Calcium phosphate seeds may accumulate under repeated loads and impair skin shape recovery
In the dermis, repeated loads may leave calcium phosphate seeds that grow and restrict elastic fibres, making recovery depend on load order. No detectable mineral phase with confirmed assay sensitivity, together with a defect carried only by transferred cells, would refute the hypothesis.
Stage of verification
- Hypothesis published2026-09-25
- Indirect evidenceAssessed at 4 of 10
- Direct testAwaited
Map of the hypothesis
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Where in the body
Ageing mechanism
Kind of knowledge gap
A double ring marks the main placement where a group contains several values.
Target map
Every target of every published hypothesis, each with the actions a hypothesis can propose on it. The targets and the actions of this hypothesis are drawn solid.

Mechanics and load
Calcium phosphate mineral growth
The growth of calcium phosphate mineral in particles within the extracellular environment
Where this hypothesis actsIn the dermis during repeated mechanical loading with transient local mineral supersaturation
Hypotheses on this target 4
Inhibition3
Activation
Function preservation
Remodelling
Load normalisation
Direct measurement

What is proposed
Inhibition
Suppress crystal growth and prevent the formation of persistent mineral nuclei
With whatNot stated in the record
HowNot stated in the record
Possible result
Possible stabilization of SPV_3 under repeated loading and reduced dependence of mechanical defects on load order
From the recordПодавление роста кристаллов должно предупреждать накопление дефекта и ослаблять зависимость от порядка нагрузок при неизменных жизнеспособности и генетическом составе клеток.
All targets of the lab
Every target read from the published hypotheses, each kind around its pictogram. A larger mark means more hypotheses act on that target. Point at a mark and the actions proposed on it branch out of it.
Solid and named: the targets of this hypothesis
Explore in depth
The logic
The train of thought that ends in this hypothesis. Each stage is the reason the next exists. The master question narrows to a goal, the goal to an unknown nobody has closed, the unknown to the hypothesis proposed here. Every step below says what it rests on and what carries it.
Skin might lose its ability to recover its shape because earlier strains leave something behind, even while measurements at rest remain normal. The unexpected move is to propose that tiny mineral particles preserve that history by surviving between loads and growing during later episodes. This is a hypothesis generated by the pipeline, not a measured result.
- Repeated mechanical loads are proposed to leave tiny calcium phosphate seeds in the supporting skin layer.
- Temporary local supersaturation, a condition in which dissolved material favors formation of a solid, allows some seeds to grow.
- Seeds below a critical size tend to dissolve; seeds that cross that size can persist between loading episodes.
- The spacing and order of later loads determine whether early seeds disappear or remain available for further growth.
- Growing deposits restrict the movement of elastic fibers and concentrate force in nearby tissue.
- Those persistent deposits are predicted to impair shape recovery after a common final loading test.
- Preventing persistent seeds from forming is predicted to prevent the accumulating recovery defect.
Repeated wetting can leave a crust on a surface: the next wetting meets what the previous one left behind. Whether that residue disappears between episodes can matter as much as the total amount of water.
Where the picture breaks: Skin is living tissue, and the proposal requires particular chemical conditions and particle sizes. The picture does not establish that ordinary skin loading creates deposits or that deposits cause the predicted recovery defect.
- Master questionstep 01 of 04
The intended therapy would restore the functional condition of middle-aged human skin to that of young people.
Rests on: The supplied goal explicitly names the population and the desired comparison with young skin.
Stated in the chain - Goal pillarstep 02 of 04
Limiting damage that accumulates through repeated recovery is selected as a route toward better skin function.
Rests on: The goal supplies the desired improvement, but does not establish that repeated recovery produces the damage responsible for the difference between middle-aged and young skin.
AssumptionThe work assumes that cumulative damage from repeated recovery contributes to the functional deficit and that limiting it would advance the stated goal.
- Gap questionstep 03 of 04
Equal total exposure could leave different amounts of damage depending on the order of loads and their timing within the daily recovery cycle. The competing account is Miner's rule, an approach that adds damage contributions from individual loads without making their order decisive.
Rests on: The preceding stage identifies cumulative damage as the target, but does not supply the daily recovery cycle or establish that measurements at rest can remain normal while damage accumulates.
