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132-814: Lane Smith was born in 1936 in Memphis, Tennessee . He graduated from the Leelanau School , a boarding school in Glen Arbor, Michigan , and spent one year boarding at the Hill School in Pottstown, Pennsylvania , before studying at the Actors Studio in the late 1950s and early 1960s along with Dustin Hoffman and Al Pacino ; he was recognized in their Hall of Fame. Smith served two years in

264-611: A "blueprint" for future incidents of police brutality nationwide. The incident also resulted in the disbanding of the city's "SCORPION" unit, which had been mandated with directly combating the most violent crimes in the city. All the officers charged with involvement in Nichols's death were members of the unit. According to the United States Census Bureau , the city has a total area of 324.0 square miles (839.2 km ), of which 315.1 square miles (816.0 km )

396-481: A 20% change in the slope of the ALSFRS-R as being clinically meaningful, which is the most common threshold used to determine whether a new treatment is working in clinical trials. Difficulties with chewing and swallowing make eating very difficult ( dysphagia ) and increase the risk of choking or of aspirating food into the lungs. In later stages of the disorder, aspiration pneumonia can develop, and maintaining

528-483: A Golden Globe nomination for his performance. He also appeared in the original Broadway stage production of David Mamet 's Glengarry Glen Ross as James Lingk . He received a Drama Desk Award for his performance. In 1990, Smith appeared in Air America playing a United States Senator , a role for which he was selected based on his resemblance to then- Minority Leader Bob Dole . Two years later, he played

660-492: A bulbar onset have a worse prognosis than limb-onset ALS; a population-based study found that bulbar-onset ALS patients had a median survival of 2.0 years and a 10-year survival rate of 3%, while limb-onset ALS patients had a median survival of 2.6 years and a 10-year survival rate of 13%. Those with respiratory-onset ALS had a shorter median survival of 1.4 years and 0% survival at 10 years. While astrophysicist Stephen Hawking lived for 55 more years following his diagnosis, his

792-472: A common disease spectrum (ALS–FTD) because of genetic, clinical, and pathological similarities. Genetically, repeat expansions in the C9orf72 gene account for about 40% of genetic ALS and 25% of genetic FTD. Cognitive and behavioral issues are associated with poorer prognosis as they may reduce adherence to medical advice, and deficits in empathy and social cognition which may increase caregiver burden. It

924-430: A definitive diagnosis of PLS cannot be made until several years have passed. PLS has a better prognosis than classical ALS, as it progresses slower, results in less functional decline, does not affect the ability to breathe, and causes less severe weight loss than classical ALS. Progressive muscular atrophy (PMA) is another subtype that accounts for about 5% of the overall ALS category and affects lower motor neurons in

1056-444: A disease, ALS itself can be classified in a few different ways: by which part of the motor neurons are affected; by the parts of the body first affected; whether it is genetic; and the age at which it started. Each individual diagnosed with the condition will sit at a unique place at the intersection of these complex and overlapping subtypes, which presents a challenge to diagnosis, understanding, and prognosis. ALS can be classified by

1188-630: A focal point of Spanish activity until, as Holmes summarizes: [T]he Treaty of San Lorenzo or Pinckney's Treaty of 1795 [implemented in March 1797], [had as its result that] all of the careful, diplomatic work by Spanish officials in Louisiana and West Florida , which has succeeded for a decade in controlling the Indians [e.g., the Choctaws ], was undone. The United States gained the right to navigate

1320-403: A genetic cause, often linked to a family history of the disease , and these are known as familial ALS (hereditary). About half of these genetic cases are due to disease-causing variants in one of four specific genes . The diagnosis is based on a person's signs and symptoms , with testing conducted to rule out other potential causes. There is no known cure for ALS. The goal of treatment

1452-424: A healthy weight can become a significant problem that may require the insertion of a feeding tube. As the diaphragm and intercostal muscles of the rib cage that support breathing weaken, measures of lung function such as vital capacity and inspiratory pressure diminish. In respiratory-onset ALS, this may occur before significant limb weakness is apparent. Individuals affected by the disorder may ultimately lose

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1584-563: A large territory in the Southeast. French explorers led by René-Robert Cavelier, Sieur de La Salle , and Spanish explorer Hernando de Soto encountered the historic Chickasaw in this area in the 16th century. J. D. L. Holmes, writing in Hudson's Four Centuries of Southern Indians (2007), notes that this site was a third strategic point in the late 18th century through which European powers could control United States encroachment beyond

1716-742: A major role as fictional television anchorman Emmett Seaborn in the HBO miniseries From the Earth to the Moon . His final film appearance was in The Legend of Bagger Vance (2000). Smith was diagnosed with amyotrophic lateral sclerosis (also known as ALS, or Lou Gehrig 's disease) in April 2004. He died of the disease at home in the Northridge neighborhood of Los Angeles, California , on June 13, 2005 at

1848-625: A multicultural mix of influences: country , rock and roll , soul , and hip-hop . The city is home to a major professional sports team , the Grizzlies of the NBA . Other attractions include Graceland , the Memphis Pyramid , Sun Studio , the Blues Hall of Fame and Stax Museum of American Soul Music . Memphis-style barbecue has achieved international prominence, and the city hosts

1980-467: A number of ALS genes that encode for RNA-binding proteins. The first to be discovered was TDP-43 protein, a nuclear protein that aggregates in the cytoplasm of motor neurons in almost all cases of ALS; however, mutations in TARDBP , the gene that codes for TDP-43, are a rare cause of ALS. FUS codes for FUS, another RNA-binding protein with a similar function to TDP-43, which can cause ALS when mutated. It

2112-510: A physician suspects the person may have a myopathy rather than ALS, a muscle biopsy may be performed. A number of infectious diseases can sometimes cause ALS-like symptoms, including human immunodeficiency virus ( HIV ), human T-lymphotropic virus (HTLV), Lyme disease , and syphilis . Neurological disorders such as multiple sclerosis, post-polio syndrome , multifocal motor neuropathy , CIDP , spinal muscular atrophy , and spinal and bulbar muscular atrophy can also mimic certain aspects of

2244-868: A powerful and corrupt United States Congressman opposite Eddie Murphy in The Distinguished Gentleman , followed by a role as a small-town district attorney opposite Joe Pesci in My Cousin Vinny , and as Coach Jack Reilly in The Mighty Ducks . In 1993, Smith was cast as Perry White in Lois & Clark: The New Adventures of Superman , which he played for four seasons until 1997. In 1994, he portrayed New York Yankees front officeman Ron in The Scout , alongside Albert Brooks and Brendan Fraser . In 1998, Smith appeared in

