FAP
Familial adenomatous polyposis (FAP) is a rare autosomal dominant genetic disorder caused by germline mutations in the APC tumor suppressor gene, leading to the progressive development of hundreds to thousands of adenomatous polyps primarily in the colon and rectum, with an untreated lifetime risk of colorectal cancer exceeding 99%.[1][2] Polyps typically emerge during adolescence or early adulthood, though symptoms such as rectal bleeding, abdominal pain, or changes in bowel habits may not manifest until later, often accompanied by extracolonic manifestations including duodenal polyps, osteomas, desmoid tumors, and congenital hypertrophy of the retinal pigment epithelium.[3][4] Diagnosis relies on genetic testing for APC variants, endoscopic identification of polyp burden, and family history, as the condition exhibits high penetrance but variable expressivity influenced by mutation site and modifying factors.[5] Management centers on prophylactic colectomy—often total or subtotal—to avert malignancy, alongside vigilant surveillance of the remaining gastrointestinal tract and targeted interventions for associated tumors, underscoring FAP's role as a paradigmatic hereditary cancer syndrome demanding early intervention to mitigate otherwise inevitable oncogenic progression.[6][7] Variants such as attenuated FAP (AFAP) involve fewer polyps and later onset due to mutations at gene extremities, while phenocopies from somatic mosaicism or biallelic MUTYH mutations complicate attribution but highlight the primacy of causal genetic defects over environmental influences in polypogenesis.[4][2]Medicine and biology
Familial adenomatous polyposis
Familial adenomatous polyposis (FAP) is a rare autosomal dominant genetic disorder characterized by the development of hundreds to thousands of precancerous adenomatous polyps in the colorectal epithelium, typically beginning in adolescence or early adulthood.[2] [4] Caused by germline mutations in the APC tumor suppressor gene on chromosome 5q21-22, these mutations disrupt β-catenin regulation, leading to uncontrolled cell proliferation and polyp formation.[4] [2] Without intervention, the cumulative risk of colorectal cancer approaches 100% by age 40 to 50, as polyps inevitably progress to adenocarcinoma through the adenoma-carcinoma sequence.[3] [4] The APC gene normally encodes a protein that maintains cytoskeletal structure and inhibits the Wnt signaling pathway, preventing excessive epithelial growth; pathogenic variants, often truncating mutations, abolish this function, resulting in polyposis.[2] Inheritance follows an autosomal dominant pattern, with a 50% transmission risk per offspring and near-complete penetrance; de novo mutations account for approximately 20-30% of cases without family history.[2] Variants in specific APC regions correlate with phenotype severity: proximal 5' mutations cause profuse polyposis (>5,000 polyps), while 3' or distal mutations may yield milder, attenuated forms with fewer polyps and later onset.[4] FAP prevalence is estimated at 1 in 8,000 to 1 in 10,000 individuals, with no significant sex predilection.[4] Early symptoms are often absent, but as polyps proliferate, patients may experience rectal bleeding, diarrhea, abdominal cramps, or iron-deficiency anemia; complications include bowel obstruction or intussusception from large polyps.[1] [3] Extracolonic manifestations occur in up to 90% of cases, including duodenal adenomas (increasing ampullary cancer risk), gastric fundic gland polyps, osteomas, dental anomalies, desmoid tumors, and congenital hypertrophy of the retinal pigment epithelium; these define variants like Gardner syndrome (with osteomas and soft tissue tumors).[6] [4] Diagnosis relies on clinical criteria—more than 100 colorectal adenomas—or genetic confirmation of pathogenic APC variants via sequencing and deletion/duplication analysis, which detects over 90% of mutations.[4] Screening initiates at age 10-12 in at-risk individuals via annual sigmoidoscopy or colonoscopy, escalating to full colectomy planning by late teens if polyposis is confirmed.[8] [4] Upper endoscopy screens for gastroduodenal polyposis starting at age 20-25.[4] Management emphasizes prophylactic proctocolectomy, typically restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) or total colectomy with ileorectal anastomosis (IRA) before age 20-25 to avert cancer, achieving over 95% colorectal cancer prevention when timed appropriately.[8] [4] Post-surgical surveillance includes annual pouchoscopy or rectoscopy for residual rectal polyps, treated endoscopically or with chemoprevention such as sulindac (an NSAID) or celecoxib, which reduce polyp burden by 30-50% via COX-2 inhibition and APC-independent pathways.[8] [4] Lifelong monitoring for extraintestinal cancers—thyroid, hepatoblastoma in children, desmoids (up to 20% post-surgery risk)—involves targeted imaging and genetic counseling for family members.[4] With early intervention, life expectancy approaches normal, though surgical morbidity includes fertility issues in women and pouchitis.[4]Fibroblast activation protein