AssumptionThe comparison assumes that total exposure can be held equal while order and daily timing are varied, and that normal resting measurements need not rule out a recovery defect. The supplied material does not establish those conditions.
- Hypothesisstep 04 of 04
Repeated loads are proposed to leave tiny mineral seeds in the dermis, the supporting skin layer beneath the surface. Seeds that survive between episodes could grow and restrict elastic fibers, the tissue strands that help skin recoil, making later shape recovery depend on earlier loads.
Rests on: The preceding question supplies the distinction between total exposure and exposure history. The hypothesis supplies its proposed physical basis through classical nucleation theory, a model of how small clusters of material cross an energy barrier to become persistent particles. It makes daily timing relevant only if conditions for mineral formation measurably change with that timing.
Stated in the chain
What is carried, and what is not. The screened literature supports one limited connection in the proposed mechanism: mineral deposits can accompany damage to elastic fibers. A 2017 review in Orphanet Journal of Rare Diseases (S8) describes deposits disrupting and breaking those fibers in pseudoxanthoma elasticum, an inherited disorder affecting elastic tissues; it does not establish load-driven seed formation, persistence between loads, order-dependent recovery, or the complete sequence in ordinary skin aging.S8
Where the reasoning is carried by something unstated · 2
- Goal pillar. The work assumes that cumulative damage from repeated recovery contributes to the functional deficit and that limiting it would advance the stated goal.
- Gap question. The comparison assumes that total exposure can be held equal while order and daily timing are varied, and that normal resting measurements need not rule out a recovery defect. The supplied material does not establish those conditions.
How a result here could mislead · 3
- Deposits produced only in an artificially mineral-promoting solution could be mistaken for evidence that ordinary repeated loading produces the same process in aging skin. Conversely, failure to detect particles could be mistaken for their absence when the measurements cannot detect the proposed seeds. What closes it: As the proposal requires, mineral formation must first be detected under conditions representative of normal tissue, and the sensitivity of the detection methods must be established. Measurements must distinguish solid calcium phosphate from dissolved calcium; the supplied material gives no numerical detection threshold.
- Improvement after suppressing crystal growth could be credited to preventing mineral accumulation even if the intervention directly changes tissue mechanics or affects cells. Added mineral seeds could likewise produce an immediate mechanical effect rather than shorten the time needed for damage to accumulate. What closes it: The intervention comparison must measure mineral accumulation alongside shape recovery and establish that the seed dose does not itself change mechanics. The proposal also requires unchanged cell survival and genetic composition, meaning the hereditary material carried by the cells, but supplies neither a dose nor a specific crystal-growth inhibitor.
- A change caused by removing cells could be confused with evidence about where the accumulated defect resides. Loss of the defect would be ambiguous if cell removal also removed mineral or damaged the extracellular matrix, the material surrounding and supporting cells; persistence there would locate the defect without proving that mineral caused it. What closes it: The proposed cell-removal comparison requires verification that both mineral and the original supporting structure are preserved. Interpreting cell transfer also requires excluding carried-over mineral or old supporting material. Evidence that the defect remains outside cells must be considered together with the mineral measurements and growth-suppression results.
What would make this wrong. The proposal explicitly identifies a combined falsifying result: no solid mineral is found despite established detection sensitivity, and the recovery defect is retained only by cells transferred to fresh supporting material rather than by the original supporting material after cells are removed. That would oppose mineral as the carrier of loading history and favor a cell-carried explanation, although it would not by itself prove the rival's specific claim that surviving cells incorporate hereditary material from dead cells.
What it would change. If the predicted sequence held under normal tissue conditions, efforts to restore youthful skin function would need to account for persistent mineral left by previous loads and for the order of those loads, even when resting measurements appear normal. Preventing that persistence would become a candidate route for preserving shape recovery. This would still not establish that mineral accumulation explains the functional difference between middle-aged and young human skin, or that preventing new deposits reverses an existing deficit.
Sources read · 9
Vascular Smooth Muscle Cells and Arterial Stiffening: Relevance in Development, Aging, and Disease. · Physiological reviews · 2017
“This review summarizes current concepts of central pressure and tensile pulsatile circumferential stress as key mechanical determinants of arterial wall remodeling, cell-ECM interactions depending mainly on the architecture of cytoskeletal proteins and focal adhesion, the large/small arteries cross-talk that gives rise to target organ damage, and inflammatory pathways leading to calcification or atherosclerosis.”
