Formal and informal human milk donation in New Zealand: a mixed-method national survey.

BACKGROUND: Mother's milk provides optimal nutrition for infants. Donor human milk (DHM) is recommended for low birthweight infants when mother's milk is unavailable. Little is known about human milk (HM) donation practices in New Zealand (NZ), where few HM banks are available. This study aimed to investigate parents' and health professionals' (HP) experiences with formal and informal HM donation in NZ. METHODS: Two electronic surveys were disseminated in 2022 to parents and HPs involved with HM donation in NZ. The surveys covered respondents' views and experiences with HM donation. HPs were also asked about HM donation practices in their workplace. Chi-squared and Fisher-Freeman-Halton exact tests were used for quantitative analysis and qualitative data were thematically analysed using inductive approach. RESULTS: A total of 232 HP and 496 parents completed the surveys. Most parents either donated (52%) or sought DHM (26%) for their infant and most donations were informal, arranged between individuals (52%) or through hospital staff (22%). HP reported DHM was used in 86% of facilities, with only 20% of donations facilitated by HM banks. Almost half (48%) of HP stated they would like to use DHM in their workplace but access was limited. The most common screening processes undertaken by parents and HP before informal HM donation were lifestyle including smoking status, medication, drug and alcohol intake (44% and 36%, respectively) and serological screening such as CMV, HIV, Hepatitis C or B (30% and 39%, respectively). Pasteurisation of DHM obtained informally was not common. Most donors were satisfied with their HM donation experiences (informal and/or formal, 91%) and most respondents supported use of DHM in hospitals and community. Participants reported HM donation could be improved (e.g., better access) and identified potential benefits (e.g., species-specific nutrition) and risks (e.g., pathogens) for the infant. Potential benefits for the donor were also identified (e.g., altruism), but respondents acknowledged potential negative impacts (e.g., cost). CONCLUSION: Informal HM donation in NZ is common. Most parents and HP support the use of DHM; however, improvements to current practices are needed to ensure safer and more equitable access to DHM.

Protocol for in vitro transcribing mRNAs with defined poly(A)-tail lengths and visualizing sequential PABP binding.

Quantifying the number of proteins that interact with mRNAs, in particular with poly(A) tails of mRNAs, is crucial for understanding gene regulation. Biochemical assays offer significant advantages for this purpose. Here, we present a protocol for synthesizing mRNAs with accurate, length-specific poly(A) tails through a PCR-based approach. We also describe steps for an in vitro (i.e., cell-free) approach for visualizing the sequential binding of Cytoplasmic Poly(A)-Binding Proteins (PABPCs) to these poly(A) tails. We detail quality control steps throughout the procedure. For complete details on the use and execution of this protocol, please refer to Grandi et al.1.

Severe familial dilated cardiomyopathy in a young adult due to a rare LMNA mutation: a case report.

Background: Familial dilated cardiomyopathy prognosis and disease progression vary greatly depending upon the type of genetic mutation. Family history and genetic testing are paramount in developing the best treatment plan for a patient. However, with rare or novel mutations, the significance may be unknown. Regarding this, the following case report highlights the importance of vigilance and suspicion when treating a patient with a variant of unknown significance. Additionally, it shows the importance of thoroughly investigating the family history of cardiovascular disease. Case summary: A 25-year-old Caucasian male was found to have a right bundle branch block and dilated cardiomyopathy upon presentation to the emergency department. Later testing showed that the dilated cardiomyopathy was due to an incredibly rare lamin A/C (LMNA) gene mutation, R349L. Despite treatment with a maximum-tolerable medication regimen and an automatic implantable cardioverter-defibrillator, the patient continued to decline and required a heart transplant. Discussion: This case provides more information on the severity of this specific LMNA mutation that has only been documented once before. Of note, the time from the initial emergency department visit to the heart transplant was approximately 2 years. Given the patient's young age and rapid disease progression, in addition to a strong family history of sudden cardiac death, the significance of this mutation should not be understated. The additional knowledge gained from this case report can be used to aid in timely interventions and prognosis evaluation.

Hydroxychloroquine and a low antiresorptive activity bisphosphonate conjugate prevent and reverse ovariectomy-induced bone loss in mice through dual antiresorptive and anabolic effects.

