different neurulation events, such as those occurring in separate regions of the developing neural tube. These genes are necessary for proper neurulation and closure of the neural tube. Signaling molecules such as Wnts, FGFs, and BMFs along with the transcription factors that include Msx, Snails, Sox8/9/10, and Pax3/7 genes play key roles in neural crest formation.
Pax transcriptional factors have an important role in early development, especially with regards to the CNS and neural crest. Pax3 and Pax7 are promoters of both neural crest cell survival along with promoting environmental stress resistance. In mouse embryos Pax3 blocks the tumor suppressor gene p53, which is necessary for controlled proliferation and genomic stability, is expressed in all cells of the neurula. During early development Pax3 is expressed at the posterior and lateral area of the neural plate, the same region that the neural crest arises from. Neural crest defects were found to occur in mouse and human Pax3 mutants, indicating an importance of functionality. Within chicks, frogs and fish Pax3/Pax7 are activated by Wnt and FGF signaling. Pax3 and Pax7 are also required for neural crest induction after depletion of the two genes resulted in the lack of activation of the specific neural crest genes Snail2 and Foxd3, which didn't allow further development or emigration of neural crest. Using knockouts has been helpful for understanding the role and functions of several genes found in the neurula. For example, Wnt-1 was found to have no role in the closing of the neural plate, despite being present at the tip of the neural folds when it is closing. Though mutants of Wnt-1 does lead to pattern defects within the brain. Notch1 is involved with formation of somites. HNF-3 is needed for development of the notochord and node. The gene Apolipoprotein B, which is involved in transporting and metabolizing fat soluble molecules in the blood, is expressed in the yolk sac and fetal liver. Within the neurula in "Xenopus laevis," development genes Xwnt-3 and Xwnt-4 are present.


Leslie M. Hicks

Leslie Hicks is an associate professor of analytical chemistry at the University of North Carolina at Chapel Hill. Her work primarily focuses on the study of proteomics and protein post-translational modifications using mass spectrometry, and identifying biologically active peptides in plants.
Career.
Dr. Hicks earned her bachelor's degree at Marshall University in 2001, and went on to earn her doctorate at the University of Illinois Urbana-Champaign in 2005. She was an Assistant Member and Principal Investigator at the Donald Danforth Plant Science Center from 2006 to 2013, and an adjunct professor in the Department of Biology at Washington University in St. Louis before beginning her current position as a professor at UNC.
Research.
Dr. Hicks' research focuses largely on the development and implementation of mass spectrometric methods for protein identification and characterization. Recent work in the Hicks Lab has focused primarily on two areas. The first is the study of post-translational modifications and their role in regulation and development. The second involves a novel analytical pipeline for the discovery and characterization of antimicrobial peptides.
Hicks' research in post-translational modifications typically employs bottom-up proteomics using label-free quantification. Much of this research involves the model organism "C. reinhardtii," an important organism in biofuel research due to its tendency to accumulate triacylglycerols. The Hicks Lab has studied the phosphoproteome of "C. reinhardtii" in order to examine underlying biological processes. Work has also been done to understand cell regulatory pathways, especially the algal analog of the mammalian TOR pathway. To a similar end, Dr. Hicks' group has extended its work to examine how the reversible oxidation of thiols plays a role in signaling and effector-triggered immunity.
The increasing threat of antimicrobial resistance has produced a need for novel antimicrobial agents. The Hicks Lab has investigated antimicrobial peptides as a potential source for new antibiotics. Recent work has involved the development of a comprehensive analytical approach using LC-MS for the identification of novel antimicrobial peptides from botanical, fungal, and bacterial sources.


