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The Evolutionary Perspective
Tag Archives: architecture
Posted: July 18, 2016 at 3:37 pm
Experiencing great architecture is like enjoying the finest of natural environments. It rewards the senses. It sparks imagination and emotions. It inspires. It enhances consciousness. SFIAs mission is to provide that kind of experience in the process of architectural education. Hundreds of architects, artists, and technologists are working on this level. These are the ones we study and learn from at SFIA. These architects work in ways that are called Organic, Evolutionary, Ecological, and even Extropian or Futurist.
Organic Architecture is integrated with environmental and human needs to a degree never seen in conventional buildings or known to most schools of architecture. The depth and impact of this integration is similar to that found in great music and the natural world. The results, at their best, are a synthesis of function and form, poetry and technology, humanity and nature . . . and extraordinarily uplifting to those fortunate enough to experience it.
Evolutionary and Ecological architectures combine Organic integration with natural process, environmental sensitivity, health awareness, and economical simplicity.
Extropian and Futurist architectures suggest that life and human consciousness can be raised to higher plateaus through visionary applications of advanced technology.
Nature Based Architecture is the overall term that describes all of the above. Nature based architecture represents, in a single phrase, the architecture that is emerging from this school, its teachers, and its students.
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Posted: June 17, 2016 at 4:52 am
A retreat is a place of refuge for those in the survivalist subculture or movement. A retreat is also sometimes called a bug-out location (BOL). Survivalist retreats are intended to be self-sufficient and easily defended, and are generally located in sparsely populated rural areas.
While fallout shelters have been advocated since the 1950s, dedicated self-sufficient survivalist retreats have been advocated only since the mid-1970s. The survival retreat concept has been touted by a number of influential survivalist writers including Ragnar Benson, Barton Biggs, Bruce D. Clayton, Jeff Cooper, Cresson Kearny, James Wesley Rawles, Howard Ruff, Kurt Saxon, Joel Skousen, Don Stephens, Mel Tappan, and Nancy Tappan.
With the increasing inflation of the 1960s, the impending US monetary devaluation, the continuing concern with possible nuclear exchanges between the US and the Soviet Union, and the increasing vulnerability of urban centers to supply shortages and other systems failures, a number of primarily conservative and libertarian thinkers began suggesting that individual preparations would be wise. Harry Browne began offering seminars in 1967 on how to survive a monetary collapse. He worked with Don Stephens, an architect, survival bookseller, and author, who provided input on how to build and equip a remote survival retreat. He provided a copy of his original Retreater’s Bibliography (1967) for each seminar participant.
Articles on the subject appeared in such small-distribution libertarian publications as The Innovator and Atlantis Quarterly. It was also from this period that Robert D. Kephart began publishing Inflation Survival Letter (later renamed Personal Finance). The newsletter included a continuing section on personal preparedness by Stephens for several years. It promoted expensive seminars around the US on the same cautionary topics. Stephens participated, along with James McKeever and other defensive investing, hard currency advocates.
In 1975, Kurt Saxon began publishing a newsletter called The Survivor, which advocated moving to lightly populated regions to “lie low” during a socio-economic collapse, and setting up fortified enclaves for defense against what he termed “killer caravans” of looters from urban areas.
In 1976, Don Stephens popularized the term “retreater” and advocated relocating to a rural retreat when society breaks down.
Writers such as Howard Ruff warned about socio-economic collapse and recommended moving to lightly populated farming regions, most notably in his 1979 book How to Prosper During the Coming Bad Years, a best-seller in 1979.
For a time in the 1970s, the terms “survivalist” and “retreater” were used interchangeably. The term “retreater” eventually fell out of favor.
One of the most important newsletters on survivalism and survivalist retreats in the 1970s was the Personal Survival (“P.S.”) Letter (circa 1977-1982) published by Mel Tappan, who also authored the books Survival Guns and Tappan on Survival. The newsletter included columns from Tappan himself, as well from Jeff Cooper, Al J. Venter, Bill Pier, Bruce D. Clayton, Rick Fines, Nancy Mack Tappan, J.B. Wood, Dr. Carl Kirsch, Charles Avery, Karl Hess, Eugene A. Barron, Janet Groene, Dean Ing, Bob Taylor, Reginald Bretnor, C.G. Cobb, and several other writers, some under pen names. The majority of this newsletter revolved around selecting, constructing and logistically equipping survival retreats. Following Tappan’s death in 1980, Karl Hess took over publishing the newsletter, eventually renaming it Survival Tomorrow.
Survivalist retreat books of the 1980s were typified by the 1980 book Life After Doomsday by Bruce D. Clayton, advocating survival retreats in locales that would minimize fallout, as well as specially constructing blast shelters and/or fallout shelters that would provide protection in the event of a nuclear war.
Several books published in the 1990s offered advice on survival retreats and relocation. Some influential in survivalist circles are Survival Retreat: A Total Plan For Retreat Defense by Ragnar Benson, Strategic RelocationNorth American Guide to Safe Places by Joel Skousen, and The Secure Home, (also by Skousen).
In recent years, advocacy of survivalist retreats has had a strong resurgence after the terrorist attacks on the World Trade Center in New York in 2001, the 2002 attacks and 2005 attacks in Bali, the 2004 Madrid train bombings in Spain, and the 2005 public transportation bombings in London.
Several books published since 2000 advocate survival retreats and relocation. Some that have been particularly influential in survivalist circles are How to Implement a High Security Shelter in the Home by Joel Skousen, Rawles on Retreats and Relocation by James Wesley Rawles, and Life After Terrorism: What You Need to Know to Survive in Today’s World by Bruce D. Clayton.
Online survival websites, forums, and blogs (such as SurvivalBlog) discuss the best locales for survival retreats, how to build, fortify, and equip them, and how to form survivalist retreat groups.
Economic troubles emerging from the credit collapse triggered by the 2007 US subprime mortgage crisis have prompted a wider cross-section of the populace to modify their homes as well as establish dedicated survival retreats. James Wesley Rawles, the editor of SurvivalBlog was quoted by the New York Times in April 2008 that “interest in the survivalist movement ‘is experiencing its largest growth since the late 1970s’. He also stated that his blog’s conservative core readership has been supplemented with “an increasing number of stridently green and left-of-center readers.”
Mel Tappan was quoted in 1981 by then AP correspondent Peter Arnett that: “The concept most fundamental to long term disaster preparedness, in retreating, is having a safe place to go to avoid the concentrated violence destined to erupt in the cities.” 
Common retreat locale selection parameters include light population density, plentiful water, arable land, good solar exposure for gardening and photovoltaics, situation above any flood plains, and a diverse and healthy local economy. Fearing rioting, looting and other unrest, many survivalists advocate selecting retreat locales that are more than one tank of gasoline away from any major metropolitan region. Properties that are not in “channelized areas” or on anticipated “refugee lines of drift” are also touted.
One of the key goals of retreats is to be self-sufficient for the duration of societal collapse. To that end, plentiful water and arable soil are paramount considerations. Beyond that, a priority is situation on isolated, defensible terrain. Typically, retreats do not want their habitations or structures jeopardized by being within line of sight of any major highway.
Because of its low population density and diverse economy, James Wesley Rawles  and Joel Skousen  both recommend the Intermountain West region of the United States as a preferred region for relocation and setting up retreats. Although it has higher population density, Mel Tappan recommended southwestern Oregon, where he lived, primarily because it is not downwind of any envisioned nuclear targets in the United States.
Mel Tappan was disappointed by the demographics of southwestern Oregon after the survivalist influx of the late 1970s. “Too many doctors and lawyers” relocated to Oregon, and “not enough plumbers, electricians, or carpent
While some survivalists recommend living at a rural retreat year-round, most survivalists cannot afford to do so. Therefore, they rely on keeping a well-stocked retreat, and plan to go there “at the 11th hour”, as necessary. They keep a bug-out bag handy, and may have a dedicated bug-out vehicle (BOV). This is a vehicle that the owner keeps prepared in the event of the need for an emergency evacuation. Typically a BOV is equipped with a variation on the bug-out bag that includes additional automotive supplies, clothing, food and water. Survivalists tend to favor four wheel drive trucks and SUVs due to their greater off-road abilities. In the event of a nuclear catastrophe, survivalists may opt into maintaining an older vehicle since it most likely lacks critical electronic components that would otherwise be damaged by the electromagnetic pulse that accompanies a nuclear explosion.
Most survivalist retreats are created by individuals and their families, but larger “group retreats” or “covenant communities” are formed along the lines of an intentional community.
