Scaling Laws Do Not Scale

Recent work has proposed a power law relationship, referred to as ``scaling laws,'' between the performance of artificial intelligence (AI) models and aspects of those models' design (e.g., dataset size). In other words, as the size of a dataset (or model parameters, etc) increases, the performance of a given model trained on that dataset will correspondingly increase. However, while compelling in the aggregate, this scaling law relationship overlooks the ways that metrics used to measure performance may be precarious and contested, or may not correspond with how different groups of people may perceive the quality of models' output. In this paper, we argue that as the size of datasets used to train large AI models grows, the number of distinct communities (including demographic groups) whose data is included in a given dataset is likely to grow, each of whom may have different values. As a result, there is an increased risk that communities represented in a dataset may have values or preferences not captured by (or in the worst case, at odds with) the metrics used to evaluate model performance for scaling laws. We end the paper with implications for AI scaling laws -- that models may not, in fact, continue to improve as the datasets get larger -- at least not for all people or communities impacted by those models

Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors

Introduction of heterologous anti–glomerular basement membrane antiserum (nephrotoxic serum, NTS) into presensitized mice triggers the production of IgG anti-NTS antibodies that are predominantly IgG2b and the glomerular deposition of pathogenic immune complexes, leading to accelerated renal disease. The pathology observed in this model is determined by the effector cell activation threshold that is established by the coexpression on infiltrating macrophages of the IgG2a/2b restricted activation receptor FcγRIV and its inhibitory receptor counterpart, FcγRIIB. Blocking FcγRIV with a specific monoclonal antibody thereby preventing IgG2b engagement or treatment with high dose intravenous γ-globulin (IVIG) to down-regulate FcγRIV while up-regulating FcγRIIB, protects mice from fatal disease. In the absence of FcγRIIB, IVIG is not protective; this indicates that reduced FcγRIV expression alone is insufficient to protect animals from pathogenic IgG2b immune complexes. These results establish the significance of specific IgG subclasses and their cognate FcγRs in renal disease

Fairlearn: Assessing and Improving Fairness of AI Systems

Fairlearn is an open source project to help practitioners assess and improve fairness of artificial intelligence (AI) systems. The associated Python library, also named fairlearn, supports evaluation of a model's output across affected populations and includes several algorithms for mitigating fairness issues. Grounded in the understanding that fairness is a sociotechnical challenge, the project integrates learning resources that aid practitioners in considering a system's broader societal context

Altered glomerular permeability induced by F(ab′)2 and Fab′ antibodies to rat renal tubular epithelial antigen

