Harry James Osman (29 January 1911 – 17 December 1998) was an English footballer who played as an outside left for Southampton for two seasons in the 1930s and went on to become manager of Winchester City where he "discovered" future England international Terry Paine.

Playing career
Osman was born in the village of Bentworth near Alton, Hampshire but moved as a child to Okeford Fitzpaine in Dorset. As a teenager, he played football for Okeford United, before joining Poole Town, playing in the Western League, in 1930.

In December 1935, he joined Plymouth Argyle of the Football League Second Division, where he remained until the summer of 1937. Despite making only five appearances for Plymouth, he had caught the eye of Tom Parker when he was manager of Norwich City. On joining Southampton in 1937, Parker signed Osman from Plymouth, as well as several youngsters from his previous club.

Osman moved back to Hampshire on a free transfer, making his debut for Southampton (in the Football League Second Division) on 28 August 1937, the first day of the 1937–38 season. Osman made an immediate impact, scoring in a 4–3 defeat by Parker's old club. His next goal came on 18 September (against West Ham United) before starting a run of form in October which saw him score eight goals in four games, including a hat-trick in a 6–3 defeat at Luton Town. On Christmas Day 1937, the Saints played a home league match against Swansea Town in which Osman scored to bring the result level at 1–1; this was the last goal scored at The Dell on a Christmas Day. Although Christmas Day fixtures continued on–and–off until 1959, all the Saints' subsequent Christmas Day matches were away from home.

Osman's form continued and he only missed two matches at the end of the season, when he was the Saints' top–scorer with 22 goals (a club record for an outside–left). His form had attracted the attention of bigger clubs, but a reported bid of £7,000 from Birmingham failed to materialise. The following season, Osman continued to play well in an unsettled Southampton side that struggled to maintain any form. Unable to find the exciting form of the previous season, Osman managed only nine goals (from 30 appearances) before he was sold to Second Division rivals Millwall in March 1939 for a fee of £2,000, a move that came as a shock to the Southampton fans, although, in hindsight, this turned out to be a very good piece of business.

His career at Millwall was interrupted by the Second World War. He returned to The Dell as a guest player in War Leagues in 1939–40, before joining the Tank Corps where he was wounded while serving in Italy. After the war, he returned to Millwall making 23 appearances (with three goals) in 1946–47 before transferring to Bristol City in October 1947.

At the end of the 1947–48 season he dropped down to lower league football with spells at Dartford and Canterbury City (where he was appointed player-manager) before returning to Hampshire with Winchester City in 1952.

Managerial career
Osman made a few appearances as a player for Winchester City before taking over as manager in 1953, while also running the Wykeham Arms pub in the city.

In 1955, Osman played a 15-year-old Terry Paine in Winchester City's Hampshire League side. Paine's potential was obvious even at this age and Osman alerted his former Southampton teammate, now Southampton's manager Ted Bates to Paine's potential. Bates had Paine watched and in August 1956, beat Arsenal to his signature.

After retiring from football management in October 1957, Osman emigrated to Palm Beach, Florida where he died on 17 December 1998.

References

1911 births
1998 deaths
People from Bentworth
English men's footballers
Men's association football outside forwards
Poole Town F.C. players
Plymouth Argyle F.C. players
Southampton F.C. players
Millwall F.C. players
Bristol City F.C. players
Dartford F.C. players
Canterbury City F.C. players
Winchester City F.C. players
Western Football League players
English Football League players
English football managers
Canterbury City F.C. managers
Winchester City F.C. managers
People from Palm Beach, Florida
British Army personnel of World War II
Royal Tank Regiment soldiers

Harry Osman


Lake Eyre is a locality in the Australian state of South Australia located about  north of the state capital of Adelaide and  north  of the town of Marree and which is associated with the occasional body of water known as Lake Eyre.

The locality was established on 26 April 2013 in respect to "the long established local name."  Its name is derived from the former Lake Eyre National Park.

The locality covers the full extent of Lake Eyre including islands within the lake's extent, the Hunt Peninsula at the southern coast of the northern part of the lake and land on the lake's east side.

The principal land use within the locality is conservation with its full extent being occupied by the following protected areas - the Elliot Price Conservation Park and the Kati Thanda-Lake Eyre National Park.

Lake Eyre is located within the federal Division of Grey, the state electoral district of Stuart, the Pastoral Unincorporated Area of South Australia and the state's Far North region.

See also
Murrili meteorite

References

Towns in South Australia
Far North (South Australia)
Lake Eyre basin
Places in the unincorporated areas of South Australia

Lake Eyre, South Australia


Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms (arrhythmia), and to protect the heart from a second heart attack after a first heart attack (secondary prevention). They are also widely used to treat high blood pressure, although they are no longer the first choice for initial treatment of most patients.

Beta blockers are competitive antagonists that block the receptor sites for the endogenous catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) on adrenergic beta receptors, of the sympathetic nervous system, which mediates the fight-or-flight response. Some block activation of all types of β-adrenergic receptors and others are selective for one of the three known types of beta receptors, designated β1, β2 and β3 receptors. β1-adrenergic receptors are located mainly in the heart and in the kidneys. β2-adrenergic receptors are located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle. β3-adrenergic receptors are located in fat cells.

Beta receptors are found on cells of the heart muscles, smooth muscles, airways, arteries, kidneys, and other tissues that are part of the sympathetic nervous system and lead to stress responses, especially when they are stimulated by epinephrine (adrenaline). Beta blockers interfere with the binding to the receptor of epinephrine and other stress hormones and weaken the effects of stress hormones.

In 1964, James Black synthesized the first clinically significant beta blockers—propranolol and pronethalol; it revolutionized the medical management of angina pectoris and is considered by many to be one of the most important contributions to clinical medicine and pharmacology of the 20th century.

For the treatment of primary hypertension, meta-analyses of studies which mostly used atenolol have shown that although beta blockers are more effective than placebo in preventing stroke and total cardiovascular events, they are not as effective as diuretics, medications inhibiting the renin–angiotensin system (e.g., ACE inhibitors), or calcium channel blockers.

Medical uses

Beta blockers are utilized in the treatment of various conditions related to the heart and vascular system, as well as several other medical conditions. Common heart-related conditions for which beta blockers are well-established include angina pectoris, acute coronary syndromes, hypertension, and arrhythmias such as atrial fibrillation and heart failure. They are also used in the management of other heart diseases, such as hypertrophic obstructive cardiomyopathy, mitral valve stenosis or prolapse, and dissecting aneurysm. Additionally, beta blockers find applications in vascular surgery, the treatment of anxiety states, cases of thyrotoxicosis, glaucoma, migraines, and esophageal varices.