2376-464: A predominantly upper motor neuron phenotype. Emotional lability is a symptom in which patients cry, smile, yawn, or laugh, either in the absence of emotional stimuli, or when they are feeling the opposite emotion to that being expressed; it is experienced by about half of ALS patients and is more common in those with bulbar-onset ALS. While relatively benign relative to other symptoms, it can cause increased stigma and social isolation as people around

2508-463: A rapid worsening of symptoms. Sudden death or acute respiratory distress are uncommon. Access to palliative care is recommended from an early stage to explore options, ensure psychosocial support for the patient and caregivers, and to discuss advance healthcare directives . As with cancer staging , ALS has staging systems numbered between 1 and 4 that are used for research purposes in clinical trials. Two very similar staging systems emerged around

2640-525: A similar time, the King's staging system and Milano-Torino (MiToS) functional staging. 2B: Involvement of the second region 4B: Need for non-invasive ventilation 4B: 30.3 months Providing individual patients with a precise prognosis is not currently possible, though research is underway to provide statistical models on the basis of prognostic factors including age at onset, progression rate, site of onset, and presence of frontotemporal dementia . Those with

2772-436: A single region for at least a year; they progress more slowly than classical ALS and are associated with longer survival. These regional variants of ALS can only be considered as a diagnosis should the initial symptoms fail to spread to other spinal cord regions for an extended period of time (at least 12 months). Flail arm syndrome is characterized by lower motor neuron damage affecting the arm muscles, typically starting with

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2904-573: A small percentage of people have a much slower progression, on average people with ALS lose about 1 ALSFRS-R point per month. Brief periods of stabilization ("plateaus") and even small reversals in ALSFRS-R score are not uncommon, due to the fact the tool is subjective, can be affected by medication, and different forms of compensation for changes in function. However, it is rare (<1%) for these improvements to be large (i.e. greater than 4 ALSFRS-R points) or sustained (i.e. greater than 12 months). A survey-based study among clinicians showed that they rated

3036-477: A smaller family, older generations dying earlier of causes other than ALS, genetic non-paternity , and uncertainty over whether certain neuropsychiatric conditions (e.g. frontotemporal dementia , other forms of dementia , suicide, psychosis, schizophrenia ) should be considered significant when determining a family history. There have been calls in the research community to routinely counsel and test all diagnosed ALS patients for familial ALS, particularly as there

3168-674: A yellow fever outbreak, 20,000 residents fled the city. The ensuing panic left the poverty-stricken, the working classes, and the African-American community at the most risk from the epidemic. Those who remained relied on volunteers from religious and physician organizations to tend to the sick. By the end of the year, more than 5,000 were confirmed dead in Memphis. The New Orleans health board listed "not less than 4,600" dead. The Mississippi Valley recorded 120,000 cases of yellow fever, with 20,000 deaths. The $ 15 million in losses caused by

3300-425: Is a national transportation hub and Mississippi River crossing for Interstate 40 , (east-west), Interstate 55 (north-south), barge traffic, Memphis International Airport ( FedEx's "SuperHub" facility ) and numerous freight railroads that serve the city. Amyotrophic lateral sclerosis Amyotrophic lateral sclerosis ( ALS ), also known as motor neurone disease ( MND ) or Lou Gehrig's disease ( LGD ) in

3432-408: Is a symptom experienced by most people with ALS caused by reduced mobility. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin ( fasciculations ). Although the initial site of symptoms and subsequent rate of disability progression vary from person to person, the initially affected body region

3564-567: Is land and 9.0 square miles (23.2 km ), or 2.76%, is water. Downtown Memphis rises from a bluff along the Mississippi River . The city and metro area spread out through suburbanization, and encompass southwest Tennessee, northern Mississippi , and eastern Arkansas . Several large parks were founded in the city in the early 20th century, notably Overton Park in Midtown and the 4,500-acre (18 km ) Shelby Farms . The city

3696-575: Is more likely to be genetic in origin than adult-onset ALS; the most common genes associated with juvenile ALS are FUS , ALS2 , and SETX . Although most people with juvenile ALS live longer than those with adult-onset ALS, some of them have specific mutations in FUS and SOD1 that are associated with a poor prognosis. Late onset (after age 65) is generally associated with a more rapid functional decline and shorter survival. The disorder causes muscle weakness, atrophy , and muscle spasms throughout

3828-657: Is not known what causes sporadic ALS, hence it is described as an idiopathic disease . Though its exact cause is unknown, genetic and environmental factors are thought to be of roughly equal importance. The genetic factors are better understood than the environmental factors; no specific environmental factor has been definitively shown to cause ALS. A multi-step liability threshold model for ALS proposes that cellular damage accumulates over time due to genetic factors present at birth and exposure to environmental risks throughout life. ALS can strike at any age, but its likelihood increases with age. Most people who develop ALS are between

3960-631: Is now a licensed gene therapy ( tofersen ) specifically targeted to carriers of SOD-1 ALS. A shortage of genetic counselors and limited clinical capacity to see such at-risk individuals makes this challenging in practice, as does the unequal access to genetic testing around the world. More than 40 genes have been associated with ALS, of which four account for nearly half of familial cases, and around 5% of sporadic cases: C9orf72 (40% of familial cases, 7% sporadic), SOD1 (12% of familial cases, 1–2% sporadic), FUS (4% of familial cases, 1% sporadic), and TARDBP (4% of familial cases, 1% sporadic), with

4092-412: Is often feasible, albeit slow, and needs may change over time. Despite these challenges, many people in an advanced state of disease report satisfactory wellbeing and quality of life. Although respiratory support using non-invasive ventilation can ease problems with breathing and prolong survival, it does not affect the progression rate of ALS. Most people with ALS die between two and four years after

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4224-532: Is often marked by walking with a " dropped foot " that drags gently on the ground. If the arms are affected first, they may experience difficulty with tasks requiring manual dexterity, such as buttoning a shirt, writing, or turning a key in a lock. In bulbar-onset ALS, the first symptoms are difficulty speaking or swallowing. Speech may become slurred, nasal in character, or quieter. There may be difficulty with swallowing and loss of tongue mobility. A smaller proportion of people experience "respiratory-onset" ALS, where