Fibroblast activation protein (FAP), also known as FAP-alpha, is a type II transmembrane serine protease encoded by the FAP gene located on chromosome 2q23 in humans.[9] It belongs to the prolyl peptidase family, exhibiting both dipeptidyl peptidase activity—cleaving N-terminal dipeptides from substrates with proline in the penultimate position—and endopeptidase activity, including collagenase-like degradation of gelatin and type I collagen.[10] [11] Expression of FAP is minimal in most normal adult tissues but upregulated in pathological states such as wound healing, fibrosis, and epithelial cancers, where it localizes primarily to activated fibroblasts in the stroma.[11] [12] Structurally, FAP is a 97-kDa monomer that forms a functional 170-195-kDa homodimer on the cell surface, requiring dimerization for full catalytic activity.[13] The protein comprises a short 6-amino-acid cytoplasmic tail, a 20-amino-acid transmembrane helix, and a large 734-amino-acid extracellular domain containing the catalytic triad (Ser624, Asp702, His734) responsible for its serine protease function.[14] This domain also includes a β-propeller structure akin to dipeptidyl peptidase IV (DPP-IV), facilitating substrate binding and enabling FAP's dual-specificity hydrolysis of peptides after post-proline or alanine residues.[11] Kinetic studies reveal FAP's preference for Gly-Pro substrates in dipeptidyl activity and its unique endopeptidase role in remodeling extracellular matrix (ECM) components, distinct from related proteases like DPP-IV or prolyl oligopeptidase.[15] In physiological contexts, FAP contributes to tissue remodeling during embryogenesis, wound repair, and organ development by modulating fibroblast growth and epithelial-mesenchymal interactions.[9] It is transiently expressed in granulation tissue during healing, aiding ECM degradation and cell migration without persistent inflammation in healthy states.[16] However, aberrant FAP expression drives pathological fibrosis, as evidenced in liver models where FAP-positive fibroblasts accelerate collagen degradation and deposition, exacerbating injury progression.[17] In lung fibrosis, FAP paradoxically exhibits protective effects by enhancing collagen breakdown, suggesting context-dependent roles in fibrotic balance.[17] FAP's overexpression in over 90% of epithelial carcinomas, including colorectal, breast, and pancreatic cancers, marks it as a hallmark of cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME).[12] These FAP-positive CAFs promote tumorigenesis through ECM remodeling, facilitating tumor invasion and metastasis via gelatinase activity and invadopodia formation.[18] [19] FAP also fosters an immunosuppressive TME by degrading cytokines and chemokines, suppressing antitumor immunity, and enhancing CAF-tumor cell crosstalk that sustains proliferation and angiogenesis.[20] In colorectal cancer, FAP correlates with advanced stages and poor prognosis, with intrinsic expression in some tumor cells further amplifying metastatic potential.[21] Therapeutically, FAP serves as a target for radioligands in PET imaging for detecting stromal-rich tumors and for antibody-drug conjugates or CAR-T therapies aimed at depleting FAP-expressing cells, though challenges include off-tumor toxicity in fibrotic sites.[22] Clinical trials as of 2023 have explored FAP inhibitors like talabostat, revealing mixed efficacy due to compensatory protease pathways.[23]Psychology and behavioral science
Functional analytic psychotherapy
Functional Analytic Psychotherapy (FAP) is a behavioral psychotherapy approach grounded in radical behaviorism that emphasizes the therapeutic relationship as the primary vehicle for client change. It posits that improvements in a client's problematic interpersonal behaviors observed during sessions—termed clinically relevant behaviors (CRBs)—can generalize to everyday life when naturally reinforced by the therapist.[24] FAP integrates principles of operant conditioning, focusing on in vivo contingencies rather than historical analysis or cognitive restructuring alone.[25] Developed by psychologists Robert J. Kohlenberg and Mavis Tsai at the University of Washington, FAP emerged in the late 1980s as an extension of clinical behavior analysis, drawing from B.F. Skinner's work on verbal behavior and relational contingencies. Kohlenberg and Tsai formalized the approach in their 1991 book, Functional Analytic Psychotherapy: Creating Intense and Curative Therapeutic Relationships, which outlined its core framework. Early influences included Kohlenberg's dissatisfaction with traditional behavior therapy's neglect of the therapist's personal reactions and the dyadic interaction.