Osteoporosis remains incurable. The most widely used antiresorptive agents, bisphosphonates (BPs), also inhibit bone formation, while the anabolic agent, teriparatide, does not inhibit bone resorption, and thus they have limited efficacy in preventing osteoporotic fractures and cause some side effects. Thus, there is an unmet need to develop dual antiresorptive and anabolic agents to prevent and treat osteoporosis. Hydroxychloroquine (HCQ), which is used to treat rheumatoid arthritis, prevents the lysosomal degradation of TNF receptor-associated factor 3 (TRAF3), an NF-κB adaptor protein that limits bone resorption and maintains bone formation. We attempted to covalently link HCQ to a hydroxyalklyl BP (HABP) with anticipated low antiresorptive activity, to target delivery of HCQ to bone to test if this targeting increases its efficacy to prevent TRAF3 degradation in the bone microenvironment and thus reduce bone resorption and increase bone formation, while reducing its systemic side effects. Unexpectedly, HABP-HCQ was found to exist as a salt in aqueous solution, composed of a protonated HCQ cation and a deprotonated HABP anion. Nevertheless, it inhibited osteoclastogenesis, stimulated osteoblast differentiation, and increased TRAF3 protein levels in vitro. HABP-HCQ significantly inhibited both osteoclast formation and bone marrow fibrosis in mice given multiple daily PTH injections. In contrast, HCQ inhibited marrow fibrosis, but not osteoclast formation, while the HABP alone inhibited osteoclast formation, but not fibrosis, in the mice. HABP-HCQ, but not HCQ, prevented trabecular bone loss following ovariectomy in mice and, importantly, increased bone volume in ovariectomized mice with established bone loss because HABP-HCQ increased bone formation and decreased bone resorption parameters simultaneously. In contrast, HCQ increased bone formation, but did not decrease bone resorption parameters, while HABP also restored the bone lost in ovariectomized mice, but it inhibited parameters of both bone resorption and formation. Our findings suggest that the combination of HABP and HCQ could have dual antiresorptive and anabolic effects to prevent and treat osteoporosis.

Optimal routing and end-to-end entanglement distribution in quantum networks.

Quantum networks are designed to transmit quantum bits (qubits) among quantum devices to enable new network resources for the applications. Entanglement distribution and entanglement swapping are fundamental procedures that are required in several network operations. However, they are probabilistic operations, which can lead to severe network performance degradation. This article investigates the engineering problem of resource allocation in quantum networks, considering factors like entanglement distribution probability, quantum memory characteristics, and fidelity. We model this as an optimization model to obtain an optimal solution. In particular, we formulate an integer linear programming (ILP) and develop a heuristic algorithm, aiming to minimize the number of required entangled qubit pairs (Bell pairs or EPR pairs) in any adjacent pair in the quantum network. Extensive simulations are performed to compare the performance of proposed ILP and heuristic. In all the cases, the heuristic produces a comparable solution to the optimal one. Simulation results ensure that the value of maximum utilized Bell pairs in a quantum network highly depends on the value of the probability of entangled pairs established, considering the time in the quantum memory besides the number of incoming requests.

Deep subwavelength topological edge state in a hyperbolic medium.

Topological photonics offers the opportunity to control light propagation in a way that is robust from fabrication disorders and imperfections. However, experimental demonstrations have remained on the order of the vacuum wavelength. Theoretical proposals have shown topological edge states that can propagate robustly while embracing deep subwavelength confinement that defies diffraction limits. Here we show the experimental proof of these deep subwavelength topological edge states by implementing periodic modulation of hyperbolic phonon polaritons within a van der Waals heterostructure composed of isotopically pure hexagonal boron nitride flakes on patterned gold films. The topological edge state is confined in a subdiffraction volume of 0.021 µm3, which is four orders of magnitude smaller than the free-space excitation wavelength volume used to probe the system, while maintaining the resonance quality factor above 100. This finding can be directly extended to and hybridized with other van der Waals materials to broadened operational frequency ranges, streamline integration of diverse polaritonic materials, and compatibility with electronic and excitonic systems.

Cell topology during coarsening of simulated three-dimensional dry liquid foams.