Jeff Cooper popularized the concept of hardening retreats against small arms fire. In an article titled “Notes on Tactical Residential Architecture” in Issue #30 of P.S. Letter (April, 1982), Cooper suggested using the “Vauban Principle”, whereby projecting bastion corners would prevent miscreants from being able to approach a retreat’s exterior walls in any blind spots. Corners with this simplified implementation of a Vauban Star are now called “Cooper Corners” by James Wesley Rawles, in honor of Jeff Cooper. Depending on the size of the group needing shelter, design elements of traditional European castle architecture, as well as Chinese Fujian Tulou and Mexican walled courtyard houses have been suggested for survival retreats.
In both his book Rawles on Retreats and Relocation and in his survivalist novel, Patriots: A Novel of Survival in the Coming Collapse, Rawles describes in great detail retreat groups “upgrading” brick or other masonry houses with steel reinforced window shutters and doors, excavating anti-vehicular ditches, installing warded gate locks, constructing concertina wire obstacles and fougasses, and setting up listening post/observation posts (LP/OPs.) Rawles is a proponent of including a mantrap foyer at survival retreats, an architectural element that he calls a “crushroom”.
Bruce D. Clayton and Joel Skousen have both written extensively on integrating fallout shelters into retreat homes, but they put less emphasis on ballistic protection and exterior perimeter security than Cooper and Rawles.
Anticipating long periods of time without commerce in the future, as well as observing documented history, retreat groups typically place a strong emphasis on logistics. They amass stockpiles of supplies for their own use, for charity, and for barter. Frequently cited key logistics for a retreat include long term storage food, common caliber ammunition, medical supplies, tools, gardening seed, and fuel. In an article titled “Ballistic Wampum” in Issue #6 of P.S. Letter (1979) Jeff Cooper wrote about stockpiling ammunition far in excess of his own needs, keeping the extra available to use for bartering.
In their books, Joel Skousen, Mel Tappan and Howard Ruff all emphasize the need to have a one-year supply of storage food.
Mainstream economist and financial adviser Barton Biggs is a proponent of well-stocked retreats. In his 2008 book Wealth, War and Wisdom, Biggs has a gloomy outlook for the economic future, and suggests that investors take survivalist measures. In the book, Biggs recommends that his readers should assume the possibility of a breakdown of the civilized infrastructure. He goes so far as to recommend setting up survival retreats: Your safe haven must be self-sufficient and capable of growing some kind of food, Mr. Biggs writes. It should be well-stocked with seed, fertilizer, canned food, wine, medicine, clothes, etc. Think Swiss Family Robinson. Even in America and Europe there could be moments of riot and rebellion when law and order temporarily breaks down.
Survivalist retreats, both formal and informal exist worldwide, most visibly in Australia, Belgium, Canada, France, Germany (often organized under the guise of “adventuresport” clubs), New Zealand, Norway, Russia, Sweden, the United Kingdom and the United States.
Construction of government-built retreats and underground sheltersroughly analogous to survivalist retreatshas been done extensively since the advent of the Cold War, especially of public nuclear fallout shelters in many nations. The United States government has created Continuity of Government (COG) shelters built by the Department of Defense and Federal Emergency Management Agency (“FEMA”). These include the massive shelter built under the Greenbrier hotel (aka Project Greek Island), military facilities like Cheyenne Mountain Complex, and the Raven Rock Mountain Complex and Mount Weather sites. Other nations’ facilities include the Swiss redoubt fortress system and its dual use facilities like the Sonnenberg Tunnel and Norway’s Sentralanlegget bunker in Buskerud County.
Robert A. Heinlein featured survivalist retreats in some of his science fiction. Farnham’s Freehold (1964) begins as a story of a small group in a survivalist retreat during a nuclear war. Heinlein also wrote essays such as How to be a Survivor which provide advice on preparing for and surviving a nuclear war, including stocking a fallout shelter and retreat.
Malevil by French writer Robert Merle (1972) describes refurbishing a medieval castle and its use as a survivalist stronghold in the aftermath of a full-scale nuclear war. The novel was adapted into a 1981 film directed by Christian de Chalonge and starring Michel Serrault, Jacques Dutronc, Jacques Villeret and Jean-Louis Trintignant.
Lucifer’s Hammer by Jerry Pournelle and Larry Niven (1977) is about a cataclysmic comet hitting the Earth, and a group of people struggling to survive the aftermath.
Patriots: A Novel of Survival in the Coming Collapse by James Wesley Rawles (2009) describes how the lead characters establish a self-sufficient survival retreat in north-central Idaho.
Jericho (2006) is a TV series that portrays a small town in Kansas after a series of nuclear explosions across the United States. In the series, the character Robert Hawkins uses his prior planning and survival skills in preparation of the attacks. Although it is not fortified, the town effectively becomes a large scale retreat, for its residents.
The text of some books discussing survivalist retreats can be found online:
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Posted: June 12, 2016 at 12:41 am
Stephanie Rogers 4 years ago
From tree house villages in Costa Rica to yoga communes in Hawaii, these 10 intentional communities are havens of peace, creativity and sustainability.
Imagine waking up to the sound of bells from a temple to share in a morning yoga ritual overlooking the mountains of Peru, or the glittering Pacific Ocean in Hawaii. Picking fresh vegetables from your neighborhood garden to cook in a community-wide meal in a spacious, shared kitchen. Building your own non-toxic, mortgage-free cob house in a low-impact neighborhood of like-minded nature lovers. Stepping out of your very own treehouse to gaze at a network of aerial walkways that look like something out of a sci-fi movie. These 10 intentional communities, from utopian eco-villages to cute historic houses in urban Los Angeles, bring people together with common goals of harmonic living, artistic exploration and sustainability.
Polestar Yoga Community, Big Island, Hawaii
What could be more relaxing than a yoga community in Hawaii? Polestar offers an energizing lifestyle of daily yoga and meditation, karmic yoga or service projects, and outdoor adventure opportunities. Though it bills itself as a spiritual community, people of all faiths are welcome at this cooperative living retreat which is home to full-time residents and also open to visitors and apprentices. Awakened each morning by the sound of music from the temple, a shrine dedicated to the teachings of Paramhansa Yogananda, guests enjoy daily routines involving organic food grown on site, volunteer service, art and lots of community involvement.
Eco Truly Park, Peru
It looks like something out of a fairy tale: adorable little cone-shaped buildings topped with colorfully painted spires, dotting the hillside on the Pacific coast of Peru. This ecological and artistic community, an hour north of Lima, was founded on principles of non-violence, simple living and harmony with nature. Both the architecture and the values of the community are inspired by traditional Indian teachings and lifestyles. Eco Truly Park has a goal of being fully self-sustainable, and currently boasts a large organic garden. Open to volunteers, the community offers workshops in yoga, art and Vedic philosophy.
Synchronicity Artist Commune, Los Angeles, California
Embodying the laid-back lifestyle of sunny Southern California, Synchronicity is a relaxed and welcoming intentional living community in the historic West Adams District of Los Angeles. Though its small nowhere near the size of the rest of the communities on this list Synchronicity is a great example of the thousands of similar shared households around the United States. Synchronicity has eleven residents and focuses mostly on artistic actions and holding monthly artistic salons that are open to the public.
Earthhaven Ecovillage, Asheville, North Carolina
Located in the mountains of Western North Carolina, Earthaven is just one of many similar intentional communities focusing on sustainable living. Youll find virtually every type of natural building here, including earthships, cob houses and rustic cabins, with construction methods that eliminate toxic materials, logged timber and mortgages. Set on 320 lush acres 40 minutes southwest of Asheville, Earthaven frequently holds natural building workshops and welcomes the public to learn about permaculture, organic gardening and other sustainable topics. They offer camping and visitor accommodations as well as live-work arrangements.
Milagro Cohousing, Tucson, Arizona
Twelve minutes from downtown Tucson, Arizona, Milagro is a co-housing community with 28 passive-solar, energy-efficient adobe homes on 43 acres. Set against the Tucson mountains, Milagro is simply a community of people who want to live a green lifestyle, surrounded by like-minded neighbors. Each resident has access to 35 acres of undeveloped open space, as well as the 3,600-square-foot Common House, which has meeting and dining space, a library, a playroom and storage space. Gardens, workshops and a solar-heated swimming pool make it even more enticing.
Finca Bellavista Treehouse Community, Costa Rica
If youve ever watched Star Wars and wished that you could live with the Ewoks in their magical tree house community, take heed: such a thing actually exists. And its in Costa Rica. Finca Bellavista is a network of rustic, hand-built tree houses in the mountainous South Pacific coastal region of this Central American nation, surrounded by a jungle that is brimming with life. The off-grid, carbon-neutral tree houses are connected by aerial walkways and include a central community center with a dining area, barbecue and lounge. Gardens, ziplines and hiking trails make it even more of a tropical paradise. Prospective community members can design and build their own tree houses. Additionally, some of the tree house owners rent out their homes, and there are visitor accommodations available.