Altered glomerular permeability induced by F(ab′)2 and Fab′ antibodies to rat renal tubular epithelial antigen. Rats injected with F(ab′)2 and Fab′ antibody fragments directed against an antigen in the rat proximal tubular epithelial brushborder (Fx1A) developed immediate proteinuria [F(ab′)2 43.2 ± 6.7, N = 6; Fab′ 9.5 ± 2.8, N = 5; normal 1.6 ± 0.9 mg/day, N = 20]), that subsided after 3 to 5 days' duration. This reaction is in contrast to one exhibited by rats given intact IgG anti-Fx1A; the rats that did not develop immediate proteinuria (2.2 ± 0.3 mg/day, N = 5), and the glomerular binding of125I-antibody fragments was significantly less than that of intact IgG [F(ab′)2 0.11 ± 0.01; Fab′ 0.03 ± 0.01; IgG 0.17 ± 0.01% administered equimolar dose] at 24 hr. No proteinuria resulted from equimolar doses of nonantibody F(ab′)2 and Fab′. Less than 8% of the proteinuria induced by antibody fragments represented injected material, and 30 to 38% was albumin. Immunofluorescence revealed faint and diffuse glomerular capillary wall deposits of F(ab′)2 and Fab′ and tubular brushborder staining. Subepithelial, electrondense deposits and focal, podocyte effacement were seen by electron microscopy in rats given the F(ab′)2 antibody. Light microscopy and colloidal iron-staining were normal. In our study antibody fragments appear to interact directly with components of the outer, glomerular capillary wall to alter permeability in the absence of recognized mediators such as complement and inflammatory cells.Modification de la perméabilité glomérulaire déterminée par anticorps chez des rats anti-épithélium tubulaire F(ab′)2 et Fab′. Les rats été injectés avec des fragments F(ab′)2 et Fab′ contra anticorps de la bordure en brosse de l'épithélium tubulaire proximal de rat (Fx1A) ont immédiatement une protéinurie [F(ab′)2 43,2 ± 6,7, N = 6; Fab′ 9,5 ± 2,8, N = 5; normaux 1,6 ± 0,9 mg/d, N = 20] qui persiste pendant 3 à 5 jours. Cela réaction est différent de ce qui est observé chez les rats qui reçoivent l'IgG anti-Fx1A intacte; les rats quelles n'ont pas de protéinurie immédiate (2,2 ± 0,3 mg/d, N = 5) quoiqu'à 24 heures la liaison glomérulaire de fragments125I de l'anticorps soit significativement plus faible que celle de I'IgG intacte [F(ab′)2 0,11 ± 0,01; Fab′ 0,03 ± 0,01; IgG 0,17 ± 0,01 en % de la dose équimolaire administrée]. Aucune protéinurie n'a été la conséquence de l'administration équimolaire de F(ab′)2 et Fab′ non-anticorps. Moins de 8% de la protéinurie déterminée par les fragments d'anticorps représentent du matériel injecté et 30 à 38% est de l'albumine. L'immunofluorescence a montré des dépôts faibles et diffus, sur les parois des capillaires giomérulaires, de F(ab′)2 et Fab′ et le marquage de la bordure en brosse. En électronique, des dépôts denses sous-épithéliaux et l'effacement local des podocytes ont été observés chez les rats qui avaient reçu l'anticorps F(ab′)2. La microscopie optique et la coloration par le fer colloïdal n'ont pas montré d'anomalies. Dans notre étude les fragments d'anticorps semblent avoir paroi externe du capillaire glomérulaire et avoir modifié la perméabilité en l'absence de médiateurs connus tels le complément ou les cellules inflammatoires

Lupus autoantibodies interact directly with distinct glomerular and vascular cell surface antigens

Lupus autoantibodies interact directly with distinct glomerular and vascular cell surface antigens. We have identified monoclonal anti-DNA antibodies derived from lupus prone MRL-lpr/lpr mice that produce glomerular immune deposits and nephritis after passive transfer to normal mice. Particularly noteworthy is that the location of immune deposition varied among nephritogenic Ig, and this was associated with distinctive histologies and clinical disease profiles. Although their autoantigen binding properties differed, they were highly cross-reactive, in a manner similar to Ig deposited in glomeruli of lupus mice. This antigen binding profile was also typical of other previously described nephritogenic autoantibodies that bound directly to glomerular antigens to initiate immune deposit formation. In this study, we questioned whether ligation of different glomerular antigens by individual autoantibodies could contribute to the observed differences in the location of immune deposits. To examine this possibility, monoclonal anti-DNA antibodies (IgG2a) that produced glomerular immune deposits in different locations were evaluated. H221 produced mesangial, intracapillary (that is, intraluminal or within the capillary lumen) and subendothelial deposits associated with heavy proteinuria, whereas H147 produced mesangial, subendothelial and linear basement membrane deposits associated with proliferative glomerulonephritis. Initially, the capacity of H221 and H147 to bind directly to glomerular and vascular cell surfaces was evaluated. As demonstrated by FACS, H221 bound preferentially to mesangial cells whereas H147 bound preferentially to endothelial cells. To identify possible target cell surface antigens, Western blots, immunoprecipitation of surface labeled cells, and 2D gel electrophoresis were employed. H221 reacted with a 108kDa protein on mesangial cells not identified by H147, whereas H147 reacted with a 45kDa protein on endothelial cells not identified by H221. These results support the hypothesis that some nephritogenic lupus autoantibodies initiate immune deposit formation through direct interaction with glomerular antigens. Furthermore, they suggest that the site of immune deposition is determined by both antigen binding properties of the relevant antibody and the location of its target ligand within the glomerulus. In a given individual, therefore, the predominant autoantibody-glomerular antigen interaction may influence the morphologic and clinical phenotype expressed. Variation in the predominant interaction may also contribute to variations in disease expression among individuals with lupus nephritis

