DDD
Domain-driven design (DDD) is a software engineering methodology that prioritizes modeling complex business domains through collaboration between developers and domain experts to create software architectures aligned with real-world processes and rules.[1] Introduced by Eric Evans, the approach was detailed in his 2003 book Domain-Driven Design: Tackling Complexity in the Heart of Software, which outlines strategic patterns like bounded contexts and ubiquitous language to encapsulate domain knowledge and mitigate the challenges of large-scale system development.[2] DDD emphasizes tactical elements such as entities, value objects, aggregates, and repositories to build robust, evolvable models that reflect causal domain dynamics rather than superficial implementations.[3] Widely adopted in enterprise applications, particularly for microservices and event-driven architectures, it has influenced modern practices by promoting domain-centric decomposition over technology-driven silos, though it requires significant upfront investment in domain exploration.[4]Medicine and biology
Degenerative disc disease
Degenerative disc disease refers to the progressive deterioration of intervertebral discs in the spine, characterized by loss of disc height, dehydration of the nucleus pulposus, and fissuring of the annulus fibrosus, which can lead to chronic low back pain or radiculopathy when symptomatic.[5] Although termed a "disease," it primarily represents age-related wear rather than an inflammatory or infectious process, with degeneration evident on imaging in up to 37% of asymptomatic individuals by age 20 and increasing thereafter.[6][7] The condition most commonly affects the lumbar spine but can involve cervical or thoracic regions, contributing to mechanical instability and secondary changes like facet joint arthritis or spondylosis.[8] Pathophysiologically, degeneration begins with reduced nutrient diffusion to the avascular disc due to diminished endplate permeability, leading to proteoglycan loss, decreased osmotic pressure, and nucleus dehydration, which shifts mechanical load to the annulus and promotes tears and herniation.[9] Genetic factors, such as variations in collagen genes, influence susceptibility, while biomechanical overload from repetitive stress accelerates matrix degradation via upregulated matrix metalloproteinases and inflammatory cytokines like TNF-α and IL-6.[10] Unlike acute disc herniation, degenerative changes are gradual, often asymptomatic until advanced stages provoke nociceptor sensitization in the outer annulus or endplates.[11] Epidemiologically, disc degeneration prevalence rises sharply with age, from approximately 20-30% in young adults to over 80% by age 60, though symptomatic disease affects only a subset, with lifetime low back pain prevalence linked to DDD estimated at 10-20% in working-age populations.[12] Both sexes are equally impacted, but men show earlier onset in some cohorts due to occupational loading, while overall U.S. diagnosis rates for degenerative spine conditions increased from 24.2% in 2005 to 30.1% in 2017, partly attributable to improved imaging access rather than true incidence rise.[13] Risk factors include smoking, which impairs disc nutrition via vasoconstriction; obesity, increasing axial load; and sedentary lifestyles, though paradoxically, moderate physical activity may mitigate progression through enhanced endplate vascularity.[5] Symptoms typically manifest as axial pain exacerbated by flexion, prolonged sitting, or lifting, with radiation to buttocks or legs if nerve compression occurs, but many cases remain painless despite radiographic severity, underscoring that imaging findings alone do not correlate strongly with symptoms.[8] Neurological deficits like weakness or numbness arise in fewer than 5% of cases without herniation.[14] Diagnosis relies on clinical history and imaging: plain radiographs reveal disc space narrowing and osteophytes, while MRI detects early dehydration (T2 hypointensity) and Modic endplate changes indicative of inflammation, though guidelines caution against routine imaging in acute nonspecific pain to avoid overdiagnosis.[5] Provocative discography, once common, is now limited due to risks of accelerating degeneration.[9] Management prioritizes conservative approaches: physical therapy focusing on core stabilization yields pain relief in 60-80% of patients within 6-12 weeks, alongside NSAIDs or acetaminophen for inflammation, with epidural steroids offering short-term radicular relief in select cases.[5] Surgery, such as anterior lumbar interbody fusion or total disc arthroplasty, is reserved for refractory cases with instability or myelopathy, showing 70-90% success in reducing pain but higher complication rates than nonoperative care; evidence from meta-analyses favors fusion over disc replacement for long-term outcomes in multilevel disease.[15] Emerging regenerative therapies, like stem cell injections, lack robust randomized trial support and are not standard.[16] Lifestyle modifications, including smoking cessation and weight control, address modifiable causes empirically linked to slower progression.[13]Dense deposit disease