Does not settle: Источник не устанавливает образование, сохранение или рост зародышей фосфата кальция в дерме при повторных нагрузках, их влияние на эластические волокна и восстановление формы кожи, а также роль порядка воздействий, pH или активности ионов.
Chameleon-Inspired Stress-Responsive Multicolored Ultratough Films. · ACS applied materials & interfaces · 2020
“Under the applied cyclic stress, the HNLs embedded in the polymer network can reversibly arrange into a highly ordered crystal arrays owing to the driving action of polymer chains.”
Does not settle: This artificial polyvinyl alcohol film does not establish calcium phosphate seed formation, persistence, dissolution between load cycles, or effects on elastic fibers and shape recovery in dermis.
Dual-Drug Nanomedicine Assembly with Synergistic Anti-Aneurysmal Effects via Inflammation Suppression and Extracellular Matrix Stabilization. · Small (Weinheim an der Bergstrasse, Germany) · 2024
“In SMCs, it inhibits apoptosis and calcification, thereby stabilizing the extracellular matrix and reducing the risk of AAA rupture.”
Does not settle: The abstract does not establish calcium phosphate seeding in dermis, repeated mechanical loading, persistence between cycles, effects on elastic-fiber mobility or skin shape recovery, sequence dependence, pH or ion-activity changes, or SPV_3.
Elastoderma. · Journal of the American Academy of Dermatology · 1995
“Histologic examination of specimens from the affected area revealed increased masses of intertwined thin, elastic fibers without calcification in the papillary and upper reticular dermis.”
Does not settle: This case report does not establish whether repeated mechanical loads create calcium phosphate seeds, whether such seeds persist or grow between episodes, or their effects on elastic-fiber mobility, stress concentration, skin shape recovery, SPV_3, pH, or ion activity.
Pseudoxanthoma elasticum - Genetics, pathophysiology, and clinical presentation. · Progress in retinal and eye research · 2024
“Later it was discovered that calcium deposits consisted of calcium phosphates, including hydroxyapatite (HAP) .”
Does not settle: Источник не устанавливает накопление минеральных зародышей в дерме при повторных нагрузках, их сохранение между циклами, влияние на восстановление формы кожи или показатель SPV_3.
Pseudoxanthoma elasticum. · Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie · 2008
“Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder of connective tissue, characterized by elastic fibers mineralization and fragmentation, and affects the skin, eyes, cardiovascular system, and gastrointestinal system.”
Does not settle: Абстракт не устанавливает роль повторных нагрузок, образование и сохранение субмикроскопических зародышей, пересыщение, pH, активность ионов, последовательность воздействий, механическое ограничение эластических волокон или изменение SPV_3.
Pseudoxanthoma elasticum. · Orphanet journal of rare diseases · 2017
“Electron microscopy of the skin reveals bulky, sometimes needle-like mineral deposits that disrupt and break elastic fibers (particularly in the mid-dermis) [ , , ] (Fig. ).”
Does not settle: Источник описывает генетическое заболевание PXE и не устанавливает роль повторных нагрузок, субмикроскопических зародышей, локального пересыщения, порядка воздействий, pH, активности ионов, растворения между циклами или показателя SPV_3.
SPARC Is Highly Expressed in Young Skin and Promotes Extracellular Matrix Integrity in Fibroblasts via the TGF-β Signaling Pathway. · International journal of molecular sciences · 2023
“These data strongly indicate the critical role of SPARC in maintaining ECM integrity within the dermis of the skin.”
Does not settle: Источник не устанавливает образование или сохранение фосфата кальция в дерме, влияние повторных механических нагрузок, пересыщения, pH, активности ионов, порядка воздействий или изменение SPV_3.
[Fluorine as a factor in premature aging]. · Annales Academiae Medicae Stetinensis · 2004
“These interactions reduce the content of collagen proteins, modify the structure and regularity of collagen fibers, and induce mineralization of collagen.”
Does not settle: The source does not establish calcium phosphate seed formation in dermis, persistence between repeated mechanical loads, effects on elastic-fiber mobility or skin shape recovery, or the roles of supersaturation, pH, ion activity, and exposure order.