Tamera Peace Research Village, Portugal
Aiming to be a totally self-sufficient community, the Tamera Peace Research Village is in the Alentejo region of southwestern Portugal and is home to 250 coworkers and students who study how humans can live peacefully in sustainable communities, in harmony with nature. It includes a non-profit peace foundation, a SolarVillage test site, a permaculture project with an edible landscape, and a sanctuary for horses.
Dancing Rabbit Eco Village, Missouri
Another showcase of the beauty of natural building techniques, the Dancing Rabbit Eco Village is a sustainable community located near Rutledge, Missouri advocating low-impact living and dedication to social change. Everything from members diets to the way they use water is dictated by a commitment to living lightly on the earth. The village is on 280 acres including six ponds, a small creek and 40 acres of woodland, plus 30 acres where they have planted over 12,000 trees as part of a restoration program.
EcoVillage at Ithaca, New York
What would the ideal sustainable community look like? The EcoVillage at Ithaca is one example that is already thriving in the Finger Lakes region of upstate New York. It includes three co-housing neighborhoods called Frog, Song and Tree as well as an organic CSA vegetable farm, community gardens and over 100 acres of protected green space. The houses are all energy-efficient and share facilities like a common house, wood shop, metal shop, bike shed, playgrounds and centralized compost bins.
Conceptual Community of Tiny Houses
Its not yet a reality, but tiny house enthusiasts have a dream: idyllic neighborhoods where people who have committed to living in very small spaces can get together and share resources and camaraderie. Tiny house communities are hard to come by because of various city and county ordinances, which favor large houses and conventional utilities. At TinyHouseCommunity.com, people who live in tiny houses or want to build their own some day get together to talk about making these villages happen. There are two tiny house communities currently in planning phases, in Washington D.C. and Texas.
Top photo: Dancing Rabbit Eco Village
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Posted: June 10, 2016 at 12:44 pm
Cystic fibrosis (CF) is a genetic disorder that affects mostly the lungs but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Other signs and symptoms include sinus infections, poor growth, fatty stool, clubbing of the fingers and toes, and infertility in males, among others. Different people may have different degrees of symptoms.
CF is inherited in an autosomal recessive manner. It is caused by the presence of mutations in both copies of the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Those with a single working copy are carriers and otherwise mostly normal. CFTR is involved in production of sweat, digestive fluids, and mucus. When CFTR is not functional, secretions which are usually thin instead become thick. The condition is diagnosed by a sweat test and genetic testing. Screening of infants at birth takes place in some areas of the world.
There is no cure for cystic fibrosis. Lung infections are treated with antibiotics which may be given intravenously, inhaled, or by mouth. Sometimes the antibiotic azithromycin is used long term. Inhaled hypertonic saline and salbutamol may also be useful. Lung transplantation may be an option if lung function continues to worsen. Pancreatic enzyme replacement and fat-soluble vitamin supplementation are important, especially in the young. While not well supported by evidence, many people use airway clearance techniques such as chest physiotherapy. The average life expectancy is between 42 and 50 years in the developed world. Lung problems are responsible for death in 80% of people with cystic fibrosis.
CF is most common among people of Northern European ancestry and affects about one out of every 3,000 newborns. About one in 25 people are carriers. It is least common in Africans and Asians. It was first recognized as a specific disease by Dorothy Andersen in 1938, with descriptions that fit the condition occurring at least as far back as 1595. The name cystic fibrosis refers to the characteristic fibrosis and cysts that form within the pancreas.
The main signs and symptoms of cystic fibrosis are salty-tasting skin, poor growth, and poor weight gain despite normal food intake, accumulation of thick, sticky mucus, frequent chest infections, and coughing or shortness of breath. Males can be infertile due to congenital absence of the vas deferens. Symptoms often appear in infancy and childhood, such as bowel obstruction due to meconium ileus in newborn babies. As the children grow, they exercise to release mucus in the alveoli.Ciliated epithelial cells in the person have a mutated protein that leads to abnormally viscous mucus production. The poor growth in children typically presents as an inability to gain weight or height at the same rate as their peers and is occasionally not diagnosed until investigation is initiated for poor growth. The causes of growth failure are multifactorial and include chronic lung infection, poor absorption of nutrients through the gastrointestinal tract, and increased metabolic demand due to chronic illness.
In rare cases, cystic fibrosis can manifest itself as a coagulation disorder. Vitamin K is normally absorbed from breast milk, formula, and later, solid foods. This absorption is impaired in some cystic fibrosis patients. Young children are especially sensitive to vitamin K malabsorptive disorders because only a very small amount of vitamin K crosses the placenta, leaving the child with very low reserves and limited ability to absorb vitamin K from dietary sources after birth. Because factors II, VII, IX, and X (clotting factors) are vitamin Kdependent, low levels of vitamin K can result in coagulation problems. Consequently, when a child presents with unexplained bruising, a coagulation evaluation may be warranted to determine whether there is an underlying disease.
Lung disease results from clogging of the airways due to mucus build-up, decreased mucociliary clearance, and resulting inflammation. Inflammation and infection cause injury and structural changes to the lungs, leading to a variety of symptoms. In the early stages, incessant coughing, copious phlegm production, and decreased ability to exercise are common. Many of these symptoms occur when bacteria that normally inhabit the thick mucus grow out of control and cause pneumonia. In later stages, changes in the architecture of the lung, such as pathology in the major airways (bronchiectasis), further exacerbate difficulties in breathing. Other signs include coughing up blood (hemoptysis), high blood pressure in the lung (pulmonary hypertension), heart failure, difficulties getting enough oxygen to the body (hypoxia), and respiratory failure requiring support with breathing masks, such as bilevel positive airway pressure machines or ventilators.Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa are the three most common organisms causing lung infections in CF patients. In addition to typical bacterial infections, people with CF more commonly develop other types of lung disease. Among these is allergic bronchopulmonary aspergillosis, in which the body’s response to the common fungus Aspergillus fumigatus causes worsening of breathing problems. Another is infection with Mycobacterium avium complex (MAC), a group of bacteria related to tuberculosis, which can cause a lot of lung damage and does not respond to common antibiotics.
Mucus in the paranasal sinuses is equally thick and may also cause blockage of the sinus passages, leading to infection. This may cause facial pain, fever, nasal drainage, and headaches. Individuals with CF may develop overgrowth of the nasal tissue (nasal polyps) due to inflammation from chronic sinus infections. Recurrent sinonasal polyps can occur in as many as 10% to 25% of CF patients. These polyps can block the nasal passages and increase breathing difficulties.
Cardiorespiratory complications are the most common cause of death (~80%) in patients at most CF centers in the United States.
Prior to prenatal and newborn screening, cystic fibrosis was often diagnosed when a newborn infant failed to pass feces (meconium). Meconium may completely block the intestines and cause serious illness. This condition, called meconium ileus, occurs in 510% of newborns with CF. In addition, protrusion of internal rectal membranes (rectal prolapse) is more common, occurring in as many as 10% of children with CF, and it is caused by increased fecal volume, malnutrition, and increased intraabdominal pressure due to coughing.
The thick mucus seen in the lungs has a counterpart in thickened secretions from the pancreas, an organ responsible for providing digestive juices that help break down food. These secretions block the exocrine movement of the digestive enzymes into the duodenum and result in irreversible damage to the pancreas, often with painful inflammation (pancreatitis). The pancreatic ducts are totally plugged in more advanced cases, usually seen in older children or adolescents. This causes atrophy of the exocrine glands and progressive fibrosis.
The lack of digestive enzymes leads to difficulty absorbing nutrients with their subsequent excretion in the feces, a disorder known as malabsorption. Malabsorption leads to malnutrition and poor growth and development because of calorie loss. Resultant hypoproteinemia may be severe enough to cause generalized edema. Individuals with CF also have difficulties absorbing the fat-soluble vitamins A, D, E, and K.
In addition to the pancreas problems, people with cystic fibrosis experience more heartburn, intestinal blockage by intussusception, and constipation. Older individuals with CF may develop distal intestinal obstruction syndrome when thickened feces cause intestinal blockage.