Dense deposit disease (DDD), formerly known as membranoproliferative glomerulonephritis type II, is a rare glomerular disease defined by the presence of ribbon-like, electron-dense intramembranous deposits transforming the lamina densa of the glomerular basement membrane on electron microscopy.[17] It represents a subtype of C3 glomerulopathy, characterized by dominant C3 staining on immunofluorescence without significant immunoglobulin deposition, reflecting dysregulation of the alternative complement pathway.[18] [19] The condition primarily targets the kidneys, leading to progressive glomerular injury through excessive C3 activation and deposition.[20] DDD manifests due to inherited or acquired defects in complement regulation, most commonly autoantibodies like C3 nephritic factor (C3NeF), which stabilizes the C3 convertase (C3bBb) and perpetuates fluid-phase complement amplification.[21] Genetic mutations, such as in complement factor H (CFH) or other regulators, occur in up to 20% of cases, while monoclonal gammopathy-associated factors contribute in adults.[20] This results in low serum C3 levels (hypocomplementemia) in over 80% of patients, with normal C4, distinguishing it from classical pathway disorders.[22] The disease shows no sex predilection and predominantly affects children and young adults, with an estimated prevalence of 2-3 cases per million.[20] [23] Clinically, patients present with proteinuria (often nephrotic-range, >3.5 g/day), microscopic hematuria, hypertension, and edema, alongside declining glomerular filtration rate indicative of nephritic or nephrotic syndrome.[24] [25] Systemic features are uncommon, though acquired partial lipodystrophy or ocular drusen may coexist due to complement dysregulation.[20] Laboratory findings include persistent hypocomplementemia and elevated urinary protein-to-creatinine ratios.[26] Diagnosis requires renal biopsy, where light microscopy reveals mesangial hypercellularity, double contours of the glomerular basement membrane (tram-tracking), and MPGN pattern in 70-90% of cases.[27] Immunofluorescence demonstrates bright C3 along capillary walls and mesangium (intensity 2-3+), with minimal or absent immunoglobulins.[28] Electron microscopy confirms the pathognomonic dense osmiophilic deposits within the lamina densa, often sausage-shaped and replacing normal basement membrane structure.[29] Serologic tests for C3NeF and genetic screening for complement mutations aid in confirming pathogenesis.[21] Treatment is largely supportive, focusing on renin-angiotensin system blockade with ACE inhibitors or ARBs to reduce proteinuria and control hypertension, alongside dietary protein restriction and diuretics for edema.[30] Immunosuppression with corticosteroids or mycophenolate mofetil is used in rapidly progressive cases but lacks consistent efficacy due to the non-inflammatory, complement-driven nature.[29] Eculizumab, a C5 monoclonal antibody, shows promise in C3NeF-positive patients by halting terminal complement activation, with case reports of stabilized renal function, though randomized trials are absent.[29] Plasma exchange or rituximab targets autoantibodies in select cases.[31] Prognosis is poor, with 50% of patients progressing to end-stage renal disease (ESRD) within 10 years of diagnosis, particularly young females facing higher risk.[32] Median renal survival is approximately 10 years, influenced by initial proteinuria levels and complement genetics.[20] Post-transplant recurrence occurs in 40-60% of grafts, often leading to graft loss, though isolated deposit recurrence without full disease may not impair function.[21] Long-term monitoring for extrarenal complement effects, such as retinal drusen, is recommended.[28]Defined daily dose
The defined daily dose (DDD) is a technical unit developed by the World Health Organization (WHO) to standardize the measurement of drug consumption for pharmacoepidemiological research.[33] It represents the assumed average maintenance dose per day for a drug's main indication when used in adults, serving as a fixed benchmark rather than a recommended clinical dose.[33] DDD values are assigned by the WHO Collaborating Centre for Drug Statistics Methodology in Oslo, Norway, based on analysis of international prescribing patterns, dosage recommendations, and expert consensus, with the Anatomical Therapeutic Chemical (ATC) classification system providing the framework for categorization.[34] To calculate total drug consumption in DDDs, the amount of drug dispensed or sold (in mass or units) is divided by the assigned DDD value for that specific ATC code and strength.[35] For example, if 300 vials of cefazolin 1 g are dispensed and the DDD for cefazolin is 3 g, the consumption equates to 100 DDDs (300 × 1 g / 3 g).[35] This method enables cross-national comparisons; a common indicator is DDDs per 1,000 inhabitants per day, which estimates the proportion of a population likely receiving the drug daily, such as 20 DDDs/1,000/day implying about 2% usage prevalence under ideal conditions.