Complexometric titration

Complexometric titration (sometimes chelatometry) is a form of volumetric analysis in which the formation of a colored complex is used to indicate the end point of a titration. Complexometric titrations are particularly useful for the determination of a mixture of different metal ions in solution. An indicator capable of producing an unambiguous color change is usually used to detect the end-point of the titration. Complexometric titration are those reactions where a simple ion is transformed into a complex ion and the equivalence point is determined by using metal indicators or electrometrically.
Reactions for Complexometric titration.
In theory, any complexation reaction can be used as a volumetric technique provided that:
In practice, the use of EDTA as a titrant is well established.
Complex titration with EDTA.
EDTA, ethylenediaminetetraacetic acid, has four carboxyl groups and two amine groups that can act as electron pair donors, or Lewis bases. The ability of EDTA to potentially donate its six lone pairs of electrons for the formation of coordinate covalent bonds to metal cations makes EDTA a hexadentate ligand. However, in practice EDTA is usually only partially ionized, and thus forms fewer than six coordinate covalent bonds with metal cations.
Disodium EDTA is commonly used to standardize aqueous solutions of transition metal cations. Disodium EDTA (often written as Na2H2Y) only forms four coordinate covalent bonds to metal cations at pH values ≤ 12. In this pH range, the amine groups remain protonated and thus unable to donate electrons to the formation of coordinate covalent bonds. Note that the shorthand form Na4−xHxY can be used to represent any species of EDTA, with x designating the number of acidic protons bonded to the EDTA molecule.
EDTA forms an octahedral complex with most 2+ metal cations, M2+, in aqueous solution. The main reason that EDTA is used so extensively in the standardization of metal cation solutions is that the formation constant for most metal cation-EDTA complexes is very high, meaning that the equilibrium for the reaction:
lies far to the right. Carrying out the reaction in a basic buffer solution removes H+ as it is formed, which also favors the formation of the EDTA-metal cation complex reaction product. For most purposes it can be considered that the formation of the metal cation-EDTA complex goes to completion, and this is chiefly why EDTA is used in titrations and standardizations of this type.
Indicators.
To carry out metal cation titrations using EDTA, it is almost always necessary to use a complexometric indicator to determine when the end point has been reached. Common indicators are organic dyes such as Fast Sulphon Black, Eriochrome Black T, Eriochrome Red B, Patton Reeder, or Murexide. Color change shows that the indicator has been displaced (usually by EDTA) from the metal cations in solution when the end point has been reached. Thus, the free indicator (rather than the metal complex) serves as the endpoint indicator.