Cell topology provides a deep insight into the structure of dry liquid foams. This paper analyses the cell topology of simulated 3-dimensional monodisperse dry liquid foams through the process of coarsening, where gas slowly diffuses through the cell interfaces. The coarsened foams are polydisperse, yet show a difference in cell types to annealed, low energy foams of comparable polydispersity. These two types of foams are analysed using average face degree of the cells and a measure of combinatorial roundedness, a new concept from combinatorial topology. We see that the spectrum of cell types changes drastically through the evolution of the foam via coarsening, from cells with a face degree between 12 and 14, with many 4-, 5-, and 6-side faces, to a combination of very large cells with many faces alongside a high frequency of tetrahedra and other cells with low face degree. These results demonstrate the insight that topological methods can give into foams and other complex structures.

Patiromer to Reduce Albuminuria Through Increased Renin Angiotensin Aldosterone System Inhibition in Patients With CKD-A Feasibility Trial.

Introduction: We tested the feasibility of adding a potassium binder to enable increased renin angiotensin aldosterone system inhibition (RAASi) and reduce albuminuria in patients with chronic kidney disease (CKD). In a controlled trial design, a potassium binder was introduced exclusively in patients developing hyperkalemia after intensified RAASi, thereby mirroring clinical decision-making. Methods: We planned to include 140 patients aged 18 to 80 years with estimated glomerular filtration rate (eGFR) 25 to 60 ml/min per 1.73 m2, albuminuria, and a history of hyperkalemia to an open-label, randomized trial comparing treatment with or without patiromer alongside maximally tolerated RAASi. Patients were randomized only if developing a documented P-potassium >5.5 mmol/l during run-in with intensified RAASi (losartan/spironolactone). The primary end point was change in urine albumin-creatinine ratio (UACR). Results: Screening among 800,000 individuals with available laboratory results yielded just 317 candidates meeting major selection criteria during 18⅔ months, with 75 ultimately included. Among them, only 23 developed P-potassium >5.5 mmol/l, qualifying for randomization. Consequently, only 20 participants completed the study, falling short of the planned 98, precluding a significant effect on the primary outcome. Inclusion and randomization challenges stemmed from a limited pool of eligible patients for intensified RAASi at risk of hyperkalemia, along with a lower than expected incidence of hyperkalemia during run-in. Conclusion: Despite extensive screening efforts, few eligible patients were identified, and fewer developed hyperkalemia during run-in. Hence, a trial design limited to CKD patients at high hyperkalemia risk and including a run-in phase appears unlikely to provide evidence for a potential renal benefit from additional use of potassium binders.

Incidence and prevalence of primary biliary cholangitis in the Netherlands - A nationwide cohort study.

Background & Aims: Although primary biliary cholangitis (PBC) is considered a rare disorder, accurate determination of its incidence and prevalence remains challenging due to limited comprehensive population-based registries. We aimed to assess the incidence and prevalence of PBC in the Netherlands over time through the nationwide Dutch PBC Cohort Study (DPCS). Methods: DPCS retrospectively included every identifiable patient with PBC in the Netherlands from 1990 onwards in all 71 Dutch hospitals. Incidence and prevalence were assessed between 2008-2018 by Poisson regression between sex and age groups over time. Results: On the 1st of January 2008, there were 1,458 patients with PBC in the Netherlands. Between 2008-2018, 2,187 individuals were newly diagnosed, 46 were transplanted and 468 died. The yearly incidence of PBC in 2008 was 1.38, increasing to 1.74 per 100,000 persons in 2018. When compared to those aged <45 years, females aged 45-64 years (adjusted incidence rate ratio 4.21, 95% CI 3.76-4.71, p <0.001) and males ≥65 years (adjusted incidence rate ratio 14.41, 95% CI 9.62-21.60, p <0.001) were at the highest risk of being diagnosed with PBC. The male-to-female ratio of patients newly diagnosed with PBC during the study period was 1:14 in those <45 years, 1:10 in patients aged 45-64 years, and 1:4 in those ≥65 years. Point prevalence increased from 11.9 in 2008 to 21.5 per 100,000 persons in 2018. Average annual percent change in this time period was 5.94% (95% CI 5.77-6.15, p <0.05), and was the highest among the population aged ≥65 years (5.69%, 95% CI 5.32-6.36, p <0.001). Conclusions: In this nationwide cohort study, we observed an increase in both the incidence and prevalence of PBC in the Netherlands over the past decade, with marked age and sex differences. Impact and implications: This nationwide Dutch primary biliary cholangitis (PBC) Cohort Study, including all hospitals in the Netherlands, showed that the incidence and prevalence of PBC have increased over the last decade. The age-dependent PBC incidence rate differed for males (highest risk ≥65 years) and females (highest risk between 45 and 65 years), which may be related to a difference in the timing of exposure to environmental triggers of PBC. The largest increase in PBC prevalence over time was observed in the population aged ≥65 years, which may have implications for the use of second-line therapies. These results therefore indicate that further studies are needed to elaborate on the advantages and disadvantages of add-on therapies in the elderly population.