Congestive heart failure
Although beta blockers were once contraindicated in congestive heart failure, as they have the potential to worsen the condition due to their effect of decreasing cardiac contractility, studies in the late 1990s showed their efficacy at reducing morbidity and mortality. Bisoprolol, carvedilol, and sustained-release metoprolol are specifically indicated as adjuncts to standard ACE inhibitor and diuretic therapy in congestive heart failure, although at doses typically much lower than those indicated for other conditions. Beta blockers are only indicated in cases of compensated, stable congestive heart failure; in cases of acute decompensated heart failure, beta blockers will cause a further decrease in ejection fraction, worsening the patient's current symptoms.

Beta blockers are known primarily for their reductive effect on heart rate, although this is not the only mechanism of action of importance in congestive heart failure. Beta blockers, in addition to their sympatholytic β1 activity in the heart, influence the renin–angiotensin system at the kidneys. Beta blockers cause a decrease in renin secretion, which in turn reduces the heart oxygen demand by lowering the extracellular volume and increasing the oxygen-carrying capacity of the blood. Heart failure characteristically involves increased catecholamine activity on the heart, which is responsible for several deleterious effects, including increased oxygen demand, propagation of inflammatory mediators, and abnormal cardiac tissue remodeling, all of which decrease the efficiency of cardiac contraction and contribute to the low ejection fraction. Beta blockers counter this inappropriately high sympathetic activity, eventually leading to an improved ejection fraction, despite an initial reduction in ejection fraction.

Trials have shown beta blockers reduce the absolute risk of death by 4.5% over a 13-month period. In addition to reducing the risk of mortality, the numbers of hospital visits and hospitalizations were also reduced in the trials. A 2020 Cochrane review found minimal evidence to support the use of beta blockers in congestive heart failure in children, however did identify that from the data available, that they may be of benefit.

Therapeutic administration of beta blockers for congestive heart failure ought to begin at very low doses (1/8 of target) with a gradual escalation of the dose. The heart of the patient must adjust to decreasing stimulation by catecholamines and find a new equilibrium at a lower adrenergic drive.

Acute Myocardial Infarction

Beta blockers are indicated for the treatment of acute myocardial infarctions. During a myocardial infarction, systemic stress causes and increase in circulating catecholamines. This results an increase in heart rate and blood pressure, therefore increasing myocardial oxygen demand. Beta blockers competitively inhibit catecholamines acting on the β1-adrenergic receptors, thus reducing these detrimental effects and resulting in reduced myocardial oxygen consumption and demand.

A 2019 Cochrane review compared beta blockers with placebo or no intervention, it found that beta blockers probably reduced the short-term risk of reinfarction and the long-term risk of all-cause mortality and cardiovascular mortality. The review identified that beta blockers likely had little to no impact on short-term all-cause mortality and cardiovascular mortality.

Hypertension
Beta blockers are widely used for the treatment of hypertension.

A 2014 Cochrane review found that in individuals with mild-to-moderate hypertension, non-selective beta blockers led to a reduction of -10/-7mmHg (systolic/diastolic) without increased rates of adverse events. At higher doses, it was found to increase the rate of adverse effects such as a reduction in heart rate, without a corresponding reduction in blood pressure.

A 2017 Cochrane review on the use of beta blockers in hypertension found a modest reduction in cardiovascular disease, however, little to no change in mortality It suggested that the effects of beta blockers are inferior to other anti-hypertensive medications.

Anxiety
Officially, beta blockers are not approved for anxiolytic use by the U.S. Food and Drug Administration. However, many controlled trials in the past 25 years indicate beta blockers are effective in anxiety disorders, though the mechanism of action is not known. The physiological symptoms of the fight-or-flight response (pounding heart, cold/clammy hands, increased respiration, sweating, etc.) are significantly reduced, thus enabling anxious individuals to concentrate on the task at hand.

Musicians, public speakers, actors, and professional dancers have been known to use beta blockers to avoid performance anxiety, stage fright, and tremor during both auditions and public performances. The application to stage fright was first recognized in The Lancet in 1976, and by 1987, a survey conducted by the International Conference of Symphony Orchestra Musicians, representing the 51 largest orchestras in the United States, revealed 27% of its musicians had used beta blockers and 70% obtained them from friends, not physicians. Beta blockers are inexpensive, said to be relatively safe, and on one hand, seem to improve musicians' performances on a technical level, while some, such as Barry Green, the author of "The Inner Game of Music" and Don Greene, a former Olympic diving coach who teaches Juilliard students to overcome their stage fright naturally, say the performances may be perceived as "soulless and inauthentic".

Surgery
Low certainty evidence indicates that the use of beta blockers around the time of cardiac surgery may decrease the risk of heart dysrhythmias and atrial fibrillation. Starting them around the time of other types of surgery, however, may worsen outcomes. For non-cardiac surgery, the use of beta blockers to prevent adverse effects may reduce the risk of atrial fibrillation and myocardial infarctions (very low certainty evidence), however, there is moderate certainty evidence that this approach may increase the risk of hypotension. Low-certainty evidence suggests that beta blockers used perioperatively in non-cardiac surgeries may increase the risk of bradycardia.

Other
A 2014 Cochrane review investigated the use of beta blockers in the maintenance of chronic type B thoracic aortic aneurysm in comparison to other anti hypertensive medications. The review found no suitable evidence to support the current guidelines recommending its use.

A 2017 Cochrane review on the use of beta blockers to prevent aortic dissections in people with Marfan syndrome was unable to draw definitive conclusions due to lack of evidence.

Performance-enhancing use
Because they promote lower heart rates and reduce tremors, beta blockers have been used in professional sports where high accuracy is required, including archery, shooting, golf and snooker. Beta blockers are banned in some sports by the International Olympic Committee. In the 2008 Summer Olympics, 50-metre pistol silver medalist and 10-metre air pistol bronze medalist Kim Jong-su tested positive for propranolol and was stripped of his medals.

For similar reasons, beta blockers have also been used by surgeons.

Classical musicians have commonly used beta blockers since the 1970s to reduce stage fright.