The gap this hypothesis explains
Something is claimed here, but it rests on evidence too thin to carry weight.
With equal total stress, does skin damage depend on the amount alone or on timing within daily recovery?
Original wording · exactly as the pipeline generated it
Определяется ли накопительный ущерб суммой нагрузок по правилу Майнера или их последовательностью относительно суточной фазы восстановления, если суммарное воздействие одинаково и показатели кожи в покое нормальны?
What this question is asking
The question concerns whether repeated stresses leave skin less able to recover even when measurements taken at rest remain normal. It compares equal total exposure delivered in different orders, with different intervals, or at different points in the daily recovery cycle. One possibility is that damage simply adds up according to Miner’s rule; the other is that the timing of each exposure changes how much damage remains. The question assumes that daily regulation provides a relevant recovery cycle, while the broader requirement concerns recovery time and remaining changes staying within specified limits over ten years of repeated stress and shifted sleep. The supplied material does not specify the stresses, resting measurements, or acceptable limits.
- Accumulated damage or fatigue damage
- Harm that builds up across repeated exposures. Here, the unresolved issue is whether its amount depends only on exposure contributions or also on what happens between them.
- Miner’s rule
- A model that adds the fractions of fatigue life consumed by individual exposures. In this question it represents the possibility that damage accumulates independently of exposure order; its applicability to skin is not established by the supplied sources.
- Daily recovery cycle
- The proposed variation in recovery capacity across the day. A phase is a position within that cycle; the supplied sources do not establish such a cycle for the skin damage being asked about.
- Recovery reserve or recovery capacity
- The ability to return toward a previous functional state after stress. Normal measurements taken without an ongoing stress do not, by definition alone, measure this ability.
- Remaining change
- A difference from the starting condition that persists after an opportunity to recover. The input does not specify which difference would be measured or how much would be acceptable.
- Mechanical strain
- Deformation, such as stretching, caused by a force. It is the exposure used in several supplied sources, although the skin stresses in the question are not specified.
- Collagen and structural matrix
- Collagen is a structural protein within the material surrounding and supporting cells, called the matrix. S1 links unravelling of collagen to damage during repeated loading.
- Ligament and tendon
- Ligaments connect bones to other bones, while tendons connect muscles to bones. Their responses to repeated loading provide background here, without establishing skin responses.
- Fibroblast
- A cell that produces and modifies the supporting material around cells. The supplied fibroblast studies concern lung or ligament cells rather than human skin cells.
- Mechanical memory
- A persistent influence of earlier mechanical conditions on later cell behavior. S4 describes this influence as changeable and potentially reversible, so memory does not necessarily mean permanent damage.
- Cell culture and three-dimensional environment
- Cell culture means maintaining cells outside the organism under controlled conditions. A three-dimensional environment surrounds cells with supporting material, rather than placing them only on a flat surface.
- Cell proliferation
- An increase in cell number through division. It was one outcome measured in S6 and is distinct from accumulated tissue damage.
- Integrin expression
- Production of integrins, proteins that help cells attach to and respond to surrounding material. S6 reports no effect of the compared strain durations on this measurement.
- Fibronectin gene expression
- Activity of the gene encoding fibronectin, a protein in the material surrounding cells. This cellular measurement in S8 is distinct from a direct measurement of lasting skin damage.
- Signaling protein
- A protein that helps transmit instructions within a cell. S8 identifies different involvement of such proteins in brief and persistent conditions.
- Aortic regurgitation
- Backward leakage of blood through the heart’s aortic valve. S8 concerns mechanical conditions associated with this heart disorder, rather than skin recovery.
- Acute and chronic
- Terms distinguishing a brief or immediate condition from a persistent one. They do not themselves imply equal total exposure, which is essential to the question.
Daily regulation provides a recovery phase relevant to accumulated skin damage, and normal resting skin measurements may coexist with reduced recovery reserve.
The assumption is that skin’s ability to recover changes across the day, so an exposure may leave different lasting effects depending on when it occurs. It also allows skin to look normal in resting measurements while having less capacity to recover from another exposure. Together, these assumptions make exposure timing and recovery capacity relevant beyond the total amount of stress.