Explaining post-traumatic stress symptoms and sleep disturbance in Ukrainian civilians: perceived threat versus objective war exposure.

Objective: This study investigated the impact of war exposure on post-traumatic stress symptoms (PTSS) and sleep disturbance across Ukraine. Subjective and objective indicators of war exposure were modelled as predictors of these symptoms.Methods: We created two predictors: first, we used governmental and crowd-sourced data to create an objective war exposure index for each of the 21 non-occupied regions of Ukraine, based on the number of air raid alarms, explosions, and proximity to frontline; and second, we obtained self-report cross-sectional data, using convenience sampling, from a nation-wide survey (N = 991) on subjective experience of threat triggered by the war. The survey also measured the outcome variables of PTSS and sleep disturbance. Hierarchical multilevel regressions modelled the relationship of this objective war exposure index with the two outcome variables, after accounting for demographics. A final regression step modelled subjective threat as predictor of these symptoms.Results: We observed strongly elevated levels of PTSS and sleep disturbance and strong regional differences in objective and subjective war indicators. Objective war exposure predicted PTSS but not sleep disturbance, whereas subjective threat predicted both symptom domains.Conclusion: The study demonstrates the utility of objective war exposure data for predicting the prevalence of PTSS in the different regions. The results further underscore the prominent role of subjective appraisal processes in the symptomatology of PTSS and sleep disturbance, thus informing theories on trauma-related disorders. Our results can guide the allocation of mental health services by identifying highly affected regions.

Objective data on air raid alarms and explosions have been prospectively collected in Ukraine.We related those objective data to symptom reports of 991 responders in most Ukraine regions.Objective data explained symptoms of post-traumatic stress but not sleep disturbance.

Local Control of Pyoderma Gangrenosum Using Human Amniotic Membrane and Transcriptome Analysis.

Pyoderma gangrenosum (PG) is a rare, chronic, ulcerative disease characterized by non-healing wounds that worsen with debridement, a phenomenon called pathergy. No consensus regarding pathogenesis, diagnosis, or treatment exists for PG. A previous pilot study using dehydrated human amniotic/chorionic membrane (dHACM), following excisional debridement, augmented PG wound healing and allowed for subsequent wound closure through split-thickness skin grafting (STSG). In this clinical trial (NCT05120726), four patients with an established PG diagnosis were enrolled to undergo treatment with dHACM and characterize the pre- and post-treatment transcriptome profiles. RNA sequencing was used to isolate the total RNA from specimens. Genes of particular interest were quantified through real-time quantitative reverse transcription polymerase chain reaction. We observed varied changes to the local expression of inflammatory response, positive regulators of cellular proliferation, and extracellular matrix disassembly cytokines. All PG wounds produced granulation tissue following treatment and were closed using split-thickness skin grafts.

Parent and healthcare professional experiences of critical congenital heart disease in New Zealand to advance health equity.

BACKGROUND: Higher odds of survival have been reported in European infants compared to Indigenous Maori and Pasifika infants with critical congenital heart disease in New Zealand. We therefore aimed to understand how to mitigate this disparity by investigating the parent and healthcare professional experiences' of critical congenital heart disease healthcare in New Zealand. METHODS: A prospective qualitative study utilising semi-structured interviews was conducted on a cohort of purposefully sampled parents and health professionals with experience of critical congenital heart disease healthcare in New Zealand. Parents were recruited after a fetal critical congenital heart disease diagnosis and offered two interviews at least three months apart, whilst multidisciplinary fetal and cardiosurgical health professionals were interviewed once. Interviews were recorded and transcribed verbatim before coding, categorization and qualitative analysis. RESULTS: During 2022 and 2023, 45 people participated in 57 interviews (25 parents: 19 mothers, 6 fathers; Indigenous Maori, n = 5; Pasifika, n = 6; Asian, n = 4; European, n = 10; and 20 healthcare professionals: European n = 17). The three lessons learned from participants were: (1) Minoritized groups experience disparate healthcare quality; (2) healthcare systems are under-resourced to provide equitable support for the differential needs of grieving parents; and (3) healthcare systems could engage minoritized families more optimally in shared decision-making. CONCLUSIONS: According to the experiences of parents and healthcare professionals, persisting inequities in CCHD healthcare quality occur by ethnic group, with the New Zealand healthcare system privileging European families. The concepts from this study could be translated by healthcare leaders, policymakers, and professionals into evidence-based healthcare system improvements to enhance experiences for non-European families more broadly.