Adverse effects
Adverse drug reactions  associated with the use of beta blockers include: nausea, diarrhea, bronchospasm, dyspnea, cold extremities, exacerbation of Raynaud's syndrome, bradycardia, hypotension, heart failure, heart block, fatigue, dizziness, alopecia (hair loss), abnormal vision, hallucinations, insomnia, nightmares, sexual dysfunction, erectile dysfunction and/or alteration of glucose and lipid metabolism. Mixed α1/β-antagonist therapy is also commonly associated with orthostatic hypotension. Carvedilol therapy is commonly associated with edema. Due to the high penetration across the blood–brain barrier, lipophilic beta blockers, such as propranolol and metoprolol, are more likely than other less lipophilic beta blockers to cause sleep disturbances, such as insomnia, vivid dreams and nightmares.

Adverse effects associated with β2-adrenergic receptor antagonist activity (bronchospasm, peripheral vasoconstriction, alteration of glucose and lipid metabolism) are less common with β1-selective (often termed "cardioselective") agents, but receptor selectivity diminishes at higher doses. Beta blockade, especially of the beta-1 receptor at the macula densa, inhibits renin release, thus decreasing the release of aldosterone. This causes hyponatremia and hyperkalemia.

Hypoglycemia can occur with beta blockade because β2-adrenoceptors normally stimulate glycogen breakdown (glycogenolysis) in the liver and pancreatic release of the hormone glucagon, which work together to increase plasma glucose. Therefore, blocking β2-adrenoceptors lowers plasma glucose. β1-blockers have fewer metabolic side effects in diabetic patients; however, the fast heart rate that serves as a warning sign for insulin-induced low blood sugar may be masked, resulting in hypoglycemia unawareness. This is termed beta blocker-induced hypoglycemia unawareness. Therefore, beta blockers are to be used cautiously in diabetics.

A 2007 study revealed diuretics and beta blockers used for hypertension increase a patient's risk of developing diabetes mellitus, while ACE inhibitors and angiotensin II receptor antagonists (angiotensin receptor blockers) actually decrease the risk of diabetes. Clinical guidelines in Great Britain, but not in the United States, call for avoiding diuretics and beta blockers as first-line treatment of hypertension due to the risk of diabetes.

Beta blockers must not be used in the treatment of selective alpha-adrenergic agonist overdose. The blockade of only beta receptors increases blood pressure, reduces coronary blood flow, left ventricular function, and cardiac output and tissue perfusion by means of leaving the alpha-adrenergic system stimulation unopposed. Beta blockers with lipophilic properties and CNS penetration such as metoprolol and labetalol may be useful for treating CNS and cardiovascular toxicity from a methamphetamine overdose. The mixed alpha- and beta blocker labetalol is especially useful for treatment of concomitant tachycardia and hypertension induced by methamphetamine. The phenomenon of "unopposed alpha stimulation" has not been reported with the use of beta blockers for treatment of methamphetamine toxicity. Other appropriate antihypertensive drugs to administer during hypertensive crisis resulting from stimulant overdose are vasodilators such as nitroglycerin, diuretics such as furosemide, and alpha blockers such as phentolamine.

Contraindications & cautions

Absolute contraindications:
 Bradycardia
 Hypotension
 Hypersensitivity to beta blockers
 Cardiogenic shock
 Second or third degree AV block

Relative contraindications, or contraindications specific to certain beta-blockers:
 Long QT Syndrome: sotalol is contraindicated
 History of Torsades de Pointes: sotalol is contraindicated

Cautions:
 Abrupt discontinuations
 Acute bronchospasm
 Acute heart failure
 Asthma: see below
 Bronchitis
 Cerebrovascular disease
 Chronic obstructive pulmonary disease (COPD)
 Emphysema
 Kidney failure
 Hepatic disease
 Myopathy
 Pheochromocytoma
 Psoriasis
 Reynaud phenomenon
 Stroke
 Vasospastic angina
 Wolff–Parkinson–White syndrome

Asthma
The 2007 National Heart, Lung, and Blood Institute (NHLBI) asthma guidelines recommend against the use of non-selective beta blockers in asthmatics, while allowing for the use of cardio selective beta blockers.

Cardio selective beta blocker (β1 blockers) can be prescribed at the least possible dose to those with mild to moderate respiratory symptoms. β2-agonists can somewhat mitigate β-blocker-induced bronchospasm where it exerts greater efficacy on reversing selective β-blocker-induced bronchospasm than the nonselective β-blocker-induced worsening asthma and/or COPD.

Diabetes mellitus
Epinephrine signals early warning of the upcoming hypoglycemia.

Beta blockers' inhibition on epinephrine's effect can somewhat exacerbate hypoglycemia by interfering with glycogenolysis and mask signs of hypoglycemia such as tachycardia, palpitations, diaphoresis, and tremors. Diligent blood glucose level monitoring is necessary for a patient with diabetes mellitus on beta blocker.

Hyperthyroidism
Abrupt withdrawal can result in a thyroid storm.

Bradycardia or AV block
Unless a pacemaker is present, beta blockers can severely depress conduction in the AV node, resulting in a reduction of heart rate and cardiac output. One should be very cautious with the use of beta blockers in tachycardia patients with Wolff-Parkinson-White Syndrome, as it can result in life-threatening arrhythmia in certain patients. By slowing the conduction through the AV node, preferential conduction through the accessory pathway is favored. If the patient happens to develop atrial flutter, this could lead to a 1:1 conduction with very fast ventricular rate, or worse, ventricular fibrillation in the case of atrial fibrillation.

Toxicity
Glucagon, used in the treatment of overdose, increases the strength of heart contractions, increases intracellular cAMP, and decreases renal vascular resistance. It is, therefore, useful in patients with beta blocker cardiotoxicity. Cardiac pacing is usually reserved for patients unresponsive to pharmacological therapy.

People experiencing bronchospasm due to the β2 receptor-blocking effects of nonselective beta blockers may be treated with anticholinergic drugs, such as ipratropium, which are safer than beta agonists in patients with cardiovascular disease. Other antidotes for beta blocker poisoning are salbutamol and isoprenaline.

β-Adrenergic receptor antagonism

Stimulation of β1 receptors by epinephrine and norepinephrine induces a positive chronotropic and inotropic effect on the heart and increases cardiac conduction velocity and automaticity. Stimulation of β1 receptors on the kidney causes renin release. Stimulation of β2 receptors induces smooth muscle relaxation, induces tremor in skeletal muscle, and increases glycogenolysis in the liver and skeletal muscle. Stimulation of β3 receptors induces lipolysis.