Exocrine pancreatic insufficiency occurs in the majority (85% to 90%) of patients with CF. It is mainly associated with “severe” CFTR mutations, where both alleles are completely nonfunctional (e.g. F508/F508). It occurs in 10% to 15% of patients with one “severe” and one “mild” CFTR mutation where there still is a little CFTR activity, or where there are two “mild” CFTR mutations. In these milder cases, there is still sufficient pancreatic exocrine function so that enzyme supplementation is not required. There are usually no other GI complications in pancreas-sufficient phenotypes, and in general, such individuals usually have excellent growth and development. Despite this, idiopathic chronic pancreatitis can occur in a subset of pancreas-sufficient individuals with CF, and is associated with recurrent abdominal pain and life-threatening complications.
Thickened secretions also may cause liver problems in patients with CF. Bile secreted by the liver to aid in digestion may block the bile ducts, leading to liver damage. Over time, this can lead to scarring and nodularity (cirrhosis). The liver fails to rid the blood of toxins and does not make important proteins, such as those responsible for blood clotting. Liver disease is the third most common cause of death associated with CF.
The pancreas contains the islets of Langerhans, which are responsible for making insulin, a hormone that helps regulate blood glucose. Damage of the pancreas can lead to loss of the islet cells, leading to a type of diabetes that is unique to those with the disease. This cystic fibrosis-related diabetes (CFRD) shares characteristics that can be found in type 1 and type 2 diabetics, and is one of the principal nonpulmonary complications of CF.Vitamin D is involved in calcium and phosphate regulation. Poor uptake of vitamin D from the diet because of malabsorption can lead to the bone disease osteoporosis in which weakened bones are more susceptible to fractures. In addition, people with CF often develop clubbing of their fingers and toes due to the effects of chronic illness and low oxygen in their tissues.
Infertility affects both men and women. At least 97% of men with cystic fibrosis are infertile, but not sterile and can have children with assisted reproductive techniques. The main cause of infertility in men with cystic fibrosis is congenital absence of the vas deferens (which normally connects the testes to the ejaculatory ducts of the penis), but potentially also by other mechanisms such as causing no sperm, teratospermia, and few sperm with poor motility. Many men found to have congenital absence of the vas deferens during evaluation for infertility have a mild, previously undiagnosed form of CF. Approximately 20% of women with CF have fertility difficulties due to thickened cervical mucus or malnutrition. In severe cases, malnutrition disrupts ovulation and causes a lack of menstruation.
CF is caused by a mutation in the gene cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, F508, is a deletion ( signifying deletion) of three nucleotides that results in a loss of the amino acid phenylalanine (F) at the 508th position on the protein. This mutation accounts for two-thirds (6670%) of CF cases worldwide and 90% of cases in the United States; however, there are over 1500 other mutations that can produce CF. Although most people have two working copies (alleles) of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when neither allele can produce a functional CFTR protein. Thus, CF is considered an autosomal recessive disease.
The CFTR gene, found at the q31.2 locus of chromosome 7, is 230,000 base pairs long, and creates a protein that is 1,480 amino acids long. More specifically the location is between base pair 117,120,016 to 117,308,718 on the long arm of chromosome 7, region 3, band 1, sub-band 2, represented as 7q31.2. Structurally, CFTR is a type of gene known as an ABC gene. The product of this gene (the CFTR) is a chloride ion channel important in creating sweat, digestive juices and mucus. This protein possesses two ATP-hydrolyzing domains, which allows the protein to use energy in the form of ATP. It also contains two domains comprising 6 alpha helices apiece, which allow the protein to cross the cell membrane. A regulatory binding site on the protein allows activation by phosphorylation, mainly by cAMP-dependent protein kinase. The carboxyl terminal of the protein is anchored to the cytoskeleton by a PDZ domain interaction.
In addition, there is increasing evidence that genetic modifiers besides CFTR modulate the frequency and severity of the disease. One example is mannan-binding lectin, which is involved in innate immunity by facilitating phagocytosis of microorganisms. Polymorphisms in one or both mannan-binding lectin alleles that result in lower circulating levels of the protein are associated with a threefold higher risk of end-stage lung disease, as well as an increased burden of chronic bacterial infections.
There are several mutations in the CFTR gene, and different mutations cause different defects in the CFTR protein, sometimes causing a milder or more severe disease. These protein defects are also targets for drugs which can sometimes restore their function. F508-CFTR, which occurs in >90% of patients in the U.S., creates a protein that does not fold normally and is not appropriately transported to the cell membrane, resulting in its degradation. Other mutations result in proteins that are too short (truncated) because production is ended prematurely. Other mutations produce proteins that: do not use energy normally, do not allow chloride, iodide, and thiocyanate to cross the membrane appropriately, degrade at a faster rate than normal. Mutations may also lead to fewer copies of the CFTR protein being produced.
The protein created by this gene is anchored to the outer membrane of cells in the sweat glands, lungs, pancreas, and all other remaining exocrine glands in the body. The protein spans this membrane and acts as a channel connecting the inner part of the cell (cytoplasm) to the surrounding fluid. This channel is primarily responsible for controlling the movement of halogens from inside to outside of the cell; however, in the sweat ducts it facilitates the movement of chloride from the sweat duct into the cytoplasm. When the CFTR protein does not resorb ions in sweat ducts, chloride and thiocyanate released from sweat glands are trapped inside the ducts and pumped to the skin. Additionally hypothiocyanite, OSCN, cannot be produced by the immune defense system. Because chloride is negatively charged, this modifies the electrical potential inside and outside the cell that normally causes cations to cross into the cell. Sodium is the most common cation in the extracellular space. The excess chloride within sweat ducts prevents sodium resorption by epithelial sodium channels and the combination of sodium and chloride creates the salt, which is lost in high amounts in the sweat of individuals with CF. This lost salt forms the basis for the sweat test.
Most of the damage in CF is due to blockage of the narrow passages of affected organs with thickened secretions. These blockages lead to remodeling and infection in the lung, damage by accumulated digestive enzymes in the pancreas, blockage of the intestines by thick faeces, etc. There are several theories on how the defects in the protein and cellular function cause the clinical effects. The most current theory suggests that defective ion transport leads to dehydration in the airway epithelia, thickening mucus. In airway epithelial cells, the cilia exist in between the cell’s apical surface and mucus in a layer known as Airway Surface Liquid (ASL). The flow of ions from the cell and into this layer is determined by ion channels like CFTR. CFTR not only allows Chloride ions to be drawn from the cell and into the ASL, but it also regulates another channel called ENac. ENac allows sodium ions to leave the ASL and enter the respiratory epithelium. CFTR normally inhibits this channel, but if the CFTR is defective, then sodium will flow freely from the ASL and into the cell. As water follows sodium, the depth of ASL will be depleted and the cilia will be left in the mucous layer. As cilia cannot effectively move in a thick viscous environment, there is deficient mucociliary clearance and a buildup of mucous, clogging small airways. The accumulation of more viscous, nutrient-rich mucus in the lungs allows bacteria to hide from the body’s immune system, causing repeated respiratory infections. The presence of the same CFTR proteins in pancreatic duct and skin cells are what cause symptoms in these systems.
The lungs of individuals with cystic fibrosis are colonized and infected by bacteria from an early age. These bacteria, which often spread among individuals with CF, thrive in the altered mucus, which collects in the small airways of the lungs. This mucus leads to the formation of bacterial microenvironments known as biofilms that are difficult for immune cells and antibiotics to penetrate. Viscous secretions and persistent respiratory infections repeatedly damage the lung by gradually remodeling the airways, which makes infection even more difficult to eradicate.
Over time, both the types of bacteria and their individual characteristics change in individuals with CF. In the initial stage, common bacteria such as Staphylococcus aureus and Haemophilus influenzae colonize and infect the lungs. Eventually, Pseudomonas aeruginosa (and sometimes Burkholderia cepacia) dominates. By 18 years of age, 80% of patients with classic CF harbor P. aeruginosa, and 3.5% harbor B. cepacia. Once within the lungs, these bacteria adapt to the environment and develop resistance to commonly used antibiotics. Pseudomonas can develop special characteristics that allow the formation of large colonies, known as “mucoid” Pseudomonas, which are rarely seen in people that do not have CF.
One way infection spreads is by passing between different individuals with CF. In the past, people with CF often participated in summer “CF Camps” and other recreational gatherings. Hospitals grouped patients with CF into common areas and routine equipment (such as nebulizers) was not sterilized between individual patients. This led to transmission of more dangerous strains of bacteria among groups of patients. As a result, individuals with CF are now routinely isolated from one another in the healthcare setting, and healthcare providers are encouraged to wear gowns and gloves when examining patients with CF to limit the spread of virulent bacterial strains.