The supplied sources do not establish a daily recovery phase governing accumulated skin damage or a mismatch between normal resting skin measurements and reduced recovery capacity. S1 describes fatigue damage in ligament and tendon, and S4 reports mechanical memory in mouse lung cells. S6 and S8 describe other cellular responses to mechanical strain, without the required skin measurements or daily timing comparison. The supplied search results therefore do not establish the premise; this does not show that it is false.S1S4S6S8
The same question asked without the part nothing read establishes:
- At equal total exposure, do the order, spacing, or time of day of repeated stresses change lasting skin damage?
- When resting skin measurements are normal, does recovery after repeated stress depend on exposure timing at equal total exposure?
- Damage depends only on accumulated exposure Under this outcome, each exposure contributes an amount of damage that adds to the previous contributions independently of order or recovery timing. Equal accumulated exposure would therefore produce equal damage within the model, so rearranging exposures alone would not preserve recovery capacity.
- Timing changes accumulated damage Under this outcome, an exposure leaves different lasting effects depending on recovery between exposures or their position in the daily cycle. Equal total exposure would therefore be insufficient to predict damage, and schedules with the same total could have different consequences for skin function.
- Neither description adequately predicts damage Under this outcome, neither adding exposure contributions nor accounting for their timing adequately explains the remaining damage. Total exposure and schedule would then be insufficient grounds for concluding that recovery capacity remains preserved.
Repeated stress can damage structural material, as the ligament and tendon finding illustrates, but that finding does not establish how skin responds [S1]. If recovery between exposures changes the damage left behind, equal total exposure could produce different outcomes depending on timing; this is the conditional mechanism the question asks about. Normal measurements at rest would then be insufficient to establish preserved capacity to recover from another stress. Conversely, if damage depends only on the accumulated amount, changing timing without changing that amount would not reduce damage within that model. Confusing these alternatives would misstate what normal resting measurements and total exposure can establish about long-term skin function.
Усталость матрикса и клеточная память описаны на RL-1; суточная регуляция, RL-2, не устанавливает переносимость повторных циклов.
Время восстановления и остаточное отклонение сохраняются в заданных пределах при повторных нагрузках и смещении сна на протяжении десяти лет.
Неизвестно, меняют ли интервалы и суточная фаза накопление ущерба при одинаковой нагрузке, делая нормальные показатели покоя ложным свидетельством сохранённого резерва.
The mechanism it proposes
The engine's own statement of the hypothesis, in full.
Проверяемая гипотеза: повторные нагрузки оставляют в дерме субмикроскопические зародыши фосфата кальция. При совпадении повреждения с временным локальным пересыщением раствора часть зародышей достигает критического размера и сохраняется между циклами. Последующие нагрузки увеличивают минеральные включения, ограничивающие подвижность эластических волокон и повышающие концентрацию механического напряжения. Порядок воздействий определяет, успеют ли ранние зародыши раствориться до следующего эпизода. Биологическая фаза влияет на исход лишь при наличии измеримых фазовых изменений условий минерализации, например pH и активности ионов. Носителем истории служит твёрдая минеральная фаза. Предотвращение образования устойчивых зародышей должно стабилизировать SPV_3 при повторной нагрузке.
Where the idea comes from
The hypothesis borrows a result from another field. This is what it borrows, and from where.
Фазовые переходы первого рода, классическая теория зародышеобразования. Для сферического приближения ΔG(r) = 4πr²γ − (4π/3)r³Δg_v; r* = 2γ/Δg_v; ΔG* = 16πγ³/(3Δg_v²). Здесь r обозначает радиус зародыша фосфата кальция в дерме; ΔG(r) обозначает работу его образования; γ обозначает свободную энергию единицы поверхности раздела минерала и окружающей тканевой жидкости; Δg_v > 0 обозначает выигрыш свободной энергии на единицу объёма при переходе растворённых компонентов в твёрдую фазу; r* обозначает критический радиус; ΔG* обозначает энергетический барьер; π является математической константой. Для образования на тканевой подложке используют ΔG*_het = fΔG*, где f является безразмерным коэффициентом влияния геометрии и смачивания подложки. Формулы задают проверяемую модель; сферическая форма и постоянство γ являются приближениями. [Учебный вывод классической модели, NPTEL](https://archive.nptel.ac.in/content/storage2/courses/113101003/parts/partIII/module2/1.9.html).