Beta blockers inhibit these normal epinephrine- and norepinephrine-mediated sympathetic actions, but have minimal effect on resting subjects.
That is, they reduce the effect of excitement or physical exertion on heart rate and force of contraction, and also tremor, and breakdown of glycogen. Beta blockers can have a constricting effect on the bronchi of the lungs, possibly worsening or causing asthma symptoms.

Since β2 adrenergic receptors can cause vascular smooth muscle dilation, beta blockers may cause some vasoconstriction. However, this effect tends to be small because the activity of β2 receptors is overshadowed by the more dominant vasoconstricting α1 receptors. By far the greatest effect of beta blockers remains in the heart. Newer, third-generation beta blockers can cause vasodilation through blockade of alpha-adrenergic receptors.

Accordingly, nonselective beta blockers are expected to have antihypertensive effects. The primary antihypertensive mechanism of beta blockers is unclear, but may involve reduction in cardiac output (due to negative chronotropic and inotropic effects). It may also be due to reduction in renin release from the kidneys, and a central nervous system effect to reduce sympathetic activity (for those beta blockers that do cross the blood–brain barrier, e.g. propranolol).

Antianginal effects result from negative chronotropic and inotropic effects, which decrease cardiac workload and oxygen demand. Negative chronotropic properties of beta blockers allow the lifesaving property of heart rate control. Beta blockers are readily titrated to optimal rate control in many pathologic states.

The antiarrhythmic effects of beta blockers arise from sympathetic nervous system blockade—resulting in depression of sinus node function and atrioventricular node conduction, and prolonged atrial refractory periods. Sotalol, in particular, has additional antiarrhythmic properties and prolongs action potential duration through potassium channel blockade.

Blockade of the sympathetic nervous system on renin release leads to reduced aldosterone via the renin–angiotensin–aldosterone system, with a resultant decrease in blood pressure due to decreased sodium and water retention.

Additional pharmacological properties

Intrinsic sympathomimetic activity
Also referred to as intrinsic sympathomimetic effect, this term is used particularly with beta blockers that can show both agonism and antagonism at a given beta receptor, depending on the concentration of the agent (beta blocker) and the concentration of the antagonized agent (usually an endogenous compound, such as norepinephrine). See partial agonist for a more general description.

Some beta blockers (e.g. oxprenolol, pindolol, penbutolol, labetalol and acebutolol) exhibit intrinsic sympathomimetic activity (ISA). These agents are capable of exerting low-level agonist activity at the β-adrenergic receptor while simultaneously acting as a receptor site antagonist. These agents, therefore, may be useful in individuals exhibiting excessive bradycardia with sustained beta blocker therapy.

Agents with ISA should not be used for patients with any kind of angina as it can aggravate or after myocardial infarctions. They may also be less effective than other beta blockers in the management of angina and tachyarrhythmia.

α1-Adrenergic receptor antagonism
Some beta blockers (e.g., labetalol and carvedilol) exhibit mixed antagonism of both β- and α1-adrenergic receptors, which provides additional arteriolar vasodilating action.

Blood–brain barrier permeability
Beta blockers vary in their lipophilicity (fat solubility) and in turn in their ability to cross the blood–brain barrier and exert effects in the central nervous system. Beta blockers with greater blood–brain barrier permeability can have both neuropsychiatric therapeutic benefits and side effects, as well as adverse cognitive effects. Central nervous system-related side effects and risks of beta blockers may include fatigue, depression, sleep disorders (namely insomnia) and nightmares, visual hallucinations, delirium, psychosis, Parkinson's disease, and falling. Conversely, central nervous system-related benefits of beta blockers may include prevention and treatment of migraine, essential tremor, akathisia, anxiety, post-traumatic stress disorder, aggression, and obsessive–compulsive disorder.

Most beta blockers are lipophilic and can cross into the brain, but there are a number of exceptions. Highly lipophilic beta blockers include penbutolol, pindolol, propranolol, and timolol, moderately lipophilic beta blockers include acebutolol, betaxolol, bisoprolol, carvedilol, metoprolol, and nebivolol, and low lipophilicity or hydrophilic beta blockers include atenolol, carteolol, esmolol, labetalol, nadolol, and sotalol. It is thought that highly lipophilic beta blockers are able to readily cross into the brain, moderately lipophilic beta blockers are able to cross to a lesser degree, and low lipophilicity or hydrophilic beta blockers are minimally able to cross. The preceding beta blockers also vary in their intrinsic sympathomimetic activity and β1-adrenergic receptor selectivity (or cardioselectivity), resulting in further differences in pharmacological profiles and suitability in different contexts between them.

Examples

Nonselective agents
Nonselective beta blockers display both β1 and β2 antagonism.
 Propranolol
 Bucindolol (has additional α1-blocking activity)
 Carteolol
 Carvedilol (has additional α1-blocking activity)
 Labetalol (has intrinsic sympathomimetic activity and additional α1-blocking activity)
 Nadolol
 Oxprenolol (has intrinsic sympathomimetic activity)
 Penbutolol (has intrinsic sympathomimetic activity)
 Pindolol (has intrinsic sympathomimetic activity)
 Sotalol (not considered a "typical beta blocker")
 Timolol

β1-selective agents
β1-selective beta blockers are also known as cardioselective beta blockers. Pharmacologically, the beta-blockade of the β1 receptors in the heart will act on cAMP. The function of cAMP as a second messenger in the cardiac cell is that it phosphorylates the LTCC and the ryanodine receptor to increase intracellular calcium levels and cause contraction. Beta-blockade of the β1 receptor will inhibit cAMP from phosphorylating, and it will decrease the ionotrophic and chronotropic effect. Note that drugs may be cardioselective, or act on β1 receptors in the heart only, but still have instrinsic sympathomimetic activity.
 Acebutolol (has intrinsic sympathomimetic activity, ISA)
 Atenolol
 Betaxolol
 Bisoprolol
 Celiprolol (has intrinsic sympathomimetic activity)
 Metoprolol
 Nebivolol
 Esmolol
Nebivolol and bisoprolol are the most β1 cardioselective beta blockers.