CF patients may also have their airways chronically colonized by filamentous fungi (such as Aspergillus fumigatus, Scedosporium apiospermum, Aspergillus terreus) and/or yeasts (such as Candida albicans); other filamentous fungi less commonly isolated include Aspergillus flavus and Aspergillus nidulans (occur transiently in CF respiratory secretions) and Exophiala dermatitidis and Scedosporium prolificans (chronic airway-colonizers); some filamentous fungi like Penicillium emersonii and Acrophialophora fusispora are encountered in patients almost exclusively in the context of CF. Defective mucociliary clearance characterizing CF is associated with local immunological disorders. In addition, the prolonged therapy with antibiotics and the use of corticosteroid treatments may also facilitate fungal growth. Although the clinical relevance of the fungal airway colonization is still a matter of debate, filamentous fungi may contribute to the local inflammatory response and therefore to the progressive deterioration of the lung function, as often happens with allergic broncho-pulmonary aspergillosis (ABPA) the most common fungal disease in the context of CF, involving a Th2-driven immune response to Aspergillus.
Cystic fibrosis may be diagnosed by many different methods including newborn screening, sweat testing, and genetic testing. As of 2006 in the United States, 10 percent of cases are diagnosed shortly after birth as part of newborn screening programs. The newborn screen initially measures for raised blood concentration of immunoreactive trypsinogen. Infants with an abnormal newborn screen need a sweat test to confirm the CF diagnosis. In many cases, a parent makes the diagnosis because the infant tastes salty.Trypsinogen levels can be increased in individuals who have a single mutated copy of the CFTR gene (carriers) or, in rare instances, in individuals with two normal copies of the CFTR gene. Due to these false positives, CF screening in newborns can be controversial. Most states and countries do not screen for CF routinely at birth. Therefore, most individuals are diagnosed after symptoms (e.g. sinopulmonary disease and GI manifestations) prompt an evaluation for cystic fibrosis. The most commonly used form of testing is the sweat test. Sweat-testing involves application of a medication that stimulates sweating (pilocarpine). To deliver the medication through the skin, iontophoresis is used to, whereby one electrode is placed onto the applied medication and an electric current is passed to a separate electrode on the skin. The resultant sweat is then collected on filter paper or in a capillary tube and analyzed for abnormal amounts of sodium and chloride. People with CF have increased amounts of sodium and chloride in their sweat. In contrast, people with CF have less thiocyanate and hypothiocyanite in their saliva and mucus (Banfi et al.). CF can also be diagnosed by identification of mutations in the CFTR gene.
People with CF may be listed in a disease registry that allows researchers and doctors to track health results and identify candidates for clinical trials.
Couples who are pregnant or planning a pregnancy can have themselves tested for the CFTR gene mutations to determine the risk that their child will be born with cystic fibrosis. Testing is typically performed first on one or both parents and, if the risk of CF is high, testing on the fetus is performed. The American College of Obstetricians and Gynecologists (ACOG) recommends testing for couples who have a personal or close family history of CF, and they recommend that carrier testing be offered to all Caucasian couples and be made available to couples of other ethnic backgrounds.
Because development of CF in the fetus requires each parent to pass on a mutated copy of the CFTR gene and because CF testing is expensive, testing is often performed initially on one parent. If testing shows that parent is a CFTR gene mutation carrier, the other parent is tested to calculate the risk that their children will have CF. CF can result from more than a thousand different mutations, and as of 2006 it is not possible to test for each one. Testing analyzes the blood for the most common mutations such as F508most commercially available tests look for 32 or fewer different mutations. If a family has a known uncommon mutation, specific screening for that mutation can be performed. Because not all known mutations are found on current tests, a negative screen does not guarantee that a child will not have CF.
During pregnancy, testing can be performed on the placenta (chorionic villus sampling) or the fluid around the fetus (amniocentesis). However, chorionic villus sampling has a risk of fetal death of 1 in 100 and amniocentesis of 1 in 200; a recent study has indicated this may be much lower, approximately 1 in 1,600.
Economically, for carrier couples of cystic fibrosis, when comparing preimplantation genetic diagnosis (PGD) with natural conception (NC) followed by prenatal testing and abortion of affected pregnancies, PGD provides net economic benefits up to a maternal age of approximately 40 years, after which NC, prenatal testing and abortion has higher economic benefit.
While there are no cures for cystic fibrosis, there are several treatment methods. The management of cystic fibrosis has improved significantly over the past 70 years. While infants born with cystic fibrosis 70 years ago would have been unlikely to live beyond their first year, infants today are likely to live well into adulthood. Recent advances in the treatment of cystic fibrosis have meant that an individual with cystic fibrosis can live a fuller life less encumbered by their condition. The cornerstones of management are proactive treatment of airway infection, and encouragement of good nutrition and an active lifestyle. Pulmonary rehabilitation as a management of cystic fibrosis continues throughout a person’s life, and is aimed at maximizing organ function, and therefore quality of life. At best, current treatments delay the decline in organ function. Because of the wide variation in disease symptoms, treatment typically occurs at specialist multidisciplinary centers, and is tailored to the individual. Targets for therapy are the lungs, gastrointestinal tract (including pancreatic enzyme supplements), the reproductive organs (including assisted reproductive technology (ART)) and psychological support.
The most consistent aspect of therapy in cystic fibrosis is limiting and treating the lung damage caused by thick mucus and infection, with the goal of maintaining quality of life. Intravenous, inhaled, and oral antibiotics are used to treat chronic and acute infections. Mechanical devices and inhalation medications are used to alter and clear the thickened mucus. These therapies, while effective, can be extremely time-consuming.
Many people with CF are on one or more antibiotics at all times, even when healthy, to prophylactically suppress infection. Antibiotics are absolutely necessary whenever pneumonia is suspected or there has been a noticeable decline in lung function, and are usually chosen based on the results of a sputum analysis and the person’s past response. This prolonged therapy often necessitates hospitalization and insertion of a more permanent IV such as a peripherally inserted central catheter (PICC line) or Port-a-Cath. Inhaled therapy with antibiotics such as tobramycin, colistin, and aztreonam is often given for months at a time to improve lung function by impeding the growth of colonized bacteria. Inhaled antibiotic therapy helps lung function by fighting infection, but also has significant drawbacks like development of antibiotic resistance, tinnitus and changes in the voice. Oral antibiotics such as ciprofloxacin or azithromycin are given to help prevent infection or to control ongoing infection. The aminoglycoside antibiotics (e.g. tobramycin) used can cause hearing loss, damage to the balance system in the inner ear or kidney problems with long-term use. To prevent these side-effects, the amount of antibiotics in the blood is routinely measured and adjusted accordingly.
Several mechanical techniques are used to dislodge sputum and encourage its expectoration. In the hospital setting, chest physiotherapy (CPT) is utilized; a respiratory therapist percusses an individual’s chest with his or her hands several times a day, to loosen up secretions. Devices that recreate this percussive therapy include the ThAIRapy Vest and the intrapulmonary percussive ventilator (IPV). Newer methods such as Biphasic Cuirass Ventilation, and associated clearance mode available in such devices, integrate a cough assistance phase, as well as a vibration phase for dislodging secretions. These are portable and adapted for home use.
Ivacaftor is an oral medication for the treatment of cystic fibrosis due to a number of specific mutations. It improves lung function by about 10%; however, as of 2014 is expensive.
Aerosolized medications that help loosen secretions include dornase alfa and hypertonic saline. Dornase is a recombinant human deoxyribonuclease, which breaks down DNA in the sputum, thus decreasing its viscosity.Denufosol is an investigational drug that opens an alternative chloride channel, helping to liquefy mucus. It is unclear if inhaled corticosteroids are useful.
As lung disease worsens, mechanical breathing support may become necessary. Individuals with CF may need to wear special masks at night that help push air into their lungs. These machines, known as bilevel positive airway pressure (BiPAP) ventilators, help prevent low blood oxygen levels during sleep. BiPAP may also be used during physical therapy to improve sputum clearance. During severe illness, a tube may be placed in the throat (a procedure known as a tracheostomy) to enable breathing supported by a ventilator.
For children, preliminary studies show massage therapy may help people and their families quality of life. It is unclear what effect pneumococcal vaccination has as it has not been studied as of 2014.
Lung transplantation often becomes necessary for individuals with cystic fibrosis as lung function and exercise tolerance decline. Although single lung transplantation is possible in other diseases, individuals with CF must have both lungs replaced because the remaining lung might contain bacteria that could infect the transplanted lung. A pancreatic or liver transplant may be performed at the same time in order to alleviate liver disease and/or diabetes. Lung transplantation is considered when lung function declines to the point where assistance from mechanical devices is required or someone’s survival is threatened.