4356-495: Is respiratory-onset, in which the initial symptoms are difficulty breathing ( dyspnea ) upon exertion, at rest, or while lying flat ( orthopnea ). Primary lateral sclerosis (PLS) is a subtype of the overall ALS category which accounts for about 5% of all cases and only affects the upper motor neurons in the arms, legs, and bulbar region. However, more than 75% of people with apparent PLS go on to later develop lower motor neuron signs within four years of symptom onset, meaning that

4488-626: Is the fifth-most populous city in the Southeast , the nation's 28th-most populous overall, as well as the largest city bordering the Mississippi River and third largest metropolitan statistical area behind Greater St. Louis and the Twin Cities on the Mississippi River. The Memphis metropolitan area includes West Tennessee and the greater Mid-South region , which includes portions of neighboring Arkansas , Mississippi and

4620-450: Is the main transporter that removes glutamate from the synapse; this leads to increased synaptic glutamate levels and excitotoxicity. Riluzole , a drug that modestly prolongs survival in ALS, inhibits glutamate release from pre-synaptic neurons; however, it is unclear if this mechanism is responsible for its therapeutic effect. No single test can provide a definite diagnosis of ALS. Instead,

4752-424: Is thought that misfolded mutant SOD1 can cause misfolding and aggregation of wild-type SOD1 in neighboring neurons in a prion-like manner. Other protein degradation genes that can cause ALS when mutated include VCP , OPTN , TBK1 , and SQSTM1 . Three genes implicated in ALS that are important for maintaining the cytoskeleton and for axonal transport include DCTN1 , PFN1 , and TUBA4A . There are

4884-403: Is thought that mutations in TARDBP and FUS increase the binding affinity of the low-complexity domain, causing their respective proteins to aggregate in the cytoplasm. Once these mutant RNA-binding proteins are misfolded and aggregated, they may be able to misfold normal proteins both within and between cells in a prion-like manner. This also leads to decreased levels of RNA-binding protein in

5016-429: Is thought to account for 10–15% of cases overall and can include monogenic , oligogenic , and polygenic modes of inheritance. There is considerable variation among clinicians on how to approach genetic testing in ALS, and only about half discuss the possibility of genetic inheritance with their patients, particularly if there is no discernible family history of the disease. In the past, genetic counseling and testing

5148-498: Is to slow the disease progression, and improve symptoms. FDA approved treatments that slow the progression of ALS include riluzole and edaravone . Non-invasive ventilation may result in both improved quality, and length of life. Mechanical ventilation can prolong survival but does not stop disease progression. A feeding tube may help maintain weight and nutrition. Death is usually caused by respiratory failure. The disease can affect people of any age, but usually starts around

5280-431: Is usually the most affected over time, and symptoms usually spread to a neighbouring body region. For example, symptoms starting in one arm usually spread next to either the opposite arm or to the leg on the same side. Bulbar-onset patients most typically get their next symptoms in their arms rather than legs, arm-onset patients typically spreads to the legs before the bulbar region, and leg-onset patients typically spread to

5412-486: The ALS Functional Rating Scale - Revised (ALSFRS-R), a 12-item instrument survey administered as a clinical interview or self-reported questionnaire that produces a score between 48 (normal function) and 0 (severe disability). The ALSFRS-R is the most frequently used outcome measure in clinical trials and is used by doctors to track disease progression. Though the degree of variability is high and

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5544-771: The Mississippi River and won control over the Yazoo Strip north of the thirty-first parallel. The Spanish dismantled the fort, shipping its lumber and iron to their locations in Arkansas. In 1796, the site became the westernmost point of the newly admitted state of Tennessee, in what was then called the Southwest United States. The area was still largely occupied and controlled by the Chickasaw nation. Captain Isaac Guion led an American force down

5676-601: The Missouri Bootheel . One of the more historic and culturally significant cities of the Southern United States , Memphis has a wide variety of landscapes and distinct neighborhoods . The first European explorer to visit the area of present-day Memphis was Spanish conquistador Hernando de Soto in 1541. The high Chickasaw Bluffs protecting the location from the waters of the Mississippi

5808-641: The Treaty of Tuscaloosa , signed in October 1818 and ratified by Congress on January 7, 1819, the Chickasaw ceded their territory in Western Tennessee to the United States . The city of Memphis was founded less than five months after the U.S. takeover of the territory, on May 22, 1819 (incorporated December 19, 1826), by John Overton , James Winchester and Andrew Jackson . They named it after

5940-711: The U.S. Army . After graduating, Smith found steady work in New York theater before making his film debut in Maidstone in 1970. During the 1970s, he regularly made appearances in small film roles including Rooster Cogburn in 1975 and Network in 1976. In 1981, Smith appeared in the Sidney Lumet -directed film Prince of the City . He also acted on television, notably playing a United States Marine in Vietnam in

6072-628: The ancient capital of Egypt on the Nile River . From the city's foundation onwards, African Americans formed large proportion of Memphis' population. Prior to the abolition of slavery in the United States , most Black people in Memphis were enslaved, being used as forced labor by white enslavers along the river or on outlying cotton plantations in the Mississippi Delta . The city's demographics changed dramatically in

6204-426: The intercostal muscles that support breathing are affected first. Over time, people experience increasing difficulty moving, swallowing ( dysphagia ), and speaking or forming words ( dysarthria ). Symptoms of upper motor neuron involvement include tight and stiff muscles ( spasticity ) and exaggerated reflexes ( hyperreflexia ), including an overactive gag reflex. While the disease does not cause pain directly, pain

6336-468: The lower motor neurons in the spinal cord. Primary lateral sclerosis (PLS) involves degeneration of only the upper motor neurons, and progressive muscular atrophy (PMA) involves only the lower motor neurons. There is debate over whether PLS and PMA are separate diseases or simply variants of ALS. Classical ALS accounts for about 70% of all cases of ALS and can be subdivided into where symptoms first appear as these are usually focussed to one region of

6468-432: The neuromuscular junction , such as myasthenia gravis (MG) and Lambert–Eaton myasthenic syndrome , may also mimic ALS, although this rarely presents diagnostic difficulty over time. Benign fasciculation syndrome and cramp fasciculation syndrome may also, occasionally, mimic some of the early symptoms of ALS. Nonetheless, the absence of other neurological features that develop inexorably with ALS means that, over time,