β2-selective agents
 Butaxamine
 ICI-118,551

β3-selective agents
 SR 59230A

β1 selective antagonist and β3 agonist agents
 Nebivolol

Comparative information

Pharmacological differences
 Agents with intrinsic sympathomimetic action (ISA)
 Acebutolol, pindolol, labetalol, mepindolol, oxprenolol, celiprolol, penbutolol
 Agents organized by lipid solubility (lipophilicity)
 High lipophilicity: propranolol, labetalol
 Intermediate lipophilicity: metoprolol, bisoprolol, carvedilol, acebutolol, timolol, pindolol
 Low lipophilicity (also known as hydrophilic beta blockers): atenolol, nadolol, and sotalol
 Agents with membrane stabilizing effect
 Carvedilol, propranolol > oxprenolol > labetalol, metoprolol, timolol

Indication differences
 Agents specifically labeled for cardiac arrhythmia
 Esmolol, sotalol, landiolol (Japan)
 Agents specifically labeled for congestive heart failure
 Bisoprolol, carvedilol, sustained-release metoprolol
 Agents specifically labeled for glaucoma
 Betaxolol, carteolol, levobunolol, timolol, metipranolol
 Agents specifically labeled for myocardial infarction
 Atenolol, metoprolol (immediate release), propranolol (immediate release), timolol, carvedilol (after left ventricular dysfunction), bisoprolol (preventive treatment before and primary treatment after heart attacks)
 Agents specifically labeled for migraine prophylaxis
 Timolol, propranolol

Propranolol is the only agent indicated for the control of tremor, portal hypertension, and esophageal variceal bleeding, and used in conjunction with α-blocker therapy in phaeochromocytoma.

Other effects

Beta blockers, due to their antagonism at beta-1 adrenergic receptors, inhibit both the synthesis of new melatonin and its secretion by the pineal gland. The neuropsychiatric side effects of some beta blockers (e.g. sleep disruption, insomnia) may be due to this effect.

Some pre-clinical and clinical research suggests that some beta blockers may be beneficial for cancer treatment. However, other studies do not show a correlation between cancer survival and beta blocker usage. Also, a 2017 meta-analysis failed to show any benefit for the use of beta blockers in breast cancer.

Beta blockers have also been used for the treatment of schizoid personality disorder. However, there is limited evidence supporting the efficacy of supplemental beta blocker use in addition to antipsychotic drugs for treating schizophrenia.

Contrast agents are not contraindicated in those receiving beta blockers.

See also
 Alpha blockers

References

External links
 Musicians and beta-blockers by Gerald Klickstein, March 11, 2010 (A blog post that considers "whether beta-blockers are safe, effective, and appropriate for performers to use.")
 Better Playing Through Chemistry by Blair Tindall, The New York Times, October 17, 2004. (Discusses the use of beta blockers among professional musicians)
 Musicians using beta blockers by Blair Tindall. A condensed version of the above article.
 In Defense of the Beta Blocker by Carl Elliott, The Atlantic, August 20, 2008. (Discusses the use of propranolol by a North Korean pistol shooter in the 2008 Olympics)

Scottish inventions

Beta blocker


Masonville is an unincorporated community and census-designated place (CDP) in Daviess County, Kentucky, United States. The population was 1,014 at the 2010 census. It is included in the Owensboro Metropolitan Statistical Area.

Geography
Masonville is located in south-central Daviess County at  (37.683612, -87.036563). U.S. Route 231 passes through the center of the CDP. The William H. Natcher Parkway forms the eastern border of the CDP, but there is no exit for the community. Owensboro, the county seat, is  to the northwest, and Hartford is  to the southeast.

According to the United States Census Bureau, the Masonville CDP has a total area of , of which  is land and , or 0.66%, is water.

Demographics

As of the census of 2000, there were 1,075 people, 381 households, and 310 families residing in the CDP. The population density was . There were 411 housing units at an average density of . The racial makeup of the CDP was 99.16% White, 0.09% African American, and 0.74% from two or more races. Hispanic or Latino of any race were 0.19% of the population.

There were 381 households, out of which 41.5% had children under the age of 18 living with them, 67.7% were married couples living together, 9.7% had a female householder with no husband present, and 18.6% were non-families. 17.1% of all households were made up of individuals, and 5.5% had someone living alone who was 65 years of age or older. The average household size was 2.82 and the average family size was 3.15.

In the CDP, the population was spread out, with 30.0% under the age of 18, 7.3% from 18 to 24, 30.8% from 25 to 44, 23.0% from 45 to 64, and 9.0% who were 65 years of age or older. The median age was 34 years. For every 100 females, there were 102.8 males. For every 100 females age 18 and over, there were 99.7 males.

The median income for a household in the CDP was $37,171, and the median income for a family was $45,795. Males had a median income of $35,089 versus $19,250 for females. The per capita income for the CDP was $20,469. About 10.9% of families and 10.3% of the population were below the poverty line, including 21.2% of those under age 18 and 10.5% of those age 65 or over.

References

Census-designated places in Daviess County, Kentucky
Census-designated places in Kentucky
Owensboro metropolitan area

Masonville, Kentucky


Kigga is a small village located at a distance of 9 km from Sringeri in Chikmagalur district. The main attraction of Kigga is Sri Rishya Shringeshwara temple (Rishya Shringa). Another attraction of Kigga is Narasimha Parvatha, the tallest peak in the Agumbe Ghats. Sirimane waterfall is located nearby Kigga.

References

Villages in Chikkamagaluru district

Kigga


Karelia (Karelian and  [];  [], historically Коре́ла, Korela [];  []) is an area in Northern Europe of historical significance for Russia (including the Soviet era), Finland, and Sweden. It is currently divided between northwestern Russia (the federal subjects of the Republic of Karelia and Leningrad Oblast) and Finland (the regions of South Karelia, North Karelia, and the eastern portion of Kymenlaakso).

Use of name

Various subdivisions may be called Karelia. Finnish Karelia is a historical province of Finland and is now divided between Finland and Russia, often called just Karjala in Finnish. The eastern part of this chiefly Lutheran area was ceded to Russia after the Winter War of 1939–40.

The Republic of Karelia is a Russian federal subject, including East Karelia, with a chiefly Russian Orthodox population.

Within present-day Finland, Karjala refers to the regions of South and North Karelia, although parts of historical Karelia also lie within the region of Kymenlaakso (east of the River Kymi), Northern Savonia (Kaavi, Rautavaara and Säyneinen), and Southern Savonia (Mäntyharju).