Newborns with intestinal obstruction typically require surgery, whereas adults with distal intestinal obstruction syndrome typically do not. Treatment of pancreatic insufficiency by replacement of missing digestive enzymes allows the duodenum to properly absorb nutrients and vitamins that would otherwise be lost in the feces. However, the best dosage and form of pancreatic enzyme replacement is unclear, as are the risks and long-term effectiveness of this treatment.
So far, no large-scale research involving the incidence of atherosclerosis and coronary heart disease in adults with cystic fibrosis has been conducted. This is likely due to the fact that the vast majority of people with cystic fibrosis do not live long enough to develop clinically significant atherosclerosis or coronary heart disease.
Diabetes is the most common non-pulmonary complication of CF. It mixes features of type 1 and type 2 diabetes, and is recognized as a distinct entity, cystic fibrosis-related diabetes (CFRD). While oral anti-diabetic drugs are sometimes used, the only recommended treatment is the use of insulin injections or an insulin pump, and, unlike in type 1 and 2 diabetes, dietary restrictions are not recommended.
Development of osteoporosis can be prevented by increased intake of vitamin D and calcium, and can be treated by bisphosphonates, although adverse effects can be an issue. Poor growth may be avoided by insertion of a feeding tube for increasing calories through supplemental feeds or by administration of injected growth hormone.
Sinus infections are treated by prolonged courses of antibiotics. The development of nasal polyps or other chronic changes within the nasal passages may severely limit airflow through the nose, and over time reduce the person’s sense of smell. Sinus surgery is often used to alleviate nasal obstruction and to limit further infections. Nasal steroids such as fluticasone are used to decrease nasal inflammation.
Female infertility may be overcome by assisted reproduction technology, particularly embryo transfer techniques. Male infertility caused by absence of the vas deferens may be overcome with testicular sperm extraction (TESE), collecting sperm cells directly from the testicles. If the collected sample contains too few sperm cells to likely have a spontaneous fertilization, intracytoplasmic sperm injection can be performed.Third party reproduction is also a possibility for women with CF. It is unclear if taking antioxidants affects outcomes.
The prognosis for cystic fibrosis has improved due to earlier diagnosis through screening, better treatment and access to health care. In 1959, the median age of survival of children with cystic fibrosis in the United States was six months. In 2010, survival is estimated to be 37 years for women and 40 for men. In Canada, median survival increased from 24 years in 1982 to 47.7 in 2007.
Of those with cystic fibrosis who are more than 18 years old as of 2009, 92% had graduated from high school, 67% had at least some college education, 15% were disabled and 9% were unemployed, 56% were single and 39% were married or living with a partner.
Chronic illnesses can be very difficult to manage. Cystic fibrosis (CF) is a chronic illness that affects the “digestive and respiratory tracts resulting in generalized malnutrition and chronic respiratory infections”. The thick secretions clog the airways in the lungs, which often cause inflammation and severe lung infections. If it is compromised, it affects the quality of life of someone with CF and their ability to complete such tasks as everyday chores. It is important for CF patients to understand the detrimental relationship that chronic illnesses place on the quality of life. According to Schmitz and Goldbeck (2006), the fact that cystic fibrosis significantly increases emotional stress on both the individual and the family, “and the necessary time-consuming daily treatment routine may have further negative effects on quality of life (QOL)”. However, Havermans and colleagues (2006) have shown that young outpatients with CF who have participated in the CFQ-R (Cystic Fibrosis Questionnaire-Revised) “rated some QOL domains higher than did their parents”. Consequently, outpatients with CF have a more positive outlook for themselves. Furthermore, there are many ways to improve the QOL in CF patients. Exercise is promoted to increase lung function. Integrating an exercise regimen into the CF patients daily routine can significantly improve the quality of life. There is no definitive cure for cystic fibrosis. However, there are diverse medications used, such as mucolytics, bronchodilators, steroids, and antibiotics, that have the purpose of loosening mucus, expanding airways, decreasing inflammation, and fighting lung infections.
Cystic fibrosis is the most common life-limiting autosomal recessive disease among people of European heritage. In the United States, approximately 30,000 individuals have CF; most are diagnosed by six months of age. In Canada, there are approximately 4,000 people with CF. Approximately 1 in 25 people of European descent, and one in 30 of Caucasian Americans, is a carrier of a cystic fibrosis mutation. Although CF is less common in these groups, approximately 1 in 46 Hispanics, 1 in 65 Africans and 1 in 90 Asians carry at least one abnormal CFTR gene. Ireland has the world’s highest prevalence of cystic fibrosis, at 1:1353.
Although technically a rare disease, cystic fibrosis is ranked as one of the most widespread life-shortening genetic diseases. It is most common among nations in the Western world. An exception is Finland, where only one in 80 people carry a CF mutation. The World Health Organization states that “In the European Union, 1 in 20003000 newborns is found to be affected by CF”. In the United States, 1 in 3,500 children are born with CF. In 1997, about 1 in 3,300 caucasian children in the United States was born with cystic fibrosis. In contrast, only 1 in 15,000 African American children suffered from cystic fibrosis, and in Asian Americans the rate was even lower at 1 in 32,000.
Cystic fibrosis is diagnosed in males and females equally. For reasons that remain unclear, data has shown that males tend to have a longer life expectancy than females, however recent studies suggest this gender gap may no longer exist perhaps due to improvements in health care facilities, while a recent study from Ireland identified a link between the female hormone estrogen and worse outcomes in CF.
The distribution of CF alleles varies among populations. The frequency of F508 carriers has been estimated at 1:200 in northern Sweden, 1:143 in Lithuanians, and 1:38 in Denmark. No F508 carriers were found among 171 Finns and 151 Saami people. F508 does occur in Finland, but it is a minority allele there. Cystic fibrosis is known to occur in only 20 families (pedigrees) in Finland.
The F508 mutation is estimated to be up to 52,000 years old. Numerous hypotheses have been advanced as to why such a lethal mutation has persisted and spread in the human population. Other common autosomal recessive diseases such as sickle-cell anemia have been found to protect carriers from other diseases, a concept known as heterozygote advantage. Resistance to the following have all been proposed as possible sources of heterozygote advantage:
It is supposed that CF appeared about 3,000 BC because of migration of peoples, gene mutations, and new conditions in nourishment. Although the entire clinical spectrum of CF was not recognized until the 1930s, certain aspects of CF were identified much earlier. Indeed, literature from Germany and Switzerland in the 18th century warned “Wehe dem Kind, das beim Ku auf die Stirn salzig schmekt, er ist verhext und muss bald sterbe” or “Woe to the child who tastes salty from a kiss on the brow, for he is cursed and soon must die,” recognizing the association between the salt loss in CF and illness.
In the 19th century, Carl von Rokitansky described a case of fetal death with meconium peritonitis, a complication of meconium ileus associated with cystic fibrosis. Meconium ileus was first described in 1905 by Karl Landsteiner. In 1936, Guido Fanconi published a paper describing a connection between celiac disease, cystic fibrosis of the pancreas, and bronchiectasis.
In 1938 Dorothy Hansine Andersen published an article, “Cystic Fibrosis of the Pancreas and Its Relation to Celiac Disease: a Clinical and Pathological Study,” in the American Journal of Diseases of Children. She was the first to describe the characteristic cystic fibrosis of the pancreas and to correlate it with the lung and intestinal disease prominent in CF. She also first hypothesized that CF was a recessive disease and first used pancreatic enzyme replacement to treat affected children. In 1952 Paul di SantAgnese discovered abnormalities in sweat electrolytes; a sweat test was developed and improved over the next decade.
The first linkage between CF and another marker (Paroxonase) was found in 1985 by Hans Eiberg, indicating that only one locus exists for CF. In 1988 the first mutation for CF, F508 was discovered by Francis Collins, Lap-Chee Tsui and John R. Riordan on the seventh chromosome. Subsequent research has found over 1,000 different mutations that cause CF.
Because mutations in the CFTR gene are typically small, classical genetics techniques had been unable to accurately pinpoint the mutated gene. Using protein markers, gene-linkage studies were able to map the mutation to chromosome 7. Chromosome-walking and -jumping techniques were then used to identify and sequence the gene. In 1989 Lap-Chee Tsui led a team of researchers at the Hospital for Sick Children in Toronto that discovered the gene responsible for CF. Cystic fibrosis represents a classic example of how a human genetic disorder was elucidated strictly by the process of forward genetics.
Gene therapy has been explored as a potential cure for cystic fibrosis. Results from trials have shown limited success as of 2013. A small study published in 2015 found a small benefit.