6600-545: The pathogenesis of ALS. It is still not fully understood why neurons die in ALS, but this neurodegeneration is thought to involve many different cellular and molecular processes. The genes known to be involved in ALS can be grouped into three general categories based on their normal function: protein degradation, the cytoskeleton , and RNA processing. Mutant SOD1 protein forms intracellular aggregations that inhibit protein degradation. Cytoplasmic aggregations of wild-type (normal) SOD1 protein are common in sporadic ALS. It

6732-572: The 1850s and 1860s, due to waves of immigration and domestic migration. Due to increased immigration since the 1840s and the Great Famine , Irish Americans made up 9.9% of the population in 1850, but 23.2% by 1860, when the total population was 22,623. Tennessee seceded from the Union in June 1861, and Memphis briefly became a Confederate stronghold. Union ironclad gunboats captured it in

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6864-453: The 1880s Memphis led the nation in sanitary reform and improvements. Perhaps the most significant effect of yellow fever on Memphis was in demographic changes. Nearly all of Memphis's upper and middle classes vanished, depriving the city of its general leadership and class structure that dictated everyday life, similar to that in other large Southern cities, such as New Orleans , Charleston, South Carolina , and Atlanta, Georgia . In Memphis,

6996-585: The 1960s, the city was at the center of the Civil Rights Movement , as its large African-American population had been affected by state segregation practices and disenfranchisement in the early 20th century. African-American residents drew from the civil rights movement to improve their lives. In 1968, the Memphis sanitation strike began for living wages and better working conditions; the workers were overwhelmingly African American. They marched to gain public awareness and support for their plight:

7128-538: The 20th century, with four lynchings between 1900 and the lynching of Thomas Williams in 1928. A Tennessee Powder Company built an explosives powder plant to make TNT and gunpowder on a 6,000-acre site in Millington in 1940. The plant was built to make smokeless gunpowder for the British Armed Forces during World War II . In May 1941, DuPont (1802–2017) took over the plant, changed the name to

7260-740: The Appalachians and their interference with Indian matters—after Fort Nogales (present-day Vicksburg ) and Fort Confederación (present-day Epes, Alabama ): "Chickasaw Bluffs, located on the Mississippi River at the present-day location of Memphis. Spain and the United States vied for control of this site, which was a favorite of the Chickasaws." In 1795 the Spanish Governor-General of Louisiana , Francisco Luis Héctor de Carondelet , sent his lieutenant governor, Manuel Gayoso de Lemos , to negotiate and secure consent from

7392-624: The Chickasaw Ordnance Works, and produced powder for the United States Armed Forces . There were 8,000 employees. The plant was dismantled after the war in 1946. From the 1910s to the 1950s, Memphis was a place of machine politics under the direction of E. H. "Boss" Crump . He gained a state law in 1911 to establish a small commission to manage the city. The city retained a form of commission government until 1967 and patronage flourished under Crump. Per

7524-585: The Ohio River to claim the land, arriving on July 20, 1797. By this time, the Spanish had departed. The fort's ruins went unnoticed 20 years later when Memphis was laid out as a city after the United States government paid the Chickasaw for land. At the beginning of the century, as recognized by the United States in 1786 Treaty of Hopewell , the land still belonged to the Chickasaw Nation . In

7656-622: The Sylvers , Jay Reatard , Zach Myers , and Aretha Franklin . On December 23, 1988, a tanker truck hauling liquefied propane crashed at the I-40/I-240 interchange in Midtown and exploded , starting multiple vehicle and structural fires. Nine people were killed and ten were injured. It was one of Tennessee's deadliest motor vehicle accidents and eventually led to the reconstruction of the interchange where it occurred. On June 2, 2021,

7788-416: The United States, is a rare, terminal neurodegenerative disorder that results in the progressive loss of both upper and lower motor neurons that normally control voluntary muscle contraction. ALS is the most common form of the motor neuron diseases . ALS often presents in its early stages with gradual muscle stiffness , twitches , weakness , and wasting . Motor neuron loss typically continues until

7920-665: The abilities to eat, speak, move, and, lastly, breathe are all lost. While only 15% of people with ALS also fully develop frontotemporal dementia , an estimated 50% face at least some minor difficulties with thinking and behavior . Depending on which of the aforementioned symptoms develops first, ALS is classified as limb-onset (begins with weakness in the arms or legs) or bulbar-onset (begins with difficulty in speaking or swallowing ). Most cases of ALS (about 90–95%) have no known cause , and are known as sporadic ALS . However, both genetic and environmental factors are believed to be involved. The remaining 5–10% of cases have

8052-418: The ability to initiate and control all voluntary movement, known as locked-in syndrome . Bladder and bowel function are usually spared, meaning urinary and fecal incontinence are uncommon, although trouble getting to a toilet can lead to difficulties. The extraocular muscles responsible for eye movement are usually spared, meaning the use of eye tracking technology to support augmentative communication

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8184-420: The above personality traits might underlie lifestyle choices which are in turn risk factors for ALS. Upon examination at autopsy, features of the disease that can be seen with the naked eye include skeletal muscle atrophy , motor cortex atrophy, sclerosis of the corticospinal and corticobulbar tracts , thinning of the hypoglossal nerves (which control the tongue), and thinning of the anterior roots of

8316-471: The age of 60. The average survival from onset to death is two to four years, though this can vary, and about 10% of those affected survive longer than ten years. Descriptions of the disease date back to at least 1824 by Charles Bell . In 1869, the connection between the symptoms and the underlying neurological problems was first described by French neurologist Jean-Martin Charcot , who in 1874 began using

8448-515: The age of 69. He was survived by his wife, Debbie Benedict Smith, and his son Robert Smith. Memphis, Tennessee Memphis is a city in the U.S. state of Tennessee . It is the county seat of Shelby County , in the southwesternmost part of the state, and is situated along the Mississippi River . With a population of 633,104 at the 2020 U.S. census , Memphis is the second-most populous city in Tennessee after Nashville . Memphis

8580-425: The age of onset. While the peak age of onset is 58 to 63 for sporadic ALS and 47 to 52 for genetic ALS, about 10% of all cases of ALS begin before age 45 ("young-onset" ALS), and about 1% of all cases begin before age 25 ("juvenile" ALS). People who develop young-onset ALS are more likely to be male, less likely to have bulbar onset of symptoms, and more likely to have a slower progression of the disease. Juvenile ALS