Anti-DNA antibodies form immune deposits at distinct glomerular and vascular sites

Anti-DNA antibodies form immune deposits at distinct glomerular and vascular sites. To investigate the capacity of lupus autoAb to produce glomerular immune deposits (ID) and nephritis, 24 murine monoclonal (m) anti-DNA antibodies (Ab), derived from either MRL-lpr/lpr, SNF1 or NZB lupus-prone mice and selected based on properties shared with nephritogenic Ig, were administered i.p. (as hybridomas) and i.v. (as purified Ig) to normal mice; at least four mice/mAb were evaluated. Three general patterns of immune deposit formation (IDF) were observed: extracellular ID within glomeruli (± blood vessels, N = 8); intranuclear ID (N = 5); or minimal or no ID (N = 11). The four MRL m anti-DNA Ab that produced significant extracellular ID demonstrated different disease profiles including: (a) mesangial and subendothelial ID with anti-basement membrane staining, associated with proliferative glomerulonephritis, PMN infiltration, and proteinuria; (b) diffuse fine granular mesangial and extraglomerular vascular ID, associated with proliferative glomerulonephritis and proteinuria; (c) dense intramem-branous ID and intraluminal ID, associated with capillary wall thickening, mesangial interposition and expansion, aneurysmal dilatation and intraluminal occlusion of glomerular capillary loops, and heavy proteinuria; and (d) mesangial and extraglomerular vascular ID, associated with mild segmental mesangial expansion, without proteinuria. These MRL mAb were derived from four different mice, and they had variable pis and isotypes. They all cross reacted with multiple autoantigens (autoAg), however, their autoAg binding profiles were distinguishable. Among the SNF1 derived mAb, four produced histologically and clinically indistinguishable disease characterized by diffuse mesangial and capillary wall ID, associated with cellular proliferation/infiltration and proteinuria. Three of the four mAb were derived from the same mouse and were clonally related; they were: IgG2b with SWR allotype, relatively cationic, highly cross reactive with similar Ag binding patterns, idiotypically related and encoded by identical VH and nearly identical VL sequences. We conclude that both the capacity of lupus autoAb to form ID and the location of IDF are dependent on properties unique to individual Ig. The results also indicate that the Ag binding region of the autoAb is influential in this process, and they suggest that multiple Ab-Ag interactions contribute to IDF in individuals with lupus nephritis. Furthermore, these observations raise the possibility that the pathologic and clinical abnormalities resulting from these interactions are influenced by the location of IDF, and that the dominant interaction, in a given individual, may be highly influential in the phenotypic expression of nephritis

U.S. Physician-Scientist Workforce in the 21st Century: Recommendations to Attract and Sustain the Pipeline

The U.S. physician-scientist (PS) workforce is invaluable to the nation's biomedical research effort. It is through biomedical research that certain diseases have been eliminated, cures for others have been discovered, and medical procedures and therapies that save lives have been developed. Yet, the U.S. PS workforce has both declined and aged over the last several years. The resulting decreased inflow and outflow to the PS pipeline renders the system vulnerable to collapsing suddenly as the senior workforce retires. In November 2015, the Alliance for Academic Internal Medicine hosted a consensus conference on the PS workforce to address issues impacting academic medical schools, with input from early-career PSs based on their individual experiences and concerns. One of the goals of the conference was to identify current impediments in attracting and supporting PSs and to develop a new set of recommendations for sustaining the PS workforce in 2016 and beyond. This Perspective reports on the opportunities and factors identified at the conference and presents five recommendations designed to increase entry into the PS pipeline and nine recommendations designed to decrease attrition from the PS workflow

Human-Centered Responsible Artificial Intelligence: Current & Future Trends

In recent years, the CHI community has seen significant growth in research on Human-Centered Responsible Artificial Intelligence. While different research communities may use different terminology to discuss similar topics, all of this work is ultimately aimed at developing AI that benefits humanity while being grounded in human rights and ethics, and reducing the potential harms of AI. In this special interest group, we aim to bring together researchers from academia and industry interested in these topics to map current and future research trends to advance this important area of research by fostering collaboration and sharing ideas.Comment: To appear in Extended Abstracts of the 2023 CHI Conference on Human Factors in Computing System