Testing and possible results
The prediction that would tell it apart
A hypothesis that predicts what its rivals predict is not worth running an experiment over. This is the observation on which this one differs.
При одинаковом наборе нагрузок неблагоприятная последовательность должна сначала увеличивать число устойчивых минеральных частиц, затем ухудшать восстановление формы после общей заключительной пробы. Добавление малой, самостоятельно не меняющей механику дозы минеральных затравок должно сокращать период до появления дефекта. Подавление роста кристаллов должно предупреждать накопление дефекта и ослаблять зависимость от порядка нагрузок при неизменных жизнеспособности и генетическом составе клеток. После удаления клеток различие в механике должно сохраняться в матриксе; очищенные клетки на свежем матриксе не должны переносить его. Отсутствие минеральной фазы при подтверждённой чувствительности методов и сохранение дефекта только в перенесённых клетках опровергнут эту гипотезу в пользу IH_Q_L3_M_G4_3_01.
Would tell it apart from at least one rival. The prediction specifies observable changes, contrasting outcomes after cell removal and transfer, and an explicit rejection condition. No rival prediction was supplied. Only a bench experiment would settle it.
What testing it would take
The engine's own read on whether this is testable with methods that already exist.
Комбинация рамановской спектроскопии, электронной микроскопии с элементным анализом и дифракции позволяет отличить твёрдую минеральную фазу от растворённого кальция. Циклические механические испытания проводят на парных образцах одного донора. Минерализацию сначала необходимо обнаружить при физиологической среде: результат только в искусственно пересыщенной среде не подтвердит механизм обычного старения кожи. Удаление клеток требует контроля сохранности минерала и исходной структуры матрикса.
Other explanations
Every other hypothesis the engine wrote for the same gap, and the observation that would separate the two.
При одинаковом наборе нагрузок неблагоприятная последовательность должна сначала увеличивать число устойчивых минеральных частиц, затем ухудшать восстановление формы после общей заключительной пробы. Добавление малой, самостоятельно не меняющей механику дозы минеральных затравок должно сокращать период до появления дефекта. Подавление роста кристаллов должно предупреждать накопление дефекта и ослаблять зависимость от порядка нагрузок при неизменных жизнеспособности и генетическом составе клеток. После удаления клеток различие в механике должно сохраняться в матриксе; очищенные клетки на свежем матриксе не должны переносить его. Отсутствие минеральной фазы при подтверждённой чувствительности методов и сохранение дефекта только в перенесённых клетках опровергнут эту гипотезу в пользу Dead-cell nuclear genetic material may enter skin-cell chromosomes and slow recovery.
- What would separate them
Dead-cell nuclear genetic material may enter skin-cell chromosomes and slow recovery predicts: В реконструированной коже с различимыми генетическими метками донорских клеток и фибробластов сравнивают перестановки одинакового набора нагрузок при двух биологических фазах. Число воздействий каждой амплитуды, продолжительность опыта и время после последнего воздействия одинаковы. Неблагоприятная последовательность должна повышать число подтверждённых соединений донорской ДНК с хромосомной ДНК реципиента и удлинять восстановление после общей заключительной пробы. Эффект должен сохраняться после переноса очищенных фибробластов на свежий неминерализованный матрикс. Разрушение ДНК донорского материала до его предъявления, при сохранении сопоставимого количества клеточных остатков, должно устранять различие между последовательностями. Для функционально значимых вставок необходимы воспроизведение дефекта и его устранение в изогенных клетках. Отсутствие устойчивых вставок при достаточной чувствительности анализа вместе с переносом дефекта только бесклеточным матриксом опровергнет эту гипотезу в пользу this hypothesis.
What stands behind it
Which of the figures above have a study behind them, which are the engine's own, and what it would take to refute the hypothesis. This audit never judges the idea.
This hypothesis states no figure and cites no study, so there is nothing here to trace.
What it would take to refute it. Nothing already retrieved carries the prediction’s terms and it names no measurement this layer can route to a public dataset, so the bench is the residual — not a finding against it.
0 citation handles extracted; 1 Europe PMC search run; 0 records examined; 0 sources stored for enrichment, 0 with full text. A citation that did not resolve is a bibliographic failure, not proof that no such paper exists, and no hypothesis is blocked by this audit.