[26] The method gained traction through subsequent publications and training programs, evolving to address transdiagnostic issues like interpersonal deficits in depression, anxiety, and personality disorders.[27] Central to FAP are five observational guidelines, or "rules," for therapists: (1) differentiate CRBs from irrelevant behaviors; (2) evoke CRBs through therapist authenticity; (3) provide natural social reinforcement for CRB1s (improvements) and distinguish from CRB2s (problems); (4) track the impact of therapist behaviors on client responses; and (5) promote client CRBs outside sessions via self-monitoring and homework. Techniques include therapist self-disclosure to model vulnerability, pausing to heighten awareness of in-session dynamics, and linking session events to real-world applications, all aimed at building a curative relational context.[28] Unlike manualized protocols, FAP prioritizes idiographic functional analyses tailored to individual client-therapist interactions, potentially complicating standardization.[29] Empirical support for FAP includes single-case designs and small trials demonstrating reductions in in-session problem behaviors and improvements in interpersonal functioning, such as decreased depression symptoms when combined with cognitive therapy. A 2018 comprehensive review of 80 studies found preliminary evidence of efficacy across qualitative, uncontrolled, and controlled designs, particularly for relational enhancements, though group-level RCTs remain scarce. A 2024 meta-analysis of randomized controlled trials and single-case studies confirmed moderate effects on targeted outcomes, but called for larger-scale replications to establish superiority over established therapies like cognitive-behavioral therapy.[30][31] Limitations include methodological challenges in isolating FAP-specific mechanisms due to its relational focus, which resists strict manualization and blinding in trials, leading to calls for more rigorous efficacy research. Critics note potential therapist burnout from intense emotional involvement and risks of blurred boundaries if reinforcement lacks ethical oversight, though proponents argue these are mitigated by behavioral precision. Cultural adaptations, such as culture-sensitive FAP, address mismatches in client-therapist values but require further validation. Overall, while FAP's emphasis on observable contingencies aligns with behavioral science, its evidence base lags behind more established interventions, warranting cautious clinical application pending expanded trials.[32][33][29]Industry and manufacturing
Fabrika automobila Priboj
Fabrika automobila Priboj (FAP), officially Korporacija Fabrika automobila Priboj, is a Serbian manufacturer of heavy-duty trucks, buses, and specialized military vehicles headquartered in Priboj.[34] Founded in 1952, the company commenced operations with the production of its first heavy-duty vehicles in 1953 under license from Swiss firm Saurer-Werke, including the FAP 4G and 6G models with 4-6 ton payloads, totaling 17 units that year.[35] By 1959, FAP had constructed new production lines, achieving output of 1,000 vehicles annually with a capacity of 3,600 units, followed by the introduction of FAP 18 and 18B models in 1962, boosting production to 2,000 vehicles per year.[35] In 1965, it launched the FAP 15B truck and developed Serbia's first domestically designed tranbus cab.[35] The company focused on rugged, off-road capable vehicles suited for Balkan terrain, exporting to regional markets during the Yugoslav era. A pivotal milestone occurred in 1970 when FAP secured a licensing agreement with Daimler-Benz (DB) to produce models such as the DB 1113/1213, elevating annual capacity to 5,000 units by integrating hybrid FAP-DB designs.[35] Production peaked in the late 1970s, reaching 7,000 trucks and buses annually by 1979 and 10,000 units overall capacity by 1975, with innovations like the FAP 2632 BDS 8x8 model in 1983 offering 20-ton payloads.[35] Infrastructure expanded, including a 45,000 m² pressed parts plant in 1984 and a wheel production line in 1987 capable of 70,000 units yearly.[35] Post-Yugoslav dissolution, FAP encountered financial challenges, operating at reduced capacity with only 24 trucks and 1 bus produced in 2013, valued at approximately €1.7 million.[35] Primarily socially owned (86.5% stake) until privatization efforts, the Serbian government acquired a 95% controlling interest in 2016 to avert liquidation amid insolvency.[36] Today, FAP emphasizes military and special-purpose vehicles, incorporating engines from Mercedes-Benz, Cummins, and MAN, while maintaining civilian truck lines for construction and logistics.[34] The firm holds ISO 9001 certification but has faced environmental compliance issues.[35]FAP 2026