The focus of much cystic fibrosis gene therapy research is aimed at trying to place a normal copy of the CFTR gene into affected cells. Transferring the normal CFTR gene into the affected epithelium cells would result in the production of functional CFTR in all target cells, without adverse reactions or an inflammation response. Studies have shown that to prevent the lung manifestations of cystic fibrosis, only 510% the normal amount of CFTR gene expression is needed. Multiple approaches have been tested for gene transfer, such as liposomes and viral vectors in animal models and clinical trials. However, both methods were found to be relatively inefficient treatment options. The main reason is that very few cells take up the vector and express the gene, so the treatment has little effect. Additionally, problems have been noted in cDNA recombination, such that the gene introduced by the treatment is rendered unusable. There has been a functional repair in culture of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients.
A number of small molecules that aim at compensating various mutations of the CFTR gene are under development. One approach is to develop drugs that get the ribosome to overcome the stop codon and synthesize a full-length CFTR protein. About 10% of CF result from a premature stop codon in the DNA, leading to early termination of protein synthesis and truncated proteins. These drugs target nonsense mutations such as G542X, which consists of the amino acid glycine in position 542 being replaced by a stop codon. Aminoglycoside antibiotics interfere with protein synthesis and error-correction. In some cases, they can cause the cell to overcome a premature stop codon by inserting a random amino acid, thereby allowing expression of a full-length protein. The aminoglycoside gentamicin has been used to treat lung cells from CF patients in the laboratory to induce the cells to grow full-length proteins. Another drug targeting nonsense mutations is ataluren, which is undergoing Phase III clinical trials as of October 2011[update].
It is unclear as of 2014 if ursodeoxycholic acid is useful for those with cystic fibrosis-related liver disease.
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Posted: March 9, 2016 at 6:43 pm
Acronym Definition DNA Deoxyribonucleic Acid DNA Department(al) Network Administrator DNA Does Not Apply DNA Genentech, Inc (stock symbol) DNA Data Not Available DNA Dermatology Nurses’ Association DNA Directia Nationala Anticoruptie (Romanian) DNA Defense Nuclear Agency DNA Do Not Adopt (used by animal shelters to refer to animal abusers) DNA Det Norske Arbeiderparti (Norwegian Labour Party) DNA Distributed Internet Applications Architecture (Microsoft) DNA Dynamic Network Administration (Ericsson) DNA De Nieuw Amsterdam (theater group) DNA Distributed Network Attack DNA Do Not Announce (hospital patient privacy) DnA Do Not Abbreviate (online gaming clan) DNA Deutscher Normenausschuss (German Committee of Standards) DNA National Dyslexia Association (humor) DNA Direct Network Access DNA Dernire Nouvelles d’Alsace (French newspaper) DNA DoNotAge (OSPF) DNA Datanetwork Associates (Software) DNA Dinebeiina Nahiilna be Agaditahe (Navajo legal counselors) DNA Did Not Answer DNA Did Not Attend DNA Do Not Ask DNA Definitely Not Attractive DNA Down Auxiliary DNA Distributed Internetwork Architecture (Microsoft) DNA Did Not Attack (Dana Carvey) DNA Do Not Approve DNA Do Not Answer (cell phone) DNA Do Not Admit DNA Drug ‘n Alcohol (band) DNA Diversified Naval Architects, Inc. (Ottawa, Ontario, Canada) DNA Dorchester Neighborhood Association (Waldorf, Maryland) DNA Digital Narrowband Analysis DNA Djibouti National Army DNA Distributed Networking Agent DNA Designated National Authority DNA Downriver Numismatic Association DNA Douglas Noel Adams (late British author of the Hitchhiker’s Guide to the Galaxy series) DNA Development Needs Analysis DNA Digital Network Architecture DNA Distributed interNet Applications DNA Do Not Abbreviate DNA Delaware Nurses Association DNA Detroit News Agency DNA Delivery Network Accelerator (BitTorrent) DNA Dynamic Network Analyzer (Lucent) DNA Dynamic Network Architecture DNA Denver Newspaper Agency (Denver, CO) DNA Digital Nonlinear Accelerator DNA Delayed Neutron Activation DNA Delta Nu Alpha DNA Doctors Net Access DNA Distributed Network Analyzer
DNA – What does DNA stand for? The Free Dictionary
Posted: January 18, 2016 at 6:42 am
Goldman Sachs is seeking to create its own cryptocurrency for post-trade settlement, according to a recently released patent filing.
The cryptocurrency, called SETLcoin, would be the architecture behind a new securities settlement system for the banking giant that would reduce delays in the transfer of assets; the time between when the transaction is initiated and finalized can take days.
SETLcoin guarantees instant execution and settlement, according to the filing, submitted October 2014.
“As implemented by the described technology, a trader no longer trades securities by meeting at an exchange with an indication of cash for security and then settles the transaction meanwhile bearing all of the associated credit risk in the interim,” it says.
Goldman isn’t the first to patent its own cryptocurrency. Citi and Bank of New York Mellon have also created them, CitiCoin and BK Coins respectively, for internal testing of blockchain technology.
Banks have become increasingly interested in blockchain technology this year. Goldman Sachs was one of the inaugural members of the R3CEV consortium, which now has 30 members and is expected to announce more soon. That firm is developing a similar distributed ledger-based settlement platform with which its members can experiment.
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Goldman Sachs Files Patent for Cryptocurrency System …
Posted: October 12, 2015 at 9:47 pm
Everything you do online can be traced back to your IP address. Even if youre accessing encrypted websites, networks can see the websites youre accessing and the websites themselves know your IP address. Use the Tor network to browse with anonymity.
Tor is an encrypted network that can route your traffic through relays, making the traffic appear to come from exit nodes. Unlike with proxies, the exit node itself doesnt know your IP address or where you are.
When you use a Tor client, your Internet traffic is routed through Tors network. The traffic travels through several randomly selected relays (run by volunteers), before exiting the Tor network and arriving at your destination. This prevents your Internet service provider and people monitoring your local network from viewing the websites you access. It also prevents the websites themselves from knowing your physical location or IP address theyll see the IP address and location of the exit node instead. Even the relays dont know who requested the traffic theyre passing along. All traffic within the Tor network is encrypted.
Image Credit: The Tor Project, Inc.
For example, lets say you access Google.com through Tor. Your Internet service provider and local network operator cant see that youre accessing Google.com they just see encrypted Tor traffic. The Tor relays pass your traffic along until it eventually reaches an exit node. The exit node talks to Google for you from Googles perspective, the exit node is accessing their website. (Of course, traffic can be monitored at the exit node if youre accessing an unencrypted website.) The exit node passes the traffic back along the relays, and the relays dont know where it ends up.
Tor offers anonymity and a path through Internet censorship and monitoring people living under repressive regimes with censored Internet connections can use Tor to access the wider Internet without fear of reprisal. Whistleblowers can use Tor to leak information without their traffic being monitored and logged.
Its not a great idea to use Tor for normal browsing, though. While the architecture does a good job of offering anonymity, browsing through Tor is significantly slower than browsing normally.
If you want more detailed information about how Tor works, check out the Tor Projects website.
The Tor Project recommends the Tor Browser Bundle as the safest, easiest way to use Tor. The Tor Browser Bundle is a customized, portable version of Firefox that comes preconfigured with the ideal settings and extensions for TOr. You can use Tor with other browsers and browser configurations, but this is likely to be unsafe. For example, Flash and other browser plug-ins can reveal your IP address the Tor Browser Bundle disables plug-ins for you and provides a safe environment, so you dont have to worry about your browser settings. It also includes the EFFs HTTPS Everywhere extension, which enables HTTPS on websites with HTTPS support. HTTPS provides encryption between the exit node and destination website.
Tor recommends that you not download document files, such as DOC and PDF files, and open them in external applications. The external application can connect to the Internet to download additional resources, exposing your IP address.
After downloading the Tor Browser Bundle, double-click the downloaded EXE file and extract it to your hard drive. The Tor Browser Bundle requires no installation, so you can extract it to a USB stick and run it from there.
Launch the Start Tor Browser.exe file in the Tor Browser folder.
The EXE file will launch Vidalia, which connects to the Tor network. After connecting, Vidalia will automatically open Tors customized Firefox browser.
Vidalia automatically launches the Tor Browser once it connects. When you close the browser, Vidalia automatically disconnects from Tor and closes.
Vidalia creates a local proxy on your system. The Tor Browser Bundle is configured to route all your traffic through it by default, as we can see here in the Tor Browsers connection settings window. You can configure other programs to access Tor through the proxy, but they may reveal your IP address in other ways.
Use the Tor Browser to browse the web just as you would with a normal browser. Its pre-configured with Startpage and DuckDuckGo, search engines that respect your privacy.
Remember not to provide any personal information say, by logging into an account associated with you while using the Tor browser, or youll lose the anonymity.