[36] The DDD system facilitates drug utilization studies, policy analysis, and monitoring of antimicrobial resistance by quantifying trends without relying on variable prescribing data.[33] It has been integral to WHO initiatives since the 1970s, when the ATC/DDD methodology was formalized to address inconsistencies in earlier volume-based metrics.[37] However, DDDs are not suitable for individual patient dosing, pediatric applications, or veterinary use (where a separate DDDvet system applies), as they assume adult maintenance therapy for primary indications.[33][38] Limitations include discrepancies between DDDs and actual prescribed daily doses (PDDs), particularly for antihypertensives or antibiotics where real-world dosing varies by patient factors like age, weight, or comorbidities; studies report PDDs exceeding DDDs by 20-50% in some classes.[39] DDDs may represent rarely prescribed averages or remain unchanged for years despite evolving guidelines, potentially skewing comparisons for new drugs or formulations.[33][40] They also overlook treatment duration, prompting alternatives like days of therapy (DOT) for hospital settings, though DDD remains preferred for aggregate population-level analysis due to its international standardization.[41]Deciphering Developmental Disorders
The Deciphering Developmental Disorders (DDD) study is a large-scale genomic research initiative in the United Kingdom, launched in 2011 as a collaboration between the Wellcome Sanger Institute, National Health Service (NHS) clinical genetics centers, and other academic partners.[42][43] It targets children with severe, undiagnosed developmental disorders—conditions involving intellectual disability, congenital anomalies, epilepsy, or autism spectrum features—where prior conventional genetic testing yielded no diagnosis.[44][45] The project recruited trios consisting of affected children and their parents, totaling nearly 14,000 families across the UK and Ireland by 2023, enabling systematic analysis of de novo mutations and inherited variants.[46][47] Methodologically, DDD employs whole-exome sequencing (WES) as its core technology, supplemented by microarray analysis for copy number variants, to identify causative genetic alterations in up to 20,000 genes potentially linked to developmental phenotypes.[48][45] This approach prioritizes de novo variants—those arising anew in the child—over inherited ones, given their higher prevalence in sporadic developmental disorders, with rigorous filtering against population databases to distinguish pathogenic changes. Data interpretation integrates phenotypic details via the Human Phenotype Ontology and feeds into the DECIPHER database for global variant sharing and comparison among tens of thousands of cases.[46] Ethical protocols include phased result return: molecular findings are fed back to NHS clinicians for validation, with only actionable diagnoses communicated to families after multidisciplinary review.[49] Key findings from DDD have identified novel disease genes and refined diagnostic yields. In initial cohorts of over 1,000 trios, approximately 27% received a genetic diagnosis, rising to about 40% in later analyses through iterative reanalysis of data as reference knowledge expands.[45][50] The study uncovered over 100 new genes associated with developmental disorders, particularly those involved in chromatin regulation, neuronal migration, and synaptic function, with de novo mutations accounting for roughly one-third of diagnoses.[51] Post-diagnosis outcomes include targeted management, such as avoiding ineffective therapies or initiating surveillance for comorbidities, though many variants remain variants of uncertain significance due to incomplete penetrance or expressivity.[52] The DDD model's impact extends beyond individual diagnoses by informing NHS genomic medicine implementation, including the integration of WES into routine pediatric diagnostics since 2019.[47] It demonstrated that large-scale trio sequencing outperforms targeted panels for heterogeneous disorders, with cost-effectiveness improving as sequencing prices decline—estimated at under £1,000 per exome by 2023.[49] Challenges include the 60% non-diagnostic rate, attributable to complex polygenic influences or non-coding variants not captured by exome data, underscoring the need for complementary whole-genome sequencing in future iterations.[42] Ongoing data sharing via controlled-access repositories like the European Genome-phenome Archive supports international replication and causal validation.[48]Computing and technology
Domain-driven design