Geography

Karelia stretches from the White Sea coast to the Gulf of Finland. It contains the two largest lakes in Europe, Lake Ladoga and Lake Onega. The Karelian Isthmus is located between the Gulf of Finland and Lake Ladoga. The highest point of Karelia, the  high Nuorunen, is located in the Russian side of the Maanselka hill region.

The border between Karelia and Ingria, the land of the closely related Ingrian people, had originally been the Neva River itself but later on it was moved northward into Karelian isthmus to follow the Sestra River (), today in the Saint Petersburg metropolitan area, but in 1812–1940 the Russo-Finnish border.

On the other side of Lake Ladoga, the River Svir is usually thought of as the traditional southern border of Karelian territory while Lake Onega and the White Sea mark the Eastern border. The River Kymi marks the historic western border of Karelian territory as it served as the boundary between the Häme Finns and the Karelians during the Middle Ages. The River Kymi is also said to have formed a boundary between the eastern and western cultural spheres by the beginning of the Bronze Age at the latest. In the North lived the nomadic Samis, but there were no natural borders except for large wooded areas (taiga) and the tundra.

In historical texts, Karelia is sometimes divided into East Karelia and West Karelia, which are also called Russian Karelia and Finnish Karelia respectively.  The area to the north of Lake Ladoga which belonged to Finland before World War II is called Ladoga Karelia, and the parishes on the old pre-war border are sometimes called Border Karelia. White Karelia (sometimes the Finnish or Karelian term "Viena Karelia", or in some English-language sources, "White Sea Karelia", is used) is the northern part of East Karelia and Olonets Karelia is the southern part.

Tver Karelia denotes the villages in the Tver Oblast that are inhabited by Tver Karelians.

Inhabited localities
Republic of Karelia
Petrozavodsk (, Petroskoi, from late 1941 to 1944 known as Äänislinna/Onegaborg to Finns)
Belomorsk (, Sorokka)
Medvežyegorsk (, Karhumäki)
Kalevala (, Uhtua)
Kem (, Vienan Kemi, compare with Kemi)
Kostomukša (, Kostamus)
Kondopoga  (, Kontupohja)
Sortavala (, Sortavala, Sordavala)
Suojarvi  (, Suojärvi)
Segeža  (, Sekehe)
Pitkjaranta (, Pitkäranta)
Olonec (, Aunus)
Karelian Isthmus
Vyborg (, Viipuri, Viborg)
Priozersk (, Käkisalmi, Kexholm)
Primorsk (Примо́рск, Koivisto, Björkö)
Svetogorsk (, Enso)
South Karelia
Imatra
Joutseno
Lappeenranta (Villmanstrand)
North Karelia
Joensuu
Ilomantsi (Ilomants)
Kitee
Kesälahti
Kontiolahti
Lieksa
Liperi
Nurmes
Outokumpu

History

During the Early Middle Ages, settlers from western Finland mixed with the local population to form the Karelian ethnic group. Possible migration from elsewhere may also have contributed to the Karelian ethnic composition.

Archeological evidence indicates that Karelian inhabitation was highest along the western shore of Lake Ladoga and the Karelian Isthmus, with multiple cemeteries and other archeological discoveries dating from AD 600 to AD 800. In South Karelia, the number of archeological discoveries from this time period is lower, though permanent inhabitation was nonetheless present. Lappee, South Karelia has been continuously inhabited for approximately 2,000 years. In North Karelia, only one archeological discovery from this time period has been found, dating to the eighth century. The considerably higher number of archeological discoveries in these regions from AD 800 to AD 1050 indicates that the Karelian population grew and expanded rapidly during this time.

Karelia was bitterly fought over by Sweden and the Novgorod Republic for a period starting in the 13th-century Swedish-Novgorodian Wars. The Treaty of Nöteborg (Finnish: Pähkinäsaaren rauha) in 1323 divided Karelia between the two. Sweden received the southern portion of the Karelian Isthmus and most of South Karelia. The province of Swedish Karelia would include this territory, plus the region east of the Kymi river, with Viborg (Finnish: Viipuri) becoming the capital of the province. Novgorod received the northern portion of the Karelian Isthmus. North Karelia, Ladoga Karelia, and the northern portion of South Karelia fell under Novgorodian control. Käkisalmi served as the main population center of this region.

In the Treaty of Stolbovo of 1617, large parts of Russian Karelia were ceded to Sweden. Conflicts between the new Swedish rulers and the indigenous population of these areas led to an exodus: thousands of Karelians, including the ancestors of the Tver Karelians, emigrated to Russia.

The Treaty of Nystad (Finnish: Uudenkaupungin rauha) in 1721 between Imperial Russia and Sweden ceded a portion of Karelia to Russia. The Treaty of Åbo in 1743 between Sweden and Russia then ceded South Karelia to Russia. After Finland had been occupied by Russia in the Finnish War, parts of the ceded provinces (Old Finland) were incorporated into the Grand Duchy of Finland in 1812. In 1917, Finland became independent and the border was confirmed by the Treaty of Tartu in 1920.

Finnish partisans were involved in attempts to overthrow the Bolsheviks in Russian Karelia (East Karelia) in 1918–21, as in the failed Aunus expedition. They also wanted to incorporate the rest of Karelia into Finland and cooperated with the short-lived Republic of Uhtua. These mainly private expeditions ended after the signing of the Treaty of Tartu. After the end of the Russian Civil War and the establishment of the Soviet Union in 1922, the Russian part of Karelia became the Karelian Autonomous republic of the Soviet Union (ASSR) in 1923.

At the beginning of the Second World War in 1939, the Soviet Union attacked Finland, thus starting the Winter War. The Treaty of Moscow, signed in 1940, handed a large portion of Finnish Karelia to the Soviet Union, and over 400,000 people had to be relocated within Finland. During the Continuation War of 1941-1944, Finland took back territory ceded in 1940, and also invaded and occupied much of East Karelia. Finland was forced out of these regions in 1944. After the war, Soviet expansion caused considerable bitterness in Finland, which lost its fourth biggest city, Viipuri, its industrial heartland along the river Vuoksi, the eastern portion of the Saimaa canal that connected central Finland to the Gulf of Finland, and access to the fishing waters of Lake Ladoga (Finnish: Laatokka). One eighth of its citizens became refugees with no chance of return. The whole population from the areas ceded to the Soviet Union was evacuated and resettled in other parts of Finland. The present inhabitants of the former Finnish parts of Russia, including the city of Vyborg/Viipuri and the Karelian Isthmus – are post-war immigrants or their descendants.