Chris Hoffman is a technology writer and all-around computer geek. He’s as at home using the Linux terminal as he is digging into the Windows registry. Connect with him on Google+.
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How to Browse Anonymously With Tor
Posted: July 21, 2015 at 12:14 pm
The Bible warned about global government with the account of Nimrod and the Tower of Babel, mankinds first global government. The Tower of Babel and Babylon were not the product of primitive cultures. It is very possible that the charismatic leader, Nimrod, who planned and organized the Tower of Babel, was a genetically enhanced super-being, who was the product of interspecies breeding between fallen angels and human women. As such, Nimrod would have been one the worlds first posthuman leaders and a Nephilim. This would have supported the thesis that some human civilizations before the Flood of Noah were highly technologically advanced and that the Tower of Babel was a stargate or portal, which allowed entities from different dimensions access to planet earth. These ancient Babylonian occult religions and their technology may have reappeared on the scene after the Flood. Francis Bacons ideas of a New Atlantis, which seems to be the secret philosophy upon which America was built, appears to be acting like a nano-technology guidance system that is reshaping Americas body electric. Just as electrical signals can cause eyes to be grown in a frogs stomach, so ideas can radically transform America as we know it. Transhumansim and global government, managed by a scientific elite, appear to be the plan for the United States of America. The NATO Summit in Chicago, which may look like something out of the movie Blade Runner, could be the dream of global governance in Daniels prophecy of a Revived Roman Empire. Instead of Roman legions, there could be Russian Special Forces troops protecting the empire.
Currently Russian soldiers are training near Fort Carson, Colorado as part of a bi-lateral exchange program between the U.S. and Russia in order to improve skills related to fighting terrorism. In an April 23, 2012 article entitled, Blade Runner: What It Means to Be Human in the Cybernetic State by John W. Whitehead, founder of the Rutherford Institute, Whitehead writes:
If Michelangelo were alive in Ridley Scotts future world, rather than portraying God on the ceiling of the Sistine Chapel, he would likely paint the human creators of the Tyrell Corporation, the worlds leading manufacturer of replicants which has just introduced the Nexus-6, a replicant with far greater strength and intelligence than human beings. These latest-model replicants represent an obvious potential danger to human society, and their introduction on Earthan offense calling for the death penaltyhas been strictly outlawed. When the replicants somehow make their way back to Earth, they are systematically retired (but not killed since they are inhuman) by special detectives or Blade Runners trained to track down and liquidate the infiltrators.
The signs of the times that Jesus Christ warned us about are happening right before our eyes. Jesus Christ predicted that there would be wars and rumors of wars, nation fighting nation, which comes from the word ethnos, which could imply conflict between ethnic and racial groups. A comprehensive translation of the words of Jesus would include earthquakes, volcanoes, tsunamis, tornadoes, floods, famines, plagues, lawlessness, anarchy and immorality, in what the Bible calls the Last Days. But Christ also warned of a coming charismatic politician who would unite the world into a one world government.
The signs are now occurring with increasing intensity and frequency. A super volcano under Yellowstone could trigger a global chain reaction connected to other super volcanoes. Earthquakes are shaking every continent on planet earth and earthquakes near the Canary Islands could send a five hundred foot high wall of water across the Pacific Ocean and submerge parts of the coastlines. The tsunamis produced by powerful earthquakes could submerge part of the West Coast of the United States and put parts of Europe under water.
A pervasive lawlessness and immorality is engulfing every nation. Human sex trafficking that includes little babies is becoming a multi-billion dollar industry. Israel was reformed as a nation in 1948, as the ancient Hebrew prophets predicted, and the Revived Roman Empire that the prophet Daniel outlined may still arise from the chaos of the European Union. Yet, one nation seems conspicuously absent from the ancient Biblical prophecies and that is the United States of America.
People ask me all the time, Paul where is America in Bible prophecy? They cannot understand how a nation as large and powerful as the United States would not be mentioned by name in the Bible. The answer to that question may simply be that America will no longer exist as a separate and distinct nation. It will either exist under a different name or America will become part of the Revived Roman Empire or coming one world government. A clue to Americas prophetic destiny may be in the architecture and symbolism of our nations capitol, Washington D.C. Washington D.C. and its architectural design are built on the ideas of ancient Rome. In fact, the Capitol building is designed after the Roman Pantheon, which was dedicated not to the Judeo-Christian God, but to the pagan gods.
Through the influence of a Rosicrucian-Masonic brotherhood, Washington D.C. seems to be constructed to be the capital of Francis Bacons vision of the New Atlantis, which is likely to become the center of the New World Order. On the back of the dollar bill we read the words Novus Ordos Seclorum, which means New Order of the Ages or New World Order. These words are found below an Egyptian pyramid with the all-seeing eye of Lucifer above it, inside of a smaller pyramid. This occult symbolism signifies that in the New World Order, a Luciferian elite will rule the masses; or to use the terminology of the Fabian socialists like H.G. Wells and Bertrand Russell, a scientific elite. This is the restructuring that is going on in America right now.
Nimrod ruled the first global government in Babylon and built the Tower of Babylon as an astrological worship portal that would place men to rule like gods in the heavens. Ancient Babylon, along with its mystery religions, is the spiritual fountainhead for the New World Order. The Freemason architects astrologically aligned the U.S. capital with the constellation Virgo (Isis). There is a picture of George Washington wearing a Masonic apron during a ceremony which dedicates the Washington capitol to these unseen pagan gods or entities that were allegedly present during the ceremony.
If you look carefully at Washingtons apron, you see the symbolism of a radiant eye or the all-seeing eye of Lucifer. The occult ceremony was an invitation for participation by the Egyptian god Horus or Osiris, which is the Greek god Apollo. The Roman gods Mercury, Venus, Mars, Jupiter, Saturn and Uranus are an important part of astrology, but they are also the names of many of the NASA space programs. Is this merely coincidence?
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America in Prophecy: A Transhuman Replicant Future | Paul …
Posted: March 26, 2015 at 10:48 am
(New York – March 25, 2015) Induced pluripotent stem cells (iPSCs) — adult cells reprogrammed back to an embryonic stem cell-like state–may better model the genetic contributions to each patient’s particular disease. In a process called cellular reprogramming, researchers at Icahn School of Medicine at Mount Sinai have taken mature blood cells from patients with myelodysplastic syndrome (MDS) and reprogrammed them back into iPSCs to study the genetic origins of this rare blood cancer. The results appear in an upcoming issue of Nature Biotechnology.
In MDS, genetic mutations in the bone marrow stem cell cause the number and quality of blood-forming cells to decline irreversibly, further impairing blood production. Patients with MDS can develop severe anemia and in some cases leukemia also known as AML. But which genetic mutations are the critical ones causing this disease?
In this study, researchers took cells from patients with blood cancer MDS and turned them into stem cells to study the deletions of human chromosome 7 often associated with this disease.
“With this approach, we were able to pinpoint a region on chromosome 7 that is critical and were able to identify candidate genes residing there that may cause this disease,” said lead researcher Eirini Papapetrou, MD, PhD, Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai.
Chromosomal deletions are difficult to study with existing tools because they contain a large number of genes, making it hard to pinpoint the critical ones causing cancer. Chromosome 7 deletion is a characteristic cellular abnormality in MDS and is well-recognized for decades as a marker of unfavorable prognosis. However, the role of this deletion in the development of the disease remained unclear going into this study.
Understanding the role of specific chromosomal deletions in cancers requires determining if a deletion has observable consequences as well as identifying which specific genetic elements are critically lost. Researchers used cellular reprogramming and genome engineering to dissect the loss of chromosome 7. The methods used in this study for engineering deletions can enable studies of the consequences of alterations in genes in human cells.
“Genetic engineering of human stem cells has not been used for disease-associated genomic deletions,” said Dr. Papapetrou. “This work sheds new light on how blood cancer develops and also provides a new approach that can be used to study chromosomal deletions associated with a variety of human cancers, neurological and developmental diseases.”
Reprogramming MDS cells could provide a powerful tool to dissect the architecture and evolution of this disease and to link the genetic make-up of MDS cells to characteristics and traits of these cells. Further dissecting the MDS stem cells at the molecular level could provide insights into the origins and development of MDS and other blood cancers. Moreover, this work could provide a platform to test and discover new treatments for these diseases.
This study was supported by grants from the National Institutes of Health, the American Society of Hematology, the Sidney Kimmel Foundation for Cancer Research, the Aplastic Anemia & MDS International Foundation, the Ellison Medical Foundation, the Damon Runyon Cancer Research Foundation, the University of Washington Royalty Research Fund, and a John H. Tietze Stem Cell Scientist Award.