Domain-driven design (DDD) is a software development approach that prioritizes modeling the core domain and business logic of a system to address complexity effectively. It emphasizes collaboration between technical and domain experts to create a shared understanding of the problem space, ensuring the software evolves in alignment with real-world business processes. Introduced by Eric Evans in his 2003 book Domain-Driven Design: Tackling Complexity in the Heart of Software, DDD provides a framework of strategic and tactical patterns rather than rigid prescriptions, making it applicable to object-oriented and other paradigms for systems where domain intricacies dominate development challenges.[2][1] Central to DDD is the concept of ubiquitous language, a common lexicon derived from the domain model and used consistently by developers, domain experts, and stakeholders within a specific context to minimize misunderstandings and embed domain knowledge directly into code. This language facilitates iterative refinement of the model as insights emerge. DDD distinguishes between strategic design, which involves high-level partitioning of the domain into bounded contexts—explicit boundaries where a particular model and language apply, preventing the "big ball of mud" in large systems—and tactical design, which details building blocks like entities (objects with unique identity and lifecycle), value objects (immutable objects defined by attributes without identity), aggregates (clusters of related objects treated as a single unit for consistency), domain services (operations not belonging to entities or value objects), and repositories (abstractions for data access mimicking collection semantics). Domain events capture significant business occurrences to decouple components and enable reactive behaviors.[2][1] Evans' methodology draws from earlier influences in object-oriented analysis and data modeling from the 1980s and 1990s but formalized them into a cohesive set of practices for evolving, expressive models integrated with agile processes like Extreme Programming. A 2014 DDD Reference by Evans and others distills these into concise definitions, aiding practical application. While effective for complex, knowledge-intensive domains—such as finance or logistics—DDD's overhead in modeling and refactoring makes it less suitable for simple CRUD applications, where empirical evidence from practitioner reports shows it can introduce unnecessary abstraction if misapplied. Context mapping patterns, like shared kernels or anti-corruption layers, guide integration between bounded contexts, promoting modular, scalable architectures over monolithic designs.[2][1]DDD audio format
The DDD designation in audio formats refers to a specific classification within the SPARS (Society of Professional Audio Recording Services) code system, indicating that a recording underwent digital processes for tracking (recording), mixing/editing, and mastering prior to final digital media production, such as compact discs (CDs).[53] Introduced in the early 1980s amid the transition to digital audio technologies, the SPARS code used alphabetic markers—"A" for analog and "D" for digital—to denote the technological pathway of each production stage, providing consumers transparency on whether elements like multitrack tape recording, console mixing, or equalization were analog or digital.[54] In practice, DDD recordings emerged as digital multitrack recorders, such as 24-track DASH (Digital Audio Stationary Head) machines, became available around 1982–1983, allowing the entire chain—from microphone preamplification through final mastering—to avoid analog tape hiss, wow, and flutter while preserving dynamic range up to approximately 96 dB in 16-bit PCM formats used for CDs.[55] Early adopters included albums like Tracy Chapman's self-titled 1988 debut, labeled DDD despite some debate over partial analog elements in pre-digital era sessions, and certain classical or jazz releases prioritizing clarity over analog warmth.[56] The code appeared on CD booklets or jewel case spines from major labels, marketed as "pure digital" to appeal to early CD buyers seeking "perfect sound forever," though implementation varied as not all digital stages excluded analog components like microphones or effects.[57] Perceptions of DDD quality have been mixed among audio professionals and enthusiasts; while it theoretically minimized generational losses and enabled precise editing, early 1980s digital converters often produced a "harsh" or "sterile" timbre due to limitations in sampling rates (44.1 kHz) and anti-aliasing filters, contrasting with the perceived "airier" or "musical" results from analog-to-digital transfers (AAD or ADD).[58] Audiophile discussions note that superior DDD examples, such as those from Béla Fleck and the Flecktones, leverage modern digital tools for dynamics exceeding analog tape's 70–80 dB range, but pre-1990s DDD rock or pop could suffer from over-compression or digital artifacts absent in well-mastered AAD counterparts.[58][55] The SPARS system, voluntary and non-binding, fell into disuse by the late 1990s as hybrid processes blurred distinctions and digital became dominant, rendering labels obsolete for post-2000 releases.[54] Today, DDD-like all-digital workflows underpin high-resolution formats like DSD (Direct Stream Digital) or 24-bit/192 kHz PCM, but the original code's relevance persists in collector markets for evaluating 1980s–1990s CDs, where provenance affects resale value for formats prized for transparency over analog euphony.[59] No standardized successor exists, as production metadata is now often proprietary or omitted from packaging.Telecommunications
Direct distance dialing