The former Karelian ASSR was incorporated into a new Karelo-Finnish SSR from 1941 to 1956, but then it became an ASSR again. Karelia was the only Soviet republic that was "demoted" from an SSR to an ASSR within the Russian SFSR.

The portion of Viipuri Province that remained within Finland following the Second World War was renamed Kymi Province, and kept this name from 1945 to 1997. The eastern part of this province is now the region of South Karelia, while the western portion is part of Kymenlaakso.

In 1991, with the collapse of the Soviet Union, the ASSR became the Republic of Karelia.

Politics

Karelia is politically divided between Finland and Russia. The Republic of Karelia is a federal subject of Russia formed in 1991 from the Karelian ASSR. The Karelian Isthmus belongs to the Leningrad Oblast. The Finnish side consists of parts of the regions (maakunta) of South Karelia, North Karelia and Kymenlaakso.

There are some small groups of Finns campaigning for closer ties between Finland and Karelia: for instance, in the Karjalan Liitto (Karelian League) and ProKarelia.

Demographics

On the Finnish side, the area is Finnish-speaking. The South Karelian dialects of the Finnish language (closely related to the Karelian language) are spoken in South Karelia. The eastern Savonian dialects are spoken in North Karelia, part of the group of dialects spoken in Eastern and Central Finland.

Ingrian Finnish dialects are spoken in Ingria, which is an area around St. Petersburg, between the Estonian border and Lake Ladoga. Ingrian Finns settled in the region in the 17th century after the Swedish conquest of the area. The settlers spoke Karelian and Savonian dialects of Finnish. The older inhabitants of the Ingria, the Ingrians, have their own language which is related to the Karelian language and the south-eastern dialects of Finnish.

Karelians evacuated from the part of Finnish Karelia ceded to Russia were resettled all over Finland. Today about one million people in Finland can trace their roots in the area ceded to the Soviet Union after World War II. In Finland, about 5,000 people speak the Karelian language.

Culture

Kalevala
Karelian Bear Dog
Karelian hot pot
Karelian language
Karelian pasties
Karelo-Finnish Laika
Music of Karelia

Tourism
Russian Karelia is a regular destination for international tourism due to its unique architectural, cultural and historical sites such as Kizhi and Valaam. The region is visited by tourists in both summer and winter when possible activities include riding in a sled behind a dog team and running from the banya to an ice hole and back. Summer hikers can visit the Kivach waterfall or the Demon's Chair plateau.

In South Karelia, Lappeenranta is a popular destination for Russian tourists, with 1.5 million visiting annually. Imatrankoski in Imatra has been a tourist attraction since the late 18th century, when the Empress of Russia Catherine the Great visited the site in 1772.

Koli National Park in North Karelia began receiving tourists when Karelianism became a major trend. Koli was a source of inspiration for numerous painters and composers such as Jean Sibelius, Juhani Aho and Eero Järnefelt, who in turn contributed to Karelianism through their work. Koli gained national park status in 1991.

See also
Asbestos-ceramic, a type of pottery made in Karelia and the vicinity.
History of Finland
Karelianism, a cultural movement in the Grand Duchy of Finland.
Karelia Suite, a collection of pieces by the composer Jean Sibelius.
Lauri Törni, born in Viipuri, a soldier and recipient of the Mannerheim Cross during the Continuation War, who later served with the German and American armies.
 Karelian pony, horse breed native to Russia.

References

Sources
"They Took My Father," by Mayme Sevander and Laurie Hertzel, a history of Finnish Americans who emigrated to Soviet Karelia during the Great Depression.

Further reading

External links

 Karelians (The Peoples of the Red Book)
 Tracing Finland's eastern border – ThisisFINLAND
Saimaa Canal links two Karelia – ThisisFINLAND
 Regional flag
 Visitkarelia.fi – Information about travel, tourism and other fields in North Karelia
 Information about Southern Karelia travel
 Pielis.ru –  travel information about North Karelia region and City of Joensuu
 Karelia will return in your dreams Article about Karelia with photos and useful tourist information.
 Genocide in Soviet Karelia: Stalin's Terror and the Finns of Soviet Karelia
 Their Ideals Were Crushed. A Daughter's Story of the Säde Commune in Soviet Karelia.

Fennoscandia
Historical regions in Russia
History of Karelia
Geographic history of Finland

Karelia


Chingford Hatch was one of the three hamlets comprising the old parish of Chingford, before the area was developed in the nineteenth century. The name is still widely used for the area immediately around Hatch Lane (A1009) at the foot of Friday Hill (OS Grid Reference ).

Saint Anne's Church serves the area and is located in Larkshall Road (at the western end of Hatch Lane). Originating in 1891 as a Mission Room, a permanent church was built and given its own separate parish in 1953.

Close to St Anne's is The Larks Hall public house, a timber-framed building that prior to the 1980s was Larks Hall Farm.

External links
 St Anne's Parish Church, Chingford

Areas of London
Districts of the London Borough of Waltham Forest

Chingford Hatch


Andrew Zachary Fire (born April 27, 1959 in Palo Alto, California) is an American biologist. He is a professor of pathology and genetics at Stanford University School of Medicine. Fire was given the 2006 Nobel Prize in Physiology or Medicine for the discovery of RNA interference. The research was conducted at Carnegie Institution for Science and published in 1998.

Education
Fire completed high school at age 15. He wanted to study at Stanford University, where he would later work, but was not accepted. He studied at the University of Californiaat Berkeley. Fire graduated with a bachelor's degree in mathematics at 19,  and earned a PhD from the Massachusetts Institute of Technology (MIT) in 1983.

Nobel prize
In 2006, Fire and Craig Mello shared the Nobel Prize in Physiology or Medicine for work first published in 1998 in the journal Nature. The paper reports that tiny snippets of double-stranded RNA (dsRNA) effectively shut down specific genes, and so caused the destruction of messenger RNA (mRNA) with sequences matching the dsRNA. As a result, the mRNA cannot be translated into protein.

Fire and Mello found that dsRNA was much more effective in gene silencing than the previously described method of RNA interference with single-stranded RNA. Because only small numbers of dsRNA molecules were required for the observed effect, Fire and Mello proposed that a catalytic process was involved. This hypothesis was confirmed by later research.