The FAP 2026 is a six-wheel-drive (6x6) off-road tactical cargo truck developed and manufactured by the Serbian company Fabrika automobila Priboj (FAP) primarily for military applications. Introduced in the late 1970s under license from Mercedes-Benz, it draws from the NG-series design and features manual locking differentials on axles and inter-axles to enhance cross-country mobility.[37] The vehicle supports a payload of approximately 6 tonnes in its standard cargo configuration, with a gross vehicle weight around 21 tonnes.[37][38] Equipped with a Mercedes-Benz diesel engine—typically the OM 402 inline-six or a V8 variant—the FAP 2026 delivers between 260 and 280 horsepower, paired with a ZF manual transmission and spring suspension for rugged terrain operations. Dimensions vary slightly by variant but generally include a length of about 7.2–7.7 meters, width of 2.5 meters, and height up to 3.1 meters, enabling transport of troops (up to 20 passengers plus 2 crew) or cargo in off-road environments.[38][39] Variants include the BS/AV model for cargo and troop transport, as well as specialized versions like three-way tippers and chassis for custom military superstructures, often seen in ex-Yugoslav and Serbian armed forces inventories.[38] Production emphasized durability for wartime logistics, with the truck remaining in limited service or surplus sales into the 2020s.[40] Its design prioritizes mechanical simplicity and field repairability over advanced electronics, reflecting Cold War-era military requirements.[37]Politics and public policy
Family Assistance Plan
The Family Assistance Plan (FAP) was a comprehensive welfare reform initiative proposed by President Richard Nixon on August 8, 1969, aimed at overhauling the existing Aid to Families with Dependent Children (AFDC) program by establishing a uniform federal minimum income guarantee for low-income families with children.[41] The plan sought to address perceived failures in the fragmented state-administered welfare system, which Nixon described as fostering dependency and disincentivizing work, by introducing cash payments supplemented by work requirements and training mandates for able-bodied recipients.[41] It targeted families below the poverty line, excluding the elderly, blind, and disabled—those groups later covered by the separate Supplemental Security Income program—and emphasized self-sufficiency through a negative income tax-like structure that phased out benefits as earnings increased.[42] Key provisions included a basic annual federal payment of $500 for the first two family members plus $300 for each additional child, yielding $1,100 for a family of four before supplements, with an income disregard of $360 per family and a 50% reduction rate on earnings above that threshold to preserve work incentives.[42] Working-poor families earning between $1,500 and $2,500 annually would receive supplemental payments to reach an effective floor around $2,000 for a four-person household, alongside enhanced food stamps and Medicaid eligibility.[42] Adult recipients deemed capable of employment were required to register with the Manpower Training Service, accept suitable job training or employment, or face benefit denial, marking an early federal emphasis on labor participation over unconditional aid.[42] The plan projected federal costs of approximately $4 billion initially, rising to $10 billion by 1975, by consolidating and federalizing benefits while freezing state supplements in high-payment areas like New York.[43] Despite passing the House of Representatives in modified form on June 4, 1971, by a vote of 288-130, the FAP encountered staunch opposition in the Senate Finance Committee, chaired by Democrat Russell Long, who criticized its work requirements as insufficiently enforced and its structure as overly generous to non-workers.[43] Liberals, including some Democrats, argued it provided inadequate support compared to existing state programs and undermined broader anti-poverty efforts, while conservatives worried it expanded federal overreach akin to a guaranteed income that could erode personal responsibility.[44] States with generous welfare benefits feared revenue losses from federal preemption, and administrative complexities in integrating payments via the IRS further stalled progress.[45] The proposal effectively died in 1972 after Nixon vetoed a Senate-altered version, though its emphasis on work incentives influenced subsequent policies like the Earned Income Tax Credit established in 1975.[45]Broad Progressive Front