Hepatic Sinusoidal Disorders.

Hepatic sinusoids are highly specialized microcirculatory conduits within the hepatic lobules that facilitate liver functions. The sinusoids can be affected by various disorders, including sinusoidal dilatation, sinusoidal obstruction syndrome (SOS), sinusoidal cellular infiltration, perisinusoidal infiltration, and endothelial neoplasms, such as hemangioendothelioma and angiosarcoma. While these disorders, particularly SOS and neoplasms, can be life threatening, their clinical manifestation is often nonspecific. Patients may present with right upper quadrant pain, jaundice, hepatomegaly, ascites, splenomegaly, and unexplained weight gain, although the exact manifestation depends on the cause, severity, and duration of the disease. Ultimately, invasive tests may be necessary to establish the diagnosis. A comprehensive understanding of imaging manifestations of various sinusoidal disorders contributes to early diagnosis and can help radiologists detect subclinical disease. Additionally, specific imaging features may assist in identifying the cause of the disorder, leading to a more focused and quicker workup. For example, a mosaic pattern of enhancement of the liver parenchyma is suggestive of sinusoidal dilatation; peripheral and patchy reticular hypointensity of the liver parenchyma on hepatobiliary MR images is characteristic of SOS; and associated diffuse multiple hyperintensities on diffusion-weighted images may be specific for malignant sinusoidal cellular infiltration. The authors provide an overview of the pathogenesis, clinical features, and imaging appearances of various hepatic sinusoidal disorders, with a special emphasis on SOS. ©RSNA, 2024 Supplemental material is available for this article.

Continuous Monitoring by a Wearable Sensor Did Not Enhance Discharge Decision-Making in an Acute Admission Ward: Results of a Randomized Controlled Trial.

Adding continuous monitoring to usual care at an acute admission ward did not have an effect on the proportion of patients safely discharged. Implementation challenges of continuous monitoring may have contributed to the lack of effect observed.

A 4.3-million-year-old Australopithecus anamensis mandible from Ileret, East Turkana, Kenya, and its paleoenvironmental context.

A hominin mandible, KNM-ER 63000, and associated vertebrate remains were recovered in 2011 from Area 40 in East Turkana, Kenya. Tephrostratigraphic and magnetostratigraphic analyses indicate that these fossils date to ∼4.3 Ma. KNM-ER 63000 consists of articulating but worn and weathered mandibular corpora, with a broken right M2 crown and alveoli preserved at other tooth positions. Despite extensive damage, KNM-ER 63000 preserves diagnostic anatomy permitting attribution to Australopithecus anamensis. It can be distinguished from Australopithecus afarensis by its strongly inclined symphyseal axis with a basally convex, 'cut-away' external surface, a lateral corpus that sweeps inferomedially beneath the canine-premolar row, and alignment of the canine alveolus with the postcanine axis. KNM-ER 63000 is distinguished from Ardipithecus ramidus by its thick mandibular corpus and large M2 crown. The functional trait structure and enamel's stable carbon isotopic composition of the Area 40 large-mammal community suggests an environment comparable to Kanapoi and other ∼4.5-4 Ma eastern African sites that would have offered Au. anamensis access to both C3 and C4 food resources. With an age of ∼4.3 Ma, KNM-ER 63000 is the oldest known specimen of Au. anamensis, predating the Kanapoi and Asa Issie samples by at least ∼100 kyr. This specimen extends the known temporal range of Au. anamensis and places it in temporal overlap with fossils of Ar. ramidus from Gona, Ethiopia. The morphology of KNM-ER 63000 indicates that the reconfigured masticatory system differentiating basal hominins from the earliest australopiths existed in the narrow temporal window, if any, separating the two. The very close temporal juxtaposition of these significant morphological and adaptive differences implies that Ar. ramidus was a relative rather than a direct phyletic ancestor of earliest Australopithecus.