8712-512: The ages of 40 and 70, with an average age of 55 at the time of diagnosis. ALS is 20% more common in men than women, but this difference in sex distribution is no longer present in patients with onset after age 70. While they appear identical clinically and pathologically, ALS can be classified as being either familial or sporadic, depending on whether there is a known family history of the disease and/or whether an ALS-associated genetic mutation has been identified via genetic testing. Familial ALS

8844-401: The altercations, which were described as "heinous" and showed "a total lack of regard for human life", according to Memphis police chief Cerelyn "CJ" Davis. The officers were fired and charged with second-degree murder, aggravated kidnapping, and other crimes. The relatively rapid dismissal and prosecution of the offending officers were favorably perceived by Nichols's family, and Davis called it

8976-493: The annual World Championship Barbecue Cooking Contest , which attracts more than 100,000 visitors each year. Higher-level educational institutions include the University of Memphis , Christian Brothers University and Rhodes College . Occupying a substantial bluff rising from the Mississippi River, the site of Memphis has been a natural location for human settlement by varying indigenous cultures over thousands of years. In

9108-679: The area annexed was slightly smaller than first proposed. In 1893 the city was rechartered with home rule , which restored its ability to enact taxes. The state legislature established a cap rate. Although the commission government was retained and enlarged to five commissioners, Democratic politicians regained control from the business elite. The commission form of government was believed effective in getting things done, but because all positions were elected at-large , requiring them to gain majority votes, this practice reduced representation by candidates representing significant minority political interests. In terms of its economy, Memphis developed as

9240-482: The arms rather than the bulbar region. Over time, regardless of where symptoms began, most people eventually lose the ability to walk or use their hands and arms independently. Less consistently, they may lose the ability to speak and to swallow food. It is the eventual development of weakness of the respiratory muscles, with the loss of ability to cough and to breathe without support, that is ultimately life-shortening in ALS. The rate of progression can be measured using

9372-497: The arms, legs, and bulbar region. While PMA is associated with longer survival on average than classical ALS, it is still progressive over time, eventually leading to respiratory failure and death. As with PLS developing into classical ALS, PMA can also develop into classical ALS over time if the lower motor neuron involvement progresses to include upper motor neurons, in which case the diagnosis might be changed to classic ALS. Isolated variants of ALS have symptoms that are limited to

9504-544: The black settlement was left in ruins. Two whites were killed in the riot. Many blacks permanently fled Memphis afterward, especially as the Freedmen's Bureau continued to have difficulty in protecting them. Their population fell to about 15,000 by 1870, 37.4% of the total population of 40,226. Historian Barrington Walker suggests that the Irish rioted against blacks because of their relatively recent arrival as immigrants and

9636-465: The body at initial presentation before later spread. Limb-onset ALS (also known as spinal-onset) and bulbar-onset ALS. Limb-onset ALS begins with weakness in the hands, arms, feet, and/or legs and accounts for about two-thirds of all classical ALS cases. Bulbar-onset ALS begins with weakness in the muscles of speech, chewing, and swallowing and accounts for about 25% of classical ALS cases. A rarer type of classical ALS affecting around 3% of patients

9768-419: The body due to the degeneration of the upper motor and lower motor neurons. Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS maintain hearing , sight , touch , smell , and taste . The start of ALS may be so subtle that the symptoms are overlooked. The earliest symptoms of ALS are muscle weakness or muscle atrophy, typically on one side of

9900-499: The body. Other presenting symptoms include trouble swallowing or breathing, cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; or slurred and nasal speech. The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first. In limb-onset ALS, the first symptoms are in the arms or the legs. If the legs are affected first, people may experience awkwardness, tripping, or stumbling when walking or running; this

10032-401: The brain to muscle, causes different types of symptoms. Damage to the upper motor neuron typically causes spasticity including stiffness and increased tendon reflexes , and/or clonus , while damage to the lower motor neuron typically causes weakness , muscle atrophy , and fasciculations . Classical, or classic ALS, involves degeneration to both the upper motor neurons in the brain and

10164-741: The city has a majority African-American population. Memphis is well known for its cultural contributions to the identity of the American South . Many renowned musicians grew up in and around Memphis and moved to Chicago and other areas from the Mississippi Delta , carrying their music with them to influence other cities and listeners over radio airwaves. Former and current Memphis residents include musicians Elvis Presley , Jerry Lee Lewis , Muddy Waters , Carl Perkins , Johnny Cash , Robert Johnson , W. C. Handy , Bobby Whitlock , B.B. King , Howlin' Wolf , Isaac Hayes , Booker T. Jones , Eric Gales , Al Green , Alex Chilton , Three 6 Mafia ,

10296-496: The city population. The Union Army's presence attracted many fugitive slaves who had escaped from surrounding rural plantations. So many sought protection behind Union lines that the Army set up contraband camps to accommodate them. Memphis's black population increased from 3,000 in 1860, when the total population was 22,623, to nearly 20,000 in 1865, with most settling south of the city limits. The rapid demographic changes added to

10428-482: The city were the lower classes, such as German and Irish immigrant workers and African Americans. None had the means to flee the city, as did the middle and upper-class whites of Memphis, and thus they were subjected to a city of death. Immediately following the Board of Health's declaration, a Citizen's Relief Committee was formed by Charles G. Fisher. It organized the city into refugee camps. The committee's main priority

10560-493: The city. A massive panic ensued. The same trains and steamboats that had brought thousands into Memphis, in five days carried away more than 25,000 refugees, more than half of the city's population. On August 23, the Board of Health finally declared a yellow fever epidemic in Memphis, and the city collapsed, hemorrhaging its population. In July of that year, the city had a population of 47,000; by September, 19,000 remained, and 17,000 of them had yellow fever. The only people left in

10692-466: The condition, but as of 2023 are not in general medical use. Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions. One of these tests is electromyography (EMG), a special recording technique that detects electrical activity in muscles. Certain EMG findings can support

10824-551: The country to come home. Though yellow fever cases were recorded in the pages of Elmwood Cemetery's burial record as late as February 29, 1874, the epidemic seemed quieted. The Board of Health declared the epidemic at an end after it had caused over 20,000 deaths and financial losses of nearly $ 200 million. On November 27, a general citizen's meeting was called at the Greenlaw Opera House to offer thanks to those who had stayed behind to serve, of whom many had died. Over