Direct distance dialing (DDD), also known as direct dial long-distance, is a telephone service permitting subscribers to initiate calls beyond the local exchange area without operator assistance, by entering a carrier access code (typically "1" in North America), followed by the area code and seven-digit subscriber number.[60] This system replaced manual operator connections for toll calls, relying on automated electromechanical switches to route signals across interconnected networks.[61] The foundational elements for DDD emerged in the mid-20th century, with North American area codes established in 1947 to facilitate automated routing across 86 initial zones, enabling the mapping of dialed digits to geographic destinations.[62] The inaugural customer-dialed interstate DDD call took place on November 10, 1951, from Englewood, New Jersey, to Alameda, California, traversing approximately 3,000 miles via Bell System's crossbar switching technology and microwave relay links.[63][64] Initial rollout was limited to select exchanges equipped with compatible end offices, expanding gradually as infrastructure supported nationwide coverage by the late 1960s, with the "1" prefix mandated for all long-distance calls starting in 1963.[65] Technically, DDD operates through hierarchical numbering plans and signaling protocols where originating switches interpret dialed pulses or tones to select trunk lines, applying automatic message accounting (AMA) equipment to record call details for billing based on duration, distance, and time of day.[66] In the U.S., it applies to calls outside local access and transport areas (LATAs), using 10-digit numbering (1 + area code + local number) to traverse interexchange carriers, with early systems handling up to 140 area codes and evolving to support multifrequency signaling for faster setup.[60][67] By the 1970s, DDD integration with stored-program control switches reduced connection times from minutes to seconds, boosting network efficiency amid rising call volumes exceeding millions daily.[68] DDD's implementation spurred competition and regulatory changes, including the 1984 AT&T divestiture, which separated local from long-distance services while preserving the DDD framework under equal access rules requiring carriers to handle dialed calls equitably.[61] Today, DDD remains the default for domestic toll calling in North America, augmented by digital overlays like SS7 signaling for caller ID and number portability, though flat-rate plans have diminished per-minute charges that once defined its economic model.[60]Arts and entertainment
Dire, Dire Docks
Dire, Dire Docks is the ninth course in the 1996 Nintendo 64 game Super Mario 64, developed by Nintendo EAD and directed by Shigeru Miyamoto, and is retained in the 2004 Nintendo DS remake Super Mario 64 DS. The level depicts a submerged dockyard with a rusted shipwreck, coral formations, and Bowser's anchored submarine, accessed through a watery portal in the castle's basement after acquiring seven Power Stars from earlier courses.[69] Primarily underwater, it emphasizes swimming mechanics, with Mario navigating currents, avoiding predators like the giant eel Unagi and manta rays, and solving platforming puzzles amid visibility-limited depths.[70] The course is unique as the only mandatory level for progression; its first Power Star must be collected to relocate Bowser's submarine, draining the dock's water and exposing a drier, elevated ship interior for subsequent stars.[70] This environmental shift— from flooded aquatic hazards to surface-based jumping and enemy encounters—alters accessible paths and respawns certain collectibles, requiring players to revisit in the altered state. The soundtrack, composed by Koji Kondo, features an ambient, string-heavy underwater theme that incorporates percussion when on dry land, enhancing the level's serene yet eerie atmosphere.[71]Power Stars
The level contains seven Power Stars, with the first obtained in the initial flooded configuration and others unlocked post-drainage or available throughout:- Big Bob-omb on the Deck: Mario defeats a giant Bob-omb atop the ship's bow by ground-pounding its rear three times, avoiding explosive minions; this star triggers the drainage.[71]
- Through the Jet Stream: In the drained state, Mario swims through five red rings propelled by underwater currents near the dock's rear wall, starting from a green ! block platform.[72]
- The Manta Ray's Sting: Mario pursues a manta ray circling the central abyss, striking its eye when exposed to claim the star before it submerges.[70]
- Chests in the Current: Following colored coral arrows guides Mario to open five treasure chests in sequence amid a whirlpool, revealing the star upon completion.[73]
- Unagi's Slide: Mario punches the eel's tail to lure it from its cave, then wall-jumps inside to slide down a hidden passage for the star.[70]
- Red Coins: Eight red coins are scattered, including inside clams, atop penguins, and in the manta ray's path; collecting all yields the star.[74]
- 100 Coins Star: Accumulating 100 coins, primarily from yellow blocks, fish drops, and penguin races, unlocks the hidden star; the level totals 106 coins maximum.[75]