Associations between hearing loss, peripheral neuropathy, balance, and survival in older primary care patients.

BACKGROUND: Both age-associated hearing loss (AAHL) and peripheral neuropathy (PN) are common in older patients, and both are associated with impaired balance, falls, and premature mortality. The objectives of this study were to document the prevalence and severity of AAHL in older primary care patients, and to explore associations between AAHL, PN, balance, falls, and mortality. METHODS: We analyzed information obtained in 1999 from 793 primary care patients recruited from practices participating in the Oklahoma Longitudinal Assessment of the Health Outcomes of Mature Adults (OKLAHOMA) Studies. Available data included demographic and health information, history of falls and hospitalizations, audiometry, balance testing, examination of the peripheral nerves, 50 foot timed gait, and dates of death up to 22 calendar years and 8106 person-years of follow-up. Proportionate hazards (PH) and structural equation modeling (SEM) were used to examine associations between AAHL, PN, balance, gait time, and mortality. RESULTS: 501 of the 793 participants (63%) had AAHL. Another 156 (20%) had low frequency and 32 (4%) had unilateral deficits. Those with moderate or severe AAHL and the 255 (32%) with PN had impaired balance (p < 0.0001), increased gait time (p = 0.0001), and reduced survival time (p < 0.0001). In the PH model, both AAHL and PN were associated with earlier mortality (H.Rs. [95% C.I.]: 1.36 [1.13-1.64] and 1.32 [1.10-1.59] respectively). The combination of moderate or severe AAHL and PN, present in 24% of participants, predicted earlier mortality than predicted by either deficit alone (O.R. [95% C.I.I] 1.55 [1.25-1.92]). In the SEM models, the impacts of both moderate or severe AAHL and PN on survival were mediated, in part, through loss of balance. CONCLUSIONS: Hearing loss and PN, both common in older patients, appear to be independently and additively associated with premature mortality. Those associations may be mediated in part by impaired balance. The Mechanisms are likely multiple and complex.

The validity of pathology codes for biopsy-confirmed kidney disease in the Danish National Patobank.

Background: This study validates the application of Systematized Nomenclature of Medicine second edition (SNOMED II) codes used to describe medical kidney biopsies in Denmark in encoded form, aiming to support robust epidemiological research on the causes, treatments and prognosis of kidney diseases. Methods: Kidney biopsy reports from 1 January 1998 to 31 December 2018 were randomly extracted from the Danish National Patobank, using SNOMED codes. A 5% sample was selected, and nephrologists assessed the corresponding medical records, assigning each case the applied clinical diagnoses. Sensitivity, specificity, positive predictive values (PPV), negative predictive values and Cohen's kappa coefficient for the retrieved SNOMED codes were calculated. Results: A total of 613 kidney biopsies were included. The primary clinical disease groups were glomerular disease (n = 368), tubulointerstitial disease (n = 67), renal vascular disease (n = 51), diabetic nephropathy (n = 51) and various renal disorders (n = 40). Several SNOMED codes were used to describe each clinical disease group and PPV for the combined SNOMED codes were high for glomerular disease (94%), diabetic nephropathy (85%) and systemic diseases affecting the kidney (96%). Conversely, tubulointerstitial disease (62%), renal vascular disease (60%) and other renal disorders (17%) showed lower PPV. Conclusions: SNOMED codes have a high PPV for glomerular diseases, diabetic nephropathy and systemic diseases affecting the kidney, in which they could be applied for future epidemiological research.

Relative numerosity is constructed from size and density information: Evidence from adaptation.

To dissociate aftereffects of size and density in the perception of relative numerosity, large or small adapter sizes were crossed with high or low adapter densities. A total of 48 participants were included in this preregistered design. To adapt the same retinotopic region as the large adapters, the small adapters were flashed in a sequence so as to "paint" the adapting density across the large region. Perceived numerosities and sizes in the adapted region were then compared to those in an unadapted region in separate blocks of trials, so that changes in density could be inferred. These density changes were found to be bidirectional and roughly symmetric, whereas the aftereffects of size and number were not symmetric. A simple account of these findings is that local adaptations to retinotopic density as well as global adaptations to size combine in producing numerosity aftereffects measured by assessing perceived relative number. Accounts based on number adaptation are contraindicated, in particular, by the result of adapting to a large, sparse adapter and testing with a stimulus with a double the density but half number of dots.