10956-447: The cytoplasm of motor neurons. In about 97% of people with ALS, the main component of the inclusion bodies is TDP-43 protein; however, in those with SOD1 or FUS mutations, the main component of the inclusion bodies is SOD1 protein or FUS protein, respectively. Prion -like propagation of misfolded proteins from cell to cell may explain why ALS starts in one area and spreads to others. The glymphatic system may also be involved in

11088-678: The danger of their work, and the struggles to support families with their low pay. Their drive for better pay had been met with resistance by the city government. Martin Luther King Jr. of the Southern Christian Leadership Conference , known for his leadership in the non-violent movement, came to lend his support to the workers' cause. King stayed at the Lorraine Motel in the city, and was assassinated by James Earl Ray on April 4, 1968,

11220-526: The day after giving his I've Been to the Mountaintop speech at the Mason Temple . After learning of King's murder, many African Americans in the city rioted, looting and destroying businesses and other facilities, some by arson. The governor ordered Tennessee National Guardsmen into the city within hours, where small, roving bands of rioters continued to be active. Fearing the violence, more of

11352-424: The diagnosis of ALS is primarily made based on a physician's clinical assessment after ruling out other diseases. Physicians often obtain the person's full medical history and conduct neurologic examinations at regular intervals to assess whether signs and symptoms such as muscle weakness, muscle atrophy , hyperreflexia , Babinski's sign , and spasticity are worsening. A number of biomarkers are being studied for

11484-487: The diagnosis of ALS. Another common test measures nerve conduction velocity (NCV). Specific abnormalities in the NCV results may suggest, for example, that the person has a form of peripheral neuropathy (damage to peripheral nerves) or myopathy (muscle disease) rather than ALS. While a magnetic resonance imaging (MRI) is often normal in people with early-stage ALS, it can reveal evidence of other problems that may be causing

11616-424: The diagnosis. Around 50% of people with ALS die within 30 months of their symptoms beginning, about 20% live between five and ten years, and about 10% survive for 10 years or longer. The most common cause of death among people with ALS is respiratory failure , often accelerated by pneumonia . Most ALS patients die at home after a period of worsening difficulty breathing, a decline in their nutritional status, or

11748-426: The disease and should be considered. ALS must be differentiated from the "ALS mimic syndromes", which are unrelated disorders that may have a similar presentation and clinical features to ALS or its variants. Because the prognosis of ALS and closely related subtypes of motor neuron disease are generally poor, neurologists may carry out investigations to evaluate and exclude other diagnostic possibilities. Disorders of

11880-567: The disease carried by river passengers traveling by ships along the waterways. During the Yellow Fever Epidemic of 1878, more than 5,000 people were listed in the official register of deaths between July 26 and November 27. The vast majority died of yellow fever, making the epidemic in the city of 40,000 one of the most traumatic and severe in urban U.S. history. Within four days of the Memphis Board of Health's declaration of

12012-423: The election of all the at-large positions. Memphis did not become a home rule city until 1963, although the state legislature had amended the constitution in 1953 to provide home rule for cities and counties. Before that, the city had to get state bills approved in order to change its charter and other policies and programs. Since 1963, it can change the charter by popular approval of the electorate. During

12144-523: The end of slavery , the city continued to grow into the 20th century. It became among the largest world markets for cotton and hardwood . Home to Tennessee's largest African-American population, Memphis played a prominent role in the American Civil Rights Movement . Dr. Martin Luther King Jr. was assassinated in 1968 after activities supporting a strike by the city's maintenance workers. The National Civil Rights Museum

12276-596: The epidemic bankrupted Memphis, and as a result, its charter was revoked by the state legislature. By 1870, Memphis's population of 40,000 was almost double that of Nashville and Atlanta, and it was the second-largest city in the South after New Orleans. Its population continued to grow after 1870, even when the Panic of 1873 hit the US hard, particularly in the South. The Panic of 1873 resulted in expanding Memphis's underclasses amid

12408-536: The epidemic reported seeing as many as 100 to 150 patients daily. The Episcopal Community of St. Mary at St. Mary's Episcopal Cathedral played an important role during the epidemic in caring for the lower classes. Already supporting a girls' school and church orphanage, the Sisters of St. Mary also sought to provide care for the Canfield Asylum, a home for black children. Each day, they alternated caring for

12540-466: The excitatory neurotransmitter glutamate , is a mechanism thought to be common to all forms of ALS. Motor neurons are more sensitive to excitotoxicity than other types of neurons because they have a lower calcium-buffering capacity and a type of glutamate receptor (the AMPA receptor ) that is more permeable to calcium. In ALS, there are decreased levels of excitatory amino acid transporter 2 ( EAAT2 ), which

12672-483: The fifth-busiest inland water port in the U.S. The Globalization and World Cities Research Network considers Memphis a "Sufficiency" level global city as of 2020. Memphis is a center for media and entertainment, notably a historic music scene . With blues clubs on Beale Street originating the unique Memphis blues sound, the city has been nicknamed the "Home of the Blues". Its music has continued to be shaped by

12804-556: The first millennium A.D. people of the Mississippian culture were prominent; the culture influenced a network of communities throughout the Mississippi River Valley and its tributaries. The hierarchical societies built complexes with large earthwork ceremonial and burial mounds as expressions of their sophisticated culture. The Chickasaw people, believed to be their descendants, later inhabited this site and

12936-682: The franchise until after the passage of civil rights legislation in the mid-1960s.) Historian L. B. Wrenn suggests the heightened political hostility of the Democratic contest and related social tensions contributed to a white mob lynching three black grocers in Memphis in 1892 . Journalist Ida B. Wells of Memphis investigated the lynchings, as one of the men killed was a friend of hers. She demonstrated that these and other lynchings were more often due to economic and social competition than any criminal offenses by black men. Her findings were considered so controversial and aroused so much anger that she

13068-683: The freedmen. Unlike the disturbances in some other cities, ex-Confederate veterans were generally not part of the attacks against blacks in Memphis. As a result of the riots in Memphis, and a similar one in New Orleans, Louisiana in September, Congress passed the Reconstruction Act and the Fourteenth Amendment to the U.S. Constitution . In the 1870s, a series of yellow fever epidemics devastated Memphis, with