The Nobel Prize citation, issued by Sweden's Karolinska Institute, said: "This year's Nobel Laureates have discovered a fundamental mechanism for controlling the flow of genetic information". The British Broadcasting Corporation (BBC) quoted Nick Hastie, director of the Medical Research Council's Human Genetics Unit, on the scope and implications of the research:

"It is very unusual for a piece of work to completely revolutionise the whole way we think about biological processes and regulation, but this has opened up a whole new field in biology".

References

1959 births
Living people
American biologists
American Nobel Prize winners
Scientists from California
Jewish American scientists
People from Palo Alto, California
Pathologists

Andrew Fire


Jilson Setters (born James William Day 1861 – May 6, 1942), who was also known to perform under the monikers Blind Bill Day, J.W. Day, and the "Singin' Fiddler of Lost Hope Hollow", was an American folk singer and fiddle player. Setters was discovered by folklorist Jean Bell Thomas, who fabricated a persona for him, arranged recording sessions with RCA Records, and promoted him around the U.S. and England until the late-1930s.

Biography

James William Day was born in Catlettsburg, Kentucky in 1861. Day was not born blind, but rather through inconclusive circumstances developed the impairment sometime in his early youth. He was a self-taught fiddle player who performed at town halls and dances, sometimes under the stage name "Blind Bill Day", and occasionally supported himself by begging on the streets. In 1906, Day had a procedure to remove the cataracts from his eyes, thus restoring his eyesight. Though he had an adequate ability to see, Day still performed with his "Blind Bill Day" moniker.

In 1926, Day was discovered by promoter and folklorist Jean Bell Thomas, who was fascinated that rural folk musicians like Day possessed traits that had been passed down from their Elizabethan English forebears relatively unaltered, especially in their renditions of folk ballads. Thomas decided to manage Day, creating and documenting a persona almost entirely fabricated from her. According to Thomas's story, Day, who changed his name to Jilson Setters per her suggestion, was blind from birth, lived in isolation in the mountains, and gained his eyesight only recently, thanks to a procedure that Thomas financed. Moreover, with his ability to see, Setters was shocked by the appearance of the civilized world. Setters recorded ten sides for RCA Records in New York City, including "The Wild Wagoner", which has become a standard in traditional folk repertoires.

In February 1930, Thomas published a heavily fictionalized article in American Magazine, entitled "Blind Jilson: Singin' Fiddler of Lost Hope Hollow", detailing Thomas first encountering Setters, their arrangement of his operation, and radio station work in New York City. In 1931, Setters traveled to London to perform at Royal Albert Hall, and for King George V and Mary of Teck. Upon his return to the U.S., Setters was the featured performer in the American Folk Song Festival, which was managed by Thomas from 1930 to 1972. However, whether it was a consequence of insufficient record sales or lack of interest, Thomas abandoned her project with Setters.

Setters continued to perform well into the 1930s and early 1940s. He died on May 6, 1942, in Cattlesburg, Kentucky.

References

External links

1861 births
1942 deaths
American folk singers
People from Catlettsburg, Kentucky
American fiddlers
Folk musicians from Kentucky
Singers from Kentucky

Jilson Setters


Observation is an activity of an intelligent living being (e.g. human), which senses and assimilates the knowledge of a phenomenon in its framework of previous knowledge and ideas.

Observation is more than the bare act of observing: Observation requires observing and seeking knowledge, often through experiment.

Observations that come from self-defining instruments are often unreliable. Such observations are hard to reproduce because they may vary even with respect to the same stimuli. Thus they are not of much use in exact sciences like physics which require instruments which do not define themselves. It is thus often necessary to use various engineered instruments like: spectrometers, oscilloscopes, cameras, telescopes, interferometers, tape recorders, thermometers etc. and tools like clocks, scale that help in improving the accuracy, quality and utility of the information obtained from an observation.

The accuracy and tremendous success of science is primarily attributed to the accuracy and objectivity (i.e. repeatability) of observation of the reality that science explores.

The role of observation in the scientific method

Scientific method refers to techniques for investigating phenomena, acquiring new knowledge, or correcting and integrating previous knowledge. To be termed scientific, a method of inquiry must be based on gathering observable, empirical and measurable evidence subject to specific principles of reasoning. A scientific method consists of the collection of data through observation and experimentation, and the formulation and testing of hypotheses.

Although procedures vary from one field of inquiry to another, identifiable features distinguish scientific inquiry from other methodologies of knowledge. Scientific researchers propose hypotheses as explanations of phenomena, and design experimental studies to test these hypotheses. These steps must be repeatable in order to dependably predict any future results. Theories that encompass wider domains of inquiry may bind many hypotheses together in a coherent structure. This in turn may help form new hypotheses or place groups of hypotheses into context.

Among other facets shared by the various fields of inquiry is the conviction that the process be objective to reduce a biased interpretation of the results. Another basic expectation is to document, archive and share all data and methodology so they are available for careful scrutiny by other scientists, thereby allowing other researchers the opportunity to verify results by attempting to reproduce them. This practice, called full disclosure, also allows statistical measures of the reliability of these data to be established.

Testing and improvement

The scientific process is iterative. At any stage it is possible that some consideration will lead the scientist to repeat an earlier part of the process. Failure to develop an interesting hypothesis may lead a scientist to re-define the subject they are considering. Failure of a hypothesis to produce interesting and testable predictions may lead to reconsideration of the hypothesis or of the definition of the subject. Failure of the experiment to produce interesting results may lead the scientist to reconsidering the experimental method, the hypothesis or the definition of the subject.

Other scientists may start their own research and enter the process at any stage. They might adopt the characterization and formulate their own hypothesis, or they might adopt the hypothesis and deduce their own predictions. Often the experiment is not done by the person who made the prediction and the characterization is based on experiments done by someone else. Published results of experiments can also serve as a hypothesis predicting their own reproducibility.

References

Related pages
Scientific method

Science
Philosophy of science
Basic English 850 words

Observation


A genetic bottleneck occurs when many individuals of a species are killed (or die) because of a natural event, such as a famine or a disease. The phenomenon is also called population bottleneck.The result of this, is that the gene pool will be smaller, and the genetic diversity will also be smaller, in future generations. This can have effects, such as an inbreeding depression.

Ecology

Population bottleneck