Eccentricity effect

The eccentricity effect is a visual phenomenon that affects visual search. As retinal eccentricity increases, the observer is slower and less accurate to detect an item they are searching for.
Visual search tends to be better (faster and more accurate) when the target is presented closest/more centrally to the fovea, and worsens when the target is further in the periphery of the retina.
This effect was first confirmed in research by Carrasco, Evert, Chang, and Katz in 1995., and was replicated by Wolfe, O'Neill and Bennet in 1998
Etymology.
The word eccentric comes from the Greek ekkentros meaning “out of the center”.
Mechanisms.
Visual explanation.
When we view an image, light passes through the cornea, and through the pupil, which is controlled by the iris. It then passes through the lens and is projected onto the retina at the back of the eye. In the middle of the retina is the fovea, which contains a high concentration of cones. Cones are responsible for colour vision and have high spatial acuity, whereas rods are not. Rods are instead responsible for vision at lower light. Cones are much more sparsely located in the periphery of the retina, where there is instead a greater concentration of rods. When a central image is projected directly onto the fovea it is sharper and processed with greater speed and accuracy due to these cones, whereas images further in the periphery (greater eccentricity) are processed more slowly and less accurately.
Cortical magnification is one such visual explanation and is referring to the variance of the number of neurons that exist in the visual cortex, which are responsible for processing a visual stimulus. This number of neurons varies according to the location of the stimulus in the visual field. This accounts for the greater spatial acuity at the centre of the fovea compared to that at the periphery, and can sometimes be counteracted through M scaling – where stimulus size is adjusted according to its location.
Staugaard, Petersen and Vangkilda (2016) wanted to see if cortical magnification could explain the eccentricity effect. They adjusted the size of their experiment stimuli according to the cortical magnification factor (through M scaling) and found no effect of cortical magnification which could fully explain the eccentricity effect.
Bao et al. (2013) also tested to see if cortical magnification was responsible for the eccentricity effect of inhibition of return (IOR). Inhibition of return is an orientation mechanism which refers to the “relative suppression of stimuli that had recently been the focus of attention”.[10] An eccentricity effect can also be seen in IOR i.e. there is a stronger IOR effect in the periphery, and Bao et al. wanted to see if cortical magnification was responsible for this. They tested their participants with different sized stimulus at two peripheral locations (scaling for the size of the location) to account for cortical magnification. Their results indicated that scaling of the stimulus size did not change the eccentricity effect of IOR and therefore cortical magnification is not responsible for this.
The results from Staugaard, Petersen and Vangkilda, and Bao et al. suggest that the potential visual explanation of cortical magnification is not an explanation for the eccentricity effect.
Attentional explanation.
Another explanation for the eccentricity effect is that of the guided search model. This model posits that when an individual is carrying out a visual search task, their attention is deployed to one item at a time. The order of this attention depends on the activation of the item – the item receives more activation if it shares similar features with the target. In the case of eccentricity, the item/s that is/are closest to the target i.e. less eccentric, will receive more activation; and items further away i.e. those that have greater eccentricity, will receive less activation, and therefore processing for these will be slower and less accurate.
Variables influencing the effect.
Target orientation.
Carrasco, Evert, Chang and Katz (1995) found that for vertical targets there was a more pronounced eccentricity effect than tilted targets, but only for single feature searches. When the search was a conjunction search, i.e. target has more than one feature, there was no difference between tilted versus vertical targets.
Display duration.
Carrasco, Evert, Chang and Katz’s 1995 research also included a free-viewing, fixed-viewing and fast-fixed-viewing condition.
Free-viewing means that display was present until observers responded; fixed-viewing means that display was only present for 104msec, and finally fast-fixed means that the display was only present for 64msec.
They found a main effect for display duration that performance is slower for the free-viewing than fixed-viewing conditions, but that accuracy decreased more in the fast-fixed than fixed viewing condition, while fixed-viewing was marginally less accurate than free-viewing.
This indicates a main effect of eccentricity on accuracy across different display duration's, and indicates that the impact of the eccentricity effect on accuracy decreases when observers have longer to respond.
Visual search type.
Carrasco, Evert, Chang and Katz (1995) also found a more pronounced eccentricity effect in conjunction searches (these are targets which are defined by more than one feature), compared to single feature searches. This effect is more pronounced in larger set sizes.
Wolfe, O’Neill and Bennet (1998) attempted to replicate these findings in a similar style conjunction search task, using colour x orientation, with either a single (red and vertical) or two target (red and vertical or green and horizontal) condition. They found eccentricity effects for both the single and two target conditions, of which the effect was larger for the two target condition i.e. performance was slower and less accurate – lending further support to Carrasco, Evert, Chang and Katz’s 1995 findings.
Set size.
Carrasco, Evert, Chang and Katz (1995) observed increasing eccentricity effects in larger set sizes throughout their experiments.
Wolfe, O’Neill and Bennet (1998) also investigated the effect of set size x eccentricity. They found that with a set size of 1, the eccentricity effect remained similar at different eccentricities, however when the set size was greater than 1 the eccentricity effect grew for greater eccentricities.


Quinestradol

Quinestradol (, ) (brand names Colpovis, Colpovister, Pentovis), also known as quinestradiol or quinestriol, as well as estriol 3-cyclopentyl ether (E3CPE), is a synthetic estrogen and estrogen ether which is no longer marketed. It is the 3-cyclopentyl ether of estriol. The medication has been studied in the treatment of stress incontinence in elderly women, with effectiveness observed.