13200-878: The likelihood of a very rare condition by a small amount. For instance an individual's lifetime risk of developing ALS might go from "1 in 400" without an exposure to between "1 in 300" and "1 in 200" if they were exposed to heavy metals. A range of other exposures have weaker evidence supporting them and include participation in professional sports , having a lower body mass index , lower educational attainment , manual occupations, military service, exposure to Beta-N-methylamino-L-alanin (BMAA), and viral infections. Although some personality traits, such as openness , agreeableness and conscientiousness appear remarkably common among patients with ALS, it remains open whether personality can increase susceptibility to ALS directly. Instead, genetic factors giving rise to personality might simultaneously predispose people to developing ALS, or

13332-508: The local Chickasaw so that a Spanish fort could be erected on the bluff; Fort San Fernando De Las Barrancas was the result. Holmes notes that consent was reached despite opposition from "disappointed Americans and a pro-American faction of the Chickasaws" when the "pro-Spanish faction signed the Chickasaw Bluffs Cession and Spain provided the Chickasaws with a trading post". Fort San Fernando de las Barrancas remained

13464-490: The middle-class began to leave the city for the suburbs. In 1970, the Census Bureau reported Memphis's population as 60.8% white and 38.9% black. Suburbanization was attracting wealthier residents to newer housing outside the city. After the riots and court-ordered busing in 1973 to achieve desegregation of public schools, "about 40,000 of the system's 71,000 white students abandon[ed] the system in four years." Today,

13596-472: The naval Battle of Memphis on June 6, 1862, and the city and state were occupied by the Union Army for the duration of the war. Union commanders allowed the city to maintain its civil government during most of this period but excluded Confederate States Army veterans from office. This shifted political dynamics in the city as the war went on. The war years contributed to additional dramatic changes in

13728-402: The next year property tax revenues collapsed, and the city could not make payments on its municipal debts. As a result, Memphis temporarily lost its city charter and was reclassified by the state legislature as a Taxing District from 1878 to 1893. But a new era of sanitation was developed in the city, a new municipal government in 1879 helped form the first regional health organization, and during

13860-735: The nucleus, translation of the RNA into toxic dipeptide repeat proteins in the cytoplasm, and decreased levels of the normal C9orf72 protein. Mitochondrial bioenergetic dysfunction leading to dysfunctional motor neuron axonal homeostasis (reduced axonal length and fast axonal transport of mitochondrial cargo) has been shown to occur in C9orf72 -ALS using human induced pluripotent stem cell (iPSC) technologies coupled with CRISPR/Cas9 gene-editing, and human post-mortem spinal cord tissue examination. Excitotoxicity , or nerve cell death caused by high levels of intracellular calcium due to excessive stimulation by

13992-705: The nucleus, which may mean that their target RNA transcripts do not undergo normal processing. Other RNA metabolism genes associated with ALS include ANG , SETX , and MATR3 . C9orf72 is the most commonly mutated gene in ALS and causes motor neuron death through a number of mechanisms. The pathogenic mutation is a hexanucleotide repeat expansion (a series of six nucleotides repeated over and over); people with up to 30 repeats are considered normal, while people with hundreds or thousands of repeats can have familial ALS, frontotemporal dementia, or sometimes sporadic ALS. The three mechanisms of disease associated with these C9orf72 repeats are deposition of RNA transcripts in

14124-456: The orphans at St. Mary's, delivering children to the Canfield Asylum, and taking soup and medicine on house calls to patients. Between September 9 and October 4, Sister Constance and three other nuns fell victim to the epidemic and died. They later became known as the Martyrs of Memphis. At long last, on October 28, a killing frost struck. The city sent out word to Memphians scattered all over

14256-456: The patient struggle to react appropriately to what can be frequent and inappropriate outbursts in public. In addition to mild changes in cognition that may only emerge during neuropsychological testing, around 10–15% of individuals have signs of frontotemporal dementia (FTD). Repeating phrases or gestures , apathy, and loss of inhibition are the most frequently reported behavioral features of ALS. ALS and FTD are now considered to be part of

14388-509: The poorer whites and blacks fundamentally made up the city and played the greatest role in rebuilding it. The epidemic had resulted in Memphis being a less cosmopolitan place, with an economy that served the cotton trade and a population drawn increasingly from poor white and black Southerners. The 1890 election was strongly contested, resulting in white opponents of the D. P. Hadden faction working to deprive them of votes by disenfranchising blacks . The state had enacted several laws, including

14520-416: The poverty and hardship it wrought, giving further credence to Memphis as a rough, shiftless city. Leading up to the outbreak in 1878, it had suffered two yellow fever epidemics, cholera , and malaria , giving it a reputation as sickly and filthy. It was unheard of for a city with a population as large as Memphis's not to have any waterworks; the city still relied for supplies entirely on collecting water from

14652-478: The publisher's summary of L.B. Wrenn's study of the period, "This centralization of political power in a small commission aided the efficient transaction of municipal business, but the public policies that resulted from it tended to benefit upper-class Memphians while neglecting the less affluent residents and neighborhoods." The city installed a revolutionary sewer system and upgraded sanitation and drainage to prevent another epidemic. Pure water from an artesian well

14784-908: The remaining genes mostly accounting for fewer than 1% of either familial or sporadic cases. ALS genes identified to date explain the cause of about 70% of familial ALS and about 15% of sporadic ALS. Overall, first-degree relatives of an individual with ALS have a ~1% risk of developing ALS themselves. The multi-step hypothesis suggests the disease is caused by some interaction between an individual's genetic risk factors and their cumulative lifetime of exposures to environmental factors, termed their exposome . The most consistent lifetime exposures associated with developing ALS (other than genetic mutations) include heavy metals (e.g. lead and mercury ), chemicals (e.g. pesticides and solvents ), electric shock , physical injury (including head injury ), and smoking (in men more than women). Overall these effects are small, with each exposure in isolation only increasing

14916-408: The remains of Confederate General and Ku Klux Klan leader Nathan Bedford Forrest were removed from a Memphis park. On January 7, 2023, after a routine traffic stop, five African American police officers brutally beat a 29-year-old African American man, Tyre Nichols . Nichols died from his injuries in the hospital three days later. Officer body cam footage and local surveillance cameras captured

15048-403: The requirement of poll taxes , that made it more difficult for them to register to vote and served to disenfranchise many blacks. Although political party factions in the future sometimes paid poll taxes to enable blacks to vote, African Americans lost their last positions on the city council in this election and were forced out of the police force. (They did not recover the ability to exercise

15180-424: The river and rain cisterns, and had no way to remove sewage. The combination of a swelling population, especially of lower and working classes, and abysmal health and sanitary conditions made Memphis ripe for a serious epidemic. Kate Bionda, an owner of an Italian "snack house", died of a fever on August 13, 1878. Hers was officially reported by the Board of Health, on August 14, as the first case of yellow fever in