The Broad Progressive Front (Spanish: Frente Amplio Progresista, FAP) was a center-left electoral and legislative coalition in Argentina, formed in June 2011 to challenge the ruling Front for Victory led by President Cristina Fernández de Kirchner.[46] The alliance primarily united the Socialist Party (PS), which had gained prominence through Hermes Binner's election as the first Socialist governor of Santa Fe province in 2007, with other progressive groups seeking to consolidate opposition forces beyond traditional Peronism and Radical Civic Union (UCR) structures.[46] This coalition aimed to promote social democratic policies emphasizing transparency, anti-corruption measures, and economic reforms amid Argentina's polarized political landscape.[47] In the October 23, 2011, general elections, the FAP fielded Binner as its presidential candidate, who secured approximately 17% of the national vote, positioning the coalition as a notable opposition contender behind Kirchner's 54% landslide but ahead of other fragmented rivals.[48] Concurrently, the FAP achieved legislative gains, including seats in the Chamber of Deputies, bolstering its presence in Congress where it formed a bloc advocating for fiscal responsibility and human rights protections. In Santa Fe, the coalition's influence facilitated the PS's continued provincial control, with Antonio Bonfatti succeeding Binner as governor under FAP backing. These results highlighted the FAP's appeal in urban and provincial centers disillusioned with Kirchnerism's economic populism, though it fell short of broader national traction due to opposition vote-splitting.[46] Post-2011, the FAP evolved through alliances, notably fusing elements with UCR factions in 2013 to contest midterm elections under broader anti-Kirchner banners, yielding mixed provincial successes such as retaining Santa Fe's governorship.[48] By 2015, core FAP figures like Margarita Stolbizer of the GEN party rebranded as Progressives (Progresistas), contesting the presidency independently but garnering only 2.6% amid further fragmentation. The original FAP structure dissolved amid these shifts, reflecting challenges in sustaining unity against Peronist dominance and emerging libertarian alternatives, though its legacy persisted in social democratic advocacy within Argentina's multiparty system.[49]Military and defense
Military Family Advocacy Program
The Military Family Advocacy Program (FAP) is the U.S. Department of Defense's congressionally mandated initiative to address child abuse and neglect, domestic abuse, and problematic sexual behavior in military families through prevention, intervention, and support services.[50][51] Implemented across all military branches, FAP aims to enhance family resiliency, ensure victim safety, and mitigate the impact of maltreatment on military readiness by coordinating multidisciplinary responses involving clinical, legal, and community resources.[52][53] The program emphasizes early identification, education, and behavioral change to interrupt cycles of abuse, with mandatory reporting and case management protocols.[54] Core services include preventive education on healthy relationships and parenting, victim advocacy for safety planning and legal referrals, clinical treatment for perpetrators to address underlying issues, and specialized programs such as the New Parent Support Program for high-risk families with infants.[55][56] FAP also facilitates transitional compensation for dependents of service members separated due to abuse convictions or court-martials, providing financial and counseling support.[50] Operations involve collaboration with installation-level teams, including medical personnel, law enforcement, and civilian child protective services, to ensure comprehensive incident response and follow-up monitoring in 90-day increments.[57][58] FAP standards are codified in DoD Instruction 6400.01, issued May 1, 2019, which prescribes uniform policies for data collection, confidentiality, and interagency coordination while prohibiting retaliation against reporters.[59] Annual reporting to Congress via the FAP Central Registry tracks incidents, with fiscal year 2023 data showing 11,854 child abuse and neglect reports (rate of 14.3 per 1,000 children), yielding 5,812 incidents meeting intervention criteria and 4,223 unique child victims, predominantly from neglect (55%) and physical abuse (22%).[60] Domestic abuse reports numbered 15,124, resulting in 8,298 incidents and 6,458 unique victims, with physical abuse comprising 68% of cases; spouse abuse incidents declined from prior averages, while intimate partner abuse rose.[60]| Abuse Type | Reports | Incidents Meeting Criteria | Unique Victims |
|---|---|---|---|
| Child Abuse/Neglect | 11,854 | 5,812 | 4,223 |
| Domestic Abuse | 15,124 | 8,298 | 6,458 |