15312-448: The spinal cord. The defining feature of ALS is the death of both upper motor neurons (located in the motor cortex of the brain) and lower motor neurons (located in the brainstem and spinal cord). In ALS with frontotemporal dementia, neurons throughout the frontal and temporal lobes of the brain die as well. The pathological hallmark of ALS is the presence of inclusion bodies (abnormal aggregations of protein) known as Bunina bodies in

15444-652: The stress of war and occupation and uncertainty about who was in charge, increasing tensions between the city's ethnic Irish policemen and black Union soldiers after the war. In three days of rioting in early May 1866, the Memphis Riots erupted, in which white mobs made up of policemen, firemen, and other mostly ethnic Irish Americans attacked and killed 46 blacks, wounding 75 and injuring 100; raped several women; and destroyed nearly 100 houses while severely damaging churches and schools in South Memphis. Much of

15576-405: The symptoms, such as a spinal cord tumor, multiple sclerosis , a herniated disc in the neck, syringomyelia , or cervical spondylosis . Based on the person's symptoms and findings from the examination and from these tests, the physician may order tests on blood and urine samples to eliminate the possibility of other diseases, as well as routine laboratory tests. In some cases, for example, if

15708-571: The television miniseries A Rumor of War and in the 1980 Hallmark Hall of Fame TV movie Gideon's Trumpet starring Henry Fonda , José Ferrer and John Houseman . Smith is also credited for playing McMurphy 650 times in the 1971 Off-Broadway revival of One Flew Over the Cuckoo's Nest . Smith made a major breakthrough in 1984 with significant roles in Red Dawn , Places in the Heart and

15840-427: The television series V . He also played on Quincy, M.E. in season 8, episode 7, "Science for Sale" as an oncologist searching for a cure to cancer. In 1989, Smith gained recognition for his portrayal of Richard Nixon in the docudrama The Final Days . Newsweek praised the performance, writing, "[Smith] is such a good Nixon that his despair and sorrow at his predicament become simply overwhelming." Smith earned

15972-419: The term amyotrophic lateral sclerosis . ALS is a motor neuron disease , which is a group of neurological disorders that selectively affect motor neurons , the cells that control voluntary muscles of the body. Other motor neuron diseases include primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), progressive bulbar palsy , pseudobulbar palsy , and monomelic amyotrophy (MMA). As

16104-404: The types of motor neurons that are affected. To successfully control any voluntary muscle in the body, a signal must be sent from the motor cortex in the brain down the upper motor neuron as it travels down the spinal cord. There, it connects via a synapse to the lower motor neuron which connects to the muscle itself. Damage to either the upper or lower motor neuron, as it makes its way from

16236-462: The uncertain nature of their own claim to "whiteness"; they were trying to distinguish themselves from blacks in the underclass. The main fighting participants were ethnic Irish, decommissioned black Union soldiers, and newly emancipated African-American freedmen . Walker suggests that most of the mob was not in direct economic conflict with the blacks, as by then the Irish had attained better jobs, but were establishing social and political dominance over

16368-509: The upper arms symmetrically and progressing downwards to the hands. Flail leg syndrome is characterized by lower motor neuron damage leading to asymmetrical weakness and wasting in the legs starting around the feet. Isolated bulbar palsy is characterized by upper or lower motor neuron damage in the bulbar region (in the absence of limb symptoms for at least 20 months), leading to gradual onset of difficulty with speech ( dysarthria ) and swallowing ( dysphagia ). ALS can also be classified based on

16500-547: The world's largest spot cotton market and the world's largest hardwood lumber market, both commodity products of the Mississippi Delta. Into the 1950s, it was also the world's largest mule market. These animals were still used extensively for agriculture. Attracting workers from Southern rural areas as well as new European immigrants, from 1900 to 1950 the city increased nearly fourfold in population, from 102,350 to 396,000 residents. Racist violence continued into

16632-506: Was an unusual case. Cognitive impairment or behavioral dysfunction is present in 30–50% of individuals with ALS, and can appear more frequently in later stages of the disease. Language dysfunction , executive dysfunction , and troubles with social cognition and verbal memory are the most commonly reported cognitive symptoms in ALS. Cognitive impairment is found more frequently in patients with C9orf72 gene repeat expansions, bulbar onset, bulbar symptoms, family history of ALS, and/or

16764-522: Was contested by European settlers as Memphis developed. By 1819, when modern Memphis was founded, it was part of the United States territory. John Overton , James Winchester , and Andrew Jackson founded the city. Based on the wealth of cotton plantations and river traffic along the Mississippi, Memphis grew into one of the largest cities of the Antebellum South . After the Civil War and

16896-439: Was discovered in the 1880s, securing the city's water supply. The commissioners developed an extensive network of parks and public works as part of the national City Beautiful movement , but did not encourage heavy industry, which might have provided substantial employment for the working-class population. The lack of representation in city government resulted in the poor and minorities being underrepresented. The majority controlled

17028-413: Was established there and is a Smithsonian affiliate institution. Since the civil rights era, Memphis has become one of the nation's leading commercial centers in transportation and logistics . The largest employer is FedEx , which maintains its global air hub at Memphis International Airport . In 2021, Memphis was the world's second-busiest cargo airport. The International Port of Memphis also hosts

17160-421: Was forced to move away from the city. But she continued to investigate and publish the abuses of lynching . Businessmen were eager to increase the city population after the losses of 1878–79, and supported the annexation of new areas; this measure was passed in 1890 before the census. The annexation measure was finally approved by the state legislature through a compromise achieved with real estate magnates, and

17292-501: Was only offered to those with obviously familial ALS. But it is increasingly recognized that cases of sporadic ALS may also be due to disease-causing de novo mutations in SOD1 , or C9orf72 , an incomplete family history, or incomplete penetrance , meaning that a patient's ancestors carried the gene but did not express the disease in their lifetimes. The lack of positive family history may be caused by lack of historical records, having

17424-534: Was to separate the poor from the city and isolate them in refugee camps. The Howard Association, formed specifically for yellow fever epidemics in New Orleans and Memphis, organized nurses and doctors in Memphis and throughout the country. They stayed at the Peabody Hotel , the only hotel to keep its doors open during the epidemic. From there they were assigned to their respective districts. Physicians of

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